Cornell University The original of this book is in the Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://Awww.archive.org/details/cu31924000012645 SPECIAL PATHOLOGY AND THERAPEUTICS OF THE DISEASES OF DOMESTIC ANIMALS BY DR. FRANZ HUTYRA Professor of Infectious Diseases, AND DR. JOSEF MAREK Professor ot Special Pathology and Therapy; both of the Royal Veterinary College at Budapest - Authorized American Edition From the Third Revised and Enlarged German Edition , JOHN R. MOHLER, V. M. D. Chief of Pathological Division, U. §. Bureau of Animal Industry, AND ADOLPH EICHHORN, D. V. S. Senior Bacteriologist, Pathological Division, U. S. Bureau of Animal Industry, Washington, D. C. - EDITORS. ee VOLUME I. Infectious Diseases; Diseases of the Blood and of the Hematopoietic Organs; Diseases of Metabolism, of the Spleen, Urinary and Circulatory Organs. With 198 illustrations in the text and 10 plates. LONDON BAILLIERE, TINDALL AND COX 8 Henrietta Street, Covent Garden 1913 (ALL RIGHTS RESERVED) he, CopyricHTeD at WasuincTon, D. Cc. BY ALEXANDER EGER 1912 TRANSLATORS OF THE FIRST VOLUME JOHN R. MOHLUER, V. M. D. Chief of the Pathological Division, U. S. Bureau of Animal Industry Washington, D. C. ADOLPH EICHHORN, D. V. 8. Senior Bacteriologist, Pathological Division, U. 8. Bureau of Animal Industry Washington, D. C. DR. PAUL FISCHER State Veterinarian, Columbus, Ohio DR. H. J. ACHARD of the Editorial Staff, American Journal of Clinical Medicine Chicago, Illinois Editors’ Preface Hutyra & Marek’s Spezielle Pathologie und Therapie der Haustiere is generally recognized as the most comprehensive and authoritative treatise on the theory and practice of veter- inary medicine in Germany, Austria and Hungary, and has been adopted as a textbook by all the veterinary colleges in these ° countries, as well as in Switzerland. The favorable reception of previous editions in foreign lan- guages has convinced us that the work has found favor with the professions abroad, and the present edition, which has been prepared in response to a frequently expressed desire for such a translation, should prove equally valuable to the English- speaking veterinarian. The chapter on infectious diseases will also appeal to physicians and sanitarians who have to deal with the diseases communicable from animals to man, and it may reasonably be anticipated that the work as-a whole will serve as an authoritative guide, and also as an admirable textbook and a standard of reference for students and practitioners, especially those who graduated before modern science had thrown its light upon the etiology of disease. . We wish to express sincere thanks to our eminent collabora- tors for their able assistance in translating portions of this work, and to Drs. Henry J. Washburn and Jacob Traum, of Washington, D. C., for their aid in proofreading and in the. preparation of the index. Acknowledgment is also due the pub- lisher, Mr. Alexander Eger, for his uniform courtesy and assist-. ance in many -ways. Washington, D. C., Aug. 16, 1912. MOHLER & EICHHORN. Table of Contents Infectious Diseases. GROUP I. Acute General Infectious Diseases. es AMDT AR: oy sos cvs eh ee HE ee tasicishe coh aalis oaaal ahs dies eee ane dene Anthrax in Man............ iia itd At aha ele wants, anew Sager Gansed osece evs 2. Malignant Hdema ........... cc ccc e ce cece cence ecenteeeeuees De. Dldeklep sre acct Gas has aie dan oahu ayard Mia ouch ease tes Sapa wanda Bradsot of Sheep................005. ears tte ets ee con Reindéer Pest) ic 42 vues see Bane aes eh we oie torte eaten els The 4, -Switle. Mrysipelas sive yas cines ae bee cure ie waa Da ehadeomes Boos The: Disease Tit Mai esse ck wars aie eri deed tees hea de deace tee dette dee ce tele k 5. Hemorrhagic Septicemia ............. cece cece cee cee teen eees (a): owl Choletan..i/csjeseb.os ncaa encase ae tated Gat Ok i cedar as Other Diseases of Fowl of a Septicemic Character......... Septicemic and Pyemic Affections of Rabbits.............. (b) Hemorrhagic Septicemia of Cattle.................-.00000- Septie Pleuro-pneumonia of Calves...............-000000e NEGUS esha s see asa okt w Wa ean swale Ma AG Se a aod acer een wTeaa oe (ce) Buffalo. Diseasé: onacccaes paced case ciesae ese owe ees as ya (ad) Hemorrhagic Septicemia of Sheep............. cece eee eee Infectious Pneumonia of Goats........ 0... cece cee eee Takosis of Angora Goats... ...ccc ccc c cece eee eee e eens (e) Swine Plague: «08 osa ioe ss esis ous onsets eee ed oh aoe ee ee Enzootic Pneumonia of Pigs............. 2: eee eee eee eee Pyobacillosis of Hogs......... sees cece eee ence eee ees 6. Septicemic Affections of Newborn Animals ............--++++++++- (a) White Secours of Sucklings............- see eee eee ee ees Various Colonbacilloses of Cattle..........: cece cece aee (b) Pyo-septicemia of Sucklings...........-.:seeee eee eee eee ee 7. Influenza of Horses .......200sceccec cece cere eee eeenene eee nees © Tn fluén gay in). Matis 2 iesctenes ces vidd ord ACTS eee OR Mase Dengue Fever ........ cc ccc ce cece c eee e rete e een enon nen eeees Three-days’ Sickness ...... 60. e cece eee e teen een ee ene nneee ‘ Malta, ever. sis foc oa Ss SAREE TIE SE ONS Me VoR aR eo FIRE ENS x Contents. PAGE 8. Distemper of Dogseciscivcecsevcie seus ae ineasw ewes aes aed aa wae 197 Distemper Of -CatSess.icotoaid greweagerdeter ieee nns crane cy 2LO Ty phus: 01 Dogsi seiiacwaragecseaguck oni eeteade ccc tan abe Oees 211 9. Purpura Hemorrhagica ......... 0c cece cece cette eens . 216 Purpura Hemorrhagica of Cattle....... rath esky ataratede = Coen aaueel eiteenr oo 232 Purpura Hemorrhagica of Dogs............ cece eee eee eee 233 Purpura Hemorrhagica of Man............. cece eee eee nee eee 233 Scarlatinoid of HorseSs css csscacseevseesciwe sso eigaeme iene geen 233 Scarlatinoid of Cattle. ....... cc cee ce cee ete en eens 234 10. Binderpest) oiis.ca5 cea eit eee ee eee eae Swe ake hele ab Oa ae Tae 234 Rinderpest of Sheep and Goats....... 0.00. cece ee cence eee eee 256 Heartwater ...0.cescavew ese vent aceera es OY Siac 5 pone ty aacsara ss abs ek 257 Ts. Hop Cholera: 5 vss anckhe c:igiditaie dod Gandy pea woed weer at Sawa a) lee ele Pies 257 12... African Horse=Sickness ccc case cae ae ee edits odie eres a ass Bae 285 13. Fowl Pest: setsictatewcie acisautehaeeawweee pridneve sans dates 290 GROUP II. Acute Exanthematous Infectious Diseases. ly Pox: “Varidla «hese iakiagun ae viaatie :enitawteeewuy ou Soe eee 295 (8) Sheep POX: ac ad Sc ed were ae pas Swe ee ee ae to eee 302 (Ib) COW. ROX as ate wih ect la adnate tian aan oylese thneuaey «ava ueuacayeel ates, Slaneel Suny 318 (ce) horse Pox. ics dace daz5 Gara) rerdpieulea Oaga ebale WAS Ae asus 324 (d)i Swine Pox ws vcecvavs cas che ede nes oes Gee wed wae dered wee es 325 (e): Goat Pox Anthrax bacilli are found in great numbers in the gelatinous-hemorrhagic con- nective tissue as well as in the swollen lymph glands. On the other hand, they are only sparingly present in the blood, and in the spleen nodules mentioned they are mostly found in a degenerated form. Symptoms. -The time of incubation of anthrax after arti- ficial infection varies from 1 to 14 days, depending to a great extent on the place and intensity of the infection. After sub- cutaneous or intravenous inoculation the manifesta- [: PR, Z12039 1401516 1% | “l=iloslam pm jam pm iam pm |am pm jam pm jam pm i) Tip! zs (2 Hy ral tions of the disease ap- ie Z pear in 24 to 48 hours. was = z Sheep usually succumb in t| =F z 2 to 3 days to the feeding Ee 2 of large quantities of EE $ spores. However, the tai 3 5 time of incubation under koyaso E ne natural conditions, when =p = the animals take up a con- panes = ' siderably smaller quan- [ilal) 7] == tity of spores, is undoubt- B + edly longer. Thus in the ha ggzs experiments of Pasteur, Roux ‘& Chamberland }&4# sheep, which were infected sed sales with food grown on in- i t fected pastures, devel- [sl4y PAR oped the disease only Sa FS after 10 days. In horses bay 50 5 amo ed %: and cattle the time of in- zy } = aaa seems 2 be hard- pa? : y less than 3 days. In horses, ‘cattle and oh sheep anthrax when de- Fig. 7. Fever curve in anthrax of a horse. veloping as a result of an ; intestinal infection usually manifests itself in the form of a general, acute infectious disease in which the individual 16 Anthrax. symptoms are only rarely characteristic of the specific affection. In the peracute cases the course of the disease simulates cerebral apoplexy (anthrax acutissimus s. apoplecticus). Well nourished and apparently healthy animals, which, however, were probably feverish, suddenly go down in the stable or in the pasture and remain lying on the ground in convulsions; the respiration is rattling; bloody foam oozes from the mouth and nose, the mucous membrane of which shows a dark bluish-red discoloration, and from the anus pure blood even may escape, until finally in a few minutes, or at most within an hour, the animal dies. This form of anthrax is observed most frequently at the beginning of an outbreak, and particularly among sheep. In the acute and subacute cases which represent by far the largest percentage of cases the disease commences with:a quick rise in the temperature to 40-42°C., at which height it remains for a time, dropping quickly just before death. (Fig. 7.) Some animals, especially cattle, manifest quite a lively disposition at the onset of the disease and take their food in the usual manner. In some cases the disease commences with restlessness and excitement which soon pass into depression. In most cases, however, the malady is preceded by symptoms of general de- pression, the animal refusing to eat and standing in one place with head hanging, staring look and dilated pupils. In the pasture the affected animals trail behind the others, remain for a long time in one place or lie down; when urged to move they stagger and sway. At the same time they have chills and their temperature is unevenly distributed over the surface of the body. The pulse is accelerated and small while the heart beats are metallic in sound. The respiration is very labored and accelerated, and the dark bluish-red cyanotic mucous membranes, which are fre- quently studded with petechial hemorrhages, are indicative of insufficient oxidation of the blood. A mechanical cause for the difficult respiration cannot be established except in those cases in which edema of the glottis is suspected, because of pharyn-: gitis, swelling of the neck and whistling inspiration. Examina- tion of the lungs reveals nothing abnormal except a harsh vesicular breathing. Very frequently disturbances in the digestion are observed. Apart from affected appetite horses manifest severe colicky pains but without any indication of meteorism or bloating. Ruminants are less restless and frequently show moderate bloating (in one case, a cow observed by Schmidt, the course of the disease manifested the symptoms of an acute paralysis of the rumen with left-sided pleurisy). At first there is con- stipation, but diarrhea soon sets in, during which the feces, particularly in cattle, are fluid and frequently intermixed with Symptoms. 17 blood, or occasionally large masses of blood may be passed by the affected animals. In horses it is sometimes possible to demonstrate a marked enlargement of the spleen by rectal exploration or by percussion. The urine is dark red and some- times even bloody. (This is a particularly frequent symptom in sheep, in which animals the compression of the nasal openings causes immediate urination.) The milk secretion usually ceases shortly after the onset of the disease ; if there is a slight secretion of milk it is yellowish or bloody in appearance, slimy, and possibly bitter. Pregnant animals frequently abort. After the difficulty in respiration has reached a high degree, death finally results with signs of asphyxiation. . Besides these symptoms, which clearly indicate the pres- ence of an acute infectious disease, in some cases, particularly in horses, more rarely in cattle and very exceptionally in sheep, acute edematous swellings develop on the surface of the body, which make a more accurate orientation of the nature of the affection possible. In any region of the body, but especially on the neck, breast, flanks, or lumbar region, a more or less extensive, rapidly growing swelling develops. The swellings are hot, and of a doughy or dense consistence, but the skin covering them usually shows no changes. Exceptionally on a circumscribed area of the skin proper a warm, painful and dense swelling develops surrounding which the subcutaneous tissue also appears greatly swollen as a result of the inflammatory edema. With the swelling of the neck there is usually associated a severe pharyngitis or edema of the glottis which considerably increases the pre-existing dyspnoea. On the rectal mucous membrane carbuncular growths develop occasionally as a result of infection introduced by a rectal examination or by manual removal of the feces. In such cases the feces are usually evacuated under severe straining, and contain dark, tar-colored blood or exfoliated tissue shreds. The rectum is prolapsed; the perineal region is edematously swollen, while the hand in- troduced into the rectum may detect flat or nodular swellings in the hot mucous membrane. A primary affection of the skin only rarely occurs in animals, and consists in the appearance of circumscribed, warm, painful and hard swellings which later become gangrenous, commencing in the center, and change into ulcers (carbuncles) which have ragged borders and are covered with necrotic tissue. ‘ According to some authors anthrax may occur in sheep in the form of an erysipelas-like dermatitis accompanied by a subcutaneous edema which starts at one extremity and soon extends to the body, whereby the patients show high fever and die inside of 14 to 2 days. The anthrax nature of the affection has not yet been positively estab- lished. The occurrence of the so-called gloss anthrax is also doubtful, as most case¢ in cattle designated under this name belong to hemorrhagic 2 18 Anthrax. septicemia. The presence of gloss anthrax can only be accepted as prob- able when the tongue is greatly swollen, cyanotically discolored, or when the buccal mucous membrane contains hard nodules and cysts filled with bloody fluid. In hogs anthrax usually runs its course with manifestations of febrile pharyngitis with marked swelling of the subparotidal and laryngeal regions. The swelling may extend from the neck to the head and cause considerable difficulty in deglutition and respiration. At the same time the mucous membranes are -eyanotic, bluish-red spots develop on the skin, diarrhea sets in, and the difficulty in respiration and swallowing reach such a state that the animals finally die from asphyxiation. In experimental cases cysts filled with bloody fluid develop on the mucous membrane of the tongue, cheeks and lips. In those cases where there is no swelling of the neck the symptoms observed are only debility, suppressed appetite and hiding under the straw. In dogs and in other carnivorous animals the disease is of rare occurrence and is usually manifested by severe gastro- enteritis as well as pharyngitis. Sometimes after eating an- thrax blood an inflammation develops on the lips and tongue, or general infection may follow the development of a ear- bunculous ulcer upon the toe pads. Course. The development of the disease and the succes- sively appearing symptoms as well as the general picture of the affection show great variations from case to case. While sometimes only half an hour passes from the onset of the dis- ease until death, in other cases the duration extends to two and more, exceptionally to 7 days. In slow cases the intensity of the symptoms may decrease temporarily so that the patients are somewhat brighter, and take some food, but the improve- ment is followed after a shorter or longer period by new at- tacks, and the disease may even assume an intermittent charac- ter (anthrax intermittens) in which the animal becomes greatly emaciated under periodical febrile symptoms. The species of the animal affected, influences considerably the manifestation of the clinical picture. Anthrax in horses . is usually marked by symptoms of a severe spasmodic colic in which quite frequently edematous swellings develop on the neck and chest. In cattle only symptoms of a general febrile affection are usually observed, but hemorrhages from the in- testines as well as edematous swellings are not very rare. Anthrax in sheep usually runs a rapid course without localiza- tion to certain regions, acting like a pure septicemia, and the apoplectic form occurs most frequently in these animals. *An- thrax in goats is less acute. Hogs usually die in 1 to 2 days with symptoms of asphyxiation due to the extension of pharyn- gitis. ” Diagnosis. 19 Diagnosis. It is hardly possible to diagnose with certainty the peracute case of anthrax on the living animal, as acute hyperemia and acute edema of the lungs as well as edema of the glottis, further congestion of the brain (sunstroke) and hemorrhages into the brain substance resulting from other causes may kill the animal under very similar manifestations. In the less acute cases anthrax is indicated principally by the appearance of the rapidly extending edematous swellings as well as by the bloody. feces and urine, but even in this respect hemorrhagic septicemia very closely resembles anthrax (on post mortem the acute swelling of the spleen is always absent in the former). Likewise anthrax may be also suspected in severe gastro- intestinal inflammations, especially when associated with in- testinal hemorrhages, while in horses, on account of the severe abdominal pain, colicky affections, invagination and volvulus of the intestine, may be chiefly confounded with it, and particu- ‘larly so when, as sometimes happens, there are no characteristic symptoms present other than those of colic. In cattle blackleg and malignant edema are differentiated by the cold and crepitat- ing consistence of the swelling in the latter diseases, as well as by the peculiar sour, disagreeable odor of the fluid which is contained in the swellings of anthrax edemas. In hogs, especially when suffering with pharyngitis as a result of an infection with the virus of buffalo disease, the resemblance to anthrax is so pronounced that a differentiation is only pos- sible by additional circumstances (prior cases in_ buffaloes). Finally, poisonings occasionally come into consideration, in which, however, a rise in the body temperature occurs only in the later stages. The diagnosis is certainly established by the demonstration of bacilli in the blood of the living animal which in size and form resemble anthrax bacilli, as there is no other disease known in which bacteria in any way resembling these would circulate in the blood; unfortunately, they can be demonstrated in the blood only a short time—not earlier than 16 to 18 hours —before death. Characteristic indications on post mortem are the dark-red color of the uncoagulated blood, the acute swelling of the spleen and the lymph glands, bloody edema in the subserous and sub- cutaneous connective tissue and also hemorrhagic enteritis. These findings retain their importance even in case of negative bacteriological examination. However, in exceptional cases the enumerated changes and also swelling of the spleen may be absent. In such cases the bacteriological examination alone will give enlightenment. If the careass is fresh, not older than 24 hours, then the presence of large, non- motile rods and short chains in the blood. which has been taken from vessels distantly located from the intestines, such as a superficial vein, 20 Anthrax. is certain proof of anthrax, particularly when by staining the presence of a capsule can be demonstrated. If, however, a longer time has elapsed after death, especially in summer time, other bacilli, first in importance bacilli of malignant edema, may have migrated from the intestines into the blood, and these in many instances can only be differentiated from anthrax bacilli by cultural methods and animal inoculations. Bacteriological diagnosis. Relative to distinguishing anthrax bacilli from other bacteria more or less closely resembling them the following is to be noted: 1. Anthrax bacilli are present in the blood of fresh carcasses; they are thick, rounded at the ends or squarely cut. They usually have a distinctly recognizable capsule and form chains of 2 to 4, rarely more, segments, in which the individual segments are separated from one another by light cross lines; they are aerobic and never produce spores inside the animal tissues and body fluids. Subcutaneous or intravenous injections kill mice, guinea pigs and rabbits, in which after death the blood usually contains the bacilli in great numbers. ; 2. The bacilli of malignant edema are more slender, motile, rounded at the ends, and besides, the edematous swelling, fluid of the abdominal cavity and blood of the portal vein contain curved thread-like forms of various lengths, some homogenous, others beaded. In older car- casses many of the bacilli contain in the center one oval spore each; they are strictly anrobic, liquefy gelatin, and form gases even in coagulated blood serum. Intravenous inoculations are harmless; sub- cutaneous inoculations into test animals produce a rapidly extending edematous inflammation with gas formation. 8. Blackleg bacilli are present only in the serous fluid of the crepitating swelling in a fresh carcass; they are comparatively short and thick, motile, never grow in form of threads, and produce in the animal body shortly after death, oval spores located either at the end or in the center of the bacillus. They may be grown anaerobically but also aerobically; liquefy gelatin slightly ; and in coagulated blood serum they do not produce gas. Intravenous inoculations are harmless; sub- cutaneous or intramuscular inoculations kill the guinea pig and mouse, but rabbits only as an exception. In the examination of material which is no longer fresh, various putrefactive bacilli (Bac. subtilis, Bac. termo) come into consideration, particularly those resembling saprophytes, the Bac. pseudoanthracis described by Burri & Baas, as well as the Bac. anthracoides found by Hueppe & Wood. They are found frequently in blood or parts of organs that have been stored, and they have some characteristics in common with the anthrax bacillus, but may be distinguished by the absence of other characteristics of the true anthrax bacillus (Hoppe). Further, they coagulate milk after a short time and do not form cap- sules in inactivated horse blood serum. The anthrax bacillus may be demonstrated in most instances in sufficiently fresh material by a microscopical examination for which the various capsule stain- ing methods are especially adapted (according to Johne, staining with heated 2% gentian violet solution followed by a quick discoloration with 2% acetie acid; according to Olt with 3% safranin solution also with heating; according to Raebiger staining of the air-dried smears with formol-gentian violet (100-150:10-15); further, Gram’s stain with subsequent eosin treatment). The material for exam- ination should be taken from the blood or spleen of very fresh carcasses; later Bacteriological Diagnosis. Prognosis. 21 from a peripheral vein (ear or jugular) as putrefaction sets in later in these parts than in the internal organs. As a result of putrefaction the bacilli change their form after a time; they become morg slender; their plasma does not stain well, and later not at all; at the same time other bacteria and especially anaerobic putre- factive bacteria multiply very rapidly. The capsule of the anthrax bacillus is preserved somewhat longer so that after a time only empty capsules or the remains of plasma envelopes can -be seen (See fig. 2 on page 3). They finally become unrecognizable (according to Olt, in the summer time in about 48 hours). Its diagnostic importance, however, should not be overestimated as a capsule may occa- sionally occur on some putrefactive bacteria resembling the anthrax bacillus (Noetzl), and on the other hand sometimes they cannot be demonstrated even on true anthrax bacilli, especially in the blood of horses and carnivorous animals. According to Cinca & Fenea the feces of affected animals (sheep and hogs) invariably contain anthrax spores which can be isolated through cultural methods by a previous heating to 65°C. This is possible even in cases in which the carcass is already putrid and the examination of the blood gives negative results. In the examination of stale blood or material from organs good results may sometimes be obtained by the mucin reaction which was first described by. Weichsel- baum (1892), later by Heim and recently recommended by MacFadyean. This reaction is manifested in smears stained with 1% methylene blue solution by the appearance of violet or purplish-red granules which are seen near the bacilli and originate from their capsules. Positive results are obtained in doubtful cases by the isolation of the anthrax tacillus by the plating method. According to Bongert the bacilli remain active in dried blood for 36 to 50 days, in putrefied dried blood or tissue fluids for a shorter period. However, they retain their virulence on an average of from 8 to 20 days. In carcasses which have lain unopened the results from the examination of smear preparations are uncertain even after 24 hours, while by the plating method they may be demonstrated for 2 or 3 days after death. Finally, the diagnosis may be proved by animal inoculations, for which the usual Jaboratory animals, with the exception of the rat, may be utilized (to prevent an intoxication only small quantities of the material should be used for inocula- tions; the scarified shaven skin is best adapted for the inoculation of putrid material). Suspicious material forwarded for an accurate bacteriological examination is best prepared by spreading the softened pulp of the spleen from 3 to 4 mm. tnick on a slide, across each end of the slide a strip of thick cardboard is placed, and another slide is then placed on these pieces of cardkoard.. They are then securely tied and forwarded in a box for examination (Kitt, Bongert). Another method consists in breaking a boiled potato in two; the blood or spleen tissue having been smeared on one of the broken surfaces, the pieces are placed together again and the whole forwarded to its destination (Olt). Further, the blood or spleen pulp may be dried on the inner surface of a test tube, or on woolen threads or cotton pads (Heim, Mazzini). : Jakobsthal & Pfersdorff, as well as Marxer and Eberle, recommend for the above purpose quadrangular pieces of gypsum rods saturated in Loeffler’s bouillon and placed in strong test tubes. Before use they are dipped in pure water, then covered with a thin layer of blood or splenic pulp, placed in the tube, which is packed in a wooden case and forwarded to the laboratory. Inasmuch as the bacilli form spores on the rods in a proper temperature the diagnosis is possible even after 14 months. Instead of gypsum rods small pieces of burned bricks are also adapted (Reinecke), or even better filterpaper rolls about the thickness of the small finger and moistened in water (Schiller, Grabert). Prognosis. Obviously anthrax terminates not infrequently in recovery, although it is hardly possible to estimate the per- centage of recoveries with any degree of certainty. In the course of various outbreaks it is a quite frequent occurrence that some of the animals which were exposed to the infection show an indisposition and fever, but recover completely in 1 to 2 days. Such passing affections are probably the result of an anthrax infection, which, however, is overcome by the energetic resistance of the animal. Toward the end of some epizootics the disease often assumes a subacute form and then nN 22 Anthrax. cases of recovery are more frequent. The prognosis is most unfavorable in the peracute cases, and most favorable in the primary local skin affections as long as there are no intensive general disturbances to indicate the entrance of the bacteria into the blood circulation. The development of edematous swellings in the course of the febrile affection is almost in- variably of unfavorable significance, while the appearance of bacilli in the blood is indicative of approaching death. Treatment. In primary local affection of the skin, sub- cutaneous tissue or the visible mucous membranes, surgical treatment is first indicated. This consists in deep incisions of the swellings, and after thorough squeezing and scraping, the wound is repeatedly washed and cauterized. Cross incisions -are advisable, while large swellings may be incised in several places. As disinfectants the following are recommended: Corrosive sublimate (1-1000), carbolic acid (3%), creolin (5%), ete. Good results are also obtained from subcutaneous injec- tions at various places in the periphery of the swelling with 2-3% carbolic acid or 5% creolin solution, and covering with a carbolic dressing. In cases of generalized disease which are not yet far ad- vanced the treatment with immune serum (see page 28) gives remarkably good results. After the intravenous injection of 40-80 g. of sufficiently active serum the temperature falls rapidly, frequently within as short a period as 6 hours, and this is followed by a complete recovery after 12 hours (Jaeger, Detre, Raebiger, Gal and others). In cases in which no im- provement is observed after a few hours, or in which the tem- perature rises, it is advisable to repeat the serum injection. Serum of high potency proves effective even in small doses and in subcutaneous applications. Sometimes favorable results may be obtained from symp- tomatic treatment, viz., repeated bathing with cold water, rub- bing with camphor, turpentine or pure alcohol. Internally wine, alcohol or camphor may be given; also subcutaneous in- jections of ether or camphor, etc. In the presence of an in- testinal infection the administration of disinfectants in large doses is indicated, such as creolin or lysol (larger animals. 20-50 gm., smaller animals 5-10 gm. or even larger doses) ; creo- sote (5-10 and 1-2 gm., respectively), carbolic acid (according to Hess 40-50 ec. of a 14% solution daily), calomel in small and frequent doses (for horses, with 14. gm. opium) and oil of turpentine (for larger animals 200-300 gm. mixed with sweet oil). Enemas with disinfecting fluids may also be tried, es- pecially in cases in which the symptoms indicate a severe af- fection of the rectum. Intravenous injections of collargol (1 gm. dissolved in 50-100 gm. of water) are also recommended. The sick animals should be provided with well-ventilated, shady and cool quarters. They should receive an abundant Treatment. Prevention. 93 supply of fresh water, preferably water which has been slightly acidified with hydrochloric acid. Bleeding, which is still practiced, produces only temporary beneficial action in the presence of pulmonary congestion, but should be performed cautiously on account of the danger of spreading the infection. Prevention. In order to protect healthy animals from in- fection care should be taken that the food, drinking water, utensils, ete., which are accessible to them, and also the ground, should not become contaminated by the excrement, blood, ete., of animals affected with anthrax. In cases, however, where this has occurred the infectious substances should be destroyed or at least propagation of the infection should be prevented. ‘This can be accomplished by the destruction of, or by rendering harmless all products and excretions of the affectéd animals and carcasses. The safest method for the destruction of the infectious material is by burning or rendering (steaming the carcasses under high atmospheric pressure should be em- ployed to the greatest extent possible owing to the advantages afforded by this method). When this is impossible the carcasses should be buried at least. 2 meters deep in out-of-the-way, fenced-off places. They should also be covered with disin- feetants, preferably powdered unslaked lime. The stalls oc- cupied by the affected animals should be thoroughly disinfected. All food and straw that has come in contact with affected ani- mals or their carcasses, or which has been contaminated by their excrement or blood should also be burned. In common practice the best disinfectants are boiling water and steam, 0.1% corrosive sublimate, 5% carbolic acid, creolin or lysol solutions; also formalin vapors. However, it is necessary for these substances to remain in prolonged con- tact with the material to be disinfected owing to the great and variable tenacity of the anthrax spores. . According to Grossenthaler peat possesses disinfecting qualities on account of the ulnie acid it contains, and this action may be increased by the addition of 3% sulphuric acid. Hides may be disinfected with 5% creolin or lysol, but this method is only absolutely successful when employed within two hours after the death of the animal (Ligniéres & Zabala), otherwise it frequently fails. As a matter of fact at the present time there is no method known for an effective dis- infection of hides without injuring them for their technical utilization (Xylander). Brekle believes that the question may be solved by subjecting the spore-containing hides in a moist condition to a temperature of 43-44°C., by which all spores would germinate and the hides accordingly would contain only sporeless bacilli which could be destroyed with milk of lime. Horse hair is effectively disinfected by dry heat at 110°C. followed by steam at 100°C. (deRossi; see also page 5). : The officially required disinfection of railroad stock cars in Germany with 5% ‘‘Kresulfol’’ (cresol-sulfonie acid) was found by Schniirer to be absolutely ineffective against anthrax spores, and he recommended instead the disinfection with 44% formaldehyde solution. When the disease appears careful search should be made for the source of the infection (origin of food, drying of hides in the hay loft, or in the stable, etc.). If suspicion is directed to the forage from certain fields or meadows this supply should not be fed, at least not while the animals are susceptible to the disease. Should the disease occur in a pasture the healthy 24 Anthrax. animals should be removed to another higher and dryer place. When necessary they should be stabled. Not infrequently a careful investigation of the’ pasture will disclose dangerous places from which the animals should be kept. In other cases it is possible to suppress an outbreak by the exclusion of pol- luted, muddy watering places. In suspected places the danger- ous character of the soil may be eliminated by draining and cultivation. If under existing circumstances the danger of infection cannot be excluded, and the presence of a threatening infec- tion exists, it is advisable to reduce the natural susceptibility of the animals by protective inoculations thereby protecting them from the danger of infection. Immunization. Domestic animals may be immunized in practice by attenuated living cultures of the bacilli, by spore- containing cultures, by immune serum, and finally by immune serum and living cultures. I. Immunization with attenuated cultures (Pasteur’s method). In 1881 Pasteur established by conclusive experi- ments that anthrax bacilli, when subjected to a temperature of 42-43°C., will continue for a time to multiply actively and no longer form spores. He further found that in such cultures the bacilli die in about a month, but that in the meantime their virulence decreases gradually, and finally he proved that the . bacilli, when attenuated to a certain degree, will retain this degree of virulence if their cultivation is continued at body or room temperature. On this experimental observation is based the practical method of protective inoculation worked out by Pasteur with the co-operation of Roux and Chamberland. ’ The vaccine is prepared by growing the anthrax bacilli in bouillon at a temperature of 42.5°C. The cultures which are at first fatal for rabbits, guinea pigs and mice are, after 12 days’ growth:at the above temperature, attenuated to such degree that they are only exception- ally fatal to rabbits. After an additional 12 days the culture kills only young guinea pigs and mice.” After the virulence of the culture has been attenuated to these degrees their cultivation is continued at 35-37°C. With such stock cultures fresh bouillon cultures are inocu- lated, and in this manner the vaccine is prepared in any desired quantity. The more attenuated culture represents Pasteur’s first, the weaker vaccine, while the less attenuated is the second or stronger vaccine (premier et deuxiéme vaccin). The protective inoculation is carried out by first injecting subcutaneously the weaker, followed in 10 to 12 days by an injection of the stronger vaccine. The immunization is based on the principle that the first inoculation reduces the natural susceptibility of the animal to such an extent, without endangering life, that it withstands Immunization. Pasteur’s Method. 45) without injury the second inoculation with the stronger vaccine. Without the first injection the second inoculation would prob- ably prove fatal, while the two inoculations confer the neces- sary immunity upon the animals. The results of the vaccination are in general satisfactory in view of the experience obtained from a large number of cases. Some of the immunized animals do not resist an artificial - infection by feeding repeated large quantities of spores (in Koch’s experiments 2 out of 10 sheep died after feeding them for days with virulent spores in quantities of the size of a’ hazelnut). These are exceptions which have no influence on the practical value of vaccination, inasmuch as under natural conditions the intensity of the infection is far below the amount given in these artificial infections. Where vaccination is prac- ticed in large herds the losses from anthrax in the year follow- ing are in general greatly reduced compared with periods in which the animals were not vaccinated. In numerous localities where the disease raged regularly year after year it has almost entirely vanished as a result of vaccination of the animals. Not infrequently vaccination immediately checks the spread of the disease in a herd. The immunity reaches the necessary degree in about 10 to 12 days after the second inoculation, and lasts about one year. (In the experiments of Azary vaccinated sheep resisted the artificial infection even after 8 months.) A longer duration of the artificially produced immunity is doubtful, and there- fore a repetition of the vaccination is indicated annually in pronounced anthrax districts. The breed, age and sex of the animals do not appear to influence the results of the vaccination, and young animals which were only shortly weaned may also be vaccinated without danger and with promising results. Pasteur’s protective vaccination is therefore indicated in all places where the annual losses from anthrax exceed the cost of the vaccination. The effectiveness of the vaccination has been proved by Pasteur beyond a doubt through control experiments which he carried out be- fore a commission appointed for this purpose in 1881 at Pouilly-le- Fort. Of 50 sheep 25 were regularly vaccinated with his two vaccines and 14 days after the second vaccination they were inoculated with anthrax material, together with the 25 control animals. The results showed that inside of 2 days all of the 25 control animals died of anthrax, while all of the 25 vaccinated sheep remained alive. Up to the end of the year 1899, 708,980 cattle and 4,971,494 sheep had been vaccinated successfully in France, as a result of which the entire annual loss over a period of 12 years dropped to an average of 0.34% in cattle and to 0.94% in sheep. In Hungary the first vaccinations were carried out in 1881 on Azary’s initia- tive.. Thuillier, Pasteur’s assistant, applied them first at the Veterinary Institute at Budapest with very favorable results, while the later ones in Kapuvar were less favorable. As vaccination gave very good results in practice, this protective treat- * ment was soon taken up very extensively. During the period of 15 years between 1886 and 1900, 53,843 horses, 1,015,700 cattle and 2,279,221 sheep were vaccinated. 26 Anthrax. The official report contains the results on 39,506 horses, 718,266 cattle and 1,247,331 Sheep, and according to its statements the percentage of vaccinated animals given below died of anthrax: Horses. Cattle. Sheep. After the first vaccination................. 0.10% 0.02% 0.26% In the course of following years............ 0.09% 0.02% 0.33% Dotal,» cvcecsankaatc si ninendecdacas sinew ts. “O19: 0.04% 0.59% In Germany the results were at first less favorable (in Packish during the period 1882 to 1888 the entire loss of vaccinated cattle amounted to 3.1% and of vaccinated sheep 2.8%). Later, particularly in Wiirttemberg and Alsace-Lorraine, the results were more satisfactory. Since 1900 in the vicinity of Magdeburg over 2,000 cattle, mostly draft oxen, have been vaccinated annually with uniformly good results, and since that time the previously frequent intestinal catarrhs (slight anthrax infections?) are no longer observed (Jungklaus). In Austria vaccination was carried out on 9,456 fattening cattle with complete success during the period between 1894 and 1898. It was observed, however, that the vaccination of such animals during the summer months caused a severe reaction. In Russia vaccination has also been followed by uniformly good results, with the exception of the fatal vaccination in the Crimea (1888), which was supposed to be due to an error in the vaccines, in which instance 4,564 sheep were vaccinated and 3,478 died in the course of a few days. The total loss in the district of Cherson, in which 20,000 sheep were vaccinated during the years 1885-1888, amounted to 0.87% compared with previous losses of 10% to 33% in former years (Wysokowicz). Similar good results followed vaccinations in Holland (Wirtz), in Switzer- land (Hess), as well as in America (Dalrymple), and Australia. Direct results from the vaccination. In the vaccinated animals a slight elevation of temperature is observed as a rule in 2 to 5 days, which, however, is rarely accompanied by perceptible disturbances in the general health. Not infre- quently in cattle an extensive subcutaneous edema develops in the vicinity of the point of inoculation, which, however, disappears in 1 to 3 days, especially if cold applications are made. Exceptionally, pregnant animals abort or give premature birth. In milk cows a diminished quantity of milk may be observed. Anthrax bacilli, however, do not pass into the milk as a result of the vaccination (Nekljudow). Fatal results may sometimes follow even when the vaccination is earried out correctly, with faultless vaccine, probably as a result of the low individual resist- ance of the animal. In several instances of this kind numerous losses were observed. Thus, excepting the case mentioned in the Crimea after the first vaccination in 1889 of 1,383 sheep in the Hungarian township of Lukacs, 77 sheep and 44 lambs died of anthrax, and in Guta in 1893 out of 1,564 vaccinated horses 72 died within 2 weeks after the first vaccination. The autopsies in this case revealed a septicemic complication in the form of a suppurative inflammation of the serous membranes, and a necrosis of the muscles at the point of inoculation, which was caused by a rod-shaped bacterium (Preisz). In Fokté, of 680 horses 38 died in 1896 of anthrax in two weeks following vaccination. In this case the post mortem revealed a severe intoxication and anthrax bacili in association with other bacilli were found exclu- sively in the edematous swellings at the point of inoculation (Preisz). In the vicinity of Debreczen, of 30 horses vaccinated in 1902 with vaccine prepared for cattle, 9 became severely affected, 6 of which died of anthrax. In Austria, 316 cattle were vaccinated in the township of Storozynetz (Bukowina) in 1893, and among these 265 were fattening cattle. On the day following all animals mani- fested fever, dyspnea, bloody, foamy discharge from the nose and rectum, and 24 died inside of a few hours from peracute anthrax. In cases in which the vaccine acted too severely the indication appears inside of a week following the first, or more frequently the second vaccination in which a marked edema develops from the point of inoculation followed by a general infec- tion and the usual post mortem lesions of anthrax. In some cases the animals do not become visibly affected until after three weeks of incubation, in the meantime manifesting a disturbed appetite, finally succumbing to cachexia, which points to a chronic intoxication. After the vaccination of already infected herds the occur- rence of deaths may be the result of latent infection (see page 8) as in these bacilli carriers the resistance may possibly be reduced by the vaccination. The attenuated bacilli contained in the vaccine retain their cultural charac- . teristics in the body of the vaccinated animal (according to Preisz they form soft, Immunization with Spore-containing Vaccines. 27 rapidly liquefying capsules) as well as their reduced virulence, which cannot readily be increased even if passed through guinea pigs (Ascoli). Technic of vaccination. The vaccine prepared by the ‘‘Institut Pasteur’’ or by the ‘‘Laboratoires Pasteur-Chamberland’’ which are established in the various countries, is marketed in small bottles closed with rubber stoppers. The vaccine is drawn up into a sterilized syringe of about 1 ec. capacity, the plunger of which is graduated into 8 parts, and sheep, calves and foals are injected subcutaneously with 1 of the contained vaccine, while mature cattle and horses receive %4 (about 0.12 and 0.25 ec.). The injections are made in sheep on the inner surface of the thigh; in cattle posteriorly to the shoulder; in horses on the side of the neck. Prior to the injection the site should be clipped and carefully disinfected. Twelve days fol- lowing the first vaccination the second injection is made at the corresponding place on the opposite side of the body. The vaccine retains its potency for several days when kept in a dark and moderately cool place. Its effectiveness, however, is changed in time. It should therefore be fresh, and the contents of an opened tute should be used up by all means on the same day. Good vaccine when shaken is only very slightly cloudy, rather opalescent; more pronounced cloudiness is an indication of deterioration (contamination with foreign bacteria), and such vaccine should not be used under any circumstances. The vaccine is prepared in a somewhat different way for the various species of animals, and therefore vaccine for a specified species should be used. This is particularly applicable in the vaccination of horses (in horses, a mix- ture of the first and second vaccine of cattle is used for the second vaccine, and is therefore Jess severe than the second vaccine for cattle and sheep). The best time for vaccination is the spring, as anthrax usually occurs during the summer months, and an attempt should therefore be made to establish an immunity of the susceptible animals shortly before the period of danger. ; Results obtained from the use of contaminated and ineffective vaccines pre- pared by the various laboratories indicate that official control is urgently desirable. Bad results from vaccination cannot be excluded with certainty. On the one hand they may be due to the uncertainty of the degree of virulence and purity of the vaccine, while on the other hand the variance in the individual resistance and ~ susceptibility of the animals must be taken into consideration; and the veterinarian making the vaccinations is unable to judge these factors. Therefore owners of animals should be informed beforehand of the possible dangers. Errors com- mitted during vaccination, especially neglect in the required cleanliness, may nat- urally endanger the results, as in such procedures other pathogenic bacteria may enter the body and produce a passing or fatal disease. During the days immedi- ately following vaccination the animals should be fed :regularly and should not be exposed to cold or heat, or overtaxed by hard work. As they are particularly sus- ceptible to the infection during this time (negative phase) they should be kept from suspected pastures. II. Immunization with Spore-containing Vaccines. Cien- kowsky (1884) in Charkow produced two vaccines by attenua- tion of living cultures at higher temperatures, the weaker of which kills the mouse and the earless marmot, but not the rabbit and sheep, while the stronger kills 30 to 50% of rabbits, and 10 to 20% of sheep. The cultivation of the attenuated cultures is then continued in bouillon at body temperatures until an- abundance of spores are formed, when it is mixed with two parts of glycerin and placed in stock. Before the vaccination fresh cultures are made from the spore-containing fluid, and with these the animals are injected (Gordzialkowsky) or ‘the spore-containing fluid itself is employed for the vaccination. According to Rajewsky the fluid containing the bacilli and spores remains effective for a longer time in a cool, dark place. Otherwise both in the technique as well as the valuation of this form of vaccination the same rules are followed as in Pasteur’s method. The dose of the vaccine consists of 0.1 cc. for sheep, and 0.2 ec. for larger animals. The animals usually stand the vaccination well, but disagree- able accidents are not totally excluded. Thus, 100 cattle were vaccinated in 1902 28 Anthrax. in one estate and in three weeks’ time 44 became affected with anthrax, 35 dying of the disease. : Satisfactory results are obtained in many places with spore-containing vaccine. This method was also employed several years ago in Hungary (according to Detre, with vaccines which he prepared by washing old agar cultures with a salt-glycerin- water mixture). -In 1901 to 1902 the losses amounted, according to Detre’s esti- mate, to 0.26% in horses, 0.03% in cattle and 0.12% in sheep. According to a report of the Veterinary Institute at Charkow, Russia, 5,584 horses, 19,572 cattle and 174,172 sheep were vaccinated in 1897 in the southwestern part of Russia with losses of 0.25, 0.09 and 0.35% respectively. In Russia a method of vaccination originated by Lange is also used. The preparation of this vaccine, however, is unknown. According to Beinarowitsch the direct loss in reindeer from vaccination amounts to 1%. 7 III. Immunization with Immune Serum. If animals sus- ceptible to anthrax are injected with increasing doses first of attenuated and later of fully virulent anthrax cultures, they will after a certain time produce a serum, which, while possess- ing no direct bactericidal action, protects rabbits, guinea pigs and sheep against a fatal infection. If injected shortly after the infection such serum even prevents the development of the disease. Such immune serum also renders good service in practice, especially in cases in which infection threatens, or where anthrax has already appeared in a herd. The action of the injected serum becomes effective in the course of a few .hours. However, the established passive immunity is only of a short duration, lasting only from 1 to 2 weeks. It is therefore advisable in cases of continued danger of infection to render the animals actively immune. This may be accomplished by a subsequent regular vaccination with attenuated cultures by one of the above described methods. Potent anthrax serum was first prepared from sheep by Marchoux, and also by Sclavo almost at the same time, in 1895. Later: Sobernheim, Mendez, Detre, ‘Carini and Ascoli carried on investigations along this line, but they employed large animals, especially horses, for this purpose. This method was also followed by Sclavo. The horses withstand after a certain time an intravenous injection of 500 ce., and even more of a virulent culture; and they produce a very potent serum. Of Sclavo’s serum 0.5 ce. protects a rabbit and from 5 to 10 ee. protect a sheep against a fatal infection. Detre’s serum has a similar effect on rabbits, while from 3 to 5 ee. will protect a guinea pig against an intraperitoneal infection, which is ordinarily fatal in from 1 to 1% days. In the experiments of Sobernheim, of whose serum 2 cc. protects rabbits against 1/1000 of a loopful of a virulent culture, the serum proved a protective agent even against the feeding of anthrax spores. San- felice prepared a serum by immunizing dogs, and 3.5 ee. of this serum per kilo weight had a protective effect, while 7 cc. had a curative effect on rabbits even when administered 40 hours after the infection. In practice the dose for large animals consists of 10 to 20 ec., while for small animals it is 5 ec. Sobernheim uses a mixed serum which is obtained from cattle, horses and sheep; Sclavo obtained it from asses. Even when exposed to the harm- ful influences of light and air the serum retains its potency for 2%4 years (Sobern- heim). In already infected herds the spread of the outbreak may be checked by treat- ing only those animals with serum in which a rise in temperature is observed; the temperature of all animals being taken twice daily (Keleti). Of course, if fever is present the serum should be used in correspondingly higher doses, and the injec- tions should be repeated until a drop in the temperature is noticed. In some cases after the administration of the serum, anaphylactic symptoms appear. These occur in from 5 to 20 minutes, and are manifested by edematous Immunization with Immune Serum. 99 swellings of the head, at the point of inoculation and other parts of the body. Nodular eruptions resembling urticaria, frothy discharge from the mouth, snorting, reddening and swelling of the mucous membranes, uneasiness, and in cattle bloat- ing, may also be observed. Kovarzik observed these symptoms in two herds in about 20% of the inoculated cattle, among which the two showing the strongest reactions died from asphyxiation. Inasmuch as the reaction appears well pronounced in animals that were especially exposed to the danger of infection, Kovarzik and also Zimmer, from his experience in horses, are inclined to believe that such an affection is a reaction, indicating an already existing latent infection (anaphylaxis due to proteids of the bacilli which circulate in the blood of the latent infected animals, against the analagous proteid contained in the immune serum). IV. Immunization with Immune Serum and Cultures (Sobernheim’s method). Sobernheim (1902) recommends for a lasting, combined, passive and active immunization of do- mestic animals a simultaneous vaccination with serum and anthrax cultures (cattle and horses are injected on one side of the body with 5.0 ce.; calves with 3.0 to 5.0 cc. and sheep with 4.0 ec. of an immune serum; and five minutes later, they are injected on the opposite side with 0.5 or 0.25 ec. of an attenuated culture, washed in salt solution, the degree of viru- lence of which corresponds with Pasteur’s second vaccine). This method has the great advantage of requiring only a single treatment of the animals, and the results obtained from it are, with the exception of a few failures, quite satisfactory. Svarde (1906) however, claims that the superiority of this method over Pasteur’s has not been established. After vaccination there is usually a moderate elevation in tem- perature of 0.5 to 1.0°C., slightly diminished appetite and milk secre- tion. A swelling often occurs at the place of inoculation. The nasal mucous membrane may be swollen, and an exanthema resembling urti- caria may be observed. Occasionally the vaccination results in the death of the animal (most often observed in work oxen). In Argentine and Uruguay this method of vaccination was employed from the spring of 1904 to September, 1905, on 140,000 cattle, 30,000 sheep and 2,000 horses. According to Sobernheim no fatalities resulted from the vaccination, and almost everywhere a complete eradication, or at least a marked restriction of anthrax was noted. In Germany, according to Sobernheim’s statistics, up to the year of 1906 about 4,500 cattle and sheep were successfully vaccinated. Raebiger & Johnk reported very satisfactory results, although some failures were also observed by them. Accord- ing to other reports, however, the results appeared unfavorable. Thus, according to Burow, of 5,000 cattle vaccinated by this method in Pommern, 8 (0.15%) died as a result of the vaccination; besides, from 4 to 7 weeks later 3 (0.08%) additional deaths resulted from anthrax. In one instance, of 39 vaccinated cattle, 3 died; in another case, of 137 cattle, 37 showed indications of anthrax inside of 5 days of which 8 died (Heine). Unsatisfactory results are further reported by Hummel (losses from vaccination, 139 sheep) and Lothes (of 78 cattle, 2 deaths, 17 severe affections, marked diminution in milk secretion in cows). V. Other Methods of Vaccination. Previous to the experi- ments of Pasteur, Toussaint (1880) vaccinated with anthrax blood heated for 10 minutes at 55°C., or mixed with 1% carbolic acid. Chauveau (1883) prepared a vaccine by heating bouillon cultures which were grown at 42.5 to 47°C., then kept at 37°C. until spore- formation, and finally heated to 80-84°C. Other vaccines were made 30 Anthrax. by subjecting the spores to a pressure of approximately 8 atmospheres, also by growing the virus in pure oxygen and under pressure of 214 atmospheres. According to Sobernheim, Chauveau’s method of immunization is used in Chile, where 80,000 to 85,000 animals are vaccinated annually by that method; the results are indicated as being favorable in cattle, but only fairly good among sheep. According to Chamberland & Roux, the action of a mild solution of carbolic acid (1:600) on anthrax bacilli for 24 days will attenuate them to such an extent that they represent protective vaccines. The same result is obtained by the action of bichromate of potassium (1:2000-5000) for 10 days, and according to Gibier by cooling to —45°C., whereas Murillo prepares a vaccine which is also supposed to be satis- factory in practice by growing the culture alternately in diphtheria toxin and in bouillon. Arloing, and also Hankins succeeded in immunizing test animals with bacteria-free filtrates of culture. Similar results were obtained by Ogata & Jasuhara with a ferment from the blood serum of anthrax animals. Aujeszky also succeeded with a mixture of anthrax bacilli and spleen tissue, and also with the spleen pulp alone. According to Emmerich, Pawlowsky, Bouchard, Gilruth and others, an immuniza- tion is possible by the treatment with organisms which are antagonistic to the anthrax bacillus (see page 6). Finally, Bail (1904) used for the immunization the sterilized edema fluid of anthrax animals. He presumed that the aggressins (lysins in the sense of Kruse) of the anthrax baillus, which are present in the edematous fiuid, favor the development of the pathogenicity of the bacillus, and.if injected into an animal they would stimulate the production of antiaggressins which would protect the animal against a bacillary infection. Sheep which received 2.5-10 ec. of such edema fluid subcutaneously developed an immunity even against severe sub- cutaneous infection with bacilli in from 8 to 10 days. If, however, a certain quantity of the edema fluid is exceeded the body is unable to use it up, and because of the increased aggressins present a hypersensi- tiveness to infection develops. This method has not yet been tried in praetice. Veterinary Police. The veterinary police regulations refer in the first place to the harmless disposition and destruction of all excrements of anthrax animals, and to the cremation, rendering or deep burying of their carcasses. Diseased animals should be kept separated from healthy ones, and their stalls should be disinfected. The food and straw which have come in direct contact with affected animals should be rendered harmless; meat, milk and raw products in general (also hides) of affected animals should not be permitted to enter the trade. On the other hand, quarantine restrictions for healthy animals with the exception of severe outbreaks do not appear justified as the disease is not directly contagious. Literature. Gerlach, Mag., 1845, XI, 113; 1846, XII, 321—_Heusinger, D. Milz- brandkrkh. d. Tiere u. d. Menschen, Erlangen, 1850 (Old Lit.)—Pollender, Viertel- jschr. f. ger. Med., 1855, 102.—Brauell, V. A., 1857, XI, 131. Davaine, C. R., 1863, LVII, 320; 1864, LIX, 393.—Bollinger, Beitr. z. vergl. Path., 1872, 122; D. Z. f. Anthrax in Man. 31 Tm., 1885, XI, 160.—Koch, Beitr. z. Biol. d. Pflanzen, 1876, II; Mitt. d. G.-A., 1881, I, 49.—Pasteur, C R., 1877, LXXXIV u. LXXXV.—Pasteur, Chamberland & Roux, C. B., 1880, XC u. XCI; 1881, XCII.—Oemler, A. f. Tk., 1800, VI, 401.—Koch, Mitt. d. G.-A. 1881, I, 184; 1884,°II, 161.—Léffler, Ibid., p. 49.—Roux & Chamberland, A. P. 1887, I, 513; 1888, II, 405 ——Kitt, Monh., 1894, V, 215 (Review on diagnosis). —Sclavo, Chl. f. B., 1895, XVIII, 744.—Sobernheim, Z. f. Hyg., 1897, XXIV, 301; Hb. f. p. M., 1904, ITI; 1904, IV, 793 (Lit. on etiol. and vaccination).—Conradi, Z. f. Hyg., 1899, XXXI, 323 (Lit. on toxins).—Bongert, Chl. f. B., 1903, XXXIV, 497.—Preisz, Cbl. f. B., 1904, XXXV, 280; 1907, XLIV, 209; 1909, XLIX, 341.— Ernst, Monh., 1905, XVII, 172 (Lit. on diag. meth.).—Oppermann, A. f. Tk., 1905, XXXII, 41 (Lit.).—Gruber & Futaki, M. m. W., 1907, 249; D. m. W., 1907, 1558.— Wyssmann, Schw. A., 1907, XLIX, 287 (Lit. on anthrax in hogs).—Xylander, Arb. d. G.-A., 1907, XXV, 457._Fischoeder, Chl. f. B., 1909, LI, 320 (Lit. on capsule formation).—Hoppe, Diss., Leipsic, 1909 (Lit. on pseudo-anthrax bacilli). Anthrax in Man. Anthrax in man usually oceurs as a local affection of the skin and subcutaneous tissue (carbuncle, pustula maligna, carbunculus malignus) as a result of skin infections. There- fore it is chiefly persons who come in contact with diseased or dead animals who become affected. The persons who most commonly receive accidental infections are veterinarians, herders, butchers and laborers who work on hides, hair, bristles and wool. In these forms of employ- ment there is also a possibility of infection through the inhalation of spores, and it appears that the so-called ‘‘rag disease’’ or ‘‘wool- sorters’ disease’? in many cases develops in this manner. Infection takes place very rarely through the intestinal canal, as the meat of anthrax animals as a rule only contains bacilli and not spores, and they are digested by the gastric juice; furthermore the virus is usually destroyed in the cooking of the meat. Therefore this method of infec- tion only occurs after the ingestion of putrefactive and improperly kept meat, or from sausage prepared from infected meat which was not fresh. It is also possible that infection is transmitted by flies. The development of the carbuncle usually commences with a lancinating pain at the point of infection and is soon followed by the appearance of a bright red nodule, from which a blackish-red vesicle forms, containing a reddish serous fluid. After the rupture of the vesicle the breaking down of the tissue commences, whereupon in the surrounding parts new nodules and vesicles form and the affected area shows marked edematous infiltration. The subcutaneous connective tissue, and the skin appear reddened as in erysipelas. In the mean- while general febrile manifestations develop until the infection becomes general and the patient succumbs from septicemia. The intestinal infec- tion manifests itself in a severe (frequently hemorrhagic) inflamma- tion of the intestines which is accompanied by severe abdominal pain, vomiting and chills, until collapse and symptoms of asphyxiation ter- minate the disease. Both forms may occur combined, and especially may an intestinal infection be followed by the appearance of edematous swellings in various parts of the body. Inhalation anthrax is mani- fested by an acute pleuritis or broncho-pneumonia. The carbuncle developing after a local infection can be cured by early surgical treatment; and frequently in such cases, as well as in intestinal infections, the administration of immune serum is followed by good results. Literature. S. Kordnyi, Nothnagel’s Handbuch, 1909, V, Bd., 1. T. 382 Malignant Edema. 2. Malignant Edema. Oedema malignum (Septicaemia gangracnosa, Septicémie gangréneuse [French]; Malignes Odem [German] ; Setticemia gangrenosa [Italian].) Malignant edema is an Tig. 8. Edema bacilli with flagella. Agar culture; flagella staining. Vg. 9. Bacillus of malignant edema. Spore formation three-day old agar culture, stained with diluted fuchsin solution. Fig.10. Bacillus of malignant edema. Peritoneal exudate from guinea pig; dried cover glass prep- aration ; fuchsin staining. acute, febrile, infectious wound disease of domestic animals, which is characterized princi- pally by edematous, later crepi- tating swellings at the place of infection. Its cause is the anae- robie bacillus oedematis maligni. History. The development of crep- itating swellings following injuries, seatons, castrations, ete., has. been known since earliest times, and Girard (1880) proved that crepitating swell- ings in sheep may be produced by putrid animal substances. Chauveau (1873) showed by experiments carried out on male goats that the living or- ganisms contained in injected putrid blood were closely associated with the development of the disease. Pasteur (1877) studied more closely the hac- terium, named by him as ‘‘Vibrion septique,’’ and also succeeded in grow- ing it in pure culture. Later Koch & Gaffky (1881) extensively investi- gated the disease produced by the in- oculation of dirt, and which they termed malignant edema. Since that time Kitt, Jensen & Sand, and Le- clainche, have contributed to the bac- teriology, while new observations re- garding its occurrence in domestic animals have been published by Jen- sen & Sand, Ratz, Fréhner, Carl and others. Occurrence. Malignant edema occurs everywhere since its caus- ative agent is ever present in the superficial layers of the soil. Nevertheless it is not a very fre- quent disease, but may occur in horses and cattle, in cows partic- ularly after parturition. Occa- sionally in sheep it causes great losses, and may in veterinary hospitals among horses assume an enzootic character as a sequel of operations (L. A. Merillat). Etiology. Pathogenicity. 33 Etiology. The bacillus oedematis maligni, Koch, (Vibrion septique, Pasteur) is an anaerobic bacterium resembling the anthrax bacillus, but appearing somewhat more slender, rod- shaped, peritrically flagellated, motile and multiplying by fission and spore formation. (Figs. 8 to 10.) Several rods unite to form longer chains in which the ends in contact with each other, as well as the free ends, appear rounded. In artificial media, as well as inside the animal body after death, the bacilli grow to long, curved unsegmented threads. In the bacilli, oval spores develop either in the middle or ends (exceptionally even the edematous fluid taken from the living animal contains spore- bearing bacilli [Jensen & Sand]). Staining. With aqueous aniline dyes the bacilli stain readily, and they also take the Gram stain after being carefully treated with alcohol. Cultivation. The cultivation of this organism is only possible under oxygen-free conditions. Stab cultures in agar or gelatin show along the stab cloudy or lentil-shaped colonies which usually develop at the bottom of the medium and close to which the gelatin is later liquefied. In coagulated blood serum and also in dextrose bouillon (not in saccharose and lactose, Smith) gas having a characteristic sweetish putrid odor is formed, which later causes disruption of the media. (Fig. 11.) Kerry found inthe gases hydro- gen, hydrogen sulphide, carbon dioxide and methane. Milk is changed in a few days into a watery fluid with gas formation and the collection of a layer of fat on the surface (Smith). In bouillon cultures the bac- teria produce toxins in small quantities (Roux and Chamberland). The spores show great vitality. Dry muscle substance and spore-containing edema fluid enclosed in glass tubes prove virulent even after years. In fluid media spores are destroyea | after heating to 100°C. for fifteen minutes (Sanfelice), while in the dry state they are killed in ten minutes at 120°C. (Arloing). Direct sunlight kills them only slowly. Disin- fectants are only effective in strong solutions and after pro- longed contact. Sporeless bacilli are quickly destroyed in the presence of air and sunlight as well as by putrefaction. Pathogenicity. After the inoculation of a Fig. 11. Stab eul- pure culture in the depth of the connective tis- ture 4 edema ba sue, a rapidly extending swelling develops at agar. the point of injection. It becomes crepitating as a result of gas formation within, and the animal soon dies of a form of septicemia. Guinea pigs and mice succumb in from 24 to 28 hours. Cattle can be infected only with great difficulty, and feeding of spore-containing material will not produce the disease even in susceptible animals. Edema bacilli injected into the blood produce the disease only when they find a suita- ble soil for their development somewhere in necrotic tissue (for instance, in previously ligated testicles [Chauveau] ). 34 Malignant Edema. Probably there are also other bacteria capable of producing a dis- ease resembling malignant edema. Thus, Novy observed the appear- ance of a similar disease in guinea pigs following subcutaneous injec- tions of milk nuclein, and he proved that an organism closely resembling the above-described bacillus was the cause. However, it was somewhat more slender and provided with strikingly long and thick flagella. It is also an anaerobic but sporeless bacillus (Bac. ed. maligni II). Klein isolated from garden soil (Bac. ed. sporogenes) and Sanfelice from guinea pigs inoculated with dirt containing putrid organic sub- stances, a similar, although only facultative anaerobic, bacillus (Bac. ced. srogenes). According to Fraenkel the Bac. phlegmones emphysema- tose produces in man a similar disease (gangréne foudroyante). On the other hand, according to Kirsten the edema bacilli, like most of the species of bacteria, form groups of varieties which may be distinguished from éach other by their morphological and biological characteristics. However, in their clinical relation the most important characteristic is the absence of pathogenicity in most of the varieties. For natural infection of domestic animals solipeds are most susceptible, while cattle, sheep and goats are less sus- ceptible. Hogs, dogs and cats are rarely affected. The infection results in most instances from the entrance of the edema bacillus into the deeper parts of the subeutaneous: or submucous tissue through breaks in the continuity of the skin or the mucous membrane of the mouth and esophagus. There are many opportunities for such infections as the bacilli are widely disseminated in the dirt, especially in dust of hay, in garden or field soil, in street dust, in household drainage, in putrid organic material, and in excrement of healthy animals. These substances are very prone to come in contact with wounds on the body, and yet the rare occurrence of the disease can be explained by the fact that successful infection occurs only when large masses of bacilli enter the lymph spaces of the connective tissue which contain but little oxygen. On the other hand, where the infectious material enters superficial wounds on the skin, granulating ulcerations, or even directly into the blood stream, the bacilli cannot propagate on account of the presence of oxygen. Hence the infection occurs either through contused or lacerated wounds or during parturition by means of contami- nated hands or instruments. In other cases the infection may also follow vaccination, castration, shearing, bleeding, intro- duction of seatons, subcutaneous injections with unsterilized medicines (eserine, morphine, creolin, arecoline), unclean syringes, bites, penetration of straws into the canthus of the eye, etc. The disease has also developed in association with necrotic processes. Lembeken observed 50 out of 600 and Gilruth 300 out of 4,000 sheep dying from malignant edema during or after shearing. Infection may also occur through injuries or necrotic ulcer- ations on the mucous membrane, whereas the healthy mucous Pathogenesis. Anatomical Changes. 35 membrane affords an effectual protection. Feeding and in- halation have failed to successfully transmit the infection to experiment animals. Pathogenesis. After the germination of the spores in the lymph spaces the bacilli continue to multiply by fission at the point of infection until large bacterial colonies develop. In the meantime gases are formed by the dissociation of the tissue fluids, and toxins are produced under the influence of which the blood vessels are dilated, allowing the blood plasma to transude into the connective tissue spaces through the relaxed walls of the vessels. With the penetration of the bacilli the swelling en- larges, and in case the point of infection is near the abdominal cavity, the bacilli multiply rapidly on the surface of the _ peritoneum where they grow into long threads. At the same time the absorbed toxins act also on the central nervous system, particularly on the respiratory and heat centers, as a result of which respiration becomes difficult and the temperature elevated. The edema bacilli are capable of multiplying in the tissues only under special conditions. The spores will germinate only in- the presence of toxins (from older cultures) in the tissues, because otherwise they would soon be taken up by the phago- ’ eytes and rendered harmless. Their propagation is also facili- tated by the simultaneous entrance into the tissues of other micro-organisms (Bac. prodigiosus, staphlyeocci, diplococcus pyogenes and others). In addition propagation is aided by the presence of particles of dirt or sand which protect the spores mechanically against the phagocytes, while toxins and substances like lactic acid, keep away the cells through negative chemotaxis (Besson, Leclainche & Vallée). At the same time the presence of other bacteria has an influence on the develop- ment of the pathological changes and gives rise to numerous cases of mixed infection. Anatomical changes. During the formation of a swelling in any part of the body the connective tissue becomes distended and infiltrated with a yellow or reddish fluid which contains gas bubbles and liberates a peculiar disagreeable odor. The gelatinous infiltration of the connective tissue may also extend between the deeper layers of the muscles, while the muscle substance proper turns pale yellow or dark red in color, be- comes brittle and tears readily. The connective tissue appears in places permeated with smaller or larger hemorrhages. The abdominal cavity contains a small quantity of reddish serous fluid; the peritoneum is markedly injected, lustreless, but is not covered with an exudate. , Tf the malignant edema has developed after parturition, the uterus is found insufficiently contracted, and the subserous con- nective tissue of the small pelvis shows edematous infiltration. The wall of the uterus is also edematous, the mucous membrane 36 Malignant Edema. swollen and covered with a dirty, pasty, ill smelling mass which also covers the cotyledons that are in the process of breaking down (Carl). The spleen as a rule appears normal in size or slightly swollen. Exceptionally, however, an acute swelling of this organ with gas formation in the pulp has been observed (Frohner). The liver shows cloudy swelling and the intestinal mucous membrane shows indications of an acute catarrh. The lymph glands are acutely swollen, while the lungs manifest well marked active hyperemia and also edema (which, according to Kitt, are occasionally the only lesions found in sheep) ; the heart muscle usually shows marked parenchymatous degeneration. The blood is slightly coagulated, and the carcass decomposes rapidly. In the fluid squeezed out from the crepitating swellings or taken from the cut surface, or frequently in the abdominal fluid, edema bacilli may be found in large numbers even in the unstained miscroscopical preparations. The bacilli, which not infrequently contain spores, occur singly, in chains or as curved threads, and are often found in association with other bacteria. Several hours after death the bacilli are found in the blood, particularly the blood of the lungs where they often oceur in long threads similar to those seen on the peritoneum. The presence of the bacilli of malignant edema is not in itself proof that the particular animal died from this disease. These bacilli occur frequently in association with other bacilli in the intestinal con- tents of herbivorous animals, and from there they may spread after the death of the animal throughout the body even to its most distant parts. This is particularly the case when the blood remains fluid, as for in- stance, in a suddenly appearing asphyxiation, and thus promotes their multiplication and dissemination. From the intestines the organisms first enter the peritoneum, next the blood vessels of the intestines and mesenteries, and then the portal vein from whence they may be dis- seminated throughout the blood. Symptoms. After infection an edematous swelling, which is not sharply circumscribed, may develop in 12 to 24 hours in any part of the body. The swelling is at first tense, warm, very painful, later cooler, soft, doughy and less sensitive, and may even become entirely insensitive in the center, so that the animal does not manifest pain when incisions are made into the swelling (at the borders, however, it shows the charac- teristics mentioned). At the same time the swelling reveals erepitation on palpation. The swelling usually develops at places where considerable loose connective tissue occurs under the skin; by spreading over the surface it may occasionally involve the entire side of the body, anteriorly to the neck, posteriorly to the upper parts of the extremities, resulting in difficult and painful movements of the body. Upon incision a reddish-yellow, reddish-brown, or a colorless serous fluid is Symptoms. 37 discharged which contains gas bubbles. In some cases the skin over the swelling acquires a dark color, and may finally become extensively necrotic. In cases where the swelling develops in association with an evident injury the wound takes on a bright color and a peculiar lustre, and a dirty red, fetid, serous fluid oozes from its surface. Later the margins of the wound become necrotic in portions. If the infection occurs through the genital passage during or shortly after parturition the first manifestation of the disease appears after 2 to 5 days. The vulva swells in the form of a cushion, and a dirty, brownish-red, very fetid, thick secretion is discharged from the vagina. Soon a crepitating swelling de- velops in the surrounding parts of the external genitals which is at first warm and painful but later cool and painless, and. gradually extends over the perineal region and the lower abdo- men. Besides high fever, bloating and diarrhea are observed. Malignant edema developing in association with parturition in cat- tle is frequently mistaken for blackleg. Recently Alrert & Carl estab- lished with a certain degree of probability that the cases described as parturition blackleg are actually malignant edema, and that blackleg never develops in this form. Following castration the first symptoms appear after a few days or sometimes after several weeks; aside from high fever, an extensive edema develops under the skin of the abdo- men, emanating from the castration wound, and later shows crepitation on palpation. In addition the animal manifests colicky pains, sensitiveness over the abdominal wall and bloat- ing; in other words, there are indications of peritonitis, and finally signs of a general infection and exhaustion. Of the other symptoms of the disease the markedly diffi- cult respiration, the cyanotic mucous membranes, the accelerated and weak heart action, and the corresponding small, wavy pulse are conspicuous. The body temperature reaches a high degree even at the onset of the disease, remains at a uniform height, but as death approaches it drops to normal or subnormal. In later stages of the disease diarrhea is very frequently observed in which fetid and watery feces are discharged. The symptoms follow each other rapidly; the crepitating ‘swelling increases in size from hour to hour, and death usually occurs in twelve hours to three days after the appearance of the first symptom. In some of the cases, however, the disease terminates in recovery, especially after appropriate treatment. Livesey observed the disease in a dog. On the left side of the head an emphysematous swelling developed and progressed to the neck and shoulders. At the same time the lips and cheeks became necrotic. Pankul demonstrated the disease in hogs; a crepitating swelling devel- oped in this instance from a wound in the skin. 38 Malignant Edema. Diagnosis. In cattle malignant edema may be mistaken for blackleg. Malignant edema is indicated by the appearance of the disease in localities where blackleg is not prevalent, further by the advanced age of the patient, the occasional localization of the swelling in parts which are poor in muscle tissue, and by the relatively severe affection of the connective tissue com- pared with the slight involvement of the muscles. Parturient apoplexy is differentiated from malignant edema by the absence of the crepitating swelling, and the different bacteriological findings. In horses and sheep the development of a crepitating swell- ing under febrile manifestations indicates malignant edema. The crepitation distinguishes the disease from edema, which often resembles it very closely, as well as from the inflammatory edema which is caused frequently by a streptococcus infection following injuries; whereas in the simple subcutaneous emphy- sema there is in addition to the pre-existing skin or lung injury an entire absence of febrile symptoms. On post mortem care should be taken not to mistake the emphysema caused by putre- faction with the crepitating swelling which develops during life. (For differential diagnosis regarding the bacilli, see p. 20.) Treatment. The only possible method of treating the patients consists in incising the swellings as they are forming in one or several places. This is to be followed by squeezing out the serous fluid and by thorough disinfection of the wounds; at the same time it is advisable to inject disinfecting substances subcutaneously into the tissue immediately surrounding the swelling. While the disinfectant treatment is practically without effect upon the spores of the edema bacilli, it indirectly prevents the germination of the spores by destroying the foreign bacteria which entered the wound and also prevents the multiplication of the bacilli. Prevention. In order to prevent the occurrence of the disease, wounds of the skin and mucous membranes should: be guarded against contamination with dirt. Those wounds which have already become contaminated should be disinfected, whereas, after difficult parturitions in which the genital pas- sages have been injured a thorough irrigation of the vagina and uterus will prevent the disease. Immunization. Experimental animals may be immunized against virulent infections by injections of spore-containing tissue fluids which have been heated for 7 hours to 92°C. (Leclainche & Vallée) ; by bouil- lon cultures heated for 10 minutes to 105-110°C., also by filtrates of the edematous fiuid, or through the toxins contained therein (Roux & Chamberland) ; further by blood serum of immunized animals which have received repeated injections of virulent material (Duenschmann, Leclainche & Morel). These inoculations protect only against malignant Malignant Edema. Blackleg. 39 edema but not against anthrax also, as was proven by Leclainche & Vallée, and which is contrary to the former views of Roux & Duensch- mann. Literature. Chauveau, Rec., 1873, 263.—Pasteur & Joubert, C. R., 1877, LXXXV, 101.—Koch, Mitt. d. G.-A., 1881, I, 49.—Affky, Ibid., S. 83.—Chauveau & Arloing, Acad. de Méd., 1884, XIII, 604.—Kitt, Miinchn. Jhb., 1883-84 u. 1884-85; Monh., 1897, VIII, 206 (Review) ; 1900, XI, 49.—Jensen & Sand, D. Z. f. Tm., 1887, XIII, 31—Roux & Chamberland, A. P., 1887, I, 561—Leclainche & Vallée, Ibid., 1900, XIV, 590.—Frohner, Monh., 1901 to 1903, XII-XIV; Allg. Chir., Wien, 1905 (Lit.).—— Carl, A. f. Tk., 1903, XXIX, 225.—Jensen, Hb. f. p. M., 1903, II, 619 (Lit.).— Livesey, Vet. Rec., 1906, 356.—Hohneker, B. t. W., 1907, 267. 3. Blackleg. Gangraena emphysematosa. (Black Quarter, Quarter Ill [English]; Rauschbrand, Kalter Brand, Rauschender Milzbrand [German]; Emphysema gangraenosum, Sarkophysema haemorrhagicum; Char- bon symptomatique, Charbon bactérien, Mal de cuisse, Mal de montagne [French]; Car- bonchio enfisematosa o sintomatico, Acetone, Quarté nero [Italian].) Blackleg is an acute, infectious, but not contagious, epizootic disease of cattle, and exceptionally of other ruminants and of swine, in the course of which crepitant swellings develop in the musculature of certain regions of the body, accompanied by febrile symptoms. It is caused by the anaerobe, bacillus gangraenae emphysematosae. Historical. Until the seventies of the last century, the disease was considered as identical with anthrax or as a particular form of that dis- ease. As early as 1782, Chabert had differentiated the disease from anthrax under the name of charbon symptomatique, while Bollinger (1875) and Feser (1876) showed that blackleg was to be separated from anthrax from an etiological point of view. Both investigators observed the bacilli contained in the crepitant swellings, and produced the dis- ease in ruminants through injection of the serous fluid; Bollinger also caused it by introducing subcutaneously mud from places in which blackleg was frequent. Later the etiology of the disease and properties of the bacteria were investigated thoroughly by Arloing, Cornevin & Thomas (1879-1884), and through these studies not only the etiology of the disease was determined upon, but they also introduced a prac- tical method of protective vaccination. The bacteria which the French call bacterium Chauveaui were developed in cultures by Roux (1887) and later by Kitasato (1889), while still later Kitt, Leclainche & Vallée, as well as Grassberger and Schattenfroh, completed our knowledge in that direction. Occurrence. Blackleg appears mostly in mountain regions and in valleys with swampy pastures, but is also observed on low lands exposed to inundation. In such regions it appears chiefly during the hot season and causes nearly every year con- 40 Blackleg. siderable losses among the young cattle, while older animals are attacked only exceptionally. During the winter, and when the cattle are fed in the stable, the disease appears very rarely. In Germany, blackleg was observed during the years 1888 to 1905 most fre- quently in the Prussian provinces, Schleswig-Holstein, Rhineland and Westphalia, and on the mountain pastures of the Rhine provinces; before the: introduction of the protective vaccination, 4 to 8%, at some places even 12 to 15%, of the young cattle were destroyed by the disease. During the 10 years 1899 to 1908, in about 188 districts 7 (?) horses, 1,193 cattle, 36 sheep and 2 goats were infected with the disease; the number of districts varied between 157 (1897) and 214 (1908), while the number of cases varied between 928 (1902) and 1973 (1906). More than two-thirds of the communities and cases were in Prussia, where the government dis- trict Schleswig was particularly attacked; then follow Bavaria, Hesse, and Wirttem- ae According to Scheibel, blackleg is often observed in Upper Hesse in sheep and goats. ' In Austria the disease appears chiefly in Lower Austria and Tyrol, while the coast regions, Silesia and Dalmatia, are nearly free from it. During the years 1891 to 1900, the average loss amounted to 552 head of cattle or 0.006% of the total stock in the involved regions. The number of infected localities varied between 142 (1892) and 227 (1898). ‘ In Hungary, the disease appears on the mountain pastures of Siebenbirgen and in the Northeastern part of the country, and also in the former inundation dis- trict of the Tisza River. Although the disease is not subject to obligatory notifi- cation, 1,460 cases were reported from 30 communities in 1907. In Switzerland the average annual loss during the years 1897 to 1802 amounted to 687 head of cattle, two-thirds of which must be charged to the cantons of Berne, Friebourg and Waadt. During the year 1908, in 272 communities, 779 animals were attacked. In the other European countries blackleg is also in evidence, and in 1908 Belgium had 274 cases of the disease, mostly in the provinces Liége and West Flanders; Italy had 407, and Norway 67 cases, while in Sweden there were 56 infected farms. In France the northerly and southeasterly mountain districts are severely infected, while in Great Britain it is Scotland, and in Denmark, Jutland. In Holland the disease causes greater losses than anthrax. In Africa, blackleg has been observed in Algeria and the southern part of the continent (there known as Spons-Ziekte and Swamm-Ziekte), and it is said that in many regions of the Transvaal 10 to 25%, sometimes even 50%, of the young cat- tle are destroyed annually by the disease. In America the disease has been observed in most of the northern states and seems to be very common. During the year 1906, from the Federal Bureau of Animal Industry alone, there were shipped 1,250,000 doses of protective vaccine to 40 states and territories. Most exposed to attacks are the vast regions between the Mississippi Valley in the east and the Rocky Moun- tains in the west. In South America (Chile) the disease has also been observed. Etiology. The blackleg bacillus, bacillus gangraenae em- physematosae (Clostrydium sarcophysematos bovis Kitt, bac- terium chauveaui) is on an average 2 to 6” long, 0.5¢ thick, slender and straight, rounded at the ends, and motile by means of flagella. At a certain stage of its development, the bacillus assumes a whetstone or lemon-like shape (clostrydium form), while in the interior a spore develops at the center or at the end. (Figs. 13 and 14.) Staining. For this the common watery solutions of aniline dyes as well as Gram’s method are suitable. Culture. Cultures develop in the presence of hydrogen and illuminating gas, with the exclusion of oxygen, as well as in vacuum, particularly in Martin’s pepton-bouillon (Leclainche & Vallée); also in chicken bouillon (Arloing), and on gelatin and agar containing blood-serum, pepton, glycerin or a re- ducing substance (Kitasato). The bacillus thrives best at 36 Etiology. 41 to 38°C., poorly at 14°C. The gelatin becomes liquefied; in the depth of the agar culture medium along the needle punc- ture radiating white growth devel- ops (Fig. 15). The bouillon at first becomes uniformly turbid, small gas bubbles appearing on the surface and later a white sediment is formed, above which the solution is clear. From dextrose and lactose (not from saccharose) the bacillus develops a gas which is either odor- less or resembles rancid butter (Preisz, Smith). Milk is curdled only imperfectly. Fig. 12. Blackleg bacilli from an Tenacity. Fresh blackleg meat is ster- agar culture. Flagella staining. ilized in 2 hours at a temperature of 80°C. or in 20 minutes at 100°C.; fresh virus inclosed in glass tubes is made inactive in 2 minutes when kept in hot water. On the other hand, in dried meat, the spores are made inactive only by heating to 110°C. for 6 hours, or boiling in water for 2 hours, while at room tempera- ture the spores in dried muscular tissue are kept virulent at least 2 years (according to Mattei even 10 years); in salted meats they are kept virulent for more than 2 years, and in decaying flesh 6 months. Temperature be- tween 85 and 100°C. decreases the virulence of the spores through the destruction of the toxins. Extreme cold has hardly any effect In the summer, exposed to direct sunlight, the dried virus loses its activity in 24 hours, and Fig. 18. Blackleg bacilli with the fresh virus in 18 hours. The spores show spores. Muscle juice from also considerably more resistance to chemical a guinea pig; unstained. disinfectants than the bacilli. The most ef- fective are carbolic acid (2%), salicylic acid (1:100), nitrate of silver (1:1000), and bi- chloride of mercury (1:5000); vapors of thy- mol and eucalyptus weaken fresh virus, as’ it is destroyed by the action of these media in 100 hours (Arloing, Cornevin & Thomas). Virus contained in blackleg meat possesses a greater resistance than do cultures (A. Schmidt). © Pathogenicity. After subcu- _ taneous or intramuscular injection of larger el aptleeiae of meat juice AY containing spores there appear in ,,. ae oe the inoculated cattle, marked fever- ee : ede ie pa ish symptoms, and, at the place of guinea pig; dried cover glass injection, a painful, warm, edema- preparation; fuchsin staining. tous, and later crepitant swelling, which, after the death of the animal produces a black color of the musculature of the in- volved region. These muscles together with the serous infiltrated subcutaneous and intramuscular tissue are found in- terspersed with gas bubbles. If an animal is inoculated subcutaneously, with only a small amount of the infectious sub- 42 Blackleg. stance, no edema will, as a rule, appear at the place of injec- tion itself, but at some distance a small swelling appears, which disappears in a few days. If the inoculated amount has been very small, the injection will only cause a small indisposition and a moderate i increase in temperature for a few days. The intravenous injection of a larger amount of virus produces typical blackleg, but a smaller amount causes only 2 or 8 days of indisposition, indicated by trembling and an in- considerable increase of temperature. A similar effect follows the intratracheal injection of the virus. In animals which have gone through the short indisposition, the disease cannot be- produced by a second injection of even a larger amount. In- oculation in the tail of the animal only causes a crepitant swell- ing and fever, if the tail is covered up, since its temperature, which is normally 29.8°C., is thus artificially raised to 38.6°C. In calves less than six months old, the subcutaneous or in- travenous injection of an amount of fresh and virulent virus which in 90% of cases would be fatal to a grown animal (1 to 6 drops) only produces a slight indisposition. Larger amounts of virus, 7 to 10 drops for 1 to 14 days old and 10 to 20 drops for 3 to 10 weeks old calves, produce typical blackleg (Arloing, Cornevin & Thomas). Small amounts of virus inoculated intramuscularly kill guinea pigs, goats and sheep within 12 to 36 hours; mice are also very susceptible, while rabbits, rats and pigeons are in- fected only in exceptional cases. In horses and asses only an inconsequential swelling appears after the injection; hogs are slightly and other animals are not at all susceptible to the infection. In artificial culture media both toxins and gases are: produced, but most abundantly in Martin’s bouillon. Intravenous injection of 10 to 12 ec. of an old culture kills horses in 5 minutes, evidently through the action of the toxin. The toxin is mostly confined to the bodies of the bacteria, culture filtrates being much less effective. The toxin very soon becomes inactive in the air, while heating for 10 min- utes at 115°C. only weakens without destroying it (Roux); its nega- tive chemotaxis turns positive at 75°C. (Leclainche & Vallée). According to Grassberger and Schattenfroh, the toxin is a product of the bacilli and is particularly in evidence in the presence of car- bonate of calcium. In calves 40 cc. of the filtrate of a culture cause edematous swelling, fever, perspiration, diarrhea, prostration and, after 5 to 6 days, death. Contrary to other bacterial toxins, these show their poisonous effect on the injected animal at once, without any distinct period of incubation (Leclainche & Valleé, Eisenberg). In many cases natural infection results from the fact that mud from the swampy and rough soil of certain regions pene- trates under the skin of the cattle, particularly through wounds on the tail and the extremities (Liipke observed the disease after castration). More frequently the infection results from the consumption Etiology. Susceptibility. 43 of infected feed or drinking water. Artificially it is successful in this way only in exceptional cases (Bollinger, Arloing), but the fact that in blackleg regions the intestinal canal as a rule contains blackleg bacilli (Leclainche & Vallée), while lesions on the surface of the body are observed only in exceptional cases, and furthermore, that crepitant areas are present in the internal organs, speaks in favor of the frequency of infection through the intestines. In the rare cases when such swellings originate in the region of the throat or in the wall of the esophagus, the infection is evidently brought about through the mucous membrane of the throat or the mouth. Attacks of the disease in swine have so far only been ob- served in fattening establishments, where the symptoms. also have indicated infection of the tonsils (Marek). Blackleg is a disease connected with infected soil, and trans- mission from animal to animal, as in contagious diseases, or through intermediary objects, evidently occurs very seldom. The blackleg bacilli seem to be capable of multiplying in the soil, and through their resisting ‘spores, to preserve their capacity of development and infectiveness even under unfavor- able conditions. This, as well as the fact that bacteria from carcasses of dead animals again infect the soil, explains the stationary occurrence of blackleg in certain regions. In fact, it appears most frequently in swampy, low pastures, and. in regions subjected to occasional inundations; also in pastures where carcasses of cattle infected with blackleg had previously been buried, and sometimes after feeding hay or other feed in the neighborhood of which carcasses had been skinned, or after drinking from creeks in which parts of blackleg carcasses had been thrown. Sauer suggests the possibility that flies which have been feeding on blackleg carcasses, and in whose bodies the bacilli have increased in number, may be capable of transmitting the infection. Susceptibility. In blackleg regions the cattle contract the disease with few exceptions only at the age of from 1% to 4 years; sucking calves are only attacked in. exceptional cases (Strebel observed the disease in a 3 days old calf), and animals over 4 years as a rule only when they are transferred at an advanced age from disease-free places to an infected. place. Whether or not the breed has any influence on the suscepti- bility is not yet determined with certainty; it is a fact that eattle of the native breed contract the disease, but not as often as the improved breed; the same also is true of the Algerian cattle (Brémond). As to the susceptibility of the buitalo, no satisfactory data are so far available (Cronevin ob- served in 2 buffaloes inoculated with virulent material only intermittent changes of temperature, while, according to Makoldy. these animals contract blackleg). In sheep Vogdt and Monseur. and in swine Marek, Battistini and Born have found 44 Blackleg. isolated cases of the disease, but it is still a matter of con- tention whether the disease appears in horses or not. According to a compilation by Tillmann, out of 614 animals suffering from blackleg, 7 were from 1 to 4 weeks old, 23 from 2 to 3 months, 94 from 3 to 6. months, 449 from %4 to 4 years, and, finally, 41 were above 4 years old. Symptoms similar to those of blackleg, and analogous anatomical changes may also be produced by other bacteria (the so-called pseudo- blackleg bacilli). Thus Kerry has isolated a bacillus from a guinea pig which had been inoculated with blood from a cow supposed to have died from blackleg. This bacillus grows at a higher tem- perature than the blackleg bacillus, produces no spores, and is patho- genic not only for guinea pigs, but also for rabbits (bac. edematis thermophilus). Preisz found in one case, which otherwise was similar to blackleg in every way, a considerably longer and thicker bacillus than in common blackleg. Ligniéres and Bidart in their clinical reports on diseases similar to blackleg in Argentine refer to an affection which is known under the name of Mancha (=spot, owing to the dark color of the skin over the edema). Calves from 6 to 10 months old contract the disease exclusively and succumb within 24 to 28 hours. The disease is caused by a bacillus similar to the blackleg bacillus, but it is pathogenic for young rabbits, horses, and ‘pigeons. Protective vaccination with blackleg virus is without effect. Pathogenesis. Toxin-free spores which have penetrated into normal healthy tissues are soon taken up by phagocytes and digested; if, however, at the same time, other bacteria or grains of dust have gathered, and the tissue, particularly the muscula- ture, is not quite sound, or if, at the involved place an extravasation of blood exists, then the spores, protected against the phagocytes, begin to germinate, and the bacilli thus created continue to multiply through fission. Under natural conditions a small disturbance in the tissue, a strain of the muscles or a hemorrhage (blow by a stick or a horn), may cause the bacteria which have reached the blood from. the intestines, and’otherwise are soon destroyed, to locate at these points, to increase in number, and excite the pathological process. eas inflammation and sometimes also small hemorrhages ig. Stak cyl. Will be observed. Under the influence of the toxins, ture of the the musculature degenerates, and, through the de- es ea struction of the nitrogenous matter, gases are aimpeaunen formed. The toxins are also absorbed by the body agar. fluids and cause the general symptoms accompanying the local process; they also reduce the power of resistance of the tissues against the pathogenic effect of the virus (Roger). According to the investigations of Leclainche & Vallée, cultures containing spores and heated from 80 to 85°C. are inactive, as the Where the bacilli appear in abundance, a serous. Pathogenesis. Anatomical Changes. 45 spores in the tissues are digested by the phagocytes within 48 hours. These spore-containing cultures cause the disease, however, if active toxin is added or if they are injected mixed with sand or saprophytic bacteria (bac. prodigiosus, proteus vulgaris, staphylococcus albus). The spores will also show a greater pathogenic activity by the addi- tion of a small amount of 20% lactic acid, salt solution or diluted alcohol, and alsu through a traumatic injury immediately before or after the infection. These saprophytic bacteria, the sand and the dead tissue protect the spores mechanically against the phagocytes and make their development possible. The same result is produced by the chem- ical substances as well as by the inoculation of toxins contained in unheated cultures, through negative chemotaxis. Anatomical Changes. Characteristic of blackleg is the crepitant swelling occurring anywhere on the rump or extremi- ties, more or less distinctly circumscribed, above which the skin appears sound, or in rare cases, partly necrotic, and therefore, stiff, parchment-like, and dark colored. The subcutaneous tissue is red or infiltrated with a yellowish, gelatinous exudate, at places intermixed with hemorrhages and gas vesicles, and in the deeper parts similarly changed connective tissue separates the single muscle fibres from each other. The musculature of the ‘swollen part is dirty brown or dark red; at the periphery it is darker red or dull yellow with black stripes, and either in- tersected with bloody serous liquid or is spongy and dry (the latter with great development of gas). The dirty red, or claret colored liquid squeezed from the swellings contains gas bubbles in abundance which give off an odor suggesting rancid butter. In the tissue surrounding the swelling the lymph vessels are sometimes distended, filled with lymph and gas, while the lymphatic glands are acutely swollen, edematously infiltrated, and sometimes intermixed with hemorrhages. Crepitant swellings appear in rare cases in the musculature of the tongue, throat, and diaphragm, from which points they may also involve the muscles of the shoulder and arm (Hen- ninger). They may likewise be found in the loin or in the muscles between the ribs. The internal organs show few conspicuous lesions and no constant changes. Relatively often a reddish serous liquid is found in varying amounts in the thoracic cavity. Further, there may be present on the pleura, as well as on the epicardium, a reddish gray fibrinous exudate sometimes mixed with dirty red, _jelly-like substances, or the parietal pleura may be covered with soft, jelly-like, wine-colored deposits (Foth, Katona, Till- mann). In the lungs, the interlobular septa may be infiltrated, and the lobules themselves edematous. In very rare cases the heart muscle at localized points is dark red and edematous (Tillmann) or necrotic (Blome), and the epicardium is covered with strips or tufts of exudate. : In the abdominal cavity lesions are frequently found which are similar to those in the thoracic cavity. The spleen is gen- 46 Blackleg. erally unchanged or only moderately swollen, but sometimes a well developed tumefied spleen is found where the capsule is distended by gas bubbles, but without hemorrhages. The liver frequently appears mottled on section, owing to ochre-yellow foci from a pea to a walnut in size, which increase after death, and owing to the development of gas, assume a porous, friable consistency (Kasselmann, Foth, Warringholz, Tillmann). According to Warringholz, there exist in the cortex of the kidneys, light gray foci of the size of a millet grain. The mucous membrane of the intestines is catarrhal, reddened and loosened; sometimes it is dark red, swollen, intersected with hemorrhages, and covered with bloody mucus. Finally, the blood is dark red and forms a coagulum in the heart and the large vessels. In rare cases with rapid course the characteristic external swelling is lacking, but by thorough examination dark red dis- colored portions of muscles may be found in hidden places, as under the shoulder blade, in the sexual organs, masseter muscles, psoas muscles or in the pillars of the diaphragm. Rebiger found vesicles under the endocardium varying in size from a pea to a pigeon egg, which were filled with a dark red, turbid , liquid containing numerous blackleg bacilli. Scheibel sometimes found a crepitant swelling of the spleen and a gray-brown, porous, and spongy appearance of the kidneys. According to Schmitt, an intes- tinal infection is especially indicated by numerous small hemorrhages in the omentum and in the serosa, particularly in the neighborhood of the spleen which is swollen on account of hemorrhagic infiltration. There is also a serous infiltration of the reticulum and a bloody dis- coloration of its mucous membrane. In swine a swelling of the region of the throat is mostly observed where the subcutaneous, intermuscular, and peripharyngeal tissues show a serous gelatinous fluid containing gas vesicles. The adjoining muscles appear striped with dark red streaks, the lymphatic glands are acutely swollen, and the mucous membrane of the throat shows a catarrhal condition with small hemorrhages (Marek). In other cases the crepitant swelling has been found on one of the posterior extremities (Battistini). In horses the occurrence of blackleg has not been definitely deter- mined. The literature contains reports by Ganter, Hafner, Schmidt, Velmelage, Fischer, and others, but, in these cases, a confusion with pseudo-blackleg or malignant edema is not only not excluded, but even probable. Hasenkamp, for instance, found in a horse a serous-hemor- rhagic fluid in the thoracic cavity and pericardial sac, hemorrhages in the serous membranes, and black, ecrepitant, softened muscles of the shoulder region, the neck, and the hind leg which were also infiltrated with a sero-sanguinolent fluid. Quadekker observed in a similar case a sweetish odor in the diseased parts which was neither pleasant nor foul. Blackleg bacilli are generally present in large numbers in the serous liquid of the crepitant swellings as well as in the yellow foci of the liver (frequently in company with various other bacteria, as staphylococci, micrococcus prodigiosus, proteus vulgaris, bacillus coli and others, particularly at the edges of the swell- ing), and a certain time after death they are also found in the transudate of the serous cavities, in the bile, in the lymphatic glands, and in the blood. In the juices Symptoms, 47 of the diseased muscles numerous clostrydian forms are seen, and if the course of the disease is not acute the bacilli will be found to contain spores at the time of death and still more 24 to 48 hours later. Miiller recommends to submit for bacteriological examination pieces of. muscles covered with salt, because the decaying process is arrested by the salt and the black- leg bacilli are stimulated to a rapid formation of clostrydian forms and spores. The gases formed in the crepitant swellings have not always the same com- position; according to Roux, they consist of carbonic acid and hydrogen in equal proportions, while Tappeiner’s chemical analysis shows 13.15% of carbonic acid, 76.51% of hydrogen, and 10.34% of nitrogen. Symptoms. The period of incubation of the disease is generally 3 days, although in exceptional cases it may be more, but does not, however, exceed 5 days. In cattle the disease starts with sudden febrile symptoms; the animals stop eating, grazing and ruminating, the tempera- ture rising in a few hours to 41-42°C. (Fig. 16.) In many cases, however, the disease seems to progress with a moderate temperature or without fever (Schiitt & Warring- holz, Steinbriick). In graz- r a. —— re ing animals lameness or 7[w[wzlz2][4+]se[uf[s stiff dragging of an extrem- ity is also frequently ob- [4 served. a + Shortly thereafter may be seen the characteristic [,,—¢ zie blackleg swelling, particu- 2 larly in portions of the body —_|.99, =e f with thick layers of muscle. a Most frequently they appear —|390 f on the upper leg, on the buttocks, in the region of 385 the loin, on the shoulder, ; : chest or neck (in exceptional Ts 18, eyercuree in blacleg. The cases also in the submaxil- previous evening. lary space [Fig. 17], on the tongue or on the throat), while they never appear below the carpal or tarsal joints or on the tail, At one of the above named places a distinctly bordered or diffuse swelling of irregular shape develops rapidly, which, from the beginning, is hot and painful, later becoming cold and torpid in the center, so that the animal finally does not feel pain on touch or when an incision is made. The skin over the swelling is dry, stiff, dark colored, incidentally black and parchment-like, and in exceptional cases also necrotic. On palpating or pressing the tumor a peculiar crepitation is observed, while percussion brings forth a pronounced tympanitic sound. If the swelling is cut at the beginning of the disease, dark red blood, later a dirty red, foamy and singularly sweet smelling liquid will be discharged from the wound. The tissues surrounding the tumor are edematously infiltrated. The lymph glands are swollen ‘and may be felt under the skin as firm knots the size of apples. 48 Blackleg. In the meantime, pronounced respiratory disturbances de- velop, while the activity of the heart is accelerated (90 to 100 contractions a minute) and becomes weak. Sometimes attacks of colic are observed. At last the animal lies on the ground stretched out motionless, the temperature is lowered to 37-35°C. or rises once more, and then death follows immediately. The disease generally lasts from 14 to 2 days; in rare cases, however, it may last from 4 to 10 days. The crepitant swelling mostly develops at one place, but in some cases tumors appear at several parts of the body, grow rapidly and coalesce to form a single large swelling, If the swelling is de- veloped in the deep layers of the hip. or shoulder muscles, its other properties can- not be exactly deter- mined, aside from the increase in volume of the involved part of the body. The skin appears relatively healthy, and no crepitation is ob- served on touch; how- ever, by a stronger per cussion, a hollow sound may be observed in the periphery of the swell ing even in these cases If the cavity of the mouth or the throat is the seat of the disease : Pissnthe lta aN a symptoms of a severe ee te Get Gene inflammation of the lary space. throat are usually ob- served whose specific nature is indicated by the crepitation of the swollen parotid region. Infection of the tongue is indicated by considerable swelling, while the tip of the organ crepitates on touch and projects from the mouth. In the extremely rare cases of primary infection of the diaphragm, the cause of the fever as well as of the difficult respiration can only be determined by autopsy. According to Arloing, Cornevin & Thomas, and also Feser, black- leg, especially in older animals, sometimes appears in a much milder form. In such eases there may or may not appear a moderate, indis- tinct swelling on any part of the body, the animals show moderate fever Symptoms. Diagnosis. 49 for 1 to 3 days, stop eating and ruminating, and also develop symptoms of colic or tympany, after which recovery takes place. After intravenous injection of blackleg virus a similar mild infection sometimes appears. Very severe’ cases of infection occur sometimes in which the animals suffer from general indisposition, tympany, and diarrhea and succumb in 8 to 12 hours, without the appearance of a distinct swelling. The existence of a genuine parturient blackleg, according to the latest investigations, seems doubtful (see page 37) and could at best be ascertained by autopsy, and then only in cases where the muscles in the neighborhood of the genital organs show the characteristic necrotic changes (such a case was observed by Kosselmann). In sheep the disease has a sudden onset, and is indicated by a stiff walk, weakness of the back, moderate tympany, champing of foam, and high fever. On the surface of the front portion of the body, particularly on the neck and lower chest, the wool is raised at one place, and here a swelling may be found the size of the palm of the hand (Scheibel). In swine blackleg mostly appears with a severe acute inflammation of the throat and heavy phlegmonous swelling of the surrounding parts (Marek, Born). The development of the tumor which’ may extend backwards and to the shoulder is also accompanied with feverish. symp- toms, by vomiting and diarrhea, and the latter symptoms are also ob- served when the crepitant swelling has developed on a posterior ex- tremity (Battistini). me are Diagnosis. The rapid course and the development of a crepitant, edematous swelling, in cases where the latter appears on the surface of the body, make the diagnosis fairly easy. If, however, the swellings are in the interior of the body, the nature of the acute feverish attack can only be surmised through other factors, particularly by the fact that blackleg frequently ap- pears in the particular region. The disease may be mistaken, especially for malignant edema, in the course of which crepitant swellings appear on the surface of the body also. The appearance of the swellings, which are restricted to certain re- gions and to young animals, in those parts of the body with abundant musculature is suggestive of blackleg. Besides, the swelling is here more emphysematous, the contained fluid dark red and foamy, and the muscles are black colored, while in malignant edema the swelling is more edematous, the fluid gray-red or colorless, and the muscles diffusely reddened or only red-gray (Gutzeit). The development of an edematous crepitant swelling in the neighborhood of the external genital organs at the time of birth will in itself be an indication of the presence of malignant edema. Blackleg is differentiated from anthrax more readily, for in the latter edematous swellings are rare and, if present, al- ways hot and painful without crepitation. In phlegmonous inflammations of the subcutaneous tissue, from pyogenic wound infection the local character of the disease is distinctly indicated 50 Blackleg. and the course, as a rule, is slower. In subcutaneous emphy- sema, leaving out of consideration the etiological factors, the. total absence of acute symptoms of inflammation and the normal condition of the skin are characteristic. At the autopsy, aside from the microscopic results and the serous-emphysematous infiltration in the region of the swelling, blackleg is indicated especially by the odor of rancid butter, the black discoloration of the musculature, and the absence of a strictly acute tumefaction of the spleen. In doubtful cases the diagnosis is verified through microscopic examination of the diseased muscles or the yellow foci in the liver and the kidneys, and through injection of such material into test animals. For this purpose Wulff recommends drying the piece of muscle in an air current at 30-32°C. and, after pulverization, to heat the material 5 minutes in distilled water at 65°C. From a mixture made of 0.1 gm. of dried muscle substance and 10 ec. water, 0.002 ec. is sufficient to kill guinea pigs by intermuscular inoculation. At the autopsy of such guinea pigs numerous bacilli are found in the liver, which, however, never form chains (Foth; forming of chains characterizes the bacilli as edema bacilli). On the other hand, pigeons, rats and rabbits are never, or at least only exceptionally, killed by 0.01 cc. of the emulsion. Owing to the extreme rarity of blackleg in other kinds of animals, the diag- nosis should always rest upon an exact bacteriological examination, because, other- wise, confusion with pseudo-blackleg and malignant edema is liable to occur. Treatment. The treatment of blackleg is hardly ever suc- cessful and only consists in a local antiseptic treatment of the swellings. For this purpose, it is advisable to incise the tumor at several places and then press it out and wash the exposed dis- eased tissue carefully and repeatedly with disinfecting liquids. The most suitable for this are: 3% carbolic acid, 5% lysoformic acid, 0.1% salicylic acid, 0.1% formalin solution, and tincture of iodine, of which liquids the first ones should also be sub- cutaneously injected at several places in the immediate sur- rounding tissue. If the swelling has developed in the middle of an extremity, a bandage or other ligature may be applied above the tumor, and the latter may then be scarified (Wallraff). Tolstouchow obtained good results from applications of ice and snow, and by rubbing with oil of turpentine. Leclainche & Vallée recommend the treatment with immune serum, of which first 60 to 100 ce. are injected into the jugular vein, and thereafter this amount is injected every 2d to 4th hour under the skin in the region of the shoulder. In the be- ginning of the infection and in cases of a protracted course, the results are said to be favorable. Prevention. As the disease seems to be limited to certain regions, and to certain places within those regions, especially damp, swampy pastures, the cattle should be kept away from such places. Through rational amelioration of the soil (draining away the water, regulating the rivers, planting trees and plowing) places which have been considered dangerous may be made harmless. In Denmark, according to Jensen, the Prevention. Immunization. 51 disease has decreased considerably in the course of the last 30 to 50 years, owing to such improvements of the ground. When this is not practicable, and the danger of infection re- mains, the appearance of the disease can be prevented by means of protective vaccination; otherwise, the immediate change of pee or stable often results in the disappearance of the isease. Immunization. Arloing, Cornevin & Thomas have stated that cattle raised in blackleg districts mostly contract the disease at a young age, while animals brought there from disease-free regions are liable to be infected at an older age. This is ex- lained by the supposition that the young animals, during their stay in blackleg districts, become immunized early by repeated absorption of smaller amounts of virus. When these authors produced a mild attack of the disease by means of injection of small amounts of virus, they also found that the inoculated animals later resisted otherwise fatal infections. Based on this experience they have devised.a very valuable and practicable method of protective vaccination, which has since been modified in many ways by other authors. I. Two inoculations with attenuated virus. (Method of Arloing, Cornevin & Thomas.). A vaccine is prepared from diseased, powdered muscles by attenuating the virus through heating to a high degree of temperature. For this purpose, the diseased part of the muscle is ground in a mortar with some water, and dried in a thin layer at 37°C.; then the dry mass is mixed with 2 parts of water, and the one half heated at 100-104°C., the other at 90-94°C. for 7 hours. The former makes the first weaker vaccine, the latter the second stronger one. The high temperature attenuates the virulence of the virus, and the longer and stronger it has been heated the more attenuated it becomes. The spores, however, in spite of the influence of the heat, remain capable of germinating, but the toxin having been weakened through heat, the spores are not capable of exerting their pathogenic influence. Being to a cer- tain degree protected against the phagocytes by the coagulated albumin, the spores begin to germinate and to multiply slowly, and thus little by little, the newly produced toxin immunizes the tissues. The immunity reaches the necessary degree in 8 to 10 days after the second vaccination. Until then, however, the animals have a lower resistance aganst an artificial or natural infection (negative phase). The practical value of the protective vaccination is already definitely established. The first experiments proved that ani- mals, vaccinated at the end of the tail, subsequently withstand the intramuscular inoculation of a very virulent culture without harm, and that the immunity obtained lasts at least 17 or 18 52 Blackleg. months. Later vaccinations on thousands of animals performed in many sections have shown that the artificial immunity also protects against natural infection. The vaccinations have re- sulted in a large decrease in cases among vaccinated animals (11 to 12 times fewer cases than among non-vaccinated animals) ; besides in the infected localities the percentage of mortality has decreased during recent years, which evidently is owing to the fact that there have been fewer diseased carcasses and less contaminated material to infect the ground. The protective vaccination is now practiced with good results in those districts where the disease usually appears as an epizootic. The method was modified by Preisz so that the powdered muscle substance is heated for 6 hours in live steam, and 0.05 gm. is used for the first, and 0.10 gm. for the second vaccination. In 1880, Arloing, Cornevin & Thomas subjected 13 head of cattle to protec- tive vaccination at Chaumont before a commission; when these cattle were later inocu- lated with virulent material they all remained healthy, while out of 12 non-vac- cinated animals 11 acquired blackleg as a result of a similar artificial inoculation, and 9 of them died. According to Strebel, out of 82,550 cattle vaccinated during the years 1884 to 1898, in Switzerland, 0.75% contracted blackleg, while out of 35,400 non-vac- cinated animals, kept under the same conditions, 2.6% succumbed. According to another compilation by Strebel, during the years 1885 to 1894, out of 325,892 vac- cinated cattle in various countries, 0.056% died from vaccination blackleg, and later 0.38% died from spontaneous blackleg. There were 129,705 vaccinated animals kept during the summer on the same pasture with 240,560 unvaccinated animals; out of the former 0.42% and out of the latter 1.76% were the victims of blackleg. Strebel considers vaccination in the tail as less dangerous than in the shoulder, since with the former, 23 out of 107,080 vaccinated animals (0.021%) and with the latter 181 animals out of 26,816 (0.67% or 31 times more) -died as a result of the vaccina- tion. On the other hand, Suchanka at Salzburg was. satisfied with the vaccination in the shoulder. In the canton of Berne in the years 1885 to 1908, out of 463,613 vaccinated animals 580 (0.125%) died after vaccination, and 1,915 (0.41%) in the following 14 months (Belavoine). In the Austrian alpine regions, during the year 1909, 33,056 head of cattle were vaccinated, out of which, during the pasture sea- son, 114 (0.345%) died, against 1.094% among the unvaccinated herd-mates. In Hungary the protective vaccinations have had good effect both on the improved breeds and on the native cattle. First the Lyons vaccine, and later Preisz’ vaccine were used. According to Hutyra’s compilations, during the years 1893 to 1900, out of 16,679 vaccinated animals 22 (0.13%) were lost. In the year 1907, out of 14,029 animals vaccinated in infected herds, 30 died after the first vaccination, and sub- sequently by the end of the year 36 had died; on the other hand, in previously unin- fected herds, the loss amounted to only 1 and 15 respectively out of 14,148 vaccinated animals. Technique of Vaccination. The 10 doses (1.0 g.) of vaccine contained in folded paper-wrappers (yellow-red powder) are ground carefully with 5.0 ce. of sterilized water in a small mortar, and the mixture is filtered through sterilized, moistened linen cloth. The filtrate is drawn into a syringe 5 ec. capacity made for the pur- pose, and the fluid kept agitated in order to avoid sedimentation. The piston of the syringe is divided into 10 divisions; after filling the syringe the indicator is placed at the Ist division. According to the original French method (Lyons), the place of injection is on the lower part of the tail; the first injection is made 3, and the second 2 hand- breadths from the end of the tail. While the animal is secured at the head and at the hind part, the tail is taken up with the left hand, the hair is shaved from the site of injection and the skin disinfected; then the trocar going with the syringe is pushed under the skin to the handle, thereby making a canal about 5em. long. The trocar is then carefully withdrawn and in its place the dull hollow needle is inserted, and one dose is injected into the canal. Then the needle is pulled out, the place of injection pressed together with the left thumb, the syringe delivered to the assistant, and the injected vaccine pressed upward by means of the right thumb; finally, the tail is bandaged with a narrow linen bandage over the place of injection. Immunization. 53 The bandage is removed after four hours, although it may safely be left on in cattle kept in the pasture. After 10 to 12 days the animals are again vaccinated in the same manner but with the stronger vaccine. Many firms ship emulsions of the vaccine powder in sealed glass tubes for immediate use. Such vaceine is easily contaminated and should be used as soon as possible, but the powder vaccine keeps unchanged for months. According to recent experiences, the vaccination, at least on fhe hardy range cattle, may be performed behind the shoulder with the same results and more conveniently (see, however, Strebel’s statistics). Here it is also advisable to per- forate the skin by means of a trocar, while the bandage after the injection of course is dispensed with. The second vaccination likewise follows 10 to 12 days later, but on the opposite side of the chest. It is advisable to apply the vaccination at the end of winter or in the spring, if possible, before the cattle are sent to pasture. Otherwise the animals are liable to be infected before vaccination, and the summer heat may cause unpleasant complications after tail vaccination, according to the Lyons method, because the animals do not keep the vaccinated part of the body quiet. Calves less than six months old and cattle over 4 years old raised in blackleg districts, as well as pregnant heifers in the last four weeks of pregnancy, should not be vaccinated. Sucking calves are not immunized by the vaccination, and old animals as a rule do not contract the disease. Immediate results of the vaccination. Vaccinations if properly per- formed only cause a slight local swelling at the place of injection, which rarely is accompanied by general indisposition and only by a slight rise in the tem- perature. Unpleasant complications are seldom observed and, as a rule, occur only when the vaccination has not been performed with the necessary care and cleanli- ness. Such complications, which usually appear 3 to 6 days after thc vaccination, consist in necrosis of the 3 or 4 last vertebra of the tail, bending of the iail, forma- tion of abscesses, inflammation, ete. Protective vaccination of sheep. Scheibel vaccinated sheep successfully with vaccine prepared from diseased muscles of sheep. The meat is dried at 30° C. ‘and ground; one half is heated at 100° C. and the other half at 85° C. for 6 hours; of this 1.0 gm. is used for every 20 sheep. The vaccination is performed, as with cattle, near the end of the tail, and in docked sheep on the inside of the leg. Such vaccinated animals prove immune against the infection with fresh diseased muscle or blackleg virus. II. One inoculation with attenuated virus. According to experiments by Kitt, a powder prepared from diseased muscles, after having been heated for 6 hours in dry air at 85 to 90°C., or still better, in live steam at 97°C., gives a suitable vaccine. One injection of such vaccine into cattle immunizes them suffi- ciently and lastingly, without causing conspicuous symptoms of disease (the vaccine kills sheep in doses from 0.2 to 0.6 gm.; smaller doses produce only slight fever). This method which is conducted in the same way as vac- cination with Lyons vaccine, except that the operation is per- formed in one act, is especially to be recommended for vaccina- tion of the more hardy native cattle, but it also gives satis- factory results in the improved breeds which have less power of resistance. In Bavaria, during the years 1898 to 1906, out of 62,178 vaccinated head of cattle 8 died shortly after the vaccination and 134 later, in all 0.22%, while in the first 5 years, on the same pastures out of 23,324 non-vaccinated animals 398 or 1.70% died from blackleg (Kitt). In the years 1903 to 1905, out of 25,609 vac- cinated animals 68 or 0.26% died later from natural infection. In Austria, accord- ing to the official reports, in the years 1891 to 1894, 28,855 head of cattle were vaccinated by one inoculation with the Kitt vaccine; out of those 47 or 0.16% died from vaccination blackleg and 86 or 0.29% from spontaneous blackleg. In Hungary, in the year 1892, Makoldy vaccinated 230 head of cattle from 1 to 4 years old by Kitt’s method, one-half belonging to the Hungarian-Sieben- biirgen breed, and the other half to the Pinzgau breed. The vaccination itself 54 Blackleg. caused no loss, and no case o. blackleg appeared among the vaccinated animais during the following year. : In the United States this method has been much in use since 1897, with the modification however that Norgaard heats the dried ground muscle intended for vacci- nation only to 93-94°C. The Bureau of Animal Industry sends out 114 millions of doses of vaccine every year, and the resuits of the vaccinations have been favorable. Thus, in the years 1907-08, out of 690,828 vaccinated animals 227 died within 48 hours after vaccination, 507 from 2 to 7 days after, and 2,734 later within a year (total loss 0.50%). : In India, Holmes obtained the best results from one injection of a mixture of the first and second Lyons vaccine, which by means of a particularly con- structed syringe was placed under the skin in the shape of a pill. III. Immunization with serum and attenuated cultures. Kitt (1893-1899) obtained from sheep which had been treated repeatedly with intravenous and later with subcutaneous in- jections of muscle juice from blackleg tumors, a blood serum which in 5 to 10 cc. doses protected sheep against an injection of the virus made 3 to 8 days later, and 15 cc. injected into a goat cured the already developing disease. According to later investigations (1899), goats, cattle and horses also produce similar active blood sera, and the last named animal partic- ularly seems to be suitable for the purpose. These results were later confirmed by Arloing, and still later by Leclainche & Vallée; besides, the latter authors have ascertained that blood serum and virus mixed together, or each for itself when injected at the same time, do not immunize, but that the successive application of blood serum and virus affords a mode of immunizing, which may be used for practical purposes. The method which has so far peen tested only in France is as follows: For vaccination two different vaccines are used. The one is blood serum from horses, which, through repeated intravenous injec- tions with bouillon cultures of the blackleg bacillus containing toxins, have been highly immunized; the other is a bouillon culture of ‘the same bacillus attenuated by being heated to 70°C. for 3 hours. First the animals are injected with 10 to 20 cc. of blood serum, according to their weight, in the region of the shoulder, and 5 to 6 days later a second injection is given subcutaneously with 0.5 to 1.0 ce. of attenu- ated pure culture at the same place or in the neck, ear or tail. This form of protective vaccination may also be applied without hesitation in already infected herds. Leclainche & Vallée vaccinated in the year 1902, 447 head of cattle without any direct loss, but subsequently one animal died from blackleg; later statistics indicate 8 deaths among 7,987 vaccinated animals (0.1002%). According to Leclainche & Vallée some of the animals on blackleg pastures harbor the virus in the intestinal canal (latent infection), but they are protected against its pathogenic action by the intestinal juices and phagocytosis; if, however, such animals are inoculated with live, even attenuated, virus, the body thus attacked from two sides, can no longer combat the infection. Through the preceding vaccina- tion with serum, the resistance of the animal is increased to such a degree through the production of passive immunity as to make it efficient even against the double danger. This conception can hardly be recognized as correct in its present form, because after vaccination of already diseased herds with live virus direct losses from the vaccination are seldom observed. To the occurrence of such losses other factors are contributory, particularly the relative susceptibility of the animal in comparison with the degree of virulence of the vaccine. Immunization. 55 IV. Protective vaccination with thread covered with spores. (Method of Thomas.) Thomas, a veterinary surgeon at Verdun, recommends a spore-containing vaccine, the prepara- tion of which is not given (supposedly through growth in frog’s bodies); with this vaccine silk threads (fils virulents, black- legine) are impregnated which he introduces into the sub- cutaneous tissue of the tail. In his opinion, this method is more effective than the original Lyons method, because a blackleg culture develops around the threads left under the skin which exerts a continued immunizing action on the organism (in an experiment with sheep, he found virulent spores and bacilli between the silk threads 328 days after the vaccination). The vaccination instrument consists in a trocar fastened to a handle of wood behind the tip of which is a eut for placing the silk threads. One dose of the vaccine consists of 7 to 8 short threads which are fastened together at the ends by means of a metal nipper. At the vaccination, after the threads have been placed in the notch and the nipper is cut away, the needle is stuck deep into the sub- cutaneous tissue near the end of the tail (in calves behind the shoulder) as nearly as possible parallel with the surface of the skin, and immediately pulled out again, whereby the threads slip off from the needle and remain in the depth of the vac- cination canal. The vaccination is either performed twice with a weaker and a stronger vaccine, or only once with the latter. In America 135,000 head of cattle were vaccinated in the years 1899 and 1900 according to this method (one single vaccination). According to the reports of the results, the vaccination itself caused no losses, while later, as a result of natural infection, 0.4 to 0.7% of the vaccinated animals died. Lately this method has also been used in Germany, and Warringholz obtained good results in 406 and Witt in 700 animals; on the other hand, in Alsace-Loraine (1901) 22 vaccinated animals out of 260 died, while in Hungary, Viasz lost 16 out of 70 vaccinated animals within 3 weeks. According to investigations by Régn, the vaccine is very impure and con- tains particularly a large number of staphylococci; in connection herewith, Guillebeau frequently observed vaccination abscesses among cattle in the canton of Berne. V. Other methods of immunization. It is also possible to immunize cattle by means of other methods, which, however, are little used in practice, and only deserve attention from a scien- tific point of view. 1, Protective vaccination with non-attenuated virus. Cattle may be immunized by subcutaneous injection of a small amount of the juice from the swellings into parts of the body with low tem- perature and dense subcutaneous tissue. The subcutaneous injection of 1 to 6 drops into the end of the tail causes neither local nor general symptoms; 10 to 15 drops will cause an increase in temperature of 1.5°C., while 20 drops will cause a local swelling. The further away from the trunk the injection is made the milder the symptoms appear ; injections in the vicinity of the root of the tail, however, often cause severe disease. According to Arloing, the direct intravenous injection, although it requires more manual skill, is the most favorable. It consists in injecting 3 to 4 drops of the serous fluid of a swelling into a vein of the animal, care being taken that none of the liquid gets into the peri- vascular connective tissue. After a regularly performed vaccination, general symptoms, such as a slight elevation of temperature and loss of appetite, will appear, after the disappearance of which tie animal 56 Blackleg. will resist a subsequent artificial or natural infection. The results of these experiments are very favorable, but the operation requires great care and skill, because, if some of the vaccine should locate in the porous tissue of the neck, fatal blackleg will almost surely result (Eloire). Intratracheal injection with fluid from the: swellings is subject to the same consideration as to the immunizing effect and the danger. Poels used virulent cultures of blackleg bacilli for protective vac- cination. As soon as the formation of spores has begun in the culture small cotton pads are immersed and afterwards dried; at the time of vaccination they are pushed under the skin of the tail where they cause a violent, but harmless, inflammation. During the years 1904 to 1906, 21,329 calves from 2 to 10 months old were vaccinated in Hol- land according to this method with an annual total loss of from 1.0 to 1.4% (Balavoine). 2. Protective vaccination with attenuated pure culture. Kitasato found that fresh bouillon cultures more than 2 weeks old or heated to 80°C. for half an hour did not kill guinea pigs, but im- munized them effectively. Kitt had a similar experience (1894) with subcutaneous injections of 1 to 5 ec. of bouillon culture in sheep and cattle, which, 6 weeks later, resisted a virulent infection. Owing to these favorable experimental results the method was used in practice for a time. (In Austria, out of 7,434 cattle vaccinated during the years 1894 to 1895, 8, or 0.11% died as a result of the vaccination and 93 or 1.25% from spontaneous blackleg.) Leclainche & Vallée injected cattle subcutaneously with a 5 to 8 days old bouillon culture which had been heated at 70°C. for 2 hours, whereafter the animals thus treated were subjected one week later to a subcutaneous injection of 2.0 ec. of a very virulent culture without any harmful effect. This single vaccination, however, has not been kept up in practice, because out of 39 animals 4 died as a result of the vaccination. Later the vaccination was performed in 2 acts, the first with a culture heated for 3 hours to 75°C. and the second with one heated to 68-70°C. The result this time was also unsatisfactory, one animal dying after the first vaccination and six after the second. Of the vaccine prepared by the sero-therapeutic institute at Toulouse 0.5 ce. is injected into calves less than 6 months old, and 1.0 ec. into older animals, under the skin of the ear or the end of the tail. Detre recommends a liquid vaccine which he prepares by separating the muscle fibers and albumin coagula from the spores and toxins in the Lyons vac- cine, obtaining a liquid which contains the same active substances as the Lyons vaceine. The spores and toxins attenuated through higher temperature at two different degrees of exposure in a hypertonic solution of salt, are offered for sale in the market, and the vaccine is said to prove its efficiency in practical experiments. 3. Immunizing with toxins. Roux succeeded in immunizing guinea pigs against blackleg by repeated injections of 15-day old bouillon culture heated to 115° C. or a filtrate of such culture, into the ab- dominal cavity, and also by subcutaneous injection of a bacteria-free filtrate of the juice of the swellings. Duenschmann obtained similar results with only the filtrate of the juiee of the swellings from animals that had died from spontaneous blackleg. Finally, Schattenfroh used pure solutions of toxins from which the bacteria had been removed by means of clearing powder, but with very unfavorable results, as 23 out of 306 vaccinated animals died from the effeet of the poison, and 40 to 50 more became very sick. Immunization. Veterinary Police. Bradsot. 57 4. Protective inoculation with immune serum. In 1905 Grass- berger & Schattenfroh injected about 800 head of cattle in Tyrol and Lower Austria with serum from an animal which had been immunized by means of toxin and afterwards with virulent material. The results were unsatisfactory, inasmuch as 8 animals later succumbed to blackleg when placed on infected pastures. ’ 5. Immunization with toxins and immune serum. Grassberger & Schattenfroh prepared a very effective antitoxic serum (0.0025 cc. of serum neutralized 1.0 cc. of toxin) by treating cattle with their toxin (page 43), 40.0 ec. of which killed young cattle, and used this for vaccination after having mixed it with toxin. According to their ex- perience immunity may be attained by means of such a mixture as well as with toxin alone, the former, however, having the advantage that it does not cause edema nor interfere with the general health of the animal. The vaccination consists in one single subcutaneous injec- tion with 5 to 10 ce. of the neutralized mixture of toxin-serum. In the Austrian mountain districts, more than 4,500 head of cattle were vaccinated in 1904 without direct loss, but later 78 died from natural blackleg while at pasture. Veterinary Police. Owing to the enzootic appearance of blackleg in many regions, as well as to the considerable losses caused by it, the disease has recently been made subject of obligatory notification in several countries, among others Ger- many and Austria. The legal methods of prevention are similar to those employed for anthrax, special attention being paid to the destruction of the carcass, and also to the indemnification of the owner and the application of vaccination. According to the results of the investigations of Sauer, hides from animais having died from blackleg may be thoroughly disinfected by being placed for 10 days in a 1:1.000 solution of bichloride of mercury, 5% creolin or carbolie acid solution, and also in freshly prepared whitewash. Literature. Bollinger, D. Z. f. Tm., 1875, I, 297.—Feser, Z. f. pr. Vet. Wiss., 1876, IV, 18; D. Z. f. Tm., 1880, IV, 371.—Arloing, Cornevin & Thomas, Le Charbon sympt. du. boeuf, Paris, 1887.—Roux, A. P., 1887, I, 62.—Kitt, Chl. f. Bakt., 1887 I, 684, and 1888, III, 572; Monh. 1893, IV; 1896, VIII, and 1901, XIII (Review) ; Hb, d. p. M., 1903, II, 600 (Etiology), and 1904, IV, 1001 (Immunization; with literature).—Kitasato, Z. f. Hyg., 1889, VI, 105.—Leclainche & Vallée, A. P., 1900, XIV, 202 and 590 (Lit.).—Thomas, Rép. de. pol. san., 1900, 31—Kerry, O. Z f. wiss, Vk., 1894, V, 228.—Marek, Monh., 1896, VII, 489; 1897, VIII, 174.—Grass- berger & Schattenfroh, Uber d. Rauschbrandgift, 1904.—Smith, Z. f. Infkrkh., 1906, T, 26.—Scheibel, D. t. W., 1907, 61.—Balovoine, Diss., Bern, 1909 (Literature and vaccination statistics).—Tillman, Diss., Bern, 1909.—Foth, Z. f. Infkrkh., 1909, VI, 201.— Wulff, Z. f. Tm., 1909, XIII, 241. ‘“Bradsot’’ of sheep (Gastromycosis ovis). This destructive dis- ease of sheep occurs on the western coast of Norway, in Iceland, and on the Faroe Islands of Denmark, in Scotland where it is known as Braxy, also in Mecklenburg and Prussia (Peters, Dammann & Opper- mann, Hilbrand). Ivar Nielsen established the fact that the disease is caused by a specific bacterium which causes severe inflammation especially of the abomasum and duodenum. The disease (Bradsot, Braasot or Brosot—quick plague) is chiefly observed late in the fall or winter when the sheep are driven from ! 58 Bradsot. the mountain pastures to the farms and are pastured on lower lands which have been infected by unburied carcasses. The disease also oceurs frequently during ‘stable feeding in the winter, and exception- ally in summer during pasturing. Yearlings are most susceptible, while lambs and animals over 3 years old rarely become affected. Well nour- ished animals appear more predisposed. Frequently the course of the disease is very rapid, and the animals die within a few hours. In the slower form a marked weakness is observed. Later the animals pass into a comatose stage, grind their teeth, respiration is difficult, and soon death results. In some cases frothy saliva drips from the mouth, and frequently tympanitis develops in association with colicky symptoms. R. Fréhner also observed swell- ing of the head, throat and tongue, bleeding from the mouth, nose and vulva, swelling and bluish-red discoloration of the vaginal mucous membrane. On post mortem the most conspicuous change is a severe acute inflammation of the abomasum and duodenum, the mucous membrane Fig. 18. Bacilli of Bradsot with Fig. 19. Bacili of Bradsot with spores. Kidney fluid from sheep; flagella. (After Tokishige.) staining by Gram. (After Jensen.) and submucous connective tissue of which appear edematously swollen and permeated with extensive hemorrhages which may sometimes be necrotic. Similar changes are occasionally found in the small intestine, whereas in some of the cases the autopsy reveals a general infection with parenchymatous degeneration of all organs and a considerable enlargement of the spleen, which may crepitate. A sero-hemorrhagic exudate is present in the abdominal cavity, and gelatinous infiltration of the subcutaneous connective tissue may be observed while the serous fiuid may also contain gases. _ Bacilli 2.6# long, 1# thick which stain by Gram, may be demonstrated in the affected mucous membrane and in the subjacent gelatinous con- nective tissue, while in a general infection they are also present in the blood. They frequently form chains, and mostly contain centrally located oval spores, and may grow into long threads. The bacillus is supplied with numerous long screw-like flagella (Fig. 18 and 19). It is an anae- robe and multiplies in the depth of the media, forming gas, and therefore resembling the bacillus of blackleg. From this, however, it may be distinguished by the formation of threads and chains. It is also patho- genic for pigeons, chickens and mice (Jensen, Tokishige). Bradsot. 59 _ -Subcutaneous injections of pure cultures produce only excep- tionally a generalized affection in sheep when the clinical picture re- sembles blackleg (hemorrhagic-gelatinous infiltrations and gas forma- tion in the subcutaneous connective tissue and muscles). In most instances only a local swelling develops which later disappears. Ani- mals thus affected which recover later resist natural infection. Guinea pigs, rabbits and pigeons are also susceptible. The natural mode of infection is at present not known with certainty, but it is possible that the infection occurs through slight injuries along the upper digestive tract. After the appearance of the disease a change of pasture and stable as well as a thorough disinfection of the premises is indicated. Immunization. Nielsen used a heated powder made from kidney tissue, containing numerous bacilli and spores obtained from sheep which had died spontaneously. This method was principally employed in Iceland, but with uncertain results. Tokishige, on the other hand, proved that horses and goats treated intravenously with the virus yielded a potent serum. Jensen worked up the three following methods: 1. Eight-day old spore-containing bouillon-serum cultures of the bradsot bacillus are rapidly evaporated at 50°C., finely pulverized and mixed with a small quantity of gum tragacanth. The dose (0.005-0.03 gm.) must be established by test inoculations, as the suscepti- bility of sheep varies in different breeds and ages. The immunity is satisfactory, and no losses were observed from the vaccinations in the Faroe Islands, while in Iceland they amounted to 1.5%. 2. Blood serum of horses immunized by intravenous injections of virulent cultures (0.02 gm. serum protect guinea pigs against fatal infection) is dried, pulverized and mixed with the vaccine described under 1. For practical purposes a mixture of 0.005 gm. each of culture and immune serum is used. ; 3. Threads are placed in 3-4 weeks old dextrose bouillon cultures and then dried at 40-50°C. These threads are inserted with a suitable needle under the skin on the inside of the thigh and left there. The practical results appear uniformly satisfactory. In some cases, how- ever the acquired immunity was insufficient. In Iceland and the Faroe’s about three quarters of a million sheep were vac- cinated by these three methods previous to 1906. The losses in the first group which included 208,805 animals amounted to 1.45% as a result of the vaccination, and 0.32% later on. In the second group of 52,327 the losses were 0.03% and 1.93% respectively. In the third group of 15,934 animals 0.03 and 4.65% succumbed, while in the unvaccinated sheep it reached 4.21, 5.04 and 5.80% respectively (Jensen). In opposition to the above conception of the etiology of the dis- ease, Miessner believes it is questionable whether bradsot represents a uniform disease, being rather a clinical-anatomical name for any dis- ease in sheep which causes death within a few hours, and which manifests on autopsy an extensive hemorrhagic inflammation of the abomasum in addition to an injection of the subcutis. He also con- cluded from his numerous bacteriological examinations of cases con- ‘sidered as representative of the disease, that the etiological significance of the bradsot bacillus is very questionable, principally on the ground that it has not been possible to produce the anatomical picture of the disease with bradsot bacilli. He also failed as a rule in demonstrating the mentioned micro-organism in fresh carcasses of animals dead of the disease or which were killed shortly before the fatal termination. He, however, failed to ascertain the true causative agent. 60 Bradsot. Reindeer Pest. Swine Hrysipelas. Literature. Krabbe, D. Z. f. Tm., 1875, I, 34.—Nielsen, Monh., 1896, VIII, 55. —Jensen, D. Z. f. Tm., 1896, XXII, 249 (Lit.); Hb. f. p. M., 1903, IT, 660 (Lit.).— Hamilton, The Vet. J., 1901, 286.—Peters, A. f. Tk., 1897, XXIII, 73.—Tokishige, Monh., 1901, XII, 1—Hilbrand, Z. f. Infkrkh., 1907, III, 325 (Lit.).—R. Froehner, Dz t. W., 1906, 359.—Miessner, Mitt. d. Inst. f. Landw. in Bromberg, 1909, I, 217 (Lit.). Reindeer Pest. This devastating disease occurs periodically (the last time in 1895 and 1896) among the reindeer herds of the Lap- landers in northern Sweden and probably also in Norway. In such outbreaks many thousands of animals, mostly calves, but also yearlings and two year olds become victims of the disease. It usually rages dur- ing the summer time when the animals drift during the warm weather from the cool high pastures into the valleys. The etiology of the dis- ease was established by Lundgreen (1897), and the virus has been more extensively examined by Bergmann (1901). The symptoms of the disease, which is usually fatal in from-6 to 12 hours, are excitement, inappetence, cessation of rumination, in- creased thirst, staggering and uncertain gait, difficult and accelerated respiration, cough, and particularly the appearance of edematous- emphysematous swellings at various points of the body. The tem- perature which is at first high, drops at the approach of death. There is bleeding from the nose, and a very repulsive odor is apparent. The post mortem examination reveals fluid containing considerable gas in the subcutaneous connective tissue, as well as collection of gas in the internal organs. In addition to a reddish transudate in ‘the body cavities a yellowish discoloration of the liver and a moderately acute swelling of the spleen may be observed. From the subcutaneous serous fluid, the transudates of the body cavities and the blood the reindeer pest bacillus, which resembles the blackleg organism, may be obtained in pure culture. It is Gram-posi- tive, motile, forms oval spores in the animal, and in artificial media at a temperature of 30-38°C. It may be cultivated on the ordinary media aerobically as well as anaerobically, and the growth is especially luxuriant at body temperature, when a great amount of fetid gas and’ acid is formed; gelatin becomes liquefied. By subcutaneous and intramuscular inoculation of pure cultures the disease may be reproduced in reindeer. Sheep and guinea pigs as well as mice and cattle are also susceptible to artificial infections, whereas rabbits, hogs, dogs and chickens are tmmune. Natural infec- tion probably results through wounds in the skin and intestinal mucous membrane. Inoeculations of sheep into the tail produce only passive elevation of temperature, and result in an increased resistance against an other- wise fatal subcutaneous infection into the rump. Animals immunized against reindeer pest are not immune to blackleg or bradsot. Literature. Lundgreen, Z. f. Tm., 1898, II, 301.—Bergmann, Ibid., 1901, V, 241. 4, Swine Erysipelas. Erysipelas suis. (Stabchenrotlauf, Rotlaufseuche [German]; Rhusiopathia suis, Rouget du pore [French]; Red fever [English]; Antrace eresipelatoso, Mal rosso [Italian].) Swine erysipelas is an acute, septicemic infectious disease of young hogs caused by a very fine, rod-shaped bacterium, Oceurrence. Etiology. 61 Bacillus erysipelatis suis, which is found in the blood of the affected animals. History. The disease which until the eighties was vot distin- guished from anthrax was first studied by Pasteur & Thuillie: (1882). These investigators did not establish the etiology of the diseasz, since they accepted as its cause the eight-shaped bacterium which was first recognized by Detmers. Nevertheless their investigations resulted in the preparation of a satisfactory serum for practical immunizations. The bacillus of erysipelas was discovered by Liffler in 1885, who together with Schiitz differentiated the disease from hog cholera. The differentiation had, however, also previously been made by Eggeling from his clinical observations. Later the etiological knowledge was advanced by the work of Lydtin & Schottelius, Bang, Jensen, Preisz, Lorenz, Voges and Schiitz, while Lorenz, Leclainche and Schiitz worked extensively on the problem of serum immunization. Occurrence. Swine erysipelas occurs everywhere on the European continent, and is usually prevalent in the infected territory in summer, with varied severity in an enzootic form, and not infrequently epizootically. During the last dec- ades the disease has become more widespread as a result of the propagation of pure-bred animals. The disease usually appears during the warmer periods, increases in intensity during the course of the summer, and abates at the approach of autumn; whereas, during the winter only sporadic cases are observed. . In Germany erysipelas is very extensive. Since the inauguration of com- pulsory reporting, the number of infected townships increased. from 8,491 in 1897 to 21,522 in 1907; and the number of individual infections in hogs from 33,950 to 75,619, of which 80% died or were killed. During the last years the disease raged in the Prussian government districts, particularly in Posen, Oppeln, Bromberg, Marienwerder, Liegnitz, and Breslau. : In France the disease also occurs extensively. Optimistic figures show that the annual losses amount to at least 100,000 hogs valued at over $1,000,000 (Nocard & Leclainche). In Austria the disease is more prevalent in Bohemia, Galicia; also in Moravia and Southern Austria; while in the Alpine countries the erysipelas invasions are very slight. During the period from 1891 to 1900 the number of infected districts increased from 953 to 2,368; that of the affected animals from 9,286, to 14,891 (0.25 and 0.32% of all the hogs). In Hungary the disease was hardly known three decades ago in the flut lands around the river Tisza, but since that time it has become quite prevalent. In the years between 1899-1908 the average number affected amounted to 30,757 hogs, but fluctuated between 7,624 in 254 townships (1899) and 56,455 in 1878 townships (1906). : The disease is also widely spread in Belgium (annually about 2,000 cases), in Holland 1,514 cases in 1908, in Denmark 330 new herds, in Russia 55,996 cases in 3,929 townships; further it prevails in the southern European countries, whereas in Sweden and Norway it occurs more rarely, while in Great Britain only sporadi- cally, and in a chronic form. The disease also occurs in the United States of North America, but in the benign form mentioned. [Urticaria but not infectious swine erysipelas occurs in the United States]. Etiology.. The causative agent, Bacillus erysipelatis suis (Bac. rhusiopathiae suis, Kitt) is a very slender, straight or slightly curved, non-motile organism which multiplies by fission, and is from 1 to 1.5 long (1-4 to 1-5 the diameter of 62 Swine Erysipelas. a red blood corpuscle, Fig. 20). In bacilli grown in cultures fine Gram-positive granules may be demonstrated which are considered by Fedorowitsch and by Rosenbach to be lasting forms (protospores). Staining. They stain readily with aqueous aniline dyes as well as by Gram’s method. Cultivation. The bacilli grow well on the ordinary artificial media with the exception of potato. It is aerobic as well as anaerobic and grows in cultures some- times as long rods or curved threads. On gelatin plates the cultures form whitish, cloudy, very fine flakes with coarse granular centers, which spread out towards the periphery, into a delicate thready meshwork. More -rarely they form bright shiny, branching small colonies, whereas in stabs pinhead sized, white points develop in 2 to 3 days which later fuse into grayish-white, cloudy colonies, from which fine horizontal radiating branches run in all directions of the gelatin (test tube-brush shape, Fig. 21). On agar and on blood serum the bacillus forms very fine punctiform, dew-drop- like colonies. Bouillon is made slightly cloudy, while later a fine, flaky sediment forms on the bottom of the tube. . $e pateeaaise os a Tenacity. The ery- sipelas bacilli manifest con- siderable resistance towards harmful influences, which ; wey probably owe to a wax- a 36 ass like capsule (Schiitz & . Voges). Drying kills them Fig. 21. Gela- only gradually as they re- tin stab culture. main alive when subjected Of Swine ery- to a temperature of 37°C, Sipelas bacilli. : . ; for 31, and to direct sun- light for 12 days (Sirena & Alessi). Heating to 70°C. destroys them in about 5 minutes. Pieces of meat not over 15 cm. thick require 24% hours boiling for a complete sterilization (Stadie). Putrefaction does not destroy the bacilli in meat in . 4 months (Stadie). Salting and pickling destroys them very slowly; pieces of meat and bacon may contain the virulent bacilli after lying in pickle for 170 days, and in a mixture of salt and saltpeter for 30 days, while in smoked ham virulent bacilli were found even after 3 months (Petri). On the other hand, continued smoking for 2 weeks or shorter periods of smoking once repeated destroys the virus of erysipelas in pieces of pickled meat not over 214 kg. in weight (Stadie). Of the disinfectants the following are effective: Chlorate of lime (1%), hot lye (1%), soda (5%), iron sulphate (3%), copper sulphate (44%), corrosive sublimate (.1%), carbolic acid, creolin and lysol (Petri). Fig. 20. Bacilli of swine erysipelas. Smear prepared from blood of a hog.. Gram-eosin staining. Pathogenicity. Pure cultures inoculated subcutaneously kill white and gray mice as well as pigeons in 2 to 4 days. In rabbits the inoculation produces erysipelas-like reddening and swelling at the point of inoculation, which is occasionally fol- lowed in 5 to 6 days by a fatal general affection. In hogs an inunction of virulent bouillon cultures into superficial wounds Pathogenicity. Natural Infection. 63 of the skin as well as subcutaneous injection produces a typical affection of erysipelas which terminates fatally in 6 to 9 days (Preisz). The feeding of cultures also makes hogs ill (Corne- vin, Kitt), but this mode of infection is not always successful. Other animals cannot be infected. Repeated passage of the bacilli through the body of hogs increases their virulence for hogs (Schiitz), and passage through pigeons results similarly for mice (Stickdorn), while the virulence is gradually dimin- ished by continued cultivation. Natural infection usually occurs through the intestinal canal, more rarely through injuries to the skin. The greater frequency of the infection per os is proven by the presence of the bacilli in the intestinal contents of affected hogs, also by the numerous affections which occur in a herd. The infection may also occur through the uninjured intestinal mucous membrane. Injuries such as those from the echinorhynchus, however, facili- tate infection. Food and drinking water are usually the carriers of the infective agent, and become readily contaminated through feces or excrement, urine and other offal of affected. animals. The infection may also occur through the ingestion of blood and meat of dead or slaughtered hogs. The disease is introduced into territories which have been free from the infection, and is thus spread mostly by animals sick or dead of the disease, or by their products. The bacilli are present both in the blood and the excrement of the affected animals, of which the infectivity has been established by the experimental work of Cornevin and Kitt. The infection is present in the excrement even when the hogs are infected through the skin. Therefore the bacilli reach the lumen of the intestines through the blood. The urine of affected animals may also contain erysipelas bacilli. Therefore pastures in which affected animals have been kept or fields which have been fertilized with the manure of such hogs are particularly dan- gerous. The annual occurrence of erysipelas in herds which have been exposed to such pastures or fields is thus readily explained. On the other hand, pastures are frequently con- taminated by improperly buried carcasses, especially since the carcasses of such animals are frequently dug up by dogs and hogs which scatter the infection over the pastures. If dead ani- mals are thrown into flowing water the infection is transmitted to herds of hogs which are pastured along the banks of the stream. Peddling of hogs and hog markets greatly aid in the dis- semination of the disease, inasmuch as affected animals driven over the roads contaminate the roads and the halting places - with their manure. The infection is further spread through the meat of hogs slaughtered in emergency, particularly when healthy animals 64 Swine Erysipelas. are given water in which contaminated meat has been washed. The spread of the disease is also frequently brought about by wandering gypsies who carry the carcasses given to them, or which they dig up, from one town to another, at the same time scattering the viscera in the pastures. Furthermore, butchers, hog herders and castrators may spread the infection, particu- larly through utensils and containers in which meat and meat offal have been kept and which have afterwards been used in feeding or watering. By the findings of Olt, Jensen, Bauermeister and Pitt it has been proven that true erysipelas bacilli may be present in the intestinal canal, particularly in the secretion of the tonsils as well as in the mucous plugs of the ileo-cecal valve of healthy animals. .It is therefore possible that on the one hand the contagion may be spread through healthy hogs, while on the other the disease may break out in healthy herds without a direct introduction of affected animals or products originating from them. Healthy carriers of bacilli may thus become affected, if through weakening influences such as cold, heat, starvation, etc., their normal resistance is reduced, and the bacilli which were present in the intestinal canal may then set up the disease process. In examining the intestines of 66 animals Pitt found the true erysipelas bacilli in 26 cases, and 28 times in 50 tonsil examinations. He believes that through their presence the hog becomes gradually immunized which explains why animals strictly guarded from exposure have been found to possess a lower resistance, such animals becoming severely affected if exposed to infection in spite of all pre- eautions. In territories once infected, erysipelas usually recurs almost annually, although with varying intensity, provided that in the meantime no measures have been undertaken for its suppression. This fact also proves that the infection may remain virulent in the soil and in stable floors for a considerable length of time. It will multiply in the summer time and infect young hogs which will then reinfect the soil with their excre- ment and carcasses. The bacillus of mouse septicemia (Bac. murisepticus) which cor- responds morphologically and in its cultural characteristics with the erysipelas bacillus, and which has been formerly distinguished from the latter by its very slight virulence for hogs must at the present time be considered identical with the erysipelas bacillus or as an at- tenuated variety of it. These conclusions were reached by Jensen, Lorenz, Loffler and Prettner, who proved that animals immunized against erysipelas are also immune against the virus of mouse septi- cemia and vice versa. As the virulence of the mouse septicemia bacillus may increase under natural conditions, and as it has been repeatedly found in stagnant, polluted water (Koch), in putrefactive meat (Johne), and in blood of cattle (Preisz), it is possible that the mice affected with septicemia contribute to the dissemination of erysipelas. Rohrbach has recently (1909) been inclined to consider the bacillus of swine erysipelas and mouse septicemia as two different micro-organisms, and to group Susceptibility. Pathogenesis. 65 them with the erysipeloids of man in a special class (Erysipelotriches: Erysipelothrix porci, EK. erysipeloides and E. muriseptica). This conception, however, appears to have insufficient foundation as the morphological differences are only slight and since the variance in the rapidity of their growth in artificial media is pronounced. (The quickest growth is obtained with the mouse bacillus; less rapid is the Bac. erysipe- loides, while the slowest is the erysipelas bacillus). Stickdorn observed similar dif- ferences in the erysipelas bacillus after passage through mice and pigeons in spite of the fact that serum examination showed no differences in the strains or species; and Overreck also found that the erysipelas bacillus and the mouse bacil- lus agglutinate practically uniformly (1:2000 to 4000) when the organism of the one - is applied to the immune serum of the other. Schipp found a bacillus in the blood of a chicken which was identical with the erysipelas bacillus. On that particular farm many animals died in a short time and the autopsies revealed principally an enteritis and a parenchymatous de- generation of the heart muscle. The same author also isolated a bacillus from the spleen of a cow which died with symptoms of anthrax and which on autopsy re- vealed only petechiae on the serous membranes and on the heart. This organism corresponded morphologically and culturally with the erysipelas bacillus. It was, however, pathogenic for field mice and was not influenced by erysipelas sera. As a secondary finding erysipelas bacilli were also obtained from a cow which died from vaginal diphteria and septic metritis, and by Hiuser in diphtheritic mem- branes of chickens. . Susceptibility. Hogs are particularly susceptible to nat- ural infection between the ages of three months and one year. Sucking pigs manifest a higher resistance while animals over one year old become only exceptionally affected as they have probably acquired immunity during their earlier life. According to Lydtin the English breeds are more suscep- tible, particularly the Suffolk and Poland China breeds, while Yorkshires are less susceptible. The German hogs are highly resistant, while the Hungarian breeds (Mangalicza) occupy a middle position in the order of susceptibility. The disease usu- ally rages more severely among imported hogs than in the hogs which have been raised in the infected locality. The disease has not yet been established in wild hogs. Pathogenesis. The entrance of highly virulent erysipelas bacilli in large quantities into the intestinal canal of healthy hogs will reduce the normal resistance of the animals, and on the other hand the entrance of such bacilli will promote the pathogenic action of such bacilli as were already present in the intestinal canal, by their weakening influences upon the system. ‘Their penetration into the depth of the intestinal mucous membrane is facilitated by injuries through intestinal parasites (strongylids, echinorhynchus gigas), whereupon they multiply in the lymph spaces of the tissues, enter the lymph glands and finally the blood circulation. The bacilli which enter the blood in this manner or through injuries in the skin will continue to multiply there, and then they accumulate in large masses in certain blood vessels, producing weakening of the vessel walls, serous transudations and small hemorrhages probably by the action of the metabolic products. The reddening of the thinner parts of the skin may be traced to this cause, whereas the necrosis of the skin which occasionally occurs is the result of the obstruction of the blood 5 66 Swine Erysipelas. vessels. The accumulation of the bacilli in certain parts is probably favored by their being engulfed by leucocytes which then adhere to the intima of the vessel. In chronic cases when they become attached to the valves of the heart they produce an affection of the valvular tissue (endocarditis verrucosa s. bacil- losa) or a bacillary thrombosis develops in some of the vessels of the corresponding valves. In some cases especially those in which the bacilli are not very virulent, their multiplication occurs only in the lymph spaces of the skin whereby reddening of the skin with circum- scribed edema develops (urticaria, diamond-skin disease) which symptoms disappear after the death of the bacilli. These changes prove that the erysipelas bacilli produce toxins in the body tissues, and in cases of general infection the fever, depres- sion, paralysis and finally death may also be traced to the action of the toxins. This is substantiated by the experience that hogs some- times die as a result of a cutaneous infection with the symptoms of the disease, yet bacilli are only found at the point of inoculation and in the immediately surrounding tissue (Preisz). Until the present time, however, it has been impossible to demonstrate toxic substances either in artificial cultures of erysipelas bacilli or in the carcasses of animals succumbing to the disease. (According to Petri & Maassen, erysipelas bacilli produce toxin in media containing hydrogen sulphide.) Anatomical changes. In the acute form of hog erysipelas the post mortem on animals which have succumbed to the disease shows in most instances only slight changes in the inter- nal organs. The mucous membrane of the stomach, particularly at the pylorus, shows an inflammatory swelling, reddening, and numerous small hemorrhages. The surface is covered with a sticky, glassy mucus. The mucous membrane of the small intes- tine, especially in the duodenum and ileum, appears catarrhal and congested. The solitary follicles and Peyer’s patches are also swollen, the superficial layer of the mucous membrane may sometimes show desquamation and even ulceration (Schotte- lius). Small ulcers also occur on Bauhin’s valve as well as in the large intestine. The spleen is usually only slightly swollen and congested. The liver and kidneys show indications of cloudy swelling; the cortical substance of the latter is mostly darker and often mottled by dark red points (glomerulonephritis). The lungs are hyperemic and edematously infiltrated; sometimes they are atelectatic at their borders as a result of catarrhal inflamma- tion. All the lymph glands are markedly swollen, rich in blood and fluids. The serous membranes may be covered with fine fibrin membranes. Small hemorrhages also occur with relative frequency on the serous and mucous membranes, under the epi- and endocardium as well as in the subcutaneous connective tissue. : Anatomical Changes. Symptoms. 67 Haase found, 2 to 4 weeks after the disappearance of the disease, small dark red areas in the kidneys and in the later stages, purulent nodules, sometimes accom- panied by extensive inflammation of the kidney tissue. _ The blood vessels, corresponding to the red spots of the skin, appear dilated, filled with blood, while the skin and sub- cutaneous connective tissue is edematously infiltrated and studded with small hemorrhages. The muscles either appear healthy or they are grayish red and lustreless, while the inter- muscular connective tissue may be edematous. In rare cases certain parts of the body (ears, tail, nostrils, etc.) or larger areas of the skin may be necrotic (e. g., on the back). In the chronic form the disease manifests an endocarditis (verrucosa or ulcerosa) in the majority of eases. In one or more orifices of the heart, particularly in the left arterial ori- fice, the convex surface of the valves is covered with a cauli- flower-like fibrin coagulum which sometimes reduces the orifice to such an extent that it is hardly possible to insert the quill of a pigeon feather. After the removal of the fibrin deposit small wart-like vegetations or ulcerations appear on the thick- ened valve. Such carcasses also manifest the secondary changes which are usually produced by affections of the heart, such as hydrothorax, passive hyperemia of the lungs, liver and spleen, infarcts of the kidneys, ete. In some cases the autopsy also reveals chronic enteritis, hypertrophy of the lymph glands (without necrotic areas), small necrotic foci in the liver and chronic inflammation of the serous membranes as well as of some of the joints. The bacilli may be demonstrated easily in acute cases in the blood in the capillary vessels of the internal organs (especially spleen, liver and kidneys), in the lymph spaces of the skin, and the subcutaneous connective tissue, in thé red areas of the skin and plaques, as well as in the regional lymph glands, In the blood they are present either free in the plasma-or inclosed in the leucocytes. In chronic cases the bacilli are usually only present in the affected tissues, particularly in the valves of the heart and in the fibrin coagulum as well as in the bile where they remain for a longer time even after the acute affection has subsided (Kitt). With Gram’s stain they may be demonstrated even in putrefactive tissues (Opalka, Rosso). However, it is advisable to cover the parts of organs with salt in order to prevent putrefaction when shipped for laboratory examination. Symptoms. The time of incubation of erysipelas after arti- ficial inoculation is 3 to 5 days (Preisz, Kitt). After natural infection from the ingestion of infectious meat or of contami- nated water the first indications of the disease appear as early as 24 hours, otherwise the time of incubation is usually 3 to 5, and exceptionally probably as long as 7 days. The clinical symptoms show a considerable variance in different cases; in general the following three readily distin- guishable forms of the disease may be observed which may also differ from each other in their course. 1, Urticaria (Diamond-skin disease) represents the mild- est form of erysipelas. In its course the animals show after 1 to 2 days a disturbance of their general health, and sharp 68 Swine Erysipelas. circumscribed, round or more frequently quadrangular or rhom- boidal spots develop in various parts of the body, especially on the chest and back, outside of the thighs and on the neck, but sometimes over the entire body, which are warm to the touch and dark red or violet in color. Later they appear elevated above the surface of the surrounding skin as much as 2 to 3 mm. The center usually becomes pale while the border retains the bright color. In other cases the raised parts remain red and even become darker, while on their surface a serous fluid exudes, which raises the epithelium in the form of small vesi- cles which later dry to crusts. As a rule the plaques are of dollar size, but by their confluence swellings may be formed as large as the palm of the hand. The development of the eruptions is usually associated with fever (up to 42.8° C.), dullness, loss of appetite, thirst, Fig. 22. Swine erysipelas. Gangrene of the skin of the back. (After Schwarzbart.) constipation, conjunctivitis, sometimes symptoms of paralysis and nausea. After the development of the eruptions the symp- toms diminish. Soon afterwards the eruptions also disappear, and after 2 to 3 days, sometimes however only after 8 to 12 days, the animal recovers. In some of the cases the changes in the skin take on a malignant character. On the parts of the body mentioned, more frequently, however, on the ears, head and tail, the skin swells considerably in certain spots, becomes dark red and warmer; soon these places become insensitive, cooler and dry, and finally become separated from the surrounding and , underlying tissues, or the animal loses one or both ears, its tail or distal digits. Sometimes the inflamed skin over the back dies off in its entire extension so that it covers the upper part of the body in the form of a shield (Fig. 22), and gradually loosens from the borders and is east off. The resulting raw surfaces heal later should the animal remain alive, causing dis- Symptoms. 69 figurement in the form of thick, sometimes cartilage-like cicatrices. In some cases an erysipelatous endocarditis develops after the disappearance of the eruptions which terminates fatally, or a paralytic condition results which may remain for a longer time. Jensen (1891), Lorenz, Liipke and others found in urticaria the erysipelas bacillus in the lymph spaces of the affected parts; on the other hand, Markus succeeded in producing a verrucose endocarditis as well as kidney infarcts in a pig by intravenous injection of 2 cc. of a bouillon culture which was derived from a dermatitis, while Schiitz observed urticaria in ordinary country hogs and erysipelas in English, breeds after the injection of the same culture. Jensen and Lorenz proved the presence of the erysipelas bacillus in the lymph spaces of the chorion to be a cause of dry gangrene. 2. Erysipelas septicemia. In this, the most frequent form of the disease, the animals suddenly cease to root and to run. They lie exhausted and dull upon the ground, they crawl under the straw in the stall and when caught they do not squeal or show the usual resistance. They show inappetence, nausea and vomiting. The body temperature rises even at the onset very high (up to 41° to 42° C.) and remains practically constant. The eyelids are frequently edematously swollen, the conjunctiva is injected, the canthus of the eye is filled with a slimy: secre- tion. At first there is constipation, later, however, diarrhea appears, when the animals pass frequently soft, mushy, later entirely fluid stools, which are light gray or dark brown from the admixture of blood. On the second day, rarely earlier, or only immediately before death the characteristic reddening of the skin appears on various parts of the body. On the abdomen, the inner sur- face of the thighs, in the axillary region, sometimes also on the neck and ears, various sized, irregular, pale red spots appear, which later take up a darker and brighter color, and confluate.. The skin over the affected areas is only slightly swollen if at all, and not painful. The redness disappears when pressure is applied but returns when it is removed. In a few cases hempseed sized vesicles containing a serous fluid de- velop on the surface of the spots which later dry and form brownish crusts. Exceptionally gangrene of the skin is ob- served in some parts, especially on the ears, nose and the point of the tail. In severe cases in addition to the described symptoms there are weakness of the hind quarters, cyanosis of the mucous membranes as well as manifestations of pulmonary edema. As the symptoms become more progressive, a sudden drop of tem- perature follows, and finally the animals die in 3 to 4 days. Exceptionally death results at the end of the first day or then only after 8 to 9 days. In milder cases the intensity of the 70 Swine Erysipelas. symptoms diminishes from the second to the third day on, whereupon the animals recover in a short time, or, on the other hand, a chronic type of the affection ensues. In France, according to Cagny, they distinguish a mild and severe form of acute swine erysipelas; to the latter belongs the ‘‘rouget foud- royant’’ which terminates in a very short time in death, and the “rouget blanc’’ in which death results so quickly that the reddish coloration of the skin cannot develop (also observed by Zschokke in Switzerland). 3. Chronic erysipelas. It occurs most frequently as chronic erysipelatous-endocarditis in animals which have recov- ered from the acute affection. After the disappearance of the acute manifestations the pigs are usually lively and have a good - appetite for a time, but on careful observation it may be no- ticed by comparison that they are stunted in their development. After 6 to 12 weeks they eat less, are dull, dislike to move around, and lie down much, and almost always on the sternum and elbows. In the meantime a cough, accelerated and super- ficial respiration as well as a bright red discoloration of the skin, ears, neck and sometimes the rump, is observed. If the animal is urged to move about the dyspnea and cyanosis in a short time become more marked. The heart action is in- creased, at times pounding, and may be easily detected over the region of the heart. The pulse is threadlike; besides this, instead of one, mostly the systolic, or both heart sounds, a blowing or harsh murmur may be heard (endocarditis verru- cosa, stenosis of theeorifices). The body temperature is nor- mal or sometimes increased from one to one and a half degrees. With such manifestations the animals may live for several weeks. However, they become emaciated, very weak, a crusty eczema frequently develops on the skin and even paralysis of the hind quarters may result. (According to Eisenmann, the duration of the disease in four cases was 34 to 112 days.) As a particular form of chronic erysipelas Cornevin, Hess and recently Eisenmann describe an affection which is in gen- eral only manifested by chronic debility. It develops several weeks after the acute affection and consists principally in accelerated and difficult respiration, digestive disturbances, emaciation, hemorrhages and ulceration of the buccal mucous membrane, hemorrhages into the hair follicles with subsequent falling out of the bristles, eczema or also necrosis of the skin, edema of the extremities as well as serous inflammation of the joints and tendons which may later result in deformity (most frequently the hip joint). Course and Prognosis. The urticaria of erysipelas termi- nates as a rule in recovery. Excteptionally, however, manifesta- tions of a general infection or a chronic disease may develop, when it results in death. The septicemic form terminates in the majority of cases in death, but the number of fatalities varies Course and Prognosis, Diagnosis 71 -within wide ranges in different years and territories. In Hun- gary it fluctuated in the last ten years between 53.2% and 83.8% ; -according to Friedberger & Frohner the average loss amounts to 50-85% ; according to Lydtin to 50-75%. Chronic erysipelas always terminates fatally. Tf, in the acute cases, the affection lasts over four days, it is a favorable indication; otherwise the disease takes a threat- ening character particularly in poorly nourished and badly de-° veloped young animals. Complete recovery is sometimes very slow and takes place only after several weeks. In most cases, however, the convalescence lasts only a few days. Nevertheless there always exists the possibility that the chronic form of the disease may develop. Diagnosis. The septicemic form of erysipelas may be especially easily mistaken for swine plague and hog cholera, but these diseases may be distinguished from it by their usual slow course as well as by the predominating affection of the lungs and intestinal tract, or by the development of symptoms indicating a diphtheritic inflammation of the throat. Red dis- colorations may occur in the course of the above diseases but they result usually from hemorrhages and therefore do not disappear on pressure. On autopsy erysipelas is distinguished from the peracute cases of hog cholera and swine plague only by the more pronounced hemorrhages, whereas from the more frequent chronic cases it can be differentiated by the necrotic pneumonia and fibrinous pleuritis or round intestinal ulcers, further, by the extensive exfoliation of the intestinal mucous membrane and caseation of the lymph glands which do not occur in erysipelas. . Anthrax, which rarely occurs in hogs, is differentiated from erysipelas by the frequent swelling in the region of the neck and the difficulty in swallowing, on post mortem by the charac- teristic affection of the tonsils as well as by the difference in the bacteriological findings. Wound erysipelas occurs only on the head when the reddened skin is greatly swollen and painful and the temperature higher. The cerebral hyperemia which causes death during transportation in the warm weather is characterized by sudden death of animals which were well only a short time previous, and usually occurs in older and well- fattened. animals. The autopsy reveals marked lesions of asphyxiation. On the other hand, there are no lesions of gastro-intestinal inflammation, or of acute swelling of the lymph lands. ? The erysipelatous nature of urticaria, is indicated by the preexisting general symptoms of the infection, whereas chronic erysipelas is distinguished from other similar affections (rheu- matic arthritis, catarrhal pneumonia, chronic swine plague) only by the post mortem lesions. 72 Swine Erysipelas In doubtful eases, especially if acute swine plague be suspected, the diagnosis of erysipelas can only be assured by microscopical demon- stration of the erysipelas bacilli in the blood or in the tissue of the spleen, kidneys or lymph glands, and if necessary by subcutaneous inoculation of such material into mice or pigeons. (See also diagnosis of swine plague.) In shipping material to laboratories for examination, squeeze preparations or thin smears from the spleen or kidneys should be made, as according to Joop, the virulence of the bacilli of such material is retained for 10 to 12 days, while they remain alive from 16 to 18 days. Treatment. In acute cases the treatment with immune serum gives the best results, provided the animals are treated immediately after the onset of the disease, as the injections when undertaken not later than 6 to 12 hours after the appear- ance of the first symptoms, exert a curative action in many eases (Leclainche; according to Schiitz the serum destroys the bacilli which are present in the body or which may enter the body later). The blood serum is the same as is used for pro- tective inoculation (see page 76), only it is necessary to use considerable amounts; 10 to 30 cc., according to the body weight, should be injected subcutaneously; it is also advisable to repeat the treatment every 6 to 8 hours until the appearance of a decided improvement. In Germany 1315 hogs affected between 1897 and 1901 with erysipelas were treated with Lorenz’s serum, of which 1111 that is 84% recovered, of 656 affected animals treated with susserin 535, that is 82%, recovered. In Hessen 1451 out of 1570 treated animals, that is 92.5%, recovered between 1901 and 1903 (Lorenz); in Hol- land 88.3% of 5830 animals were successfully treated (Wirtz); in Hungary Detre’s serum was employed in 1903 on 711 animals of which 677, that is 95%, recovered; and since then results have also been favorable in different localities in which the serum treatment has been employed. According to Nocard, in France 8483 hogs affected with erysipelas had been successfully treated up to 1901 with Le- clainche’s serum. The symptomatic treatment has hardly any beneficial influ- ence upon the disease. Nevertheless, the occasional internal administration of remedies which possess an intestinal disin- fectant action may be tried, and for this purpose is recom- mended; calomel (2-3 gms.; only in the early stages of the disease, as later when the kidneys are affected it is harmful), ereolin or lysol (5% solution in tablespoonful doses), which may be given with mild cathartics. Besides, the nervous system may be stimulated by douches and washing with cold water. Prevention. The fact that the erysipelas bacilli remain as -saprophytes for a long time in the ground in infected localities, and that they are also frequently present in the tonsils as well as the intestinal canal of healthy animals, renders the com- bating of the disease very difficult. As, however, the infection is most successfully conveyed by affected hogs and their car- casses, healthy animals must in the first place be protected from 3 Prevention, Immunization 73 this source of danger. Accordingly, healthy animals should be separated from the affected ones, and they should be kept from contaminated pastures and stables. Carcasses should be deeply buried, or still better cremated. Infected stables and premises should be properly disinfected, and the excrement of the affected animals collected and destroyed. Infected pastures should not be used as ranges for swine for a long time. If the disease has already appeared in a herd it is advisable to place the apparently healthy animals in an unsuspected pasture, or in the absence of such, pasturing should not be per- mitted until the complete disappearance of the disease; in this way it is frequently possible to eradicate the outbreak. Inas- much as the infective agent is present in all parts of the emer- gency slaughtered hogs the disease may be disseminated by the marketing of such carcasses, and therefore the sale of meat _ of such carcasses should not be permitted until it has been sterilized. Such a procedure appears the more advisable, as according to Petri’s and Stadie’s investigations ordinary con- servation of the meat and the products prepared therefrom (salting, pickling, smoking) destroys the erysipelas bacilli only after a long time. (See page 62.) When the possibility or even probability of an infection ex- ists, the occurrence of the disease may be successfully pre- vented by means of protective inoculation. Immunization. One attack of erysipelas conveys immunity to hogs against later natural infection. This experience would also indicate that the artificially produced mild affection affords a similar immunity. This idea was practically demonstrated by Pasteur in 1882 by inoculations of artificially attenuated cul- tures, while later Lorenz as well as Leclainche established the value of protective inoculation with immune serum and cultures in practice. I. Protective inoculation with attenuated cultures (Pas- teur’s method). Pasteur showed in his experiments that the passage of erysipelas virus through the body of rabbits in- creases its virulence for these animals. On the other hand, it reduces it for hogs, so that the inoculation with such virus in the latter animals causes only a slight febrile disease. Virus attenuated up to a certain degree retains this degree of viru- lence even if transferred from the rabbit hlood to a suitable artificial medium, for instance, bouillon and if further cultivated at body temperature. The bouillon culture attenuated by the above method produces the vaccine which is injected subcu- taneously into young pigs in form of a weaker and a stronger modification. The effectiveness of Pasteur’s protective inoculation has been positively established. Besides Pasteur, Schiitz, Schotte- lius and others found that vaccinated hogs cannot be infected 74 Swine Erysipelas either by subcutaneous injections of highly virulent virus nor by feeding with organs from animals which died of erysipelas; on the other hand, the experiences made in practice proved that the immunity produced by the inoculation, protects the animals against natural infection. In Hungary the considerable losses caused by erysipelas have been reduced to 1 to 2% in formerly badly infected herds. In the great majority of cases erysipelas has not caused losses either immediately after the inoculation or later during the favorable summer weather among the vaccinated animals, whereas among the control animals which were not vaccinated, the disease raged, and in many cases the vaccination suppressed already existing outbreaks. The age of the animals influenced the results of the vaccination in such a way that the inoculation failed to produce in the sucking age a sufficient im- munity or none at all; on the other hand, it has not proven dangerous in animals even up to 3 years of age. The vaccinated animals were partly of the native Mangalicza breed. However, animals of the Poland-- China and Suffolk breeds were also vaccinated with the same beneficial results (Wirtz also found that vaccination of the Mangalicza breed was without danger), whereas in Yorkshire hogs sometimes dangerous affections resulted (Bleyer). Pasteur’s protective inoculation accordingly appears to be especially effective in herds of common or less highly bred animals, particularly in localities where erysipelas annually causes considerable loss, and it may be employed without dan- ger in already affected herds of such breeds. At the initiative of Azary, Pasteur’s vaccination has been extensively used in Hungary since 1887. From 1889-1894, 1,085,686 hogs were vaccinated and after the first vaccination 0.14%, after a second 0.07%, and later in the year 0.54% died of erysipelas. On account of hog cholera which appeared in 1895 the results of the later inoculations cannot be determined accurately as the affections and deaths which resulted from the heretofore unknown hog cholera were often simply attributed to erysipelas. But since greater stress was placed on differential diagnosis the re- sults appear favorable. Thus in 1907 of 28,642 hogs in already infected herds 637 died after the vaccination, later 421 additional fatalities were observed. In healthy herds out of 288,950 vaccinations 125 and 623 died. Pasteur ’s vaccination is used less extensively in France and Russia probably on account of the fact that in some of the herds the losses following vaccination amounted to 6 to 10%, which condition may be attributed to a feebler resistance of the native breeds. In Germany this method has not attained extensive ap- plication owing to the unfavorable results obtained by Lydtin & Schottelius, but in recent years it has been more extensively used, especially in the southern part of the Empire. Technique of Vaccination. The vaccination is carried out in the same way as anthrax vaccination in sheep (see page 27); the quantity of the im- munizing material is in this case also 0.12 cc. (% of the contents of Pasteur vac- cination syringe), and:the second vaccination follows 12 days after the first. It is advisable to vaccinate pigs in the spring after weaning at the age of 3-5 months, before the appearance of hot weather. Direct results of vaccination. This is manifested in some eases by debility lasting from 1 to 2 days, impaired appetite, and sometimes a weakness of the hind quarters; on the second and third day after the vaccination the temperature rises on an average of 0.8°C. Sometimes, however, it may rise up to 41.7°C. (Mihaly), whereupon the animals rapidly recover their normal condition. Occa- sionally a swelling of considerable size may appear at the point of inoculation, and stiffness of the joints may also develop, particularly in the higher breeds, and here and there death may result from erysipelatous endocarditis, Immunization 75 _ II. Protective inoculation with immune serum and cultures (Simultaneous method of Lorenz and of Leclainche; sero- vaccination). Blood serum of animals which have been highly immunized by repeated subcutaneous or intravenous injections of living cultures of the erysipelas bacillus will protect healthy animals for a short time against fatal infection. The passive immunity produced in this manner may be changed into active immunity by simultaneous or subsequent injections of virulent cultures of the bacilli. After Emmerich and Mastbaum (1891) found that the blood serum of rabbits which had been immunized against erysipelas possessed im- munizing properties, Lorenz (1893) produced an effective serum from artificially immunized hogs. This serum, concentrated to one-third of its original volume, was effective for protective inoculation of hogs. As hogs as well as sheep (Voges) produce only small quantities of serum, Leclainche (1898) and Schiitz & Voges hyperimmunized horses for that purpose, and at the present time serum for the inoculation of hogs is obtained almost exclusively from these latter animals. Potent blood serum may also be prepared from cattle (Schreiber, Kitt), and the “double serum’’ of Landsberger consists of a mixture of horse and cattle immune serum (Schubert). The results of protective inoculations with immune serum and bacilli culture have generally given good satisfaction in practice. Hogs which have not yet become infected withstand the vaccination as a rule without marked reaction, and they will later resist natural infection. As a sequel of the vaccination, however, urticaria, swelling at the point of inoculation extend- ing to the throat, stiffness of the joints, occasionally erysipe- latous endocarditis, and even death after 36 hours from severe toxic action, have been observed to follow injections of the culture. The advantage of this method over Pasteur’s consists in the development of the passive immunity immediately after the serum injection, which condition in case of immediate dan- ger of infection is of great importance—and further it is well tolerated even by breeds of hogs with low resistance. The some- what high cost of the vaccinating material is a disadvantage. Latent diseased processes are unfavorably influenced by the inocula- tion. Thus, it was repeatedly observed in Germany that chronic pneu- monia of pigs (the so-called chronic swine plague of pigs). became aggra- vated after vaccination, and in Hungary also it was noticed that the first year after the appearance of hog cholera severe outbreaks of the latter disease developed following the vaccination of herds against erysipelas. In Prussia 217,376 hogs were vaccinated in the years 1897-1899 by Lorenz’s method, and after the first injection 0.018%, after the second 0.042%, later in the course of the year 0.058% died as a result of erysipelas (Joest & Helfer). In Baden 102,448 hogs were vaccinated in the years 1899-1906 of which 21,466 animals received the serum alone; of these 116 (0.09%) died inside of 3 days, later until the close of the year, 108 (0.08%) succumbed. In Hessen only 2 out of 35,258 in- oculated animals died in the period from 1901 to 1903 (Lorenz). In Wiirttemberg 76 Swine Erysipelas only 4 out of 59,625 hogs vaccinated in the years 1904-1905 died of acute erysipelas; of the original number, however, 29,249 animals received the usual two injections (Beisswanger), while in the Province of Saxony in the year 1904-1905 of 175,150 animals, 12 died of vaccination erysipelas, 6 of endocarditis, and 15 succumbed to erysipelas later (Raebiger). In Holland in the years 1899 to 1905 out of 165,884 inoculated hogs 136 (0.08%) died as a result of the vaccinations. Reports from Baden (Fehsenmeier), Moravia (Rudovsky), Cantonzurich (Zschokke) and others are much in favor of the value of the simultaneous injections, and the Leclainche method is also used extensively in Hungary with favorable results. Preparation of the immune serum. For this purpose healthy horses are used which receive weekly injections, into the jugular vein of virulent bouillon cultures of erysipelas bacilli in increasing quantities (50 to 500 cc.). The animals react to the injection with fever, muscular trembling and sometimes with diarrhea. After 2 to 3 months of such treatment they produce a blood serum which strongly agglutinates the erysipelas bacilli of which 0.5 ce. protects a pigeon against a like quantity of virulent culture which ordinarily would kill it in 2% to 3. days (Leclainche); exceptionally 0.1 of such serum has such a protective action (Deutsch) ; it retains this action for months after heating for 1% hour to 55° U. In Germany only serum can be marketed, 0.015 ec. of which will protect a mouse of 15- grams weight against a simultaneous subcutaneous (Lorenz), or against an intra- peritoneal (Marx) injection of 0.1 cc. of virulent bouillon culture 24 hours later. The immune serum used for the inoculation of hogs must possess the strength mentioned and should not be more than one year old, but the virulent bouillon cultures should be fresh and not over a week old. In Germany the immune serum is prepared in various laboratories under different names (Prenzlauer & lLands- berger’s serum, Susserin), and is placed on the market with the necessary direc- tions for its use. Technique of vaccination. Leclainche’s method: In a carefully sterilized syringe of 10 cc. capacity, 1 ce. of the bouillon culture is drawn up and then the syringe is filled up with the immune serum. After the contents are well mixed hogs of not over 50 kg. weight are injected subcutaneously with 5 cc. on the inner surface of the thigh. If the hogs are heavier, 1 cc. of additional blood serum is given for each 10 kg. above 50 kg., or in general each heavy hog is injected sub- cutaneously with 9.5 ec. of serum and 0.5 ce. of culture. The second injection follows 10 to 12 days after the first, when the syringe is filled with Louillon culture, and of this each animal receives 0.5 cc. without consideration of the animal’s weight. The injection is also made on the inner surface of the thigh. Method of Lorenz. In this method the immune serum is first injected under the skin of an ear and immediately afterwards 0.25 to 1 ce. of culture is in- jected into the other ear; 12 to 15 days later the hog is injected with double the quantity of the culture used in the first dose. The second injection is also made under the skin of an ear. Relative to the results of the inoculation, it is immaterial whether the blood serum and virus are injected in a mixture (Leclainche) or simultaneously, but in different parts (Lorenz, Schiitz), or if the virus is in- jected several days following the serum (Lorenz). A sufficient protection is only assured after both inoculations, as the first simultaneous inoculation produces only a passing rise in the resistance as proven experimentally by Prettner, inasmuch as the bacteria are influenced by the injected serum to such an extent that a sufficient quantity of immune bodies is not pro- duced. III. Passive immunization. The immune serum may also be used by itself for the immunization of already infected herds (5 to 10 ce.). The serum very rapidly produces a passive im- munity which prevents the development of the disease in ani- mals threatened by the infection or when the infection is in the stage of incubation (see also page 72). The immunity produced in such a way lasts, however, only a short time. (According to Leclainche, 17 days.) Therefore, these animals should be given the combined or Pasteur’s inoculation after their recovery or from 8 to 10 days after the serum treatment in order to produce a lasting immunity. Immunization. The Disease in Man 77 _ Veterinary Police. Police measures adopted for other con- tagious diseases may also be recommended for erysipelas, and particularly quarantine of the premises—in more extensive outbreak even the township, prohibition of marketing the ani- mals, harmless disposition of carcasses, disinfection of infected localities, ete. From the quarantined premises or townships the transportation of animals to abattoirs for immediate slaughter should be permitted. The observation period after the apparent disappearance of the disease should extend from 1° to 15 days. Literature. Pasteur, Rev. vét., 1883, 39.—Pasteur & Thuillier, Bull. de Acad. de méd., 1883, Nr. 45.—Eggeling, D. Z.'f. Tm., 1884, X, 234,—Loeffler, Arb. d. G.-A., 1885, I, 46.—Schiitz, Ibid. p. 56.—Lydtin & Schottelius, D. Rotlauf d. Schweine, Wiesbaden, 1885.—Bang, D. Z. f. Tm., 1892, XVIII, 27.Jensen, Ibid., p. 278.—Kitt, Monh., 1894, V, 19.—Lorenz, D. t. W., 1897, 91; Obl. f. Bakt., 1893, XIII, 357.—Leclainche, Soc. biol., 1897, 428; 1899, 346—Voges & Schiitz, A. f. Tk., 1898, XXIV, 173.—Bauermeister, 1902, XXVIII, 66 (Lit.).—Preisz, Hb. d. p. M., 1903, ITI, 710 u. IV., 1236 (Lit. on etiol. and immunization).—Stadie, Diss., Berlin, 1904 (Lit. on biol. of erysip. bae.).—Eisenmann, Monh., 1906, XVII, 07.— Schipp, D. t. W., 1910, 98. The Disease in Man. From the literature a considerable number of cases are known (Casper, Nevermann, Welzel, Hennig, Gleich, Zipp and others) to have occurred in men occupied in handiing hogs affected with erysipelas, or who worked with cultures of the bacilli (immuniza- tion). It was observed that after slight injuries to the skin erysipelas- like reddening of the skin and swelling of the neighboring lymph gland developed sometimes even exfoliation of the blackish-red epidermis with exudation of serum, and occasionally even swelling of the neighboring joints. The disease usually terminated within four weeks in recovery (in: RGder’s case it lasted for 12 weeks), which is considerably hastened by subcutaneous injections of immune serum (10 ec.). From eating meat of hogs affected with erysipelas no attacks have been observed. Lubowsky, however, found large quantities of bacteria in the feces of a boy which were identical with the erysipelas bacillus. The boy suffered from jaundice and intestinal catarrh, the cause of which was unknown. Literature. Rosenbach, Z. f. Hyg., 1909, LXTIT, 343 (Lit.).—Roder, Mitt. d. bad. Ta. 1908, [J.—Gleich, B. +. W., 1909, 576.—Zipp, Tijdsskr., 1909, 98.— Lubowsky. Dem. W., 1910, 116. 5. Hemorrhagic Septicemia, Septicaemia Hemorrhagica, Hueppe (Septicaemia pluriformis, Kitt; Pasteurellosis, Ligniéres.) Under the collective name of hemorrhagic septicemia are included all those diseases which are produced by varieties of the bacillus bipolaris septicus (Bac. multocida s. plurisepticus, Kitt; Pasteurella, Ligniéres) and in which the acute cases are characterized by manifestations of a general infection and hemorrhagic inflammatory processes of the internal organs. History. Perroncito and Semmer (1878) and later Pasteur (1880) by the study of chicken cholera, Gaffky (1881) of rabbit septicemia, 78 Hemorrhagie Septicemia Kitt (1883) of Bollinger’s Wildseuche, and Léffler (1886) of swine plague, proved that these diseases are caused by small bacilli, all of which showed the same characteristics by taking the stain intensely at the poles and only very slightly or not at all in the middle, therefore resembling somewhat the figure 8. Based on a comparative study of these four diseases, Hueppe (1886) came to the conclusion that their causative agents coincided in all their principal morphological and biological characteristics, and that the diseases greatly simulated each other in their course and anatomical changes. From these he concluded that the causative agents of the diseases mentioned represent one species of bacteria, and that the existing differences, especially with reference to their virulence, justified his conclusion that they were varieties of the same species. Inasmuch as in the acute cases there are manifestations of a general blood infection and the presence of hemorrhages in the internal organs, Hueppe inciuded the four diseases in one group and recommended the name of hemor- rhagic septicemia for their designation. The observations made since these investigations proved the cor- rectuess of this conclusion, and have at the same time shown that similar bacteria play an important part in the etiology of other diseases. Thus, this was established by Poels (1886) for the infectious pleuro-pneumonia of calves, by Oreste and Armanni (1887) for the barbone disease of buffalo, by Galtier (1889) for the infectious pneumo-enteritis in sheep. Therefore these diseases may also be included in the group mentioned. In the diseases mentioned and also others of less importance the bipolar bacteria appear to be the exclusive factors in the development of the pathological processes. Ligniéres (1900), however, includes those diseases in which the bipolar bacilli are usually involved only indirectly, by predisposing the body for an infection with other bacteria. Such diseases are influenza or pleuro-pneumonia of horses, and distemper of dogs and cats, to which Nocard, on the strength of his own investiga- tions, added white scours and the catarrhal pneumonia of calves which are due to navel infections. In the meantime Ligniéres in supporting Trevisan’s suggestion, named the bacteria of chicken cholera and of the related diseases, pasteurella, and the diseases caused by these bacteria pasteurellosis. This nomenclature has been accepted in general by the French authors. Recent experiences with the diseases mentioned and a more accurate consideration of the etiological part of the ovoid bacteria, make the cor- rectness of Ligniéres’ conception very doubtful, and at least they appear to be remote. While it cannot be doubted that the bacteria under dis- cussion may independently produce diseases, their occurrence in affected organs and tissue fluids is not a sufficient proof that the disease was originally produced by them. ‘Since they may not infrequently be met in healthy animals, it is possible for them to invade secondarily the tissues which have been already affected from other causes. It will require further investigations to establish the significance of their pres- ence. However, their part in distemper of dogs, in pneumonia of calves and pigs, in the pectoral form of hog cholera, and in influenza, may even now be accepted as secondary. On these grounds it appears advisable to restrict the conception of Ligniéres’ pasteurellosis, and therefore only those diseases will be considered here in which it has been positively established that the ovoid bacteria play the primary etiological part. The results of investigations in the future will show whether a change of this viewpoint will be necessary. History. Morphology and Biology vis) In the designation of the diseases belonging to this group the former appropiate name of hemorrhagic septicemia will be used as it appears justifiable from a pathological-anatomical standpoint. The causative agent is the species of bacteria known as bacillus bipolaris septicus, while the various organisms of the group causing this disease will be designated according to the species of animals affected, viz., Bac. avisepticus, Bac. bovisepticus, Bac. suisepticus, ete. Morphology and Biology of the Infective Agent. The bacillus bipolaris septicus (Bac. multocida s. plurisepticus, ‘Kitt; pasteurella, Ligniéres, ovoid or girdle bacterium) mani- fests the following charactéristics without consideration of the diseases belonging to this group or from what species of ani- mals it originates (Ligniéres). It is short, stains intensely at the poles but only slightly in the middle, polymorphous, non-motile, does not form spores, principally aerobic; does not stain by Gram, grows in bouillon, gelatin and agar, but does not grow on acid potatoes, nor liquefy gelatin, nor coagulate milk; it does not produce indol in pancreatic bouillon, nor redden Wirtz’s agar; the bouillon cultures have a peculiar characteristic odor. ; Besides these characteristics of the bipolar bacillus, the special characteristics of the bacteria belonging to this group are the following: Form. In the tissue fluids and stil) more so in cultures the bacillus _ represents a short rod about 14 long, with rounded ends (Fig. 23). It also occurs in the form of cocci, diplococci; exceptionally also as longer rods, threads and streptobacilli. Its dimensions vary according to the origin of the disease in certain although not wide limits. Fig. 23. Bacillus bipolaris septicus. Fig. 24. Bacillus bipolaris septicus. Smear prepared from a fresh Smear from the blood of a chicken agar culture of the bacillus dead from fowl cholera. Polar of fowl cholera. Fuch- staining with fuchsin, and subse- sin staining. quent washing with a 1% acetic acid. Staining. The bacilli stain quite readily with the aqueous aniline dyes, and in the preparations made from the tissues or from the body fluids (best in the blood of affected chickens) they appear stained only at the poles, while the middle remains unstained (Fig. 24). These results are obtained when the preparations are not stained too intensely 80 ; Hemorrhagic Septicemia or after subsequent washing in alcohol or 14 to 1% acetic acid. On the other hand, it is difficult to obtain the polar stain in bacilli originating from artificial cultures. Cultivation. The bacilli are easily isolated from cases of an acute septicemic character, while from Te chronic cases this is more difficult and sometimes im- =a possible. The requirements of artificial cultivation are: temperature of 13-28°C. and alkaline or at least neutral reaction of the medium. In vacuum the bacteria grow only when the medium is inoculated with numerous organisms, and then only for a short time. A frequent characteristic of the cultures is their viscosity (this is also striking in the peritoneal exudate of Inoculated guinea pigs), probably due to the sticky eapanls which covers the bacteria. The colonies fricnea on gelatin are no larger than a millet seed. They are at first transparent, often resembling a dew-drop, and frequently iridescent. Later they are whitish, of a hyaline- cartilage-like appearance. In the depth of the medium the punctiform colonies unite along the stab and form a con- tinuous white streak (Fig. 25). Sim- ilar colonies develop on the surface of the agar cultures, but do not extend. to the wall of the test tube (Fig. 26) ; cultures several days old are viscid; when still older they adhere firmly to the medium. On coagulated blood serum a very fine membrane forms which is at first transparent and later whitish. Bouillon with the addition of peptone or blood serum usually be- comes more or less uniformly cloudy; \ ; eas Se aes in some of the varieties, however, the Tig, 86. Agar tin stab culture fluid clears, sometimes first forming a slant culture of ofthe bacillusbi- slimy and later a fine granular sedi- the bacillus bi- polaris septicus. ment; occasionally also a delicate, polaris septicus. whitish membrane develops on the sur- face. The addition of sugar or glycerin does not promote, but rather retards the growth. Dextrose bouillon is not fermented. ‘No growth takes place on potatoes with a natural acid reaction; when artificially alkalinized a grayish-yellow deposit forms. Animals inoculated with a certain variety produce a serum which will have the highest agglutination for that particular variety (up to 1:60,000), but it will. also agglutinate to a lesser degree other varieties (1:1000-6000). Sometimes, how- ever, some of the varieties are in no way influenced. Therefore the agglutination eannot be utilized for the identification or separation of the different varieties. (Chamberland & Jouan). ‘ Cultivation. Pathogenicity 81 Pathogenicity. In contradistinction to the common char- acteristics described, there are marked differences in the viru- lence of the bacilli which depend on their origin, the nature of the disease and the species of animals affected. However, all the varieties coincide in exerting their strongest pathogenic action when inoculated with blood or exudate of animals which died of the disease (aggressin action, see page 84). Another common characteristic of the bacteria belonging _to this group is that they develop the highest virulence towards that species of animals for which they are naturally pathogenic, while towards other species their action shows a great variance. It is, however, possible to increase the virulence for other species through repeated reinoculations, but such a strain of the bacilli will even then possess the strongest pathogenic action for the species from which it originated. The animals which are susceptible to the bipolar bacteria, although not to the same extent, are the guinea pig, rabbit and mouse, while the domestic animals show a great variation in susceptibility. The guinea pig is best adapted for test inocu- lations, and by using this test animal for repeated intraperi- toneal reinoculations the virulence of any of the varieties may be greatly increased. The result of artificial infection depends also on the nature and method of the inoculation. The most pronounced action is obtained by direct injection into the circulation, by which means the disease may be transmitted to any species. Somewhat less effective is the intraperitoneal and intratracheal injection of cultures, whereas the subcutaneous and intramuscular ‘inocula- tion produces a severe affection only in very susceptible species of animals. The feeding of virulent material only exceptionally gives positive results, these being most frequently obtained when the cholera virus of chickens is fed. ' Variability of the Virulence. The bipolar bacilli are very widely spread, and may produce disease in any species of ani- mals, particularly in the domestic animals. As original sapro- phytes they occur in nature in the soil, in slow-flowing or stagnant water, on various plants, and in all kinds of dead organic material. Under normal conditions they do not mani- fest pathogenic characteristics. Hence they occur not infre- quently in the digestive tract and in the air passages. Under certain conditions, which at present are still unknown, they be- come virulent and then they may attack the tissues of the healthy body. On the other hand, their pathogenic action is favored by all those influences which weaken the resistance of the organism, as colds, exertion, anemia, starvation, mixed in- fection, catarrhs, etc. Parasites‘in the air passages and digestive tract also favor the development of infection by loosening the epithelium of the mucous membrane, or by causing penetrating injuries to the mucous membrane, whereby the entrance of the bacteria into the lymph vessels is facilitated. 6 ’ 82 Hemorrhagic Septicemia The bacteria which through some cause become parasitic lose in some of the cases their pathogenic character after leav- ing the affected animal, and may change again to saprophytes. In the majority of cases, however, after having become accus- tomed to-the organism of a certain animal, they attain an in- creased virulence for animals of this particular species, and therefore infect the animals more easily even without the influences of predisposing causes. This relative virulence may even increase for a time in the course of further generations, or may become constant. More frequently, however, it dimin- ishes again after a certain time. These characteristics of the bipolar bacteria explain the variation which is observed in the appearance and spread of the diseases belonging to this group. The common experience with these diseases is that they appear periodically in certain localities without any apparent connection to which the intro- duction could be traced. In such cases the outbreaks can be explained by a sudden increase in the virulence of the bacteria which are present in the soil or in the healthy animal favored by influences which reduce their resistance. Some of the infec- tions develop through such conditions. In these the disease does not, or only exceptionally, spread from animal to animal, and it therefore remains sporadic, or at least confined to cer- tain localities. In other cases although the disease appears spontaneously the organisms which pass through the body of the animals retain their pathogenic character for a long time, thus spreading the disease by direct or indirect infection, and disseminating the contagion to distant localities. Further, among the diseases of this group there are some in which the bacteria adapt themselves in the course of time to the animal body to such an extent that as saprophytes they are no longer capable of propagation, and therefore these diseases spread almost exclusively by being introduced from outside or by direct communication. The acquired or inherited virulence of the different varie- ties of the bacteria is usually only manifested for certain species of animals, so that a certain disease spreads usually only among the animals of the same species. Exceptionally how- ever, the infective agent may become dangerous for other species. Thus frequently the infection of buffalo disease and hemorrhagic septicemia of cattle causes in hogs symptoms re- sembling swine plague. On the other hand, the virus of swine plague sometimes produces a septicemic affection in sheep, while feeding it to chickens causes a disease which corresponds to fowl cholera. Ligniéres succeeded in artificially producing a variety of forms of hemorrhagic septicemia in different animals by injections of cultures of the bipolar bacillus of different origin. Koske successfully infected different species of fowl per os with swine plague bacteria. On the other hand, he failed in hogs to produce a disease resembling swine plague with the fowl cholera organism. The ovoid bacteria may retain their virulence for months in the original Pathogenesis 83 exudates or body fluids under artificial conditions, if light and air are excluded; whereas, in artificial media in the presence of air they are sometimes very rapidly attenuated and finally lose their virulence. Pathogenesis. Bipolar bacilli which penetrate into the tissue fluids of the animal organism, produce different patho- logical changes, according to the degree of their virulence and the susceptibility of the animals. In case of a severe infection a peracute hemorrhagic septicemia develops. The bacilli mul- tiply very rapidly and in a short time permeate the entire body, causing death in from 18 to 24 hours. The animals manifest high fever, weakness of the heart, debility, sometimes diarrhea. Autopsy reveals numerous hemorrhages in the tissue of the serous and mucous membranes and parenchymatous organs. The spleen is only slightly swollen, while the lymph glands show a marked acute swelling. When the infection is somewhat less severe the acute attack lasts for several days when frequently a sero-fibrinous inflam- mation develops on the serous membrane, while the mucous membranes are affected with a hemorrhagic inflammation. With these an inflammation of the joints and tendons is not infre- quently associated. The autopsy reveals in these cases a mod- erate acute swelling of the spleen and a pronounced swelling of the lymph glands in addition to blood extravasations. An infection of a milder degree, for instance an intravenous injection of a small quantity or very weak virus, results in some cases in a chronic affection, lasting for several weeks or months. The animals become emaciated slowly but gradu- ally, frequently in spite of their good appetite; they have an intermittent fever, and inflammatory processes develop in dif- ferent joints, especially in the knee, carpal and tarsal joints. The animals also show a marked predisposition for secondary infections, especially for catarrhal pneumonia. The bipolar bacillus may produce these varied clinical manifestations independently. In the acute cases the organism is found in great numbers in the blood and also in the exudates in pure culture. The pathological processes in some of the chronic cases may be also attributed to its action even if the bacilli have since disappeared from the body. The local action of bipolar bacilli is manifested in the production of serous and fibrinous inflammations, later in degeneration of the exudate and tissue elements, as a result of which dry caseous masses occur, while necrotic areas develop in the affected organs. The necrosis is very probably the result of the action of toxins. Filtrates of bouillon cultures free from bacteria usually produce only a very slight or no toxic action. Killed masses of bacteria, however, possess distinct toxic prop- erties. Inasmuch as in the body of the animal both multipli- cation and destruction of bacilli take place, and as dead bacilli are dissolved in the tissue fluids the toxins which are eliminated may cause general effects and local necrotic processes. There 84 Hemorrhagic. Septicemia is also a possibility of the bacteria producing strongly acting exogenic toxic substances and aggressins in the living body. According to the investigations of Klett & Braun, the bacilli of fowl cholera and swine plague secrete even in artificial fluid cultures soluble poisons in large quantities which can be demonstrated. These toxins have an identical poisonous action (in pigeons and chickens lethargy and intoxication) and their endotoxins are also identical; a difference is indicated in that the Bacillus avisepticus produces greater quantities of filterable toxins and endotoxins, and these are also more constant. According to Weil the virulence of the bacteria is considerably increased when heated to 44° C. in the exudate of artificially. infected animals, and also, according to Citron, in extracts of cultures. Accord- ing to Bail’s theory the bipolar bacilli, like the other pathogenic bac- teria, produce specific substances in the animal body (aggressins) which possess the character of changing non-fatal amounts of bacteria to fatal ones, without themselves having marked toxic properties. Further, Tschistovitch believes that virulent fowl cholera bacilli contain strictly specific thermo-stable antiphagins which protect them from the digestion by leucocytes. The bipolar bacilli manifest a particular affinity towards certain organs, and therefore pathological changes develop in the less acute cases only in certain organs. In such predisposed organs either acute or chronic inflammations may be present. The serous membranes in general, the lungs, the synovial mem- branes of the joints and tendons and probably the liver are the favored organs. According to Ligniéres the bipolar bacilli may also give rise to the development of secondary disease processes. Through their toxins and probably indirectly through a tem- porary arrest of the phagocytosis, the resistance. of the body may be reduced, whereby bacteria which are more or less harm- less may produce disease processes, while the bipolar bacilli may in the meantime disappear from the body. Even in many of the acute cases which are associated with an inflammation of the lungs and joints other probably pathogenic organisms may be found in the affected tissues, or in the inflammatory products in addition to the bipolar bacilli. However, in the chronic cases only secondary bacteria are as a rule present. The intravenous injection of a weak virus, for instance older cultures of the bipolar bacillus, produces as has already been mentioned, a chronic affection which results in cachexia. In these cases the bac- teriological examination of the affected tissues and exudates discloses other bacteria (streptococci, colon bacteria, ete.) in spite of the fact that the infection was brought on by the bipolar bacilli. Similar results may occasionally be obtained from the injection of filtrate free from bacteria made from cultures of the bipolar bacillus. The very frequent occurrence of mixed infections makes it possible for other bacteria to prepare the field for the propa- Pathogenesis, Immunization. 85 gation of the bipolar bacilli. Through the destruction of the tissues by the other organisms the entrance and propagation of the ovoid bacteria are favored. Their invasion is without doubt of a secondary character in those cases in which a general septic affection is caused by an ultravisible virus, as for instance in dog distemper and hog cholera (see those diseases). In these affections disease proc- esses may develop subsequently which are exclusively or at least partly the result of the action of the ovoid bacteria. In recognition of this fact, the etiological importance of these bac- teria has already been considerably limited. Immunization. Pasteur proved that cultures of the chicken cholera organism when attenuated by keeping in the air pro- duce a suitable vaccine for the immunization of chickens against artificial infection.. Similar results are obtained with cultures attenuated by higher temperature or by disinfectants. How- ever, the results of such immunizations which are mostly limited to laboratory experiments are by no means uniform. This irregularity is probably due, on the one hand, to the variance of the virulence of the cultivated bacteria, and on the other hand, to the difference of action of the methods employed in the attenuations, accurate control of which is almost impossible. More recently J. and M. Ligniéres (1902) produced a potent vaccine for all the diseases of this group from cultures which had been reinoculated several hundred times from agar to agar at two days’ intervals, as a result of which they possessed a uniform virulence. Flasks with a wide bottom are filled to a height of % em. with peptone-bouillon and inoculated with the stock culture. The flasks are then placed in a thermostat and kept at a temperature of 42-43° C, The cultures which are grown for five days at this temperature produce the first, while those grown only for two days, the second vaccine. With the attenuated cultures immunity may be produced not only against the same variety but also against related varieties of the bipolar bacillus. Kitt was the first to point out the possibility of a uniform procedure for the control of the diseases of this group. He successfully immunized chickens against fowl cholera with the virus of rabbit septicemia. Later Jensen obtained the same results with the virus of infectious pneumonia of calves. Ligniéres also proved that this reci- procity obtains with regard to all strains of the varieties of bacteria belonging to this group. He succeeded in demonstrat- ing experimentally that a vaccine prepared from a culture of a certain variety is potent in the first place against this variety, but that it also has a protective action, although of a lesser degree, against the bipolar organism of the other diseases of this group. But its protective action for the latter diseases is so slight and uncertain that it does not meet with practical requirements, and besides the preparation of the different vac- cines for each of the diseases would be very troublesome. Ligniéres therefore prepared a so-called polyvalent vaccine 86 Hemorrhagic Septicemia. which is potent against all the diseases of this group. The vaccine is prepared from mixed cultures of the hemorrhagic septicemia bacteria of sheep, cattle, dogs, horses, hogs and chickens and attenuated at a temperature of 42-43°C. The vaccine prepared from the six varieties of virus is supposed to immunize against all of the six diseases. Test animals inoculated with this vaccine will show a resistance against a virulent infection, while control animals will die or become severely affected (with the exception of very virulent intravenous infections). In practice the vaccinations are supposed to have given good results, especially against the acute septicemic forms of hemorrhagic septicemia, as for instance against chicken cholera and hemorrhagic septicemia of sheep. On the other hand, the re- sults in the slower forms which are frequently associated with mixed infections were less favorable, although even in these cases the mortality has been supposedly reduced from 50% to 12%. The immunization consists in a subcutaneous or intraperitoneal injection of the vaccine; the second inoculation follows in from 12 to 15 days. In infected localities it is advisable to undertake the vaccination on sucking animals 8 to 10 days after their birth, or at least shortly before weaning. The immunity produced by the vaccination lasts for about a year, and therefore it is advisable in infected localities to repeat it annually. : Serum Immunization. Kitt (1897) found that animals (among others, horses and cows) which have been injected with the virus of chicken cholera produce a,blood serum which protects chickens against an artificial infection of virulent material. This fact was later confirmed in connection with swine plague by Schweinitz and Leclainche while Ligniéres & Spitz (1902) showed that this principle applies to all diseases of the hemorrhagic septicemia group. With regard to the immune sera, there exists a similar reciprocity as in the case in which the vaccines are prepared from living cultures. Kitt & Mayr have established these facts for swine plague and fowl cholera, Grosso for hemorrhagic sep- ticemia of cattle, fowl cholera and swine plague, while Ligniéres generalized the principle. Accordingly an immune serum pre- pared from certain varieties of the bipolar bacillus protects, in the first place, against a virulent infection caused by the respec- tive varieties. However, it is also protective, although in a lesser degree, against the other related varieties. Blood serum of’ animals which have been hyperimmunized with different varieties of the bipolar bacillus has likewise a protective action against all the varieties which were used in the preparation of the serum. , Based on these experimental observations Ligniéres & Spitz pre- pared a so-called polyvalent immune serum against all the pasteurellose. The serum is prepared by inoculating peptone bouillon with the above mentioned six varieties of the bipolar bacillus, and with the mixed cultures prepared in this manner horses are at first subcutaneously, later intravenously injected with increasing quantities (5 to 20 ec.). Horses highly immunized in this way produce a serum which affords protection against all of the diseases of this group, and it even possesses a curative action to a certain degree if employed in the early stages of the disease. Similar results were also obtained by Klepzoff, while Broll Fowl Cholera. 87 & Angeloff showed that by the use of swine plague serum the opsonic index is not only raised for swine plague but also for the bacteria of hemorrhagic septicemia of cattle and fowl cholera. _ . The polyvalence should be considered here in a different sense from that applied in the Wassermann-Ostertag’s polyvalent swine plague serum (see swine plague). The very close morphological resemblance of the bipolar bacilli from the various sources, the similarity of the cultures in their principal cultural characteristics, the great similarity of the pathological processes produced by them, the possibility of intertransmissibility to the different species of animals, like- wise the common immunizing properties, indicate that the bipolar bacilli belong to one species of bacteria, while the few deviating characteristics such as the variance of virulence are only characteristics peculiar to the different strains or varieties. The bacteria which probably developed from a common strain originally have undergone modifications in the bodies of the different species of animals by adapting themselves to exist- ing environments similar to that which occurs in other species of bacteria, and which may also be produced artificially. On the other hand, the differences in the pathological processes in the various diseases may be satisfactorily explained by the special characteristics of the different animal species. The close relationship of the causative factors of the several dis- eases brings the affections produced by them into closer rela- tion. Moreover, the similarity of the etiological factors also indicates uniformity in methods to be used in the control of these diseases. Literature. Hueppe, B. klin. W., 1886, 753.—Ligniéres, Bull. 1900, 329, (Lit.).—Kitt, Hb. d. p, M., 1903, II, 559, (Lit.). (a) Fowl Cholera. Cholera Gallinarium. (Fowl typhoid; Pasteurellosis avium, Choléra des poules [French]; Hihnercholera [German]; Cholera . dei polli (Itahan].) Fowl cholera is an acute, contagious and usually an epizo- otic affection of fowls, particularly of chickens, geese and ducks, and is manifested in a general infection associated with a profuse diarrhea. It is caused by a bacterium of the type of the hemorrhagic septicemia organism, the bacillus avi- septicus. History. This dangerous fowl plague was described by_veter- inarians as early as the 18th century, and in the middle of the last century some of the authors (Benjamin, 1851, Delafond & Renault, 1851, and Hering, 1858) have recognized its contagious nature and also substantiated it experimentally. Perroncito (1878) and also Sem- mer described a diplococeus as the cause of the disease which they constantly found in the blood of chickens dead of the disease. Toussaint 88 Fowl Cholera. (1879) and later Pasteur (1880) confirmed their findings and succeeded in growing the bacteria in artificial bouillon, thus enabling them to study their pathogenic characteristics. Pasteur carried out his first fundamental experiments on the attenuation of bacterial cultures and on immunization with such attenuated cultures with the bacilli of fowl cholera. Valuable contributions regarding the etiology of the disease were also furnished by Kitt and Ligniéres. , Occurrence. Fowl cholera occurs extensively in Europe (with the exception of Great Britain), in North America and in South Africa, and causes very heavy losses, especially among the finer breeds. The extent and value of the losses cannot be accurately estimated; as a matter of fact, in some of the localities, occasionally half or even a larger proportion of the flocks are annihilated. Aside from the money value of the dead and slaughtered. fowls, the total loss is considerably in- creased by the temporary retrogression of fowl breeding in the affected localities as well as by the reduction of the egg production. In the year of 1908, 14,397 chickens, 13,877 geese, 4,795 ducks, 272 pigeons and 256 other fowls died or were slaughtered in 776 townships in Germany on account of cholera. The greatest number of losses occurred in the government districts, Potsdam, Bromberg, Oppeln, Allenstein, andPosen (in the last 3 years the number of cases was reduced from 74,329 to 33,597). The losses of the other countries are not known, but the disease exists at the present time to a great extent in Russia, Italy, Austria, Hungary, France, Bulgaria, California, etc. Etiology. The bacillus (bipolaris) avisepticus (bacillus cholerae gallinarium s. avicida, pasteurella avium) belongs to the smallest of the bipolar bacilli with which it, however, cor- responds in the morphological and cultural characteristics (see page 79). In fowl blood the bipolar staining is particularly well marked (see fig. 24 on page 79); peptone bouillon is made uniformly cloudy with or without the formation of a slimy sedi- ment (according to Hertel the bacilli sometimes pass through a porous Berkefeld filter). Tenacity. The bacteria of fowl cholera remain alive in manure for at least 3 months (Gaertner), in putrefactive carcasses and in garden soil for 3 months (Kitt), in water with the exclusion of air and at a temperature of 5 to 6 de- , grees for 18 days (Hertel). They also show a considerable resistance to eld (according to Kitt they resist freezing for 14 days, and according to Hertel their virulence is gradually reduced at minus 13 degrees), but they are less resistant towards other harmful influences. Thus, when dried in exudate in the air, and under the influence of sunlight they lose their virulence in 48 hours, if the light is excluded in 72 hours (Helfer), whereas organs of carcasses are sterilized by a temperature of 45 to 50° C. in % hour, and in 10 minutes at a temperature of 80-85°C. (Kitt). The following disinfectants have a destructive action on the organ- isms: 1% carbolic acid, 44% sulphuric acid (Salmon), 1% chlorate of lime, and 5% milk of lime (Jager). The blood and loose excrements are positively disinfected by thoroughly mixing them with a 5% copper sulphate solution (Colin). Turf dust has also a disinfecting action (Ulmic acid), for when bloody intestinal con- tents i mixed with it the infectiveness of the bacilli is destroyed in 48 hours (Hertel). Pathogenicity. The blood of chickens affected with cholera as well as fresh pure cultures produce the disease in fowls after Pathogenicity. 89 cutaneous or subeutaneous injection even in minimal doses. The transmission may be made successfully by taking the point of a needle dipped in blood and scarifying or pricking the skin at any part of the body. In this manner as well as by subcutaneous and intramuscular inoculations most of the dif- ferent species of domestic fowl (chickens, ducks, geese, turkeys, pigeons, pheasants and fancy birds) and small wild birds (sparrows, finch, etc.) are easily infected. These birds also become affected by the dropping of a culture into the conjunc- tiva, nose or the laryngeal mucous membrane, as well as on superficial wounds of the comb, wattles and feet (Hertel). Further, the disease may be produced by feeding of blood, meat, organs and intestinal contents of affected animals as well as of pure cultures. The disease produced by inoculation usually results in death in from 12 to 24 hours, while when produced by feeding of the virus it terminates only after a longer period (according to Semmer sometimes only after 8 to 12 days). Of other animals rabbits and mice are susceptible to the disease, whereas in guinea pigs (Pasteur), cattle, sheep and horses (Kitt) the subcutaneous inoculation produced only an abscess at the point of injection (guinea pigs, however, are easily infected by intraperitoneal inoculation). Intravenous injections of very virulent cultures are pathogenic for domestic mammals (hogs, dogs and cats), while through feeding of such material infection is successful only in rabbits. Stange & Persdorf observed a simultaneous infection in chickens and hogs which they traced to an infection with the fowl cholera virus. On the other hand, Koske has not succeeded in infecting hogs artificially with the cholera virus. On man the eating of affected fowl has apparently no harmful effects. Repeated passage of the bacteria through the bodies of chickens, pigeons or sparrows increases their pathogenicity which is still more increased by passage through guinea pigs (intraperitoneally). In this way the virulence may be increased to such an extent that intravenous injections of such virus may kill domestic mammals in a few hours (Ligniéres). On the other hand, the air, and more so the combined action of air and sunlight, attenuates the virulence of the bacteria (Pasteur, see page 94). The bacteria produce toxins in artificial cultures. Pasteur found that the subcutaneous injections of large quantities of filtrate of bouillon cultures free from bacteria cause in chickens a somnolence and stupor lasting for several hours, similar to that seen in the disease. This fact was later confirmed by Salmon, Stange, Kitt, as well as by Klett & Braun. (See page 84.) On the other hand, Calamida obtained from a 12-day old bouillon culture a hemolysin which has the strongest ‘action on rabbits, less on guinea pigs and still less on the red blood corpuscles of chickens. Natural infection usually results from the ingestion of droppings or saliva of affected fowls, contaminated feed, viscera 90 Fowl Cholera. of slaughtered or any parts of the body of affected animals; besides, when healthy fowl drink from the same vessels or from a pond from which infected birds have watered. The infection from cages as well as from the premises may also be dissemin- ated in various ways to neighboring localities where an outbreak may follow. . The disease is mostly introduced into premises, which have been free from the disease, by the introduction of infected fowls, and less frequently by the sale for food purposes of birds which have been slaughtered while ill. The disease is also very frequently disseminated by poultry shows in which the veteri- nary supervision is very deficient. Further, it may also be disseminated by pigeons which take up the contagion in in- fected premises, become infected themselves and by their in- testinal excrements infect the other birds of the premises (Cagny, Nocard). Finally, the disease may be spread by wild birds, particularly sparrows (Hertel demonstrated virulent bacilli in dermanyssus mites which he took from the body of sick chickens). The possibility of the spontaneous occurrence of fowl cholera in localities in which this disease or one of this group has existed is not excluded in view of the general statements made on page 81, but this possibility has not yet been demonstrated by satisfactory observations (according to Gamaleia the intestinal canal of healthy pigeons contains fowl cholera bacteria, but Joest did not succeed in demonstrating them in the intestinal contents of chickens. Ostertag & Ackermann likewise failed to find them in chickens and geese). A fluctuation of virulence in the cholera virus is observed under natural conditions as some outbreaks are limited to certain species of fowls, while other species in spite of exposure to the infection fail to contract the disease (for instance, chickens and water fowl] are exclu- sively affected). These observations show a still closer accommodation of the virus to the organism of a certain species, as a result of which such accommodated bacteria are strongly virulent for only a certain species of fowl, whereas for another species they are less virulent or non-pathogenic. However, such differences in the virulence are rare and are not constant, and therefore the infections of various species of fowls should not be considered on this basis alone as independent affections. Susceptibility. Purebred and water fowl are particularly susceptible to natural infection, whereas the common breeds of fowl show greater resistance. Fowl which have withstood an infection by ingestion a short time before are more suscepti- ble to a second infection. Pathogenesis. The bipolar bacilli penetrate the intestines, probably even through the uninjured mucous membrane, into the lymph spaces of the intestinal wall, and soon gain entrance to the blood stream where they multiply with great rapidity and cause the death of the animals. If the entrance of the bacilli takes place through a separation of the continuity of E81 Pathogenesis. g{ the skin or mucous membrane directly into the blood stream, death results in a shorter time (Tiede found bacilli in the in- ternal organs of a mouse 15 minutes after subcutaneous inocul- ation). Death is caused in the first place by the action of the toxins which without a doubt form in the animal body in such a manner that through the negative chemotaxis of the virulent bacteria the phagocytes are unable to exert their action (Gabrit- schewsky, Silberbeg & Zeliony). The chemotaxis of the at- tenuated bacteria is on the other hand positive, and this ex- plains the local suppurative inflammation which usually ter- minates in recovery after a subcutaneous injection of such a virus. Injections of attenuated virus into the chest muscles of chickens produce a serous inflammation of the connective tissue and degeneration of the musculature (see page 95). The bacteria penetrate from the blood circulation into eggs, and they have been found in the yolks of eggs of affected animals (Celli & Marchiafava, Barthelémy). The first two authors have also demon- strated the transmission of the disease to the progeny; on the other hand, Kitt found that young rabbits (4-6 weeks old) descending from artificially immunized animals resist a virulent infection. Anatomical changes. The principal anatomical findings in acute cholera consist in an acute hemorrhagic inflammation of the intestines and lungs in association with small hemor- rhages on the serous membranes and sometimes a fibrinous exudate on the same. The blood vessels of some of the loops of the intestines are injected and their peritoneal covering also contains small punctiform hemorrhages. The intestinal con- tents are fluid, mixed with mucus and fine bloody streaks, or of a uniform reddish color from the admixture of a considerable quantity of blood. The intestinal mucous membrane appears reddened sometimes only in spots and again in longer portions, particularly in the duodenum. It shows an inflammatory swell- ing and is studded with dark red hemorrhages; exceptionally small round diphtheritic ulcers are also found on the intestinal mucous membrane (frequently in water fowl). The serous content of the pericardium is frequently cloudy and contains small fibrinous flakes; the epicardium appears as if sprinkled with blood and is frequently covered with fine fibrinous membranes, particularly in water fowl. The lungs are congested and edematous, sometimes dark brownish red in spots and hepatized as an indication of a croupous hemorrhagic inflammation which is sometimes as- sociated with a fibrinous pleuritis. The mucous membrane of the upper air passages shows catarrhal reddening and swelling. In the parenchymatous organs the first stages of parenchy- matous degeneration may be observed. The regional lymph glands of the spleen and cecum are almost invariably decidedly swollen and hemorrhagic. Exceptionally a fibrinous inflamma- 92 Fowl Cholera. tion (Kitt, Ratz) is present in all the air cells and on all serous membranes. In the less frequent chronic cases yellowish, grey, dry caseous foci are frequently present in lungs, liver and on the intestinal mucous membrane, sometimes also under the en- docardium, which may become quite extensive, especially in the lungs. Exceptionally even both lobes of the lungs may show hepatization resembling caseous pneumonia (Jungklaus). At the same time there may be a fibrinous pleurisy and pericarditis, and in some of the joints and tendon sheaths a caseous exudate may be present (Sticker, Hensel, Willach). In the acute form bacteria may be found in great numbers in the blood, between the blood corpuscles and only sparingly in the white blood corpuscles as well as in the exudates. The intestinal contents are also virulent. In chronic cases the caseous foci also contain virulent aad bacilli, while they are present in only small numbers in the ood. Symptoms. Ostertag & Ackermann’s experiments showed the time of incubation after a single feeding with organs of fowl affected with cholera to be 1 to 2 days in geese, and 4 to 9 days in chickens. After the recovery from a feeding in- fection a new infection produced death in geese (feeding) as early as 19 hours and in chickens (subcutaneous infection) as early as 8 hours. The-time of incubation is very likely the same in natural infection. The acute form of the disease sometimes runs a very rapid ~ course; the animals drop to the ground while running, or they fall to the ground from an elevated place, such as the rod of a cage, or from a tree, and die after flapping their wings a few times. In the large majority of cases, however, conspicuous symp- toms precede death. The birds suddenly become depressed, they assume a crouching position, seek secluded places, and_- sit trembling. Sometimes the head is hidden under the wing or it may be turned backwards. The plumage is ruffled, the wings may droop, and if they move a staggering and wabbling gait is manifest with the wings hanging and the head drooped. The appetite is impaired from the onset, while thirst, on the other hand, is increased. A foamy slime drips from the nasal and oral openings; and from time to time the birds turn their necks convulsively, or stretch out their heads on which the bills, combs and wattles show a bluish-red discoloration. At the same time they may vomit a greyish-yellow slimy mass. At the height of the disease a profuse diarrhea develops; the droppings are at first yellowish-grey, mushy in appearance, later very fluid, dirty, greenish or reddish, mixed with coagu- lated albumin-like flakes, and of a repulsive odor. The plumage around the rectum becomes soiled and matted with the feces. The affected birds show difficult respiration which is mani- Symptoms 93 fested by opened mouth, inspiration as well as expiration being associated with moist rales. As the weakness progresses they lie with closed eyes and in a stupor in one place. If they at- tempt to rise they soon collapse and finally die with manifesta- tions of convulsions or coma. In the chronic form of the disease progressive anemia de- velops after the disappearance of the acute symptoms, or from the onset of the disease, attended by emaciation; finally a per- sistent diarrhea occurs. Sometimes one or more joints of the wings or feet swell; later the swelling bursts, whereupon a caseous purulent mass containing bacilli is discharged from the joints. The arthritis interferes to a great extent with the movements of the already weakened birds. The duration of the disease is from 1 to 3 days in the majority of acute cases with the exception of the peracute cases. It may, however, exceptionally extend from 7 to 12 days. In these cases the symptoms are less severe from the onset, and the exhaustion appears later. The course of the chronic form extends over several weeks. The prognosis is very unfavorable. Frequently entire flocks of chickens succumb to the infection, while in other cases a cer- tain percentage of the birds escape probably owing to a slighter intensity of the infection. However, in exceptional cases re- coveries may take place. Diagnosis. Chicken. cholera in its course and symptoms greatly resembles chicken pest. The latter comes into con- sideration particularly when it affects chickens exclusively. From this as well as from other septicemic affections of fowls, and also from acute poisonings which are frequently suspected by the owners, the disease can be differentiated with certainty by an autopsy and bacteriological examination (see also chicken pest.) Intestinal worms (for instance, the trichosoma collare) may also produce cholera-like symptoms. Chronic eases, particularly those which are associated with arthritis, may be mistaken for tuberculosis and gout. A dif- ferentiation is here also only possible by microscopical exam- ination of the exudates from the joints, as well as by autopsies. On autopsy the presence of intestinal inflammation, the fibrinous exudate contained in the serous cavities, and the hemorrhages are strongly suggestive of fowl cholera, but to establish a definite diagnosis even in such eases a bacteriological examination of the blood and the inflammatory products is necessary. The microscopical examination consists in the preparation of cover-glass smears in which usually large masses of bipolar rods can be easily recognized by the aid of the previously mentioned staining methods (see page 79). Pigeons are best suited for test inoculations, especially since they are not susceptible to chicken pest. For this purpore the point of a knife is dipped into blood or exudate and then used for searifying the skin, or a small quantity of the material is injected, sub- eutaneously or it may be introduced into the breast muscles. The inoculation usually results in a short time in the death of the test animals and when the in- 94 -Fowl Cholera fection is produced by an injection into the breast muscles, a yellow gelatinous in- filtration of the subcutaneous tissue develops at the point of inoculation around which the surrounding muscles show a yellow discoloration and necrosis. Mice may also be used for diagnostic purposes. In these the bipolar bacilli may be demonstrated in large numbers in the blood. Treatment. At the onset of the disease the treatment of the affected as well as the exposed fowls with highly potent immune serum is indicated (see page 95); otherwise, the af- fected birds are given the customary weak solutions of disin- fectants, which may be added to the drinking water. These solutions, viz., iron sulphate, salicylate acid, tannin (14 to 1%), sulphuric or hydrochloric acid (2:1000), may also be given in tablespoons or teaspoons (Ward and Stange give a 1 to 1500 or 2000 corrosive sublimate solution as drinking water). The same methods may be also applied as preventive measures against the disease in healthy birds which are threatened by infection. The subcutaneous injection of a 5% carbolic acid ° solution (Nocard, Barberio) is followed by little or no bene- ficial results. Prevention. Great care should be exercised in order that the introduction of the disease by the purchase of new birds may be prevented. In addition to careful examination of the source, it is advisable to keep new birds separated for at least 1 week, and only after that period should they be allowed to mingle with the birds of the flock. If the disease has already appeared in a flock, entirely healthy birds should be taken to an absolutely clean place with- out delay. Those already affected or suspected should im- mediately be slaughtered or taken to a separate place for treat- ment. The carcasses should be buried deep, or, still better, burned. After burning or burying the droppings, the walls and roosts of the chicken houses as well as the drinking vessels and containers used for feeding, should be scalded with hot water or washed with hot lye. They should also be sprinkled with lime, and the previously cleaned floors should be sprayed with a 3% creolin or lysol solution. Airing of the chicken houses for several days promotes good results from this method of prevention. The droppings from the affected as well as the healthy birds should be collected at least once daily and burned. Immunization. Formerly attenuated cultures were used for this purpose, while recently the immunization with blood serum is more extensively employed. I. Immunization with attenuated cultures (Pasteur’s method). According to the investigations of Pasteur (1880) the bacteria of chicken cholera in bouillon cultures are gradually attenuated under the influence of the atmospheric air until after about two months standing they lose their virulence entirely. Tf allowed to stand for a shorter time the bacteria are attenuated Immunization. 95 to a certain degree, which virulence they retain if their culti- vation is continued. Cultures attenuated to two different de- grees produce two vaccines with which chickens may be im- munized against virulent infections. This method of immunization is of great scientific im- portance but has not proven successful in practice. Irrespec- tive of the inconvenience of this method, in consideration of the relative small value of fowls, the inoculations in their prac- tical applications sometimes cause considerable losses. Fur- thermore, the desired protection is not afforded which is very probably due to the uncertainty of the applied attenuation. Pasteur’s vaccine produces local necrosis of the muscles and serous inflammation of the connective tissue when injected under the skin of the breast of chickens. The corresponding part of the breast muscle separates from the living tissue towards the end of the second week, whereupon the sequestrum is reabsorbed in 3 to 4 weeks, or is cast off through a fistula which may have formed. Kitt found by repeating Pasteur’s experiments with the two original vaccines that both produced such local affection in chickens and ducks, and in the majority of these birds produced an effective immunization. On the other hand, pigeons, rabbits and small birds were killed by the inoculation. Attempts to prepare suitable vaccines from cultures through attenuation at higher temperatures (Salmon, Jess) and through the addition of chemicals (Jess) were unsuccessful. Ligniéres recommends his polyvalent vaccine (see page 84) against chicken cholera, and in this disease the best results are supposed to have been obtained. The dose consists of 14 ce. (subcutaneously). II. Immunization with immune serum. Kitt (1892) es- tablished by experiments that the blood of chickens immunized against cholera has an immunizing effect upon healthy chickens, and further that the white and yolk of eggs of immune chickens (5 to 10 ec.) possesses a similar effect. Later Kitt & Mayr (1897) prepared a serum by means of intravenous injections of virulent cultures in horses of which 2 to 20 cc. produced pas- sive immunity in rabbits and 14 to % ce. in mice, nevertheless it was ineffective in chickens. Still later Kitt (1902-3) produced an active immunity in rabbits by injecting them subcutaneously first with immune serum from chickens or horses (1 to 10 cc.) and following this with the injection of virulent cultures. Rabbits highly immunized in this manner produce a serum of which 1%4 to 3 ec. protect rabbits and mice against a virulent infection, and in some cases chickens and pigeons were also immunized with it. Finally Kitt obtained a serum from horses by subcutaneous injection of virulent cultures, of which 2 to 5 ec. conveyed effective protection to rabbits, geese, ducks, chickens and sometimes also to pigeons against a fatal cutaneous or subcutaneous infection. The immunity develops not later than 24 hours, and is also effective against intestinal infection. The serum inoculations naturally produce a passive im- munity lasting only from 1 to 2 weeks, and therefore their 96 Fowl Cholera. application is indicated only in flocks already infected or in those which are threatened by infection. (Experiments to change immunity through subsequent inoculation of virulent material into an active form have thus far been unsuccessful.) Through a procedure similar to that of Kitt & Mayr, Schreiber succeeded in preparing a blood serum of which .5 ce. protected a pigeon against a virus which was fatal in 24 hours. The dose of this serum is for geese or ducks 1 cc., for smaller birds .5 cc. Hartel obtained a serum by treating an ass with living bouillon cultures (intravenous) of which .5 cc. protected a pigeon against a dose of virus of which 1-10,000 part was fatal. : Jess & Piorkowski inject fresh horse serum containing alexin under the skin of fowl before the use of the immune serum in order that the antibodies contained in the horse serum may find a sufficient quantity of alexins in the tissue fluids. The single dose is .5 to 4 cc. of immune serum, depending on the size of the bird, and 1 to 8 ce. of normal serum. The mixture is supposed to effect also a curative action when applied not later than 6 hours after the infection has taken place. Mosler found the mixture also more effective in mice than the immune serum alone. The experiments made in Prussia are, however, contradictory (Rae- biger). ‘ iced & Braun immunize horses with 4-day old bouillon cultures of the fowl] cholera bacteria which have attained the highest degree of virulence by passage through the bodies of sparrows. The treatment commences with a dose of .25 ce. of culture subcutaneously and intra- venously, which quantity of culture is gradually increased to 20 cc. and is later injected only into the circulation. Horses thus prepared produce an immune serum of which 0.0015 to 0.005 ce. will protect gray mice for a period of about 3 weeks against the fatal action of a loopful of a 4-day old bouillon culture. The results obtained in practice met the expectations based on the laboratory experiments, and the sera sometimes appear to have a curative action in animals already affected. In consideration of the close etiological relation of swine plague and chicken cholera Schreiber employed for the inoculation of fowl a serum (septizidin) which affords protection against the former disease, and some other authors (Hartenstein, Graffunder, Schmidt and others) also obtained with it satisfactory results. The official reports, however, of Prussia and Saxony are mostly unfavorable. Finally, Ligniéres’ polyvalent serum may also come into consideration. The ‘‘Hochst Farbwerke’’. prepare a polyvalent serum (Galloserin) with which Kovaes, Széke & Szab6 and others obtained quite satisfactory results in ex- posed as well as already affected birds. Raebiger made comparative experiments with the various vaccines on the market and found that pigeons inoculated with Héchst serum or with septizidin withstood the infection in 66%, while those injected with Gans’ (Frankfurter) and Piorkowski’s (Berlin) sera died. The serum of Klett- Braun proved effective in laboratory experiments and also once in practice. Del- fino found Ligniéres’ vaccine effective in rabbit experiments. Technique of vaccination. Pasteur originally inoculated into the point of the wing, later the inoculation was made under the skin of the breast or into the breast muscle. According to the suggestion of Jess it is more satisfactory when made under the skin of the neck. An assistant secures the bird with both hands on the rump while the operating veterinarian raises a fold of the skin of the neck with his left hand. The dose to be inoculated is indicated specially for each preparation. III. Immunization with Aggressins. Weil employs, according to the procedure of Bail, a pleural exudate produced by injections of Immunization. 97 fowl cholera bacteria into rabbits. After the addition of .5% carbolic acid this is heated for 3 hours at 44° C. Repeated injections of small doses (.5 to 3 cc.) or a single injection of 5 cc. protected guinea pigs and rabbits as well as a hen and a pigeon against a subsequent lethal infection. Rabbits highly immunized with sterile exudate produce serum of which .5 ec. protected rabbits against a dose of the culture which is fatal in 20 hours. According to the aggressin theory (see page. 30) the body is supposed to form an anti-aggressin as a result of the injec- tion of aggressins which destroys the aggressiveness of the bacteria and their unlimited power of multiplication. Huntemiiller, however, found that similar good results may be obtained in rabbits with wash- ings of cholera cultures heated to 44° C. He also learned that the filtrate of exudates was ineffective, and he therefore concurs in his belief with Wassermann and Citron, that in immunization the toxic body substances of the bacteria are the effective agents. Bisanti’s experiments suggest also the possibility of a toxin immunization. This investigator sewed collodium sacs filled with virulent cultures into the abdominal cavity of rabbits and thereby protected them against a cerebral infection. Veterinary Police. Chicken cholera has been recently in- cluded among the diseases requiring compulsory official notifica- tion in Germany, Austria and Hungary. Upon the appearance of the disease the infected premises or in case of a greater ex- tension, localities and even entire townships are quarantined against traffic in fowls. The inland and foreign traffic in fowls as well as the premises of dealers are subject to official super- vision. Literature. Renault, Rec., 1851, 321—Hering, Spez. Path., 1858, 355 (Lit.).— Perroncito, A. f. Tk., 1879, V, 22.—Toussaint, Ree., 1879, 946.—Pasteur, C. R., 1880, XC. u. XCI.—Ziirn, D. Gefliigelkrankh., Weimer 1882.—Kitt. D. Z. f. Tm., 1888, XIII, 1; Hb. a. p. M., 1903, II, 543 u. 1904, IV, 969 (Lit. on etiology and immunization).—Ligniéres, Bull., 1900, 332, u. 1902, 444.—Klett & Braun, D. t. W., 1904, 545.—Weil, A. f. Hyg., 1905, LIT, 412; 1908, LVX, 85.—Ostertag & Ackermann, Z. f. Infkr., 1906, I, 431—Jungklaus, Diss. Leipzig 1906. Other Diseases of Fowl of a Septicemic Character. Various ob- servers have described in the course of the last decade different epi- zootie affection in fowl in addition to chicken pest which simulate chicken cholera more or less. In some of these their identity with chicken cholera was established. Others, however, were shown to be different, while the nature of some of the diseases is doubtful even at the present time. On account of their relatively slight importance and their prevention by other means than immunization for which it is essential to establish the causative agent, the same principles mentioned for chicken cholera are also applicable. Therefore these diseases will only be briefly mentioned here, emphasis being placed on their most important differences from fowl cholera. The following diseases are identical with chicken cholera: Lisi’s chicken septicemia (Clin. vet., 1895, 176), and the hemor- rhagic septicemia of ducks and chickens described by Rabieanx (Soc., biol., 1900, 141). 98 Fowl Cholera. Diseases simulating chicken cholera: Infectious enteritis of chickens; observed repeatedly in England and Ireland by Klein. The causative agent (Bac. gallinarum) greatly resembles the bacillus of fowl cholera. However, it does not kill pigeons and only exceptionally rabbits. (Obl. f. Bakt., 1889, V, 689; 1895, XVIII, 105.) Enzootic pneumo-pericarditis of turkeys; observed by M’Fadyean and later by Jowett. The bacillus also resembles that of chicken cholera. However, it is motile and non-pathogenic for chickens as well as for water fowl. (J. of Comp. Path., 1893, VI, 334; Ibid., 1908, X XI, 324.) Cholera of water fowl; observed in Germany, by Willach. The bacillus is distinguished from that of fowl cholera by its motility, is only slightly pathogenic for hens, and non-pathogenic for pigeons. (Cbl. f. Bakt., 1896, XX, 187.) Disease of swans; observed in the Zoological Garden of Antwerp by Trétrop. The bacterium develops only slightly on potato, and causes in swans a caseation of the lymph glands; chickens are not susceptible. (A. P., 1900, XIV, 224.) Diseases apparently different from fowl cholera: Cholera of ducks; observed in the Zoological Garden of Paris by Cornil & Toupet. The bacillus stains well by Gram’s method dnd grows well on potato; chickens, pigeons and guinea pigs are not sus- ceptible, rabbits to only a slight extent. (C. R., 1888, CVIII, 1747.) Epizcotic dysentery of chickens and turkeys; described by Lucet. The course of the disease is from 9 to 13 days. The bacillus thrives well on potato and kills guinea pigs by intravenous inoculation. (A. P., 1891, V, 312.) Disease of ring-dove; observed in France by Leclainche, and is characterized by its rapid course, somnolence and diarrhea. The bacillus (Bac. cholere columbarum) thrives on potato; chickens are not at all susceptible, while other fowl show only a slight susceptibility. (A. P., 1894, VITI, 490.) Disease of pigeons; observed in New Jersey by Moore. Cerebral symptoms predominate in this disease. On autopsy meningitis is found to be present, while intestinal symptoms are absent. The bacillus re- sembles Bac. suipestifer; it grows on potato. (Bur. Anim. Indus., Bull. No. 8, 1895, 71.) Infectious enteritis of pheasants; observed in the Zoological Gar- den of Milan by Fiorentini. The affected animals are not somnolent. Autopsy does not reveal small hemorrhages. The bacillus is not motile; it forms on potato a honey-like growth and produces indol in peptone bouillon. Chickens, guinea pigs and rabbits are not susceptible. (Soc. ital. di. se. nat., 1896, 89.) Septicemia of ducks; observed in Italy by Lisi. The affected birds show purulent conjunctivitis and keratitis. The bacillus liquefies gelatin gradually and forms a brownish growth on potato; chickens are not susceptible to artificial infection. (Il Med. zooiatrio, 1890, 415.) ed Differentiated Diseases. 99 Hemorrhagic septicemia of swans; observed in the Zoological Gar- den of Milan by Fiorentini in pheasants and Egyptian geese. The bacillus is motile, bouillon is made cloudy and of a yellowish discolora- tion, grows on potato in the form of chocolate-brown colonies; the cul- tures liberate a fetid odor. (Chl. f. Bakt., 1896, XIX, 932.) Exudative septicemia of geese; diagnosed first in Mecklenburg by Riemer, later in Stralsund by Frosch & Birnbaum (the disease described by Bugge as infectious inflammation of the air-sacs of geese is probably identical). Characteristic lesions; pronounced sero-fibrinous pericarditis and fibrinous peri-hepatitis. The slender rod-shaped bacil- lus (Bac. septicemiz anserum exsudative) which resembles Pfeiffer’s influenza bacillus forms threads in cultures, is not motile, does not form spores, decolorizes by Gram, and is strongly pathogenic for geese and less for ducks. (Lit. Chl. f. Bakt., 1909, LII, 433.) Epizootic pneumo-enteritis of turkeys; described by Dodd, is char- acterized by swelling of the sub-orbital region, emaciation and diarrhea or hepatization and small necrotic nodules in the lungs, as well as fibrinous exudates in the pleural cavity. The causative agent resembles the ovoid cholera bacillus. (J. of Comp. Path., 1905, XVIII, 239.) Infectious leukemia of chickens; studied in the United States by Moore; its course extends from 1 to 3 weeks with symptoms of a severe leukemia. The causative agent (Bac. sanguinarium) ; forms yellowish- white colonies on potato. (Bur. Anim. Indus: Rpt. 1895-96, 185). Chicken plague; observed by Mazza in northern Italy. In the course of the disease caseous foci develop in the lungs. The bacillus is motile, develops gases in bouillon containing sugar, grows on potato in the form of colorless, lustrous deposits; rabbits are slightly sus- ceptible. (Chl. f. Bakt., 1899, XX VI, 181.) Disease of canary birds; described by Rieck. A soot-like dis- coloration of the skin develops, while the liver contains punctiform necrotic foci. The bacillus is motile and grows on potato in the form of yellowish-gray colonies. (D. Z. f. Tm., 1889, XV, 69.) Cholera of canary birds; studied in Budapest by F. Kern. The bacillus does not take bipolar staining, is not motile, develops fetid gases in agar containing sugar, and forms yellowish colonies on potato, the medium showing a bluish discoloration. Chickens and pigeons are not susceptible. (D. Z. f. Tm., 1896, XXII, 171; according to Nocard Ziirn’s canary plague is supposed to be identical with this disease. ) Infectious malady of canaries; described by Pfaff as a different disease from the above. The bacillus is somewhat larger than that of Kern, forms fine flakes in bouillon, does not grow on potato, is harmless for chickens, and pathogenic for pigeons. Constant lesions; small ne- crotie foci in the liver and spleen (Cbl. f. Bakt., 1905, XX XVIII, 275) ; a similar disease was described by Wasielewsky & Hoffmann (A. f. Hyg., 1903, XLVII, 44) and recently by Zwick (Z. f. Infkr., 1908, IV, 33.) Septicemia of canary birds; described by Freese as a very severe disease similar to the cholera of canaries, but does not liquefy gelatin 100 Fowl Cholera. and is Gram positive; milk is coagulated and it does not ferment dextrose. There. is no necrosis of the liver or spleen. (D. t. W., 1907, 501.) Infectious necrosis of canary birds; described by Miessner & Schern as a very infectious disease which is characterized principally by ne- erotic foci in the spleen and liver, and is also frequently associated with diphtheria of the buecal mucous membrane. The causative agent is a short stubby, Gram negative, non-motile organism (Bac. canariensis necrophorus). (A. f. Tk., 1908, XXXIV, 133.) Typhoid of canary birds. As Joest had done before him, Zsupén mentions under this name a disease of canary birds caused by bacteria of the enteritis group. It runs a rapid course with symptoms of marked debility, difficult respiration and diarrhea. The constant lesions are acute gastro-intestinal catarrh, and besides, from case to case acute spleen-tumor, fibrinous inflammation of the serous membranes, cloudy swelling of the liver and kidneys. The causative agent (Bac. typhi canariensis) is very similar.to Eberth’s typhoid bacillus, and is patho- genic in general for small birds, as well as for rabbits, guinea pigs, rats and mice. (Dresdn. Ber. pro 1906; Kozl., 1909, VIII, 149.) Disease of guinea keets (Mykosis intestinalis phasianidum) ; ob- served in Germany by Enders; affects exclusively species of chickens. The causative agent resembles that of fowl cholera, is pathogenic for pigeons and water fowl, and grows well on potato. Autopsy shows hemorrhagic enteritis and osteomyelitis. Maggiora & Valenti consider the disease identical with chicken pest, and the described bacillus is supposed to be a frequent inhabitant of the healthy intestines of fowl (D. t. W., 1902, 339). Septicemia of chickens caused by coli bacteria; according to Claussen it is supposed to develop spontaneously in chickens which are exposed in long railroad transportations to thirst, hunger and cold as a result of which the normal coli organism becomes virulent. The symptoms and post mortem lesions resemble those of fowl cholera, but the blood contains bacteria of the coli bacillus type (Z. f. Infkr., 1907. IIT, 69). White diarrhea of chicks; according to Rettger this disease affects chicks in the first three weeks of life, and is caused by a bacterium of the coli-typhus group which is present in the blood, internal organs and also in the yolk (J. of Med. Research, 1909, XXI, 115). Salmonellosis of chickens; described by Ligniéres & Zabala as an infectious and mostly fatal disease which in its course resembles fowl cholera (spleen always swollen). The bacillus resembles the Bac. suipestifer, but is non-motile. Besides chickens, pigeons and rabbits are also susceptible (Bull. 1905, XXXII, 453). Mycosis of parrots (Psittacosis) ; a disease of parrots imported to Europe from Africa and America, characterized by dullness, diarrhea and later by marked debility. In its course small grayish-white foci develop in the internal organs, especially in the liver. The causative agent is, according to Ajello & Parascandolo, a specific bacillus; ac- cording to Rho, a paracolon bacillus which produces toxins in eultures. Differentiated Diseases. 101 With this disease the cause of some forms of pneumonia in man is associated, but according to the investigations of Lichtenstein this sup- position is not well founded (O. M., 1902, 385; Chl. f. Bakt., 1899, XXV, 651). Grouse disease; described by Klein as a very fatal disease of Scottish grouse. The principal symptoms are quick tiring on flying, hoarseness, cyanosis of the conjunctiva, emaciation. On autopsy ne- crotic foci in the liver and small blood extravasations are observed. The bacillus is motile, Gram negative, thrives on potato, quickly ao milk, and produces indol (Cbl. f. Bakt., 1899, VI, 36; 1890, ; ‘ Cholera-like gastro-enteritis of fowl (Vibrionen-cholera, gastro- enteritis cholerica avium). Gamaleia, who observed the disease in Odessa, described as the cause a short, curved bacillus (Vibrio Metschnikovi), which morphologically and culturally closely resembles the comma bacillus of Asiatic cholera. Affected fowl die with symptoms of somnolence and diarrhea within 2-3 days. The bacilli are present in the lumen of the inflamed intestine, and produce the symptoms by the eliminated toxins (A. P., 1888, II, 482). Apoplectic septicemia of chickens; this very disastrous American disease runs its course in from 12 to 24 hours with paralytic symptoms and is caused, according to Norgaard & Mohler, by a very virulent streptococcus which in addition is pathogenic for chickens and also for rabbits, mice, ducks, pigeons and dogs. It is harmless for guinea pigs and sheep (Bur. Anim. Industry, Bull., 1902, No. 36). Sleeping sickness of chickens; was found by Dammann & Mane- gold in the vicinity. of Hannover, later by Greve in Oldenburg. The most striking symptom is the more or less pronounced somnolence. Further, reddening and swelling of the conjunctiva, if the course is prolonged, also paleness of the comb and wattles, diarrhea and emacia- . tion. In the heart blood the Gram-positive encapsulated streptococci are found in great numbers (Str, capsulatus gallinarum) thriving best on coagulated blood serum and in milk. It is also pathogenic for pigeons, rabbits, mice and lambs (D. t. W., 1905, 577; 1908, 213). Septicemic and Pyemic Affections of Rabbits. Among rabbits mostly in laboratories, but not infrequently also in valuable rabbit breeding establishments septicemic affections occur, some of which will be described briefly. Rabbit Septicemia. Davaine, later Koch & Gaffky produced this disease in rabbits by subcutaneous injections of putrid fluids, unclean river water and putrid pickling fluid. After such injections the animals die in from 16 to 20 hours with rapid falling of the body temperature, diarrhea and convulsions. On autopsy the spleen and lymph glands are swollen, the lungs hyperemic, the intestinal mucous membrane in- flamed, serous membranes sprinkled with petechiae. The blood con- tains small bacteria (Bac. cuniculisepticus s. cuniculicida), which in their form and cultural characteristics are practically identical with the fowl cholera bacterium and are very probably identical organisms (Kitt). Cultures kill fowls with manifestations of septicemia. On the other hand, rabbits infected with the virus of fowl cholera also 102 Rabbit Septicemia, Ete. die within a short time. Therefore there is a possibility that the appearance of fowl cholera may be associated with the cause of rabbit septicemia and vice versa. Selter observed the disease in a spontaneous enzo-otic form, and found swine plague serum effective in the treat- ment. (Koch & Gaffky, Mitt. d. G.-A., 1881, L—Ligniéres, Bull., 1900, 356 [Lit.]—Selter, Cbl. f. Bakt., 1907, XLI, 482.) Pleuro-pneumonia of Rabbits. Various authors describe the dis- ease under different names, thus Beck, and recently Kurita as ‘‘pleuro- pneumonia,’’ Kraus as ‘‘influenza-like rabbit plague,’’ Volk as ‘‘rabbit plague,’’ Siidmersen as ‘‘infectious rabbit pneumonia,’’ Eberth & Mandry as ‘‘spontaneous rabbit septicemia,’’ all these are, however, probably identical or closely related. In all cases there was a fibrinous inflammation of the pleura, sometimes also of the pericardium, fre- quently associated with a catarrhal pneumonia. The symptoms con- sisted in a purulent nasal discharge, difficult respiration, emaciation and rapid course. As the causative agent a fine, Gram-negative, spore- less aerobic bacillus was described which resembles the influenza bacillus of man. They are distinguished from each other by unimportant char- acteristics. (Lit. see Z. f£. Tm., 1906, X, 429; also Chl. f. Bakt., 1906, XLIX, 508.) Rabbit Distemper. Described by Lucet as ‘‘septic disease of rabbits.’’ It manifests itself in a phlegmonous swelling of the tracheal and laryngeal regions, nasal discharge, difficult respiration and emaciation. The autopsy shows, in addition to a purulent inflammation of the subcutis at the places mentioned and regional inflammatory edema, pronounced acute swelling of the spleen, enteritis and serous exudate in the thoracic and abdominal cavities. A small bacillus (Bac. septicus cuniculi) is indicated as the causative agent. (A. P., 1892, VI, 558.) Pyemia of rabbits; observed by Koppanyi in Belgian hares usually as a severe affection. In acute cases purulent fibrinous pleuritis and pericarditis are present, while in chronic cases subcutaneous cold abscesses develop which may reach the size of a man’s fist. After rupturing, which sometimes only occurs after 6 to 8 months, recovery follows not infrequently. The disease is caused by a polymorphous ee bacillus (Pyobacillus capsulatus cuniculi). (Z. £. Tm., 1906, X, 429. Streptothrichosis of rabbits is characterized by a progressive necrosis of the skin which extends to the muscles and tendons. Thrombi develop in the blood vessels and as a result emboli occur in the inter- nal organs, especially the lungs. The streptothrix cuniculi which was demonstrated by Schmorl as the causative agent of the disease, is identical with Bang’s bacillus necrophorus. Basset produced an effec- tive immune serum by treating a horse with pure cultures. (D. Z. f. Tm., 1891, XVII, 375; Bull., 1908, 345.) Myxomatous affection of rabbits; observed by Sanarelli in Monte- video and by Splendore in Sao Paolo. At the onset a purulent blepharo- conjunctivitis develops and is rapidly followed by a large swelling of the head, also in. the vicinity of the rectum and the opening of the urethra and genital organs. Post mortem examination reveals tumors in the subeutis which have a gelatinous appearance. Further, there Hemorrhagic Septicemia of Cattle. 103 is hypertrophy of the lymph glands, orchitis and spleen tumor. The disease is very easily transmitted artificially and appears to be caused by a filterable virus. (Cbl. f. Bakt., 1898, XXIII, 865; 1908, XLVIII, 300.) (b) Hemorrhagic Septicemia of Cattle. Septicaemia hemor- rhagica bovum. (Bollinger’s Wild- und Rinderseuche, Hemorrhagische Septi- kamie der Rinder [German]; Pasteurellosis bovum, Pasteurellose ou Sépticémie hémorrhagique : du boeuf [French].) Hemorrhagic septicemia is mostly an acute, less frequently a subacute, infectious disease. In its course the febrile symp- toms are usually accompanied by manifestations of an acute gastro-enteritis, inflammatory edema of the skin or frequently a necrotic pneumonia associated with edema of the interalveolar connective tissue. The causative agent is Bac. bovisepticus. History. Bollinger described in 1878 a very fatal disease, which was previously unknown, occurring in the vicinity of Munich among the deer and wild boars. Later it was observed in cattle, and in some instances among horses and domestic hogs. The infectious character of the disease has been established by Bollinger and later by Franck (1881) as well as. by Friedberger (1881). The causative agent, how- ever, was discovered by Kitt (1885) and somewhat later studied by Hueppe (1886). Recently especially Jensen (1889) and Ligniéres (1898 and 1900) investigated the etiology of the disease. Occurrence. The disease occurs everywhere either sporadi- cally or enzootically, especially during the summer. Some- times it originally occurs in deer and wild hogs, spreading later a see a cattle, and from the latter hogs may often become affected. ; In the beginning of the eighties of the last century the disease was repeatedly ob- served in northern Bavaria, but it has been since found in other parts of Germany as well as‘in different European countries. The losses were sometimes consider- able. In the year 1878, 153 deer and 234 wild hogs died in the Reservations in the vicinity of Munich; in 1887 in the District of Bindlach more than 100, and in one district of Prussia the annual loss was more than 100 cattle. In recent times it is principally observed in Prussia (Government districts Posen and Bromberg) as well as in Bavaria. In 1905, 57 cases were reported from Posen and 30 from Hannover, In Austria the disease occurs in Bohemia, Moravia and Silesia. In Moravia 155 cattle and 29 hogs were affected in 1900, in 44 townships, of which number 15 cattle and 15 hogs died. One hundred and one cattle and 14 hogs were slaughtered in emergency (Taufer). In Hungary the disease was first observed in 1900 in the County of -Gémér, in one township where 17 cattle were affected. During the period from 1901 to 1902, 12 yearlings and 2 cows died in Hansag; in 1904, 14 ont of a herd of 49 yearlings in the vicinity of Kapuvar became affected. From time to time sporadic eases occur in fattening establishments. In France the disease was observed by Leclainche and in Switzerland by Guillebeau and Hess. The disease also exists in North America (the broncho-pneumonia of cattle deseribed by Nocard is a form of this disease), in Indo-China, in the Malayean Peninsula, in the Philippines and in Java. 104 Hemorrhagic Septicemia of Cattle. ‘There is sometimes observed a septic pleuro-pneumonia in calves which occurs simultaneously with hemorrhagic septicemia in adult cattle. This disease is either closely related to or identical with hemorrhagic septicemia of cattle (See page 111). Etiology. The cause of the disease is the bacillus (bipolaris) bovisepticus which is a variety of the bacillus of hemorrhagic septicemia. In its principal characteristics it conforms to the organisms of this group (see page 79). Hueppe succeeded in growing it in spring water containing a large amount of organic substances, and also in garden soil. It grows best at body temperature, while at a temperature from 12-13°C. it no longer propagates. A 1:5000 sublimate solution kills it in 1 minute, 3% carbolic acid in 6 hours, moist heat of 80°C. in 10 minutes (Hueppe). The gastric juice appears also to have a bactericidal action (Taufer). Dried virulent blood loses its infectiveness in 14 days (Kitt). The virulence of the contagion varies in the different enzo- otics within wide limits. Deer and wild hogs are very suscep- tible, cattle and domestic hogs are somewhat less predisposed. Under natural conditions the disease affects only animals of these species, but sometimes solipeds and also goats may be- come affected. Subcutaneous inoculations of virulent bouillon cultures produce a severe inflammatory edema which is fol- lowed by suppuration and finally by recovery. Calves, how- ever, have died within several days after such an injection. Intravenous injection acts more energetically. By this method calves may be killed with 10 cc. and cattle with 100 cc. of the culture in 1 to 3 days, with manifestations of acute septi- cemia. After a less severe infection the animals gradually emaciate in spite of a good appetite; at the same time an in- flammation develops in the knee and hip joints, as well as a broncho-pneumonia, whereupon the animals die from extreme exhaustion. Autopsy reveals in such cases as a rule only foreign bacteria in the inflammatory products (Ligniéres). Among other animals rabbits are susceptible to artificial infec- tion; horse, guinea pig, dog and pigeon are less susceptible, while domestic fowls are not susceptible to this disease (Bollinger, Kitt, Taufer). The natural infection results in most cases through the digestive tract; exceptionally the virus may enter the circula- tion through injuries in the buccal mucous membrane and the skin. The latter method of infection is possibly transmitted through flies and mosquitoes (Franck, Dammann & Oppermann recently connected an outbreak of the disease in the Province of Hannover [1905] with swarms of insects [Simulia ornans] as they succeeded in finding in their bodies bipolar bac- teria, although these were only slightly virulent for rabbits). Bollinger also believes a pulmonary infection possible, but this mode of infection has been proven so far only in rabbits. The virus may also be disseminated into remote localities through the meat and hides of affected animals. The sporadic cases as well as the first attacks of an enzo- Natural Infection. 105 otic outbreak occur as a rule through infections of the soil, the causative agent in some localities acquiring a strong viru- lence through unknown influences, or they may he due.to a diminished resistance of the animals. As local enzootics fre- quently develop first among deer and black game the moist soil of the forests appears to be especially favorable for the propa- gation of the bacteria and for the change in their virulence mentioned above. The warm spring weather is particularly favorable for the development of the bacteria. During this period the disease occurs most frequently among cattle. The virus which originates from the soil retains its in- creased virulence for a certain time in the body of the animals, and this may even be increased further. The blood is highly infectious. in the latter stages of the disease, and during this time the blood as well as other body fluids and excrements may also infect other animals, and in this way the enzootic may continue to spread in a contagious form. (Bollinger observed an infection in a steer which died from pneumonia within 54 hours after the ingestion of 1 gram of feces from a calf affected with an acute form of the disease.) After a certain time these enzooties which do not as a rule extend over large territories, usually subside very probably as the result of an attenuation of the virus which takes place in the meantime (Carrougeau. observed a gradual attenuation of the virus from repeated re- inoculations of cattle). The cornstalk disease or corn fodder disease which occurs among cattle in America, especially in the middle and upper Mississippi Valley, is also supposed to be caused by an ovoid bacterium, and to be identical with hemorrhagic septicemia of cattle. This disease usually oceurs in the fall and early winter after the animals are turned into the cornstalk fields. It is characterized by a very rapid course. The autopsy reveals numerous hemorrhages in the internal organs, espe- cially in the serous membranes. Recently, however, Moore showed that the disease was not of an infectious nature, but was due to toxic substances (according to Mayo, potassium nitrate) which are sometimes present in large quantities in the stalks, and which are responsible for the intoxication. As a matter of fact the disease may be actually prevented by cutting the stalks early and only feeding them after they have been carefully cured and removed from the field. Anatomical changes. The autopsy reveals a marked hyperemia of the internal organs as well as fresh hemorrhages in the serous and mucous membranes, and in some of the organs, especially the lungs and muscles. The spleen has either a normal appearance or contains circumscribed bloody areas; the liver and kidneys show cloudy swelling. The other ana- tomical changes vary in the different cases. Tn the edematous or exanthematous form the subcutaneous connective tissue of the head, the throat region and the neck, show a gelatinous infiltration, which may in some places be studded with hemorrhages. The serous infiltration may extend 106 Hemorrhagic Septicemia of Cattle. to the deeper layers of the muscles. The tongue appears more or less enlarged, dark, of a dirty brownish-red color, and of a very firm consistency. On incising this organ a large quantity of a light yellow serous fluid escapes, while in parts of the infiltrated tissue, especially under the mucous membrane, flat, diffused, fresh hemorrhages are present. The frenum of the tongue and the surrounding parts as well as the submucous Fig. 27. Pneumonia in hemorrhagic septicemia of cattle. Above, brownish-red hepatization with hemorrhages; below, grayish-red hepatization with commencing necrosis. Inter-lobular connective tissue edem- atously infiltrated, lymph spaces dilated in parts. connective tissue of the pharynx and the larynx show gelatinous infiltration and appear as flabby masses. The mucous mem- brane of the upper air passages shows a catarrhal swelling and is sometimes covered with croupous membranes. The retropharyngeal lymph glands and those of the neck show pro- nounced acute swelling. Anatomical Changes. 107 The abdominal cavity sometimes contains several liters of a yellowish or reddish serous fluid. The small intestine mani- fests lesions of a pronounced acute hemorrhagic inflamma- tion, which while also present in the large intestine are less marked there. The content of the intestinal canal is thin, fluid, yellowish-gray, or from an admixture of blood, dirty- reddish in color. The spleen is normal, or at most in parts, somewhat swollen. The blood is also normal in color. In the pectoral form the thoracic cavity contains serous or sero-fibrinous exudate which is sometimes mixed with blood. The pleura is inflamed and studded with small hemorrhages, especially the visceral layer which appears to be covered with fibrinous membranes. In one or both lungs smaller or larger connecting parts are hepatized and friable. The cut surfaces are uniformly dark, brownish or reddish in color, finely gran- ular, and contain, in less acute cases, small, dry, caseous areas. Sometimes the interlobular connective tissue septa appear thickened and yellowish-white through serous infiltration, so that the cut surface of the lung has a mottled marbled appear- ance (the appearance in such cases is very similar to the lungs in contagious pleuro-pneumonia [Fig. 27]). The parts which are not hepatized show marked hyperemia and edema. The pericardium may also contain an exudate mixed with fibrinous flakes. The connective tissue of the mediastinum is gelatinously infiltrated and studded with hemorrhages. The peribronchial lymph glands are acutely swollen; usually there is also an acute enteritis present, while the spleen preserves a normal ‘appearance even in severe cases. Nocard, who diagnosed the disease in cattle imported from America to Paris, (broncho-pneumonia of American cattle) emphasizes the fact that the serous fluid in the lungs differs from that of contagious pleuro- pneumonia. It is not so markedly yellow, and has not the appearance of lymph, also the thickened lymph spaces are filled with a whitish, tenaceous, fibrinous coagulum. The individual lobules appear firmer in the center and more markedly hepatized than in the periphery, which is probably, on account of the fact that the inflammatory process extends from the bronchi and not from the interlobular connective tissue. According to the anatomical findings in the different cases, Bollinger distinguished a pectoral and an exanthematous form of the disease, the former occurring principally in wild animals, while the latter is supposed to be more frequent in cattle. Later a so-called intestinal form was also described, which, however, does not occur independently, but only in association with one of the previously mentioned forms (the designation ‘‘exanthematous form’’ is not appropriate as there is no exanthema present but only an inflammatory edema). Symptoms. The time of incubation of the disease in inocu- lation and feeding experiments proved to be from 6 to 24 hours. In natural infections it is probably somewhat longer, but it hardly ever extends over 2 days. 108 Hemorrhagic Septicemia of Cattle. As the first symptom a rapid rise in the body temperature to over 40°C. is observed. This is accompanied by an acceler- ated pulse, dullness, rough coat and muscular trembling. At the same time the surface of the body feels alternately hot and cold, while the muzzle is cold and dry. There is also cessation of appetite, rumination and milk secretion. The peristalsis of the rumen and intestines is retarded; constipation at this stage may also be noticed. Later, symptoms of colic appear with much straining when the animals pass instead of the usual dry, dark brown feces, a mushy and finally a thin, fetid fluid which is not infrequently mixed with fibrin and mucous flakes as well as with blood. In.the meantime blood frequently exudes from the nose and sometimes the urine may also con- tain blood. In addition to these manifestations one or the other form of the disease finally develops during the further course of the malady. According to Carrougeau as well as Reynolds, Wilson and Brim- hall, the temperature may be either normal or subnormal, and Mezey observed in a fallow deer a temperature of only 37° C. with symptoms of a marked apathy, inappetence and bloody excrements. Guerrieri observed the disease in Sardinia (Male della ferula) in a peracute form when the animals, while ruminating. or feeding, sud- denly ran away like mad, staggered, collapsed, and died with escape of blood from the nose. In the edematous (exanthematous) form the head and neck swell, especially in the region of the throat and dewlap, as a result of the rapidly increasing inflammatory edema of the subeutaneous connective tissue, causing a deformity of these parts. There is also swelling of the legs and in rare cases the swelling may commence at one of the extremities and spread from there to the neck and body (Ratz). In such cases in- flammatory enlargement of the different joints may be observed. Over the swollen parts of the body the skin is very tense, warm and sensitive. On the eyes an acute conjunctivitis develops, frequently with a yellowish coloration of this membrane. There is profuse lachrymation, the tears running down the face. The buceal mucous membrane is bright red, warm, dry and swollen. Deglutition is difficult or impossible, so that the saliva accumu- lates in the mouth, and dribbles from the corners of the mouth’ in long, tenacious strings. The tongue swells to such an extent that it entirely fills the buccal cavity, and a part of it may even protrude between the teeth. It is bluish-red, or dirty reddish- brown and shows on its lower surface impressions of the teeth, while at both sides of the frenum the mucous membrane of the floor of the mouth is bunched up in thick, flabby, gelatinous rolls. Respiration is very difficult and frequently stertorous. All the mucous membranes are cyanotic, often studded with hemor- rhages, and finally the. animals die of asphyxiation, or the Symptoms. Course. Diagnosis. 109 ue which is caused by the marked enteritis, produces eath. Taufer observed the following additional symptoms during an outbreak of the disease: A very extensive infiltration of the masticatory and cheek muscles as well as of the back of the nose, the lips and the nasal mucous membrane (hippopotamus head), cloudiness of the cornea (in two cases also panophthalmia). In one case he observed necrosis of the cheeks and lips, and lastly in 24 cattle a skin eruption over the entire body. These skin lesions were developed most extensively above the carpal and tarsal joints, and resulted in circumscribed necrosis. Carrougeau has also observed skin eruptions in the form of nodules which were closely set in rows, from which the thickened epidermis separated in thick shreds. According to Robertson and Spreull the disease of cattle known in South Africa as ‘‘lamziekte’’ is supposed to belong to hemorrhagic septicemia. However, a confusion with ‘‘heart water’’ (see this disease) is not excluded. The pectoral form is characterized by symptoms of an acute pleuro-pneumonia. The animal stands immovable with back arched, has a dry and painful cough, and a colorless or reddish, foamy serous discharge from the nose. On one or both sides of the thorax there is dullness over different areas with bronchial breathing and vesicular rales. There may be a total absence of respiratory sounds. Friction sounds may be heard over the hepatized areas. Respiration is greatly accelerated and labored. Rumination ceases. Peristalsis of the ramen and intestines is frequently suppressed. Constipation is followed by bloody diarrhea, whereupon the greatly weakened enimal rapidly succumbs. According to Carrougeau the disease may take a chronic course. The emaciated, feverless animals cough frequently; their appetite is capricious, and there is profuse lachrymation. At the same time a persistent diarrhea is present in which feces mixed with blood are passed. Over the lungs rales can be heard, and percussion sounds are sometimes dull. The disease may terminate in recovery, but in such cases the cough persists for a long time. In other cases the animals die from exhaustion as a result of the long continued sickness and emaciation. The autopsy of such animals reveals caseated areas in the lungs, chronic catarrh of the stomach and intestines, enlargement of the lymph glands and indications of cachexia (in some cases only the latter lesions are present). The belief of Simader that the ‘‘endemic pharyngeal paralysis (Wasenmeister- krankheit) ’’ is a form of hemorrhagic septicemia is not substantiated as aside from the different post mortem findings and its continuous afebrile course (Schmid) there are no proofs, and especially since an identical etiological factor has not been established. Course and prognosis. The duration of the disease varies, with the exception of the chronic cases, between 6 hours and 8 days. The edematous form usually runs the more rapid course, mostly from 12 to 36 hours, while the pectoral form, 110 Hemorrhagic Septicemia of Cattle. which occurs very frequently in some enzootics, rarely ter- minates in less than 3 days. The prognosis is very unfavorable. According to past observations 85 to 95% of the affected animals die. Recovery may exceptionally be observed in the pectoral form, but even in these cases it is not complete, as in the patients a chronic lung affection usually follows. Diagnosis. The disease resembles first of all those cases of anthrax in which edematous swelling and signs of enteritis are present. Hemorrhagic septicemia is indicated by the de- velopment of edematous swelling of the throat, marked swelling of the tongue and the fact that hogs may be simultaneously affected. On the other hand, in anthrax the edema which is less frequent is more apt to develop on the neck, dewlap and in front of the chest; hogs are only exceptionally, while sheep are frequently affected. On autopsy the absence of acute swelling of the spleen excludes anthrax with a high degree of certainty, while bacteriological examination of the blood from carcasses recently dead of the disease makes differentiation easy on ac- count of the great difference in the appearance of the causative agents. If the carcass is no longer fresh cutaneous or sub- cutaneous inoculations of the blood or inflammatory products are advisable, as the blood of such test animals (mice, rabbits ‘ and pigeons) contains the respective bacteria in great numbers. From rinderpest hemorrhagic septicemia may be differ- entiated by the fact that the latter may occur without being intro- duced from outside into a locality, and that in its course the mucous membranes, especially those of the air passages, do not show an intense croupous inflammation and ulceration. Blackleg and malignant edema are characterized by crepitating, edema- tous swellings; moreover, these diseases cannot be transmitted to test animals by cutaneous or small intravenous injections. The pectoral form of hemorrhagic septicemia can easily be mistaken for pleuro-pneumonia. In the majority of cases hemorrhagic septicemia may be recognized by the appearance of inflammatory changes in the lungs, as they occur in this disease in larger extension or in numerous centers of the same stage of development. Occasionally, however, the lesions may simulate acute or subacute pleuro-pneumonia to such an extent as to render diagnosis from the macroscopic findings almost impossible. In such cases a microscopical examination will establish the correct disease, as in hemorrhagic septicemia the serous fluid of the lungs contains bipolar bacilli, while in pleuro- pneumonia the findings are negative. Test inoculations may also be made to differentiate the disease, as the virus of sep- ticemia is pathogenic for practically all test animals, while that of pleuro-pneumonia is harmless (in calves infected sub- cutaneously with the latter an edematous swelling develops at the point of inoculation in 1 to 2 weeks). The presence of Diagnosis. Treatment. 111 small hemorrhages in the tissue of the inflamed pleura, and the sudden appearance and rapid course of the disease are suggestive of hemorrhagic septicemia. Sometimes bacteriological examination may be diffieult as occasionally the blood as well as the exudates of animals affected with hemorrhagic septicemia con- tain few bacteria and the virus may be greatly attenuated. In doubtful or negative cases, it is therefore advisable to inoculate several test animals, especially rabbits. Lastly, the disease is differentiated from simple asphyxia- tion by the absence of inflammatory changes; from spontaneous (mycotic) or toxic enteritis by the absence of hemorrhages in other organs which will also differentiate septicemia from in- flammatory changes in the lungs and inflammatory edemas of the subcutaneous connective tissue. : Treatment and prevention. The treatment of affected animals has so far been unsuccessful and can at best consist in the searification of the swellings, washing of the wounds and disinfection of the intestinal canal. For the suppression of the disease it is advisable to re- move cattle and hogs from the infected premises to dry, and if possible, to elevated places. When the disease has appeared in a stable, it is well to withhold the suspected feed and to dis- infect the premises. The method of immunization which has been recommended by Blin & Carrougeau against buffalo disease (see page 118) might perhaps be applied to hemorrhagic septicemia in cattle. Veterinary police. Before requiring the inclusion of hem- orrhagic septicemia among the diseases for compulsory report- ing, it is necessary to take into consideration the fact that it is a disease of the soil. Far reaching traffic restrictions do not appear justified, while hides may be rendered harmless by simple drying. Ostertag found in his investigations that dried hides from affected cattle are always free from the infectious agent as soon as their moist and pliable condition is lost and they become hard. Submerging pieces of skin in milk of lime or in fresh tanning fluids destroys the organisms in 24 hours. In meat the infective agent is destroyed by advanced putrefaction, by heating to 70°C. (immediately), with less certainty by salting, pickling or injections of brine (sometimes only after 45 days). Literature. Bollinger, Ub. eine neue Wild- und Rinderseuche usw. Miinchen 1878.—Franck, D. Z. f. Tm., 1881, VII, 293.—Friedberger, Mch. Jhb. 1880-81, 21.— Kitt, Sitzgsber. d. Ges. f. Morph. Miinchen 1885; Mech. Jhb. 1885-86 u. 1886-87.— Nocard, Bull, 1891, 424.—Jensen, Monh., 1894, IT, 188.—Ligniéres, Bull., 1897, 761; 1900, 537 (Lit.).—Taufer, Fortschr. d. V.—_Hye., 1904, II, 188 (Lit.) — Ostertag, %. £. Infkr., 1908, TV, 1—Simader, W. f. Tk., 1908, 397 (Lit.). Septic pleuro-pneumonia of calves. The disease was first described by Poels in Holland (1886) and since that time by other authors (Jensen, Liénaux, Bongartz, Galtier and others). It evidently represents a form of hemorrhagic septicemia of cattle, and the close 112 Septic Pleuro-pneumonia of Calves. relation of the two diseases appears especially indicated by the fact that in certain herds adult cattle and calves are frequently affected at the same time. The causative agent (Bac. vitulisepticus) is identical with the organism of septicemia, and natural infection appears to occur princi- pally through the digestive tract. All excretions of the infected animals may transmit the infection. | ; The autopsy reveals a large amount of sero-fibrinous- exudate in the pleural cavity, punctiform hemorrhages in the serous covering of the lungs, reddish-brown or grayish-red hepatizations with serous infiltration of the interalveolar connective tissue in the lungs, and sometimes dilatation of the lymph vessels contained therein (marbled appearance). The finding is. completed by the presence of small hemorrhages in the serous and mucous membranes, acute catarrh of the air passages and the gastro-intestinal canal, acute swelling of the lymph glands, and cloudy swelling of the parenchymatous organs. The symptoms consist in high fever, weakness, inappetence, indi- cations of acute pleuro-pneumonia such as painful cough, difficulty in respiration, sensitiveness over the thorax, dullness over the lower parts of the lungs with friction sounds, bronchial breathing, or a total absence of respiratory sounds. Difficulty in respiration increases, and in most eases death results in 1 to 2 weeks after diarrhea sets in, or after a temporary improvement a chronic form of the disease may develop. For prevention immune sera (calf-pneumonia serum, septizidin) prepared from horses and cattle by injecting them with cultures of the bipolar bacillus were used with varied results. According to the investigations of Schirop promising results can be expected only from the use of polyvalent sera (see page 85). However, he succeeded in immunizing rabbits and guinea pigs with aggressins. On the relation of the disease, especially in its chronic form, to other pneu- monias of calves see the chapter on enzootie volume IT. Literature. Poels, Fortschr. d. Med., 1886, IV, 388.—Jensen, Monh., 1890, II, 1.—Liénaux, Ann. vét., 1892, 465.—Bongartz, B. t. W., 1892, 529.—Schirop, Zbl. f. Bakt., 1908, XLVII, 307 (Lit.). Hidebound. Enteque. The disease is designated in Argentine by this name, and occurs there especially along the shores of the Atlan- tic Ocean in certain marshy localities, where the outbreaks cause considerable annual losses. It was described by Monfallet, Even, and particularly Ligniéres who gave a careful and full description of the disease. In acute cases occurring in animals from 12 to 24 months old, a persistent painless diarrhea and gradual emaciation are observed in spite of a good appetite, until the animals finally die of exhaustion in from 3 to 4 months. In the cachectic form of the disease, which occurs mostly in animals which recover from the acute affection, the course may extend over several years. In these cases the progressive emaciation and anemia which develop in- the meantime and a marked exhaustion are the most conspicuous symptoms. Normal appetite is suppressed, but the animals manifest a desire to eat bones. Along the neck in the jugular groove the calcified carotid may be felt. in some animals, while in others inflammation of the joints appears, resulting in deformities. On autopsy in acute cases besides the general anemia and emacia- tion, sometimes a pleuritis, broncho-pneumonia or a fibrinous pneu- Hidebound. Buffalo Disease. 113 monia may be observed. In the chronic cases the lungs sometimes show islands or cords consisting of spongy osseous tissue which crepi- tate on pressure and which have developed by ossification of the vessel walls. In the large blood vessels of the body, and in exceptional cases in the small arteries, especially those of the heart, a pronounced arterio-sclerosis exists; the endocardium may show a chronig endo- carditis, while the different joints may show indications of chronic inflammation (similar changes were found by Moussu in France in chronic forms of diarrhea and by Brusaferro in a yearling steer slaughtered in Turin). The disease was also observed in horses and sheep but the lungs failed to show the processes of ossification. According to the investigations of Ligniéres, the causative agent of the disease is a very small variety of the Bac. bipolaris septicus. Intra- venous injections of large quantities of fresh cultures produce septi- cemia which is fatal in 1 to 3 days; following injections of older cultures in cattle and sheep an articular and peri-articular inflammation develops which results in the formation of new connective and cartilaginous tissue. Natural infection occurs in marshy localities from the water and food. The results are sometimes an enteritis, or a chronic inflammation of the joints and an affection of the vessel walls. Ligniéres obtained satisfactory results in the treatment of the acute form of the disease by intrajugular injections of diluted blood serum of healthy animals (400 cc. serum and 500 ce. sterile water), or artificial serum (1000 ce. boiled water, 9 grams sodium chloride and 4 grams sodium sulphate). In cases where recovery was prolonged, the injections were repeated. Literature. Even, Revista vet., 1896, 301—Ligniéres, Bull., 1898, 761. (c) Buffalo Disease. Septicaemia hemorrhagica bubalorum. (Barbone disease, Pasteurellosis bubalorum, Pasteurellose des buffles [French]; Biffelseuche [German]; Barbone bufalino [Italian].) This affection is an acute, febrile, infectious disease of buffalo, and is characterized by febrile manifestations, difficult respiration and especially by an edematous swelling of the throat region. It is caused by the bacillus bubalisepticus. History. The disease was first studied in Italy by Oreste & Armanni (1886), and included in the hemorrhagic septicemia group. They also undertook immunization experiments, In Hungary the oc- currence of the disease was first established by Sequens (1889), while Ratz undertook a more thorough investigation of the pathogenicity of the infective agent. Occurrence. Buffalo disease occurs frequently in localities where large numbers of buffalo are kept during the summer, and at times causes considerable loss in some herds. It usually occurs as a disease of the soil in marshy pastures and in dry stubble fields. Exceptionally, however, cases may occur in animals fed in stables. The economic importance of the disease 8 114 Buffalo Disease. is increased by the fact that it may be transmitted to hogs, among which it may also cause considerable loss. In Italy the infection is especially widespread in the districts of Salerno, Rome and Terra di Livorno. In Hungary the disease occurs almost exclusively in the southeastern counties (in 1908, 98 buffaloes were affected in 56 townships, and 95 of them died; considerably less than in former years). In Russia, Egypt, East and West Indies, and Indo-China the disease frequently occurs in enzootie form. j The dangerous character of the disease is readily recognized by the following data: In Italy, in a herd of 1,400 buffaloes, 200 died in the year 1882 within ten days; in another herd of 1,300 buffaloes, 530 succumbed. In one township of the infected districts of Hungary, 52 of 237 buffaloes died within one week; in another, of 663, 89 died within a short time. The losses in the Netherland-West Indies (in Bantam and Batavia alone) amounted, between 1888 and 1891, to 11,000 buffaloes. Etiology. The established cause of the disease, the bacillus (bipolaris) bubalisepticus, appears in all its principal charac- teristics as a variety of the bacillus bipolaris septicus (see page 79). Tenacity. Blood dried in the air loses its infectiveness in 24 hours. On the other hand, when kept in closed glass tubes at room temperature its virulence is lost in 40 days. Carbolie acid (2%), sulphuric acid (5%), and alcohol (87%) render equal quantities of blood harmless (Oreste & Armanni, Sanfelice). Pathogenicity. According to the investigations of Ratz, rabbits are most susceptible to artificial infec- tions; somewhat less susceptible are the guinea pig, the mouse and the pigeon; to a still lesser degree, chickens, while the dog and duck are not at all susceptible. Of the large animals the horse succumbs to sub- cutaneous infection in an average of 20 hours, cattle in from 20 to 48, and Fig. 28. Bacillus bubalisepticus. hogs in, from 20 to 40 hours. The in- Smear preparation from rabbit Oculations result in manifestations of blood. Polar staining. a general infection with edematous ; swelling at the point of infection. Buffalo calves die from a cutaneous or subeutaneous infection inside of 24-36 hours with similar symptoms, while infection is not successful when virulent cultures are fed, but buffalo calves treated in the latter manner will develop an immunity against a subsequent virulent infection. Sheep inoculated with virulent buffalo blood die with symptoms of an acute. pharyngitis (Reischig). 40. The bacteria are present in large numbers inthe blood, in the serous exudates and the feces of the infeeted'.animals. They may also pass into the saliva, bile, milk and the urine. Natural infection may occur through wounds of the skin and mucous membranes. Such infections are favored in pas- tures which contain thorny plants and pools of water in which the animals lie for hours, thus constantly reinfecting the water. In the great majority of the cases, however, natural in- Natural Infection. Anatomical Changes. 115 fection probably results from the ingestion of infected food and water through the uninjured mucous membrane of the digestive tract. This mode of infection is indicated by the con- stant swelling in the region of the throat and also by the relatively frequent acute inflammation of the abomasum. On the other hand, infection through the air passages is less prob- able, as intratracheal injections of virulent material fail, in most cases to produce the disease. | terminations are ex- = F >| ceptional, and only 3 ~] occur when severe a r =| complications become = aspiration positive |, associated with mild = s| forms of the affec- 5 aI’ =| tion (pneumonia, hy- n ATH =| peremia or acute in- Ee =| flammation of the +e =| brain, enteritis, de- ae AHA itriiittit.) generation of the SE mee =| heart muscle, etc.). Ba si _ _Much more va- a napkrated tethers | ried is the course of Z 4 + the pectoral form of 8 i a + influenza. In the F 1 + typical cases in which nn ,| the different stages Z r Peer taut cere of lobar pneumonia e i H - follow each other Ei MMMIDS=He= AE SS UHL - with regularity, and s ii 4 = the resolution is also Z 1 ‘| undisturbed, the & reall ‘| pleurisy being pres- I | ent in a mild form or g 1 8! not demonstrable at 3 ‘ | all, the fever may <4 AE ; tt} subside at the end of the first or at the be- ginning of the second week. Here, however, complications and sequelae which develop frequently in association with the dis- ease, more often cause a deviation of its regular course. Especially in cases of pleurisy in which a great quantity of exudate develops, the affection may extend for weeks (Fig. 37), and even for months, the patients manifesting temporary im- Symptoms. 187 provement and repeated relapses, until finally the animal dies from exhaustion, or remains broken-winded for the rest of its life. Death may result however even earlier at the height of the pneumonia, usually following paralysis of the heart. Convalescence in this form of influenza takes a considerably longer time, and as a rule extends over a period of more than two weeks. The termination of the disease is naturally also influenced by the existing hygienic conditions, and especially the continued working of animals already ill will usually render the course of the disease, which otherwise might have been only mild, an unfavorable one. After the termination of the acute disease, chronic processes sometimes develop as sequelaca After a severe pneumonia, and especially when the tissues in different parts have become gangrenous, chronic granulating inflammatory proc- esses, with shrinkage of the lung tissue, may develop. This condition may also result in the formation of bronchiectasis, while after an exudative pleuritis, adhesions of the pleural layers may follow, as a result of which the animal may suffer from dyspnea until its death. A frequent result of pleurisy is the paralysis of the N. recurrens vagi, which causes roaring inthe animal. The acute catarrh of the intestines may develop into a chronic form, which results in the gradual emaciation of the animal. Other after affects that may occur are paralysis of the hind parts, shortening and even necrosis of some of the tendons, chronic inflammation of the joints, exostoses, hemo- globinemia, and as a result of the inflammation of the eye, amaurosis. Finally, horses recovering from influenza may later become affected with purpura hemorrhagica, and the internal inflammation of the eye may also develop only two to three weeks after the passing of the disease (Hell). - The character of the disease varies greatly in the different outbreaks. While in some periods the course of the disease is very mild, so that the great majority of the animals are only slightly affected with the catarrhal symptoms, and while also the infrequent pneumonia almost invariably terminates in re- covery, there are outbreaks in which the disease is of a re- markably malignant character. This form is characterized especially by frequent hemorrhages, as well as by pneumonias which frequently assume gangrenous forms. The character of the disease may also change in one and the same outbreak; thus in some instances it may occur that at the beginning of the outbreak only cases of the catarrhal form of influenza are observed, while later the pleuro-pneumonic form becomes more frequent, and towards the termination of the epidemic the affections return again to the milder form. Diagnosis. The catarrhal form of influenza may he easily mistaken for catarrhal manifestations of the mucous mem- 188 Influenza of Horses. brane from other causes, while pectoral influenza may easily be confounded with sporadic croupous pneumonia. Although the edematous infiltrations of the subcutis, as well as the tendonitis and the tendo-vaginitis, also the icteric discolora- tion and chemotic infiltrations developing in association with the conjunctivitis, are quite characteristic of influenza, these symptoms are not infrequently absent, especially in the early cases of an outbreak. In such cases the infectious character of the disease, and its rapid spread among horses, reveals the nature of the affection. In practice it is advisable therefore to suspend diagnosis in the first cases, until the appearance of new cases, or dependable data disclose the infectious nature of the disease, or until characteristic symptoms develop, or on the other hand, until the infectiousness of the affection may be excluded. In consideration of these diagnostic difficulties every suddenly appearing catarrhal affection, and particularly every croupous pneumonia, should be considered as if it were an attack of influenza, that is, as an infectious disease, Ac- cordingly an immediate isolation of the affected animal is in- dicated in all such cases. Influenza is distinguished from the non-infectious catarrhs, principally by the fact that in the former the catarrhal manifestations are preceded by high fever of sudden development, while in the latter the catarrhal symp- toms are rather latent and develop only with slight rises in temperature. If influenza has been established in a stable, or if the dis- ease is present in nearby localities, all febrile affections should be considered as suspicious of the disease. Further, as the febrile rise of the temperature represents the first symptoms of influenza, it is advisable in order to separate immediately the newly affected animals, to take the temperatures of the horses in the infected or endangered stables systematically twice a day. A rise in the temperature of two degrees or over is sufficient to indicate the probable presence of the disease. Infectious anemia may possibly be mistaken for the eatarrhal form of influenza, especially when it is associated with severe intestinal disturbances. The condition of the blood affords a means of differentiation since in anemia it coagulates incompletely, at the same time the serum frequently appears opalescent and of a more reddish color (Vallée). The appear- ance of pneumonia, or pleuro-pneumonia, or the development of similar symptoms in other horses of the stable would be indications of influenza; on the other hand, rapid emaciation and cachexia, without organic affection, as well as the pres- ence at autopsy of a greatly enlarged spleen, would suggest the presence of infectious anemia. Strangles may also be considered in the beginning of the affection, from the standpoint of a differential diagnosis; in this, however, the swelling and suppuration of the lymph glands reveals the nature of the affection. (oa * Prognosis. 189 Prognosis. The prognosis of the catarrhal form of in- fiuenza is usually favorable, as deaths seldom occur except as a result of complications, the appearance of which are com- monly associated with unfavorable hygienic conditions. Under favorable conditions the loss hardly ever exceeds 0.5 to 1%; it may however reach 4% and even more. Accordingly in the prog- nosis all existing circumstances, as well as the benign or the malignant character of the disease should be taken into con- sideration. The prognosis of the pectoral form of influenza is much more unfavorable. In this form the losses are never less than 4 to 5%, and frequently considerably higher (according to Dieckerhoff the average is 16%). Besides it should be also considered that in addition to the losses resulting from death some of the animals do not completely recover, and that their protracted convalescence may greatly diminish the value of the animals through the lessening of their ability to work. The life of the affected animal is imperiled in the first place by danger of paralysis of the heart. Indications of a weak heart always render the prognosis unfavorable, and in the presence of a soft empty pulse of over 80 beats, as well as when a venous pulse can be detected, the chances of recovery are very slight. The termination of the disease depends also on the extent of the pneumonia and pleurisy. A unilateral pneumonia with only slight pleuritis usually terminates favorably; on the other hand a bilateral affection, and especially the formation of great quantity of pleural exudate is always grave. In such cases, even at the best, the course of the disease is very pro- longed, and chronic changes of the respiratory organs usually remain as a sequel to the disease. Moderate fever, and at least a fair appetite, are favorable prognostic signs. The more regularly the different stages of the disease follow each other, the more favorable is the prog- nosis, while a rapid change for the worse in the respiration, with very high fever, without a distinctly demonstrable dullness (pneumonia centralis!), usually results in death after a few days. The dangers from cases of a hemorrhagic character are in most instanees great (bloody nasal discharge, similar pleural exudate!). According to Fréhner, prognostic conclusions can be made in every case of contagious pleuro-pneumonia, from the consistence of the exudate which may be obtained by aspiration. If the exudate contains no bacteria the prognosis is always favorable; on the other hand, in the presence of bacteria (streptococci) the disease as a rule has a fatal termination. The course of the fever is of great importance in the prog- nosis, especially in the pectoral form of influenza. If the tem- perature, after rising rapidly, remains for several days ap- proximately at the same height, and if it falls towards the end'of the first week just as rapidly, or even gradually, the prospect of a favorable termination is excellent. If, on the 190 Influenza of Horses. other hand, the fever curve shows a remittent character, and if the febrile condition lasts over a week, and also if a new rise in temperature takes place after the appearance of the apyrexia, an unfavorable prognosis is indicated. In the latter instance a rise in the temperature lasting only for one day (perturbatio critica), has no special importance; continuous fever is, however, always grave, as it either points to an ex- tension of the pleurisy, or to the development of some other complication. Unfavorable terminations are also indicated by the pres- ence of severe inflammations of the tendons, which interfere with the standing of the animal; also persistent diarrhea, hem- orrhages in the lungs or other organs, the appearance of pulmonary gangrene, or an affection of the brain, ete. A rapid reaccumulation of the pleural exudate after aspiration is also an unfavorable sign, although in exceptional cases, even after repeated aspirations recovery may finally take place, which, however, is usually incomplete. In all of these cases the dictetic conditions, the care and nursing of the patients, as well as the general strength of the animals should be given relative consideration. The more favorable the conditions are in this respect the milder a course of the disease may be ex- pected. In the Prussian army, during the period of 15 years (1894 to 1908), out of 26,678 horses affected with the catarrhal form of influenza, 40 died (or 0.15%), in most instances as a result of subsequent pleuro-pneumonia; while in the same period 38,671 horses were affected with the pectoral form of influenza, of which 1,527 succumbed (3.94%). Among the horses of private stables in which the hygienic conditions are usually more unfavorable, the losses are correspondingly higher. “ Treatment. This consists in the first place, in a suitable regulation of the dietetic conditions. It is of particular im- portance that the animal should immediately be taken from work and placed in a clean, quiet and moderately cool stable. If the weather is favorable it should be allowed to remain outdoors, although protected against wind or rain. The diet should consist of easily digestible, palatable, and if possible, of fresh green food, and the animal should be given fresh drinking water in sufficient quantity (when the disease ap- peared among army horses the bivouacking of all the animals in the open air has repeatedly proved beneficial). As long as the course of the disease is normal, and there are no alarm- ing symptoms, the expectant method of treatment may be fol- lowed. In such cases medicinal treatment may be omitted, with perhaps the exception of aleohol rubs which are always favor- able, and the regulation of the bowels. In the presence of an extensive bronchial catarrh, inhalations of turpentine or tar vapors are advantageous (Lugano recommends also intra- tracheal injections of 10 to 12 ce. of a 4% formalin solution). The fever does not require special treatment, as it usually Treatment. 191 subsides, without interference, after several days. Cold water in the form of douches, once or twice a day, or as rectal enemas, gives favorable results, especially during warm summer weather. Its beneficial action, however, is due rather to the stimulation of the nervous system and the heart’s action, than to its antipyretic action, although continued application of cold water douches does reduce the temperature from one to two degrees. Direct antipyretic treatment appears to be indicated, when the body temperature remains abnormally high, even in the later stages (over 40.5 to 41°C.). In such instances the internal administration of antipyrin and of anti-febrin (15 to 30 g.).1s advised. If pneumonia or pleuro-pneumonia develops in association with catarrh of the air passages, or if the affection develops in this form from the beginning the application of Priessnitz bandages, as well as rubbing with camphor and spirits of tur- pentine, act favorably. During the summer weather, cold douches once or twice daily may be applied advantageously. The heart’s action requires special watching, and in case it is accelerated, while still strong, the administration of alcohol in drinking water (25 to 50 g. alcohol, 1%4 to 1 liter of wine) will give beneficial results. In case the heart’s action is greatly accelerated, and the pulse is weak, heart stimulants are in- dicated, such as digitalis leaves (2 to 5 g.), tincture of strophan- thus (10 to 25 g.), caffeine (1 to 2 g.), camphor (2 to 5 g. subeutaneously every 3 to 4 hours), or barium chloride (2 g.). Strophantine may be given subcutaneously (0.003 g. in 10 g. of water, injected at 2 places). Fréhner recommends instead of the natural campbor, the cheaper preparation made artificially from oil of turpentine, for the treatment of contagious pleuro-pneumonia. The horses should receive daily 100 to 200 g. of oleum camphoratum (syntheticum) forte, or as a single dose 50 to 100 g. injected on both sides of the thorax. ~ Recently Eberlein & Toepper obtained very favorable results in the treatment of influenza by oxygen inhalations. The animals were given the oxygen inhalations twice daily for 10 to 15 minutes. According to observations in the German army, however, the effect of this treat- ment consists only in a general improvement for 15 to 30 minutes, as well as a diminution of the rate of respiration and pulse, while the treatment has no influence on the pneumonic process, and even if inaugurated at the onset of the disease does not prevent an unfavorable course (Fiichsel). Hermann observed rapid absorption of the exudate and recovery in a severe case from two subcutaneous injections of a 25% iodipin solution (50 g. for each injection) ; such an effect, however, was not observed in the Budapest clinic. The German army veterin- arians had variable results from the intravenous injections of tallianin (10 g. doses). (Eichhorn found this remedy effective in the beginning of the disease.) If the exhaled air indicates by its fetid odor that decompo- ‘sition of: the secretion in the air passages, or gangrene of 192 Influenza of Horses. of the lung tissue is progressing, the inhalation of finely atomized disinfecting fluids is advisable. For this purpose a solution of corrosive sublimate is recommended (1 to 2000-4000). If this treatment is applied sufficiently early the fetid odor frequently disappears; extensive gangrene of the lungs how- ever is not checked by this method of treatment, likewise has it no influence on the development of a general infection as the result of absorption of septic substances. Masson & Vazeux recommend for the treatment of pulmonary gangrene, daily intratracheal injections of creosote (20 ce. of a solution of 1 g. of creosote in each 40 g. of alcohol and water), while Gotti recommends formalin (10-20 cc. of a 4% solution). The pleurisy should be treated in the beginning with cold applications or cold douches; however after the subsidence of the symptoms of irritation these should be changed to warm, moist compresses. The accumulation of fluid pleural exudate should be relieved by an early aspiration of the thoracic cavity. Repeated aspirations result sometimes, even in severe cases, in recovery, but in such cases the chances are not very promis- ing, as the pleurisy frequently develops in conjunction with gangrenous processes of the lungs. The absorption of the exudate may also be promoted with diuretics, such as potas- sium acetate (100 to 180 g.), oil of turpentine (10 to 15 g.), juniper berries (15 to 25 ec.), ete., as well as by rubbing with irritating liniments (6 to 10% mustard, or chloroform liniment 10 to 40), followed by the application of moist; warm com- presses. The aspiration of the fluid should be stopped as soon as the patient manifests uneasiness, accelerated respiration, or coughing spells. The subsequent irrigation of the pleural cavity with a physiological salt solution, or a mild disinfecting solution does not appear to act favorably. Strictly aseptie technique is naturally the most essential requirement for satisfactory results. Boucheriou, after aspiration, recom- mends a subcutaneous, while Almy, an intravenous injection, of 2 to 8 liters of a physiological salt solution. Fairise advises an intrapleural injection of 1.5 to 4 liters of a 1 to 1.5% gelatin solution in order to prevent a possible hemorrhage, as well as the rapid re-accumulation of the exudate, the injections to be made immediately after the aspiration of the fluid. In the presence of symptoms of a gastro-intestinal catarrh laxative salts should be given daily to the patients, or Karlsbad salts (40 to 60 g.), with bitter remedies (rheum, gentiana, oak- bark, ete.). In consideration of the infectious character of the catarrh, especially in the presence of fetid excrements, in- testinal disinfectants are indicated, such as resorcin (10 to 15 g.), creolin or lysol (10 to 20 g.), creosote (5 to 10 g.), naphthalin (10 to 15 g.), ete. If diarrhea exists astringents (oak-bark, bismuth sub-nitrate, etc.), with opiates, as well as enemas containing powdered starch are beneficial. If, however, the diarrhea is profuse, which usually is an indication of a general septic infection, the results from such treatment are not favorable. Prevention. 143 The conjunctivitis may be treated with washes of mild collyriums, such as boracic acid or creolin solution, later astrin- gent washes may be applied (0.5 to 1% tannin, or sulphate of zine solution, collyrium adstringens luteum). In the presence of a chemotic swelling of the conjunctiva, and keratitis, moist warm applications are advantageous. If the iris is also affected a 1% atropine solution may be dropped into the eye. Swellings of the skin are benefited by rubbing with alcohol containing oil of turpentine. Acetate of lead (5%) or Burow’s solution, with the addition of camphor, may also be applied to this form of affection. In the convalescing stage the animals require good nourish- ment and rest, although moderate exercise in favorable weather is rather profitable than injurious. Animals should be used for work only when all symptoms of the disease have disap- peared, and after they regain their former strength. The symptomatic treatment is similar to that followed in the pneumonia or pleurisy and enteritis resulting from other causes; see accordingly their respective chapters in the second volume. Serum Treatment. Ligniéres recommends his polyvalent Pas- teurella serum for the treatment of influenza (see page 86). In acute eases of the catarrhal form of influenza, in the presence of a fever (40.5 to 41°), he injects 40 to 60 ce. of the serum intravenously, where- upon the fever is reduced, the patient becomes brighter, and recovers inside of a few days. In subacute cases (39 to 39.5°), the temperature usually rises somewhat after the injection, but drops after 10 to 12 hours, to normal. He also observed improvement in the presence of pneumonia, when the serum was administered within the first 24 to 36 hours, while later treatment promises little result, because of the associated streptococcus infection. Believing that the inflammatory processes may also be caused or aggravated by streptococci, Joly recom- mends the subcutaneous injection of anti-streptococcus serum(25 to 30 ec. daily). Prevention. Healthy horses should be separated from affected animals, as well as from attendants and utensils that come in contact with diseased animals or with their secretions. It is advisable to isolate a newly acquired horse for two weeks for observation, and it should be placed among the other horses only after that period. This applies particularly to regions in which the disease is prevalent. If the disease has already appeared the affected animals should first of all be separated, and their stalls, as well as the neighboring stalls, should be thoroughly disinfected. As in the first place the immediate neighboring animals are under suspicion of becoming affected, they, as well as all animals showing an elevated temperature or catarrhal symptoms, should be segregated in different isolated places. At the same time the healthy animals which have no fever should be kept out of doors, as far as place and weather conditions permit, or in places which are free from the infection. They should be divided in groups, and only animals which are entirely free. 13 194 Influenza of Horses. from fever should be used for work. The infected stable should be thoroughly disinfected, and scrupulous cleanliness, as well as free ventilation of the stable, should be carried out. As the development of the disease is favored by influences which: have a weakening effect on the animals, the protection of the horses from such influences, and especially from taking colds, should be given due consideration. Animals which have passed through the disease may, in the majority of cases, and usually in the catarrhal form of influenza, be considered as recovered and free from the in- fection two weeks after cessation of the fever, and the dis- appearance of all the symptoms. Convalescent patients from the pectoral form of influenza if the changes in the lungs have not entirely disappeared, and especially if in the meanwhile relapses have occurred, are for a much longer time capable of infecting other animals. Immunization. Shortly after the discovery of Schiitz’ diplo- coccus, Hell undertook the inoculation of over 1000 animals, with bouillon cultures of this bacterium... Healthy animals were injected 3 or 4 times with 40 ce. of the culture into the trachea, and some of the animals were given in addition subcutaneous injections of 5 to 10 ee. The injection was followed by a fever lasting from one to two days, whether the. animals had had the disease or not. The subcutaneous inoculation was also followed by abscess formation. Further observa- tion showed that animals immunized against the Schtitz diplococcus did not withstand the influenza infection, and therefore this method of immunization was later entirely abandoned. Immunizations with blood serum from horses which had shortly before recovered from the pectoral form of influenza have not given uniform results. Although Hell, at first, reported favorable results, the continued experiments among the horses of the German army showed that the serum treatment of affected animals was entirely unsuccessful and moreover produced such contradictory and even unfavorable results, that this method has also been gradually aban- doned. According to the tabulation of Christiani, in the years of 1892 to 1898 the results of 17 inoculation tests showed that in 9 cases they were favorable, and in 8 they were unfavorable. In opposition to the advocates of immunization (Eichhorn, Toepper, Garrey, Giancola and especially Friis, Jensen & Nielsen), others (Pilz, Neusse, Wittich, Zschokke, Troester, Mieckley) found it ineffective. The contradictory results may he explained to some extent by the fact that the effective- ness of the serum varies in accordance with the intensity of the disease, and also with the time which has elapsed since the recovery of the animal. At best serum inoculation affords the animals a passive immunity which lasts but a few weeks. Such results do not meet the require- ments of practice, even when the serious difficulties encountered during the execution of the inoculations are not taken into consideration. It would therefore be indicated only when it appears desirable to protect the animals, even for a short time, against a threatening infection, such as immediately before or during cavalry maneuvers. Vaccination Technique. For the serum inoculations blood is taken under strictly aseptic precautions from a horse which has recovered from the pectoral form of influenza not more than six weeks previously. The quantity of blood drawn ~ Immunization. 195 is usually between three and four liters, collected in sterilized high test tubes, and stored in a dark, cool place. The serum which separates on the following day from the blood clot, may be utilized for the inoculations immediately, or several days later. Until its use it should be kept in a cool place. The serum is injected subcutaneously in doses of 40 to 100 ce., and the procedure is repeated four to six times during the following days (Krueger recom- mends the intravenous, Della Noce the intratracheal injection). To the serum several drops of chloroform may be added (Friis, Jensen, Nielsen), or 0.8% of oxalic acid, in the proportion of 1 to 10 (Prussian army). The inoculation causes in most instances only a transitory indisposition, but in one Prussian regiment, among 195 horses, extensive swellings and abscess formations were also observed (evidently the serum was contaminated). Recently various serum preparations have been recommended, for the purpose of immunization, which however have not proved satisfactory in practice; thus the results which were obtained by Bues with Deutsch- mann’s yeast serum (and with polyvalent hog serum), gave absolutely negative results in contagious pleuro-pneumonia. Thomann experienced similar unsatisfactory results with the vaccines prepared by Lorenz from cultures of his pleomorphic bacterium. The same probably also applies to the serum of Willerding, prepared from the cultures of a diploccocus which he isolated from the secretions of the nose and eye, as Lorenz found it equivalent to his own in his laboratory experiments. Immunization with Killed Cultures. Vallée & Carré used a vaccine prepared from killed cultures of six varieties of ‘‘Pasteurella’’ for the immunization of horses. The administration of this vaccine to the horses of an infected stable was followed in several animals by severe symptoms of depression and dullness, some became affected with the typical form of contagious pleuro-pneumonia, and three of them died as a result of the infection (latent infection ?). Veterinary Police. In the German Empire compulsory notification of influenza in horses was inaugurated in the year of 1908. The official measures require the separation of the affected and suspected animals, quarantine and disinfection of the infected stables. The observation period extends over five weeks. Literature. .Falke, Die Influenza des Pferdes usw., Jena 1862.—Dieckerhoff, Die Pferdestaupe, Berlin, 1882.—Siedamgrotzky, Sachs. Jhb., 1£91-1893.—Sehiitz, A. f. Tk. 1887, XIII, 27.—Hell, Z. f. Vk., 1890, JJ, 97; 1892, IV, 452; 1906, XVIII, 159. Jensen, Monh., 1891, II, 196.—Foth, Ibid., 1891, ITI, 192.—Leclainche, Rev. vét., 1892, 78 (Lit.).—Ligniéres, Bull., 1897, 355 u. 437; 1900, 524 (Lit.); Rev. gén., 1907, IX, 599.— Jensen & Nielsen, Maanedsskr., 1897, VIII, 401.—Sturhan, Z. f. Vk., 1905, XVII, 248.—Dreyer, Z. f. Vk., 1908, XX, 307.—Ostertag, Z. f. Infkr., 1909, V, 180.—Pfeiler & Hempel, Ibid., 1909, VI, 28. Influenza in Man. In human medicine influenza represents an acute, contagious, infectious disease, which at times spreads with extra- ordinary rapidity. The symptoms consist in pain in the joints and muscles, occasional muscular tremors in different parts of the body, sudden and intense fever with severe headache. There is also marked debility, and a progressive acute catarrh of the air passages, conjunc- tivitis, and frequently gastro-intestinal catarrh. The disease usually terminates in from two to six days in recovery, however it may extend to two weeks. In older, and exceptionally among younger persons, severe disease processes may develop in association with catarrh of the mucous membrane, such as pharyngitis, catarrhal and croupous pneumonia, occasionally also pleurisy and pericarditis, as well as inflammation of the middle ear. In the latter cases the course is usually protracted and not rarely fatal. The disease, which has no association with influenza of horses, is caused by the very small influenza bacillus, which has been discov- ered. by Pfeiffer (Beck, Ergebn. d. allg. Atiol., 1896, I, 742). 196 Dengue Fever. Dengue Fever. This disease of man occurs in the tropics, espe- cially in America, East Indies and on the coast of the Mediterranean. It sometimes is very widely distributed, and is characterized by suddenly appearing chills, pains in the joints and muscles (dengue-dandy, so called from the peculiar stiff gait as the result of pain in the knee joints), further in a polymorphous, exanthema of the skin. According to some observers (DeBrun, Cubillas, Martialis), the disease also occurs among domestic animals. Piot-Bey observed in 1895, in Egypt, enzootic affection of cattle which he identified with dengue fever. The animals suddenly became affected with a striking muscular weakness, which was so marked that they staggered and trembled in walking, or béecom- ing exhausted they lay down on the chest. The body temperature was moderately elevated (89.5 to 39.6°C.), respiration and pulse accel- erated (25 to 30, and 60 to 90 per min.). At the same time there was complete inappetence and constipation. Usually after three to four days diarrhea appeared, which was soon followed in all cases by complete recovery. (Fiévre dengue sur l’espéce bovine, Extrait du Bull. de 1’Inst. Egyptien, Le Caire, with literature). Three Days’ Sickness, Stiff Sickness, Ephemeral Fever. In South Africa there occurs a disease among cattle which Schweinfurth observed in 1867, but to which the attention of the experts has only in recent years been directed, when it spread extensively in Rhodesia, in the Transvaal, Natal and in the Cape Colonies. It was first demonstrated in November, 1906, by Edmonds, and later described by Bevan, Theiler and Freer (it is possibly identical with dengue fever). The symptoms in the majority of cases develop and disappear within three days, or the disease may terminate in death. Manifesta- tions are, stiffness of the muscles of one or all extremities, extending to the neck, or even over the entire body. As a result of this condition the animals are lame, and later they are hardly able to move and seem obliged to lie helplessly on the ground. Development of this condition is preceded by diminishing appetite and rumination, and also by an elevation of the body temperature, while later on there appears a conjunctivitis, with swelling of the parts surrounding the eyes, frequent respiration, very weak pulse, distinct veinous pulse and constipation. The termination is usually favorable, as not more than 3% of the affected animals succumb, and part of these as a result of inhalation pneumonia. The cause of the disease is unknown at the present time, but Robertson and Theiler showed that it may be transmitted with the blood of affected animals, in which case the symptoms develop after an incubation of from 2 to 3 days. It is possible that the infection is communicated by insects (mosquitoes?). Animals which have recovered from the disease acquire an immunity which only lasts about six weeks (Robertson), reinfections being therefore not infrequently observed (Freer). Literature. Bevan, J. of comp. Path., 1907, XX, 104.—Theiler, Rep. of the Transvaal Gov. Bact., 1907.—Freer, V. J., 1910, 19. Malta Fever. (Mediterranean Fever.) Malta fever is a febrile disease of man, which most frequently occurs on the Island of Malta, then in the countries around the Mediterranean Sea, and probably also in other tropical countries. The disease is very protracted, remit- tent in its course, and associated with anemia, headaches, rheumatic difficulties, constipation, and swelling of the joints. A fatal termination Malta Fever. Distemper of Dogs. 197 occurs only in about 3% of the cases. Bruce (1887) established as its cause a very small, motile, Gram-negative, oval coccus (micrococcus melitensis). The organism can be cultivated on the ordinary media, and shows considerable resistance against drying. In affected persons the coccus is usually present in the blood, from which it is frequently eliminated with the urine. Natural infection occurs in most cases through the ingestion of raw goat milk. Zammit (1905) proved that about 10% of the goats at Malta eliminate the causative agent of Malta fever with their milk, and that many of these animals harbor the organism in their blood. He further found that the serum of about 50% of all goats gives a positive agglutination reaction. As it has been proved that the infec- tion may be readily transmitted through ingestion of infected milk, the drinking of raw goat milk was prohibited in the army, whereupon the morbidity immediately dropped to one tenth of its former rate. Goats which pass the microccocus melitensis with the milk, and also with the urine, usually show no, or only slightly marked symptoms, but if they are killed, hyperemia and acute swelling of the spleen, together with swelling of the lymph glands, especially of the mesen- teric and inguinal will frequently be found. Exceptionally nephritis and lobular pneumonia are present. The causative factor may be isolated by culture procedures from the lesions in the organs, as well as from the blood and from the udder (in chronic cases only from the latter). Goats are easily infected per os, and it appears that the natural infection occurs by this method, especially by the ingestion of feed contaminated by urine of affected animals. The virus then becomes localized in the internal organs and in the udder, where it produces inflammatory changes, from which the bacteria pass into the milk. Intravenous or subcutaneous injections of cultures produce, sometimes, a severe affection, with symptoms of septicemia. It is also possible to produce a mild form of the disease in monkeys. The infectious properties of the goat milk may in some cases he established by the presence of the virus; it may also be considered infectious if: the blood serum of the suspected animals agglutinates cultures of the organisms in dilutions of at least 1 to 30. The aggluti- nation test may be also made with milk (Zammit), or with milk serum (Pulvirenti), and Wright’s opsoniec test also gives good results. Literature. Babes, Hb. d. p. M., 1903, ITI, 438, Report of the English Com- mission, London, 1905-1907, Vol. I-VII—Mohler & Hart, Bureau Anim. Industry, 1908, 279. 9. Distemper of Dogs. Febris catarrhalis et nervosa canum (Dog ill; Pasteurellosis canwm, Maladie des chiens, Maladie du jeune age [French]; Staupe der Hunde | German] ; Cimurro, Moccio canino [Itahan]. Distemper is an acute, contagious infectious disease of young carnivorous animals, and is characterized by febrile manifestations, and an acute catarrh of the mucous membranes, which is frequently followed by catarrhal pneumonia, and in some cases by the development of nervous symptoms. The disease is caused by a filtrable virus. 198 Distemper of Dogs. History. The frequency of the disease among dogs, and its im- portance, is well illustrated by the fact that it is known in almost all languages as the ‘‘dog disease.’’ In Europe it is supposed to have occurred since the second half of the eighteenth century, having been introduced from Asia (Spinola) or from Peru (Heusinger). The infectious nature of the disease was proved in the middle of the last century, by successful experiments of transmission, with the nasal dis- charge (Renner & Karle, Weisz, Laosson, Krajewsky), with saliva ‘(Venuta), and with the contents of the skin pustules (Trasbot), from affected animals to young dogs. Its etiology, however, was first cleared up by the investigations of Carré (1905), which established that the disease is caused by a filtrable virus. Occurrence. Distemper is a remarkably frequent disease of young carnivora, especially of young dogs, so much so that the great majority of the latter become affected before reaching the age of one year. In kennels young animals usually become affected in great numbers, but not infrequently the disease occurs in an epizootic form affecting entire townships or even large territories. It is more prevalent during warm weather, but is also quite frequent during the winter. ’ Etiology. According to the investigations of Carré which have since been confirmed by Ligniéres, distemper is caused by a filtrable virus which in the beginning of the disease is contained in the nasal discharge. Subcutaneous injections of two drops of the serous dis- charge from the nose kills young animals within 6 or 7 days with symptoms of coma and a fall of the temperature at the termination of the disease. The autopsy shows only an accumu- lation of clear, yellow serous fluid in the pericardium. Injec- tion of a filtered nasal discharge, or of filtered pericardial fluid produces a rapid rise in temperature after 3 or,4 days, eatarrh of the conjunctivae and the nasal mucous membrane, cough, and after 8 to 10 days a pustular exanthema on the parts which are thinly covered with hair. The nasal discharge becomes more profuse and purulent, whereupon death results in from 2 to 3 weeks. The autopsy reveals catarrhal pneu- monia, the heart muscle appears to be sprinkled with small hemorrhages and yellow spots, while the pericardium, some- times also the pleural and the abdominal cavity, contains a serous fluid in varying quantities. The exudate is only ex- ceptionally virulent, unlike that of acute cases. The blood is only virulent at the beginning of the fever, while later, even in an unfiltered condition, it will not produce the disease; this applies also to the nasal discharge which has become purulent, and to material from the hepatized lungs. Healthy dogs may be artificially infected by cohabitation. In view of the results of the investigations, the different bacteria which have been found by various investigators in the tissues of dogs affected with distemper must be considered as secondary participants Etiology. 199 in producing the disease processes. The filtrable virus which attacks the body, prepares the field of action for the other organisms which produce inflammatory local changes. Thus Jensen found strepto- cocci, staphylococci and a slender bacillus, Mathis isolated a diplo- coccus from pustules on the skin, the cultures of which resembled the ordinary staphylococcus, Schantyr obtained a motile bacillus resembling the organism of abdominal typhus, Perez incriminated the cocco-bacillus ozoenae foetidus, while Galli-Vallerio found a bacillus resembling the colon bacillus, which, however, stains by Gram. Ligniéres, Ceramicola and Wunschheim attributed the disease to an ovoid bacterium, and Pior- kowski obtained a slender, delicate capsulated bacillus, ete. ; All of these organisms appear to be normal inhabitants of the dog organism. In different cases one or the other, or several of these organisms commence to multiply more rapidly in the affected dog, and then exert their pathogenic action. This applies especially to the bacillus bipolaris septicus, which was considered by Ligniéres as the true cause of the disease. Cultures of this organism (they can only exceptionally be isolated) produce severe septic symptoms in dogs after intravenous injections, and frequently also secondary inflamma- tions in various organs. Whether there exists an independent pas- teurellosis of dogs, as claimed by Ligniéres, in addition to the distem- per caused by the filtrable virus, is not established at the present time. Contrary to the described etiological findings, Kregenow succeeded in producing the disease with filtrable virus in only two instances out of 10 inoculations, and even the two positive cases he attributes to natural infection. Accordingly he is of the opinion that the virus is not filtrable, and must be one of the numerous visible organisms. However, the experiments, as indicated by his notes, were not carried out as suggested by Carré, with the serous nasal discharge, but with a puru- jent discharge and material obtained from pneumonic lungs. It is possible, therefore, that the filtrable virus contained therein was retained during filtration. Natural infection occurs through direct or indirect contact with affected animals. The virus is present in the catarrhal secretion of the mucous membranes and is evidently in most instances taken into the digestive canal with the food and water. The infection is probably favored by influences which reduce the resistance of the body, such as colds, insufficient or im- proper food, such as bread, kitchen refuse, etc. The disturb- ances of digestion caused by these, together with loss of blood, exhaustion, weak constitution, etc., favor the development of the disease. Young animals are most susceptible. They may excep- tionally become affected when only 2 to 3 weeks old (Fried- berger & Fréhner), but usually dogs several months old up to one year suffer most frequently from the disease (this is prob- ably due to the fact that the animals at that age move around ‘more freely and are more exposed to the infection). The susceptibility diminishes with advancing age, so that animals over three years old are but rarely affected. The great re- sistance of older animals is in all probability due to the fact that the great majority have been affected with the disease at a younger age and have thereby become immune to it. Pampered and weakly dogs, as well as animals recently 900 Distemper of Dogs. imported, especially those of the finer breeds, are more sus- ceptible and usually become more severely affected than do dogs which are kept in the country and are hardened. Pathogenesis. The action of the specific virus produces a febrile condition, and in direct association with it catarrh of the mucous membranes, as well as inflammation of the serous membranes, especially of the pericardium. If the animal lives through the acute attack, its weakened resistance favors the development of secondary processes by other micro-organisms. These are usually facultative pathogenic bacteria, which are mostly, or probably invariably, frequent habitants of the healthy dog. Of the secondary inflammations the most frequent are pneumonia, purulent inflammations of the conjunctivae, the mucous membranes of the air passages and of the intestinal canal, pustules on the skin, and also inflammatory changes in various parts of the nervous system as a result of metastasis. The later course of the disease depends on these secondary diseases, while the filtrable virus usually disappears before, or not later than at the beginning of their development. Anatomical Changes. In the rare peracute cases a large quantity of serous fluid is present in the pericardium, and possibly there are small hemorrhages in the heart muscles. In the great. majority of cases the respiratory organs, es- pecially show severe changes. The mucous membranes of the air passages are bright red, swollen, and profusely covered with sero-purulent secretion. If the smallest bronchi are af- fected simultaneously numerous small purulent plugs may be squeezed out of the cut surface of the lungs (bronchitis capillaris). In most cases there is also a catarrhal pneumonia. Sometimes small broncho-pneumonic areas may be disseminated throughout the lungs, or larger lung portions, especially near the anterior and lower borders are found dense, hepatized, and according to the duration of the inflammation either dark brown-red or grayish-red. The cut surface is smooth or finely granulated, and sometimes studded with small purulent foci. The borders of the unaffected lobes of the lungs show bluish-red, depressed, club-shaped atelectatic areas. The pleura covering the affected parts of the lungs is either smooth and lustrous, or dull and covered with fine fibrinous membranes. The mucosa of the stomach and intestines show frequently manifestations of acute catarrh; the solitary follicles, as well as Peyer’s patches are swollen. Exceptionally there may also be superficial erosions and catarrhal ulcerations present. The lymph glands of the thoracic cavity, and of the mesentery show inflammatory swellings; the pericardium con- tains sometimes a great quantity of a clear serous fluid. The heart muscles may be interspersed with small hemorrhages and yellow fatty degenerated areas. The liver and the cortical portions of the kidneys show parenchymatous or fatty de- Symptoms. - 201 generation. The spleen is only slightly, or not at all enlarged. ‘The eyes are usually affected with a more or less intense catarrh _of the conjunctivae sometimes an ulcerative keratitis, and oc- easionally by a panophthalmitis. The central nervous system may in some cases show changes corresponding to a myelitis disseminata (Mazulewitsch, Bohl, Dexler). According to Dexler’s investigations the changes of the central nervous system show a pronounced disseminated myelitis and poliomyelitis, in which the inflam- , matory foci are not confined to the gray anterior lobes alone, but are always present in the entire nervous system without any regular arrangement. Virulent streptococci are frequently found in the affected areas. Confirming similar reports of Standfuss, Lentz describes small roundish or oval formations which he calls distemper corpuscles and which are supposed to develop from the action of the distemper virus on the plastin substance of the nerve cells which is destroyed, and causes the chromatin substance to roll together in peculiar granules. These formations which have been found in dogs dying from. a severe nervous form of distemper are distinguished from the somewhat similar Negri’s rakies bodies, in that they occur outside of the nerve cells, or in the greatly degenerated cells, and possess no inner structure. Symptoms. The time of incubation after an artificial in- ' fection is usually from 3 to 4, and at least 2 days (Carré); although it is probably somewhat longer under natural con- ditions (according to Krajewszki it may extend up to 21% weeks). The peracute form of the disease is manifested in a sud- denly appearing inappetence, depression, groaning, fatigue, as well as high fever. After 2 or 3 days the temperature rapidly drops below normal (to 35-33°C ), whereupon death soon ap- pears under comatous symptoms (Carré). The acute form also is inaugurated by high fever (Fig. 35), the temperature rising rapidly to 40°C. or over, and remains at this height for 1 to 2 weeks or it falls slightly in 1 to 2 days, and then there exists only moderate fever, of a continuing or remittent character in the further progress of the disease. In severe cases the temperature rises again owing to the de- velopment of pneumonia, but towards the termination of the disease it falls gradually or rapidly below normal (to 32°). The beginning of the disease is usually indicated by a change in the disposition of the animal. The animals, or- dinarily bright and playful, become capricious and less lively; they obey the call only with hesitation and unwillingly, pre- ferring to find secluded places where they remain lying for long periods. Meanwhile they tremble over the entire body, or at times appear suddenly startled. The hair is roughened, the appetite diminished and capricious. After 1 or 2 days the more characteristic symptoms of the disease develop. In most cases an acute catarrh of the air passages appears. The animals feel an itching in the nose because of which they frequently sneeze and puff, wiping the nose with their paws or on the forelegs. There is at first a serous or mucous, later a purulent secretion from the nose, which soils the surrounding 202 . Distemper of Dogs. parts and dries around the nasal openings in brown crusts. The secretions may also contain streaks of blood, or become ichorous, and irritate the skin of the upper lip and of the nasal wings, which then become raw. If the swelling of the © nasal mucous membrane is pronounced the respiration becomes sniffing (this is an ZEEFEEBLESEELEER especially frequent " Talk le le Is lel le SUIS Is ls Ie 06 manifestation in w is Is _ lo Is SsLisc vis Is Ie Io Js ft 2 |. Ts ts le lelle sls lg ig le | breeds of dogs with rss ~| short heads). $ TT - - The catarrh of ‘ | Less Live . eT | & the larynx and the § =| bronchi is indicated . 1 «| by a cough which at cE Depresied 3| first is short and dry, & HH = [vumerous ales =| Such cases it tortures Bo ea =| the animals greatly, ge Ua . and also causes vom- ° z, =| iting. Respiration is Bo HL = accelerated. and lab- oes a : ored. Auscultation of Le + the thorax reveals BE [Bae sean i + rough vesicular eB: are Ty -| breathing, and dry ge CT - or moist rales, as well 3 ll in Mt i = as other catarrhal ro aati -| sounds. If in the fur- = (ICEL i “| ther course of the 3 TTT | Gisease capillary @ PADUTEECTEE SUNN MHA HTER UE “| bronchitis or ca- 3 TOTO =| tarrhal pneumonia FS AVATAR TanONT TRG see ill 3! develops, the number e ae ea TREES] «oof respirations ‘in- a Bina ®| creases to 60-80 and gs Steet} «even more per min- : Prabial Breathing HAs cs) ute. The accessory Be TEETH ttre its] respiratory muscles are utilized to a great extent, and at each expiration the cheeks become dis- tended. In such cases percussion shows dullness, or a tym- panitic sound in places, while on auscultation, extensive catarrhal murmurs are heard, in other places bronchial breathing or no respiratory sounds at all are observed. The cough now becomes very weak and feeble. The affection of the eyes mostly develops simultaneously with the catarrh of the respiratory organs. It commences with Symptoms. 203 conjunctivitis, to which are added photophobia, pain and swell- ing of the eyelids. The conjunctiva is bright red, has a moist luster, and at times is raised above the cornea. The lachrymal secretion is increased from the onset, but later the tears are mixed with a mucous and purulent secretion, which, to some extent accumulates in the inner canthus, sticking the eyelids together, especially at night. Ulcerative keratitis develops with relative frequency in association with the con- junctivitis, small depressions appearing in different parts of the cornea, which may later heal entirely. Sometimes, however, these lesions extend rapidly in size, so much so that even on the first day loss of substance may result which reaches the extent of a lentil, and penetrates to Descemet’s membrane, or in some instances the entire cornea may be destroyed. The borders of the depressions, as well as the entire cornea may at the same time be clear, or pus may be present only at the base of the depressions. Descemet’s membrane thus exposed is then forced out as a result of the internal pressure from the eye, and in this manner a staphyloma may develop, the rupture of which may result in the prolapse of the iris, followed by the well-known severe results. In other cases a parenchymatous keratitis develops, associated with a uniform cloudiness and a marked ciliary injection of the cornea, which retains its char- acter until the termination of the disease, is not followed by ulceration, and gradually disappears or results in a permanent white cloudiness. The pupil usually becomes constricted, while severe iritis with accumulation of a plastic or a purulent exudate in the anterior chamber occurs only rarely except in cases in which there is a perforation of the cornea. The involvement of the digestive organs is shown early by diminished appetite. At the onset of the disease an increased thirst, as well as vomiting is observed, which is an indication of acute gastritis. The patients vomit mostly slimy, yellowish material mixed with bile. At the same time the buccal mucous membrane is dry and warm, the tongue is coated, and the region of the stomach sensitive. As a result of the intestinal catarrh which 1s usually present together with the gastritis, there is at first constipation; which soon changes to diarrhea. The excrements which are often passed under severe straining are in a fluid state and may contain mucous flakes or blood. The feces are very fetid. The abdomen is at first somewhat bloated, later however it becomes drawn up and painful. In some eases. the urine contains albumen, and occasionally bile pigments as well as hyaline and cellular casts. Nervous symptoms are hardly ever absent even in the cases which are not very severe, and sometimes they may reach such a degree that they practically control the entire disease. Besides the dullness and the change in the disposition of the animals already mentioned, the patients sometimes manifest considerable excitement which, however, usually lasts only a 204 Distemper of Dogs. few hours. In many cases muscular tremors or clonic spasms develop, and are either confined to certain groups of muscles, or extend over the entire body. Local spasms are usually observed in the face, especially on the lips, nasal wings, cheeks, and in the muscles of mastication (chattering teeth and foaming lips). In other cases spasms occur in the muscles of the neck or extremities so that the affected portion of the body, in the former case the head .and the neck, trembles sometimes con- stantly or only at certain periods, or again it may be moved regularly in a certain direction. The spasms of the entire body muscles which frequently develop from the above condition are manifested either by con- tinuous trembling or by periodical epileptiform fits. In the latter case the animal becomes restless, then suddenly collapses unconscious, while chronic spasms occur over the entire body, and the rapid movements of the jaws churn the saliva to a foam. . The expression of the face is distorted, and the head is forcibly extended forward or turned sidewise. During the attack feces and urine may be passed involuntarily. These attacks exhaust the animals greatly, and sometimes occur several times within an hour, whereupon a deep coma develops which soon is fol- lowed by death. As the reflex irritability is greatly increased the local, as well as the general spasms may be brought on by slight external irritations, such as loud calling, irritation of the skin, sudden exposure to light, ete. Occasionally involuntary movements may be also observed. The convulsions may gradually become less frequent and finally disappear; in some cases, however, they terminate in paralysis, which may appear in certain parts of the body, while others are still irritable. The paralysis is most frequent in the hind parts, and is associated with movements of incoordina- tion, and not infrequently by paralysis of the sphincter muscles of both bladder and rectum. Paralysis of a facial nerve results in a distortion of one-half of the face; paralysis of an oculomotor nerve causes an abnormal position of the eye, strabismus and inequality of pupils. Simultaneously with the paralysis contractions may develop in some of the extremities. According to Dexler the virus of distemper may produce three great groups of nervous disturbances: 1, local clonic-tonic continued spasms of different parts of the body, and chorea-like movements; 2, flaccid paralysis of the extremities and sphincters; 3, clonic-tonic epi- leptiform fits occurring during attacks of unconsciousness. All these symptoms are brought on by isolated or general inflammatory changes which can be demonstrated histologically (see p. 201), and since the motor disturbances differ from those of chorea of man, Dexler appears to be justified in his conception that the convulsions of distemper do not represent a neurosis, and accordingly should not be designated as chorea, but that the affection should be considered as an independent condition, and for the present should be named ‘‘distemper-Tic,’’ or rhythmical post-infectious convulsions. Course. 905 In about one-half of all cases a peculiar pustular exanthema (distemper exanthema) is observed on the skin. Small red spots may appear on the inner surface of the thigh, on the contiguous abdominal wall, or more rarely on the parts sur- rounding the nose and the eyes, in the external ear, on the conjunctiva, and exceptionally on the entire surface of the body. At these places small nodules soon develop, which change to lentil-sized purulent vesicles. They dry to brown crusts, or burst, leaving reddened moist places which later become also covered with scabs. If the eruptions become extensive the animals at this stage diffuse an unpleasant sweetish odor. Finally the scabs drop off, and in their place reddish spots covered with epithelium are left, which gradually become paler, and finally disappear entirely. In rare cases the pustular exanthema may also develop on the borders of the lips, whence it may even extend to the buccal mucous membranes, and there produce a severe ulcerative condition which may even lead to a general septic infection. (Semmer, Arnous, Hiirlimann; see also typhus of dogs, p. 213.) Trasbot considered the pustules of the skin as true pox eruptions, and this conception appeared to be strengthened dy successful experiments of transmission. Alowever, their rapid development, as well as che lack of the characteristic structure of the true pox vesicles, further the fact that the artificial production of such vesicles does not influence the susceptibility of the dogs for distemper infections, contradicts this supposition. Moreover, Carré succeeded in producing the exanthema even with the virus of foot-and-mouth disease. The action of the heart is more or less disturbed according to the severity of the different cases. In severe cases the heart beat is greatly accelerated, irregular, throbbing, and the pulse wiry, owing to the parenchymatous degeneration of the heart’s muscles. Lange observed in about 50% of animals affected with distemper, a painless external otitis, with a thin fluid secretion and moist eczema of the external ear passage. Sabrazés & Muratet found in the blood of dogs affected with distemper a neutrophilic polynuclearcytosis and hypoeosinophilia, as well as an iodophilia. The animals usually become greatly emaciated in the course of the disease. At the approach of death they lie in a deep stupor, trembling on the ground, until they finally die of the convulsions. Course. The disease shows a most varied course. Fre- quently, especially in benign cases, only a certain group of the symptoms described are present, and even these may be developed in different cases with varying intensity. Thus in some cases catarrhal symptoms are present exclusively, while in others only nervous manifestations are seen. Sometimes the disease is manifested by pustular exanthemata of the skin only. Taking the etiological identity of these cases into consid- 206 Distemper of Dogs. eration, a catarrhal, a nervous and an exanthematous form of distemper may be distinguished. Such sharp characteristic forms of the disease, however, are only rarely observed, as in most instances the symptoms of two or even of all three forms are present simultaneously, although in such a way that the symptom complex of one of the forms usually predominates. Most frequently the catarrhal or nervous form occurs separ- ately, while the skin exanthema usually occurs conjointly with one or the other. Besides the character of the disease may not infrequently change during its course, as it is often noted that nervous manifestations associate with the catarrhal symp- toms, and later these may even predominate. Just as there are great variations in the clinical appearance of the disease, so its duration varies greatly from case to case; very mild cases may thus terminate in recovery inside of a week, whereas severe cases may extend over several months. The average duration, however, is from three to four weeks. The recovery is not infrequently incomplete, or it may become complete only after a long time. The symptoms of paralysis are most prone to persist, or may improve only after several weeks. Incurable degenerations may be present in some of the nerves of the brain, leading sometimes to blindness, deafness, loss of the sense of smell, ete. Occasionally after the acute stage of the disease has passed ‘a certain predisposition of the mucous membranes for catarrhal affections becomes noticeable which leads for months after- wards to repeated catarrhs. The catarrhal pneumonia may develop into a chronic inflammatory condition leading to casea- tion of the exudate and an increase of the connective tissue, which considerably interfere with the later development of the young animals. Permanent changes sometimes develop in the eyes, such as white cicatrices at the sites of the cornea ulcerations, synechiae after a perforation of the iris, and occlusion of the pupil or atrophy of the eyeball after a severe iritis. Diagnosis. Distemper may be readily distinguished from other catarrhal affections whenever nervous or pustular exan- thema are present in addition to catarrhal symptoms. This also applies to older animals, in which the diagnosis is other- wise more difficult. In the presence of purely catarrhal symp- toms, the high fever which occurs in the beginning. of the disease, the pustular exanthema, the early age of the animals, and frequently also the possibility of tracing the infection, may reveal the nature of the disease. Gastro-intestinal catarrhs originating from other sources, such as for instance from. dietetic errors or from poisoning, are differentiated from dis- temper by the absence of the catarrh of the air passages and conjunctivae. The change in the disposition of the animals, Prognosis. Treatment. 207 especially the occasionally noticeable excitement and also the convulsive mastication with the formation of foam at the mouth, may create a suspicion of rabies. However, this condi- tion exists in distemper only for a very short time, and is soon followed by a period of depression, then by muscular spasms, while the paralysis of the muscles of the pharynx and of the muscles of mastication which are characteristic of rabies, are absent. The severe convulsive attacks are distinguished prin- cipally from those of epilepsy by the fact that in distemper they occur at frequent intervals, are preceded by iocal muscular glpette and that these spasms are present even between the attacks. Prognosis. The average mortality in the disease amounts to about 50%. The cases in which the purely exanthematous and catarrhal symptoms are present are the most favorable with about 70% recoveries. Least unfavorable are the cases in which the nervous manifestations predominate, as in these the recov- eries sometimes do not reach 10 to 15%. The more rapidly the symptoms increase in severity and the higher the degree they attain, the more unfavorable becomes the prognosis. The convulsions which affect the entire body, as well as the appear- ance of catarrhal pneumonia, and a severe persistent diarrhea are unfavorable prognostic indications. Continuous high fever indicates a severe infection as a result of which grave changes in the myocardium may be expected. A still more unfavorable sign is the rapid fall in the temperature below normal, as it usually indicates the approach of death. Pampered, very young or improperly nourished dogs usu- ally become more severely affected than older and hardened animals of ordinary breeds. The existing hygienic conditions should also be given consideration in the prognosis. According to statistics of Wirth, which include 2855 cases, an average of 35 8% succumb to the disease. In these cases the mortality was the lowest among fox terriers, and highest in hounds. Nervous symptoms were observed in 15.1% of the cases, females appearing to be more predisposed to this form of affection; in some outbreaks the exanthema was entirely absent. In tocalities i which the disease occurs only periodically as a result of intro- duction trom the outside, it rages with peculiarly destructive force, and it has been observed, for instance in Greenland, that sometimes such outbreaks destroy about one-third of the entire number of dogs (Hjortlund). Treatment. First of all the hygienic condition, and espe- cially the diet, should be suitably regulated. The affected animals should be placed ini a clean, uniformly warm place, they should be protected from draughts, and if possible should be furnished concentrated nourishment. For this purpose milk and good strong meat broth, with the yolk of an egg beaten into it, is most suitable. Several daily feedings with chopped, salted meat cooked in steam, is very beneficial (Gerstner). In the presence of gastro-intestinal catarrh, gruel may be given to advantage. is 208 Distemper of Dogs. As an abortive treatment subcutaneous injections of tri- chloride of iodine (3 times daily, 3-5 g of a solution of 1 to 1000-500), as recommended by De Bruin, are indicated. This method of treatment when applied in the early stages of the disease is very beneficial, as the animals after a few days become much brighter, their temperature returns to normal, and the catarrhal manifestations diminish. In some of the ani- mals, however, in spite of the greatest care, a necrosis of the skin at the point of injection develops. Bass recommends for the early treatment, Ichthargan (Ichthargan, gummi arab. aa. 5.0, aqu. 100.0, 3 times daily in teaspoonful to tablespoonful doses), while Liebert & Schmidt recommend tannargentan (1 g. 2 or 3 times daily). | For the depression and weakness nervous stimulants are recommended, such as alcohol (wine, cognac) in proper dilu- tions, and in small but frequently repeated doses. In severe cases coffee or caffeine, liquor ammonii anisatus in any desired infusion, also subcutaneous injections of 30 ce. of a physiological salt solution (Parent) are indicated. To the salt solution it is advisable to add 10-20 cg. caffeine (Cuny). The fever does not require any special treatment, unless very severe (over 40°), when the administration of antipyretics (phenacetin, antipyrin, in doses of 0.25-0.50 g.) is recommended. The catarrh of the respiratory organs is treated to the best advantage with inhalations of warm vapors, containing expectorants (1 to 3% solution of carbonate or bicarbonate of soda). If the secretion is very profuse inhalations of disinfec- tant fluids (creolin 2-3%, creosote 0:5%, turpentine, aqua-picis, septoform) may be given three or four times daily with Siegel’s or Bulling’s apparatus. In painful dry cough antispasmodics such as Morpheum salts (morphii muriat 0.10, aqua. amygd. amar. 12.0, 10 to 15 drops every 2-3 hours), or codein (cod. phosph. 0.30, aqu. 150.0, 1 to 2 teaspoonfuls every 2-3 hours) give beneficial results. In the presence of profuse secretions, however, suppression of the cough is rather harmful. In such cases ipecacuanha infusions and senega decoctions, given either with apomorphine (1 to 2 mg. per dose) or with ammonium chlorate (0.1-0.5 g.) may be used to better advantage. If pneu- monia has appeared inhalations of oxygen may be tried (Kantorowicz). The gastro-intestinal catarrh should be treated first by regulating the diet as already described, and in the first days of the affection a cathartic such as castor oil or calomel (0.02- 0.05 g. 2-3 times daily), as well as salol, should be given. If vomiting 1 is present this may be controlled by the administration of ice, water containing soda, salicylate of bismuth (0.5 g.), in emergency with opium (0. 05 to 0.10 g.). For the stimulation of the digestion hydrochloric acid (0.2 to 0.5 g.) in-the drinking water, or pepsin (0.1 to 0.5 g.) alone or with the hydrochloric acid, is advisable. Besides the various bitter tinctures (Tinct. Treatment. 209 rhei aquosa and vinosa, Tinct. gentianae, Tinct. chinae com- posita 5-10 g. per dose) are often used. If diarrhea has appeared it is advisable to administer opiates (0.1 to 0.2 opium or 5 times that amount of the opium tincture every 3-4 hours) ; this may be given together with tannin (0.1 to 0.5 g.), bismuth sub- nitrate (0.2 to 0.5 g.), tannoform, tannalbin, tannopin (0.5 to 1 g. of each), or with red wine (in teaspoonful doses). Raleigh obtained recoveries in 60% of his cases by treating the affected animals first with 0.25 to 0.40 g. of calomel, and followed four times daily with 0.60 g. sodium hyposulphite, while Liebert & Schmidt obtained splendid results from the administration of tannargentan (2-3 times daily 1 g. doses). In the presence of nervous symptoms anodynes and anti- spasmodics are recommended. However a beneficial action from their use on the neuritic or myelitic affection, can hardly be hoped for. Of these may especially be mentioned bromide of potassium and bromide of sodium (1:250 4 or 5 times daily in tablespoonful doses), chloral hydrate (0.5 to 2 g.), sulfonal (1 to 2 g.), or morphium in larger doses (0.05 to 0.1 g.) sub- cutaneously. Paralysis may be treated with massage, alcohol rubs, or by the application of electricity, as well as by sub- cutaneous injections of veratrin (1 to 5 mg.) or strychnia (0.5 mg.). The conjunctivitis, while the symptoms of irritation last, should be treated with warm applications 2-3 times daily, and washing with a 1% creolin and boracie acid solution, while astringents are indicated only after the subsidence of the acute symptoms. Of such astringents may be mentioned 0.5 to 1% solutions of sulphate of zine, alum, or tannin, as well as the ‘‘eollyrium adstringens luteum’’ (diluted 1-3 to 1-2). If the catarrh has become chronic, or if there exists a continuous purulent secretion, the painting of the eye with a 1% silver nitrate solution may be tried. It should be applied with very great care, and the superfluous portion should be neutralized with a 1% salt solution. For the keratitis, as well as for the internal inflammations of the eye, warm applications and the dropping of a 1% atropin solution into the eye are recommended. For clearing away the cloudiness in the cornea, the applica- tion of powdered calomel! or iodide of mercury salve (1-20), with subsequent massage of the eye, is often beneficial; this, however, should be only undertaken after the disappearance of the acute symptoms. For threatening blindness as a result of paralysis of the optic nerve, injections of strychnia into the temporal region might be favorable. : ; The exenthema of the skin does not require a special treat- ment, but the sprinkling of the moist surfaces with a drying powder, or the application of a salve, may assist in the healing of these lesions. Prevention. Since the affected animals easily infect others, they should be kept from healthy young dogs and cats, and the 14 210 Distemper of Cats. place where they are kept should be disinfected. Young animals should be kept from contact with sick ones, and by this the advantage will at least be gained that the animals may not become affected until an older age, when, according to observa- tions the chances for recovery are much better. Immunization. The various sera for distemper.are not very prom- ising, as they are prepared with the aid of bacteria, which at best are of importance only in the secondary organic lesions. Ligniéres uses for this purpose partly attenuated cultures of bipolar bacilli obtained from affected dogs, partly his polyvalent vaccine and his polyvalent serum (see pp. 85 and 86). Physalix uses cultures of the same organism grown in glycerin bouillon, while Piorkowski prefers a serum prepared with the aid of his ‘‘ distemper bacillus.’’ But with none of these preparations was it possible to obtain satisfac- tory results in practice. Richter proved that the vaccines of Physalix and Piorkowski are valueless for the treatment of the disease, and Boden also found that Piorkowski’s serum at the best only produced an improvement in the first stages of the purely eatarrhal form of distemper. Bissauge & Naudin recommend the antistreptococeus sera of the Pasteur Insti- tute, and of Dassonville & Wissoeq (twice daily 2-4 doses of 4 ec. each); and at the same time the administration of Pury’s Swiss yeast in warm milk. The yeast serum (antistreptococeus serum), obtained by Deutschmann by treatment with increasing amounts of yeast, is according to Lamche absolutely useless as a prophylactic agent, and as a curative it has only a moderately beneficial action in those cases which show no complicating intestinal affections. Blanck and Wolff, however, report favorable results from this method of treatment. The distemper-antigourmin (Furonculine), which has been highly recommended by Diffiné and is prepared from equal parts of yeast and starch, proved unreliable in the experiments of Meltzer, Hochstein, Meckelburg and Lamche both as a curative and prophylactic. : Literature. Bollinger, A. f. Tk., 1878, IV, 214.—Krajewski, Rev. f. Tk., 1881, 177 (Lit.); D. Z. f. Tm., 1887, XIII, 324.—Laosson, Diss. Dorpat, 1882 (Int.).—Dexler, Arb. d. Wiener Inst. f. Nervenanat., 1892; D. t. W., 1909, 313 (Lit.).—Jensen, Maanedsskr., 1895 and 1896.—Jess, Zbl. f. Bakt., 1899, XXV, 541.— Ligniéres, Bull., 1900, 469 (Lit.); 1906, 622.—Physalix, Bull., 1901, 131.—Carré, Bull., 1905, 335; Rev. gén., 1906, VII, 649; C. R., 1906, 962.—Piorkowski, B. t. W., 1905, $30; 1906, 377.—Wirth, T. Zbl., 1908, 200.—Richter, Die Hundestaupe, Diss. Bern, 1908 (Lit.)—Kregenow, Zbl. f..Bakt., 1909, L, 326 (Lit.).—Lamche, Diss. Zirich, 1909 (Lit. on yeast treatment). Distemper of Cats. Although young cats are also suscep- tible to the virus of distemper (Krajewski, Laosson), the dis- ease occurs in these animals much less frequently than in dogs. The symptoms and the anatomical changes correspond with those of dogs affected with distemper, but according to Fried- berger & Frohner nervous symptoms are less common and the exenthema of distemper is usually absent. In the treatment the above-described principles should be followed. (Literature same as in dog distemper.) A new disease of cats was described by Gaertner, in which the symptoms consisted of depression, conjunctivitis, muco-purulent dis- charge from the nose, and marked difficulty in respiration. The disease usually terminated in death in from three to six days; exceptionally, however, it lasted for several weeks. The autopsy revealed a multiple necrotic pneumonia, principally of the posterior lobes of the lungs, and as the causative agent a bipolar ovoid bacillus (Bact. pneumoniae felis) was established (Cbl. f. Bakt., 1909, LI, 232). Typhus of Dogs. 911 An ovoid bacterium (Bae. felisepticus) was also found by Boucek in young cats, which died in an enzootic. These animals suffered from disturbed appetite, vomiting and convulsions, while the autopsy revealed a mild intestinal catarrh, moderate swelling of the spleen and of the mesentery lymph glands, as well as punctiform hemorrhages - in the pericardium and in the heart muscles (Cbl. f. Bakt., 1909, LIT, 279). II. Typhus of Dogs. Typhus canum. (Hundetyphus, Stuttgarter Hundeseuche; Gastro-enteritis haemorrhagica.) Typhus of dogs is an acute infectious: disease which periodically occurs in an epizootic form, in the course of which severe symptoms of a gastro-intestinal inflammation are ob- served frequently complicated by ulcerative stomatitis and severe nervous symptoms. The etiology of the disease has not been determined up to the present time. History. Hofer described the disease under the name of ‘‘typhus’’ in 1850; however, it did not create a general interest until it appeared in Germany in 1898, and in the following years also in other countries, as a severe plague. In this outbreak the disease was first described clinically by Klett; who observed it in the fall of the year in and around Stuttgart (hence the name ‘‘Stuttgart dog disease’’). Other outbreaks of the affection, and also deviations from the usual mani- festations were described by Scheibel of Frankfort, Albrecht of Munich, Zschokke of Switzerland, Trevisan & Gambarotte of Italy, Bimes & Sérés and others of France, Hébrant of Belgium, Némo of FEdin- burgh, Mattel & Tremmel of Vienna and vicinity. A similar disease was observed in 1903 at Budapest, when several cases came under observation. . Occurrence. According to the above mentioned writers the disease existed in the years of 1898-1900 in Middle Europe in the form of a wide spread, epizooti¢ extension; since that time however it has again disappeared. In the period mentioned the disease caused great losses especially among older dogs of the affected localities. Etiology. The epizootic occurrence of the disease in various localities which are not far apart, appears to indicate its infectious nature. On the other hand various investigators have observed almost uniformly that direct transmission has no, or only an insignificant, importance, In its appearance and spread. Frequently dogs became affected which had not pre- viously come in contact with affected animals, while on the other hand among dogs kept in kennels, not infrequently only isolated cases were observed. Test inoculations have not given uniform results up to the present time. In the outbreaks which have occurred usually the older dogs and not infrequently those over 10 years old became 212 Typhus of Dogs. affected. Some of the animals contracted the disease in spite of the fact that they had passed through an attack of distemper. The condition, sex and breed of the animals appeared to have no noticeable influence on their susceptibility. Attempts at artificial transmission have so far given variable results. Pirl observed after subcutaneous injection of the bile of a severely affected animal (5.0 or 2.0 em.) into two healthy dogs, that an inflammatory edema developed at the point of inoculation, followed by fever, salivation, vomiting, bloody diarrhea and convulsions. One of the dogs died after three days, the other recovered after six days. The subcutaneous injection of blood, fluid from the lungs, or an emul- sion prepared from the walls of the stomach or intestines, produced only a local suppuration (Albrecht, Scheibel), while the feeding of organs and of the contents of the stomach of animals dead from the disease proved harmless. Scheibel observed in only one instance the development of a gastro-intestinal inflammation, after he had previously neutralized the gastric juice in the animal which was fed with the infected material. Scheibel & Zschokke found a bacterium in the blood resembling the organism of fowl cholera or swine plague, while Leclainche & Vallée demonstrated in the pathologic secretions and tissues the presence of a ‘‘Pasteurella.’’ Based on these findings Bimes & Sérés identified the disease with dog distemper (?). In the winter of 1903 to 1904 several cases were observed at the Budapest clinic which in their manifestations, except for the absence of the ulcerations in the mouth, were similar to the cases observed in Germany. From the contents of the severely inflamed and hemor- rhagic intestines, also from the intestinal mucous membrane and the mesenteric lymph glands, a colon bacillus and a virulent type of proteus has been isolated in every instance. An intravenous injection of 1 g. bouillon culture of these bacilli per 1 kg. of body weight, produced in dogs a very intense hemorrhagic gastro-enteritis, which produced death inside of six hours, while the subcutaneous injection of the colon bacillus caused extensive but painless suppuration, and necrosis of the skin. It was impossible to produce the disease by feeding the bouillon or meat cultures, not even after a previous neutralization of the hydro- chloric acid of the stomach (Hutyra). Anatomical Changes. The autopsy establishes in all cases severe inflammatory changes in the digestive tract. The mucous membrane in the entire stomach and in the duodenum, is greatly swollen, corrugated, and of a blackish-red color. Its surface shows numerous hemorrhages varying in size from that of a lentil to a pea, and is covered profusely with mucous or with a chocolate brown, semi-liquid mass which has an alkaline reac- tion (exceptionally fresh blood may be also present in the stomach). Similar, but less plainly marked inflammatory changes, are present in the intestinal canal, especially in the small intestines and in the cecum. The peritoneum over the stomach and the intestines is markedly injected, the mesenteric lymph glands, and to a greater or lesser extent the spleen also show acute swelling. The liver and the kidneys are hyperemic, the latter also contain small hemorrhages; the bladder is Symptoms, 913 usually distended, its mucous membrane is usually smooth and pale red. The lungs show only hyperemia and acute edema. The muscle of the heart often tears easily, and on the cut surface it is sprinkled with butter-yellow streaks. The brain and its meninges are hyperemic. The buccal cavity frequently con- tains inflammatory. as well as necrotic changes (see symptoms), Symptoms. The disease almost invariably commences with sudden vomiting, which usually attacks the animal while eating or drinking, and which may re-appear very frequently. The vomited material consists of remains of the ingested food or water stained yellow by ‘the bile, but may later become bloody. From this stage on, the animals refuse to eat, or they accept food unwillingly; on the other hand they drink water very fre- quently and feverishly. There is first constipation, but later diarrhea appears. ‘ The animals are greatly depressed from the beginning of the disease, and are unwilling to move about, and in doing so they manifest a staggering gait. They show indifference to their surroundings, which condition later develops into great dullness and sleepiness. .'The animals become greatly emaciated as a result of the frequent vomiting, and persistent inappe- tence, and the disease develops in its characteristic form in from 3 to 5 days. The conjunctivae show a brownish-red discoloration, are greatly injected, the eyeballs are sunken in their sockets, the pupils are dilated. The nasal mucous membrane is of a similar color and dry. The mouth emits a very unpleasant, penetrating odor, which sometimes may be noticeable at a great distance. The buccal mucous membrane is dry, dark brownish-red, and covered with a tenacious coating which is at first gray, later thick and chocolate brown; this coating is especially noticeable on the tongue. Later the mucous membrane loses its luster in spots, these areas soon changing into erosions, and becoming covered with pale yellow or dirty brown, tinder-like scabs; sometimes they are surrounded by bright red inflammatory tissue. These lesions are principally observed on the inner surface of the cheeks opposite the rows of teeth, on the gums, in the corners of the mouth, on the inner surface of the lips, especially in the region of the corner teeth, and on the borders of the lower surface of the tongue. Later the scabs drop off and in their place dark red ulcerations appear, which are covered with tissue shreds or with a dirty brown debris. In severe cases the ulcers may confluate forming large ulcerative areas, while the tongue may change into a dry, chapped, frequently entirely insensitive, shrunken body. ; The abdomen is very sensitive, especially over the region of the stomach, and it is either bloated or drawn up; loud peristaltic sounds may be heard when close to the animal. The 214 Typhus of Dogs, movement of the bowels is at first retarded, sometimes the animals after severe straining, pass balls of feces covered with mucous or blood, which may also contain blood; in other cases again severe diarrhéa may appear, the feces being fluid, bloody and very fetid. The mucous membrane of the rectum is occa- sionally greatly inflamed, very painful, and exceptionally also ulcerated. The body temperature is usually normal, only to- wards the end of the disease it sometimes drops below normal. The heart’s action becomes accelerated in the later stages of the disease, being weak and beating arhythmically. The respira- tion is quiet, and deep, exceptionally however in the presence of pneumonia it becomes accelerated. The urine which fre- quently can be passed only on pressing the greatly distended bladder, contains in severe cases a great amount of albumen, and more or less bile pigment. In some cases clonic spasms of the muscles of the head, or over the entire body, may be present. From the described clinical appearance of the disease, which was observed by Klett at the time of the outbreak at Stuttgart, various deviations are observed in the different outbreaks, especially in the extension and intensity of the ulcerative and necrotic processes on the buccal mucous membranes, which may even be entirely absent in fatal cases (Albrecht). In other cases there occurs considerable swelling of cheeks and lips, without ulcerations, a livid discoloration of the buccal mucous membrane, profuse salivation, and an acute swelling of the cervical lymph glands (in Scheibel’s cases the disease was always introduced by high fever). In some of the outbreaks nervous symp- toms predominated over the clinical manifestations (Bimes & Sérés). Among other symptoms may also be mentioned rigidity and ten- derness of the muscles, similar to those occurring in rheumatism; total paralysis of the hind quarters, hematuria (Mattel); in some of the otherwise typical cases the body temperature may be high at the beginning of the disease, and may be associated with severe chills (Mattel, Tremmel). There may be hemorrhages into the anterior chamber of the eye (Richter) with which keratitis may become asso- ciated (Pirl). Some patients may become hard of hearing, and later deaf (according to Richter probably as a result of the extension of the inflammatory process from the pharynx to the internal and middle ear). Course and Prognosis. The average duration of the disease is usually from 8 to 10 days; in most severe cases the animals usually die in from 4 to 6 days, exceptionally however death ensues towards the end of the second day. The rate of mortality fluctuates between wide limits in different epizootics. In the beginning of an outbreak sometimes almost every animal dies, while later the course of the disease becomes less and less severe. A very rapid development of the disease, complete inappetence, profuse diarrhea and great debility indicate un- favorable terminations, whereas a slow course and mild symp- toms warrant hopes for recovery. Young animals are more apt to withstand the disease than older ones. Diagnosis. Treatment. 215 In the favorable cases the animals sometimes recover en- tirely within a short time, even the ulcers in the mouth heal with remarkable rapidity; as a rule it requires from 2 to 3 weeks for the animals to regain their former appetite and dis- position. The recovery is usually complete; permanent sequelae develop only in exceptional cases (paralysis of a posterior ex- tremity, deafness). Diagnosis. The sudden vomiting, the inappetence and great depression, the ulcerations on the mucous membrane of the buccal cavity, the striking injection of the sclerotic conjunc- tiva, in connection with the infectious character of the disease, usually afford sufficient grounds for a diagnosis. Distemper is distinguished from this disease by the almost invariably present eatarrh of the conjunctivae and air passages, as well as by the fact that in distemper usually young animals become affected. In cases of gastro-enteritis resulting from dietetic errors or poisonings (meat poisoning), the ulcerative condition in the mouth is absent, besides the more uniform development of the clinical manifestations, the appearance of the disease in numer- ous localities, as well as the exclusive affection of dogs, are indications against poisoning. Ulcerative stomatitis and scor- butus develop more slowly, furthermore the violent vomiting and great depression seen at the beginning of this disease are absent. Treatment. For the violent vomiting washing of the stom- ach appears to be indicated; besides this Klett recommends sub- cutaneous injections of morphine, swallowing of ice, and the placing of ice bags over the region of the stomach. Mattel advises the administration of mild Russian or bitter tea, Wohl- muth prefers a tablespoonful of black coffee every hour, and tincture of valerian, 15 drops 3 times daily, later warm or Priesznitz bandages applied to the abdomen may diminish the pains. In obstipation or diarrhea, enemas (4% boracic acid, 1% alum solution) may be used. Bass administers internally ichthargan (ichthargan, gummi arab. aa 15.0, aqua 50.0, tea- spoonful doses every 2 hours), and ichthargan ointment exter- nally to the inner surface of the thighs. It is advisable to wash the buccal cavity carefully several times daily with fresh water or a mild disinfectant (potassium hypermang. in a 1% solution). The animals should be kept in a quiet place, and if they evince great weakness or lose considerable blood, subeu- taneous infusions of luke warm salt solution (0.8%) are indi- cated (Klett). a : ; After the vomiting subsides it is advisable to give the animals water acidified with hydrochloric or citric acid, while in the period of convalescence the animals should be given highly nutritious food (gruels, milk, eggs, and later meat). 916 Purpura Hemorrhagica. Literature. Hofer, Repert., 1852, XIII, 201.—Hiirlimann, Schw. A., 1896, 120.—Klett, D. t. W., 1899, 43.—Scheibel, B. t. W., 1899, 73.—Albrecht, D. t. W., 1899, 189.—Zschokke, Schw. A., 1900, 241.—Mattel, O..M., 1900, 491.—Tremmel, T. Zbl., 1900, 454——Wohlmuth, T. Zbl., 1905, 113. . 9. Purpura Hemorrhagica. Morbus maculosus equorum (Petechial fever, Acute haemorrhagic-anasarcous toxemia, Typhus equorum, Anasarque essentielle ou rdiopathique, [French]; Blutfleckenkrankheit der Pferde, [German]; Febbre petechiale, Morbo maculoso, [Itahan].) Purpura hemorrhagica represents an acute, non-infectious disease or process, probably caused by a septic bacterial intoxi- cation, as a sequel to a specific infection. It is principally characterized by extensive edematous infiltrations of the stb- cutaneous connective tissue, and by hemorrhages in the sweil- ings as well as in the mucous membranes, and in the internal organs. History. In olden times the disease was grouped among the putrid fevers (Febris putrida) or with the typhus affections (horse typhus), and it was thought to be essentially a primary decomposition of the blood. Later it was considered by some to be a form of anthrax (Roell), by others an affection related to scarlet fever of man (Perci- vall, Zschokke). Hering (1841-1850) recognized. its non-infectious nature and at the same time separated the disease as an independent af- fection (petechial fever) from other similar ailments. Recently the idea became generally accepted that the disease is to be taken as an intoxi- cation caused by bacterial toxins (Dieckerhoff, Ligniéres and others). The names given at the present time to the disease (petechial fever, Hering, purpura hemorrhagica) are based upon important symptoms, particularly the hemorrhages into the mucous membranes. The designation of horse typhus which was used in former times does not appear to be appropriate, as the disease differs decidedly from typhus affections of man, and especially from the abdominal typhus. Occurrence. The disease usually occurs sporadically, but many cases may appear within a short time, especially in stables where. influenza and strangles have existed. The disease is of importance on one hand because of its frequently fatal ter- mination, and on the other hand by the very slow course and the loss sustained by the continued disability of the patient for work. According to Javorsky in 1892-1901, 544 eases occurred in Moscow; the mor- tality among the animals received in the city hospital was as high as 0.3 to 0.8%, the average being 0.42%. Etiology. Purpura hemorrhagica with rare exceptions develops as a secondary affection, as a sequel to diseases in which suppuration or necrosis of tissue have occurred in any part of the body. Such diseases are especially strangles, pneu- Etiology. O17 monia, pharyngitis, influenza, in rare cases catarrh of the upper air passages or of the intestines, and pyemia of the sinuses of the head, caries of bone, exanthema of the skin, abscesses from any cause, and gangrenous areas in the subcutaneous connective tissue, or in the internal organs. As all of these diseases are associated with the presence of micro-organisms, and as the purpura hemorrhagica sometimes occurs in the form of an en- zootic, it may be accepted that micro-organisms are either directly or indirectly incriminated in the development of the disease. The indirect influence of the microbes, and the appear- ance of the disease, is substantiated by the fact that the affec- tion is not transmitted from infected to healthy animals, and cannot be transmitted artificially either by inoculation of secre- tions from the affected animals, or with blood (Haubner, Her- ing), nor by direct transfusions of blood (Arloing). The characteristic hemorrhages and serous exudations in the disease indicate a severe affection of the vessel walls which in all probability may be explained by the fact that chemical substances which circulate in the blood reduce the normal elas- ticity and resistance of the vessel walls. While this may be the result of a change in the blood, through which the nutrition of the walls of the vessel becomes diminished, and the watery consistency of the blood in itself facilitates the transudation of the blood plasma, a direct toxic action appears much more probable in consideration of the quick, sometimes very abrupt hemorrhages and serous infiltrations. Since, according to observations, pathogenic bacteria produce toxic substances, poison of similar origin may be suspected as the etiological fac- tor of this disease. ' According to Dieckerhoff’s conception these toxins form in necrotic or suppurative lesions which develop in any part of the body through the action of the. micro-organisms during the course of the primary disease. This supposition is very prob- able, as the diseases preceding petechial fever as a rule are those in which the abscesses or gangrenous areas which develop in the course of the disease communicate either originally or later with the outside world, whereby micro-organisms may readily gain entrance into the body. These organisms may then multiply in the exudates or the necrotic tissues, and produce chemical poisons which are later absorbed by the circulation. In-rare cases petechial fever apparently develops independently of other diseases, or in connection with fresh injuries (castra- tion), but even in such cases local necrotic processes cannot be excluded with certainty. Accordingly purpura hemorrhagica should be considered as an infectious disease in which, however, the incriminated virus (probably the pyogenic streptococcus which because of its ubiquity easily gains entrance into the necrotic tissue), exerts its pathogenic action indirectly with its specific toxic products. 218 Purpura Hemorrhagiea. According to the bacteriological examinations of Ligniéres (1895- 1898), the internal organs and the blood of animals dead from purpura hemorrhagica contain, as a rule, besides other bacteria, streptococci, principally pyogenic, and more rarely streptococci of strangles. The bacillus equisepticus is also met with relative frequency (among 26 cases this organism was found in 9 instances), and this seems to indicate that both diseases are closely related. This may be also substantiated by observations in Argentine where influenza occurs mostly in a very acute form without inflammation of the thoracic organs and purpura hemorrhagica very frequently develops as a sequel (similar observa- tions were made by Theiler in Transvaal). Accordingly both bacteria play a part in the etiology of purpura hemorrhagica, the severe symp- toms, however, are caused by the streptococci or their toxins. Ligniéres failed to produce the disease even in a single instance in its characteristic form, in spite of the fact that he injected horses intravenously with quantities up to 8000 g. of streptococci culture, and subsequently exposed the animals to cold rains. He considers the im- portance of the streptococci proven, however, from the cbservations made by Frasey, who has seen a disease corresponding clinically with purpura hemorrhagica develop in two horses, which had been injected with highly virulent cultures of streptococci for the preparation of anti- streptococcic serum. The fact that purpura hemorrhagica develops quite frequently as a sequel to strangles and influenza, appears te indicate the indirect association of streptococci with the disease (Bruin observed the development of purpura hemorrhagica in its severe form in two cases after the accidental injury of a vein in puncturing an abscess in strangles) Cadéae also considers purpura hemorrhagica as an intoxication, which, according to his view develops as the result of vasodilatatory toxins of various bacteria, especially of different pyogenic cocci, in animals which have been weak- ened by another disease. Mouilleron & Rossignol, as well as Cormier, also attribute the greatest importance to the streptococci, especially on the ground of the favorable results which they have obtained in the treatment of the disase with antistrepto coceus serum, although they do not deny the possible action of other micro-organisms. Coquot considers the disease as a Pasteurellosis. Contrary to other observers Javorsky succeeded in only 7 cases out of 148, in demonstrating the occurrence of purpura hemorrhagica as a sequel to other affections (twice strangles, 5 times pleuro-pneumonia). Wohlmuth also believes that the disease may develop independently, and therefore he distinguishes an idiopathic and symptomatic form, in which the vascular system, especially the intima of the capullaries, is always the point of attack for the toxins which produce the disease. Recently Baruchello & Nori, and later also Perrucci expressed the improbable view that purpura hemorrhagica represents a piroplasmosis, as they found protozoa resembling piroplasma in the red blood corpuscles of four affected horses. However, the severe initial symptoms (high fever), which were observed ir these cases indicate that these affections were not true cases of purpura hemorrhagica. The mode as well as the determining factors of natural infections are not yet sufficiently clear. It has been observed that the disease occurs principally in badly ventilated stables, with dirty floors, but it also occurs in well groomed horses kept under favorable conditions. The disease is most frequent in the spring and in the beginning of summer. The age of the animals appears to have no influence except that colts under two years of age do not become affected (Dieck- erhoff) ; otherwise there appears to be no factor which affects Anatomical Changes. 219 the susceptibility of the animal, nor does the care the horses receive or the work they do exert any influence. Anatomical Changes. The characteristic lesions of the dis- ease are the hemorrhages in the skin and in the mucous mem- brane, as well as in the subcutaneous and submucous connective tissue, in association with extensive, very marked, edematous swellings. Inflammation and tissue necrosis may develop as ee i processes with swelling of the affected parts of the ody. Upon the cut surface of the edematous swelling the subcu- taneous connective tissue forms a yellow, gelatinous layer of several centimeters thickness, which shows dark red hemor- rhages and in some cases contains cavities filled with purulent ichorous fluid, or with necrotic tissue. The gelatinous infiltra- tion extends also between the muscles while the muscle sub- stance itself appears pale grayish-brown or clay color, and friable, as a result of parenchymatous and fatty degenerations of the muscle fibers. The affected muscies feel greasy to the touch, and are sprinkled with small hemorrhages. In different places small areas of the muscles are necrotic and changed to a clay-like detritus, which sometimes appears dirty brown-red from admixture of blood. Hemorrhages may also occur in the tendons and tendon sheaths, under the periosteum, or in the joints; in the latter the cartilaginous tissue may even become necrotic (Prevost). Of the mucous membranes those of the nose, pharynx and larynx become affected in the first place, then those of the stom- ach and the small intestines. The mucous membrane is affected less frequently in the deeper air passages and in the cther parts of the digestive tract, as well as in the genital organs. In addi- tion to catarrhal injection and swelling, the mucous membrane, as well as the submucous connective tissue of the intestinal canal, also in the muscular layer and under the serosa, small punctiform or streak-like or even larger hemorrhages may be present. The loose connective tissue surrounding them is always more or less gelatinously infiltrated. Over the larger extravaza- tions the mucous membrane is often necrotic, or after the pale yellow necrotic parts have been thrown off, irregularly formed ulcerations develop which are covered with dirty tissue shreds. In the intestines they may extend to the peritoneum, or the intestinal wall may be perforated and lead to purulent or ichorous peritonitis, while in the nose the ulcerative process may cause a destruction ot the nasal septum. Hemorrhages are as a rule present also in some internal organs, especially in the lungs and the spleen, and also under the capsule of liver and kidneys. The lungs may contain hemor. rhagic areas the size of a fist, the cut surface may show spots like those of a tiger’s skin, which are the result. of blood aspirated into the bronchi. The spleen is sometimes consider- 990 Purpura Hemorrhagica. ably enlarged due to hemorrhages in its tissue and under its capsule, and sometimes a rupture of the spleen and a fatal internal hemorrhage may be observed. Far less often are instances of fatal bleeding into the retroperitoneal or into the perirenal connective tissue, into the digestive tract, or into the air passages; finally hemorrhages may also be found in some cases in the inside of the eyes, in the bone marrow, in the heart muscles, and under the pericardium. The immediate cause of death usually is septicemia, pyemia or gangrenous pneumonia, less frequently asphyxiation may be observed. Autopsy may reveal the mode of origin of the disease by disclosing the presence of older organic changes. Symptoms. The disease usually commences with the appearance of small punctiform or linear hemorrhages in the nasal mucous membrane. In some.instances the animals do not manifest any indications of disturbed health, while in other cases the appetite becomes somewhat diminished in the earlier stages, and the patient manifests slight dullness and depression. Later the hemorrhages in the mucous membranes become more numerous, and those lying close together confluate, so that extensive blood extravasations result. At the same time there is a yellowish mucous discharge from the nasal mucous membrane which dries on the surface first to yellow, later to dirty brown crusts. In severe cases the mucous membrane covering the hemorrhages becomes necrotic, and ulcerations develop. In this condition the discharge which at first is scanty becomes more profuse, discolored, mixed with shreds of necrotic tissue, and not infrequently also with blood The discharge emits a fetid odor. In the meantime swelling of the eyelids is frequently observed and if they are forcibly spread apart a reddish fluid or even pure blood flows out of the slit; in such cases the bulbar as well as the tarsal conjunctiva, shows shallow hemorrhages (exceptionally necrosis of the conjunctiva and hemorrhages into the inside of the eyes [Roell] may be observed, also atrophy of the optic nerve [Schindelka]). In all of the 148 cases observed by Javorsky hemorrhages were present on the nasal mucous membrane On the other hand they were found in only 58 cases in the mouth and in only 38 cases on thu conjunctiva. ‘Immediately after the appearance of the hemorrhages in the nasal mucous membrane, swelling of the skin and the subcu- taneous connective tissue make their appearance. In some cases numerous urticaria-like vesicles develop over the entire body, which disappear after a certain time, or confluate form- ing dollar-sized flat roundish swellings (Figure 39; Kleinpaul observed simultaneous shedding of the hair). In most instances, however, diffuse swelling developed, especially on the extremi- ties, on ‘the chest and abdomen, especially on the sheath and udder, and sometimes on the front part of the head (Figure Symptoms. DYAL 40). The swellings often grow rapidly assuming great dimen- sions, so that the outline of the affected part of the body which is much deformed, becomes lost. In severe cases the circum- ference of the extremities becomes enormous, so much so that sometimes the legs from the coronary band to the elbow or to the knee swell to 2 or 3 times their normal size, and they appear like posts on which some transverse furrows are the only indications of the joints. On the head the swelling first affects the alae of the nose and the lips, soon however the lower part of the face becomes affected, and the fore part of the head pete Soe caper i eee Sel PA Aa | Sa Fig. 39. Purpura hemorrhagica. Eruptions resembling urticaria at the beginning of : the disease. may become so broad that the transverse diameter greatly ex- ceeds that of the upper portion of the head, the nose piece of the halter making a deep impression, and the head in such cases resembles somewhat the head of a rhinoceros (Figure 40). The swellings are characterized by being always sharply defined from the healthy surrounding parts. They are firm, almost of the hardness of a board, so that the surface may be pitted only with difficulty, the resulting depressions disappearing but slowly. The skin over the swelling becomes stretched, and from its surface a yellowish tenacious serous fluid oozes out which later dries, forming brown crusts. In the flexor side of the 999 Purpura Hemorrhagica. joints the skin shows cracks which expose a moist reddened wound. In places where the stretching of the skin is the great- est, therefore, especially over the bony protuberances, as well as in the places where it is exposed to outside pressure, excep- Fig. 40. Purpura hemorrhagica. Swelling of the forehead and of the lower chest. tionally also in other parts of the body, for instance on the upper lip (Figure 41), the skin becomes insensitive in circum- scribed areas, cold and dry, and takes on a darker color. Soon dry, round portions of skin as large as‘a dollar or even larger, dark brown and parchment-like are separated and fall off. The Symptoms. 993 gangrenous process may extend deeper, affecting the muscles, while on the bridge of the nose and below the carpal and tarsal joints it may extend to the bone, leading to ugly ulcerations, which continually discharge a purulent, ichorous, fetid secretion containing necrotic tissue shreds. According to Javorsky’s statistics swellings on the abdomen are observed in 47.3%, on the posterior extremities in 74.3%, and on all 4 extremities in 45.5% of the cases. : The swelling impairs the physiological functions and the mobility of the affected part of the body. With the increase of the swelling of the nasal mucous membrane the res- piration becomes snuffing, and is especially difficult during the act of inspiration. The labored respira- tion is still more severe -when the swelling extends to the folds of the mucous membrane in front of the larynx, or to the mucous membrane of the larynx itself. In such cases the animals show all the indications of an inspiratory dyspnea (anxious look, whistling or rattling respira- tion, spreading of the legs, forced €X- Fig. 41. Purpura hemorrhagica. Commencing necrosis tension of the ; of the skin on the swollen upper lips. thorax, with the intercostal spaces sunken in) and with further progress of the stenosis asphyxiation may result. The great swelling of the forehead renders the motion of the jaws and with it mastication more difficult, while the infiltra- tion of the pharyngeal mucous membrane and of its underlying connective tissue interferes with deglutition, so that in severe cases the animals are unable to take nourishment, although their appetite is not impaired, or they succeed only with great effort in swallowing small quantities of food or a little water. The swelling of the extremities interferes more or less with the gait of the animals. At first and even later in mild cases, 224 Purpura Hemorrhagica. the disturbance is manifested only by stiffness and clumsiness in gait and inability to lie down, or if they succeed in this, in their inability to rise. In the presence of large swellings they remain motionless-in one place, and it is impossible to make them move (the inability to move may be partly due to involve- ment of the muscles). The swelling of the sheath hinders the animal from protruding the penis, so that the urine trickles out of the narrow opening of the sheath, and its borders as well as the surrounding parts of the skin become irritated by it. The nutrition of the animals, except in the very mild cases, is always insufficient, through the difficulty in mastication and deglutition which has already heen mentioned. Although the ap- petite remains unimpaired fo: a considerable length of: time, and in mild cases even during the entire course of the disease and the thirst is even increased; in severe cases disturbances in the appetite are noticeable which are due to the involvement of the gastric mucous membrane. Symptoms of colic some- times follow the severe changes, and these indicate hemorrhages and inflammatory edematous infiltrations of the gastric and intestinal wall. The colic may occur either in severe attacks or less severely but more continuously. In some cases they are followed by manifestations of a rapidly progressing anemia and by collapse, which is an indication of an internal bleeding into the abdominal cavity, while in other cases paralysis or perforation of the intestine lead to sudden death. Feces are passed in moderate quantities, a bloody consistency pointing towards intestinal bleeding, while frequent movements of ‘the bowels and a covering of the feces with a muco-purulent ma- terial points to inflammation of the rectum. In the presence of a severe inflammation of the intestines profuse diarrhea appears. In severe cases the urine contains albumen and also blood. In mild cases the body temperature remains through the entire course of the disease at normal height, or is only very slightly elevated. In the presence of necrosis and ulceration of the skin, and of the mucous membrane, the fever may rise high from absorption of septic substances. The character of the fever in such cases indicates a septic form. The tempera- ture may also change in those cases in which the affection devel- oped immediately after a febrile affection (Fig. 42), or if com- plications arise during the course of the disease. In the beginning the heart’s action is somewhat accelerated but sufficiently strong. Later it becomes excited, and because of the difficult respiration or the changes in blood pressure due to hemorrhage and to pyemia or septicemia, the heart’s action becomes very rapid and throbbing, while the pulse steadily diminishes in volume. A microscopical examination of the blood shows nothing characteristic, with the exception of an occasional hyperleuco- eytosis (according to Smith the quantity of albuminous sub- ied stances and fats in the blood is increased and iron is diminished). Modification of the Course. The clinical picture de- scribed may show marked modifications. The disease may become checked in any stage of its de- velopment, and pass on to re- covery. On the other hand in some cases in the early stages the original disease, to which purpura hemorrhagica forms a sequel, may yet per- sist; but in a still greater number of eases the disease itself may be changed by the appear- ance of compli- cations arising during its de- velopment. One of the most frequent complications ig pneumonia, which usually is lobular in character, and develops in connection with hemorrhages into the lung tissue; and may Fever Course. §_ [3 is ee % pb 03 eh ey rt log os Fag se 0% PoTRSG f) 004 i ar O%RS.14 so losdazy os 0: aT | Pharyngitis Urticaria [T] \Petechiae in the Nose Swelling of Legs TTT TTT TTT TTT TUTTE . Swelling of Nostrils Ye} 6 ' New Petechiae 92, 12} 98 | sz] iz] es] se] te testina ns New Petechiae WOW CUT TT | I Swellings almost CTT TT disappeared, } T 1 condition d Healthy €% | 2h | [OF | Ge] ee | ze] 98] se | te] ce} 2c] te] oc | ez DTT mil LTETTHTT , that of fibrin, water Fever curve in purpura hemorrhagica. Fig. 42. be, less frequently, the result of the aspiration of necrotic parts ef mucous membrane, assuming then often a gangrenous form. 226 Purpura Hemorrhagica, Rapid and labored respiration, especially in cases when the upper air passages are not markedly constricted, in associa- tion with a rise in temperature, are indicative of pneumonia, and renders a careful examination of the thoracic organs necessary. A severe and not infrequently ulcerative inflammation of the stomach and intestinal mucous membrane also develops with relative frequency, and causes a putrid diarrhea, which greatly weakens the animal. In the cases with unfavorable termination the clinical symptoms are almost invariably terminated by manifestations of pyemia or septicemia. They usually develop either from the above cited causes, or from the sores which develop on the body of the animals when they persistently lie down. According to Payrou petechial fever as it is observed as a sequel to distemper, may be™manifested either as a toxemic (lymphatic) form, brought on by the absorption of toxins into the blood, or in a septicemie form caused by a strepto- coceus infection of the blood. The former develops in the second week after the beginning of strangles, when, in the presence of a moderate fever, the extremities slowly swell from below upwards, and the nasal mucous membrane manifests only small petechiae. The course is frequently mild. The second form develops with high fever, and extensive petechiae, running a peracute course, causing swellings everywhere, especially on the head and on the conjunctivae, which have a great tendency to necrosis. In these cases the disease usually terminates fatally in from 8 to 10 days. As a result of the great frequency of intermediate forms the sepa- ration of these two types might often be very difficult, and it is doubtful whether such a classification is justified. ; Course. The course of purpura hemorrhagica varies from case to case. From the very mild forms which manifest only petechiae of the nasa] mucous membrane, and a slight simulta- neous swelling of the skin and the symptoms of which may dis- appear inside of two or three days, to the cases of extreme distortion of the body and resulting in death from asphyxiation or sepsis, all the possible degrees may be observed. In the successive development of the symptoms the affection of the nasal mucous membrane usually appears first, and it is hardly ever absent. This is followed in one or two days by a swelling of the skin, and only later by the affection of the pharynx, whereas the involvement of the intestinal canal is usually ob- served only in advanced stages of the disease. However, there are rare cases where the sequence of symptoms differs; thus the edema of the-skin may precede the development of petechiae i in the nose, or severe colicky symptoms may develop in the begin- ning of the disease. The evolution and course of the disease depends eapacially on the localization and the more or less rapid development of the hemorrhages and of the edematous swellings. Apparently severe cases, in which however the changes are exclusively con- fined to the nasal mucous membrane, the skin and the subcu- taneous connective tissue may terminate in complete recovery even when the skin becomes necrotic over a considerable area; on the other hand affections of the internal organs, as well as hemorrhages and inflammations, exert an unfavorable influence al Course. Diagnosis. 227 on the course of the disease, and such cases usually terminate fatally. ; In the favorable cases the swellings after reaching a certain degree retrogress either rapidly or gradually. Frequently, however, the improvement is only temporary, as the condition later becomes aggravated again, and with such variations the disease may run for several weeks until finally the animal recov- ers. The average duration of the mild cases may be placed at about two weeks, although it may occasionally extend over a period of 6 to 8 weeks. In cases where large areas of the skin become necrotic it may require several months until a definite recovery takes place, and even in such cases the recovery is not complete, as in place of the extensive wounds contracted scars remain which interfere with the function of the extremities, and thereby reduce the value of the horse for work. In fatal cases the duration of the disease also varies. There are cases in which the swellings form with such rapidity and become so extensive that death ensues in from 3 to 5 days (Dern- bach saw a horse in which death occurred after 7 hours as a result of a hemorrhage in the neighborhood of the medulla oblongata). Complications (gangrenous pneumonia, enteritis, pyemia, septicemia) usually develop only after the swellings have progressed extensively and have produced functional dis- turbances as well as necrotic processes; up to that time, how- ever, usually 1 or 2 weeks have elapsed. If any of these com- plications have appeared death always ensues after several days. Diagnosis. Recognition of the disease is difficult as a rule only when it is associated from the beginning with fever, or when edematous swellings and hemorrhages appear in the course of a preceding febrile affection. Hdematous infiltrations may develop from local causes (phlegmons, lymphangioitis) as well as in general infectious diseases (anthrax, malignant edema) ; they may, however, be distinguished from the swellings of purpura hemorrhagica by the diffused borders and by the localization of the inflammatory processes. Besides this the swellings in purpura hemorrhagica are usually sharply circum- scribed and occur in most instances symmetrically on both sides of the body; they also appear after or simultaneously with the development of petechiae on the nasal mucous membrane. In the early stages of the disease urticaria may also come under consideration, as it is sometimes manifested by extensive and sharply circumscribed swellings of the skin; however, in this affection the petechiae are absent on the nasal mucous mem- brane, and the eruptions disappear entirely after a short time. Acute glanders may likewise resemble purpura hemorrhagica to some extent, especially in cases in which the swelling of the nasal mucous membrane and its surrounding tissue, as well as of the extremities and abdomen develops rapidly; however, in 998 Purpura Hemorrhagiea. such cases there are no petechiae on the nasal mucous mem- brane, but nodules and ulceration, and at the same time there is also a swelling of the submaxillary lymph glands. In addi- tion to this, the rapid development of the swellings on other parts of the body is always accompanied by fever and by symp- toms of a general infection (it must be remembered that pur- pura hemorrhagica may develop in the presence of glanders). Prognosis. This is very uncertain in consideration of the varied course of the disease, and therefore should be made with especial care. Although with proper treatment on an average 40-50% (according to Javorsky 60-65%) of the affected animals recover, the mortality fluctuates between wide limits. The slow development of the hemorrhages and swellings, and their pres- ence in small numbers, are indications of a favorable course, whereas their rapid increase and extension point toward an unfavorable prognosis. There are cases, however, which show a very severe affection from the onset, and in which after a certain time sudden improvement: is noticeable, the animals finally recovering. This is especially the case when by proper treatment the development of threatening complications is pre- vented. A recovery may be expected as long as the patients are without fever or have only a slight fever, and take nour- ishment at least in moderate quantities. High fever renders the situation usually grave, as it points to septic infection or to inflammation of internal organs. Other unfavorable indications are pronounced cyanosis or yellow discoloration of the mucous membranes, the presence of albumen, or blood in large quan- tities in the urine, continuous lying down, frequent and weak heart action, further the excessively rapid disappearance of the swelling. The latter apparently favorable symptom indicates in most instances a rapid breaking down of the tissues, or that great quantities of blood or blood plasma have, under the influ- ence of the high fever, transuded into the internal organs. The development of after affections should also be taken into con- sideration in forming a prognosis, as they are of a decided influence in determining whether treatment extending over a long period of time is justified, in view of the inability of the animals to work and the expense of such prolonged treatment. At the clinic at Budapest between 1887-1908, out of 296 affected horses 167 (56.4%) recovered; the numbers of maximum and minimum recoveries in these years was 20 and 95%. In the Prussian army in the years of 1895-1903, 149 horses became affected, of which 110 (79%) recovered (the maximum and minimum recov- eries in these years were 56.2 and 85%). Treatment. Symptomatic treatment has a great influence on the further development of symptoms and on the termina- tion of the disease, especially as it is not infrequently possible to avert the danger of asphyxiation, and to prevent the appear- ance of complications. Above all it is necessary to assure suitable feeding of the Treatment. 229 affected animals, and to provide a sufficient supply of fresh water. Hydrochloric or sulphuric acid (8-10 g. to a pail) may be added to the water and in the presence of fever wine or alco- hol (11%-1 liter to a pail). If the animals show difficulty in mastication and swallowing they should be given green food and bran—or flour—gruels. If this condition becomes aggra- vated the animals may be fed artificially per rectum, and in this manner they may retain their strength for a considerable time. Pure fresh air is likewise an important requirement for a favorable course, and it is advisable to keep the animals out of doors in the summer time and in bad weather in roomy box stalls. The halter should be removed as it may have a harmful effect by its pressure on the swollen cheeks and nose. Wounds, ulcers and abscesses require antiseptic surgical treatment. In the presence of a considerable swelling of the nasal mucous membrane the nasal cavities should be carefully syringed 2 to 3 times daily with a non-irritating disinfecting solution (3-4% boracie acid, 2-3% creolin or lysol solution, 144-1% alum solution). The swellings of the skin are in many eases favorably influenced by rubbing with spirits of turpentine 2 to 3 times daily, since under this treatment gangrene of the skin occurs more rarely. Various other fluids may be used for the same purpose, especially Burow’s solution with camphor, which is highly recommended by Dieckerhoff (Camphorae 50.0, Plumbi acet. 200.0, Alum. 100, which is used in the proportion of 1 tablespoonful to 1 liter of water), Goulard’s extract, sub- acetate of lead or alum solution (5%), spirits of camphor, etc. Counterirritants should positively be avoided as the stimula- tion of an inflammation enhances the development of necrosis of the susceptible skin. If in spite of this treatment gangrenous abscesses develop over the swellings of the skin, such defect as well as tears ‘ should be treated after the removal of the necrotic tissue shreds, by washing with one of the above mentioned solutions, or still better they may be dusted with a drying powder. For this pur- pose charcoal powder containing corrosive sublimate (charcoal mixed with a 1% corrosive sublimate solution and then dried), further Dermatol, Alumnol, Iodoform, Thioform, Tannoform, etc., may be used to good advantage. A 5-7% creolin liniment (smeared on wool and placed on the wound) may also act bene- ficially whereas tinctures (tincture of myrrh, tincture of aloes) are less effective. This treatment should be continued until the wound has filled up and healed over, but in the meantime pro- tuberant granulations which may develop should be controlled by cauterization (nitrate of silver or with fuming nitric acid). Sores of decubitus should be treated in like manner. 'T'he con- junctivitis may be controlled by blowing sodium borate into the eye, while in gangrene of the conjunctiva washing with a 2% creolin solution is advised. If the patient is threatened with asphyxiation as the result 930 Purpura Hemorrhagica. of marked constriction of the upper air passages, the perform- ance of tracheotomy is advisable. The stenosis of the nose may be relieved by elevating the median alae of the nostrils passing threads through them and tying them together over the bridge of the nose, or according to Johne’s suggestion, by the introduction of tin tubes into the nostrils. These | methods, how- ever, are not to be recommended as the threads and even more the tin tubes may produce necrosis of the skin and of the mucous membrane. The wounds caused by tracheotomy should be cleaned 2 or 3 times daily, and in order to prevent a harmful pressure between the outer plate of the tube and the skin a ring of cotton should be inserted. The operation may even be undertaken before asphyxiation threatens, especially in cases when a rapid development of the swellings indicates the ap- proach of a dangerous nasal stenosis. In consideration of the difficulty in swallowing which is present in most instances only such remedies should be used in the treatment of gastro-enteritis as may be administered in the drinking water or in soft food. Calomel is to be mentioned as a remedy, as it not only has a disinfecting action, but also facilitates the absorption of the transudated serous fluid as a result of its uniting with the blood albumen (Jendrassik) (3-4.0 g. daily, divided in several doses), then boracic acid, tannin, sugar of lead, also ichthyol (sodium or ammonium, sulfo-ichthy- olicum, 20-30 g. pro die), cinchona bark, etc., may be given. In cases where the rectum is severely affected enemas of astrin- gents and disinfecting fluids (for instance 2-4% lukewarm boracic acid) are indicated. If improvement becomes apparent the convalescing animals should be exercised out of doors for a short time 2 or 3 times a day, as soon as the fever disappears, and the loss of the body fluids should be restored through profuse, rich nourishing. Various remedies were recommended for the purpose of an abortive treatment, but none of these can be considered as specific. Thus Azary recommended the fluid extract of hydrastis canadensis (5-8.0 g. subcutaneously). Payrou advised adrenalin (15-25 drops in Y, 1. of water) early in the disease, because of its vasoconstrictor action; while recently iodine and silver preparations are used very extensively. Dieckerhoff employed intratracheal injections of Lugol’s solution (iodi puri 1.0, potass. iodati 5.0, aquae dest. 100-200.0; 30-40 g. for one dose; at the same time 10-20 g. of iodide of potassium may be added to the drinking water). This treatment has been given extensive trial in practice, but without any remarkable results. The literature shows that out of 96 cases treated in this manner only 61 horses (63.5%) recovered (in the Prussian army inside of three years out of 41 horses 31 recoveries, 75% ) and some of the authors (Zschokke, Cadéac, Lemke, Johne) have even observed bad effects from this treatment (gangrene of the mucous membrane of the trachea, symptoms of poisoning). Jodvasogen, which has been introduced into veterinary practice by Jess, has also been tried (intratracheal injections of 15-20 g. of a 6-10% solution, or 50-80 g. per os daily). The results, however, have ee ee Treatment. 931 been doubtful, as alongside of the favorable results reported by Straube, Thomas, Clausen, Richter & Feuerhack, there are those of Zerler & Giesenschlag as well as Gutzeit, which are unfavorable. The value of the iodipin treatment as recommended by Franz, Thomas and Tantos (10 g. of a 25% solution of iodipin injected daily subcutaneously, and on every second day 50 g. of a 10% iodipin solution per os), cannot be judged at the present time. _ Of the silver preparations Dieckerhoff recommended Crédé’s colloid silver or Collargol (50 g. of a freshly prepared 1% solution intra- venously 2-4 times a day at the beginning of the disease) ; the results from this method of treatment varied. While Thomassen, Zimmermann, Roder, Dresdow, Mollerau and others obtained satisfactory results, the experiences with this method in the Prussian army were not so encour- aging; in the years 1899-1902, 51 animals were treated, with Collargol, of which 40 (78.5%) recovered, while of 35 animals which were treated by other methods or were not given any treatment 26 (74.3%) recov- ered. At the Budapest clinic in the years of 1898-1902 25 animals received the silver treatment, and 14 (56%) recovered, while 16 other cases were treated otherwise, of which 8 (50%) recovered. It was observed that even when this remedy was employed at the earliest stages of the disease it did not influence its normal course (Fettick). Payrou declared this remedy to be worthless, and Brohle observed a fatal termination in three cases as a result of embolism of the pulmonary arteries following an intravenous injection of 0.4:40.0 g. Collargol. Conditions are similar in the case of Ichthargan (50 g. of a 1% solution intravenously), as recommended by Lange and Jost. The results obtained with this preparation in the Prussian army in the years of 1904-1905 were not uniform. Ztirn calls attention to the hemolytic and strongly irritating action of this remedy, and therefore recommends only 0.1 to 0.2% solutions for intravenous injections. (Lévy saw after an injection of 0.5 g. of a 1% solution, the development of severe toxic symptoms in a horse of advanced age). Bertelotti employed spirits of turpentine (5.0 g. intravenously), Howe oil of turpentine (per os), Pelz, Thomas and Feuerhack tallianin (10-30 ec. intravenously), Gorjaew corrosive sublimate (10 ec. of a 1% solution intravenously), Beck lastate of silver or Actol (40 ce. of a 1% solution 3 times daily intravenously), apparently with good results. Serum Treatment. Stimulated by the good results obtained in human medicine with Marmorek’s anti-streptococcus serum in strepto- coccus infections, various authors used the serum for the treatment of purpura hemorrhagica in horses, according to the prevailing idea that the disease is also caused by a streptococcus infection. This appeared justi- fied in view of Ligniéres’ assertion that the streptococci associated with purpura hemorrhagica was identical with the pyogenic streptococci of man, and in view of his good results with Marmorek’s serum in mice. The treatment consists of subcutaneous injections of 10-40 g. serum, 3 to 6 times daily, or repeated even every hour. (Sommermeyer injects first 10 g. of immune serum subcutaneously and later 20 g. normal serum intravenously). The reports published so far on the use of Marmorek’s serum are favorable (Ligniéres, Mouilleron & Rossignol, Peuch, Pecus, Maier who used in one case 190 and in another 440 g. serum inside of two weeks!), as well as about the Jess-Piorkowski serum prepared in a similar way (Sommermeyer, Bolz). Ligniéres’ results show only two deaths in 232 Purpura Hemorrhagica, 15 patients, the tabulation of Mouilleron and Rossignol only 11 deaths with 62 patients, while of 209 cases treated by other methods 126 suc- cumbed to the disease. The Pasteur Institute of Paris has recently prepared a polyvalent serum with: the aid of streptococci of man and of the horse, and with this serum Payrou obtained favorable results in army horses (of 45 cases only 7 died, 15.5%). However, as in the’ etiology of purpura hemorrhagica other bacteria appear to have also a part and Cadiot obtained equally good results with normal blood serum (100-125 g.), the value of the rather expensive serum treatment cannot be definitely judged at the present time. Literature. Percivall, The Vet., 1844.—Hering, Spez. Path., 1858, 871 (Lit.).— Dieckerhoff, Spez. Path., 1392, 417; "BL t. W., 1898, 541 —Mouilleron & Rossignol, Bull., 1898, 168. —Lange, Z. f. Vk., 1903, XV, 117.—Jost, B. t. W., 1904.—Ligniéres, Bull., 1895, 587; 1898, 702; 1903, 363.—Javorsky, A. £. Tk., 1905, XXXI, 601.— Payrou, Bull, 1905, 491,—Mollerau, Rec., 1905, 24.—Drouin, Rev. gén., 1906, VII, 289.—Barthel, Z. f. Vk., 1906, XVILL, 430 (Lit.).—Franz, D. t. W., 1906, 38, Purpura Hemorrhagica of Cattle. Recent literature contains several reports (Schleg, Eichhorn, Frank, Réder, Plate, Ehrhardt, Kop- pitz, Reinhardt and others), which render the occurrence of purpura hemorrhagica among cattle, especially younger animals, and perhaps also in buffalo (De Does) probable. In the respective cases there was a diminished appetite and cessation of rumination, as well as great depression and weakness. At first small, later more extensive hemor- rhages occurred in the skin, and in the subcutaneous connective tissue, in the conjunctivae, in the mucous membranes of nose and lips, and in the udder; while in some cases edematous swellings, although usually only: in a moderate development, were observed on the extremities, and on the abdomen. From the surface of these swellings a bloody serous fluid oozed out. At the same time a bloody discharge from the nose and the vagina was occasionally observed, and the mash-like excrements were also mixed with blood. In exceptional cases there appeared a necrosis over the hemorrhages in the buccal mucous membrane, and in the conjunctivae, as well as in the skin. In some of the cases the temperature remained normal, in others, however, the disease was inau- gurated with high fever. In the cases where the animals were not slaughtered during the disease, recovery usually followed in from six to ten days, but in some instances not for three weeks, while some of the animals died from intestinal hemorrhage or septicemia. Autopsy usually revealed more or less extensive hemorrhages in the muscles, in the serous and mucous membranes, in the subserous and submucous connective tissues,as well as in the internal organs. In some cases there was also yellowish-gray or grayish-brown discoloration of the liver. The spleen usually appeared normal. In the majority of cases the healthy animals became affected with- out any apparent cause; exceptionally the disease developed in connec- tion with a local inflammatory process, especially mastitis (Robert), puerperal inflammation of the uterus (Augstein), or rheumatism of the joints (Zehl). The disease was also observed as a stable infection, although a transmission from animal to animal could not be established in these cases. ; Before establishing a diagnosis of purpura hemorrhagica it should be differentiated from other diseases in which hemorrhages occur, espe- cially the various kinds of septicemias (anthrax, malignant edema, hemorrhagic septicemia, ete.). The disease is mairily distinguished from these affections by the absence of fever in the early stages. In Dogs. In Man, 933 In the treatment the same principles apply as given in purpura hemorrhagica of the horse. In the cases where in one stable several animals became affected consecutively, the disease was checked by changing the feed and the drinking water (Minder) as well as by dis- infecting the stable (Eichhorn). Literature. See Reinhardt, Monh., 1909, XXI, 221.—Zehl, B. t. W., 1909, 715. Purpura Hemorrhagica of Dogs. Lellmann observed in a 6-year old dog symptoms which indicated an affection of purpura hemorrhagica. The emaciated animal, which had no fever, showed weakness and a weak heart action, also swelling of the hind parts, ascites, epistaxis, hematuria, and bloody excrement. The autopsy revealed hemorrhages in the spleen, liver, kidneys, in the serous membranes, in the skin, in the subcutaneous connective tissue, and in the muscles. In another case there was anemia (pale mucous membrane, small pulse, anemic heart murmurs) bloody vomiting and diarrhea, also numerous hemor- rhages in the skin which comprised the principal manifestations. The autopsy findings in this case resembled those of the first. Lellmann considers both cases identical with purpura hemorrhagica of the horse. (B. t. W., 1897, 509; 1902, 266.) Raitsits observed in a dog bluish-red, later confluating spots on the abdomen and on the inside of the thighs, petechiae on the con- junctivae, swellings of the gums, hazel-nut sized abscesses on the phre- num of the tongue, albuminuria and hematuria. The autopsy revealed hemorrhages under the skin, also in the conjunctivae. and a hemorrhagic inflammation of the rectum. (A. L., 1906, 421.) Purpura Hemorrhagica of Man. This disease (morbus maculosus Werlhofii, purpura hemorrhagica), is caused according to Kolb, by a small Gram-positive bacillus, the bacillus haemorrhagicus, while accord- ing to Letzerich it is caused by the bacillus purpurae haemorrhagicae. The hemorrhages which appear in different parts of the body in asso- ciation with the disease cause it to somewhat resemble purpura hemor- rhagica of animals; however, the possible relations of the two diseases have not yet been established. It should be mentioned that in a case reported by Bock a stable attendant became affected with Werlhof’s disease several days after the death of a horse with purpura hem- orrhagica. Literature. Kolb, Arb. d. G.-A., 1891 VII, 60.—Bock, Z. f. Vk., 1902, XIV, 117. Scarlatinoid of Horses. Under this name Champetier described a disease of young horses which resembled scarlet fever of man. In a mild form of the affection there is a fever reaching 103-104°F., inappe- tence, frequent pulse and cough, injection and petechiae of the mucous membranes, further a peculiar pustular exanthema of the skin, and edematous swellings of the extremities. In the more severe form the enumerated symptoms are more intense and bronchial catarrh, catarrhal pneumonia, and nephritis may also develop. (Les maladies du jeune cheval. Paris, 1892.) : The latter of these forms has also been observed by. Marek in an 8-year old mare. Simultaneously with a marked swelling of the nasal mucous membrane diffuse edematous swellings appeared on the abdomen and on the hind extremities; nodules developed on the skin of the rump, the head and neck, and later round ulcerations appeared 934 Scarlatinoid. Rinderpest. in their places. The autopsy on the animal, which died sixteen days after the appearance of the disease, revealed a partial necrosis of the nasal mucous membrane, fresh ulcerations on the tracheal mucous membrane, and a hemorrhagic nephritis. There was also present a striking inflammation of the lymph vessels, and a pronounced acute congestion of the lymph glands of the mesentery. (Monh., 1896, VII, 346.) Scarlatinoid of Cattle. Hetzel observed in a 114-year old steer an- affection resembling the clinical appearance of the preceding disease of the horse. The symptoms consisted in a high fever with sudden onset, great depression, catarrh of the pharynx and larynx. Two to four days later petechiae appeared on the nasal mucous membrane, and various kinds of erythematous spots on the skin. At these places nodules developed in the later course some of which disappeared, while others developed into pea-sized vesicles containing clear serous fluid. Later the contents of these vesicles became purulent, and finally they turned into thick scabs, the animals manifesting severe itching. Purulent con- junctivitis and bronchitis had also developed, and diarrhea exhausted the animals to a great degree. The fever subsided after a duration of six to twelve days, the catarrhal symptoms became milder, and after a desquamation of the scabs complete recovery took place. (A. L, 1903, 33.) 10. Rinderpest. Pestis Bovina (Cattle plague, Typhus bovum contagiosus, Peste bovine; Ty- phus contagieux [French]; Orientalische Rinderpest [German]; Peste bovilla [Italian].) The oriental rinderpest represents an acute febrile, con- tagious, infectious disease of cattle, caused by an ultra-micro- scopical micro-organism, and which aside from its typical course is characterized by a croupous diphtheritic inflammation of the mucous membrane. Exceptionally the disease passes from cattle to other ruminants. History. The attention of experts has been directed to rinderpest from earliest times, because of its destructive character, and the most varied theories have been formulated regarding its nature. At times the affection was considered identical with human pox (Ramazzini, Vieq D’Azyr, F. Miller), and again with typhus (Veith, Spinola) and dysen- tery of man (Lorinser). Its infectious nature was recognized early, and was established by successful inoculations (Dodson, 1744; Camper, 1770), and veterinary police measures were inaugurated against the spread of the disease (in Prussia in the year of 1711, in France in 1714). Since the beginning of the last century the belief of a spon- taneous origin of the disease has been more and more abandoned, but the causative agent remained unknown up to the most recent times in spite of the numerous investigations conducted along this line (Semmer, Gamaleia, Nencki and others), until Nicolle & Adil-Bey (1902) estab- lished its filterability through porcelain filters. Deliberate experiments conducted by Semmer & Raupch, more recently by Nencki and his co-workers in Russia, Koch, Danysz & Bordet, Edington, Koller & Occurrence. 235 Turner in South Africa, Nicolle & Adil-Bey in Turkey, led to the elaboration of several methods of immunization adapted for practical requirements. _ . Occurrence. Rinderpest causes enormous losses in the infected herds of cattle, and may even result in the almost com- plete extinction of animals in large territories. Sometimes it may also cause considerable losses among flocks of sheep and goats. At the present time it prevails in Europe only in the southern part of the Balkan peninsula, but in Asia it is con- tinually present, and recently it has become prevalent in Africa. ; Rinderpest was probably known in the early ages, and not only in its original home, Asia, but also in Europe. With the great migra- tions of people it was introduced from the Black Sea over the entire continent westward, where it has raged almost continuously since that time until the ’70’s of the last century. Extensive outbreaks usually appeared associated with great wars, inasmuch as the cattle which were driven after the troops disseminated the disease over distant territories. Such invasions occurred in Germany during the period of Charles the Great in connection with his wars; in France and Italy at the same time; in the thirteenth century after the intrusion of the Mongolians; at the time of the thirty-years’ war, etc. In the first two decades of the eighteenth century the disease existed throughout Europe with such vehemence that for instance in the years 1711-1714, one and a half million of cattle fell victims to it (Paulet). Later Holland lost almost its entire stock of cattle as a result of the disease. Through the great Napoleonic wars the disease attained again a great extension especially in Germany and in France (the first French veterinary schools were established as a result of the great losses caused by rinderpest at that time). Since the middle of last century it has generally been accepted that the disease spreads only by infection through which knowledge the only rational way of control and eradication of the disease has been estab- lished. The complete eradication of the disease, which in some coun- tries caused severe losses, appeared as a very urgent necessity, and consequently the European governments adopted measures by which they succeeded in pressing it back to the far East. The plague attained considerable extension in middle Europe for the last time during the Franco-Prussian war, but in the course of the following decade it was completely suppressed, so that since 1881 it is confined to Russia and Turkey and more recently has apparently disappeared even from Euro- pean Russia. The losses in Germany during the eighteenth century are estimated at 30 million cattle. The disease was distributed most extensively in the beginning of the last century during the Napoleonie wars, in the ’30’s through the Polish Revo- lution, and. later through the Franco-Prussian war. During the latter, 13,000 cattle and 4000 sheep died in Alsace-Lorraine, while in Germany 8151 cattle suc- eumbed or were killed (the disease was also brought to Switzerland by the eastern army which entered that country). In 1877 the disease was spread from Poland to Posen and from Austria to Wiesbaden and caused a loss of 1591 cattle, and in the following year 2349 cattle died in Prussia from the disease. It appeared for the last time in 1881 in the province Schlesien, and since its eradication from this territory the German Empire has remained free from the plague (Dieckerhoff). In France the disease raged to an alarming extent during the great Revolu- tion and the Napoleonic wars, especially after the unsuccessful Russian expedition. 936 Rinderpest, It appeared for the last time after the Franco-Prussian war, and caused in the course of two years, in 43 districts, a loss of 56,533 cattle valued at 15,000,000 frances. Great Britain was free of the disease from the middle of the eighteenth century for a period of 120 years. In 1865 the disease was brought to the London stock market, and at the same time to different provincial cities by a cattle boat from Finland, and towards the end of that year 85 counties were infected. During the 1%4 years of its prevalence 500,000 cattle died, valued at 100,000,000 francs. The last outbreak occurred in 1877 as a result of its introduction from Hamburg, and caused a loss of 1198 cattle. : In the middle of the year 1866 the disease spread from England to Holland, where it extended rapidly and in barely a year’s time had affected 156,594 cattle, of which 78,110 died and 36,919 were slaughtered, while 41,565 recovered. The disease was introduced into Italy toward the end of the eighteenth century by Austrian troops, and spread southwards with such rapidity that inside of three years over 3,000,000 cattle became its victims. Later in the years 1862-1868, the disease was widely distributed, having been introduced from Dalmatia, in which time the kingdom of Naples alone sustained. a loss of 50,000 cattle. Rinderpest occurred in Italy for the last time in 1878 in the province of Naples. 2 In Austria, Galicia and Bukowina sustained great losses in the middle of the last century. In both of these crown possessions about 54,000 cattle succumbed in the years of 1848-1864, and about 35,000 head in the years 1868-1877. In the first period Moravia suffered a loss of 12,000, while southern Austria lost 4,500 head. The plague invaded Dalmatia for the last time during the Bosnian War, in the year of 1878, and towards the end of the following year Slavonia, Styria and the Krain experienced a visitation. During this outbreak, in a period of three months 1785 cattle died of the disease. Since the year 1880 Austria has been free of the disease. Hungary suffered most severely after the invasion of the Mongolians, and during the time of the Turkish wars, but the disease appeared repeatedly in that country in later years. During the time of the Russian-Turkish war, in the years 1827-1828, the disease was introduced from Moldau and from Roumania, and prevailed continuously until 1842, the losses in the first two years amounting to 30,000 head of cattle. After the conclusion of the wars of 1848-1849 the disease was almost entirely eradicated from the western part of Europe, but was brought to Hungary in 1849 by the Russian army, where it raged continuously until 1861. (The loss in this period amounted to over 350,000 cattle.) After the war between Austria and Prussia the plague again increased, and lasted up to 1874. From the middle of the year of 1861 until the end of 1873 the total loss was 165,732 eattle, valued at over 8,000,000 florins; while the execution of the veterinary police measures required an expenditure of over half a million of florins (Roll). The creation of the Rinderpest law in 1874 finally resulted in a complete eradication of the disease in the year of 1881. 3 In Russia during some of the outbreaks more than a million cattle, in some localities even 3 to 5% of the total stock, were annihilated by the disease (Jewta- chiew). In more recent years it was possible, with the aid-of the measures of eradication adopted in 1879, to restrict the disease within narrow limits. In 1892 it again commenced to spread westward, but gradually diminished since 1894, and since 1897 it recurs only east of the Caucasian Mountains, where it prevailed in 1907 in six government districts affecting 812 townships. In November, 1908, three infected transports were brought from Petropawlowsk (Siberia) to the abattoir of St. Petersburg, but the localization of the disease appears to have been successful. Rinderpest occurs continuously in Turkey, and appears especially in the vicinity of Constantinople, as well as on the coast of the Marmara Sea. Detailed statistics of its oceurrence are not available. The entire territory of Asia, including the East Indian groups of islands, is infected; and in Asiatic Russia alone the losses in 1906 amounted to 25,093 cattle; (according to Yersin the disease rages in Indo-China also among the buffaloes). In 1892 the plague was carried from Corea to Japan, but in two years its successful eradication was accomplished with energetic measures. Previous to 1864 rinderpest was known to exist in Africa only in Egypt, but during the Italian invasion of 1890 it spread southward along the Nile, and inside of five years reached the South African States as well as the West African Colonies of Germany. Transvaal lost 980,000 cattle in 1897, while in the Cape Colony 1,300,000 animals died of the disease in the years of 1897-1898. After that time the plague diminished somewhat, but gained again in severity in the years of 1901 and 1904, until during recent years it has been considerably limited by the persistent employment of protective vaccination. According to Littlewood the disease was again introduced fnto Egypt from Minor Asia in June, 1903, appearing in the Province Behera, where it spread with great severity, and according to Etiology, Pathogenicity. 237 official reports, 147,285 animals, out of a total number of about 3,000,000 cattle and buffaloes, had fallen victims to the disease up to the end of 1906. Ninety-three thousand cases of these occurred in northern Egypt. Arloing estimates the losses at 5,000,000 cattle, and the valuation at 150,000,000 francs. Etiology. Nocard, as well as Tartakowsky, proved that the pure tissue fluids of affected animals contain no micro-organ- isms visible with the microscope, and that no organisms could be cultivated with the ordinary methods of procedure. Nicolle & Adil-Bey demonstrated that brain emulsion, intestinal con- tents, cerebro-spinal fluid or peritoneal exudate, when diluted with water pass through the Berkefeld or Chamberland filter; that such filtrates are infectious, and that therefore the contagion belongs to the group of ultramicroscopical micro- organisms. Pathogenicity. The contagion is present during the entire disease in all tissue fluids (the nasal seeretion of inoculated ani- mals is infective twenty-four hours after inoculation according to Raupach). Blood taken at the height of the disease and injected subcutaneously into a full grown animal in as small a quantity as 0.001 g. will produce the disease with the same intensity as if for instance 41. of blood had been injected subcutaneously (Nicolle & Adil-Bey). Besides the tissue fluids the virus is present in the different secretions (saliva, nasal dis- charge, urine, feces, bile, tears, vaginal discharge, perspiration), while the infectiousness of the exhaled air is doubtful. Infec- tion with such substances is readily accomplished by subcutane- ous injections or by feeding, while by intravenous injections in- fection results only exceptionally (Kolle). Repeated passage of the virus through the bodies of cattle does not modify its virulence (Nicolle & Adil-Bey) ; on the other hand when passed through the bodies of sheep and goats it becomes attenuated (Galambos, Koch). Besides cattle and buffaloes, sheep (Galambos) and goats (Woronzow & Eckert) as well as camels (Tartakowsky) may be infected by subcutaneous injections, while infection is less cer- tainly transmitted by feeding infectious material. The question whether hogs are also susceptible to the virus of rinderpest has not yet been positively established. While Carré & Fraimbault succeeded in infecting these animals with subcutaneous injections of virulent blood, and Penning obtained positive results on wild hogs, and later reinfected calves from them, Theiler failed in all attempts to produce the disease in hogs in a similar manner. ‘Tenacity. Blood or other infectious fluids, sealed in a glass tube, remain virulent for several months (Semmer); the same applies to spleen tissue when kept in a dark place. Distilled water mixed with blood loses its virulence within 4 to 5 days (Nencki), and if mixed with glycerin inside of 8 days (Edington); blood mixed with an equal quantity of. bile becomes avirulent in two hours (Lingard). According to older observations (Haubner, Dieckerboff) the virus remains virulent on hay kept.in the stable, or in the hay loft for 3 to 4 months (2), but when exposed to the sunlight it is destroyed in two days. When dried on wool out of doors it becomes avirulent in three days (Woronzow & Eckert). Hides salted for two 238 Rinderpest. to three days, then kept for 4 or 5 days in a shady place, also bone marrow after the kone has been dried for 30 days, may still contain infectious virus. By heating to 58-60°C. it is destroyed immediately, whilé a temperature of 20-25°C. destroys its virulence only after it has been subjected for a longer period. Blood becomes avirulent when subjected to a temperature of 37°C. for 2 to 3 days (Theiler). According to older data the virus is destroyed very slowly by putrefaction. Thus meat which has been buried for three months is supposed to have been still infective (Vieq D’Azyr). Arloing, however, found that the virus retains its virulence in meat only for 4 days. The infectiveness of manure which has been contaminated with the excrements of affected animals contains the virus for one month, according to Bouley, and according to Krajewski it may sometimes be infectious even after five months. More recent investigations in this direction proved, however, that the virus is destroyed by putrefaction in a few days (Kolle). Besides glycerin carbolic acid (2%), sublimate (1-1000), milk of lime (1%) are effective as disinfectants; on the other hand the virulence of the klood is not modified by a 144% carbolic acid solution (Kolle). Natural infection results either by direct contact with affected animals or is transmitted through the raw products of such animals, such as parts of carcasses, as well as by persons contaminated by such carcasses or by infected secretions and excretions. Food, drinking water, stable utensils, clothes, etc., may also transmit the infection. In most instances, however, the infection is disseminated by affected animals in the ordinary traffic with cattle, which mode of transmission is the more im- portant as some animals may be only very slightly affected and. yet retain the virus in the body for 14 days, in chronic cases probably even somewhat longer (Stockman; the maximum time in which the animal may be infectious for others is supposed to be 30 days). The infection usually occurs through the digestive tract, probably through the lymph spaces, even of healthy mucous membranes. The possibility of infection through the air pas- sages has not been positively established, as it is questionable whether the contagion is disseminated through the air. Out of doors the spread of the disease may be prevented by digging a trench around the infected herd which the animals are unable to pass, and in such eases cattle on the other side of the trench remain healthy (Raupach). Likewise it is possible to prevent its spread by isolating affected cattle for a distance of 10 meters, when it will be found that healthy animals will not contract the disease (Piot-Bey). In the stable healthy cattle may be protected from the neighboring infected animals by simple board partitions (Nencki). The susceptibility is very great in cattle, especially in the young animals, although there appears to be considerable differ- ence in the various breeds. According to some authors (Jessen, Haupt) cattle exposed to the infection become affected as a rule without consideration of the breed. Some Russian authors, however, claim that the long horned ranch cattle are less sus- ceptible to the infection than the breeds of Western Europe. Cattle of the gray breeds show a greater resistance to artificial infection, and the course of the disease in them is usually milder. According to Semmer only 5 to 10% of ranch cattle succumb to an artificial infection with virulent.virus; against 90 to 98% of other breeds. Nicolle & Adil-Bey Pathogenesis, 239 also observed that the time of incubation after virulent inoculations is 24 hours shorter in the higher bred animals, and death as a rule follows half a day earlier than in the black Anatolian cattle, and that these latter may be much more readily immunized. In South Africa (Stockman) and in India (Rogers) the cattle of the mountains appear to be much more susceptible than the animals in the lowlands. _ Buffaloes are much less susceptible. During the existence of an outbreak they become affected only exceptionally, and even young animals may withstand artificial infection (Nicolle & Adil-Bey; although the disease exists among buffaloes on the ‘Hast Indian islands in an epizootic form, Van Ecke, Blin & Carrougeau). Of other animals camels are susceptible (according to Tar- takowsky the disease is always mild in these animals); also sheep, goats and ruminants living wild, especially deer, zebu, gazelle, etc., and these animals bear an important part in the distribution of the disease. Solipeds and carnivora are not sus- ceptible, and the reliability of the observations relative to the occurrence of the affection in hogs (Percari, Driessa, Pluning) has not been proven beyond a doubt (see p. 237). Man is not susceptible to rinderpest. One attack of the disease usually abolishes the susceptibility of the animal; and while repeated attacks were observed in exceptional cases the infection was usually of a mild form. (In the Vaccine Institute of Karlowka it was not possible to repro- duce the disease in a steer which had recovered from the affec- tion produced by inoculation six years previously.) Calves from cows which became ill during advanced pregnancy are also resistant against the infection (Gerlach, Semmer, Rogers), or they become affected only with mild symptoms (Yersin). Pathogenesis. The first symptoms are apparently produced by the virus which enters the blood and propagates with great rapidity. The virus appears to have a predilection for exerting inflammatory changes on the mucous membranes, producing eatarrhal symptoms in the very beginning of the disease. The croupous-diphtheric inflammation which then develops with great rapidity is evidently the result of secondary infection by other micro-organisms from the digestive tract attacking the weakened mucous membrane. These bacteria cannot be desig- nated exactly at present (colon and necrophorus bacilli ?) in the absence of accurate bacteriological and histological examina- tions. The tissue changes consist principally in that the ep- ithelial layer of the hyperemic and swollen mucous membrane changes together with the exudate which comes from the blood vessels into an easily detachable and friable pseudo-membrane. Sometimes the tissue of the mucous membrane proper becomes necrotic to a certain depth, forming thicker membranes that are more adherent. The mucous glands, especially those of the intes- tinal mucous membrane swell as a result of cellular infiltration, and later become necrotic. The inflammatory process is some- 240 Rinderpest. times also observed in the cutis of the skin, which is a direct result of the softening and sloughing of the epithelial layer. The continuous high fever and great debility, the weakness of the heart, the hemerrhages of the serous and mucous mem- branes, as well as the pronounced difficulties in respiration, indi- cate also a severe action of the filterable virus on the central nervous system. Anatomical Changes. Carcasses dead of rinderpest are greatly emaciated. The skin surrounding the sunken eyes, the nostrils and the lips are profusely covered with tenacious mucus and saliva, the anal region is soiled with dried feces, the mucous membrane of the rectum is greatly swollen and cyanotic. In some of the cases the skin shows the changes which can be noticed already during life (see p. 246), while in the sub- cutaneous connective tissue the flabby and easily torn veins are dilated and filled with blood. The abdominal and thoracic cavities contain in some cases a yellowish-red or dirty-brown fluid, which is odorless or may have a sickening, sweetish odor. The most important changes appear in the mucous mem- branes, and especially on that of the digestive tract. In the mouth, especially on the mucous membrane of the lips, lying opposite the gums, under the tongue and on the phre- num, more rarely on the cheeks and on the hard palate, on the soft palate and on the borders of the tongue, there are yellowish- gray nodules and granular pulpy deposits. There may be also areas the epithelial layer of which has exfoliated, or even deeper ulcers, while in other spots the mucous membrane usually shows reddish maculae, or appears as if it had been sprinkled with bran as a result of a necrosis of the epithelial layer (sometimes pin-head sized ulcerations are present on the tongue, gums and in the pharynx). The mucous membrane of the pharynx is hyperemic, and contains small hemorrhages, while in the cesoph- agus it is usually normal; exceptionally a necrosis may be observed in the superficial layers of the esophagus which are of hemp-seed to lentil sized dimensions. The omasum contains very dry food; the abomasum, which usually contains only a small quantity of a tenacious mucus, shows the most varied shadings from a brick-red to a dark- brown coloration in its mucous membrane. The reddening is most intense in the region of the pylorus, and especially on the tops of the folds. At the same time the mucous membrane is swollen, and the submucosa thickened as a result of an edema- tous infiltration. In a later stage plate-like deposits may be observed, especially on the folds of the mucous membrane, which are hemp-seed to lentil in size, dirty-gray or brownish in color, and flat or rounded in form. These deposits are only loosely attached with their soft borders, while in the center they adhere more strongly to the base. If they are picked off highly red- dened depressions remain in their places. Anatomical Changes. 241 The intestinal canal contains dirty-gray or from the admix- ture of blood, darkish-brown, very liquid feces which have a sweetish stale odor and are often mixed with membranous shreds.. The mucous membrane is much reddened, the subjacent connective tissue gelatinously swollen. The mucous membrane of the duodenum and of the jejunum shows plate-like deposits similar to those in the abomasum, and occasionally they are also found in the ileum. The solitary follicles are swollen to the size of a hemp seed or even larger, and form small nodules from which a purulent or yellow caseous mass may be squeezed. (If the necrotic epithelial cells are not thrown off, they together with the swollen glands cause the mucous membrane to resemble the skin of a boiled eel.) The Peyer’s patches are at first uni- formly swollen, and rise with a flat prominence over the sur- rounding tissue; later small dirty-gray deposits appear around them, which subsequently confluate to a dry, caseous and strongly adherent or a mush-like, soft deposit, several millimeters in extent. In rare cases the epithelial layer forms with the coagu- lated exudate a membranous cylinder several millimeters thick on the inner surface of the intestinal tube; in other cases the necrotic tissue of the mucous membrane changes into a friable, dry, caseous mass, when after its removal the smooth muscular layer is exposed. The large intestines show similar changes, but in these the lesions are less pronounced than in the small intestines. Fre- quently they show only indications of a simple acute catarrh, or the mucous membrane appears as if sprinkled with bran because of the superficial necrosis of the epithelial layer. Some- times the mucous membrane of the large and small intestines presents broad, bright-red transverse stripes or extravasations of blood so that it greatly resembles the skin of a zebra (Verney). In the bright-red air passages, punctiform or linear hemor- rhages and catarrhal swelling of the mucous membrane, as well as edematous infiltration of the submucous connective tissue, especially in the nose and in the larynx, are almost constant lesions. There are frequently croupous, pseudo-membranous deposits in the nose, and especially on the nostrils, also in the larynx and in the trachea, under which ulcerative erosions are found. The mucous membrane of the bronchi usually manifests only a ring-form deposit, and is covered with a purulent secre- tion, which may in places entirely fill the small bronchi and pop out on the cut surface on slight pressure in the form of white plugs. Similar changes may frequently be observed on the mucous membrane of the female genital organs, and especially in the anterior part of the vagina, while further back the lesions are usually less marked. mS The liver shows parenchymatous or fatty degeneration. The gall bladder is distended and contains thin, green or yellow, 242 Rinderpest. or even dirty-gray bile. The mucous membrane is in some instances at first covered with vesicles and ulcers, later with greenish-yellow patches of necrotic tissue. The spleen is usu- ally unchanged, sometimes, however, it may here and there be acutely swollen. The kidneys manifest cloudy swelling or fatty degeneration, the mucous membrane of the hylus of the kidneys and of the urinary bladder shows catarrhal swelling and small hemorrhages. The lungs show an acute hyperemia, and sometimes contain scattered areas of catarrbal pneumonia. Frequently an inter- stitial emphysema is present, and in some cases air bubbles are found under the pleura, in the mediastinum, in the surrounding tissue of the trachea, as well as in the subcutaneous and sub- peritoneal connective tissue. The heart is flabby, the muscles are friable, of a dull, grayish-brown color, sometimes showing butter-yellow streaks. Under the pericardium as well as be- neath the endocardium, hemorrhages are frequent. The blood is dark red and only partially coagulated. The lymph glands, especially in the mesentery, show an acute swelling, their tissue is reddened and moist, but contains no hemorrhages. In the brain and in the cerebral meninges only a hyperemia and moderate edema of the white brain Substance may be found. The described anatomical changes are present in animals which die at the height of the disease, or which were killed not earlier than on the third or fourth day of the affection. Pronounced lesions on the mucous membrane of the digestive tract, and especially in the abomasum, are present in almost every instance, while the mucous membrane of the air passages and genital organs may only occasionally manifest an acute catarrh. However the affection of the intestinal tract is not always uniform, for instance, the very decided affection of Peyer’s patches which was observed in every case by Gerlach is according to Bristowe, Murchison and Dieckerhoff in some cases en- tirely absent. Again Koch observed in South Africa, and Nicolle in Turkey, that the diphtheritic changes in the buccal cavity and in the intestines were only slightly pronounced in those countries in the rinderpest of cattle. In the gray range cattle the anatomical changes are usually less prominent than in cattle of Western European breeds. Symptoms. The time of incubation in cattle extends from 3 to 9 days. Raupach inoculated 865 cattle, of which 70 (8.1%) developed the disease on the fourth, 227 (26.25%) on the fifth, 303 (35%) on the sixth, 208 (24.15%) on the seventh, and 57 (6.6%) on the eighth day. Sanderson and Semmer have observed in exceptional cases a febrile rise in temperature 36 to 48 hours after inoculation. Of 390 animals inoculated by Tode 55 became affected on the fourth to tenth, 21 on the eleventh to twentieth, 20 on the twenty-first to twenty-sixth day. Of the more recent authors Koch observed the development of fever as the first indication of the disease in from 3 to 9, Theiler from 3 to 6, Nicolle & Adil-Bey from 4 to 6 days. The establishment of the accurate time of incubation was of special impor- tance during the time when cattle imported from Roumania and Russia to Austria- Hungary and Prussia, were subjected to a quarantine on the borders. For this reason the international veterinary congresses repeatedly discussed this question (in Symptoms. 9A 1863 in Hamburg, in the years 1865 and 1867 in Vienna). Nine days was estab- lished as the maximal duration, and after the international hygienie conference in 1872 had also substantiated this finding, the duration of the quarantine was reduced from 21 to 10 days. The first symptom of the disease which usually precedes the other manifestations by one or two days is the rise in the temperature which in the Western Huropean cattle reaches on the first or not later than on the second day 40-42.2°C. (Gerlach). In range cattle however it usually does not reach that height (Medvedski. According to Dieckerhoff the rise in the tempera- ture commences in exceptional cases only 10 to 20 hours after the appearance of the other symptoms). : At the same time the animals manifest a marked depression and dullness. They stand in the stable, or apart from the other animals in the barnyard or pasture, with head drooped, sometimes supporting it on the crib, the ears drooped, and the back arched. Exceptionally the affected animals first show great excitement, constantly moving about, attempting to break loose when tied, shaking their heads, tearing up the ground with their horns and feet, and sometimes even assuming a fighting attitude. This excitement however lasts only a short time, not longer than a few hours, and is soon relieved by the above-mentioned depression. The appetite is depressed, the thirst on the other hand being sometimes increased (according to Dieckerhoff many animals manifest frequent yawning, and the swallowing of pieces of mortar); rumination is delayed or sometimes ceases, the feces which are passed at long intervals are dry, dark- colored, and do not form curled cakes. The urine is diminished in quantity and of a darker color. The milk secretion is con- siderably diminished from the beginning of the disease. In the meantime the animals tremble, shaking severely over the entire body at short intervals. They grind their teeth, and certain groups of muscles, especially on the neck and near the flank, show fibrillar twitching. The temperature is unevenly distributed over the body surface, the horns and the ears feel warm to the touch, the muzzle is dry, the skin at the flexor surfaces of the extremities and in the surrounding parts, is covered with perspiration, the hair especially over the vertebral column is lusterless and erect. Respiration and pulse become somewhat accelerated, and the frequency of the pulse is affected by even slight external influences. Many of the affected animals cough frequently, even in the first stages of the disease, without it being possible to detect any changes in the thoracic organs. From the second day of the manifest affection inflammatory changes of the mucous membrane appear in the foreground, which render the symptoms of the disease characteristic. The conjunctivae are bright red, the lids are swollen, cushion-like, while tears run profusely from the narrow opening of the eye. Later the secretion becomes mucous and soon 944. Rinderpest. purulent. On forcibly separating the lids a great quantity of discharge runs out, and dries below the inner canthus of the. eye into-dry crusts. On the surface of the inflamed conjunctivae fine pseudo-membranes form, and sometimes the cornea becomes cloudy (according to Krajewski especially in dry warm weather). From the nasal opening there is first a glassy transparent, tenacious, later a more purulent and at last a dirty gray or brown, fetid, ichorous or bloody discharge running down the Fig. 43. Stomatitis in rinderpest. (After the reports of the English Commission of the year 1866.) muzzle. The nasal mucous membrane as far as it may be examined, is at first spotted, later uniformly reddened, and sprinkled with dark red, punctiform hemorrhages. The itching produced by the inflammation of the mucous membrane causes the animals to blow frequently, and to continuously move the head up and down, or from right to left, and sometimes to even shake it violently. As a result of the developing difficulty in respiration the animals sometimes shake their whole bodies, Symptoms, 245 thus causing a rattling of the chain with which they are fastened by the head or neck, by the sound of which affected animals may frequently be recognized in an infected ‘stable. In the buceal cavity the mucous membrane is at first red- dened in spots, later assuming a uniform, livid or bright red color, and not infrequently becomes covered with dark red ecchymoses; these changes appear first on the gums, and on the inner surface of the lips, later in the corners of the mouth, on the borders of the tongue, in the vicinity of the phrenum of the tongue, on the upper lips, and on the cheeks. Soon hemp-seed to lentil-sized gray spots appear on the surface, which confluate forming larger, connecting, gray or grayish- yellow, patch-like deposits; after their loosening, wiping off or throwing off, the bright red, bleeding, deeper layer of the mucous membrane becomes visible (so called erosion ulcera- tions; see Fig. 43). As a result of the affection of the intestinal tract, there is in the first two days obstipation, later profuse diarrhea. The feces which at first were firm and sometimes mixed with blood, become softer and later very thin; they are passed under great strain, in which the dark red, or livid, greatly swollen rectal mucous membrane protrudes. The parts surrounding the anus are soiled by the watery, later dirty gray and then dark brown, fetid, sometimes bloody feces, which contain mucous shreds, gray detritus, or even large pieces of pseudo- membranes. Towards the end of the disease, about the fifth day, involuntary passages of the bowels take place at short intervals and in small quantities, from the flabby and open rectum of the animals which lie on the ground at this stage. Even in the earliest stages a mucous or muco-purulent dis- charge, which is sometimes mixed with blood- flows from the vagina of cows and heifers, the vulva showing a swelling and higher temperature. The mucous membrane of the vagina and the vulva is reddened, and on the surface small gray, or yellow, pseudo-membranes form, which later are thrown off leaving dark red, bleeding, superficial erosions in their places. The animals urinate frequently. The urine flows almost continually in drops at short intervals, and is sometimes yellowish-red to coffee brown in color (Eggebrecht). As an indication of an affection of the respiratory organs a frequent painful cough is observed as the first symptom, which however disappears after the disease has completely developed (Dieckerhoff). The respiration is accelerated, 40-60 per minute, later it is labored to a high degree, and the grunt- ing of the animal is audible for a great distance. Percussion of the thorax reveals nothing abnormal, or only a louder per- cussion sound. Auscultation reveals intensified vesicular breath- ing, later dry and moist rales. In some cases a subcutaneous emphysema develops in association with the interstitial lung emphysema, which results from the very difficult respiration. 246 Rinderpest. In such cases the emphysema is first indicated on both sides of the vertebrae, then on the neck, shoulders and thorax. The heart’s action is-at first sufficiently strong, but grad- ually weakens. The constantly increased frequency in pulse is at first 50-60, later 80-100 and even more per minute. The pulse is weak, small, and toward the end of the disease wiry. The leucocytes increase in the blood with the onset of the fever up to the fifth day of the affection. From this time on their number diminishes to 4,000 per cubic millimeter in the unfavorable cases. If the animal remains alive their number increases towards the sixteenth or seventeenth day of the disease to 28,000-30,000, which is again followed by a rapid diminution, whereupon by the twentieth day the normal condition is re-established. Tl2lalelslelzi alate The continuous fever usu- . ally reaches its height on #5 . the fifth or sixth day, the Fy daily differences varying by 8 7 | one degree, and rapidly drops Pe | with the onset of the diarrhea f in the severe cases to below to is normal; whereas if there is an indication of improvement 295) t the fever subsides gradually 7 y, (Fig. 44). The height of the 390 = | fever does not always cor- Pee pan: respond with the severity of ¥ the other symptoms. aso : In some eases, particularly Fig. 44. Fever curve in rinderpest, follow- in range cattle, the skin be- ing a subcutaneous injection of a drop of comes affected in a peculiar virulent blood ; three year old cow. (Af- manner. Two or three days fering pend SUL ise) after the appearance of the disease, sometimes even earlier, small protuberances and vesicles develop on the neck, before and behind the shoulders, along the vertebral column, on the shanks, on the udder or on the scrotum, and in the flank. Over these areas the hairs stick together, later thick scabs cover the wrinkled skin. In case the animal improves the scabs are thrown off, the epithelium desquamates, at the same time the hair falls out, and sometimes the animals may even lose the hair from the tips of their tails. Russian authors and also Zlaml, laid great stress on the affection of the skin which occurs quite frequently in range cattle, and accord- ingly they distinguished an exanthematous form of rinderpest, from one in which no exanthema developed. In confirmation of older con- ceptions, they consider the appearance of the exanthema a favorable prognostic indication. The skin affection however which develops in some of the outbreaks quite frequently, in others but rarely, may exceptionally occur also in Western European cattle and in spite. of this favorable symptom the disease may terminate unfavorably. (The exanthema was frequently observed in Hungary in the outbreak of 1852, pea Course of Disease. 247 whereas in the years 1861-1863 it was not observed in a single instanéé. [Zlamal] .) ee With the diminishing milk secretion the udder becomes. flabby, wrinkled and cold; the milk which is secreted in small quantity is watery and of a pronounced yellow color. Pregnant animals usually abort at the height of the disease. _ During the development of the described symptoms the animals have no appetite and do not ruminate, become rapidly emaciated and steadily lose in strength. The skin loses its elasticity, becomes stiff and dry, the hair dull and Iusterless: The advanced stage of the disease appears characteristic in the presence of a dull look from the deeply sunken eyes, purulent secretions from the eyes, dirty nasal discharge, foamy. saliva in the corners of the mouth, grinding of the teeth, accelerated and grunting respiration accompanied by shaking of the body, muscular trembling, and the peculiar repulsive odor of the excrements. Soon the animals are not capable of standing up, they lie constantly on the ground with head extended or turned on the shoulder, and finally they succumb, completely exhausted, in convulsions or without struggle. Course. The described symptoms do not all develop in every case of rinderpest. Furthermore according to Lorinser the entire symptom complex is never present in one animal or even in the herd, but from case to case the changes in the respiratory organs, or those of the digestive tract predominate, and in other instances symptoms of the genital organs; in most instances all the organs mentioned may be affected, at the same time but in varying intensity. In the great majority of the severe cases the disease lasts on an average of from 4-7 days. The affection of the mucous membrane can usually be detected on the second day after the appearance of the febrile symptoms. The clinical mani- festations develop in their full intensity on the third or fourth day; in exceptional cases the condition becomes very rapidly aggravated, when death may result on the second or third day, while in other cases the course may extend from 14-16 days. The convalescence lasts from 2-3 weeks, and the symptoms, especially those of the intestinal inflammation diminish very gradually. In the milder cases, such as are usually observed among range cattle, the symptoms do not develop to such a degree, and usually commence to recede about the fourth or fifth day. Ac- cording to the observations of Russian authors and Eggebrecht, the disease among these breeds of cattle may be manifested “only by a febrile condition lasting for a few days, and by a mild catarrh of the mucous membranes of the respiratory organs, as well as of the digestive tract. As a result of these the disease may sometimes even pass unnoticed in the larger herds. This mild form of rinderpest is observed in very 948 Rinderpest. exceptional cases also among cattle of the Western European breeds (Dieckerhoff; according to Stockman the disease some- times may run a very chronic course in the presence of mild symptoms). In Turkey, Russia and Africa animals frequently become affected which have previously been infected with the parasites of infectious hemoglobinuria, or coast fever. In such animals rinderpest runs the usual course, but at the same time the piroplasma which were present prior to the infection with rinderpest only in unimportant numbers in the blood inerease very rapidly (Nicolle & Adil-Bey, Kowalewsky, Theiler, Koch). Latent cases of trypanosomiasis are likewise influenced by rinderpest (Holmes, Woolley). Rinderpest as a plague does not spread very rapidly in large herds. After placing an affected animal in a stall, usually after 1-2 weeks the animals in -close proximity first become affected, whereupon however the disease attacks the other animals with a greater rapidity in a similar way. According to Haupt it requires from 5-6 weeks for the disease to affect all the animals in a herd of 15-20 head. Diagnosis. The sudden appearance and the rapid develop- ment of the symptoms, among which the characteristic affection of several mucous membranes is of great importance, aid in the recognition of the disease. In establishing a diagnosis careful data on the history, first on the possibility of an intro- duction of the infection as well as the mode of spreading in the affected herd, must be carefully considered, because of the far-reaching consequences which may follow the presence of the disease. The diagnosis is formed with difficulty, in the beginning of an outbreak, especially if the disease affects the first animals in an unusually mild form, but a sudden rise in the temperature is sufficient to justify a suspicion of the pres- ence of rinderpest. From the standpoint of differential diagnosis the follow- ing diseases are principally to be considered: 1. Coccidiosis (red scour). The resemblance consists in the fact that in this disease there is also a febrile diarrhea and rapid loss of strength; further autopsy may reveal necrosis of the epithelium and even of the deeper layers of the gastric and intestinal mucous membrane. It is distinguished from rinderpest in that the digestive disturbances precede the febrile rise in temperature, further the excrements retain their original color for a longer period, but may become mixed with blood even at the beginning of the disease. The affection remains exclusively confined to the gastro-intestinal canal, and in older animals the affection of the rectum is especially marked; whereas the mucous membranes of the head, and of the eyes, remain normal. Further the disease is not contagious, and cannot be transmitted, even by inoculation. Similar differences Diagnosis, Prognosis. 249 exist between the acute gastro-intestinal catarrh, the mycotic and toxic enteritis, on one side, and rinderpest on the other. Tschudinow observed an affection in cattle after feeding swill heated to a temperature of 53-54°, which consisted in fever of 40-42°, difficult respiration, red spots on the buccal mucous membrane, catarrh of the conjunctivae, scanty hair, mucous discharge from the nose, and a bloody mucous diarrhea. The autopsy revealed in one case hyperemia, and hemorrhages in the mucous membrane of the rumen and of the intestinal canal. 2. Malignant catarrhal fever of cattle, with which rinder- pest has been frequently confounded. This disease resembles rinderpest inasmuch as it also runs a severe course, and as all mucous membranes may become affected. However the most severe changes are found in the mucous membranes of the eyes, nose and sinuses of the head, while the digestive tract and the genital organs are usually only slightly affected. The head feels warm to the touch, the horns sometimes fall off, the depression of the animals is pronounced from the onset of the disease. Besides cloudiness of the cornea, a fibrinous iritis may also develop, and it should be taken into consideration that the disease is not contagious and usually occurs only sporadically. 3. Foot-and-mouth disease can only be mistaken for rinder- pest when the ulcerations in the mouth extend to the deeper parts, and when the ulcerations later become covered with tissue detritus and coagulated exudate; further when high fever and indications of enteritis can be associated with the disease. In foot-and-mouth disease however the ulcerations develop at the site of the vesicles; the nose and the eyes are not affected, while frequently inflammatory changes are present in the interdigital spaces; furthermore foot-and-mouth disease spreads more rapidly through the affected herds than rinderpest. 4. Piroplasmosis may cause suspicion of rinderpest, especially on autopsy, in cases where the mucous membrane of the abomasum and of the small intestines contain ulcerations, and even patch-like deposits. Normal appearance of the mucous membrane of the mouth, air passages and genitals, the presence of hemoglobin in the urine, acute swelling of the spleen, yellowish discoloration of the subperitoneal fat, as well as an enzootic character of the outbreak, afford sufficient grounds for excluding rinderpest. However the establishment of the piroplasmosis, or the presence of piroplasma in the blood does not exclude the simultaneous presence of rinderpest, as mixed infections of this kind occur quite frequently (see pp. 248 and 255; according to Arloing & Ball the swollen lymph glands are free from hemorrhages only when piroplasmosis exists in asso- ciation with rinderpest). A demonstration of trypanosomes in the blood also has no importance from the standpoint of a differential diagnosis. Prognosis. The termination of the disease depends in the first place on the character of the outbreak, and on the breed 250 Rinderpest. : of the affected animals. The mortality fluctuates within wide limits, and is estimated among cattle of the colored breeds at 75%, in range cattle at less than 50%. In England during the outbreak in 1866 the affected animals died almost without exception, whereas at the same time in Holland only two-thirds of the diseased animals succumbed, and in France in 1871 the mortality amounted in places to only 20%. In Hungary the losses in 1852 did not exceed 10%, on the other hand in the years 1861-1863 they reached 75%. According to Krajewski the disease sometimes runs a mild course, especially after a rapid spread through large herds (losses of 15 to 20% or even less), but occasionally, even among range cattle, 85% may die. In India the mortality among cattle of the lowlands is ‘about 20%, while in mountain cattle it reaches 90%. Experience has shown that if the disease returns after a long period of absence, a greater number of animals fall victims, and on the other hand the mortality immediately after the out- break is greater than in its later course. Under favorable hygienic conditions, pure air and dry weather, the losses are lighter than under adverse conditions. Treatment. Medicinal treatment of the affected animals gives no result, as was proven by the completely negative re- sults obtained in experiments in England and Holland on the occasion of the last outbreak. A favorable influence can be hoped for only from serum treatment, in which the patient should be given 40-80 cc. of immune serum subcutaneously or intravenously at the beginning of the febrile stage, or not later than the appearance of the first manifestations (see p. 252; Fedetzky found the curative inoculation valueless). The opportunities for therapeutic treatment are remote, as all of the European countries which are free from the disease, with the exception of Turkey, require the killing of all affected and suspected animals. Immunization. The possibility of an effective immuniza- tion against rinderpest is indicated by the numerous instances in which recovery from the disease has afforded the animals an immunity lasting for a long time, usually as long as they live. The intensity of the immunity thus obtained develops in a degree relative to the severity of the affection. However, as affected animals infect others during the course of the dis- ease, and as they may disseminate the infection, immunization except with pure serum inoculations, is only indicated in badly affected localities, in order that the otherwise very great losses may be reduced. As this purpose was not attained with older methods of immunization, owing to the considerable losses from the im- munization, it has been abandoned not only in the Central and Western European countries but also recently in Russia. The occurrence of the disease with great severity in the last decade, especially in South and North Africa, has again placed the * question in the foreground and the experiments conducted Immunization. 251 there have resulted in more effective methods by which more satisfactory results are being obtained in affected localities. _ I. Immunization with Secretions of Affected Animals. Stimulated by the favorable results of smallpox vaccination, immunization against rinderpest was undertaken in the middle of the eighteenth century (1744) in England (Dodson), in France and in Germany, as well as in Holland, and later was employed to a great extent in Russia. The procedure consisted in the introduction of the nasal discharges or lachrymal secretions of affected cattle into healthy animals, under the skin of the tail or other parts of the body. After the inoculation the disease developed in a very mild form, especially in the gray range cattle, and the mortality reached only a small percentage. Jessen experimented later with a supposedly attenuated virus, which he carried through several generations of cattle. After such inoculations in the Vaccine Institute of Karlowka, in the years 1857-1873, the entire loss among 2629 cattle amounted to only 5.97%. This method of immunization, however, did not appeal to Western Europe, -- inasmuch as the breeds of cattle in those countries became severely affected from the inoculation and the losses were considerable, and further than this, the inoculated animals endangered the lives of those which had not been treated. After the inter- national conference in Vienna in 1872 had resolved that the immunization against rinderpest should not be considered as a valuable method, it was abandoned even in Russia, and in 1874 the last serum institute was given up. II. Immunization with the Bile of Affected Animals. The blood and the bile of animals dead from rinderpest has been used for a long time for immunization purposes by the Boers in the Transvaal and in the Orange Free States. Koch later demonstrated (1897) that the bile of such animals in quantities of 100 cc. injected into healthy animals afforded them a very valuable immunity against the infection. The immunity can be established by the tenth day following the immunization, and is of such intensity that the immunized animals withstand an injection of 40 cc. of virulent blood without ill effects even four weeks after the inoculation, and they are also able to resist natural infection. The immunity probably results from the virus contained in the bile which gives the animals a mild local affection, due to the retention of the virus at the point of inoculation through the action of certain ingredients of the bile (Kolle). The immunization employed in practice showed that the immunity following the injection of bile sometimes appears on the sixth day, and lasts from four to six months (Kolle). Jn other cases, however, it lasts only from 3-4 weeks (Kohlstock), and the inoculation occa- sionally causes not only a local swelling at the place of inoculation, but it may also cause a severe general affection, and exceptionally the death of the animal, especially if the bile contained some blood (Theiler). Further, as the bile inoculation in already infected animals ‘during the time of incubation is entirely without effect, the applica- tion of this method could only come into consideration if rinderpest suddenly broke out in certain localities and a more effective method of immunization could not be employed. Potent bile can be obtained only after the seventh day of the dis- 952 Rinderpest. = ease; it should be of a green color, odorless, and on shaking should form a white foam. An animal dead from the disease produces a quantity sufficient for not more than 20-25 cattle. In South Africa in the years from 1896 to 1898 over 2,000,000 cattle were immunized with bile with apparently satisfactory results, and according to Adani it has proved beneficial in Erythraa. Rogers also found this method effective in India, however only in cattle of the lowlands, since mountain cattle, which are much less frequently exposed to the infection, nearly all succumbed to the disease, when inoculated with virulent blood 10 days to 41%4 months after they had been immunized with bile. (In some localities of South Africa the immunizations were repeated every three months, and in spite of this deaths from the disease were occasionally observed). Edington mixes bile (2 parts) with glycerine (1 part) and injects this mix- ture subcutaneously, 20 to 25 cc. to adult cattle and 15 cc. to calves. According to Turner immunity cannot be established by this method, as the glycerin kills the virus contained in the bile; Rogers likewise asserts the ineffectiveness of the addition of glycerin. Filtering the bile before the injection through a porcelain filter (Turner & Kolle) also reduces its immunizing action, and at best only has the advantage that by this procedure bile which is no longer fresh may be utilized for immunization (Rogers). Lingard on the other hand found that bile from healthy animals if subeutaneously inoculated four times at several days intervals in 50 cc. doses, also gave an effective immunity against subcutaneous virulent infections. Lingard uses instead of fluid bile a precipitate which he obtains by the addition of Almen’s reagent (5 g tannin, 10.0 ce. acetic acid, and 240 cc. of 45% alcohol). The precipitate which is washed in a 1% soda solution, neutralizes the virus in vitro, and inoculations by this method are supposed to have given good results in India even in the mountain cattle. Active immunization with bile and with virulent blood. In order to produce a more lasting immunity, Kohlstock, and later also Henning & Edington injected subcutaneously virulent blood (0.2 ec.) about two weeks following the bile inoculation. The animals thus injected became sick, however with only a few exceptions they re- covered and later proved that they pessessed a lasting immunity. In German South Africa this method has found extensive use, and with its aid the disease was successfully eradicated in a few months at the time of the severe outbreak of 1897 (Rassau). It has likewise proven satisfactory in Tientsin (Asia) where of the immunized animals 66% showed no disease whatsoever, while 24% became only slightly affected, and 10% died as a result of the inoculation (Haedicke) ; Edington on the other hand observed at Kimberley great losses from such combined inoculations. III. Immunization With Blood Serum. Semmer found in 1893 that blood serum from cattle which recovered from rinder- pest possessed immunizing properties, and these findings have since been confirmed. However such serum exerts its protective action only when relatively large quantities are used (100-200 ec.), still its action may be increased by injecting the animals with large quantities of virulent blood. The passive immunity produced by the serum inoculation only lasts from 10-21 days, and the duration cannot be increased to over four months even by the use of greater quantities of serum (100-200 ce.). Accordingly it may be suitably applied whenever, after the slaughtering of the affected animals, the remaining cattle, if treated with serum, will not be likely to become exposed later to the infection; farther it may be used where infection is threatened by outbreaks in neighboring Immunization. 253 localities when the serum will be found to afford protection for at least a short time. One advantage of this method lies in the fact that it is also effective during the period of incuba- tion, and that the inoculated animals do not become affected and therefore do not spread the disease. Tokishige (1897) in Japan, and Pitchford & Theiler, as well as Bordet & Danysz, during the invasion of the disease in South Africa, aimed to increase the potency of the blood serum of recovered (so- called salted) cattle, by injections of virulent blood. Kolle & Turner injected at first 100 cc. subcutaneously in recovered animals after the disappearance of the fever, then at intervals of several days increasing quantities of virulent blood (the last time 5 liters in one injection). After 3-4 pronounced reactions the animals produced a serum of which 20 ce. protected an animal weighing 300 kg. against a pathogenic action of 1 ec. of virulent blood (for use in practice the blood serum must have at least such a potency). Animals which have not recovered from rinderpest must be treated first with bile, or with blood serum and blood, and only later with virulent blood. Nicolle & Adil-Bey observed in Constantinople that animals which recovered from rinderpest could not again be made sick by a sub- cutaneous or intraperitoneal injection of a large quantity of virulent blood (up to 10 liters), even when inoculated immediately after the recovery. Accordingly recovered animals were injected subcutaneously at first with 4 liters of blood, and later the quantity was increased. Another method of these authors consists in the injection into the abdominal eavity of an affected animal which already has diarrhea, of 6 liters of a physiological salt solution containing peptone. Three to six hours after the injection the animal is bled to death, and a healthy animal is then injected subcutaneously with 2-3 liters of the fluid collected from the abdominal cavity. The blood taken after 10, 15 or 20 days from this animal produces a potent serum; later the animal again receives the abdominal fluid subcutaneously, and the method is continued in this manner. Two weeks following the injection of 4 liters of blood the animals produce a similarly potent serum, no matter whether this quantity has been injected immediately after the first opportunity or only in gradually increasing quantities. Sheep are also adapted to the production of immune serum, the horse and the goat however are not. By adding to the immune serum 14 to %% of earbolic acid and keeping it in a dark place it remains potent for four years (Theiler). The dose of the serum is 50-100 cc., according to the size of the animal. In India the very susceptible mountain cattle are injected with 18 times larger doses than are given to the cattle of the lowlands, and the quantity also depends on the severity of the disease before the inoculations have been undertaken (Walker). According to the statistics of Turner, in 1897 33 herds on several farms, with a total of 3318 cattle, of which 455 animals had already been affected, were subjected to the serum treatment. Of these inoculated animals 455 died, while 2857 (86.1%) remained healthy. In the English Egyptian Soudan Head lost 2% out of 7386 inoculated animals. The serum inoculation has been applied in China to about 11,000 eattle, with very satisfactory results (Keylock). ie As it is sometimes difficult to obtain virulent blood, Ridiger injects cattle intraperitoneally with 5 liters of a 4% potassium citrate solution. The animals are slaughtered an hour later. The fiuid thus injected proves very virulent and when mixed with equal quantities of virulent blood produces a very effective and @ correspondingly cheaper material for the preliminary treatment of serum cattle. 254 Rinderpest. Dschunkowsky & Kupziz produced a dry preparation from the liquid serum by evaporation, at 30.32°, and by adding at the same time 1-5% of sodium hydrate; this has, however, not yet been tested in practice. IV. Immunization With Immune Serum and Virulent Blood. (Simultaneous Method.) Kolle & Turner produced an immunity in cattle which lasted for at least five months, by injecting the animals subcutaneously on one side of the rump, with one ce. of virulent blood, and on the other side, according to the size and age of the animal, 8 to 25 ec. of immune serum. This immune serum is the same as that which is used for ordinary serum inoculations, while the blood originates from animals either affected with the natural disease or from such as were artificially infected, and should be taken on the fifth or sixth day of the disease (sheep infected with blood are also suitable for this purpose). Some of the animals inoculated by this method react with a fever lasting for several days, while about 10% of the vaccinated cattle, especially common range cattle, do not manifest any reaction whatsoever. The blood of the reacting animals. is infectious during the febrile stage. In exceptional eases severe symptoms of rinderpest develop in the inoculated animals, and some (about 1%) may even die with the disease. The simultaneous method has the advantage over the other methods that it causes a relatively small loss, and with very rare exceptions it produces a lasting immunity. However while only a small proportion of the inoculated animals become affected with severe symptoms, they may transmit the disease to healthy animals, and therefore its application is only indi« cated in already infected territories, and in these localities only under assurances that the blood does not contain other poisonous substances in addition to the virus of rinderpest, and it should especially be free of protozoa (see p. 255). This method has been employed for several years in Africa, in Asiatic Russia (Nencki, Siebert & Wyznikiewiez), in Turkey (Nicolle & Adil-Bey), and in India (Rogers), and the first reports from all these places indicated favorable results. In India, however, in the less resistant mountain cattle the immunity obtained was not sufficient, although the dose of the serum was increased 6 to 9 times. Rogers therefore injects another 10 cc. of virulent blood subcutaneously 10 days after the simultaneous inoculation. The simultaneous method may be also adopted for the immunization of buffaloes as well as goats (8 to 5 ee. of blood serum, and 1 ee. of blood). According to Turner, 10,407 cattle were inoculated by this method in South Africa (Rhodesia, Cape Colonies and Pretoria), and the loss from inoculation amounted to 136 animals (1.31%); Head inoculated 7,386 animals in the Egyptian Soudan, with a loss of only 2%, Fedetzky and Gorain observed a loss of 1-2%, Stockman on the other hand observed in one herd deaths amounting to 12%. Very good results are reported by Eggebrecht in Eastern Asia. For a time another method of immunization was used in South Africa, which has since been introduced into practice by Bordet & Danysz, as well as by Pitchford & Theiler, and which consisted in injecting subcutaneously into the animals 100-200 ce. of defibrinated blood from animals which had recovered from rinderpest. Complications. Quarantine. 255 This injection was followed by rubbing infectious saliva or blood into the nose, and after five days 100 cc. of blood was again injected subcutaneously. Conti immunized animals with 20 ce. of serum from animals which had recovered from the disease, to which 3 ce. of blood from an animal which had been affected for 47 hours with rinderpest was added. The author reports favorable results from this method of immunization. Complications. Several years ago Koch (1904) and later Theiler and Woolley, pointed out the dangers in the application of the simul- taneous inoculation. In localities where piroplasmosis or trypano- somiasis 1s prevalent there is the danger that parasites of the mentioned diseases may be transmitted with the blood from cattle affected with rinderpest, causing diseases from which the animals die; thus in Egypt in 1903 of animals which had been inoculated with serum obtained in Constantinople (25 ec.), and virulent blood (1 ee.), 80-90% died within a short time, and the losses appeared at least partially to be caused by a piroplasmosis which resembled the East African coast fever. The existence of this disease in Egypt has been established by Koch (he therefore recommends large serum doses of 100 cc. to be used repeatedly instead of the simultaneous inoculation). Theiler also observed a mortality of 6.8% among 452 cattle in South Africa which were inoculated by the simultaneous method. In cattle coming from localities free of Texas fever (124 head), for which a possible piroplasma infection is much more dangerous, the loss amounted to 27.4%. As it is impossible in practice to exclude the blood from animals which have recovered from Texas fever, but still contain in their blood piroplasms, it was deemed advisable in the Transvaal to abstain from the simultaneous inoculation, and serum has been used exclusively, by which means an eradication of rinderpest was accomplished in 1903. ‘Woolley reports a case in which all of the 56 cows imported from the United States to the Philippines died after the simultaneous inocula- tion, probably from piroplasmosis, while according to Nesom’s observa- tions, in the Philippines, the otherwise effective simultaneous inocula- tion causes a loss of 4% as a result of trypanosomiasis, which develops after the injection. Spirillae, or the virus of heart water, may also be the cause of possible bad results from this method. Veterinary Police. The safest prophylactic measure con- sists in a quarantine against countries in which rinderpest pre- vails. Since the practical application of this principle Western and Central Europe have been freed of the disease, although the plague has appeared repeatedly in an epizootic form in Russia and on the Balkan Peninsula. The introduction of the. disease may also be prevented to some extent by establishing a carefully executed registration of cattle at the endangered borders of the countries, which would considerably facilitate the establishment of the origin of the disease, if it has been in- troduced. If the disease should make its appearance in any locality the immediate slaughter of all affected, as well as all exposed animals, together with the thorough disinfection constitutes the surest method for its eradication. If however such a procedure cannot be executed it is advisable to segregate the infected herds into small groups, keeping them completely isolated under observation. (According to Piot-Bey better results were ob- 956 Hinderpest. tained in Egypt with this method than from serum inocula- tions.) At the same time the other ruminants, especially sheep and goats, should also be considered as carriers of the virus. In the meantime the losses in infected herds may be diminished by the application of one of the above-described modes of im- munization and in neighboring herds the animals should all be given serum inoculations thereby producing an immune zone around the infected herds. Literature. Dieckerhoff, History of Rinderpest and Its Literature, Berlin, 1890.—Semmer, B. t. W., 1893, 590.—Koch, Zbl. f. Bakt., 1897, XXI, 526; Veréff. d, G.-A., 1904, V, 681.—Kohlstock, Ibid., 1897, XXII, 787—Kolle, Z. f. Hyg., 1898, XXVII, 45; Ergebn. d. allg. Path., 1899, VI, 470 (Lit.)—Kolle & Turner, Z. f. Hyg., 1898, XXIX, 309.—Theiler, D. t. W., 1898, 205; Monh., 1901, XIII, 145.— Rogers, Z. f. Hyg., 1900, XXXV, 59.—Nicolle & Adil-Bey, A. P., 1899, XIIT, 329; 1902, XVI, 56.—Blin & Carrougeau, Bull., 1902, 107.—Yersin, A. P., 1904, XVIII, 417.—Hidicke, B. t. W., 1904, 823.—Arloing, Journ. de méd. vét., 1905, LVI, 385.—Holmes, J. of comp. Path., 1905, XVIII, 207.—Stockman, Ibid., p. 207.— Head, Ibid., 1906, XIX, 12.—Rassau, Z. f. Infkr., 1906, I, 382.— Woolley, Rev. gén., 1907, X, 68.—Kowalewsky, J. vét., 1908, 146.—Riidiger. D. t. W., 1909, 400.— Eggebrecht, Z. f. Infkr., 1910, VII, 54. Rinderpest in sheep and goats. In 1861 Galambos established with certainty a disease in sheep identical with rinderpest, and he succeeded also in transmitting it artificially to sheep (6 animals in- oculated became affected on the 10th day). Since that time the sus- ceptibility of sheep as well as of goats has been confirmed repeatedly, and according to Roll only about 55% of these animals resist artificial infection. Extensive outbreaks among sheep were observed in 1862 in Poland, where 64-74% of the flocks became affected (Seifmann) ; in 1863 in Sicily, where 20,000 sheep and goats succumbed to the disease (Chicoli) ; further in 1870-1871 it affected the sheep in France and Alsace-Lorraine, in the latter provinces causing a loss of 4,000 animals (Zundel). The clinical manifestations consist in the milder forms, in fever, catarrh of the conjunctivae and the nasal mucous membranes, accelerated respiration, dry cough, and passing of very dry feces. In severe cases there is great debility and apathy, a yellowish-white discharge from the eyes and nose, moist cough and frequent passage of thin, greenish- brown excrements mixed with mucus. In favorable cases the patients improve very rapidly after an illness lasting 4-5 days, while in severe cases death ensues in the same ‘length of time. The mortality in sheep and goats is generally smaller than in eattle, rarely exceeding 25-30%, Tamilini however observed a loss of 75%. The anatomical changes resemble those in cattle, but extensive pseudo-membranes and ulcerations on the mucous membranes do not usually occur. The ordinary changes consist in a hemorrhagic inflam- mation of the mucous membrane of abomasum and intestines, with reddish-yellow, loosely adhering deposits. Similar changes are also present in the mucous membrane of the air passages and in the bladder. There is also anemia of the lungs, and an interstitial emphysema (according to Réll a catarrhal pneumonia is noted with relative fre- quency). Literature. Galambos, Gyégydszat, 1862, Nr. 4.—Maresch, 0. Vijschr., 1863, XIX, 34.—R6ll, Rinderpestihnl. Krankh. d. Schafe u. Ziegen. Wien., 1864. Heartwater. Hog Cholera. 257 Heartwater. According to Theiler a disease of cattle occurs in several localities of Transvaal, which is known there as Veldt-sickness. The most striking symptom of the disease is the filling of the pericardium with a colorless or yellowish fluid (hence the name heartwater). There is also a pronounced indication of acute gastro-enteritis present. The micro-organism is, according to Counsbury, transmitted from the af- fected to the healthy animals, by a tick (Amblyomma hebraeum) ; sheep and goats are also very susceptible. The same disease occurs also among sheep and goats, and may readily be produced by the subcutaneous or intravenous injection of blood, but not of the pericardial fluid. The transmission may be made from sheep to cattle, and vice versa. The symptoms develop 5-15 days after the injection, and consist of high fever, dullness, exceptionally also in nervous symptoms, such as continuous moving of the tongue and the jaws, turning in a circle, later a stiffness of the neck (hence the name ‘‘brainwater’’). The autopsy reveals a great quantity of fluid in the pericardium and pleural cavity, also petechiae on the peri- cardium, edema of the lungs and moderate acute swelling of the spleen. The disease, which has been known in South Africa for about 40 years occurs only in certain localities, principally during the summer time, and in pastures located upon high lands. The Kaffir goat and the native fat-tailed sheep are not susceptible, while the Persian sheep are only slightly susceptible to the disease. Hyperimmunized cattle, sheep and goats produce an effective serum for their respective species, a practical immunization however has not yet been established. The supposition of Edington that the disease is identical with ‘‘horse-sickness’’ is considered by. Theiler as incorrect, as horse-sickness can be transmitted artificially only to horses (see page 286). According to Edington’s view the disease is identical with the. African horse- sickness (see that disease). Spreull on the other hand contends that the diseases of cattle occurring in South Africa under the names Lamziekte, Gall-sickness, Veldt- sickness, Blood-lung and Inapunga are identical with Heartwater, and he considers their causative agent to be a motile bipolar bacillus. Clinically he distinguishes an edematous form, with swellings on the neck and head, a thoracic form with con- gestion and hepatization of the Jungs, and a paralytic form which is associated with a stiffness of the gait. a 2S yee Literature. Theiler, The Vet. J., 1904, IX, 300; The transv. agric. J., 1904, II, 163; Bull. Pasteur, 1905, III, 617; J. of comp. Path., 1905, XVIII, 155.—Eding- ton, J. of comp. Path., 1904, XVII, 141——Spreull, V. J., 1908, 358. | 11. Hog Cholera. Pestis suum. (Swine fever, Typhoid fever; Schweinepest [German]; Cholera suum, Peste du pore [French]; Peste porcina [Italian].) Hog cholera is usually an acute, sub-acute or chronic, more rarely a peracute, contagious, infectious disease of hogs, caused by a filterable virus. In the course of the disease, with the excep- tion of the peracute cases, inflammatory and necrotic processes develop, produced either by the bacillus suipestifer when the lesions occur in the intestinal canal and in the abdominal lymph glands, or by the bacillus suisepticus when the lesions are mani- fested in the lungs. 958 Hog Cholera. - History. The disease has been recognized in their studies - of American diseases of hogs by Salmon & Smith (1885) as an independent affection (hog cholera) as the cause of which they designated a short motile rod. Based on these findings they sharply separated the disease from swine septicemia (swine plague), considering this as identical with swine plague of Germany, which was recognized just about that time. At the same time they proved that the two diseases are frequently present in one and the same animal, and that the severity of the American outbreaks is brought on by such mixed infections. The same stand- point was accepted in America by Moore and de Schweinitz, in Europe by Raccuglia and Affanasieff. The frequent simultaneous occurrence of the two forms of diseases, that is the frequency of the mixed infec- tions, caused Billings in America, and Silberschmidt and Voges in Europe, to take a stand against the identity of these two diseases and their supposed causative agent (the common name of ‘‘pneumonoentérite infectieuse’’ used in France and England corresponds with this con- ception), while Bang, Schiitz, Jensen and Preisz (1898) confirmed the correctness of the original stand of Salmon and Smith. Through the experimental investigations of the last decade the etiol- ogy of the disease appears to have been definitely established. In 1904 the American investigators de Schweinitz & Dorset made the discovery that a disease occurring in the State of Iowa which clinically resembled hog cholera was transmissible from affected animals to healthy hogs by filtered bacteria-free blood. Soon afterward Dorset, Bolton and McBryde proved that the disease was identical with hog cholera, and therefore that this disease is also caused by a filtrable virus, whereas the formerly supposed causative agent, the bacillus suipestifer, produces the characteristic changes in the intestines only secondarily in the already affected animal. Similar results were also obtained in Michigan almost at the same time by Boxmeyer (1904), while Hutyra (1906), then the Board’s Laboratory of England, Ostertag (1907), as well as Uhlenhuth, Xylander, Hiibener & Bohtz (1907), later Carré, Leclainche & Vallée, also Wassermann, confirmed the correctness of the new conception of the disease in Europe and Theiler in South Africa, At the same time the views concerning the part of the bacillus suisepticus in the production of the secondary affection of the organs were changed, whereby the disease formerly considered swine plague, is now considered in most cases to be a complication of hog cholera. The accurate determination of its etiology directed the combating of the disease into new lines, and the attempts at immunization by Dorset, McBryde and Niles, as well as those by Uhlenhuth and his co-workers, also those by Hutyra, have given valuable practical results. Occurrence. Hog cholera is at present very widely spread in America, and in almost every European country, causing annually great losses among hogs. The disease, which in itself is not very malignant, becomes very fatal as a result of the frequent, secondary inflammatory processes in the in- testines and in the lungs, which, especially in young animals, exist in an epizootic form. It causes the greatest loss in places where hogs are kept in large herds, whereas in localities with smaller droves the disease is combated with better success. Hog cholera is supposed to have first appeared in North America in the State of Ohio in 1833, and from there it spread over the entire Occurrence. 959 territory of the United States. It was probably carried to Europe in the 60’s of the last century. Its occurrence was first established in England in 1862 (swine fever, typhoid fever), where it has since appeared from year to year, causing in 1896 the loss of as high as 30% of all hogs in the country. From England it was supposed to have been spread to Sweden in 1887, with an importation of boars, and from there in the same year to Denmark, to the Island of Amagar, and from there it later extended to other localities in the country. At the same time it appeared in France in the vicinity of Marseilles (it is supposed as a result of an introduction from Algeria), spreading to all parts of this country, as well as Spain and Italy. Roloff reported in 1866 in Germany the occurrence of an infec- tious ‘‘caseous intestinal inflammation’’ in young hogs of English breed in the Province of Saxony, which according to the accurate de- scription of the changes in the caecum and colon was possibly identical with hog cholera. Hog cholera was observed in 1893 as a severe fatal affection in Posen, and shortly afterwards in Prussian-Silesia, from which country it has been disseminated to the neighboring territories of Austria. Extending in an eastern and southeastern direction it reached Hungary in 1895, where it first made its appearance in the fattening establishments of Kébanya and Gyér, causing great losses. At the occurrence of the outbreak at Kébanya of the 180,000 animals 8,368 died, or had to be slaughtered in May; 10,288 in June, and at the end of that year with the exception of Siebenbiirgen, all counties were infected. In the following year the disease existed throughout the entire country. In Germany during the period of 1898-1906 the number of townships infected with hog cholera and swine plague increased from 1,817 to 11,513, and the number of the affected animals from 11,813 to 104,728. Subsequently up to the year of 1908 the number of townships infected diminished to 8,782, and the number of cases to 75,688. The total loss amounted in 1908 to 60,101 hogs, and the disease was most widely spread in the government districts of Breslau, Liegnitz, Posen, Bromberg, Potsdam, Frankfurt, and Oppeln. At the end of 1907 there were infected 1,339 townships, and 86.6% of all outbreaks were confined to Prussia. Hog cholera is widely spread in France, and all parts of the country are infected with the disease. In 1908 from 13 to 20 districts were said to be infected during different months; however the reports are not accurate. For a time the disease has greatly diminished in Great Britain, as a result of the measures of eradication which were inaugurated in 1893. While in 1894 5,862 outbreaks were established in 73 counties, in 1905 only 817 outbreaks occurred in 58 counties. In 1894 to 1896 the number of hogs, which were excluded from traffic on account of the disease or on suspicion, amounted to 56,296, 69,931 and 79,586, while in the year 1905 only 3,876 animals were affected by this measure. In 1906 the disease spread again more extensively, and in 1908 there occurred 2,067 outbreaks in 68 counties, and 14,096 affected or suspected hogs were slaughtered. . The disease diminished in Austria as a result of regulations passed in 1895, and consequently from 1896 to 1898 a gradual decrease in the number of outbreaks resulted; later however it again spread to a considerable extent. In 1895, 2,767 outbreaks with 28,142 affected animals were recorded; in 1898, 654 outbreaks with 4,610 affected animals; and in 1900, 1,100 localities with 35,984-affections. In 1908 the weekly number of outbreaks fluctuated between 104 and 208. The disease was most extensive in Galicia, Bohemia, Moravia and Lower Austria, while Dalmatia was free from it. ; ie od In Hungary in the first year (1895) after the appearance of the affection 1,478 and in the following year 3,569 townships, with 413,562 and 868,777 animals, were affected. From this time on the disease gradually diminished, but even in 1908 2,200 townships were noted, with 263,945 cases, of which 148,110 (56.8%) died (in‘the first 2 years the mortality amounted to 81.4% and 73.6%). _ The disease is most widely spread in the section south of the Tisza and Danube rivers. Of other countries the disease was discovered in 1908 in Bulgaria, affecting 260 Hog Cholera. 73 townships, in Italy 14,499, in Roumania 1,829, in Russia 27,223, in Servia 45 cases, while in Denmark and in Holland the disease appeared less frequently, in Sweden and Norway (in 1903 468 cases, of which 450 occurred in Dép. Akershus) only sporadically. In the United States the disease (hog cholera and swine plague) caused in the year of 1873 losses amounting to 20 million, in 1882 13 million, in 1884 and 1885 25 and 30 million dollars respectively, while in 1888 the loss was estimated to have affected 45,000,000 hogs of a value of 200 million dollars, and in 1903 Salmon estimated the loss at 50 million dollars. Etiology. According to the results of investigations by Dorset and his co-workers which, a8 already mentioned, have since been substantiated by other investigators, hog cholera is caused by an ultra-microscopic virus, which passes the ordinary porcelain filter. Attempts at cultivation, or even increasing the amount of virus have up to the present been fruitless. Pathogenicity. Subcutaneous injections of 1-2 cc. of filtered, defibrinated blood, blood serum or organ juices, produce in young hogs, after an average incubation period of 8 to 10 days, sometimes however in four days or only after 20 days, and without any local reaction, an acute febrile affection with inflaam- January February T. 13 | #4 | 15 | 16 71 18 Io 20 | 21 | 22) 29 | 24] 25 | 26) 27 | 28} 29) 30) ui z 3 4 6 4t|5 SERRE By pa] 5 ‘ea == a) rae] att él 8 a a os > 1. va aa 405) e 3 if a Ps 3 5 2 = it 40 |. t At £ 3 + + o it nay + Kt 395 4 + ris a 4 fica 139 t # i Fa if 38. oy rs t 3S 76 Fig. 45. Hog Cholera. Artificial infection with filtered material from a hog affected with cholera. The first rise up to the fourth day of sickness is caused by the primary infection, the second by the secondary infection. matory swelling of the conjunctivae, eczematous eruption of the skin, followed by diarrhea (Fig. 45; the quantity of blood does not affect the outcome of the disease). In some of the cases the animals die in 3 to 4 days with an acute affection, whereupon the autopsy reveals exclusively hyperemia and acute swelling of the internal organs, as well as hemorrhages on the serous and mucous membranes (sometimes also a great quantity of serous transudate in the pericardium). If the animals remain. alive for a longer time ulcerative and necrotic processes may be found in the intestines, in other cases again pneumonic changes will be observed which are similar to those found in the acute pure swine plague. If the animals remain alive still longer the affection of the intestines and the lungs develops in a more chronic form, whereupon the animals die greatly emaciated, Pathogenicity. 261 or recover completely. Such recovered animals are subsequently immune against artificial, as well as against natural infection. Animals artificially infected in the above manner may readily transmit the disease to healthy hogs by cohabitation, and their blood even in a filtered condition, and in small quan- ‘tities, is also infectious. By serial re-inoculations the virus may be propagated from generation to generation. The artificial affection is, although with less certainty, also successful, by the administration of blood and blood serum in gelatine capsules per os, or by feeding the same with food, when unfiltered material acts more strongly than filtered. The virus is as a rule also present in the bile and the urine, while the intes- tinal contents frequently prove noninfectious (Uhlenhuth). By. feeding internal organs of diseased hogs the disease may readily be produced artificially. Other species of animals aside from the hog are not susceptible to the virus. Tenacity. Fluid material containing the virus retains its virulence at room temperature for 10 to 14 weeks. Heating for one hour at 60 to 70°C. destroys the virus, while in the dried condition subjected to 72 to 76° it requires an hour to destroy its virulence. Blood frozen below —18° and thawed out after 24 hours, proved fully virulent, likewise blood which had been dried for three days. The addition of a 1:1000 corrosive sublimate solution in the proportion of 1 to 2, or of a 5% glycerine-carbolic acid solution in the proportion of 2:5 does not destroy the virus inside of 8 days; on the other hand the virus in serum is rendered ineffective by the addition of 2% formalin in 15 days, by 2.5% antiformin in 2 hours. The virus in old putrefied organs loses its virulence in eight days (Uhlenhuth). Besides the filtrable virus, two species of bacteria, the bacillus suipestifer and the bacillus suisepticus, play an impor- tant part in the etiology of hog cholera. The secondary affec- Fig. 46. Bacillus suipestifer. Agar cul- Fig. 47. Bacillus suipestifer, with fla- ture, fuchsin staining. gella. Agar culture. tions of the intestines and of the lymph glands or of the lungs are usually produced by the pathogenic action of these bacteria. 1. The bacillus suipestifer (Bac. cholerae suis) resembles the colon bacillus and belongs to the paratyphus B-group. It is motile, possessing peritrically arranged (3-9) flagellae, and multiplies exclusively by fission (Fig. 46 and 47). In tissues 262 Hog Cholera. it occurs singly or in pairs, in cultures however it also forms longer chains or even slightly curved filaments. Staining. With aqueous aniline dyes the organism usually stains uniformly, sometimes, however when stained with diluted methylene blue solution, it may: stain more intensively on the poles. It does not stain by Gram’s method. Cultivation. The bacillus grows aerobically as well as anaerobically on all artificial media, in room temperature as well as body temperature; in the latter however con- siderably faster (the temperature limits are according to Frosch +8 and +42°C.). On gelatin plates bluish, trans- parent, uniformly rounded. colonies de- velop, while in stab cultures a continuous grayish-white streak forms along the stab, surrounding which the nutritive medium is sometimes turbid. Gelatin is not lique- fied (Fig. 48). On agar bluish, trans- parent, flat, round colonies develop which do not closely adhere (Fig. 49) ; the growth on coagulated blood serum ‘is similar. On Loffler’s malachite-green plates, and on endo-plates, colorless colonies form, while on Drigalski’s plates the colonies are blu- ish. Peptone bouillon becomes uniformly cloudy, later a loose sediment settles on the bottom of the tube; indol does not form in the cultures. On potatoes a color- less, moist, lustrous, or a brownish-yellow deposit forms (the variance is probably due to the different kinds of potatoes). Milk becomes grayish, in 3 to 4 weeks sa- ponified, and still later it is changed to a stiff, alkaline jelly. Litmus milk is some- what reddened, but after 2 to 4 days it be- comes decidedly bluish. Dextrose is fer- mented by the bacillus, lactose on the other hand is not. Tenacity. The cholera bacillus withstands pope ae Eo ang Ppa eg a the a : uence of sunli an ernate drying an : qo moistening it is. quickly islled. In ordinary drink. ae a more stab cultureof i2g water, also in soil infected with feces of uiture of the the bacillus ®ftected animals, it retains its virulence for 65 4 acillus sud suipestifer. +%0 95 days, while atemperatureof 50° destroys it pestifer. in 66 hours, and one of 55° in one hour (Preisz). Of the disinfectants the growth of the bacillus in inhibited by 1:4000 sulphuric acid, 1:900 potassium hydrate; it is destroyed in one minute by a 1% carbolic acid, solution, 1:10,000 corrosive sublimate, 1% creolin, in 10 minutes by 1% milk of lime, inthree minutes by a 1% copper sulphate solution, in 114 minutes by 0.1% formalin solution, and in three hours by a 2% iron sulphate solution (Koppanyi & Erdés). The bacillus suipestifer is considerably more resistant than the bacillus suisepticus, Pathogenicity. Mice are susceptible to artificial infections, and after an inoculation with 0.1 mg. of bouillon culture they die of septicemia in from 3 to 5 days. The guinea pig and rabbit Pathogenicity. Natural Infection. 263 are less susceptible (after a successful subcutaneous infection they die in 6 to 7 days; showing enlarged spleen and necrotic foci in the liver). Pigeons are only very slightly susceptible (muscle necrosis develops after an intra-muscular infection), while. chickens are not susceptible. If the culture is injected into the cecum of a rabbit, small white dots at first develop on the mucous membrane (swollen lymph follicles) ; later ulcers appear in sizes up to a lentil. By feeding large quantities of cultures or injecting cultures into the intestines of hogs, either acute or more chronic inflam- matory and necrotic processes develop, in some cases according to the intensity of the infection (dysenteric necrosis and ulcera- tions on the intestinal mucous membrane, swelling and caseation of the lymph glands, etc.). After previous starvation or neu- tralization of the hydrochloric acid of the stomach, the disease results in a much more acute and severe form, and the animal may die on the third day with symptoms of septicemia (Salmon & Smith). The subcutaneous injection of the culture results in an inflammation of the neighboring lymph vessels and lymph glands, leading to necrosis, and the animals die in from 2 to 3 weeks, or even later. In some of the cases ulcerations develop in the meanwhile on the intestinal wall, and metastatic, caseous areas appear in various internal organs. Intravenous injec- tions may result in a hemorrhagic septicemia producing death in 1 to 3 days. The infection cannot be produced by inhalation. Contrary to the infection produced by virulent blood, hogs which are infected with pure cultures of the bacillus suipestifer do not transmit the disease to healthy hogs, and if they recover they continue to be susceptible to natural infection. 2. The bacillus suisepticus is in every particular identical with the organism of pure swine plague (see p. 125). Natural infection results apparently from the digestive tract and appears to be transmitted especially by the strongly viru- lent urine of affected animals, while the excrements are fre- quently only slightly or not at all virulent, and therefore play a less important part in the transmission of the disease. In piggeries of localities which were previously free of the disease it always results from an introduction from the outside, while in already infected premises and stables the affection may re- peatedly appear without a new introduction, as the virus retains its virulence for a long time outside of the animal body, in fluids as well as in a dry material. This is proved by the fact that the disease which was formerly unknown in Europe spread in the course of the last decade along the road of swine traffic, and then remained permanently in the infected countries, caus- ing severe losses from year to year. ; ; The very extensive traffic in hogs which exists everywhere and which is difficult to control, is generally the most effective disseminator of the disease, and in this the hog markets, the 964 Hog Cholera. stock dealers, castrators and wandering gypsies (the latter by taking with them the hog carcasses and throwing the viscera about in different pastures) contribute materially to the spread of the contagion. In herds of hogs which have been healthy the disease is in most cases introduced by sick animals, and not alone by those in which acute symptoms may be detected, but also through the so-called runts in whose bodies the filterable virus may also be concealed. Infection may also occur during the pasturing of the animals, in the piggeries, during driving on highways or transportation in railroad cars, which have been contaminated by the excrements of affected animals days or weeks previously. The contagion may be spread from one locality to the other by flowing water, into which carcasses of hogs have been thrown, and carcasses which have been left in pastures or which have not been buried satisfactorily may also occasionally be the cause of an outbreak of the disease. Although hogs of all breeds and of any age may become affected with hog cholera, the higher bred stock and young hogs are much more susceptible to the disease. Sucking pigs become affected only very exceptionally, and as a rule the influence of age is especially marked in localities in which the disease has existed for a long time. Thus during the first years of the existence of the disease in Hungary the older hogs became affected quite frequently, while since that time the disease is confined more and more to younger animals. The greater resistance of the older animals in infected localities is in all probability due to the fact that they passed through a mild form of the disease while young. Pathogenesis. According to the most recent experimental investigations the disease is without a doubt caused by a fil- terable hog cholera virus, which enters the body fluids and multi- plies there. It causes directly a febrile condition, with acute eatarrh of the mucous membrane, and in ease of a severe infec- tion death results with manifestations of hemorrhagic septi- cemia. In the great majority of cases however secondary inflam- matory changes of different organs may become associated with the general blood infection. Such secondary changes occur espe- cially in the pharynx, stomach and intestines, in the correspond- ing lymph glands and in the lungs, being caused without a doubt by the bacillus suipestifer or the bacillus suisepticus. The etiological part of these organisms came into the proper light only after the virulence of the filtered blood of affected animals had been established. Contrary to the former conception by which the bacillus suipestifer was considered as the original and true cause of the disease, there now exists hardly any doubt that it participates only in a secondary manner, yet though it is only granted an inferior part in the transmission of the disease it is very active, Pathogenesis. 965 and has a great share in the development of the organic affec- tions which develop in association with the primary affection. According to Dorset, McBryde and Bolton the following factors proved that this organism is not the primary cause of hog cholera: 1. The artificial transmission of the disease can be much more readily affected by blood from an affected animal, than by subcutaneous injection of pure cultures of the bacillus suipestifer. 2. Hogs which were affected either by natural infection or by subcutaneous injections with virulent blood transmit the disease very readily to healthy animals, whereas animals which were infected with cultures of bacilli do not infect healthy hogs. 3. Blood from hogs which have been infected with blood, proves virulent by subcutaneous injection, while the blood from hogs infected with cultures of the bacilli is harmless for healthy animals. 4. Recovery from the natural or the artificially produced disease confers a lasting immunity, whereas hogs inoc- ulated with the bacillus suipestifer continue to be susceptible to the natural infection. _ Besides these considerations it should also be noted that the bacillus suipestifer cannot be demonstrated bacteriologically in all cases of true hog cholera. Thus Uhlenhuth found the organism only in 76 out of 178 affected hogs, while in the other cases in seven so called varieties of this organism (some of which do not ferment dextrose) three times varieties resembling the paratyphus A-Group, once the bacillus en- teritidis Gartner, 50 times the bacillus pyocyaneus, 36 times streptococci, 27 times staphylococci, and 110 times colon bacilli, were isolated from the organs; while in 14 cases the organs proved sterile. In some of the outbreaks the bacillus appears to occur only rarely, as Boxmeyer in Michigan and Theiler in South Africa failed to demonstrate the bacillus in typically affected hogs. These findings make it probable that in different localities various bacteria, especially of the paratyphus B, or of the hog cholera group, may produce the usual changes in the intestines found in hog cholera. According to views accepted at the present time the bacillus suipestifer forms a group in common with the bacillus paratyphi B and Bac. botulinus, which are pathogenic for man, also including the mice typhus and the psitticosis bacillus, as well as the Bac. Sanarelli. This group is designated as the hog cholera, or the paratyphus B-Group, and the various organisms of this group cannot be distinguished from each other, either by their morphologic and culture characteristics, or by sero-diagnostic methods (agglutination). The only distinguishing signs consist, excepting when their origin may be demonstrated, in certain, not constant, and therefore not characteristic pathogenic prop- erties. The very close relation which almost borders on identity, would explain in hogs, for instance, why it is that various representatives of this group may produce very similar pathological changes, and attain pathogenic properties for man (this theoretical possibility has not yet been proven for the true suipestifer bacillus). Bang and Th. ‘Smith, also Uhlenhuth and his co-workers cultivated strains of the bacillus suipestifer from hog cholera pigs, which showed certain deviations from the common type, and therefore are considered as varieties (some strains produce no gas in dextrose, others coagulate milk, and Smith & Moore even described a non-motile variety). 266 Hog Cholera. Against the idea that the bacillus suipestifer is the primary virus of hog cholera are the experimental observations of Uhlenhuth and his co-workers, who found that virus which was treated for one hour with 2.5% antiformin still proved virulent, while cultures of the bacillus suipestifer lost their pathogenic action even for the very susceptible rabbit, after being subjected to such a solution from 30 to 40 minutes, the organism being readily dissolved by the antiformin. A similar difference is also shown to exist by the fact that the hog cholera virus is destroyed by shaking with a 10% uric acid only in four days (Marxer), whereas the bacillus suipestifer is killed in 23 hours (Stiling); the observation that the bacillus suipestifer agglutinates the serum from hogs affected with acute cholera in dilutions of only 1:5-20 (Uhlenhuth), whereas in animals artificially infected with this bacillus the agglutination takes place in higher dilutions (1:1000 and over) should also be noted. Moreover in virulent hog cholera serum there are no opsonins or bacteriotropins, which have an influence on the bacillus suipestifer (Broll). . Recently (1907) Lourens took a stand relative to the importance of the bacillus suipestifer as the primary cause of hog cholera, when he proved that this bacillus passes through the porcelain filter in a granular form, and that it may later multiply in the filtrate. Filtrates containing bacilli, however, produce inflammatory changes at the place of injection, and since the disease always develops in one to two days, Lourens’ findings are in no way sufficient to weaken the importance of the results obtained with fresh blood and filtrates of organs, or to shake general belief in the correctness of recent discoveries. Moreover McBryde found recently that the bacillus suipestifer may pass through some of the Berkefeld filters, but not Chamberland B and F, which however allow the hog cholera virus to pass. The same applies to the theory of Schreiber, according to which the blood of hogs affected with hog cholera supports, through the agressins which it contains, the pathogenic action of the bacillus suipestifer, or mobilizes the same, the bacillus being a frequent habitant of the intestines of hogs. This theory stands in contra- diction to the fact that even small quantities of blood, and especially from hogs which have not yet developed intestinal changes, produce the disease, and further that artificial infection may also result from feeding such blood, and that antiformin- blood mixtures prove effective, in spite of the fact that the endotoxins of the bacillus suipestifer are destroyed by this product. The view that the bacillus suipestifer plays only a secondary part in the etiology of hog cholera is further substantiated by the discovery that bacilli which morphologically, culturally, and biologically corres- pond to the bacillus suipestifer not infrequently occur in the intestines of entirely healthy hogs; thus Garbert succeeded in demonstrating such in seven out of 23, Uhlenhuth in 8.4% of 600 healthy hogs. Similar results are also reported by Morgan from England, Gardenghi from Italy, and Velzen from Holland. Furthermore Titze & Weichel found organisms in the intestinal contents of calves affected with white scour, which absolutely corresponded to hog cholera bacilli, and also in one healthy calf. The facts mentioned here, as well as the experimental observation that hogs which were inoculated with the filtrable virus develop intestinal changes caused by the bacillus suipes- tifer, lead to the belief that the bacillus suipestifer being a frequent normal habitant of hog intestines, penetrates into the tissues injured by the filtrable cholera virus, and exerts in the same its pathogenic properties. Pathogenesis. 267 A similar view would probably also apply to the part-of the bacillus suisepticus. Ovoid bacteria which correspond in all their characteristics to these organisms occur as saprophytes in healthy hogs (see p. 129). Animals which have been injected subcutaneously with filtered cholera blood frequently develop acute, fibrinous, catarrhal or necrotic pneumonia, in which the ovoid bacteria are present in great numbers. These findings can be explained satisfactorily only by con- sidering that the bacillus suisepticus, like the bacillus suipes- tifer, finds favorable conditions for its propagation in the body affected by the cholera virus, and thereby exerts its pathogenic action in the production of a multiple necrotic pneumonia. .From case to case one or the other of these bacilli, and fre- quently both at the same time or following each other, may become conspicuous in the pathological changes. Therefore in association with the primary cholera infection there may be not only the characteristic anatomical changes of hog cholera present, but also those of swine plague; thus not only the anatomical hog cholera, but also the anatomical swine plague as it occurs in outbreaks of cholera, either in association with the former, or alone, is primarily brought on by the filtera- ble cholera virus. In all of these cases only one disease comes into consideration, and that is hog cholera, which however mani- fests itself in various clinical and anatomical pictures, depending on the secondary infection, namely either as a pure septicemia, as hog cholera or as pure swine plague, or the changes may indi- cate a mixed infection with the last two forms. Accordingly a septicemic, a pectoral and a mixed form of hog cholera may be distinguished. It should however be distinctly understood that the intestinal and the pectoral changes in the organs are only secondary complications, and that strictly they should not be considered as belonging to the manifestations of hog cholera. Contrary to the above-aescrived views relative to the secondary action of the bacillus suisepticus, Ostertag contends that pure swine plague may occur as an independent acute disease even under favorable hygienic conditions, infecting old, as well as young animals, and causing losses amounting to 75%. He further claims that chronic swine plague is directly connected with the acute, destructive, classical swine plague. He bases this view mainly on the observation that the acute form may pass into chronic, and as such may again introduce the acute fatal form, and that with the material of both forms, either of the forms may be alternately produced (see also p. 128). On the other hand Uhlenhuth and his co-workers perfectly agree with the view of Hutyra. They found that pigs infected with filtered blood frequently develop a pleuro-pneumonia, and that the treatment of pigs with immune serum protects them also against a secondary pneumonia. They therefore emphasize the suggestion that changes in the lungs belong to the accompanying hog cholera symptoms, and therefore are to be considered as symptoms of the disease. Therefore the so called pure cases of swine plague in outbreaks of cholera should be considered as cholera infections, and the previously considered mixed 2968 Hog Cholera. forms, that is the cases which were heretofore considered as results of two entirely different infectious diseases, are etiologically due to ohe primary cause, namely to the infection of the body by the cholera virus. At the present time it cannot even be imagined in what way the filterable virus exerts its pathogenic action; on the other hand the pathogenicity of the bacillus suipestifer and the bacillus suisepticus is quite well understood. Regarding the first one it must be accepted that as a rule it penetrates into the follicles of the already catarrhal intestinal mucous membrane, where it produces a cellular infiltration of the follicles, with which a necrosis of the tissues soon becomes associated. In this manner nodules first develop, then small, deep round ulcerations covered with caseous material, which gradually become larger. At the same time usually, but in some instances quite independently, a necrosis of the epithelium and of the superficial layers of the mucous membrane results from the immigration of the bacilli into the lymph spaces of the mucous membrane, whereupon diphtheritic or croupous inflammation results. Such deposits also develop very fre- quently on the mucous membrane of the stomach, and of the pharynx. From the intestinal wall the bacilli pass through the lymph vessels into the mesenteric lymph glands, where they produce a cellular infiltra- tion, and consequently a tissue necrosis, as a result of which dry caseous areas develop in the enlarged glands. In chronic cases the process may remain confined to the intestinal wall and to the mesenteric lymph glands, and may by disturbing the digestion finally result in complete exhaustion of the animals. In other cases the bacilli may be disseminated along the lymph vessels, to distant lymph glands and into the blood circulation. The infection of the blood may sometimes occur in the early stages, and contribute to the aggravation of the already existing septic condition. Besides bacillary emboli may cause the development of metastatic inflammatory lesions, which will later caseate beginning at the center (such caseated areas are most frequently found in the lungs, kidneys, spleen and the liver). The necrosis (caseation) which is quite characteristic of hog cholera, is probably to some extent the result of an obstruction of the blood vessels by masses of bacilli, and the consequently developing nutritive disturbances. In the first place however it is probably due to the toxic action of the bacilli. Up to the present time experiments for the demonstration _of toxins in eul- tures of the bacillus suipestifer have not given uniform results. While Preisz found. that neither inactivated cultures nor bacteria-free filtrates of cultures were toxic for test animals, Voges and Karlinski claimed that the killed bacteria contain an intra-cellular toxin (according to Voges 10 mg. of killed bacteria ate fatal to guinea pigs). De Schweinitz produced a ptomaine from cultures by precipitation with, aleohol (Sucholotoxin) and also a poisonous albumose (Sucholoalbumin). He fur-, ther found two kinds of enzymes in aqueous extracts of agar cultures, as well as in milk in which the bacilli were grown for three weeks, of which the one converts starch into dextrose (Diastase), while the other liquefies gelatin and digests fibrin and albumen (trypsin-enzym). Prettner also found in the cultures bacteriolytic enzymes, which slowly dissolve gelatin. According to the investigations of Prett- ner and Emmerich the bacillus produces nitrous acid in material containing nitrates, as well as in the intestinal canal, which may cause a nitrite poisoning in the body of the animal (cyanosis, necrosis of the intestinal epithelia, paralysis or gangrene of the sympathicus, serous transudations in the intestinal lumen, formation of methemoglobin in the blood). F. Schmidt aimed to obtain specific substances from cholera bacilli, by the use of Brieger’s method (suspension of cultures grown on agar in water "and shaking) as well as through the method of Conradi (autolysis), Pathogenesis. 269 and further with the aid of McFadyean’s apparatus for breaking up bacteria, but he failed in immunizing test animals with the substances obtained by any of the three methods. The toxicity of killed bacilli (endotoxins) is shown by the experi- ments of Uhlenhuth and his co-workers, who succeeded in producing a typical ana- tomical picture of hog cholera by intravenous injections of cultures heated to 60°C. According to Bang’s investigations, the necrophorus ‘bacillus is also a partic- ipant in the production of the necrotic processes, and as a matter of fact it is very frequently found in large clumps at the base of the ulcers as well as in the nodules along the border between the necrotic and living tissue. The bacillus suisepticus exerts its pathogenic action in a similar way in cases of pure swine plague (see p. 127). In the peracute cases it is found quite frequently in the blood more often than the bacillus suipestifer. The lesions of hemorrhagic septicemia which are found at-the autopsy of such cases are evidently largely due to its action. Often, however, the frequent pneumonia and pleurisy is directly asso- clated with the activity of this organism. The fact that the bacillus suipestifer and the bacillus suisep- ticus are very frequently actively concerned in hog cholera besides the filtrable virus, explains why clinical as well as ana- tomical findings should vary to such a great extent from case to case. In the majority of the dead or emergency slaughtered animals in infected herds examination discloses an ulcerative inflammation of the intestines and caseation of the lymph glands, also necrotic inflammation of the lungs, fibrinous deposits on the serous membranes, as well as hemorrhages, while careful bac- teriological examinations prove the presence of both species of the bacteria mentioned. In the course of some outbreaks, as well as after the artificial infection of herds (by introducing affected animals into healthy herds, the placing of a healthy herd on infected premises), septicemic affections usually pre- dominate. The first animals dead from the disease, which probably had the least resistance, show acute catarrh of the mucous membranes ‘exclusively, and more or less numerous ‘hemorrhages, somewhat later pleuro-pneumonia may also be ‘present, while on the mucous membranes of the intestines small follicular ulcerations or superficial desquamation of the mucous membrane may be seen here and there. Later the characteristic intestinal changes of cholera develop, in constantly greater ex- tension and intensity; first a superficial desquamation of the epithelium, then a follicular ulceration, or a diffuse, diphtheritic inflammation of the mucous membrane. At the same time the pleuro-pneumonia occurs with greater frequency, so much so that toward the end of the outbreak it is present in«the great majority of cases. In the animals which still remain debilitated after the acute outbreak has passed off changes. of a chronic character are present either in the intestines orin the lungs. These successive anatomical findings may be explained by the fact that the most susceptible and the least resistant animals are killed by the specific cholera virus at the beginning of the outbreak, whereas the more resistant withstand the primary infection for a time and are only exhausted by the organic affec- tions which develop later. 270 Hog Cholera. Anatomical Changes. According to the presence and the nature of the secondary infection, the following forms of the disease may be distinguished: 1. Pure Hog Cholera (septicemic form). In this the autopsy findings correspond to those of an acute hemorrhagic septicemia, namely hemorrhages in the serous membranes and in the mucous membranes of the pharynx, stomach and intestines, in the acutely swollen lymph glands and probably also in the kid- neys. Jurther there is also a moderately acute swelling of the spleen. In the meantime in some cases the peritoneum is covered with a fibrinous pseudo- membrane, and the intestinal walls are hemor- rhagic. Even in such cases fine, croupous pseu- do-membranes may frequently be found on the swollen and hy- peremic mucous membranes of the stomach and intestines, some- times also a dif- fuse, superficial necrosis (bile stained, mushy deposits), orhere and there yel- lowish scales. 2. Intestinal Form. In this most frequent form of the dis- ease, the intes- tinal tract, es- pecially the cx- Fig. 50. Intestine of hog with follicular ulceration of hg cum and the a aaa large intestines, show intensive changes. In the less acute cases a hard round nodule may be felt on palpation of the wall of the large intestines, or the wall is thickened either in part or uniformly Anatomical Changes. 271 in its entire length. At the same time the flexures of the intes- tines may stick together, and this condition may also be seen in the convolutions of the small intestines, or there may even be adhesions. In acute cases there are lentil to dollar-sized, flat, round, yellow, greenish-yellow, brown or blackish-gray, dry scabs on the mucous membrane of the colon and cecum, espe- cially around the Bauhin’s fold (ileo-caecal valve), and some- times also in the adjoining small intestines, under which the sub- mucosa or the muscularis is infiltrated or thickened. Between these the follicles are swollen to hemp-seed size hard nodules, from which a caseous mass may be squeezed. In some cases the affection may be confined exclusively to an ulceration of the follicles, in which deep ulcerations, with raised, thickened margins, cover the mucous membrane of the intestines. These ulcerations increase in numbers posteriorly, and are of the size of lentils, round and covered with dry tissue debris (Fig. 50). In more chronic cases the inner surface of the intestines usually contains thick, hard scabs, in small numbers, sometimes flat, at other times hemispherical, colored similarly to the above- described lesions, so-called buttons or boutons, which protrude over the neighboring mucous membrane (Fig. 51). The cut sur- face of these buttons appears sometimes in layers, they adhere firmly to the submucosa or the muscularis, and are surrounded by a thickened ring of the mucous membrane. Around these nodules the intestinal wall is frequently thickened and stiff. In some cases the mucous membrane may be necrotic over large sections of the large intestines; in less advanced cases the necrotic epithelium forms a mushy deposit on the surface of the mucous membrane, while later it may change in its entire thickness to a dirty yellow, or greenish-yellow, dry, mushy detri- tus. At the same time the outer layers of the walls of the large intestines are greatly thickened, so much so that the affected sec- tion represents a stiff tube with a constricted lumen. The mucous membrane of the stomach, especially in acute eases, shows a pronounced hemorrhagic inflammation, and is frequently covered with croupous pseudo-membranes. me Tn the acute cases the lymph glands are swollen, hyperemic, and even hemorrhagic. In the later stage they contain small, grayish points, disseminated in reddish tissue; in still more severe cases they change to hard growths up to the size of a hen’s egg, which on the cut surface prove to consist of a gray- ish-red, dry, homogenous necrotic tissue, or of a dry or soft caseous mass. These changes are most frequently and most prominently present in the mesenteric glands, less frequently in the other lymph glands of the abdominal cavity, are sometimes also to be found in the pg ak : no i cavity, and in even in the body lymph glands. ee eee cases tumor-like lesions which resemble those of the lymph glands may be found in other internal organs, which 972 Hog Cholera. may reach the size of a walnut, and contain caseous masses. Such are most often found in the liver, the kidneys, lungs, spleen, udder, bone marrow, etc. The lungs may in exceptional cases also contain circumscribed pneumonic areas, with a yellowish- gray cut surface, without necrosis or pleurisy (Preisz). In the pharynx, at the base and on the borders of the tongue, sometimes also in other parts of the buccal cavity, and in the larynx hemorrhagic inflammations of the mucous membrane, with croupous psendo-membranes and ulcerations, together with a superficial or deep necrosis may very frequently be found. Among other changes which may occur are necrosis of the mucous membrane of the gall bladder, the vagina, and the blad- der, localized or extensive necrosis of the skin, cloudy swelling of the parenchymatous organs, ete. Fig. 51. So called button on the mucous membrane of the large-intestine in hog cholera. The intestines of animals slaughtered during convalescence show at the places of the thrown-off necrotic nodules, ulcera- | tions with a granulating base, or small white scars may serve to indicate the pre-existing ulcerations (Gerosat and Bilitz ob- served in exceptional cases cicatrized constrictions of the intes- tines). The lymph glands of other organs may at times also contain caseous foci. The bacillus suipestifer may be demonstrated only in acute cases in the blood, and even then only in small numbers, while in the spleen it may be present in greater numbers. The same organism may also be found in the affected lymph glands, in the necrotic nodules of the intestinal mucous membrane and in the caseous metastatic lesions of the internal organs. The necrotic and ulcerative processes on the intestinal mucous membranes develop quite slowly. Thus in an animal 12 days after the infection there. are, besides the bean-sized mesenteric lymph glands, only hemp-seed size yellow deposits of exudate on the intestinal mucous membrane; after 14 days they attain the size of a lentil, and after 18 days the exudate or ulcerations may be the size of a dime. At this stage the mesenteric lymph glands reach the size of an almond; een Anatomical Changes. - 9793 21 days after the infection large sections of the intestinal mucous membrane may be covered with a deposit or exudate, and the intestinal wall may be 3 to 4 mm. in thickness. The- mucous membrane of the cecum however may show necrotic areas as large as a quarter in size. ; According to Marek’s histological examinations the nature of the changes in the intestinal mucous membrane are those of a croupous, or croupous-diphtheritic character. The epithelial layer and the propria mucosae changes through a coagu- lation necrosis, into a homogenous layer, which contains fibrinous threads and okstructed blood vessels. This layer is surrounded by a wall of polynuclear leuco- eytes. The bacillus suipestifer and the Bac. necrophorus are found in great numbers on the border line between the necrotic and healthy tissue. The patho- Fig. 52. Hog Cholera. Pig affected for two weeks. logical process. frequently commences in the follicles, occasionally however the necroti, layers may contain healthy follicles. {f larger bacterial colonies develop in othr organs they may cause coagulation necrosis in such places, which later result’; in the formation of sequesters. i : 3. Pectoral Form. This form is characterized by an acute, usually croupous, more rarely catarrhal pneumonia, which in the later stages passes into multiple necrosis. Frequently there is also a fibrinous or sero-fibrinous pleurisy and in some instances also a similar pericarditis. Besides this, the mucous membrane of the gastro-intestinal tract reveals a diffuse, acute inflamma- tion, while in acute cases the other organs indicate a general septic infection. Otherwise the autopsy findings are identical with those of swine plague (see p. 130), and the disease can only be distinguished from this by the fact that the filtered blood or material from the organs is virulent (see diagnosis). 4, Mixed Form. The great majority of cases which are found in infected herds belong to this class. The lesions of the intestinal and pectoral forms, with the corresponding changes of the organs, are present simultaneously from case to case _ but in varying intensity; therefore the autopsy findings vary greatly, even in the animals of one and the same herd. In 974 Hog Cholera. acute cases the mucous membranes of the gastro-intestinal tracts, as well as of the lungs, are simultaneously affected in the above-described manner, while in chronic cases one or the other form is often exclusively present. Symptoms. The time of incubation of hog cholera in arti- ficial infections, carried out as closely to the natural mode of infections as possible (cohabiting healthy animals with affected hogs, or in infected premises, Preisz, Hutyra), is at least 4 days, usually however 13 to 18 days. After a subcutaneous injection of virulent blood the first symptoms also appear at the earliest on the fifth day, more frequently however in 8 to 10 eke and in some cases only after from 2 to 3 weeks (Uhlen- huth). 1. Pure Hog Cholera (septicemic form). Excepting the very rare peracute cases which develop almost exclusively at the beginning of an outbreak and terminate in from 2 to 3 days with manifestations of an acute hemorrhagic septicemia, the clinical development of the acute cases is usually somewhat slow. One of the first indications of the presence of the disease is impairment of the appetite. The animals take their food less eagerly, they separate, apparently quickly satisfied, from the other animals of the herd, stand at one side, alone, or crawl into some secluded corner of the stable or yard. Later they appear only hesitatingly or not at all for their feed. If urged to leave their place they show great reluctance to move, and do so slowly and feebly. They soon stop, and remain for long periods in one place with back arched, and with head depressed. One of the first symptoms and one almost invariably present is an acute conjunctivitis, with the production of a mucous or muco-purulent secretion. Vomiting is frequently observed on the first or second day, the vomited material containing mucus and being stained yellow by bile. There is at first constipation, but diarrhea sets in after a short time. The feces are thin and sometimes bloody. In this stage the patients become more or less weakened, and if the disease does not turn toward im- provement, or if it does not become chronic, death ensues in from 4 to 7 days, with septic manifestations. 2. Intestinal Form. This develops like the first form, but is less acute. The more intense affection is indicated by a dis- tinctly yellowish or greenish coloration, and by the very fetid odor of the feces. At the same time inflammatory or diphtheritic changes appear on the buccal mucous membrane. The borders, the dorsum and the base of the tongue, the cheeks and the pharynx become covered with a dirty gray or yellow, loose de- posit of exudate, the tonsils are greatly swollen, or ulcerations covered by a mushy mass develop upon them. These changes may be observed by examining the buccal cavity. There is also eee Symptoms. 275 pharyngitis, associated with difficulty in swallowing, frequently also by difficult, rattling respiration, and death may result from asphyxiation. ; In the less severe form these symptoms continue to exist, and in some eases several small or larger growths may after a time be felt in the abdominal cavity by palpating the relaxed abdominal wall (lymph glands and adherent intestinal loops). Tn severe cases the animals, having lost their appetite, be- come more and more emaciated, the diarrhea alternates with constipation (this is sometimes also observed in extensive ulcera- tions of the intestines), they become very weak and anemic, move only with difficulty and with a staggering gait, or they stand in one place with back arched, and with croup sunken (Fig. 52). Towards the end they continuously lie on the ground, and die completely exhausted, at the earliest on the 11th day after the infection, mostly however in from 2 to 3 weeks. "Tn other cases the acute symptoms of an intestinal affection diminish in 1 to 3 weeks, the appetite gradually improves, the diarrhea ceases, the animal moves about more lively, and finally a complete recovery takes place. Sometimes the animals con- tinue to be sickly, in spite of the fact that the acute symptoms become milder. The appetite remains irregular, normal move- ment of the bowels alternates with diarrhea, the animals do not show a normal development, gradually a severe anemia and cachexia sets in, which finally leads after some months to com- plete exhaustion. 3. Pectoral Form. With the initial symptoms of pure hog cholera manifestations of an acute pneumonia or pleuro-pneu- monia become associated after several days and from this stage on the clinical development is identical with the acnte or chronic swine plague (see p. 132). 4, Mixed Form. In this form symptoms of varying inten- sity develop in connection with the symptoms of hog cholera infection, which indicate gastro-intestinal trouble, as well as an affection of the thoracic organs. Besides inappetence and diarrhea there is a cough, and increasing difficulty in respira- tion, and in unfavorable cases death results as a rule directly from the affection of the thoracic organs. In the later course the symptom-complex of both forms may exist for a long time, and they are not infrequently observed simultaneously even in the chronic cases; while occasionally the manifestations of the lung affection are less pronounced in the early stages, they later ° become milder, and the dominating symptoms then consist of a changeable or depraved appetite and diarrhea. The cases belonging to this form manifest with relative frequency changes in the skin. Aside from the extensive necro- sis which is sometimes present, resulting from the action of the hog cholera bacillus, and being principally observed on the ears, 276 Hog Cholera. ; red spots frequently appear on the finer parts of the skin, which develop as a result of a simple dilation of the vessels. Later small vesicles form in these places, and soon the superficial epithelial layer separates in fine lamellae. The abdomen some- times shows numerous punctiform hemorrhages, which remain noticeable for a long time even after recovery. Occasionally urticaria may develop, when vesicles will appear on the flat, raised lesions (Schindelka). In some cases the bristles may fall out on different spots or over the entire body, animals with dark pigmented skin may become white, and‘if the animals re- main alive white bristles grow on the bald places, which however may later be replaced by black. Diagnosis. The clinical symptoms do not afford sufficient grounds for the establishment of a positive diagnosis. Although they cause a well-founded suspicion of hog cholera, especially in already affected herds or if the disease is prevalent in the local- ity, the determination however must be made dependent on the autopsy findings. As in accordance with the present state of our knowledge the bacillus suipestifer or other bacteria of the hog cholera group under natural conditions produce only in the body weakened by the filtrable cholera virus follicular lesions on the intestinal mucous membrane, and the ulcerations and buttons resulting from these with simultaneous caseation of the regional lymph glands, these changes must be considered as characteristic of hog cholera. Therefore where they are pres- ent the diagnosis of hog cholera may be established without consideration of accessory circumstances. The fact that it is sometimes possible to produce the anatomical hog cholera artificially, with the bacillus suipestifer alone, does not indicate that this occurs under natural conditions, especially as positive results have only been obtained in feeding experiments with very large quantities of culture. Glasser is nevertheless of the opinion that an organism which he isolated from two apparently sponta- neously affected pigs, and which biologically differed from the bacillus suipestifer resembling more the human typhoid bacillus (Bac. typhi suis), may independently produce a contagious epizootic infection (typhus of hogs). However the occurrence of such a spontaneous enzootic, or even epizootic, has not been confirmed from any other source. According to a preliminary report of Stedefeder the bacillus suipes- tifer also may produce spontaneous affections independently, without any pre- existing accessory influence of an ultravisible virus. Contrary to the formation of intestinal lesions, the presence of a necrotic pneumonia, even in a typical form, has not the same pathognomonic significance, as this form may occur inde- pendently without any participation of the filterable hog cholera virus, and in such case it must be considered as pure swine plague. The decision whether in a single case one is dealing with pure swine plague, or hog cholera with swine plague symp- toms, is in practice sometimes very difficult. If besides the inflammatory infection of the lungs there are at the same time seabs, round ulcers with discolored covering, or even button- like scabs on the mucous membrane of the intestinal canal, with or without swelling of the lymph glands, a cholera infection Diagnosis. 217 must always be considered. On the other hand, 1t there is pres- ent a pure hemorrhagic septicemia, or only an acute croupous catarrhal, hemorrhagic, or a necrotic pneumonia, with or with- out a fibrinous pleurisy, or if the case shows chronic remnants of a pre-existing acute pneumonia(large necrotic areas, seques- ters) then the anatomical changes, together with the micro- scopical and cultural findings, do not clear the true nature of the affection. In such cases filtration tests are final, and if a positive result is obtained with these the presence of a cholera infection is thereby established. Still, a negative result of - such a test is not conclusive; as the cholera virus which has been present in the body fluids may already have disappeared from the body to a great extent or entirely. In such cases the diag- nosis must depend upon whether the animal comes from a herd infected with hog cholera, and whether in any of the other ani- mals there were any lesions pointing to an infection of hog chol- era, or if a case represents a sporadic affection from a herd which has proved healthy. It is essential therefore, in such cases, to consider the epidemiologic factors, and to attach to them their appropriate value, establishing the diagnosis. Of course this presents far greater difficulty in reaching a diagnosis, when compared with the former conditions, in which the bacteriological demonstration of bipolar ovoid bacteria or cholera bacilli in the organs showing the inflammatory changes were alone sufficient for the determination of the disease. By such findings the disease was designated as hog cholera or swine plague. At present however the demonstration of these bacteria, whether in the blood or in the organs, is not of con- clusive importance for the establishment of the diagnosis of hog cholera or swine plague. It now becomes necessary to consider the gross anatomical changes of the organs, in doubt- ful cases also the epidemiologic accessory circumstances, and the nature of the affection of other animals in the same herd. In bacteriological examinations the simple microscopic examination does not always give positive results, but with the aid of culture and agglutination tests it is in most isistances possible to demonstrate the bacteria which participate in causing the pathological processes. Animal inoculations with material from lesions as a rule is only adopted for the demonstration of the septicemia bacillus, as small animals are killed by these organisms in from 24 to 36 hours, and their blood or the exudate of the abdominal cavity contains in such instances only this bacillus, even though the inoculated material also contained the cholera bacillus. Swine erysipelas frequently greatly resembles a septi- cemic form of hog cholera, especially when there are only few and small hemorrhages present in the internal organs, such cases usually occurring in the beginning of outbreaks. The microscopical finding of erysipelas bacilli in the blood or in the spleen of course establishes the diagnosis of erysipelas. It is advisable however to postpone the final decision in negative findings and to depend on the autopsies of other animals which may die or which are slaughtered in emergency. If hog cholera 978 Hog Cholera. exists it is certain that in one of the other animals there will be found intestinal or pulmonary lesions pointing to the disease. Chronic cases of hog cholera may be mistaken for tuber- culosis; a distinction is only possible by a bacteriological exami- nation, unless the intestines contain the characteristic uleera- tions of hog cholera. Neither the allergic cutaneous, the ophthalmo-reaction, nor the complement fixation method can be utilized for the diagnosis of hog cholera (Uhlenhuth and others; the authors also failed to obtain satisfactory results with the second of these methods). Course and Prognosis. The septicemic and the intestinal form of hog cholera is considered among the less fatal dis- eases, as it leads to recovery with relative frequency. In herds infected with the mixed infection those animals usually recover in which symptoms of a lung affection are absent or occur only in a mild form. On the other hand the pectoral and the mixed form has a much more malignant character, but even in these cases the mortality fluctuates within wide limits. While in localities in which the disease has appeared for the first time, the mortality, especially among the young hogs, may reach 80-90%, in later years it will be much lower. In herds which are kept under favorable hygienic conditions very frequently only 10-15% of the animals may die, and by taking proper precautions it is possible to reduce even this number. Herds in which cholera has already caused a loss of about 15% and over usually resist later infections permanently, there- fore a repeated appearance of the disease in the same herd is observed only very exceptionally. The case reported by Téth is probably isolated, in which in a herd of 550 hogs 18% died first, several months afterwards 32%, and after another two months 12%. : In giving a prognosis the character of the disease should be considered, that is the more the septicemic and the pectoral . manifestations predominate, the less favorable is the prognosis. Hemorrhages from the body cavities are almost certain fore- runners of approaching death; likewise the severe pneumonias terminate in most instances unfavorably. On the other hand in cases where only the intestinal affection appears to be pres- ent, the recovery of the animal is more or less certain, accord- ing to its intensity. Treatment. At the beginning of the disease, when no com- plications, especially of the thoracic organs, have become asso- ciated with the affection, therefore in the first 4 or 5 days of the febrile condition, treatment with the specific immune serum frequently gives good results. Quite often a rapid recovery takes place after a single injection of serum, while in other Treatment. Prevention. 279 cases 1 to 2 repetitions of the injection bring about recovery. (See further under immunization.) Medicinal treatment has not given any decided results. In consideration of the supposition that the infection results from the intestinal canal, the administration of disinfectants was tried, but without much benefit. Of such remedies milk of lime, naphthol, iron sulphate, carbolic acid, calomel (2 g.), creolin (2% solution), arsenous acid (0.2 g.), and formalin milk (14-44%) have been tried. According to observations such a treatment could be only considered for the purpose of protecting if possible healthy animals from the infection. (The carbolic -acid enemas recommended by Trevisan, 800-1500 g. of a 0.5% solution twice daily, has also been found effective in several eases by Kolisch). : Some authors recommended the intravenous or subcuta- neous injection of antiseptics; thus Marenghi advised corrosive sublimate (1 part corrosive sublimate, 3 parts salt, 1000 parts water ; 0.5 to 2 g. of this injected into the auricular vein) ; Hajnal suggests lysol (subcutaneous injection of 5 g. of a 20% alcoholic solution) and also antipyrin; Révész chinosol (3 ec. of a 2% solution subcutaneously). The.effectiveness of these treatments however has not yet been confirmed by other observers. __ It is essential to place the patients in a clean airy place, and they should be given easily digestible feed; if the clinical manifestations indicate a severe infection the early slaughter of the animal should be recommended. Prevention. Herds which are free from the disease should be protected as much as possible from infection. Animals just purchased should be kept isolated for at least three weeks. In large herds infection of the animals is not infrequently avoided by preventing the contact of the herd with strange hogs, espe- cially with those belonging to the farm hands, as well as by keeping them from strange pastures and highways. Cleanli- ness of the piggeries and their’surroundings, as well as peri- odical disinfection aid considerably in maintaining the health of the hogs. If the disease has already appeared, the affected animals should be slaughtered or left in the infected locality, while the healthy hogs should if possible be divided into small groups, and driven to uninfected places. Should new cases develop in these parts the procedure should be repeated, and the infected pasture should always be avoided. If the disease has appeared in the public pasture, and if it is not possible to remove the remaining healthy animals to a clean pasture, the spread of the disease may be prevented by subjecting the animals to a con- tinuous stabling, for at least two weeks. Of course the premises should be placed under veterinary supervision, and where the disease appears the contagion should be destroyed rapidly by early slaughter of the affected animals and thorough disinfec- tion of the stables. 280 Hog Cholera. Immunization. Practical results can be only hoped for from: a method of immunization which will afford effective protection against primary infection with the filterable cholera virus. After the demonstration of the latest facts regarding the etiology of the disease by establishing the virulence of the filtered tissue fluids of affected animals, experiments were undertaken to work out a suitable method of immunization, and they have already led to valuable results. . Purely practical observations showed years ago that animals recovering from hog cholera were usually immune for their entire lives. This fact has been utilized by Hungarian hog feeders, as they prefer to feed animals from herds in which the disease has already caused some losses. As a matter of fact they pay consid- erably -higher prices for such animals. The idea of using serum from hogs which soncieanedl from cholera for immu- nizing purposes, was first utilized by Preisz (1897). He obtained serum from a hog which had been convalescent for three weeks after a severe attack of cholera, and in which the autopsy revealed marked lesions of cholera in the intestines and mesenteric lymph glands. The serum was injected into 30 pigs from 3 to 4 months old, each animal being injected with 10 ec. of such serum. These 30 animals were later placed in a stable with 30 healthy pigs, and with several affected hogs. In the course of one month, 18 of the inoculated animals became sick, and 9 of them died, while all of the control animals succumbed (the last one after 4 months). As a result of these findings immunization with blood serum from slaughtered or recovered animals has been used extensively in Hungary. The results however failed to come up to expectations, which probably was due to the fact that the material was not always taken from recovered animals which had passed through a severe form of the affection. After the presence of the causative factor of the disease had been recognized in the filterable virus, the attempt was imme- diately made to hyperimmunize hogs artificially, according to the method of immunization used against rinderpest, and thereby prepa: > a suitable serum for passive immunization, and by the simultancous use of virulent blood to produce, if possible, an active immunity. These expectations have been fulfilled, insofar as satisfactory methods of immunization have been de- veloped which are practical for both purposes. : 1, Immunization with Immune Serum, (Passive Immuniza- tion.) According to the experiments of Dorset, McBryde & Niles, Uhlenhuth, Xylander, Hiibener & Bohtz, Ostertag and Stadie, as well as Hutyra & Wetzl, hogs which acquired an immunity from a natural or artificial infection of hog cholera, when injected by a single large dose, or by several small doses of virulent blood, produce a serum which protects susceptible hogs for at least three weeks against artificial, as well as against natural infection. This immunity is also effective during the first six days of the incubation period (Hutyra & Wetzl). The results in practice proved satisfactory, as with the aid of this method it is possible to considerably reduce the losses in herds which have been affected only for a short time, and in many eases to check the outbreak abruptly. Besides this, in animals which are in the stage. of incubation, or which have only been affected for a few days, the serum possesses a curative action. It was found further that in infected herds the animals which Immunization. 281 were protected by the serum inoculation will not become affected by, the disease later on, or only exceptionally, in spite of the existing dangers of infection. This leads to the belief that the animals which were given a passive immunity by the immune serum, have acquired an active immunity as a result of a natural infection which has taken place in the meantime. On the basis of this experience it is advisable to treat all herds which are threatened by the infection with the immune serum, and especially those in which the disease has already appeared, and to retain the drove in the same place until the infection is eradicated. At the same time the apparently affected animals should be separated, and those which are af- fected severely should be slaughtered. In case the disease appears again in the herd it is advisable to repeat the injection with the immune serum. Dorset, McBryde & Niles (1905-1907) treated immune hogs by two methods. In the ‘‘quick method’’ they injected one dose of 900 to 1500 ec. of virulent blood (10 ce. per pound of body weight) sub- eutaneously, in the ‘‘slow method’’ gradually increasing doses of 500 to 900 ec. (1 to 5 ce. per pound of body weight) of such blood at intervals of 3 to 4 weeks or even longer periods. About three weeks after the single injections, or after the last injection, as well as later at various intervals, they have drawn blood from the injected animals. The serum from such blood when obtained by defibrinating, or by allow- ing it to stand immunized animals weighing from 25 to 50 pounds when injected in 20 cc. doses, against a simultaneous infection of 1 to 2 g. of virulent blood, and also against subsequent natural exposures. Later the forced immunization was accomplished by injecting the hogs once or twice intravenously with 5 ce. of virulent blood per pound of body weight, or with 10 cc. intraperitoneally by a single injection. The immune serum is used in the United States mostly for simultaneous inoculations (see below), and is only rarely employed alone. Experiments regard- ing the curative action of the serum showed that if the serum treatment is under- taken not later than four days after infection, the outbreak of the disease may be prevented. According to the reports of the Bureau of Animal Industry the results from the practical application of the serum are very satisfactory. Uhlenhuth and his co-workers (1907) produced a similarly potent serum from hogs, to which they had given several subcutaneous injec- tions 6f 25 to 100 cc. of virulent material, mostly blood. The serum in doses of 10 to 50 ec. protected healthy pigs from a subsequent severe, natural infection, while animals which were not inoculated, ‘or which were given large doses of horse serum, died from hog cholera. Doses of 10 to 20 ce. also protected against the pathogenic effects of 0.5 ce. of virulent blood, when injected subcutaneously at the same time. Potent serum can be prepared only from hogs, not from horses or asses. Practical experiments with immune serum have been made in various herds, most of which were severely affected, 330 out of 743 hogs being immunized while 413 were not given the treatment. The loss among the inoculated hogs was 61 (18.4%), among those which were not inoculated 212 (51.3%). The dose of the serum was 20 to 50 ce. Ostertag’s laboratory experiments with serum of successively highly immunized hogs have also given good results. With this serum 9892 Hog Cholera. pigs may be protected against an infection of cholera, and Stadie & Raebiger have obtained mostly good results in practice with his serum, testing it upon 24 herds. In Germany a serum prepared by Gans is also in use, and Spitzer, Stock and Pfeil obtained beneficial results from its application. Hutyra & Wetzl treat hogs weighing from 60-100 kg. which have recovered from the disease, either with a single injection of 1000-1200 ee. or 2-3 injections of 500-600 ec. of fresh defibrinated blood from slaughtered hogs affected with hog cholera. Ten days after the last subcutaneous injection, and at intervals of 2 to 3 weeks afterwards, they are bled from the tail, and finally they are bled to death. The blood is used for immunizing purposes, either defibrinated, or it is used after centrifugation as pure serum. Finding that the pre- liminary tests gave favorable results, serum immunizations have been employed regularly in Hungary since 1909,' and on the whole with satisfactory results. In the preliminary tests 285 hogs of five herds were injected once or twice with 10 cc. of filtered serum, or 15 cc. of defibrinated blood, while 240 animals were not injected. After placing the animals in badly infected stables, the losses among the inoculated animals in the various herds amounted to 6.1 to 35.4%, among the hogs which were not inoculated 40 to 66%, the difference in favor of the inocu- lated animals amounting to 20 to 60%. Up to October 15, 1909, reports from 106 farms, with a total of 10,661 apparently healthy hogs, gave the results of the serum treatment as follows: in 42 herds with 3,125 inoculations the disease was immediately checked; in 22 herds with 3,754 inoculations the loss amoufted to 1.9%, in 7 herds with 730 inoculations the loss was 8.2%, in 14 herds with 1611 inoculations 15.7% succumbed, in the remaining 21 herds the losses amounted to 23.7 to 57.6%. In 46 herds in which 4,189 animals were inoculated, 5,008 hogs not being given the treatment, 8.8% of the inoculated animals died, and 30.9% of those which were not inoculated. The inocu- lations were absolutely without results in only eight herds, with a total of 599 inoculated, and 659 non-inoculated animals, ‘The losses in these cases amounted to 63.8 and 57.9%, respectively. The treatment of animals which were already manifestly diseased (2,681 cases) was in only a few cases successful and then the animals improved very rapidly and recovered. The recurrence of the disease in herds which had been treated previously with the serum, and from which the disease had been eradicated, has up to May, 1910, been observed in only five instances. (The dose of serum was 10 ce. per animal weighing from 20 to 40 kg.) : Favorable results with the serum are also reported by Szuran, Szab6, Tokayer and Ma4rton, but Szurin andMa4rton failed to obtain good results in one herd each where the majority of the animals were already affected. In one instance the outbreak was abruptly checked by the immunization, but 55 days later the disease recurred with great severity. 2. Immunization with Immune Serum and Virulent Blood. (Simultaneous Method.) In the United States this method is mostly used according to the procedure of Dorset, McBryde and Niles, the animals being injected subcutaneously with 20 ce. of immune serum, and 1-2 ec. of virulent blood. This treatment has also by our numerous observations been proven to confer an active immunity upon the animals which lasts at least six months, and probably even a longer time. Nevertheless the practical application of this method does not, at least for the present, appear to be altogether without danger, as some of the inoculated animals apparently become affected, and scatter Immunization. 283 the virus. Such accidents cannot be excluded at the present time, as the virulence of the blood fluctuates considerably in the affected animals, and there is no satisfactory method by which the virulence of each can be established rapidly; there is likewise no quick method for the standardization of the serum. In 1905-1906 168 hogs were treated in the United States by the simul- taneous method (2.5-20 ce. serum, and 0.25-5.0 cc. of virulent blood, each separately, but simultaneously injected). Of these 35 (21%) became slightly affected, while 15 (9%) succumbed. On the other hand 54 hogs became affected after the injection of the same quantities of virulent blood, and 50 (92.5%) of these succumbed to the disease. When the hogs which had been treated by the method described were exposed on infected premises, they remained healthy with very few exceptions, while all control animals became severely ill, and most of them died. Some experi- ments on suckling pigs showed that immunization may also probably be used with good results at a very early age (Dorset, McBryde & Niles). Up to November, 1909, about 2,000 hogs were treated with satisfactory results, the losses among the inocu- lated animals in infected herds amounting to 5-15%, in herds free from the, disease 0%, whereas among the animals which were not inoculated the losses amounted to 75-89 and 35% (Melvin). 3. Other Methods of Immunization. The preparation of a potent serum from horses and cattle has not been successful (Uhlenhuth and Hutyra), and except for the method described above there is at the present time no procedure which has been tried in practice sufficiently. Marxer prepared a vaccine by shaking. virulent hog blood at 37°C. for four days in 10% uric acid, or for three days with 25% galactose, this vaccine proving effective in immunizing pigs in laboratory experiments. Inoculated animals did not become infected, and failed to infect healthy pigs. For its practical appli- cation it is recommended to inject the animals at intervals of several months, from 3 to 4 times, with 5 cc. of the vaccine. Uhlenhuth and his associates found on the other hand that pigs treated by this method do not acquire an immunity, and that it is not possible to establish an immunity with virus attenuated or killed by either physical or chemical means. King employed for a vaccine the serum of horses which had shortly before been injected intravenously with 85-200 ce. of virulent hog serum. On the assump- tion that the virus is gradually attenuated in the body of the horse, he used the blood of a horse which was drawn six hours after the intravenous injection as a vaccine. He treated several hundred hogs by this method in practice, the results however were varied. While apparently favorable results were obtained in several herds, the disease appeared shortly after inoculation in 11 other herds which had hitherto been free from the disease. Immunization Against the Bacillus Suipestifer. Before the establishment of the etiology of hog cholera, the immunization experiments were directed against the bacillus suipestifer, as the supposed causative factor of the disease. The prac- tical results however proved entirely unsatisfactory in spite of the apparent good results in laboratory tests on small animals. At present the tedious experimental investigations are only of generally scientific interest, as it appears very improb- able that the treatment of hogs with a serum which, although successful against the secondary infection of the bacillus suipestifer, will ever prove of any advan- tage in its practical application. ; ; . Recently Stedefeder reports on several experiments in which he succeeded in immunizing pigs against the suipestifer disease, which is said to occur independently (see p. 276). The serum was obtained by a preparatory treatment of rabbits, horses and hogs. Veterinary Police. The observations made in recent years have proved repeatedly that hog cholera may be limited to single premises or farms, and the losses be reduced in a great measure by the immediate application of suitable methods of 284 Hog Cholera. prevention and eradication. Accordingly the veterinary police measures (compulsory reporting, isolation of affected animals, . farm or town quarantine, isolation and if possible slaughtering of the affected animals, destruction of the carcasses, closing up of the hog markets, and prohibition of the peddling of ani- mals, ete.), when applied at the right time and if energetically executed will lead to favorable results. As hog cholera always develops as the result of the intro- duction of the virus, and as it is of a decidedly contagious nature, there remains no doubt that it may be eradicated from large territories by obligatory slaughter of the affected and sus- pected animals. This procedure, when vigorously executed, has brought good results in several places in which the disease has not become prevalent to a great extent, and where hogs were kept in small groups, and the traffic with these animals was not very extensive (for instance in Sweden and Norway). Such a method of eradication would also bring about the desired re- sults in countries in which hog breeding is well developed, where the traffic in hogs is very extensive, and the disease has already spread considerably. Eradication based on this principle would of course necessitate a corresponding indemnity to the owners, and would also have to be aided by immunization. At the present time the most powerful obstacles in the way of such a procedure are the financial difficulties. The eradication has been in progress in Great Britain since 1893, and the results are indicated, at least up to 1905, by a marked reduction in the number of cases (see p. 259). ' In Austria a law of 1899 requires the obligatory slaughter of affected, exposed and suspected animals, for which an indemnity reimburses the owners. Until the end of 1901 102,769 hogs were slaughtered, and the entire cost of the eradica- tion amounted to 2,625,470 crowns. The results of the eradication did not come up to expectations, as repeated introductions from foreign countries have greatly hampered it, although in recent years a diminution of the disease has been observed in the Alpine countries. ¥ Veterinary police measures may be aided greatly by im- munization, inasmuch as outbreaks may be checked and the spreading of the disease to surrounding herds may be pre- vented by serum inoculations. In the United States a procedure is followed to a great extent, in which the newly infected herds are treated with serum, and the droves of the immediate vicinity which are not yet infected are inoculated by the simultaneous method. At the same time further extension is prevented by quarantine of the infected herds, slaughter of the affected animals, and the disinfection of the premises (Melvin). Literature. Up to the year 1905 Joest, Hog Cholera and Swine Plague, Jena, 1906.—De Schweinitz & Dorset, Bureau of Animal Industry, XX, Rep., 1903, 157.—Dorset, Bolton & McBryde, Ibid., XXI, Rep., 1904, 138; Ibid. Bull. Nr., 102, 1908.—Clintock, Boxmeyer & Siffer, Journ. of Diseases, 1905, II, 351.—Hottinger, Schw. A., 1905, XVII, 255.—Hutyra, B. t. W., 1906, 607._Ostertag, Ibid., p. 623.— Ostertag & Stadie, Z. f. Infkr., 1907, II, 113 u. 425,—Theiler, F. d. Vhyg., 1906, IV, 121.—Glasser, D. t. W., 1907, 617.—Lourens, Zbl. f. Bakt., 1907, XLIV, 420.— Uhlenhuth, Xylander, Hiibener & Bohtz, Arb. d. G.-A., 1908, XXVIT, 1 (Lit.); 1909, XXX, 217 (Lit.).—Marxer, B. t. W., 1908, 401—Hutyra & Wetzl., Z. f African Horse-Sickness. 285 Infkrkh., 1909, VI, 1; B. t. W., 1909, 863,—Stadie, B. t. W., 1909, 113.—Stede- feder, D. t. W., 1909, 546. 12. African Horse-Sickness. Pestis equorum. (Stidafrikanische Pferdesterbe, [German]; Peste du cheval, [French]; Paardenziekte, Perreziekte, [Holland].) _ African horse-sickness is an acute or subacute, infectious disease of solipeds, caused by an ultravisible virus. It exists im an epizootic form in Africa, and is characterized by exten- sive edematous swellings, and hemorrhages of the internal organs. History. The disease, which has been known in South Africa for over a century, has in recent times been confused either with anthrax (Lambert, Sander), or with piroplasmosis (Rickmann, Eding- ton).. Both views were abandoned since McFadyean (1900), and later Nocard (1901), proved that the virus passes through the porcelain filter. The disease has been studied especially by Theiler, from its etiological and clinical standpoints, while the question of immuniza- tion has also been investigated by Edington, Koch and Rickmann. Occurrence. The disease occurs annually in South Africa during the rainy, warmer months, January to March, especially in low, moist localities. In years with great precipitation the disease rages among horses and mules to such an extent that in the affected localities 35% of the animals succumb, and some of the localities are devastated to such a degree that not a sin- gle horse remains alive unless some of the animals have pre- viously withstood the disease in some other place (has: been ‘“salted’’). In the Cape Colony 64,850 horses and mules perished from horse-sickness in 1854 and 1855. Since that time the annual losses are estimated at 14,000 animals. In German Southwest Africa the losses amounted in some years to 66%, in Rhodesia to as much as 90% of the entire number of animals. According to Memmo and Brumpt the disease occurs also in Abyssinia, and according to Friedrichsen in East Africa. Etiology. The causative factor of the disease belongs to the ultra-microscopical micro-organisms, as the filtrate of the blood diluted: with physiological salt solution (Berkefeld or Chamberland B and F filters) proves infectious. Blood taken from affected horses in any stage of the disease, and injected subcutaneously, intratracheally, intravenously or into the lungs (0.01-1.0 ce., or only 0.0005 ec.) or administered per os (100-150.0 ec.), produces the disease in the horse. The exudates and the bronchial secretions also contain the virus, but the infectious- ness of the excrement is considered to be doubtful. Blood from recovered animals.has no infectious action. Horses are highly susceptible to artificial infections, mules and asses to a lesser extent. According to Edington it is also possible to infect cattle fatally, and to produce febrile reactions in goats and sheep. Theiler & Stockman found, however, that 986 African Horse-Sickness.., this is only possible in young Angora goats, their blood becom- ing infectious to horses and mules, but not for other goats. On the other hand they succeeded by intravenous injections of large quantities of unfiltered horse blood, to cause severe illness in dogs, and to infect other dogs as well as horses with their blood; McFadyean however failed to observe any manifestations of disease in three dogs after subcutaneous injections of small quantities of virus. Man is not susceptible, as has been estab- lished by Rickmann and Kaestner through ‘subcutaneous injec- tions on their own bodies. Edington and Morton Coutts consider horse sickness and heart water (see p. 257) as identical, or at least as closely related diseases. They succeeded in producing in horses a disease resembling horse sickness, with the virus of goats affected with heart water. The virus of this disease however possessed only a slight virulence for horses. This view is disputed by Theiler and Stockman, as their experiments have shown that goats treated with the virus of horse sickness remain susceptible for heart water, and likewise horses inoculated with heart water blood may later become affected with horse sickness. Whether there exists a close relation between horse sickness and infectious anemia (see that disease), in the sense that the anemia rep- resents a mild form of horse sickness, is not conclusively established, and requires closer investigation. Natural infection occurs in the periods of the year men- tioned, usually out of doors and at night; keeping the horses in the same places in day time from the time when the dew dries until sunset, as well as during rainy weather, is not dangerous for them. The first frost usually terminates the disease, so that from the eighth day following it no more cases occur (in dry weather the disease occurs only very exceptionally). Although the disease may be produced by feeding great quantities of virus, the observation that in the dangerous pastures horses are not protected by muzzles, indicates that the infection is trans- mitted by some insect or fly. According to Pitchford anopheles mosquitoes and stegomya which have been within 48 hours upon the body of an affected animal serve to transmit the disease to healthy horses; Reinecke succeeded by a test in Germany in producing a fatal disease in one horse by subcutaneous injec- tions with an extract from ticks which he had collected in the African horse-sickness district one year before. This may ex- plain why smoke near the horses (Theiler), or keeping them in a stable protected by a net (Pitchford), prevents the disease. Anatomical Changes. The autopsy reveals in locations varying from case to case, a gelatinous infiltration of the sub- cutaneous and intermuscular connective tissue, especially around the eyes and the region of the throat. There is acute swelling of the superficial lymph glands, severe catarrhal swell- ing of the mucous membrane of the-stomach, the anterior por- tion of the small intestines and occasionally also of the large Anatomical Changes. Symptoms. 987 intestines. The intestines may also show hemorrhages and ulcerations, and in about two-thirds of the cases a well marked, acute edema of the lungs with serous infiltration of the inter- lobular connective tissue; sometimes gelatinous pseudo-mem- branes will be found on the pleura, and hemorrhages under the peri- and endocardium, as well as in the heart muscle. The spleen is normal or only slightly enlarged, the liver hyperemic, the kidneys show hyperemia, or an acute inflammation with small hemorrhages. _ Symptoms. Horse-sickness usually develops after a period of incubation averaging 6 to 7 days in two forms (Theiler). __ In the acute cases (Dunkop-Paardenziekte, Dun-Perre- ziekte, pulmonal form) the body temperature rises within a few days up to 40-42°. The patients show corresponding signs of feeling ill, although the appetite remains unimpaired for a long time. At the height of the disease, towards the end of the first week, the animals are strikingly feeble, the pulse is frequent and small, the heart throbbing, the respiration accelerated and labored. In a small number of cases improvement and subse- quent recovery take place in the course of the second week, the fever diminishing. In most cases however at this time, 1 to 2 days before death, manifestations of edema of the lungs de- velop, as a result of which the animals show very labored respiration, at the same time passing great quantities of a yellowish-white foam from mouth and nose, which is also ex- pelled by spasmodic coughing. Swelling of the superficial lymph glands may also be observed, and frequent manifestations of metritis (Friedrichsen). In rare cases the course takes a sudden unfavorable turn, after slight prodromal febrile mani- festations lasting 4 to 6 days. The condition of the animal becoming worse from hour to hour, the temperature drops and death ensues inside of from 4 to 6 hours with symptoms of dyspnea and heart weakness (Theiler’s peracute septicemic form). yy the subacute form (Dikkop-Paardenziekte, Dikkopziekte) the disease develops in a similar manner, although considerably more slowly. At the height of the fever, or possibly somewhat later, the parts surrounding the orbits become edematously swollen, and at the same time an exophthalmia develops; then in some cases edematous swellings appear on the forehead, on the head, on the chest and abdomen, on the back and on the extremi- ties, and sometimes even the tongue is swollen to a great extent (blue tongue). In the meantime marked muscular weakness is noticeable in the animals, in the majority of cases however recovery finally takes place. Frei demonstrated by extensive physical-chemical blood and serum examinations the following differences from normal blood: the volume of red blood corpuscles and the viscosity is increased at the height of the disease, later diminished; specific gravity, inside friction, and 288 African Horse-Sickness. conductivity of the serum is always below the normal average. Similar changes are also present in immune horses. The course of the acute and peracute horse-sickness is usu- ally unfavorable, inasmuch as horses, especially those brought from non-infected territories, frequently succumb almost with- out exception, while the subacute form runs a much milder course. The disease is distinguished from anthrax by its slower course, and especially by the absence of the pronounced, acute enlargement of the spleen; from piroplasmosis, by the absence of icterus, by the edematous swellings, the severe inflammation of the left half of the stomach and by its occurring only at cer- tain periods of the year. Microscopical examination of the blood in the diseases mentioned gives positive results, however the presence of piroplasmas does not exclude horse sickness. Prevention. The treatment attempted up to the present time has generally proved ineffective. In order to prevent the disease, horses are in the summer driven to high pastures, which are known to be non-infectious, and in suspected places they are allowed to pasture only in day time. By persistent breeding of immune horses and mules it will probably be possible to produce resistant breeds in the infected localities (Rickmann). Immunization. Recovery from the disease reduces the sus- ceptibility of the animals, but does not entirely eliminate it, as even comparatively immune (‘‘salted,’’ ‘‘gezouten’’) horses may become affected by a virulent infection (Theiler). Never- theless this acquired immunity protects the animals from natural infection, in about two-thirds of the cases, and when they do become affected the course of the disease is much milder. Immunity may be produced artificially in various ways, but only in mules without great losses. In these animals immuniza- tion has been applied in practice in South Africa for several years, but it must be repeated annually, as the immunity gradu- ally vanishes. Koch’s Method of Immunization. Koch obtained a serum from ‘‘salted horses’’ which were injected subcutaneously and intravenously with inereased doses (up to 2000 cc.) of virulent blood at intervals of from 3 to 4 weeks, which produced passive immunity on being injected into healthy horses without exerting a hemolytic action, as was the case with sera prepared by other methods. Further experiments showed that by repeated injections of virulent blood and then of serum horses may be actively immunized. The quantity of virus and serum must be proportioned in such a way that the animals become affected by the disease without dying of it. It was found most effective to make an inoculation of 0.01 cc. of virus and 100 ce. of serum for the first injection, the dose of the virus to be increased to 0.05 and 0.2 ec., at the same time reducing the serum to 50 ec. and finally continuing the inoculations with the pure virus (0.5, 1.0, 2.0 ee.). The serum is Immunization. 989 always injected four days after the virus, while each subsequent inoculation is made 12 days after the last. In 14% to 2 months the horses may be immunized to such an extent that they withstand 5 cc. of virulent blood without any reaction. The blood necessary for the immunization is taken from affected animals shortly before death, it is defibrinated, filtered, mixed with an equal quantity of glycerin and water, and 5:1000 carbolic acid, and allowed to stand from 2 to 3 weeks. After repeated filtration it is stored in small bottles. Immediately before es the required quantity of virus is diluted with 5 ec. of physiological salt solution. . For the preparation of the immune serum older (salted) horses are injected in the jugular with fresh defibrinated virulent blood at two-weekly intervals (the first time 2,000 ec., later somewhat smaller doses). The blood, which is subsequently drawn, produces the serum, and is preserved by Ehrlich’s method (to 90 parts serum 10 parts of a mixture of 5.5 parts carbolic acid, 20 parts glycerin and 74.5 parts of water is added). Theiler’s Method of Immunization. According to Theiler the safest immunization consists in the injection of immune serum (300 ec.) into the jugular, and virulent blood (1-2 ec.) under the skin; after the appearance of the febrile reaction a second serum injection (50-100 ce.) appears indicated. In the Transvaal and Rhodesia 8,766 mules were treated by this method, with a loss of 3.7% from the inoculation. Subsequently only 1.3% fell victim to the disease from natural infection in affected territories. As it has since been found that serum prepared with a certain virus is sufficiently effective, only against this virus, Theiler recommends the preparation of a polyvalent immune serum. Other Methods of Immunization. Rickmann employs material originating from mules which are first injected subcutaneously with 0.1 ec. of virulent blood, three days later with 100-200 cc. of serum, and after 12 to 14 days again with 1 ec. of virus (incubation method). A second method consists in the simultaneous but separate sub- cutaneous injection of 0.2 cc. of virus, and 200 ec. of serum, and 21 days later the subsequent subcutaneous inoculation of 25 ec. of virus (simultaneous method). According to Reinecke of 280 mules treated by the first method, and of 160 injected by the second method 8% died, and the percentage being somewhat higher in the simultaneous than in the incubation method. Practically all of the inoculated animals remained well, while the losses among the mules which were not inoculated, and kept at the same place, amounted to 3.3% as a result of natural infection. : Leipziger gives for the first dose subcutaneous injections of 1 ec. of virus, and 300 cc. of highly potent serum; for the second dose 20 ec. of virus. The losses from the inoculations amounted to 3.5%. For the immunization of horses he recommends first the subcutaneous simultaneous method, with 0.1 ec. of virus and 400 ce. of serum; three weeks later an injection of 0.3 ee. of virus and 100-200 ce. of serum; then the animals should be injected daily, first subcutaneously, later intravenously, with diminishing quantities (down to 0.01 ee.) and later again with increasing quantities of virus, until a reaction takes place. Literature. Theiler, Schw. A., 1893, 145; D. t. W., 1901, 209; Bull. P., 1905, III, 617; Rep. of the Gov. Vet. Bact., 1905-1908.—Edington, The Vet., 1895, XLI, 595; J. of comp. Path., 1900, XIII, 223 u, 281.—Rickmann, B. t. W., 1895, 289; A. £ Tk, 1907, XXXTII, 372; B. t. W., 1908, 883.—Sander, A. f. Tk., 1896, XXI, 249.—MacFadyean, J. of comp. Path., 1900, XIII, 1; 1901, XIV, 103.—Nocard, Bull., 1901, 37.—Koch, A. f. TE., 1905, XXXI, 330.—Reinecke, Diss. Bern, "1909 (Lit.); Z. f. Vk., 1910, 7 6.—Leipziger, Diss. Bern, 1909 (Lit.).—Frei, Z. f. Infkr., 1909, VI, 363. Vol. 1—19 990 Fowl Pest. 13. Fowl Pest. Pestis avium, (Pestis gallinarum, Typhus exsudativus gallinarum Rivouta & Dexprato, Peritontis epizootica ScHEvERLEN & Buu, Kyanolophiaea Lovt & Gruser; Peste aviaire, [French]; Gefligelpest, [German].) Fowl pest is an acute, contagious, infectious disease of fowls, especially of geese, which in its course greatly resembles chicken cholera; it is however caused by an ultra-microscopical virus. History. The disease was first described in 1878 by Perroncito, and was shortly afterwards recognized as a disease differing from fowl cholera by Rivolta & Delprato (1880). Later on Italian authors treated the disease repeatedly as a dangerous plague, which caused great losses especially in Northern Italy. Centanni & Savonuzzi (1901) proved that the virus passes the porcelain filter, and similar results were also obtained by Maggiore & Valenti, as well as by Lode & Gruber, Ostertag & Wolfthiigel, Maue and others. Recently Kleine, Mdller, Rosenthal and Schiffmann established the occurrence of the disease in geese, Prowazek, Kraus & Doerr, as well as Marchoux contributed to its etiology, and Freese to its pathological anatomy. Occurrence. The disease raged, especially since the year 1894, independently of chicken cholera, as a very fatal plague in Northern Italy, from which region it was recently introduced into Tyrol and Germany, and later into Belgium and France. In Southern Germany it appears to have occurred since 1898 (Scheuerlen & Buhl), but was spread more extensively by the Brunswick fowl exposition in 1891, at first in Wiirttemberg, later in the Northern states, especially in Prussia. In 1908 the disease was officially recognized in Germany in 51 townships, affecting 1,826 chickens, 159 geese and 3 ducks (considerably less than in previous years). In Hungary it has been known since 1903. Marcone observed the disease in Capodimonte in a pheasantry, Eggebrecht in Tsingtau as a severe plague of chickens. Etiology. The infective agent is contained in the blood, in the nervous system, in the nasal secretion and in the droppings, as well as in the exudate of the serous cavities and in the bile of the affected animals. By the inoculation of minimal quan- tities of these substances (for instance 0.000,001 cc. of blood), the disease may be positively transmitted to chickens. Simi- larly effective, although in a lesser degree, are the filtrates of the above mentioned substances through porcelain. According to Landsteiner the virus appears to adhere to the blood corpuscles as serum alone proved only slightly or not at all.virulent. Rosenthal, Kleine and Schiffmann found in the brain, intra- and extra-cellular, round or oval, sometimes also ring-shaped bodies, the true nature of which (protozoa or products of degen- eration?) has not been established at the present time. Prowazek could not confirm these findings, and believes that the carriers of the virus are 1 to 1.5 yw sized, some- times dumb-bell shaped, forms in the brain, which frequently lie closely against the red blood corpuscles; further fine single and double granules in the filtrates. Marchoux reports the successful cultivation of the virus by spreading blood on peptone-agar containing sugar; 0.2 ec. of culture of the 10th generation killed a chicken in two days. Etiology. Pathogenicity. 291 Tenacity. Blood placed in glass tubes, the ends of which were closed by melting, and kept in a dark place, retained its virulence for three months, while the filtrate was virulent for only one week. Heating to 55° destroys the virus within a half hour, at 60° in 5 minutes, at 65° immediately (Centanni). According to Maue the virus remains active in dried spinal cord, or liver substance, for 200 days, in blood mixed with glycerin (4%) for 270 days. According to Ostertag & Bugge it is destroyed by drying in a thin layer, or. by putrefaction after 39 days; on being subjected to a temperature of 70° it is killed instantly. A 1% corrosive sublimate solution destroys it in 30, a 1% sulphuric acid and a 3% chlorate of lime solution in 10 minutes (Lode). A hot 2% soda solution, as well as a hot 5% creolin solution are also effective (Ostertag & Bugge). Pathogenicity. Chickens and turkeys, pheasants, sparrows, plack-birds, sparrow-hawks, owls and parrots are susceptible to the virus, while water fowls and pigeons as a rule resist the natural, and frequently also the artificial infection; mammalia are not at all susceptible. 7 Old geese can be infected only by subdural inoculations, those only half a year old however by subcutaneous or intramuscular inocula- tions, as well as per os. In these birds the disease manifests itself principally in nervous symptoms (see symptoms). Lode & Gruber and Centanni succeeded in infecting pigeons only by repeated injections of large quantities of virus, Maggiore & Valenti only after previous starvation with blood injections; Freese however produced the disease in them by letting them live with chickens. Successful infections in ducks are reported by Leclainche, and spontaneous infection of a parrot by Stazzi. The natural infection is probably transmitted mostly by the droppings and the nasal secretion of affected birds, and also by the blood of: killed animals and by the organs of those dead from the disease, which are ingested with the food by healthy chickens (by feeding such material the disease has been produced arti- ficially). Occasionally the virus may enter the body through injuries of the skin; at least it was found that the disease may be produced artificially very easily and positively in this manner (it is sufficient to dip the needle of a syringe into infected blood, and slightly scarify the skin with it; Kleine & M@dllers succeeded in pro- ducing the disease by dropping the virus into the conjunctival sac). Parasites living on affected fowls (Dermanyssus avium) cannot transmit the disease, and it cannot be even produced by subcutaneous injections of such macerated parasites (Centanni). Anatomical Changes. In very acute cases the autopsy sometimes reveals negative findings, or frequently only punc- tiform hemorrhages on the inner surface of the breast bone, on the visceral layer of the pericardium, on the peritoneum, in the fat tissue of the gizzard, and on its peritoneal attachment, as well as in the mucous membrane of the air passages. There may also be hyperemia of the spleen and of the kidneys. In less acute cases there is an edematous swelling of the subcu- taneous connective tissue on the neck and breast, also a great amount of a pale yellow, slightly cloudy fluid in the pericardium, which rapidly coagulates in the air. The layers of the pericar- dium sometimes appear to be adherent by fine fibrinous threads. Italian authors mention as a frequent finding a fibrinous exu- date on the pleura and peritoneum (therefore the name of ““Typhus exudativus’’). The comb and the wattles are dark, bluish-red, the con- junctivae show catarrhal swelling. There is a considerable 992 Fowl Pest. quantity of mucus in the mouth and in the nose, which is some- times bloody. The lungs are congested and sometimes contain atelectatic areas. The intestinal tract contains on the smooth mucous mem- brane grayish-white, sometimes greenish excrement; at the pas- sage between the glandular and muscular stomach, as well as between and on the conical protuberances of the glandular stomach, there are superficial or deep hemorrhages, sometimes only very small (Freese). The mucous membrane at the begin- ning of the small intestines shows sometimes only catarrhal reddening, in other cases it is inflamed more markedly. The liver and spleen show no striking changes. The kidneys are either grayish-brown in color and cloudy or dark brown and moist on the cut surface. The serous membrane of the egg yolk is markedly congested, revealing sometimes hemorrhages which may also be present in the yolk itself (Freese). Symptoms. The time of incubation in the natural infection is, as a rule, 3 to 5 days, exceptionally 2, or on the contrary it may be even 7 days (Freese), while after artificial infection death ensues not infrequently inside of 36 to 48 hours. The disease commences with depression and diminished appetite, which condition soon changes to a conspicuous dullness and sleepiness. The chickens creep into dark corners, and sit with drooping head and wings cae as when brooding, or crouch motionless in one place. Even at the onset of the disease they do not resist being caught, and some of the birds give a peculiar 43:0 loud ery when picked up. When driven about they move with a staggering, irregular walk, later it is hardly possible for them to move at all. Setting them on the perch they find their eqni- librium only after long balanc- T. 4. 2. LA TTL e Was n 3 PIO I teed ll ebay us 0 ing, or not at all. a = In the meantime the comb SA and the wattles become dark kine red, and finally are blackish- red in color (hence the name ie. Kyanolophiaea), while towards the termination of the disease Fig. 58. Fever curve in chicken pest grayish seales sometimes de- Following inoculation of virulent blood ° ac pba velop on the skin. This febrile infectious disease, which is usually observed in enzootic extension and in the course of which hemoglobin appears in the urine as a result of the breaking down of red blood corpuscles, is caused by the piroplasma bigeminum, which is in various localities inoculated into the bodies of cattle by various kinds of ticks. History. The disease was first studied bacteriologically in Roumania by Babes (1888), who considered as its cause a bacterium which usually was present in the red blood corpuscles (Haematococcus bovis) ; he has also proved that the disease may be transmitted with the blood and kidney substance from affected cattle to healthy animals. Shortly after him (1889), Th. Smith, later in association with Kilborne, estab- lished for the Texas fever which is prevalent in North America, the fact that the parasite represents a hemosporidium, and that the disease, as already claimed by Reverley in 1881, is spread by a tick, the Boophilus bovis, in such a manner that the tick inoculates blood containing the parasites from affected animals into the bodies of healthy cattle. The publications which have followed each other rapidly since that time, have established the occurrence of a disease which is identical with Texas fever, or at least very closely related to it, in many different locali- ties. Thus Krogius & Hellen established it in Finland, Krageriid in Nor- way, Celli & Santori in a Nicolle & Adil-Bey in Turkey, Jackschath and Zieman in Germany, Ligniéres in France, Gasille and de Jong in History, Occurrence, Etiology. 765 Holland, Hutyra in Hungary, Nocard, later Stockman in England, Bettencourt in Portugal; further Koch in East Africa, Theiler and Hutcheon in South Africa, Stockman in India, Sanarelli and Ligniéres in South America, finally Pound and Tidswell in Australia. Kossel & Weber (1899) showed further for Finland, and later in association with Schiitz & Miessner (1903) for Germany, that the infec- tion in Europe is transmitted by the Ixodes reduvius. These same authors, as well as Smith & Kilborne, and also Ligniéres before them, have suggested a satisfactory method of immunization for the practice. Occurrence. The disease occurs usually in the form of an enzootic in the spring and in the summer in certain localities, especially in marshy and forest pastures, whereas in the cold periods, and during stable feeding it occurs only exceptionally. The so-called forest disease (hemoglobinuria), which was for- merly attributed to the ingestion of various plants, especially to those containing turpentine, and which was accepted as an intoxication caused by resinous substances (turpentine), is identical with the disease is question. According to general experience older cattle become usually affected, and the disease sometimes causes very decided losses among the improperly wintered cattle of poor owners. The disease causes great losses in Germany, especially in those localities in the northern part, where, as a rule, all animals are pastured, and among these in unfavorable years an emphatic decimation of the animals may result. It occurs especially frequently in Prussia and Oldenburg, then in Bavaria, Wiirtemberg, Baden, Hessen, Mecklenburg, Braunschweig and in the imperial domains, but it .is also observed as a permanent disease of spring and summer in other localities in marshy and moorland pastures. In Roumania it occurs most destructively in the inundated territories of the Danube Delta, where the disease in some years causes a loss of 30,000 to 50,000 cattle. In Hungary the ‘‘forest disease’’ prevails, especially in the mountainous regions of northern Hungary and Transylvania and occurs there in some localities almost every spring; it has also been observed in the southern part of the country. Texas fever has for a long time been known in America around the sea-girt portions of Mexico; in the middle of ‘the last century the disease was introduced to the United States with herds driven from Texas, and while it showed in its original home a very mild course, in the North it caused enormous losses among the native cattle, the money value of which has been estimated in some years as $2,000,000. In the northern part of South America it also causes periodically great losses, especially among imported cattle. It also occurs as a dangerous disease in India (Schein observed it there also among buffaloes), in Central and South Africa, further in Australia, where it was introduced by American cattle. Etiology. The cause of the disease, the Piroplasma bigemi- num (Babesia bovis, Pirosoma bigem., Apiosoma bigem., Ixidioplasma bigem.), occurs in the blood of febrile cattle, mostly inside of red blood corpuscles, more rarely on their surface, or free in the blood plasma. The parasites are found either singly as roundish bodies of 1-2 “ diameter which in a fresh state show ameboid movements, or in pairs in which case the somewhat larger, non-motile, and pear-shaped para- sites (pirum=pear) frequently hang together with their elongated ends in a straight line, or at an angle (Fig. 128 on p. 760 and Fig. 130). Smaller diplococcus-like, as well as 766 Piroplasmosis of Cattle. rod and lancet forms are found rarely, and the presence of more than two parasites in one blood corpuscele is also infre- quent. The cultivation and propagation on artificial media has not yet been successful with a certainty. According to Ligniéres and Miyajima they are supposed to multiply in blood- bouillon for a time, and here, according to the observations of the Japanese investi- gator, forms containing flagellae similar to the trypanosomes are supposed to appear after 3-4 days; the propagation reaches its height on the 10th to 14th day; on the 45th day, however, the culture died (it is possible that they represented mixed infections). According to Smith & Kilborne, as well as Laveran & Nicolle, their propagation results by fission, or schizogony, while according to Theiler’s former view, which was also accepted by Koch, the parasites assume, in certain stages of development, rod- and ring-shapes, and then appear similar to the causative factor of African horse fever (Fig. 131). Such forms are usually found in the blood of cattle that are immune against Texas fever, and they also appear in the blood of calves, which have heen infected with the blood from such cattle, during or after the second reaction. Recently, however, these forms were deseribed hy Theiler as a new variety, (Piroplasma mutans), (see p. 782). Fig. 130. Piroplasma bigemi- Fig. 1381. Piroplasma bigemi- num. Spherical and pear num. Rodand ring shapes. Blood shapes. Cattle blood; stained of a cow ina stage of commencing with methylene blue. convalescence; stained after Lav- eran. Koch examined material from ticks which sucked themselves full of blood from affected animals, and found that, after leaving the blood corpuscles, the parasites become elongated to club shape in the intestines of the ticks and develop lancet-like projections, which may be slowly drawn in and extended (morning star shapes). Later the extensions become shorter, and diminish in number, whereupon the parasites change into round or pear-shaped bodies. Such bodies are found, also, in the eggs of infected ticks, but as they are 3-4 times the size of the piroplasma in the blood of cattle, it is possible that between the two there are still other transitory forms. (Kleine observed star forms also in dog piroplasma, which he placed in strong salt solution. Hartman, however, considered them as manifestations of degeneration. ) Pathogenicity. 767 : Tenacity. Defibrinated blood kept at 8° ©. is still virulent after 42 days, while in the blood of cattle which have died or have been slaughtered by bleeding the parasites remain alive for nine days. In the meat of slaughtered animals they die at latest after twelve hours (Kossel, Schiitz, Weber & Miessner). Their rapid death may possibly be due to lack of oxygen, as well as to the acid reaction of the media which acts destructively on the piroplasma (Jackschath). Pathogenicity. The disease may be transmitted to healthy cattle with blood containing piroplasma of affected animals. After an intravenous, subcutaneous, or intramuscular inocula- tion of 5-10 ce. of defibrinated blood, the parasites appear usually in from 8 to 9 days in the blood of the inoculated ani- mals. At approximately the same time the body temperature becomes elevated, whereupon, during the reaction which lasts for 7 or 8 days, the number of red blood corpuscles diminishes, and in some of the cases hemoglobin appears in the urine. After 25 to 30 days another febrile reaction follows, usually with milder symptoms. In some animals the artificial disease terminates in death, in the majority of cases however recovery takes place in one to two weeks. In the blood of such recovered animals the parasites may be demonstrated for a long time, although in smaller numbers (in one case the blood was still infectious 531 days after an artificial infection, and according to Schroeder & Cotton the parasites may persist for 10 to 12 years). The disease may also be produced, although with less certainty, by the injection of blood containing piro- plasma into the serous cavities, lungs, brain, further by rubbing upon the scarified skin; feeding is, on the other hand, always ineffective. To an infection which causes a severe affection among older cattle, cattle under one year of age usually react only with an elevation of temperature lasting for several days. ‘Other species of animals are not susceptible to the infection. In America, Africa, Australia and Eastern Asia, as well as probably in Southern Europe, the natural infection is trans- mitted by the boophilus species, in middle and Northern Eu- rope, on the other hand, by the Ixodes ricinus (I. reduvius). According to Salmon & Stiles, the carrier of the parasite is the bo- ophilus annulatus, in North America, and, according to Motas, also in Roumania; in South America, Cuba, Porto Rico, in the Philippines and Australia, the B. australis, in South Africa the B. decoloratus (accord- ing to Theiler also the Rh. appendiculatus), act as carriers, while of the sub-family ixodiae, the Ixodes ricinus has only been known with cer- tainty to transmit the disease in Europe (according to Kragertid the I. hexagonus acts in a similar way in Norway). ; ; The piroplasmas of cattle transmitted by various ticks in different localities do not appear to be entirely identical, but probably represent varieties of one species, and Liihe even separates them into two species, apparently on account of the differences in size, namely, into the small, Babesia bovis, which is found in Europe and North America, and the larger, Babesia bigeminum, which is prevalent in America, Australia and South Africa. Their difference appears also to be substantiated by the fact that animals immunized against one of the varieties are not always immune against the other varieties, This has been established 768 Piroplasmosis of Cattle. by Ligniéres for the European and Argentine piroplasmosis, by Theiler for the English and South African redwater; (on the other hand, cattle from Texas and from Queensland were immune against the South African redwater). Ligniéres describes a special species, the piroplasma Argentinum, which is considerably smaller, usually only found singly in the erythro- cytes, and produces in Argentine, Uruguay and Paraguay, an atypical form of Piroplasmosis, which is frequently characterized by a protracted and fatal course, and by nervous symptoms. ene aide : as: SPATE | Fig. 132. Ivodes reduvius. 1. eggs; 2. larvae; 3. nymph, several days old; 4. sexually mature female; 5. male. Enlarged 16 times. (After Kossel, Schiitz, Weber & Miessner.) The parasites of East African coast fever, and of tropical piro- plasmosis represent a decidedly independent species (see p. 779 and p. 782). Development of the Ticks. The Boophilus annulatus (Margaropus s. Rhipicephalus annulatus, Boophilus bovis) transmits, according to the investigations of Smith & Kilborne, the infection in the following way: Development of Ticks. 769 The larvae migrate from the grass onto the bodies of cattle, and suck their blood. After about eight days they change into pupas, and after another eight days into nymphs, which after another molting develop into sexually mature ticks. The nymphs, as well as the sexually mature ticks nourish themselves with the blood of the host animal, following im- pregnation however the female drops from the body of the cattle and lays from 2000 to 4000 eggs in the grass, from which the larvae hatch out in 3-4 weeks. They remain for a time in the grass, occasionally how- ever they crawl on the skin of the pasturing cattle, and if the female tick from which they originated has sucked infected blood during its life, the larvae, and subsequently also the nymphs, inoculate the virus into the body of the new host. Larvae and nymphs may also pass over directly from affected animals to healthy cattle, in which case they transmit the blood parasites in a direct manner. (?) The Ixodes ricinus s. reduvius transmits the infection, according to the investigations of Kossel, Schiitz, Weber & Miessner, in a singular manner; the female tick dropping from the body of cattle lays in the grass 100-1000 eggs, from which the larvae hatch out after an average of six weeks. If the larvae attach themselves to the skin of cattle or of other animals, they suck themselves full of their blood, and drop: off after 3-6 days, whereupon they change to nymphs on the ground inside of four weeks. These attach themselves again to the skin of a mammal, from which they drop to the ground in from 3-5 days, where they de- velop in eight weeks to sexually mature ticks, which again look for a host, where they suck the blood, and copulate. Therefore the total development from the laying of the eggs until the dropping off of the impregnated female takes about nineteen weeks, provided that the ticks! in their different stages of development always meet a suitable host and that the weather conditions are favorable for their development. Ac- cordingly the Ixodes distinguish themselves from the Boophilus among others, in that they leave the host twice during their development, while the Boophilus passes through all the stages of its development on one and the same host. The eggs of the Ixodes reduvius are 0.50-055 mm. long, and 0.27 to 0.33 mm. broad, of oval shape, and brownish-yellow to brownish-red in color. The larva is 0.7-0.8 mm. long, 0.42-0.50 mm. broad, has a mite-shaped body, and three pairs of legs; filled with blood it attains a Jength of 1.25 mm. and a breadth of 0.8 mm., when it takes on a blackish-brown color. The nymph is 1.3 mm. long, 0.74 mm. broad; the body resembles the larva, but possesses four pairs of extrem- ities; sucked full with blood it is about 2.0 mm long and 1.25 mm. broad and of a dark grayish color. The developed female is 3-4 mm. long and 1.5-2.5 mm. broad; impregnated and sucked full with blood it reaches a length of 10-15 mm, and a breadth of 5-8 mm.; it is then blue or ash-gray in color, sometimes slightly brownish or yellowish, and has four pairs of extremities. The male is similar in appearance, although somewhat smaller (Fig. 132). The larvae, nymphs, and the sexually ripe ticks may, with suffi- cient moisture, remain alive for months outside of the animal body, and they also withstand the cold of the winter without harm. In cold weather they are benumbed, but as soon as warm weather appears they liven up, and if conditions are otherwise favorable they continue in their devel- opment. They are harmed however by direct sunlight. Experiments of infection conducted with both species of ticks showed that when larvae, hatched out from an infected female in a glass container, are placed on the skin of healthy - 770 Piroplasmosis of Cattle. cattle, the piroplasma appear in the blood in about eight days, and in some cases fever and hemoglobinuria sets in (Fig. 133). The results of experiments conducted with nymphs which as larvae sucked blood from affected cattle, are similar, and the disease may be also produced with larvae, which have wintered in the open (the infectiousness of the sexually mature ticks of the species described here is as yet questionable). ; According to these experimental results, which correspond with practical observations, the natural infection of cattle occurs usually on previously infected pastures in which one of the mentioned species of ticks are present, and in which the larvae and nymphs originated from females which had the opportunity to suck blood from affected animals or in which the nymphs themselves in a previous stage of development sucked infected blood. As these ecto-parasites subsist as a Ga Wunq0r AQOA. I 40.7 44. [ 42.) 93. [44 [ 45. | 16. [ 47 [4a 7 9. 20. | 29 | 22.1 23.7 24 [ 25 | 26. Wo r rN estong Lostestes ty eSics. —— ™ telah Gale ¥ 7 zi & K+ = Fk 39:5 ar ma LW i i wi 7 A. ii Ava i 39:0 ¢ - F ¥ + 7 x y SER ORR IR eeEas Ezy t {—» fi“ monte EE. + } —t— & » —}— — 43-5 7o™ rh y yao sa eg ee + o..5 Cum oe Sat Sa Sod Hae it ae ap 35 A oh, ee SE SE = piooay! 280 aged “——- |S = =e eoey E.34 - z Urine 23¢a wat gt 8st Bet Bet sf atozty | 9 Gi 5 o 4 fy Ki 4 ere zeae Sab 235 234+ Sat sat ea t'eg t set 3 4 Baza gatas; bt bet bet So PAST get 8 Read Set st get cet est Ae t “st ee t 3, 370) AERE ot pa OT > A aie t re Fig. 133. Hever curve in piroplasmosis of cattle. After placing several thou- sand infected larvae on the animal. (After Kossel, Schtitz, Weber & Miessner.) rule in marshy places, especially in forest pastures or near. forests and bushes, the disease usually affects cattle driven to such pastures. On the other hand its annual reappearance may be explained by the facts that the virus passes from the impregnated female ticks to their progeny, and that they are capable of offering considerable resistance to unfavorable weather conditions, especially the cold of winter. If at the onset of warmer weather the larvae have already hatched from the eggs, the first cases of disease among cattle driven, to in- fected pastures usually appear after two weeks and, in case the respective pasture was badly infected the previous year, a great number of the animals may become affected within a short time. With stable feeding, however, the disease is observed only very exceptionally, and only in cases in which Development of Ticks. 771 infectious ticks were introduced into the stables with the grass or foliage from infected pastures. The introduction of the disease into localities which had been free from the infection, may be brought about by infected animals, and the more so as piroplasma may be present in the blood of cattle years after their recovery from the disease. In such cases the disease may be artificially produced with the blood of such apparently healthy cattle. If ticks which are suitable for the transmission of the virus are present in these localities, they suck blood from the cattle introduced into that locality, and pass the piroplasma to their progeny, which then infect healthy animals. Affected or healthy cattle may carry ticks about on their bodies, and these will continue to propa- gate in the new locality, provided the requirements for their development are favorable, where they may then infect fresh animals. In both cases the pasture, formerly free of the in- fection, becomes a new source of infection, in which the disease may possibly recur from year to year. The extensicn of the disease was strikingly observed in America, where in the 60s and 70s of the last century it was introduced by cattle driven from- Texas to the north, to the states of Indiana and Illinois, whence it extended later in a similar manner almost through the entire territory of the United States up to -Lake Michigan. After the trailing of the cattle from the south, as a rule in from 30-50 days, which period corresponds’ to the cycle of development of the Ee get the native cattle became affected with severe symptoms (Reverley, _-Smith & Kilborne). The disease was introduced into Australia by American cattle, with the Boophilus ticks, which had been unknown there up to that time, and it causes there great loss from year to year. It also spread recently in Finland to territories which had heretofore been free from the affection (Krogius & Hellen). Although the disease develops exclusively through infec- tion by ticks, certain accessory conditions have an influence on its appearance, and more so on its course. Thus as a rule very young animals show a greater resistance against the in- fection than older cattle. Poorly nourished, as well as gener- ally weakened animals usually become affected with severe manifestations; unfavorable weather conditions, especially damp, cold weather, also exert an unfavorable influence on the course of the disease. This explains the experience that the affection is often observed in a severe form in the damp, cold spring periods, and especially among improperly wintered ani- mals of poor owners (Kragertid observed it repeatedly in such a form in cows 12 to 14 days after parturition). Native cattle raised in affected territories usually become affected under much milder symptoms than animals brought from uninfected localities. The greater resistance of the for- mer may be explained by the supposition that they became “infected while young, and thereby acquired for their later lives a relative immunity, which was still more increased by infec- tions developing in the meanwhile. Such animals, however, may also carry the virus in their blood in spite of their healthy appearance, and this may sometimes multiply rapidly on ac- 772 Piroplasmosis of Cattle. count of harmful influences, and produce a severe affection (such acute outbreaks of the previously latent disease have frequently been observed after artificial infection with rinder- pest blood) (see p. 255). Anatomical Changes. Animals dead from the disease show changes in the digestive organs and in the spleen. The mucous membrane of the abomasum shows a catarrhal swelling and manifests, especially in the pyloric region, numerous small hemorrhages and erosions. Similar changes are present on the mucous membrane of the intestines and especially on those of the rectum, the contents of which is colored reddish on account of the numerous and extensive hemorrhages of the mucous membrane. The liver is enlarged, the substance flabby, lusterless, and covered with yellowish streaks and spots on a dull reddish-brown base. The gall bladder frequently con- tains great quantities of thickened bile. The spleen is always strikingly enlarged, its pulp is very rich in blood, brownish-red, or brownish gray-red, and frequently softened, almost liquefied, the capsule extended or even ruptured (Witt). The bladder contains a great quantity of pale or dark-red urine, its mucous membrane is sprinkled with red discolorations. The autopsy findings are further: Hemorrhages in the serous cavities, sometimes also in the brain substance and bone marrow, cloudy swelling of the kidneys, frequently with puncti- form hemorrhages, serous infiltration of the subcutaneous and subserous connective tissue, hypostatic hyperemia of the lungs, exceptionally also catarrhal pneumonia with sero-fibrinous pleurisy. The blood is pale-red and thin, the red blood cor- puscles of the spleen and liver contain piroplasmas in a propor- tion even up to 80%. In some cases icterus is also present. (According to Piot the temperature in the abdominal cavity rises after death to 44° and over.) Symptoms. According to experimental investigations with larvae of ticks, the period of incubation ranges from 8 to 10 days. The disease commences with a rapid rise in temperature, and usually with pronounced dullness and debility, accelerated respiration and -heart action. The temperature remains for several days at 40° to 42° C., whereupon in mild cases it grad- ually returns to normal, while in severe cases it rapidly drops below normal before death. In pasture the animals rest frequently, fall back behind the herd and ruminate with long interruptions; exceptionally symptoms of irritation, involuntary -movements, and even- delirium are observed at the onset of the disease. At first there is constipation, later the animals show symptoms of colic and tenesmus, dry yellowish-brown, later thin, mashy feces, mixed with mucous or blood coagulum. The milk secretion Symptoms. 773 is immediately diminished; the milk drawn in small quantities is sometimes yellowish and has a bitter odor. In a later stage the animal manifests a staggering gait, and at times may knuckle over with the hind feet. Muscular trembling may be observed in some parts of the body, especially on the upper arm, shoulders, and croup. There is profuse lachrymation, the flanks are sunken, the skin feels dry and hard. The lymph glands in the knee folds swell early in the disease to a great extent (Schmidt). The mucous membranes are at first’ reddened, later they become pale, and show symp- toms of icteric discoloration. The blood drawn from a vein is more or less pale red and watery; after coagulation the separated blood serum also shows a red discoloration. The number of red blood corpuscles drops in several days from 7 to 8 millions per cmm., to one-half or one-third, in fatal cases even one-fifth to one-sixth of the above number. Within them piroplasma may be found in varying proportions, in severe cases from 5 to 58% (Fig. 130 and 131). The hemoglobin content may drop to 12% (Fleischl). The microscopical demonstration of the parasites may be successful even in fresh blood specimens, where they appear in the blood cells as pale, shining, on a warm object stage somewhat motile, coccus-like bodies (easily mistaken for the plasma extensions of the crenated blood cells!). A certain result is obtained from dry specimens fixed in absolute alcohol, or in a mixture of alcohol and ether aa, and stained with a 1% aqueous, miethylene blue solution. The parasites on such slides appear colored blue. For the demonstration of the finer structures, and especially of the chromatin bodies, Romanowsky’s method of staining or one of its modifications (Giemsa stain!) must be used. The red blood corpuscles proper show indications of a poikilocytosis and in their interior basophilic granulations. The urine contains even in the early stages, albumen in various quantities; even when normal in color it has a high specific gravity, later, sometimes as early as on the second day, it becomes of a reddish or greenish color, as a result of the appearance of methemoglobin, probably also of bile pig- ments. The color gradually becomes more intense and brownish to blackish-red; at the same time in shaking much foam forms on its surface, while on boiling it coagulates to a jelly-like mass. On standing a great amount of sediment appears, in which numerous yellow granules, likewise also kidney epithelia and casats may be demonstrated, while red blood corpuscles are found only very exceptionally. The passing of the urine is always accompanied by severe straining. In the cases with unfavorable termination the patients become weakened after 3 to 4 days to such an extent that they constantly lie down, the respiration is very labored, and from time to time a painful grunting may be heard. At the same time convulsions may appear in certain groups of muscles, tears ooze out from between the swollen eyelids, and saliva drops out of the mouth, until finally under a rapid sinking of the body temperature death ensues, which however may 774 Piroplasmosis of Cattle, occur suddenly under symptoms resembling those of anthrax (de Jong), or even without any previous indication. In mild cases the fever disappears about the middle of the first week of illness, at the same time the urine clears up, and the appetite as well as rumination returns. The animals which in the meantime have become greatly emaciated, do not regain their former condition for several weeks. In some eases, especially in young animals, only a moderate fever which lasts but a few days, somewhat accelerated respira- tion and pulse, diminished appetite, as well as evidént dullness are observed. The color of the urine does not however undergo any change, and the moderate destruction of the red blood corpuscles is only indicated by the paleness and slightly yel- lowish discoloration of the mucous membranes. Such patients recover very rapidly after the disappearance of the described symptoms. , Sexually mature ticks may be found on the body surface of affected animals, frequently in very great numbers in the parts surrounding the vulva and the rectum, on the udder, on the inner surface of the thigh, and in the inguinal region, while the larvae and the nymphs lodge on the head, in the . vicinity of the muzzle, on the eyelids and ears, as well as on the udder. According to Dschunkowsky & Luhs a piroplasmosis of the type of Texas fever occurs in Trans-Caucasia, which runs a very rapid course of 2-3 days. It is always associated with hemoglobinuria and char- acterized by a high mortality. No parasites are found in the peripheral blood, while almost all erythrocytes of the parenchymatous organs are infested. Course and Prognosis. If affected animals continue to remain on infected pastures, they sometimes die with a rapid aggravation of the symptoms as early as from 4 to 7 days, but the course may also extend over a longer time. If they are however removed immediately after the appearance of the first symptoms to an uninfected place, recovery follows in most cases. Dampness and cold, likewise very hot weather, influence the course of the disease unfavorably. Accordingly the mor- tality varies within wide limits (5 to 50%), and is usually higher in southern warmer localities than in the temperate zone. Rapid sinking of the body temperature to 37° and below, during continual excretion of hemoglobin with the urine, in- dicates threatening danger, while a gradual diminution of the febrile symptoms with strong pulse, and clearing of the urine, indicates improvement: Sometimes however the improvement is only temporary, and may later, as a result of a reinfection, or under the influence of unfavorable weather conditions, again become aggravated. Cattle which have passed through an attack of the disease are usually immune against later infec- tions. Diagnosis, Treatment. 775 Diagnosis. Hemoglobinemia and hemoglobinuria which ap- pear rapidly under febrile symptoms, characterize severe affec- tions, and in cattle on known infected pastures a red discolora- tion of the urine is sufficient for a well founded suspicion of the disease. If however the last-named symptom is absent, the presence of the disease may be suspected on the ground of febrile symptoms, only when at the same time other animals in the herd are affected with characteristic symptoms, in which the probability of the diagnosis is considerably increased by the presence of ticks in various stages of development on the body of the animals. Absolute certainty is obtained by the demonstration of piroplasmas in the red blood corpuscles on microscopical examination (see p. 773), or by artificial pro- duction of the disease in healthy animals (10 cc. of fresh or defibrinated blood subcutaneously or intravenously). Anthrax and hemorrhagic septicemia may be confused with the acute cases of piroplasmosis, as in those diseases the febrile symptoms are sometimes also accompanied by a red-colored urine, but their course is more rapid, no anemia develops, the urine contains red blood corpuscles, the examination of fresh blood shows long rods, or small bipolar bacilli, between the blood corpuscles. The disease is distinguished from hematurias brought on by other causes, by the absence of red blood cor- puscles in the urine, from the so called ‘‘chronic hematuria’’ it is distinguished by its less chronic course, and the much more rapid development of anemia. On autopsy the above-mentioned diseases should also be kept under consideration, and especially anthrax, on account of the acute swelling of the spleen, and the numerous hemor- rhages which may be present. Treatment. After an outbreak of the disease in a pasture the herd should be removed immediately from the infected locality to a moderately cool, shady place, and most appro- priately to stables where they can be given careful attention. At the same time suitable and sufficient feeding (good dry food, with the addition of potatoes or beets), is of great importance. In addition to this, the ticks should be picked from the body of the patients, or destroyed by washings with creolin, lysol or salt solutions. Internal treatment has so far been of but little value. Salines may be administered against constipation, and the diarrhea treated with slimy gruels, combined with astringents or opiates. In great weakness stimulating treatment (rubbing with alcohol, internally, alcohol or black coffee) is indicated. The quinine treatment (10-20 gm. of quinine hydrochlorate per os), which has been recommended (Padovani, Hellens, Kréning), probably on account of the similarity of.the disease with malaria in man, has not given uniform results. Kragertid recommends intravenous injections of formalin or collargol (100-500 gm. of a 1% solution), and later carbolic acid or lysol internally 776 ‘ Piroplasmosis of Cattle. (Acid. carbol. or lysol 10.0, Spir. frumenti 100.0, Aqua 500.0; one tablespoonful every hour until clearing of the urine). Evers warmly recommends damholid (a hemoglobin preparation). The treat- ment should be introduced with the administration of 50 gm. (three times daily). per os. If no improvement results or if even an aggravation follows, the remedy should be injected subeutaneously or even into the blood circulation (200 gm. damholid is dissolved in one liter of 14% itrol solution, and of this 500 ce. or more is injected subcutaneously, or of a 10% solution 100-250 ee. is injected into the jugular; after the subcutaneous injection of simple watery solutions malignant edema has repeatedly been observed). Westermann and Grabe have obtained good results with this treatment. : Recent experiments of Nuttall & Hadwen, which have since been confirmed by Stockman, appear to indicate that the piroplasmas are greatly influenced by trypanred. In five artificially infected cattle in which the blood already contained numerous parasites and the urine was red colored, a marked improvement followed immediately after an intravenous or subcutaneous injection of 180-200 ec. of a 15% solu- tion, the urine cleared rapidly, and the number of blood parasites diminished to a great extent. Later the blood was entirely free of par- asites for 5-18 days, they again reappeared, although in moderate num- bers; but all of the five cows remained alive, whereas one of four controls, of which only two were affected with hemoglobinuria, died. The try- panblue solution should always be prepared fresh with distilled water. It stains the body tissues blue. After the disappearance of the symptoms in the presence of marked anemia, subcutaneous or intravenous injections of physiological salt solution (1-2 liters daily), and the internal administration of iron preparation (5-10 gm. iron sulphate daily), is indicated. Prevention. The disease may be prevented absolutely by keeping the animals from infected pastures and excluding grass and foliage fodder from such localities for food purposes. On the other hand such pastures may become harmless by draining their swampy areas. Such means of prevention however fre- quently cannot be carried out on account of the lack of funds of the owners. As some animals show very little resistance to infection, as a result of improper wintering, care should be taken that weakened cattle are not driven to low forest pastures in the spring and early summer (according to Ligniéres alfalfa is supposed to keep the ticks away from pastures). In order to prevent the introduction of the disease to pre- viously uninfected territories, it is aimed in America and Australia to free the suspected animals of ticks. For this purpose animals in the southern part of the United States are dipped in vats containing 20% petroleum or Beaumont oil, while in Australia washing with various insecticide fluids (lysol, petroleum) is employed for such purposes. In order to destroy the ticks farmers in South Africa usually spray the animals in 12 to 19 day intervals, with a mixture of oil and water (10-25:100) (Lounsbury). For the same purpose a fluid is also suitable consisting of 0.2% arsenic .and 0.2% wood tar. Prevention, Immunization. T7177 In the United States and North America the destruction of ticks was inaug- urated on a large scale in 1906. On this occasion 220,780 cattle were infested with ticks in 29,315 examined herds, and 328,064 were found to be free (Steddom). The procedure consists in placing the herds for three weeks in enclosed pastures free of ticks, until the young ticks become mature anu drop to the ground. Then the animals are driven to another uninfected pasture, and their former stands are disinfected. It is also aimed to clear the cattle pasture from ticks by keeping the cattle away for about six months, when the ticks are destroyed by starvation, or large pasture areas are burned over in the spring. _ Immunization. As cattle recovering from the disease ac- quire a long-lasting immunity in North America (Schroeder) and Australia (Gray), cattle brought from non-infected terri- tories into affected localities are infected artificially with blood of calves born in infected territories or of recovered cattle, which, as a rule contain piroplasma sparingly. After such inoculations the animals become sick after 8 to 10 days, some- times with symptoms of anemia, hemoglobinuria, frequently also with bloody diarrhea, and at the same time the number of red blood corpuscles, some of which may contain typical piroplasma, diminishes 10% or more. This symptom disap- pears after 8 to 10 days; after a month, however, a second reaction usually appears, which lasts 8 to 10 days, and the red blood corpuscles contain only atypical piroplasma in very small numbers (Theiler). If cattle so treated are driven to infected pastures after the lapse of about two months, a number of animals resist the natural infection, in the others, however, fever appears again as a result of the tick bites. In most of the animals récovery finally takes place, but a certain percentage succumb to the disease (Francis). Inasmuch as this percentage is considerably smaller than the loss observed from non-inoculated animals under the same conditions, the inoculation appears to be advantageous in strongly infested localities, in spite of the fact that the inocula- tion itself causes disturbance of nutrition, and sometimes even direct losses. * Blood from older cattle which have recovered shortly before from the disease is also suitable for immunization, and gives similar results. The immunizing action of the blood from animals shortly before recovered has been confirmed through experiments, by Smith & Kil- ‘borne, also Schrveder in North America, Francis in Texas, Hellens in Finland, Koch in Africa, Theiler in Kossell, Schiitz, Weber & Miessner in Germany. In Germany the immunization is carried out with blood of artificially infected ealves, and has recently been employed extensively in practice; until the end of 1909, 6,153 cattle were immunized, principally in Prussia. According to the reports on 4,261 inoculated cattle, 1.97% became mildly and 0.49% severely affected, and recovered, and 0.09% died or were slaughtered. Besides, during pasturing 2.98% became mildly, 0.54% severely affected and recovered, 0.54% died or were slaugh- tered. The percentage in young stock amounted to only 0.04%, in adults 1.46%. In 10 herds of the immunized animals 4.14% were mildly, 0.46% severely affected ; of those not immunized 19.63% mildly, and 7.48% severely affected (Schmitt). Satisfactory results are reported by Graffunder and Bugge. Less satisfactory 778 Piroplasmosis of Cattle. were the immunizations in Texas, where up to the end of 1901 out of 1,251 immun- ized cattle 116 or 9.2% died later; likewise in Australia (Queensland, where immun- ization of 35,000 cattle caused a loss of 3-4%, and besides, of 17,960 immunized animals 679, that is 3.6% succumbed later to the natural infection. But in one experiment, out of 95 previously immunized animals all remained healthy after pe ticks to them, while 30 non-immune cattle became affected as a result of it. Technique of Immunization. For the inoculation, blood is taken from the jugular vein of cattle which have passed through a natural or artificial affection about two months previously. The blood is defibrinated, and either used immediately or kept in the ice chest until the inoculation. According to Kolle, blood containing parasites from calves reared in infected localities is best adapted, according to Schiitz blood from artificially infected calves which have recovered at least within 83 days. Three ce. of the defibrinated blood are injected subcutaneously, and if possible the operation should be undertaken during the winter or at the beginning of spring. It is best to undertake the inoculation on calves. Cows in advanced pregnancy, poorly nourished, or in general animals which are not entirely well should not be immunized. The immunized animals should be kept in the stable for three weeks and fed moderately before they are driven to pasture. Other Methods of Immunization. Dalrymple, Morgan & Dodson also obtained satisfactory results in America, by taking from the body of affected animals ticks sucked full with blood, grinding them, and inoc- ulating cattle subcutaneously with the material, while Connaway & Francis, in America, recommended the application of infected larvae or nymphs (the first time 20-50, after a month again 200-400) on the skin of healthy animals. Ligniéres produces vaccine by cultivating (?) the piroplasma in defibrinated blood from affected animals, which produce in healthy cattle only a very mild affection at the same time immunizing them (the immunization requires three inoculations. The experiments carried out in Buenos Aires and Alfort gave satisfactory results, as immunized eattle resisted artificial as well as natural infections, but there are no reports available relative to its application in practice. The method of preparing the vaccine is likewise unknown. Blood serum of cattle which have recovered from the disease is not suitable for the immunization of cattle. Literature. Babes, C. R., 1888. CVIT. 692; V. A., 1889. CXV. 81. Smith & Kilborne, An. Ind., 1893. Bull. Nr. 1. — Theiler, Schw. A., 1895. XXXVII. 3; Fortschr. d. Vhyg., 1903. I. 133; V. J., 1910. 98; Bull. Soc. Path. exot., 1910. III. 135. — Ligniéres, La tristeza, etc., Buenos Aires 1900; Arch. de paras., 1903. VII. 398. — Kossel & Weber, Arb. d. G.-A., 1900. XVII. 460. — Techn. Dep. f. d. Vet. — Wesen. A. f. Tk., 1901. XXVII. 41. — Krageriid, Z. f. Tm., 1901. V. 284. — Kossel, Hb. d. p. M., 1903. I. 840 (Lit.). — Kossel & Schiitz, Weber & Miessner, Arb. d. G.-A., 1904. XX. 1. — Schmidt, A. f. Tk., 1904. XXX. 42, — Knuth, Diss. Leipzig 1905. — Koch, Z. f. Hyg., 1906. LIV. 1. — Evers, B. t. W., 1908, 458. —- Witt, ibid., 1908. 628, — Nuttall & Hadwen, ibid., 1910. 38. (b) East African Coast Fever. (East coast fever, Rhodesian redwater, Rhodesian tick fever; Ostafrikanisches Kiistenfieber [German].) This dangerous form of piroplasmosis in cattle is dis- tinguished from the previously described affection especially in that it cannot be transmitted from animal to animal by the blood. Its cause is the Piroplasma parvum. Occurrence, Etiology, Natural Infection. 779 The nature of the disease was determined by the investigations of Theil the Transvaal, and of Koch in Buluwayo. s es eet Occurrence. The disease formerly existed in a latent form along the Hast African coast, a severe outbreak however oc- curred in 1900 when some very susceptible cattle were brought to the Portuguese territory, to Beira (Koch; Creutz believes that the Australian cattle introduced the virus). With the severely affected cattle it was then spread into the interior of Africa, especially to German East Africa, Natal, the Trans- lee and Rhodesia, where it caused great loss among the cattle nerds. In 1905 about 500 farms were infected in the Transvaal, and inside of a year about 50,000 cattle succumbed to the disease. Etiology. The Piroplasma parvum (Babesia parva), the smallest of piroplasma known at the present, may be seen in its characteristic form as a fine rod-shaped intracellular body, which on one end contains a chromatin granule, and fre- quently appear arranged in cross or willow leaf-shaped form; ring and dise shapes also occur, while pear-shaped twin forms are never present (Fig. 134). The disease cannot be produced artificially by the inoculation of blood containing the parasite. Healthy cattle withstand subcu- taneous, intravenous or intraperi- toneal injections of such blood with- out harm, only when they are inocu- lated two weeks later for the second time, a rise in temperature sets in immediately, and after 10 or 12 days more a mild form of the disease ap- pears, whereupon parasites may be demonstrated in the blood. Meyer obtained positive results by intro- Fig. 134. Piroplasma parvum. ducing large pieces of spleen from fe blood, chromatin stain. 2 : fi er Theiler.) affected animals into the abdominal cavity of healthy cattle, whereupon after 12 days the parasites appeared in the blood with a simul- taneous rise in temperature. The natural infection is transmitted by various ticks, especially by nymphs of the sexually mature forms of Phipice- phalus appendiculatus, further by sexually mature forms of Rhip. evertsi, Rhip. simus, Rhip. nitens, and Rhip. capensis, which in the earlier stages of their development have sucked blood from affected cattle. The parasite does not pass through the egg of the tick as is the case with the piroplasma bigeminum, neither is it transmitted from immune animals to health cattle (Theiler, Lichtenheld). Its development in the body of the 780 East African Coast Fever. tick is similar to that of the piroplasma bigeminum (Koch see p. 766). Stockman succeeded in producing the disease in cattle in England with nymphs of the brown ticks sent there from Africa. The infection always occurs during pasturing, especially easily after the appearance of the rainy season and during the high grass season when the ticks, which are present in great numbers, easily jimp from the high grass blades to the cattle. As a matter of fact, previously healthy cattle become affected with a dangerous form of the disease after they are pastured in the same field with animals from infected localities, or if they are driven over infected pastures. In the endemicly infected territories on the coast and in lowlands cattle under one year of age usually become affected. In these the loss usually amounts to 60 to 90%, while older animals are immune if they have already passed through the disease. The infection in the highlands is less severe, as there hardly more than 15% of the increase in stock die of the disease. For this reason older cattle in these localities are immune only to a slight extent, and a certain number of them fall victims to the disease (Lichtenheld). Contrary to the described conception on the etiology of coast fever, Ollwig, as well as Fiilleborn is of the opinion that the cause is possibly ultra-microscopic, as it does not produce anemia, is not directly transmissible, and that the disease leaves an absolute immunity. Piroplasma mutans and Piroplasma parvum are, according to their views, uot only morphologically but also etiologically identical, and both types probably produce the piroplasmosis which extends in all tropical and sub-tropical localities, and which shows variations only in its manifestations. This conception is also substantiated by the experience that cattle which have recov- ered from coast fever are no longer infectious for ticks, and thereby they ara apparently free of the virus. 2 Anatomical Changes. The autopsy reveals punctiform hemorrhages in the subeutis and the subserous connective tissue, medullary or hemorrhagic swelling of the lymph glands, edema of the lungs and of the mediastinum, hyperemia, or ulcerative inflammation of the intestinal mucous membrane and of the abomasum; further grayish-white spots in the liver sub- stance, and as a specially striking leston hazelnut-sized, wedge- shaped infarcts in the cortex of the kidneys. The spleen is not swollen. The specific bodies, so-called plasma spheres (Koch), are present in the swollen lymph glands, in the spleen, further in the spots of the liver and in the infarcts of the kidneys, as well as in the borders of the ulcers of the mucous membrane, likewise also in the blood. By Giemsa’s stain they appear as sharply circumscribed, blue-colored spheres, con- taining point or comma-shaped chromatin granules, or they are covered by such. Collaud considers the formation of infarcts to be due to an injury of the endothelia of the vessels by endocellular toxins of the piroplasma. Similar toxins are supposed to be also produced by the Piroplasma bigeminum, only that they attack the erythrocytes, Symptoms, Prevention. 781 Symptoms. The incubation period is 10 to 12 days (Theiler, Kleine), visible symptoms however appear usually only 20 days after the time of exposure in infected pastures. These con- sist in high fever, difficult respiration sometimes associated with a cough, salivation, passing of very dry or bloody, tar-like feces, marked swelling of the submaxillary lymph glands, emaciation and weakness of the hind quarters. Contrary to Texas fever the appetite remains normal for a long time, and anemia, icterus and hemoglobinuria are only seldom observed. At the height of the fever parasites may be demonstrated in the red blood corpuscles, sometimes infesting 80 to 90%. At the same time the destruction of blood corpuscles is only slightly evident. Cattle infected with Piroplasma bigeminum may later become affected with coast fever, in which case the symptoms of Texas fever are also pronounced, and the para- sites of both diseases may be found side by side in the blood. The disease is very destructive, as in previously non- infected herds 95% of the animals die, whereas in native cattle on the coast of East Africa deaths are rare. Prevention. The infection may be kept at least temporarily from healthy herds by the careful segregation of suspected or affected animals (fenced in!). Dipping and spraying for the destruction of ticks, after fresh outbreaks, and driving the cattle into non-infected fields are advantageous preventive measures. In severely infected pastures the ticks may be in- fectious even after eight months, and even when there have been no cattle pastured there in the meantime. The danger of the pasture is eliminated after 1514 months, if during that time it is pastured only by horses, goats or sheep. Immunization. (Koch). Animals which have recovered from the disease are protected against a second attack even if remaining in an ‘infected pasture, repeated injections of blood containing the parasites likewise produce a lasting immunity. For this purpose cattle are in- jected subcutaneously at two weeks intervals for 4-5 months with 5 ec. of defibrinated blood from cattle, which have recovered from a severe attack of the disease. Cattle treated in this manner remain healthy in infected pastures, and even their offspring are supposed to resist a later infection after they have recovered from a mild form of the disease. Theiler & Stockman failed to obtain favorable results from Koch’s method, and the conference of South African veterinarians, held in Cape City in 1907, also denied its practical value. According to Gray the method has been employed in the Victoria District on 5,700 cattle without any results, as the animals became spontaneously infected, even after 11 to 12 inoculations. | : Cattle which have recovered from Texas fever are immune against the coast fever, while animals which have recovered from the latter are not immune against _ Texas fever. Literature. Koch, A. f. Tk., 1904. XXX. 281 u. 586; D. med. W., 1905. 1867. — Theiler, Fortschr. d. V.-Hyg., 1903. I. 133; 1905, II. 256; J. of the Roy. Army Med. Corps, 1904; Comp. Path., 1907. XX. 1; 1909. XX. 115; Rep. of the Gov.-Bact., 1906-1908. — Theiler & Stockman, Comp. Path. 1904. XVII. 3, — Gray, ibid., page 203. — Kleine, D. med. W., 1905. 912. — Collaud, Diss. Ziirich 1906. — Soulié & Roig, C. R., 1908. CXLVII. 192. — Lichtenheld, A. f. Hyg., 1908. LXI. 261; 1910, LXV. 378. — Meyer, Comp. Path., 1909. XXII. 213. 782 East African Coast Fever. Tropical Piroplasmosis of Cattle. Dschunkovsky & Luhs observed in southern Russia a disease of cattle resembling coast fever, in which in the acute cases, up to 80-96% of the red blood corpuscles contained a ring and punctiform, also a rod-shaped piroplasma, which could not be reproduced artificially by inoculations of blood containing the para- site, (up to several liters were injected subcutaneously, intraperi- toneally, or intravenously). On the other hand, according to more re- cent experiments, larvae of females of the Boophilus decoloratus, which later suck the blood of infected cattle caused, aiter 10-15 days, a fever lasting for several days, mostly however without any parasites in the blood. The symptoms were fever up to 40°-41° C., at intervals of 8-12 days, then continuous at 40°-42° C., symptoms of nervous irritation, sometimes with attacks on persons, accelerated heart’s.action and res- piration, general icterus and pronounced emaciation, frequently bloody diarrhea, and shortly before death sphincter paralysis. The urine was only rarely reddish-yellow, the number of erythrocytes diminished to as few as 800,000 per cubic millimeter—The autopsy revealed large hemorrhages in all organs, ulcerations corresponding to the hemorrhages, in the abomasum and small intestines, and acute swelling of the spleen. The disease also runs a more chronic ecachectic form when only 10-40% of the erythrocytes contain the parasite, and on autopsy striped and variegated lesions of the mucous membrane of the abomasum are found with an ocher-yellow or dark base. (Chl. f. Bakt., 1904. XXXV. 486.). A similar disease was observed by Kowalewsky in Taschkend, only it ran a more rapid course, and in some cases grayish-yellow deposits developed on the mucous membrane of the lips and cheeks, and also on the tongues. (J. vet., 1907. 330.) Further it appears that the disease observed by Penning in Java is identical with the above. There it attacks buffaloes, and a transmis- sion to sheep with larvae of the Boophilus australis was successful. (Tier- arztl. BL. f. Niederl.-Indien, 1906. XVIII. 102.) Pseudo-Coast Fever. Lichtenfeld designates by this name a dis- ease of African cattle which manifests itself with fever up to 41° C., emaciation, diminished appetite, and which sometimes causes death. The blood appears watery, and up to 10% of the erythrocytes contain a small rod or ring-shaped parasite resembling closely the Piroplasma parvum, which had been found previously in sparing numbers, by Theiler in the blood of cattle, usually simultaneously with the Piroplasma bigeminum, and described as Piroplasma mutans. (Fig. 135.) After the inoculation of such blood the piroplasma appears after an incubation of 10-25 days in the blood circulation of the inoculated animal, and produces anemia with poikilocytosis, but Fig.135. Piroplasma mutans. never hemoglobinuria. The natural mode (After Theiler. ) of infection is still unknown. Theiler formerly considered the parasite as an immune form of the Piro- plasma bigeminum, while Koch was of the opinion that such cases were mixed infections of coast fever and Texas fever. Recently, however, Theiler showed that Pseudo-Coast Fe ver. 783 the Piroplasma mutans oceurs also in localities free from coast fever, on the other hand he proved that cattle immune against Texas fever may be infected with it; therefore it could not be a ee form of the piroplasma bigeminum. ; Parasites resembling the Piroplasma mutans were also found by Miyajima & Shibajama in Japan, by Martini in China, by Does in Netherlands-India, by Schein in Indo-China; moreover, the parasites seen by Dreyer in Egyptian fever, and by Springefeldt in Camerun in cattle, appeared to be identical with them, Lichten- held observed their appearance in calves 32-91 days after birth, although the animals showed no symptoms of disease. He, as well as Broden & Rodhain, suc- ceeded in propagating them by the injection of blood containing piroplasma. Literature. Theiler, Rep. of the Gov.-Bact., 1905/06-1907/08; Comp. Path., 1909. XX. 115. — Schein, A. P., 1908. XXII. 730. — Lichtenheld, Z. f. Hyg., 1910. LXV. 378. ; Gall Sickness. (Galziekte). Under this name the farmers of South Africa designate in general those diseases in the course of which a dis- coloration and thickening of the bile, as well as an icteric condition of the tissues develops. With the more accurate study of the diseases it was found that the most varied diseases are grouped under that name, (rinderpest, coast fever, Texas fever without red urine, heart water, and poisoning by plants). Nevertheless there are enzootic infections of cattle which cannot be classed with any of the known types of disease, and which are also designated by professional men as gall sickness, in the restricted sense. The etiology of these affections has not yet been established satis- factorily. While Hutcheon, who.in 1897 described them first as jaun- dice or biliary fever, attributed them to a primary affection of the liver from an unknown cause, Spreull identified them as Pasteurellosis with the Lamziekte (see p. 109), Eddington with heart water (see p. 257). Theiler was formerly inclined to connect it with Trypanosoma theileri, later with Piroplasma mutans; according to his recent investigations however he determined that they are produced by the anaplasma mar- ginale (Fig. 129 on p. 763), in which the blood corpuscles are attacked and destroyed, whereby an oligocythemia is produced, which is associated with high fever, and which later leads to a degeneration of the large parenchymatous organs. According to Theiler’s conception the disease would be identical with the mild form of Texas fever described by Smith & Kilbourne, which is observed espe- cially in North America in the fall, as a second attack in cattle that recovered from the acute affection in the summer. According to Knuth’s observations it oceurs in a similar manner also in South America, and the cachectic form of piro- plasmosis described by Dschunkowsky & Luhs in Trans-Caucasia is supposed also to belong to it. The disease named Anaplasmosis by Theiler attacks cattle exclu- sively, and especially when they are brought from highlands into low- lands, or from less infected localities into more infected territories. African cattle are less suscéptible, as they have mostly passed through the disease as calves, whereas fresh, imported animals usually become affected severely. ; The parasites may be transmitted to healthy cattle with the blood of affected and recovered animals, whereupon in the first case they appear in the blood after 27-32 days, in the second after 16 days, and may be demonstrated during the febrile period, exceptionally also for some time after. Animals which have recovered from the disease show a great resistance against new infections, but they serve as virus reservoirs for the Boophilus decoloratus tick, which according to Theiler is sup- posed to transmit the natural infection in a way similar to Texas fever. 784 Gall Sickness. Mixed infections occur especially frequently with redwater. According to Theiler’s view, Texas fever, as it has been formerly described, constitutes two different diseases, namely the Texas fever in the restricted sense (piroplasmosis, redwater), and the gall sickness (anaplasmosis). As the Piroplasma bigeminum and the Anaplasma marginale occur very frequently simultaneously in the same animal, the development of redwater with piroplasma in the blood is first observed after an inoculation of blood; when the animal has recovered and the time of incubation for the anaplasmosis has elapsed a new disease results, which was for- merly considered as a relapse of redwater. Mixed infections occur also with Piroplasma mutans, and with Spirochaeta theileri. The symptoms of gall sickness are high fever with great debility, labored respiration, and very frequent heart’s action. Constipation or diarrhea, further moderate swelling of the eyelids; with lachrymation. Edematous swellings may also appear in different parts of the body; in the later course, anemia and icterus is observed, when the animals rap- idly become emaciated. Some animals die within a few days, others in 1-2 weeks; the greater part of the patients, frequently even 80-90% recover, but outbreaks with losses up to 50% may occur (Leipziger). According to the course of the disease a more or less rapid multipli- cation of anaplasma, with a corresponding reduction in the number of erythrocytes is found in the blood at the beginning of the fever. Pale- ness of the remaining blood corpuscles is observed, and in less acute eases polychromatophilia, and basophilia, still later the appearance of normoblasts. : The anatomical changes consist in pronounced anemia and icterus, moderate gastro-intestinal catarrh, diffuse swelling of the lymph glands, acute spleen tumor with reddish-brown, soft but not liquefied pulp, small hemorrhages and degeneration of the heart muscles. ; For the prevention of the disease it is aimed to keep animals from marshy pastures, especially from overgrown banks of rivers. If the disease has already appeared it usually subsides after the herd is driven to a dry elevation. Literature. Edington, Comp. Path., 1905. XVIII. 155. — Theiler, ibid., 1907. XX. 1; Z. f. Infkr., 1910. VIII. 39. — Spreull, ibid. 1908, XXI. 193. — Leipziger, D. t. W.. 1910. 150. (c) Piroplasmosis of Horses. Piroplasmosis Equorum. (Biliary fever; Babesiosis equi; Pferdemalaria [German]; _Piroplasmose équine [French].) History. Guglielmi (1889) in Italy found in the red blood corpus- cles of horses parasites resembling the piroplasma bigeminum, but the disease has become better known only since the study of the South Afri- can horse sickness (see p. 285). Although Rickmann still considered the blood parasites as the cause of this affection, Theiler: proved that in South, Africa there exists another disease of horses which may fre- quently be complicated with the latter; the same author also established more closely the symptomatology, and pathological anatomy of piro- plasmosis of horses, and recently showed also its identity with a similar affection of mules and donkeys. The parasites were also studied by Laveran, Koch and Marzinowski, while Italian, English, French and Russian veterinarians contributed especially descriptions of its spread and symptomatology. co lia res 7 Piroplasmosis of Horses. 785 Occurrence. The disease appears to occur frequently in Italy and Russia, in localities with forest and marshy pastures. Native horses as a rule become affected only when young, while animals brought from uninfected territories into infected localities are affected at all ages, and almost exclusively in the warm season (in Russia it is wrongly termed ‘‘Spring dis- ease’’). The disease occurs also frequently in Africa and India. In Germany only one case has been diagnosed by Ziemann in Oldenburg, while in Sweden Brickmann attributed a disease of horses to an infection with piro- plasma.—In Italy Baruchello & Pricolo, also Mori are inclined to identify piro- plasmosis with catarrhal influenza, while Perrucci connects it with purpura hemor- rhagica. This supposition is based principally on the similarity of the symptoms and evidently does not apply to other localities—In Russia the disease was observed in various localities after the demonstration of piroplasma in horses by Michailof (1902), also by Bielitzer, Marzinowski, Feinschmidt, Michin and Yakimoff, espe- cially frequently, however, in southern Russia (here, also, in donkeys), causing sometimes losses up to 50%. It is widely spread in Africa, where it has been diagnosed and carefully studied in the south by Theiler, in the German protectorates by Koch, also by Roger as well as by Lafargue, Lussault & Savary in Algeria, by Piot in Egypt, by Dupuy & Pierre in the Sudan and in Senegambia, by Thiroux in Madagascar. Lingard & Jinnings, Axe and Williams reported on its occurrence in India. Etiology. The Piroplasmia equi (Babesia equi) is a small blood parasite resembling the Piroplasma parvum. It is 0.5-2.5 in size, of coccus, ring, spindle, rod or also pear shape. In the red blood corpuscles it is present singly, in pairs, or in fours in rosette form, which latter probably originated by direct division of the single individuals. In the blood plasma they are found only singly. By the Giemsa stain a clump of chromatin granules and sometimes also a second chromatin granule (Blepharoplast?) may be in their body. Marzinowski & Bielitzer observed in the intestinal contents of ticks which previously had sucked blood from infected horses, transitory forms similar to those described by Koch in piroplasma of cattle, and by Christophers and Kleine in piroplasma of dogs. They are also inclined to consider oval and worm-shaped -bodies with large granular cytoplasm and small nucleus as one form, and those with a still smaller nucleus and paler cytoplasm, as other sexual forms from which new, worm-like actively motile forms (Ookinetes ?) develop, which occur in great numbers in the saliva of the ticks with which the eggs are moistened. The demon- stration of parasites in the egg of. the ticks was not successful, but various stages of development, especially the worm forms, were found in the larvae in consider- able numbers. Marzinowski also reported successful cultivation experiments in blood con- taining 10% sodium citrate solution, in which the parasites passed through similar stages of development as in the intestines of ticks. Their multiplication was only moderate, and they died in the third generation. Theiler succeeded in producing by subcutaneous or intra- venous inoculations of blood of immune horses a febrile affec- tion in mules and donkeys which developed after an incubation of “5 to 9 days, and in the course of which the parasites appeared in the blood. The first attack was followed by a second one, during which the number of the red blood corpuscles diminished to one third, and which frequently resulted in death. The disease was likewise reproduced in horses with the blood of immune mules Vol. 1.—50. 786 Piroplasmosis of Horses. and donkeys. Positive results, also with the blood of affected horses, are reported by Perrucci, Pricolo, Edington and Bie- litzer. According to Theiler the natural infection is transmitted in Africa by the Rhipicephalus evertsi, in Russia according to Marzinowski & Bielitzer by the Dermacentor reticulatus, that is by sexually mature ticks which have sucked blood containing piroplasma as larvae or nymphs. As horses which have re- covered from the disease harbor piroplasma for years in their blood, such animals may spread the virus by transmission to ticks. Zebras and quaggas appear also to serve as virus carriers. In infected localities native horses, donkeys, and their bas- tards, become affected in later periods of their lives only when their acquired resistance is reduced by overexertion, poor nutri- tion, or by intercurrent affections to such an extent that their latent piroplasma again rapidly multiply. Such relapses occur especially in affections of horse sickness, the course of which frequently becomes severe because of such relapses. Animals of the horse genus which are brought from locali- ties free from piroplasma to infected localities are very sus- ceptible; thus during the Boer War in South Africa great losses were sustained in horses brought there from Europe and Aus- tralia, au in India horses from Australia become especially affected. Anatomical Changes. On autopsy the icteric discoloration of the subcutaneous and of the subserous connective tissue, as well as of the internal organs is conspicuous, after a somewhat protracted course a general anemia is present which is also man- ifested in the watery consistence of the blood. The lymph glands and the spleen always show pronounced acute swelling, the pulp of the spleen being moderately softened but not blackish red. Numerous hemorrhages are present on and in the serous and mucous membranes, as well as under the endocardium, the’ intestinal mucous membranes show inflammatory swelling, that of the large intestine in some cases also contains follicular ulcera- tions. The lungs are edematous, the kidneys may be sprinkled with punctiform hemorrhages, or only anemic and filled with serous fluid, the liver lobules are yellow, on their borders greenish colored. The muscles, including those of the heart show cloudy swelling, in places also fatty degeneration. The urinary bladder frequently contains more or less reddish colored urine. : Symptoms. After an average incubation of about two weeks the disease commences with slow or rapid rise of the body temperature, whereupon the fever continues for a long time remittent in character. The first visible symptom is a pale-yel- low, or reddish-yellow coloration of the mucous membranes, the intensity of which is proportionate to the severity of the affec- Symptoms. 787 tion. In the severe cases, hemorrhages occur later in the con- junctiva in varying number and extent. At the same time the patients look dull, tears ooze from the half-closed eyelids, the animals droop their heads, lie down frequently, and in general show great dullness, which is very pronounced, especially in cases with a chronic course, so that the disease greatly resembles chronic encephalitis. During the fever the heart’s action is in the acute cases, greatly accelerated and weak, the respiration is of the abdominal type and markedly labored. In some cases urticaria, and exceptionally herpes labialis is observed in the meantime. The appetite is depressed from the onset, while thirst is in- creased; at first or through the entire disease there is constipa- tion, the feces are passed sparingly in small balls, which are covered with a yellowish mucus; later diarrhea appears in some of the cases, sometimes with colicky symptoms. The urine shows icteric or reddish-brown coloration, and is passed in large quan- tities. The animals rapidly emaciate, their legs swell, the tissue at the same time showing a very slight resistance against trau- matic influences, accidental injuries healing very slowly. Blood drawn from a vein coagulates rapidly; the coagulum separates immediately in an upper intensely yellow, and a lower red layer, while the serum appears brownish yellow. According to the physico-chemical examinations of Frei in Pretoria, the blood shows during the disease a continually diminishing volume of red blood corpuscles, and a reduction of conductivity, as well as of viscosity, which correspond with the progress of hemolysis; these changes set in very rapidly, sometimes 24-48 hours after the infection, and therefore even before the rise of temperature. In the urine a diminution of the osmotic concentration, of conductivity, and of specific gravity may be shown, changes which appear to be dependent on the condition of the serum, and on the polyuria which is usually present, and with which in some cases an increase of the total quantity of the eliminated solids is associated. Stazzo found in one instance only 2% millions cf red blood corpuscles per cubic millimeter of blood. \ In some cases the course is very mild, inasmuch as the dis- ease is manifested, only by a slight icteric discoloration of the ‘mucous membranes, and by febrile manifestations, recovery fol- lowing in a few days. In severe cases death ensues with a sharp drop.of the temperature, usually in 2 to 5 days, while in a pro- tracted course the disease lasts from 2 to 4 weeks, and may even extend over several months. In chronic cases the disease is manifested by the presence of an almost continuous fever, in gradual emaciation, edematous swellings, anemia and the discharge of a brownish urine (Stazzi). In the disease observed by Brickmann in Sweden (‘‘Vesterbol- ae tenslau’’), which also usually followed a chronic course, the symptoms consisted in fatigue and dullness, itching, nodular skin eruptions, per- spiration and yellowish discoloration of the conjunctiva. The disease rarely terminates in death. ; : Tn mules icterus is rarely present, while discoloration of the urine never occurs; on the other hand frequent urination is almost regularly 788 Piroplasmosis of Horses. observed (Hassie frequently observed a luxation of the patella as a result of a relaxation of the thigh muscles). In donkeys icterus is also rarely present, while the urine frequently shows a red coloration; a vesicular eruption is also observed in some cases on the back, less fre- quently also on other parts of the body, and is followed by loss of the hair. The autopsy reveals a large quantity of pale yellow fluid in the abdominal cavity and in the pericardium. Piroplasma may be demonstrated in the circulating blood in variable numbers. While in severely acute cases and at the height of the fever they may be found in 50-60% of the red blood corpuscles, and some of these may contain as many as 5-6 parasites, in chronic cases hardly 1-2% are infested. Course and Prognosis. Cases with severe onset, especially great debility, high fever, numerous hemorrhages and hemo- globinuria, likewise cases of a chronic character, usually run an unfavorable course, whereas cases which are acute, but without severe symptoms, promise a favorable termination. In these cases the improvement sets in after about eight days, whereupon recovery progresses slowly (according to Rickmann the benign forms are as a rule relapses). Diagnosis. The disease differs from horse sickness princi- pally by the presence of marked icterus, and on the other hand by the absence of extensive edematous swellings. A positive diagnosis is however only possible by the demonstration of piro- plasma in the red blood corpuscles, or then by the infectious- ness of the filtered blood in horse sickness, as well as in perni-' cious anemia. The microscopical examination makes a positive differentiation of pirolasmosis from trypanasomiasis possible aside from the fact that this disease is less acute, and does not show icterus and such marked debility. Besides this the symp- toms of piroplasmosis to which Italian observers have repeat- edly pointed, closely resemble also those of influenza and pur- pura hemorrhagica. Treatment. Horses which are attacked in the pastures should immediately be placed in stables or in dry shady places; where they should be freed from ticks, and nourished as freely as possible. The threatening heart weakness is combatted with digitalis or camphor, the constipation first with calomel, later with salines. Arsenical preparations are recommended for the after treatment. , The specific treatment has so far failed to give uniform results. Formerly large doses of quinine (10-20 gm.) alternating with ammonium chloride were given, whereas recently mercurial and arsenical preparations are preferred. Thus Baroni recommends the Hydrarg. biiodatum injected into the muscle, and Lafargue, Lussault & Savary also obtained good results from this treatment (1 gm. Hydrarg. biiod., 2 gm. iodide of potassium, 100 gm. aqua; 10-20 gm. daily). Saikowitsch and Marzinowski & Bielitzer praise intramuscular injections of corrosive sublimate (10 cc. of a 2% solution daily, 3-5 times in all), and according to Michin & Yakimoff it is possible to reduce the mortality by this treatment to 20%. The subcutaneous application of arsenious acid, and of’ atoxyl has not proved effective. Treatment, Prevention. 789 Prevention. This consists in keeping non-immune animals from infected pastures especially in the warmer periods when ticks are numerous. Solipeds from countries free from piro- Papas should be imported only while young, and during the nter. : _ Immunization, Based. on the experiences on immunization against piroplasmosis of cattle with infectious blood of calves, Theiler recom- mends the immunization of horses with 1 cc. of blood of artificially in- fected donkey colts, from the fourth generation upwards. Horses thus inoculated remain healthy, Pregnant mares and run-down animals should not be inoculated. «: The inoculation was also well borne by horses, mules and donkeys imported from Argentine. Literature, Guglielmi, Clin. vet., 1899. 220. — Theiler, Schw. A., 1901. XLITI, 233; D. Z. f. Tm., 1904, VIII. 382; J. of comp. Path., 1905. XVIII. 229 ; 1906. XIX. 283; Rep. of the Gov. Bact., 1905/06-1907/08..— Laveran, Soe. biol., 1901. 385, —Rickmann, B. t. W., 1902. 4. — Roger, Bull., 1906. 120. — Baroni, Clin. vet., 1906. 1033. — Perrucci, ibid., 1907. 159. — Stazzi, ibid., 1907. 46. — Axe, Comp. Path., 1906. XIX, 222. — Williams, ibid., 1907, XX. 23. — Lafargue, Lussault & Savary, Rev. gén., 1908. XII. 489. — Marzinowski, Z. f. Hyg., 1909. LXII. 417. — Marzinowski ‘&:Bielitzer, ibid., 1909. LXIII. 17. — Michin & A ae ev] Z. £. Infkr., 1909. VI.:265. — Frei, ibid., 1910. VII. 105. — Bielitzer, ibid., : eects (d) Piroplasmosis of Sheep. Piroplasmosis ovum. (Malarial catarrhal fever; Haemoglobinuria s. Ictero-Haema- turia ovum; Babesiosis ovum; Carceag, Rowmanian.) History. In Roumania a disease occurs among sheep, known as **Carceag,’’ which was first observed by Mazureano (1884), and in which Babes (1892) found similar bodies in the red blood corpuscles to those occurring in the infectious hemoglobinuria of cattle. He also succeeded in infecting healthy animals with pulp of the spleen from affected animals. Since then the disease has been found by Bonome in northern Italy, Leblane & Savigne in France, Dschunkowsky & Luhs in Trans-Caucasia, Laveran & Nicolle in the vicinity of Constantinople, Ziemann in Venezuela and the West Indies, Eggebrecht in China, and Paschen believes that it occurs also in Germany. Its etiology was studied in detail by Motas in Roumania. Occurrence. The disease is distributed in Roumania in the flats of the Danube and especially in the islands of the Danube which are frequently exposed to inundations, to such an extent that in some years up to 20% of the sheep die. It is observed in infected localities almost exclusively during the warmer season, especially in the low, swampy pastures, more rarely in mountainous pastures. Native sheep are considerably more resistant than animals brought from territories free from the affection, which succumb in great numbers under conditions favorable for infection. Etiology. The piroplasma ovis (Babesia ovis is similar to the piroplasma bigeminum, only somewhat smaller, 1-1.8 Hw) is usually found in the red blood cells, singly or more rarely in 790 Piroplasmosis of Sheep. double pear shapes, also in rod and cross shapes (Fig. 136). The disease may be transmitted with the blood of affected ani- mals artificially to older sheep, but still more easily to lambs. bi © @ The inoculated animals _ show, a a after 8 to. 10 days, febrile symp- @ eS) a y.) toms, and at the same time para- @ e "3.29 sites may be found in their red 6”, @a® © @ blood corpuscles. Cay @ The disease is transmitted @ ge%® @ under natural conditions by sex- @e ually mature ticks (Rhipicephalus & F bursa), which as larvae or nymphs @e @ have sucked the blood of affected @ @ & sheep (the infection also succeeds artificially with such females, if Fig. 1386. Piroplasma ovis. Stained with carbo-thionin. (After Motas.) they are placed in the fleece of lambs [Motas]). Dschunkowsky & Luhs have observed the disease also in goats, and according to their observations in Trans-Caucasia these animals are affected simultaneously with sheep, although they are of the opinion that the piroplasma of goats (Ppl. hirci) differ from those of sheep, . jin that they are only one-half the size of the latter (0.43-1-71 + long). Similar bodies were observed in goats also by Panse, in East Africa. Anatomical Changes. The autopsy findings disclose hem- orrhagic inflammation, sometimes also superficial necrosis of the mucous membrane of the pyloric half of the abomasum, of the duodenum and rectum; further an acute swelling of the spleen, parenchymatous degeneration of the liver and kidneys (their dark brownish-red coloration frequently shows a greenish hue), finally a gelatinous or gelatino-hemorrhagic infiltration of the subcutaneous and the mediastinal connective tissue. Ap- proximately 5-6% of the red blood corpuscles in the pulp of the spleen contain piroplasma. — Symptoms. The disease commences, after an incubation of 8 to 10 days, with a rise in the body temperature to 40-42° C., weakness, loss of appetite and muscular trembling. Soon diffi- culty in respiration, painful bleating appear, and 1 to 2 days later indications of anemia, icterus, and lumbar weakness. The initial constipation is followed by diarrhea, in which the animals pass bloody feces under symptoms of colic. In some cases the urine is red colored, as a result of oxyhemoglobinuria,. fre- quently however also through hematuria. The number of erythrocytes in the blood diminishes to 114 millions per cubic millimeter, under the microscope they contain the small, mostly roundish or oval parasites, which are also found on their surface and in the blood plasma. About 50-60% of the affected animals, mostly older sheep and 3 to 4 months’ old lambs, die in 2 to 5 Symptoms, Treatment. 791 days, while the others recover after a convalescence of several weeks. In some cases however the affection manifests itself only by fever lasting 2 to 4 days, slight intestinal catarrh, and symptoms of anemia. Recovery from the disease conveys to the animals an im- munity of long duration against new infections. Treatment and Prevention. Leblanc & Savigné recommend for the treatment internal administration of sulphate of quinine (0.5 gm. twice daily), and Glauber salts (30-60. gm.). Prevention consists in avoiding affected pastures. Immunization. According to Motas the inoculation of blood con- taining only a few parasites produces a mild affection, after recovery from which the sheep withstand an injection of 16 cc. of virulent blood, 5 ec. of which would otherwise be fatal. Blood serum of hyperim- munized animals has no parasiticidal properties (in vitro), and at best protects animals only against mild subsequent infections, while bile is supposed to be effective against simultaneous and also against subse- quent infection. Immunization with a mixture of blood containing parasites and bile, in which the blood corpuscles are destroyed and the piroplasma eliminated, are supposed to produce an active immunity, although no febrile reaction appears either after the inoculation or after a later injection of virulent blood, and no parasites appear in the blood of the immunized animals. Literature. Babes, C. R., 1892. CXV. 359. — Bonome, V. A., 1895. CKXXIX. 1. — Laveran & Nicolle, Soc. biol. 1899. 800. — Hutcheon, Vet. Rec., 1902. XIV. 629. — Motas, Soe. biol., 1904. 1523; Kongr. Haag. 1909. — Paschen, Hyg. Rundschau, 1905. XV. 545. — Dschunkowsky & Luhs, Kongr. Haag. 1909. (e) Piroplasmosis of Dogs. Piroplasmosis canum. (Malignant protozgoon jaundice, Malignant malarial fever; Bosartige Gelbsucht [German]; Fiévre bilieuse, Jaunisse maligne [French].) History. After Piano & Galli-Valerio (1895) had first discovered the blood parasites in Italy, the disease was observed in South Africa, where it is one of the most dangerous diseases of dogs, by Purvis, Duncan, Hutcheon, Lounsbury and Robertson, in East Africa by Koch in Senegal by Marchoux. In France it was diagnosed by Nocard & Almy, at the clinic of Alfort, principally among hunting dogs, and was later studied more closely by Nocard & Motas. In addition to the work of these authors the biology of the parasites was studied by Nuttal & Graham Smith, Kinoshita and Christophers, their artificial cultivation by Kleine and Nuttall, while Nuttall & Hadwen obtained remarkable results with the specific treatment of the disease. Occurrence. The disease appears to occur with special frequency in tropical countries, and particularly in imported dogs it runs a very severe course. On the other hand in mod- erate zones it is considerably more rare, and usually runs a 792 Piroplasmosis of Dozs. chronic course. In these locations hunting dogs usually become affected, which have previously hunted in the forests. In Europe the disease has been diagnosed, besides in Italy and France, by Wetzl in Hungary, by Ljubenetzkij and by Dschunkowsky & Luhs in Russia; Holterbach believes that a disease of dogs which he observed since 1907 in German Offenburg, should from its clinical picture be considered as a piroplasmosis. Of the tropical countries, excluding South Africa, India and China are especially infected. Fig. 137. Piroplasma canis. Fig. 138. Piroplasma canis. Stained with methylene blue. Stained after Laveran. Etiology. The piroplasma canis (Babesia canis) is mor- phologically closely related to the piroplasma bigeminum (Figs. 137 and 138), only that the parasites found in the red blood corpuscles and. those in the blood plasma are relatively larger (.7-3.6 “), and that single blood cells contain more of the para- sites, sometimes as many as 16 individuals. The extracellular ones are roundish, those inclosed in cells are pear-shaped or poly-angular. While living they show an active motility, in which they send out very fine pseudopodia. The homogeneous plasma encloses a spherical or oval nucleus. Propagation, which 1s especially prolific during the duration of the fever, is, accord- ing to Nocard & Motas, supposed to occur by direct fission, in which the splitting of the nucleus precedes that of the plasma body. . According to Nuttall & Graham Smith propagation is also supposed to occur by direct fission. They observed free pear-shaped parasites in the blood plasma, actively swimming around, apparently propelled by flagellae, and subsequently to penetrate red blood corpuscles. In these they assumed a spherical shape, sent out pseudopodia, and divided into two pear-shaped bodies, which subsequently separated, slipped out of the blood corpuscles and looked for new erythrocytes. If they failed to find them they died. Kinoshita saw similar phenomena, but believes that the individuals resulting from fission should be differentiated into male, possessing flagellae, and female forms without flagella. If the defibrinated blood of affected dogs is mixed with equal parts of physi- ological salt solution and is kept at a temperature of from 24°-27°.C., the piro- plasma remain alive for four days, they show similar stages of development (star shapes) to those described by Koch for the piroplasma of cattle in the intestines of ticks (see p. 766) (Kleine, Nuttall). Similar forms were observed by Chris- tophers in the intestines of nymphs and of mature ticks, besides the pear shapes are supposed to penetrate the cells of the salivary glands and the eggs in the body of the tick, where they break up into sporozoites (7), which then leave the body of the tick with the saliva. Etiology, Pathogenicity. 793 Pathogenicity. The disease may easily. be transmitted to healthy dogs by subcutaneous or intramuscular inoculation of blood containing parasites. These appear in the blood after 2 or 5-6 days, and the infected animals usually die in from 3-5 or 9-11 days, sometimes however the disease may extend even to 60 days, or exceptionally recovery may take place. Other animals are not susceptible to the infection. Tenacity. Blood containing piroplasma remains infective for 25 days when kept in a cool and dark place. At summer temperature, however, it becomes inactive after 14 days; the parasites die at 44° C., in 1% hours, at 50° in a half hour. In France the natural infection is according to Nocard & Motas transmitted by the Dermatocentor reticulatus (possibly also by the Ixodes ricinus). In South Africa, according [In z2{/at»|sofef2i[sj9 to Lounsbury & Robert- Ar Uy son, by the Haemophysalis POS 2e5 ram Leachi, in India according {44.043 osu to Christophers and Nuttall =f rr = by the Rhipicephalus san- proof guineus. The two last =e Sa named species of ticks pass P232-E Rt their development as larvae and nymphs on three hosts, possibly also on other ani- — |shoo| soft A mals than dogs. Females A which have sucked the blood = [P420h3s n of healthy dogs transmit the : virus by their eggs to the =e larvae, in which, as well as _— fagdzolss vite in the nymphs it remains latent, and only the sexually —begeo|» ras sas os mature ticks are capable of again transmitting the piro- Fig. 139. Fever curve in piroplasmosis of plasma to dogs (Lounsbury, dems, After swveutancous injection of view eee i ee ee eee (After Wetzl.) le oe lon does not succeed wi mature ticks taken from affected dogs. Ticks capable of infec- tion may carry virulent piroplasma in their bodies even for ‘Seat months, and transmit them in the meantime to dogs uttall). Young dogs are much more susceptible to the infection than adults. It is questionable whether the piroplasma of dogs are identical in different parts of the world. MacFadyean and Nuttall found dogs, which had recovered from the piroplasmosis of India, to be still susceptible to infection with the African para- sites. La} eee. Ha Anatomical Changes. The autopsy of dogs dead with the disease shows pronounced acute swelling of the spleen, with a dark, bluish-red, somewhat soft pulp, hyperemia of the liver, 794. Piroplasmosis of Dogs. kidneys, and the bone marrow. In these, and also in the lungs and pericardium small hemorrhages, and in some cases acute catarrh of the stomach and duodenum, with bloody contents in the intestines may be found, and in many cases also general icterus. The changes are generally less pronounced in very acute cases, while in chronic cases icterus is frequently absent, on the other hand a severe anemia is present. Piroplasma may be demonstrated in great numbers, especially in the kidneys and in the spleen. Symptoms. After an incubation of 7 to 10 days, a rise of the body temperature which inside of 2-3 days reaches 40°-43° C., and which is associated with languor, is observed in the acute cases as a first symptom. The visible mucous membranes appear at first a pale red, later cyanotic, and in about half of the cases also icteric. The pulse and the respiration are accelerated, the latter is moreover very labored: and panting. The patients re- fuse food, but drink a great deal. They move listlessly and stagger, and towards the end they can scarcely stand on their eet. The urine contains sna tcf fj91%/ albumen from the onset, Vidladad and in some of the cases up to 314% hemoglobin, howecjeo— & { sometimes also bile pig- =e ments; for this reason: podiio| 55 | aieare it shows a more or less bedede =e f _ intense red coloration eee Fhe AY / witha greenish hue. Ac- herd i pitt htt §6cording to Maignon the | 7M 4 f- quantity of urea in- 36-980 |%0 f vt creases at each febrile aa== aa AA! = attack (up to 95 gm. per 595/35 7 ms liter of urine), and sugar | 4 Re : also appears in the urine. rae ran The blood is pale Ldso 2 ¥ red, the blood serum also | sostietaptie reddish or greenish-red 5 0]20 +t in color. -The number of ; Sed es erythrocytes diminishes fer sutoutenoous injection er yincient Moos; 00 1/8 to 1/3 of the-mor- T-year-old dog; recovery. (After Wetzl.) mal or even more, while the leucocytes appear to be increased. Piro- plasma are found at first exclusively in the red blood corpuscles, later also in the blood plasma. In the later course of the disease their number increases, so that finally even 30% of the erythrocytes may be infested with them. With their in- crease the percentage of the red blood corpuscles diminishes, and an increase of hemoglobin in the plasma occurs. Symptoms, Diagnosis. 795 In the chronic cases, which frequently result in recovery, fever is observed only in the first days of the affection or may be entirely absent. In rare cases intermittent fever may be present. On account of the severe anemia the animals are list- less and languid, their mucous membranes are strikingly pale, while icterus is usually absent. The appetite diminishes, and the patients become greatly emaciated. The urine frequently con- tains albumen, while hemoglobin is only exceptionally present, and even then only in small quantities. The number of red blood corpuscles in the blood diminishes up to 1/4-1/5 of the normal while a simultaneous and marked increase of the colorless cells, especially of the polynuclear leucocytes occurs. After the disease has lasted for 3 to 6 weeks the symptoms of anemia gradually disappear, and finally complete recovery takes place. Such recovered animals however harbor the parasites for a long time in their bodies, as their blood proves infectious even after one year (Theiler), and sometimes even after 2% years (Robertson). If fever is produced in such animals, the parasites reappear in great numbers (Marchoux). Diagnosis. This can be established with certainty only by the demonstration of piroplasma; in those cases especially in which no hemoglobinuria and icterus but only anemic symptoms are observed. There exists in dogs a disease which in its clin- ical manifestations corresponds completely with piroplasmosis (anemia with disintegration of red blood corpuscles transition forms and hyperleucocytosis, albuminuria and hemoglobinuria), which probably develops as a result of the ingestion of putrefied meat. In this disease however piroplasma cannot be demon- strated microscopically or by animal inoculation (Szoyka). Nevertheless the suspicion of piroplasmosis is justified in the presence of the symptoms mentioned, especially if it concerns hunting dogs and if ticks are found on their bodies. In the case of negative microscopical findings a positive result may some- times be obtained by inoculation of blood into very young dogs, for which especially intravenous or intraperitoneal inoculations are adapted; for after this mode of infection the disease usually develops in a few days. Treatment. .Nuttall, Graham Smith & Hadwen showed by accurately controlled laboratory experiments, that trypan red, and trypan blue, have a specific destructive action on the piro- plasma of dogs. In dogs which already have harbored numer- ous parasites in their blood, they disappear from the circulating blood inside of 20 to 96 hours with the simultaneous subsiding of the fever, after a single subcutaneous injection of 5-6 cc. of a 1% solution of one of these substances. At first the pear-shaped subside later the roundish ameboid forms, although they re- appear after 9 to 12 days, but the animals show no symptoms outside of a short rise in temperature, and finally they recover Malaria of Man. 797 Leishman have observed their transformation into trypanosome-like flagellates in blood mixed with sodium citrate, and for this reason Donovan himself placed the parasites under the genus Herpetomonas. Blood-sucking bugs are supposed to transmit the natural infection to man. Similar ‘bodies were found by Nicolle & Comte in a dog, and Nicolle is also supposed to have succeeded in infecting dogs artificially with splenic blood from man; Patton and Donovan however had abso- lutely negative results. (Mathis & Léger also report a leucocytozoon in a Chinese dog). The parasites of endemic boil disease, (Delhi or Aleppo boils), dis- covered by Wright and named Helcosoma tropicum, later as Leishmania tropica, are similar to the Leishman bodies. _,. hiterature. Liihe, Handb. d. Tropenkrankh., 1906. III. 202. — Leishman, ibid., S. 521, — Donovan, J. of trop. Med., 1909. XII. Malaria of Man. This disease, which occurs in all parts of the world in marshy localities, and: in an especially severe form in the tropics, is caused by a blood parasite the malaria pasmodium, discovered by Laveran (1880), which differs entirely from the piroplasma of animals. According to the duration of their asexual development, on which also the appearance of the recurring attacks of fever depend, Tertiana, Quartana and Perniciosa parasites are distinguished, which correspond with each other in that besides their multiplication in the red blood corpuscles of man by schizogony, they also multiply sexually in mosquitoes (Anopheles-species). By the inoculation of young forms (sporozoites) of the parasites, with the saliva of mosquitoes into human blood, where they continue to propagate, a brief febrile attack sets in after each development of a generation of the parasite which is mani- fested by chills, then fever, and perspiration. As at each attack a number of red blood corpuscles are destroyed, an anemic condition de- velops gradually which in severe cases increases to a pronounced cachexia; in the tropics however febrile attacks may result in early death under manifestations of hemoglobinuria, (black water fever). The disease is combatted successfully with préparations of quinine. (Ziemann, Menses Handb. d trop.. Krankheiten, 1906. III. 269;— Ruge, Hb. d. p. M., Ergzsbd., 1907. 85.) 2. Trypanosome Diseases. (Trypanosomiases, Trypanoses.) Investigations during the last three decades have proved that various tropical diseases of domestic animals and also of man are caused by blood parasites of the flagellate class of protozoa, the so-called trypanosomes or trypanozoa. In the thorough investigation of these parasites in various localities as well as in different species of animals, and in various dis- eases, certain differences, though of slight significance, have been established in their morphology, and especially in their pathogenicity, which led to the classification of a number of not always distinctly characteristic forms of trypanosomes or 798 Trypanosome Diseases. varieties, and of several diseases. Considering the marked resemblance of the morphological characteristics of most of the parasites belonging to this group, there exists a possibility that the diseases discussed in the first part (Nagana, Surra) repre- sent a pathological unit, while the unimportant differences noted in the others depend chiefly on the variability in virulence of the several kinds of trypanosomes, likewise also on the geo- graphical and climatic conditions, whereby the differences in the mode of natural infection, as well as the course of the disease can be explained readily. In deference to the general concep- tion, the diseases considered at present as independent affec- tions will be treated separately, after previously explaining these points of view. Besides the pathogenic trypanosomes there exists a great number of others which occur as harmless blood parasites in domestic animals and in other species of animals. General Morphology. and Biology of the Causative Agents. The trypanosomes are unicellular, animal microorganisms, containing a nucleus, a blepharoplast, and a flagellum. They propagate by longitudinal division, possibly also sexually. The parasites known to be producers of disease possess slender, spindle-shaped bodies, the posterior ends of which are more or less blunt; they are enclosed by a periplastic membrane. The parasites are mostly 21-35 4 long, and 114-3 broad, in the middle portion they contain a spherical or oval nucleus and close to the posterior end a shining nucleolus (centrosoma, blepharoplast, flagella root, trophonucleus) (see Table IX). From the latter a fine flagellum runs out, which extends forward on the outside borders along the undulating membrane, which is present on one side of the body, and terminates in a free portion at the anterior point of the body. In the fine granulated protoplasm there are distributed one or more vacuoles, and also various sized granules in varying numbers. By means of lashing movements of the flagellum and spiral contraction, the trypanosomes are capable of lively motions in fluid as well as in the blood between the blood corpuscles, usually in the direction of the flagellated extremities. On the addition of certain substances, especially of immune serum, the trypanosomes unite in pretty rosette shapes (agglomeration), by approaching each other, usually with the posterior ends, in radiating arrangement and executing whip-stroke movements with the free flagel- lated extremities directed outwardly. Propagation occurs thus that first the centrosome, then the flagellum and nucleus split longitudinally in two parts, and finally the plasma hody breaks into two halves from front to back. Sometimes the division of the body does not follow that of the centrosome and the flagellum immediately, so that irregular General Morphology and Biology. 799. ameboid forms result, which contain two or more chromatin substances, and only later separate into more individuals. Besides this simple mode of multiplication, a sexual propagation, or a special development is considered possible in the transmitting in- sects as intermediary hosts (Ziemann, Prowazek, Koch, Schaudin, Stuhlmann, Kleine and others). This opinion is based principally on the investigations of the intes- tinal contents of stinging flies (Glossinae), infected with trypanosomes, in which besides typical, broad forms rich in plasma, very thin forms are found containing only a small quantity of plasma with elongated nucleus, and sometimes without flagella. According to Koch the former are considered as females, the latter as male trypanosomes, and they are supposed to copulate with each other. According to Kleine’s investiga- tions of sleeping sickness, the development is supposed to extend over. several weeks, so that infected flies may be capable of causing infection for that period. According to the experimental results of Battaglia, obtained by a study of the multiplication of the Trypanosome Lewisi and the Trypanosome Brucei, a mul- tiplication by sporogeny occurs also in the blood of the same animal, inasmuch as after an infection with small motile, intra-globular ameboid forms, : first similar extra-globular forms develop, later larger, roundish or pear-shaped unflagellated forms, and only from these finally result the fully developed forms, and these then multiply by longitudinal division. This conception is supported by the experience that it is possible to transmit the disease artificially with filtrates of infected blood, after passing it through Berkefeld (not Reichel or Chamberland) filters. Staining. The trypanosomes are even with slight magnification easily recognizable by their peculiar form, and by their lively snake- like movements. They stain uniformly with the ordinary aqueous anilin dyes, while the structure may be brought out by the use of Roman- owsky’s or a similar stain by which the nucleus, the Blepharoblast and the flagella appear pale red (chromatin stain) and the plasma pale blue. Recently Giemsa’s stain is used almost exclusively with the azure prepared by him in pure form. Staining fluid: to each ec. of distilled water, one drop of Giemsa’s: solution, always to be freshly, prepared. Staining of the smear prepara- tion which has been fixed in alcohol or alcohol-ether (44) for 15-20 minutes, then washing in running water. Cultivation. Novy & McNeal succeeded in cultivating the try- panosomes of rats and later also those of nagana on agar to which had been added about 50% of blood, at a temperature of 25°-34° C. In the cultures non-motile forms develop 1-2, up to 50-60+ long, and the first of them may pass through porous filters. Trypanosomiasis was produced artificially in rats with Berkefeld filtrates of cultures. Since then the cultivation of other disease-producing trypanosomes was successfully ‘carried out in a similar manner (Irikura cultivated them in blood bouillon of 14-2:10). Tenacity. The parasites can be kept alive outside of the animal body for several days, but only in defibrinated blood, to which pure serum is added. Cool temperature usually lengthens their lives, while against higher temperatures (43° and over) and chemical influences they are in general very sensitive. The differentiation of the various types depends, aside from marked deviations in the form of the trypanosomes, almost ex- 800 Trypanosome Diseases. clusively on their occurrence in certain species of animals and in well-defined localities, further on the variance in their pathogeni- city towards the different species of animals; and also on the fact that animals immunized against one type are still suscepti- ble to others. However these differences are not constant, as it is often possible to increase the virulence of one strain of trypanosomes for otherwise slightly susceptible or apparently immune species of animals by passage-inoculations. Morpho- logically the trypanosomes of surra, nagana, and dourine, as well as of sleeping sickness, correspond absolutely, and those of Mal de Caderas are supposed to be different from them only in that their blepharoblast is smaller, and that they are more difficult to stain. Distinctly different types are: the relatively large (50:3.5-4.0+) Trypanosome Theileri, the even much larger Trypanosome giganteum some non-flagellated trypanosomes, thus especially the Tr. dimorphon (see p. 837), further the Tr. Lewisi occurring in the blood of rats, which has been most thoroughly studied, and in which the nucleus is not in the center, but in the posterior third of the plasma body. Pathogenicity. Artificial transmission to susceptible ani- mals succeeds most readily by subcutaneous, intraperitoneal, or intravenous inoculations, with less certainty by applying blood containing trypanosomes to fresh wounds. After a cer- tain time the parasites appear in the blood in large numbers, . when in certain species of animals, especially in dogs, cats and rabbits, fever appears as a usual symptom, in addition to edematous swellings on different parts of the body, resulting sometimes in the loss of hair, emaciation, sometimes also in- flammation of the cornea and of the eyelids, whereupon the anemic animals emaciate rapidly and succumb. If virulent blood is inoculated into an animal of the same species from which it originated, a severe or mild disease results, which is identical with the original affection. ; Dourine may be produced artificially by applying material containing trypanosomes on the uninjured mucous membrane (Vrijburg obtained in one case positive results in a horse with surra material). The virulence of the trypanosomes varies in different species of animals, and may be increased for certain species and reduced for others by passage experiments. Generally native animals are less susceptible in infected localities than those brought to such places from non-infected countries. Natural infection in the domestic animals, exclusive of dourine in which it occurs by coitus, usually results from the stings of flies, namely, Glossinae, Tabanidae and Stomoxys species, they transmit the trypanosomes mainly in a purely mechanical manner by sucking blood from affected animals and inoculating it to healthy individuals. If, however, the trypano- Natural Infection, Pathogenesis. 801 somes may undergo sexual propagation in the insects as inter- mediate hosts, as appears probable from recent investigations (see p. 799), there would be a possibility that they may harbor the parasites in their bodies for a longer time, and in the mean- time transmit it to susceptible mammals. The infection results apparently only exceptionally through fresh wounds in the skin and mucous membranes, whereas an infection through the uninjured mucous membrane of the diges- tive tract, as it was accomplished experimentally by Yakimoff & Schiller, has not been observed. Pathogenesis. As trypanosomes are always present in the blood plasma and the tissue fluids, they apparently exert their pathogenic action only indirectly by the production of toxic products, which principally cause the destruction of the red blood corpuscles, and thereby anemia. They probably influence the metabolism of the host in other harmful ways. The fever, the marked emaciation (with good appetite!), as well as the affection of the nervous system (neuritis, later degeneration) can be explained only by a toxic action, but it has so far not been possible to demonstrate the supposed toxins of the trypanosomes objectively (Laveran, Mesnil, Mayer and others). The fact however that the parasites multiply outside of the animal body only on media containing a great amount of hemo- globin appears to indicate that they require hemoglobin, and the destruction of the erythrocytes may be explained by the fact that they abstract this substance from them. Following the infection a marked increase of trypanosomes in the blood occurs periodically in the animals, and this is usually accompanied by an elevation in temperature. Then again they disappear rapidly, only to return again in great numbers after a longer or shorter time, having probably matured meanwhile in certain organs (spleen, bone marrow?) from the young forms. Their disappearance is according to the investi- gations of Massaglia and Rodet & Vaillet, supposed to be due to trypanolytic substances, which appear in the blood of in- fected animals and the quantity of which increases until the crisis. To what extent the leucocytes participate in this has not yet been determined; as a matter of fact their number greatly increases during the disease simultaneously with a hyperplasia of the spleen, and a great number of leucocytes which contain in their bodies broken-down products of trypano- somes are to be found in the spleen tissue, as well as in the bone marrow. General Symptoms. They appear after a longer or shorter incubation period, and excluding the acute and peracute cases, which are manifested under severe febrile symptoms, consist in general in intermittent or recurrent fever, transitory or ‘constant edema of the lower parts of the body, and progressive Vol. 1—51. 802 Trypanosome Diseases. anemia ag well as emaciation, with usually a good. appetite.. Nervous functional disturbances, especially peripheric paraly- ses, are algo frequently observed. Death is usually preceded by a comatose. condition. Treatment. While in former years the trypanosome affec- tions have been treated mainly with quinine, corrosive subli- mate and iodine preparations, although without apparent re- sults, Lingard obtained in surra, and Bruce in nagana, note- worthy results with arsenious acid, inasmuch as with this treat- ment the number of the blood parasites was sometimes reduced very markedly. The improvement was however usually only temporary, as after a certain time the trypanosomes reappear in the blood, so that the final results, at best, showed only a prolongation of the course of the disease. More recent investigations, above all the great laboratory experiments of Ehrlich and his school, show that certain chemical substances have a specific destructive action on trypanosomes in the infected animal bodies, or at least exert an inhibitive action on their development, and in suitable ap- plication may even result in permanent recovery from the disease. Such substances, excluding some of the basic tripheny]- methan dyes (parafuchsin, methylviolet, pyronin), are certain azofar stains, such as the trypan red, the trypan blue, the trypan rosan, and the trypan violet, certain arsenical deriva- tives, especially atoxyl, arsazetin, the arsenophenyglyzin,. and the dioxydiamidoarsenobenzol (Ehrlich-Hata 606), also some antimony preparations, such as tartar emetic. Special study was given to atoxyl (sodium arsanilate) first recom- mended by Thomas and Breinl, and Mesnil & Nicolle. It was found that this remedy, different from the basic stains mentioned, which are effective even in test-tube experiments, does not even in concentrated solution affect the trypanosomes harmfully in vitro, while in the animal body it causes the disappearance of the parasite even in a dilution of 1:120000. Ehrlich believes that the action of the atoxyl in vivo is due to the fact that the substance is reduced to paraaminophenylarsenoxyd, which kills the trypanosomes also in the test tubes, even in dilutions of: 1:1000000. This is corroborated by the experimental results of Levaditi, Yamanouchi & Brimont, as these authors have found that the atoxyl is reduced in the animal body (to a hypothetical trypanotoxyl) ; al- though later they supposed that the reduction product in such a reduced condition, combines with proteid molecules, to form a toxic arsentox- albumin. Breinl & Nierenstein however believe that the atoxyl combines with the serum proteids, whereupon arsenic is set free through oxydation of the atoxyl in the serum, and this, in statu nascendi exerts a de- structive influence on the parasites. The correctness of this conception appears to be substantiated by the experimental results of Loeffler, who obtained the best and most lasting recoveries in nagana-guinea pigs and cats from the administration of atoxyl, together with arsenious acid in subtoxic doses (3-5 mg. arsenic per os., and 315 cg. atoxyl subcutan. Treatment. 803 \ eously). Similarly Holmes observed excellent curative results in horses affected with surra, after the use of arsenious acid. However in order to make the recovery complete all trypanosomes, even the latent forms in the internal organs must be destroyed (therapia sterilisans magna), therefore the remedy should be used in as heavy doses as possible, that is in sub-toxie doses (as formerly the arsenic has been used in too small doses, and the parasites which were not destroyed were capable of causing relapses). The good results obtained with the auripigment can also be explained by the fact that it usually contains free arsenious acid. In the experimental treatment it was further observed that the trypanosomes are capable of adapting themselves to the remedies under discussion, for instance trypanosomes which, after atoxyl treatment with incomplete recovery, remain alive in the animal and later again multiply, are no longer influenced by the same remedies, and likewise not by other derivatives of phenyl arsenious acids. This resistance is transmitted by subsequent passages through the same species of animals from generation to generation. This condition may become objection- able in practice, inasmuch as from animals which have been subjected to such specifie treatment and which have not completely recovered, flies may later transmit to other animals atoxyl- (arsenic-, trypanblue., fuchsin-, etc.) resisting trypanosome strains. Such animals then resist treatment with the same or with a related remedy. Most recently how- ever Ehrlich succeeded in producing new arsenical preparations, the arsenophenyglycin, and the above-mentioned arsenobenzol, which, with a slight toxicity for mammals are capable of attacking even arsenic- resisting strains of tryponosomes and which have also otherwise proven most satisfactory for trypanosome affections out of the great number of chemicals that have been tested. Ehrlich aimed to explain the mechanism of the specific therapeutic action through certain groupings (chemoceptors) in the protoplasm of the trypanosorres, which possess for certain chemical substances, for instance for the trivalent arsen as' it occurs in arsenical acids, a special affinity, and are capable of anchoring such to the plasma. ‘The resistance of already treated strains may result from the fact that the respective chemoceptor experiences a reduction of its affinity to the applied remedy, therefore its resistant strain is destroyed only by a greater quantity of the remedy, or by a more strongly avidious remedy, for instance the arsenophenylglycin. 3 Based on these experimental results, which have repeatedly been substantiated especially by Uhlenhuth, Htibener & Woithe for the treatment with atoxyl of experimental dourine, by Loeffler with arsenic in experimental nagana, by Levaditi and his co-workers for the action of atoxyl on various strains of trypanosomes, arsenical preparations are used in practice for the treatment of these diseases. They are employed either combined with each other, or alternately; further antimony preparations, especially tartar emetic, and with these treat- ments satisfactory results are generally obtained, or at least encouragement for further therapeutical experiments. In general, the rule should be observed to administer the remedy as soon as possible after the infection, in a single, or at most in two subtoxic doses, as only in this manner can relapses and the development of hypersensitiveness be prevented. (For details see the individual affections. ) 804 Trypanosome Diseases. Prevention. Excepting dourine, which can be controlled by comparatively simple measures in the supervision of breed- ing and may be entirely eradicated, the prophylaxis of the trypanosome diseases consists above all in the eradication of the flies which play a part as transmitters, and probably also as hosts for the virus. The procedure must of course be suited to their habits of life and their modes of development. In the glossinae and tabanidae, which confine themselves to certain forests and marshy localities, and probably also to certain wild species of animals, the eradication in practice succeeds at least in small territories, by cutting of the. bushes, and draining of the meadows. Besides regular cultivation of the soil, the de- struction of the game, or keeping it from the roads of traffic, or confining it to certain reservations would aid in the elimina- tion of the source of infection. The species of stomoxys which exist in close proximity to living houses and stables, may be reduced in numbers by cleanliness, as well as by the destruction of all vegetable refuse. As the flies do not accompany the cattle herds for great distances, and as they do not swarm during the night, threatened herds may be protected from infection by driving them at night to non-infected localities, avoiding rivers, thus keeping them from the virus carriers. In practice the control of trypanosomiasis is rendered more difficult by the fact that not only affected, but also apparently perfectly healthy, and especially the animals which have re- covered from the disease harbor trypanosomes in their blood for years. Such virus carriers constantly produce virulent material for flies in infected territories, and may, on the other hand, disseminate the virus into previously non-infected terri- tories. By the destruction of all such virus carriers the source of the infection for the flies could be destroyed, but such a pro- cedure could only come into consideration in small, freshly infected territories. For countries which are free of certain trypanosome affec- tions careful quarantine measures, or even the prohibition of the importation of susceptible species of animals from infected territories, comes into consideration. Immunization. Immunization experiments with serum of recov- ered animals and those repeatedly treated with virulent blood (Zie- mann), or with blood containing parasites and subjected to high or low temperatures, have not yet given manifest results (Uhlenhuth, Gross & Bickel). The same applies to the experiments which have been carried out by passage of the virus through various species of animals (Koch, Schilling, Martini). In the efforts to work out a method for active im- munization the fact must be considered that the immunized animals harbor the parasites for years, and these may later become virulent, and sometimes may be transmitted to healthy animals in such a condition. The fact that animals acquire, through recovery from certain trypanosomiasis, a lasting although not an absolute immunity against the same and not against other Immunization. 805 trypanosomes, indicates that strictly specific immune bodies develop in the affected animals. Such, however, have not yet. been demonstrated with certainty in an objective manner. In this regard the complement fixation method, in which hlood containing parasites or material from organs was used as antigen, gave uncertain and varying results (Weber, Manteufel & Woithe). Better results were obtained by Levaditi & Mutermilch, when they carried out experiments with trypanosomes separated from blood corpuscles. They could always demonstrate complement fixing bodies in the serum of guinea pigs treated with trypanosome extract or in the course of infection. These substances were specific for the genus trypanosoma, but not for the individual species and varieties, therefore they could not be differen- tiated by this method. Further, the complement fixing substances proved different from the trypanolysines, which form in great numbers at the height of the infec- tion (see p. 801), and exert their dissolving action also in test tube experiments. According to Laveran & Mesnil, human blood serum has a similar destructive action on the trypanosomes of nagana, surra and mal de caderas, as the arsenic acid. Serum of animals, even of those which have recovered from the disease, or which have been repeatedly infected, has no such action, and on the other hand the human serum is harmless for the trypanosomes of sleeping sickness. _ Literature. Nocard & Leclainche, Maladies microbiennes, Paris 1903. IT. 575. — Laveran & Mesnil, Trypanosomes et trypanosamiases, Paris 1904. —Lithe, Handb. d. Tropenkrkh., 1906. III. 92. — Sander, ibid., 690. — Nocht & Mayer, Hdb. d. p. M. Erganzgsb., 1906. 1. — Sauerbeck, Ergebn. d. allg. Path., 1906. X. 305. — Kaestner, ibid., 1907. XI./1. 455. — Ehrlich B. kl. W., 1907. Nr. 9-12, — Man- teufel & Woithe, Arb. d. G.-A., 1908. XXIX. 452. — Koch, Beck & Kleine, ibid., 1909. XXI. 1. — Levaditi & Yamanouchi, Soc. biol., 1908. LXV. 23. — Levaditi & Mutermilch, Z. f. Immf., 1909. II. 702. — Kleine, D. m. W., 1909. 924 u. 1257, -— Doflein, Protozoenkunde, II. Aufl. 1909. 350. (Mostly with literature.) (a) Nagana. (Tsetse disease.) History. The disease was described as a destructive cattle disease by Livingstone (1857) during his voyage in Zambesia, and was connected by him with the sting of the native tsetse fly. Its cause was discovered by Bruce in 1894, in the territory of the Zulu Kaffirs, (nagana=without strength, debilitated), and the first detailed deserip- tions of the clinical symptoms were also made by him. Shortly after- ward the disease, as well as its cause was investigated thoroughly by Kanthack, Durham & Blandford and by Plimmer & Bradford, while Theiler deserves special credit for the epidemiology. The problem of the propagation of the nagana trypanosomes was studied by Koch and recently by Kleine and Battaglia, while McNeal, and Laveran & Mesnil were successful in their artificial cultivation. Occurrence. The disease used to be spread widely through the entire Central and South Africa, where it annihilated at times the cattle of entire districts. Recently it disappeared from the south, so that at present it occurs only in some out- of-the-way localities of Zulu land. The infected territory was limited partly by the driving northwards of the game, prin- cipally however by the invasion of rinderpest in 1896 and 1897, as at that time besides cattle, numerous game animals and buffaloes. fell victims, and at the same time the tsetse fly also disappeared from those localities (Theiler). Trypanosome affections occur also in Northern Africa, but the classification of these, with the exception of dourine, has not been cleared 806 ; Nagana. up with certainty. Some enzootics have a great similarity to nagana, while others are more closely related to surra (see also p. 837 and p. 812). Etiology. The Trypanosoma brucei, recognized as the cause of nagana, is on an average 25-33 “ long, 1.5-2.5 “ broad, and possesses a central oval nucleus, a blunt, Indian-club-shaped posterior end, slightly developed undulating membrane, and long flagellum (Fig. 141). Under the microscope it exerts a lively snake-like movement, but without pronounced locomotion. Pathogenicity. Inoculation of blood containing trypano- somes, under the skin or into the blood circulation of horses, causes after from 2 to 6 days a marked elevation of temperature and in the first case also a painful swelling at the point. of injection. About the end of the first week the fever diminishes but reappears later at certain inter- vals, and during the duration of the febrile attack trypanosomes may be ‘demonstrated in great numbers in the blood. In the meantime edematous swellings appear on the lower abdo- men, and in the vicinity of the ex- Gitte. a eae ternal genital organs; the animals cei. “Guineas pig blood. Stain. emaciate in spite of continuous, and ed after Romanowsky-Ziemaun. often ravenous appetite; marked mus- cular atrophy and also pronounced anemia develop. Sometimes turbidity and ulceration of the cornea results with subsequent iritis. Finally a condition re- sembling lumbar paralysis sets in, whereupon the animals die from 15 days to 4 months after the appearance of the first symptoms. In donkeys and mules the clinical picture is similar, although sometimes with a still more protracted course after artificial infection; the zebra is. also susceptible to artificial inoculations (Martini). In cattle, also in sheep and goats the inoculation usually ‘results in a chronic disease. Dogs and cats are very susceptible to infection, and likewise become affected under symptoms of recurrent fever, edamatous swelling of head, . chest, gradual emaciation and loss of strength. Guinea pigs, rabbits, rats and mice, are very easily infected artificially, while hogs show consider- able resistance to artificial inoculation. Monkeys are very susceptible and usually die a few weeks after the infection. Of fowls only geese (Schil- ling) and chickens (Goebel) could be infected artificially, while other birds showed no symptoms of disease. Horses and other solipeds, then cattle, more rarely sheep and other ruminants, become most frequently affected as a result of natural infections. Pathogenicity. 807 The infectién is transmitted by the so-called tsetse fly, which somewhat resembles the house fly although it is some- what larger, principally by the glossina morsitans (Fig. 142), in such a way that it sucks blood from the infected animal, and then carries the parasites into the body by its bite. Freshly molted flies are harmless, if however they have alighted upon an affected animal only a single time they may transmit the disease and trypanosomes may be demonstrated in their pro- boseis and stomach shortly after sucking the blood. By the transportation of affected flies the disease was successfully produced in previously non-infected localities, while on the other hand animals driven during the day in infected localities became affected even when they had not partaken of food nor water while en route. Furthermore, the extension of the in- fected territory corresponds accurately with the geographical distribution of the tsetse fly (between the 10th deg. north, and 30 deg. south latitude), where its appearance in great numbers is usually followed by: severe outbreaks. Fig. 142. Glossina morsitans. A with closed, B with spread wings, OC anterior part in profile. A and B enlarged 2.5times. (After Bruce.) Where affected animals are present or those which have passed through the disease within a short time, the fly is afforded ample opportunity for taking up trypanosomes; flies may also obtain the infectious material from wild animals (buffaloes, antelopes, hyenas, zebras and quaggas), in the blood of which it may occur as a harmless parasite. The tsetse fol- lows these animals everywhere; with the appearance of the summer season the infectious material is then taken from them by the young flies, and transmitted to domestic animals, while with the eradication of the game the tsetse fly also disappears, so that infected territories may thus become free. According to Koch’s experience in western and northern | Africa, where the glossina morsitans is unknown, the disease is transmitted by the closely related Gl. fusca. According to Brumpt the Gl. pallidipes, 808 Nagana. the Gl. longipennis, the Gl. palpalis and the Gl. Decorsei are also capable of transmission. According to former views the tsetse fly transmitted the infection only mechanically, and as trypanosomes could be demonstrated in their intestines 48 hours after sucking the blood, it was supposed that after that time healthy animals could become infected only when. the flies had in the meantime again alighted on infected animals. According to the newer results of investigations on the generation changes of the parasites (see p. 799), the possibility must be considered that the flies may transmit the parasites for weeks. In accordance with the part played by the insects in the transmission of the disease this usually rages in low-lying localities with damp soil, especially during warm periods and rainy seasons, the animals being exposed to the infection es- pecially during the day, as long as they are in the vicinity of marshes, lakes, water canals and rivers. The transmission of the disease from animal to animal is also possible by contamina- tion of fresh wounds on the skin or mucous membrane, with blood containing parasites, while the possibility of natural in- fection through the uninjured mucous membrane of the digestive tract has not yet been proven. Anatomical Changes. The autopsy usually reveals pro- nounced anemia and emaciation. The subcutaneous connective tissue shows in many places gelatinous infiltration, and in the serous cavities transudate is found in variable quantities. Small hemorrhages may be present in the serous membranes, in the mucous membrane of the stomach and intestines, as well as in the kidneys. If the animal dies during a febrile attack the spleen shows acute swelling, whereas otherwise a chronic splenic tumor is usually present; sometimes however it may have an entirely normal appearance. The lymph glands are moderately swollen. In some cases hemorrhages and catarrhal pheumonie¢ areas are present in the lungs. No trypanosomes can be demonstrated in the blood or in the internal organs 24 hours after death. Symptoms. The manifestations of the disease are similar in their nature in the different species of animals. In horses the temperature rises rapidly after an incubation of 2 to 10 days, according to the severity of the imfection, to 40° to 41° C., and at the same time other febrile symptoms, such as languor, accelerated and weak pulse or diminished appetite make their appearance. The mucous membranes are reddened, there is profuse lachrymation, and at the same time edematous swellings form on the extremities and lower abdo- men, especially around the genital organs, also in the sub- maxillary space, and on the eyelids. The febrile condition remains unchanged for 2 to 3 days, sometimes for a week, then the temperature drops rapidly Symptoms. 809 to normal or below, whereupon the animals become livelier and the other symptoms diminish or may disappear entirely. If the fever has lasted for a longer time the patients have in the meantime become emaciated in spite of the fact that the appetite has not been impaired much. After a certain time the afebrile period is again followed by fever, and from then on several fever days alternate with fever-free intervals, only that the rises of temperature in the later course are lower than in the first attack. Under such variations of temperature the animals become emaciated, although their appetite continues very good, and a pronounced anemia usually develops in which the hemoglobin content may drop to 25% of the normal, while the number of red blood corpuscles may diminish to 214 millions per cubic mm. with a simultaneous moderate increase of leucocytes (Sehilling; Nierenstein found in experimental nagana an in- ereased acidity of the blood, probably due to the production of amido acid). Accordingly the mucous membranes appear pale and in the later stages frequently icteric in color. The edematous swellings which develop on different parts of the bodies vary in the first period in their intensity and may sometimes disappear entirely; in the later course, how- ever, they remain constant. Urticaria sometimes appears especially at the beginning of the affection, but soon disappears again. With the progressive emaciation and anemia the animals become steadily weaker, their motions are incoordinated and staggering, the animals knuckle frequently, and gradually a condition resembling lumbar paralysis develops, so that the patients, in which difficulty in respiration has appeared in the meantime, remain continually lying down until they die, greatly emaciated and completely exhausted. After artificial infection of dogs, Spielmeyer observed recent degeneration of nerves in the posterior roots of the spinal cord, in the roots of the sensory tri- geminus, and of the optic nerve. ‘In some of the chronic cases an opalescence or an ulcerative breaking down of the cornea results later or a hemorrhage follows into the anterior chamber of the eye, which becomes associated with an iritis, and finally leads to blindness. The urine periodically contains albumen in varying quan- tities. The blood contains trypanosomes in great numbers dur- ing the first febrile attack, while later they are found more sparingly, usually only during the febrile attack. In the very acute cases they usually occur constantly, and their number may amount to 70,000 per cubic centimeter of blood. They may also frequently be demonstrated in the serous fluid of the swellings. The course usually extends to 114 or 2 months, but may sometimes last for 4 or 5 months. In some cases, which for 810 Nagana. a time show a chronic course, a sudden aggravation of the con- dition may develop during a febrile attack, whereupon the ani- mals die in a few hours (cerebral embolus). Some cases may be very acute and in these almost continuous fever is present, the animals emaciate very rapidly, and death ensues after 2 or 3 weeks. Recovery has so far been observed only very exceptionally (most likely in donkeys). In cattle the symptoms, which consist of emaciation and anemia, periodical fever and edematous swellings (especially on the dewlap), sometimes do not become manifest for several weeks, or even months after the infection, and even later they become aggravated only very gradually. The eyes are rarely affected. The disturbance in their movements is only slightly pronounced, while the emaciation may reach a very high degree. Trypanosomes are present in the blood only. in very small numbers, and frequently can only be demonstrated by inocula- tion of the blood into susceptible animals. Acute cases are observed only exceptionally. Recovery is more frequent than in horses. The disease in sheep and goats manifests similar symptoms to those exhibited by cattle. Parasites are also found only in small numbers. In the advanced stages of the disease in dogs, emaciation, labored labial respiration, acute swelling of the lymph glands, shifting edema, especially on the extremities, edematous swell- ings of the feet, incoordination of movements, keratitis and iritis, as well as general falling of the hair may be observed. Diagnosis. The sudden and rapidly changing edema as- sociated with febrile manifestations, in the later stages the emaciation, anemia and muscular weakness in association with recurrent fever which progress in spite of good appetite, offer in infected localities a sufficient basis for a probable diagnosis of the disease. Absolute certainty however is only obtained by the demonstration of the trypanosomes in the blood and in the fresh edematous swellings. For the examination of trypanosomes a drop of blood should be taken from a superficial vein, mixed with several ce. of physiological salt solution, and the mixture examined in fresh, unstained or stained specimens (see p. 799). The inoculation of blood into small test animals (also dogs) is valuable in the establishment of a positive diagnosis, especially since it accomplishes its pur- pose not infrequently, even in cases of negative microscopical findings. Montgomery & Kinghorn recommend puncturing of the swollen lymph glands, as, according to their experience, trypanosomes may frequently be demonstrated in the glandular juice thus obtained, even when the examination of the blood gave negative results. Treatment. At present the reports on the results of Ehrlich’s chemo-therapy (see p. 802), which has been employed in nagana of domestic animals in Africa are quite insufficient (in sleeping sickness of man which is also prevalent in Africa, Treatment, Prevention. 811 atoxyl has been used successfully for several years). Ziemann mentions that atoxyl acts favorably in horses in chronic cases, while Schilling recently warmly recommends arsenophenylglycin (dose for horses: 0.05 gm. per kg. body weight) (see also the treatment of surra on p. 814). Bruce found that affected horses and donkeys treated with arsenical prepara- tions lived longer than those which were not treated, and Laveran & Mesnil also obtained favorable action from arsenious acid in experiments on animals artificially infected with nagana trypanosomes (rats, mice and dogs). According to Bruce & Theiler, also Schilling, the arsenical treatment is useless in nagana of cattle. Thiroux & Teppaz recently reported lasting recoveries with auripigment and atoxyl, in the closely related trypanosomiasis of horses in Senegambia (Tryp. dimorphon, Cazalboui and Pecaudi). The treatment consisted either in the admin- istration per os of 7-12 doses auripigment of 20-30 gm. each at 3 days’ intervals, or alternating with atoxyl at 2 days’ intervals (12-25 gm. auripigment per os; 5 gm. of a 1% atoxyl solution subcutaneously). Aceording to Diesing the serum of hyper-immunized donkeys is supposed to improve the general condition of artificially infected horses and cattle, inasmuch as the number of blood parasites considerably diminishes after each injection. Prevention. In addition to general prophylactic measures (see p. 804), attempts are made in infected localities to protect the animals from the infection by keeping the flies away from the animals by smoke and also by inunctions with disagreeably smelling salves or oils (creolin, petroleum, also stomach and intestinal contents of ruminants, etc.). Limiting pasturing to the night-time also reduces the chance of infection. (In Uganda it he found that citronella grass keeps the dangerous flies away. Literature. Bruce, Further rep. on the Tsetse-fly disease or nagana, London 1897. — Theiler, Schw. A., 1901. XLIII. 97. — Schilling, Chl. f. Bakt., 1902, XXXI. 452. — Laveran & Mesnil, A. P., 1902, XVI. 1 u. 785 (Lit.). — Koch, D. m. W., 1905. 1865. — Sauerbeck, Z. f. Hyg., 1905. LI. 31. — Schilling, A. f. Schiffs- u. Trophyg., 1909. Nr. 1. — Battaglia, Cb]. f. Bakt., 1910. LITI. 113 (Lit.). — See also the general Lit. on page 805. (b) Surra. History. Griffith Evans found in 1880 in the territory of Punjab, in the blood of horses, mules and camels affected with the disease known there under the name of surra (=spoiled), a flagellated parasite, the etiological importance of which he immediately succeeded in establishing by successful inoculation experiments. Several years later the parasite was recognized as a trypanosome. English physicians and veterinarians, especially Lingard, have studied the disease in detail. Rogers was the first to discover the agency of the insects as transmitters of the virus. Occurrence. The disease occurs in eastern and western India, also in the adjoining Chinese territories. It has also been established on the coast of Persia, on the Mauritian, Malayan and Philippine Islands, and,in Java and Sumatra (it appears that it has only recently been introduced to these islands). It exists everywhere in marshy localities, especially during the warm season, and causes great losses among solipeds_ 812 Surra. and camels, while cattle and dogs are affected less severely. According to some authors (Laveran, Pease and others), Mboire and the El Debab of the camels in North Africa (see p. 838) is supposed to be identical with surra, having been introduced with camels from India. Surra appears to occur also in north- eastern Africa. In 1906 the disease was brought to New York with an importation of cattle from India, but was suppressed by the slaughter of the infected, and prolonged quarantine of the other animals. Camels have introduced the disease from India to Australia. Etiology. The Trypanosoma Evansi is morphologically cumost identical with the producer of nagana. As an only, although not constant difference is given a somewhat more slender form, somewhat longer flagella, a more pointed posterior part of the body, and a smaller proportion of chromatin granules, and finally more active motility. The possibility of differentiating surra from nagana consists at the present time principally in the fact that goats and cattle immunized against the usually more virulent nagana virus, are still susceptible to surra (Laveran & Mesnil, Nocard & Vallée), which although a differ. ential sign, is declared by Koch to be not conclusive. As Trypanosoma vivax, Ziemann described in Kamerun a trypanc- some which is characterized by very lively motility and resembles the virus of surra in other particulars. Relative to the pathogenicity between the trypanosomes of surra and those of nagana, the only difference is that in artificial infection experiments the nagana trypanosomes are usually slightly more virulent. The natural infection is transmitted according to Rogers and Musgrave & Clegg by horse flies, namely, the Tabanus tropicus, the T. lineola and the Stomoxys calcitrans, according to Leese also by the Hamatopa fly. Carnivora may infect them- selves also by the ingestion of blood from affected, or of meat from dead animals, also through losses of substance in the skin and mucous membranes (Lingard; Vrijburg succeeded in infecting a mare by smearing the urethral secretion of an in- fected stallion upon the mucous membrane of the vagina). — Cattle and zebus are generally considered in the first place as virus carriers (virus reservoirs), although they are only slightly susceptible to the disease and usually become affected but mildly; nevertheless they may harbor trypanosomes in their blood for years. In the second place camels, when recovering from the disease, may likewise carry the parasites in their blood for a long time. Wild animals (foxes, jackals, hyenas) may also supply the virus to stinging flies. ; For all stinging flies which have hitherto been considered as transmitters of the natural infection of surra, it is generally accepted that they transmit the trypanosomes entirely in a mechanical way; at least the experiments carried out failed to show that the surra trypanosomes pass through any stages of development Etiology, Anatomical Changes, Symptoms. 813 (Leese) in the bodies of the flies, which latter are infectious only the first day after sucking the blood. The question as to the mode and nature of natural infection cannot yet be considered as solved, and only recently Holmes, among others, expressed himself negatively on the exclusive transmission by horse flies, pointing out that the disease rages sometimes in the months from October to December inclusively, whereas the flies usually fly only in the months of June to August. : Anatomical Changes. Besides marked emaciation and changes indicating anemia and cachexia, a yellow, gelatinous infiltration of the subecutis is present in different regions of the body, also small hemorrhages in the serous and mucous membranes, serous exudates in the pericardium and in the ab- dominal cavity, more or less pronounced acute swelling of the spleen (especially in acute cases), and swelling of the lymph glands; in some cases superficial ulcerations also appear on the tongue and on the gastric mucous membrane. Symptoms. These resemble in general those of nagana. In solipeds, which are the most susceptible animals to natural infection, the disease commences after an incubation of 4 to 13 days (Lingard) with fever (rise of temperature up to 40.5-41°), great languor and weakness, whereupon petechiae soon develop on the mucous membranes, especially on the conjunctiva. Urticaria-like eruptions appear on the skin, and edematous swellings on the extremities, the genital organs, in the sub- maxillary region, and on the lower abdomen. A fatal termination may result even in the first days of the disease, usually however a marked improvement sets in after several days, but the febrile attack returns after a short time. The febrile stages usually last for four days, and alter- nate with fever-free periods lasting for several days, whereby the animals become more and more weakened, the paleness, and later also the icteric discoloration of the mucous membranes becomes more pronounced, the superficial lymph glands swell, the respiration becomes accelerated and labored, the pulse fre- quent and small. In spite of good appetite the animals become greatly emaciated, their gait is staggering, finally they lose the use of their hind parts and die with symptoms of severe dyspnea. Of other symptoms there may be observed hemorrhages in the anterior chamber of the eye, diffuse keratitis, petechiae in the mucous membrane of the vagina, albuminuria during the febrile attacks, continuous erection of the penis (formation of thrombi in the corpus cavernosum?), ete. Trypanosomes are found in the blood especially at the be- ginning of the febrile attacks, otherwise their number finctuates in the course of the disease within wide limits. The course extends usually from 1 to 2 months, more rarely from 1 to 2 weeks, or on the contrary for 3 to 4 months, the febrile attacks becoming gradually weaker in the later stages, 814. Surra. The disease appears almost without exception to terminate in death. In cattle the disease occurs much less frequently and is manifested by less pronounced intermittent febrile symptoms, becoming apparent only with the gradual development of anemia and emaciation, which sometimes reach a very high degree. In most cases ultimate recovery takes place. There occur however outbreaks in which the disease ap- pears in numerous cattle with severe manifestations, such as high fever, reddening of the mucous membranes, diarrhea and hemorrhages, and runs an unfavorable course, although even in such instances recovery may follow. Buffaloes rarely become affected, and then usually only in very chronic form, although their blood frequently contains the parasites. In camels the disease usually has a fatal termination, and-as in solipeds it may run an acute and severe course, or it may occur in a chronic form. Thus Pease & Gaiger observed two camels affected for four years, during which time they noted more than 100 febrile attacks. Of dogs, animals used in hunting become affected most frequently. The symptoms consist in a periodical febrile temperature, reddening of the conjunctivae, swelling of the head, the throat region and extremities, also incoordination of movement. In some cases there is a bloody serous infiltration in the joints, keratitis, and falling outof hair. Among im- ported hunting dogs in Indo-China the disease is severe, while native animals sometimes recover (Blin). Treatment. Lingard recommended arsenious acid in daily doses of 0.8 gm. for the treatment of horses affected with surra, Holmes recently reports continuously good, permanent results in ten ponies after the use of considerably larger, namely, subtoxie doses, at the height of the febrile attack. For ponies of 150 kg. weight, 1 gm. is recommended, while for horses of 450-500 kg. weight, 3 gm. should be given in the form of bolus, or electuary immediately after feeding, 5 to 10 doses being . administered with intervals of one day. It is not reeommended in solution either per os, subcutaneously, or intravenously. Somewhat less satisfactory were the results from Loffler’s treatment with arsenious acid and atoxyl, inasmuch as out of 16 solipeds thus treated, four failed to recover (alternately 4% atoxyl solution subcutaneously and arsenic in bolus form with one-day intervals; the dose of the atoxyl solution is 30-50 ec. for ponies, 100-150 ce. for horses and mules; of the arsenic 0.5-1 — for ponies, 1.5-3 gm. for horses and mules ; 5 doses in all Thiroux & Teppaz found auripigment effective in 1 experimental surra; they used it either alone, in doses of 15-25 gm. every 3-4 days, or alternately with tartar emetic (1.0-1.2 gm. intravenously), continued for weeks. Gaiger, Hallot and Holmes obtained only a temporary disappearance of try- panosomes from the blood with atoxyl, and likewise little satisfaction was obtained from the treatment with corrosive sublimate, soamin, atoxyl and tartar emetic (Holmes), with atoxyl and corrosive sublimate (Fraser & Simmonds), also with methylene blue (Gaiger). Treatment, Prevention. 815 Prevention. In this general principles apply (see p. 804 also the precautions advised for ae cont of ee ts 811). In fresh outbreaks it is advisable to select the infected animals with the aid of taking their temperature, blood examina- tions, and inoculation of mice and rats, and subsequently their isolation or destruction. In this way it was possible in Java, among other places, to eradicate the disease which had been introduced there not very long before. Literature. Evans, Vet. J., 1881. 1.; 1882. 97. — Lingard, Rep. on Horse- Surra, Bombay, .1893. — Rogers, Proc. -of the Roy. Soe. 1901. LVIII. 163. — Vrijburg, Bull., 1907. 293. — Ziemann, Cbl. f. Bakt., 1905. XXXVIII. 307. — Schein, Trop. Vet., 1908. III. 191. — Leese, ibid., 1909. IV. 107. — Holmes, ibid., 1910. V. 1. — Thiroux & Teppaz, A. P., 1910, XXIV. 220 u. 234. — (See, also, general Lit. on page 805.) (c) Dourine. (Eaanthema- coitale paralyticum, Polyneuritis infectiosa; Beschdlseuche [German]; Maladie du coit.[French]; Marbo cotitale maligno [Italian].) Dourine is the name of a usually chronic, contagious in- fectious disease of breeding horses, which commences shortly after an infective coitus and is at first characterized by a local infammatory affection of the external genital organs, with which subsequently symptoms of paralysis become associated as a result of an affection of the peripheral nerves and the inter- ones ganglia. It is caused by the Trypanosoma equiper- um, History. The disease was first described by Ammon, based on his experience (1796-1799) in the Prussian stud at Trakehnen. At the be- ginning of the last century it had already been recognized that it is most effectively spread during coitus, and the disease has frequently been confounded with coital exanthema of the genital organs. At the same time, however, it was also assumed that the affection is identical with syphilis in man, with which it doubtlessly has much similarity. This view was also prevalent long since in Algeria, where the Arabs, in their belief that syphilis can be cured by copulation with asses, followed such unnatural intercourse whereby the disease was supposed to have been transmitted from the affected female asses to the stallions (Daumas; hence also the old designation of the disease: Lues venerea equi, which has been introduced by Veith into the literature of this subject.) Laquer- riére aimed to prove this view in France, in 1883, by theoretical con- sidérations; its incorrectness, however, was esablished by Knauert & Haxthausen (1837), and the negative results of experiments for the transmission of syphilis to domestic animal also proved these concep- tions conclusively as erroneous. The difference of dourine from coital exanthema of the genitals was established by Hertwig in 1842, and still more conclusively in 1847, and he, also Mares and later Prince & Lafosse, proved further that the disease results exclusively through specific infection. . In the second half of the last century it was observed especially by French veterinarians in Algeria (Signol, Viardot), and by Rodloft in 816 Dourine. Russia. In Hungary the Department of Agriculture appointed in 1877 a special commission for the study of the disease, at which occasion Thanhoffer (1882) examined histologically the organs of more than 30 affected horses, while Azary, besides making artificial experiments of transmission, thoroughly studied the clinical manifestations. Rouget (1894) found in Constantine in the blood of a stallion af- fected with dourine, a trypanosome in which he immediately suspected the cause of the disease. This finding and its etiological importance was later confirmed in Algeria by Schneider & Buffard, in Netherland- ish-India by- Does, in India by Pease, in Hungary by Marek, and in Germany by Kleinpaul & Neumann, and Lorenz. Artificial experiments of infection were recently carried out by Schneider & Buffard, Marek and Zwick & Fischer, while careful clin- ical investigations were undertaken by Marek and Fréhner. Occurrence. Dourine was fairly prevalent in Europe previous to the middle of the last century, and caused heavy losses by its frequent enzootic extension, especially.in the horse- breeding establishments. The veterinary police measures sub- sequently adopted resulted in a rapid diminution of the dis- ease, so that at present it prevails only in some southern and eastern states, whereas in other parts of the world it occurs more frequently. In Germany the disease was formerly widely disseminated, especially in the northern territories (Hanover, Silesia, Posen), but has been eradicated since the inauguration of the infectious disease law. After a decade of freedom from the disease it was, through a mare imported from Russia, introduced again in 1906 into the districts of eastern Prussia, Angerburg and Lotzen, from which it spread into the districts of Johannisburg and Lyck. By the end of 1908, 82 horses had been affected on 62 premises, in 40 townships. In Hungary the disease was first observed in 1819 at Mezohegyes, and later by Pillwax (1833) in the stud of Babolna. As a result of the measures adopted in 1877 the disease has been observed only sporadically since the year of 1890, and after the eradication of two local outbreaks in the counties of Abauj-Torna and Szaboles in 1896, the entire country has remained free since 1901. In 1905, how- ever, the disease was imported from Croatia into the county of Zala, where it spread to 16 townships. In this, and in the following year, a total of 129 horses were affected, but in May of 1907 the entire country was free. In Croatia dourine was widely prevalent at the end of 1901 in nine town- ships of three districts (26 horses had to be destroyed during the year). In Austria it was first observed in 1813 at the veterinary school of Vienna, the last time in 1878 in Bohemia. In France it has recently always been confined to small territories, occurring as a result of importation from Algeria and Spain, and par- ticularly in the Department of Basses-Pyrénées cases occur almost annually. Spain appears to be infected considerably, likewise Russia, where the disease was diagnosed by Tschernogoroff in 1897-1902 among 37 stallions in the stud of Oldenburg. In Roumania, where it was found by Motas in 1898, it is also widely distributed (Pav- losevici). Dourine (= dirt, unclean copulation) is widely disseminated in North Africa, and especially in Algeria, where it causes an annual loss of at least 150,000 francs, it likewise occurs in Asia Minor, Syria and Persia. In America the disease was recently encountered repeatedly in the States of Illinois and Nebraska, and also in Chili; the principal focus of infection, however, exists on the Indian reservation of South Dakota, where in 1903, on the occasion of the examination of the horses, 511 were found to be affected,-277 suspected, and 1,889 stallions had to be castrated. The energetic measures appear to have been crowned with good results, as since 1906 no other cases have been noted. Etiology. Dourine is caused by the Trypanosoma equider- dum, which strikingly resembles the trypanosome of nagana. Etiology, Pathogenicity. 817 According to Laveran & Mesnil the only distinguishing signs are the sometimes pointed, at other times blunt, or sometimes split posterior extremity, further in the parasites originating directly from the horse, the absence of granulations is mentioned. Pathogenicity. Material containing trypanosomes taken directly from horses is always virulent for horses, while it ap- pears to possess for other animals a varying virulence, while in Algeria, rabbits and dogs are usually infected very easily, and a virus constantly effective for rats and mice was obtained by further inoculations, similar material from horses in Hun- gary proved pathogenic only for solipeds. During the last invasion in Prussia, similar experiences were recorded, although in. some instances mice were successfully infected. Zwick & Fischer then cultivated a strain by further passage through mice with which they succeeded in infecting not only small test aorta but also dogs, cats and sheep, and likewise goats and cattle. Mares covered by stallions, the urethral secretions of which contains trypanosomes, develop after about 2 to 4 weeks, some- times even later, an acute inflammation of the vagina and an edematous infiltration of the surrounding tissue, while later ‘‘dollar-spots’’ and still later symptoms of paralysis appear which continually become more intensive until the animal dies. During the existence of the inflammation of the vagina, try- panosomes may be demonstrated in the vaginal discharge, in the edematous swellings and in the dollar-spots, much less fre- quently also in the blood. An affected mare may also infect the stallion, in which case the effects are first manifested in an edematous swelling of the sheath and an accumulation of mucous secretion in the urethra which contains trypanosomes. The disease may also be produced artificially by smearing such secretion or blood containing. trypanosomes on the mucous membrane of the vagina or urethra, as well as by dropping it into the conjunctival sack. The injection of an emulsion of the spinal cord substance from an affected horse, into the anterior chamber of the eye of a healthy animal, is also effective (Nocard; Hutyra observed in a pony in such an instance the appearance of dollar spots as early as in one week, and subsequently a rapid development of paralysis.) After the inoculation of virulent blood under the skin of a horse an edematous swelling appears at the point of injection in 7 to 12 days; after 3 to 6 weeks transitory swellings of the skin appear on different parts of the body, especially in the vicinity of the genitals; after six weeks, sometimes not until after five months, a paralysis of the hind parts develops with knuckling of the hind legs, until the animal, which has become greatly emaciated in spite of constantly good appetite, suc- cumbs with symptoms of a lumbar paralysis. During the course of the disease intermittent fever is observed. In some cases Vol. 1—52. 818 Dourine. periods of improvement are observed in the course of the dis- ease or complete recovery may take place. In rabbits a subcutaneous or intravenous injection results sometimes in acute, septicemic, at other times in a chronic affection. In the latter an inflammatory swelling of the genital organs, falling of the hair, necrosis of the skin, crustaceous eczema on the forehead, purulent conjunctivitis, or panoph- thalmia is observed, while copulation of an affected with a healthy animal produces in the latter a gangrenous inflamma- tion of the genitals. Infected guinea pigs remain apparently healthy in spite of the periodical appearance of the parasites in their blood, and suddenly succumb months later. In dogs a warm and painful swelling appears at the point of inoculation, also extensive edematous infiltration of the abdomen, in the parts surrounding the genitals and in the inguinal region; also acute balanitis; in bitches inflammation of the vaginal mucous membrane with a profuse discharge is observed. The back is sensitive, round flat swellings of the size of the palm of the hand which again disappear within 2 to 3 days appear on the skin, in some cases an inflammation of the joints, purulent conjunctivitis, and ulcerative keratitis may be present. In the later stages rapid emaciation, in spite of good appetite, stiffness of the hind parts, general hyperes- thesia, and in the last stages complete inappetence without fever, marked emaciation, as well as very laborious respiration are noted. In dogs that are paired with affected animals an acute inflammation of the external genital organs develops, in which the discharge contains trypanosomes, and similar results are obtained from an injection of blood containing trypanosomes into the vagina of the bitch. In sheep plaques develop in different parts of the body, which leave in their places large bare spots; besides this an inflammation of the genitals develops while the general condi- tion remains undisturbed for months. In cattle a positive result of the infection can be only established by the demonstration of trypanosomes in the blood. Fowl] can be infected only ex- ceptionally (positive results are reported by Yakimoff & Kohl). The natural infection is usually transmitted by coitus. Dourine affects almost exclusively stallions and breeding mares, and the disease has repeatedly been reproduced intentionally by allowing affected mares to be covered by healthy stallions, and healthy mares by affected stallions (Prince & Lafosse, Trasbot, Azary, Marek). In studs it is, as a rule, mares covered by certain affected stallions that become affected, and only much later are other stallions infected ag a result of an infection through affected mares, and these may in their turn infect many mares. During coitus the healthy genital organs are infected by the secretion of the urethra or of the vaginal mucous mem- Natural Infection. 819 brane. Trypanosomes at times in varying numbers are present in these for months even before the appearance of the symp- toms, and also in the later course of the disease, even when the animals otherwise show no symptoms or at most only a very moderate swelling of scrotum or vulva. During the periodical aggravations of the local manifestations, an increase of their number may usually be demonstrated. In the rare cases in which the disease appears in horses not used for breeding, sometimes even in geldings, the infection is probably conveyed by sponges or by the hands of the at- tendants. The possibility of transmission by stinging flies cannot be discarded entirely. Lingard has already indicated such a possibility, and Sieber & Gonder have observed the infection in a horse which stood in a stable alongside of an artificially infected animal. Schubert & Kuhn also succeeded in an intentional transmission with the aid of the stomoxys ealcitrans. Further than this Rabinowitsch has infected laboratory animals with dourine trypanosomes through lice and fleas, while Uhlen- huth & Woithe, Manteufel, also Zwick & Fischer, have proved in rats the possibility of infection through the intact skin. As however try- panosomes occur at least in northern countries, only rarely in the blood ‘of horses, and even then but few in numbers, stinging flies have only slight opportunity for taking up the parasites (most likely from the fresh plaques). Therefore such a mode of transmission is apparently of very minor importance as is also confirmed by experience in practice (according to Sieber & Sender the trypanosomes remain viable only for three hours in the stomachs of flies). In former times an important part in the extension of the disease was attrib- uted to heredity (Roloff, Jessen). With the experience acquired in its eradica- tion, and with the establishment of the etiology of the disease, this conception is no longer tenable. In general the susceptibility of solipeds for infection is considerable, but it varies individually, as not all mares covered by an infected stallion become affected. This may however be explained by a temporary disappearance of the trypanosomes from the secretions of the genitals. According to Roll about 66% of mares which are exposed to the infection become affected. Rodloff in Sierakowo observed in all of 107 mares which were covered by: an infected stallion,mild or severe symptoms occurring later on (54 of these died), while in the experiments of Prince & Lafosse only 10 out of 15 mares became infected under similar conditions. Kern reports 24 cases in 105 mares. which were covered by an affected stallion. Pathogenesis. The trypanosomes which penetrate into the mucous membrane of the external genital organs first multiply at the point of entrance where they produce a serous and in part a cellular inflammation. Later they enter the blood and with it pass to distant parts of the body. This mode of dis- semination is indicated not only by the possibility of demon- strating at times the parasites in the blood, but also by the fact 820 Dourine. that in some cases paralysis develops in the region of some of the peripheral nerves (Facialis!) even in the early stage of the disease, and further that in the affected tissues the round cell infiltration is always observed in the immediate vicinity of small blood vessels. The intermediate attacks of fever appear to be produced by periodical invasions of large masses of trypanosomes into the blood stream, or by their temporarily rapid multiplication in the blood. Their disappearance appears to be the result of the development of trypanolytic substances. The trypano- somes apparently exert their pathogenic action by the produc- tion of certain toxins, which have not yet been demonstrated ; these on the one hand produce a serous inflammation of the walls of the vessels, on the other hand they principally attack the substance of the peripheral nerves, and the intervertebral ganglia. In these a cellular infiltration of the nerve tissue develops (neuritis interstitialis), whereupon the nerve fibres, as well as the nerve cells, degenerate and finally disappear entirely. The sensitive nerve bundles become involved in great numbers, and in a more severe form than the motor fibres, ‘the affection of which results in a degeneration of the cor- responding muscle fibres. The disturbances observed in the. movements and in the sensibility of the living animals are the direct result of the inflammation and degeneration of the peripheral nerves, while the emaciation indicates the action of a toxin circulating in the blood. In cases in which the parasites disappear entirely from the body a complete recovery may result even in cases in which conspicuous nervous symptoms have already appeared, and such instances are not rare in northern regions. As long as the motor cells of the medulla and the spinal cord are intact, new nerve fibres may form from the nerve cells or from the stumps of their prolongations of the axis cylinder. This is proved by the microscopical examination of cases in which the disease process showed improvement, when the nerves will be found to show fine pale stained, new nerve filaments (Marek). The dourine trypanosomes have a pronounced predilection for the mucous membrane of the genitals, for they may be demonstrated in these even after subcutaneous, intravenous or conjunctival infections. They are evidently capable of passing out of the blood vessels, producing exudation of blood plasma and a cellular infiltration on the irritated place, and thus cause among other symptoms an urticaria-like eruption of the skin, the so-called dollar spots. Anatomical Changes. Carcasses of animals dead from dourine are extremely emaciated, and show on the prominent parts of the body sores resulting from continuous lying down. The subcutaneous connective tissue is poor in fat, and in places shows gelatinous infiltration. In stallions the connective tissue of the scrotum is in many Anatomical Changes. 821 cases edematously swollen; the layers of the tunica propria are adherent by tough connective tissue in their entire extension or only in parts, or they may be covered by shredded granula- tions, while the cavity contains a clear or slightly clouded serous fluid. In rare gases small purulent foci are also found in the tissues of the te&ticles or between the pseudo-membranes, otherwise the tissue of the testicles and the epididymis appears unchanged, although the cord may show gelatinous infiltra- tion. In mares the tissne of the udder and the vulva may some- times show an edematous infiltration or sclerotic thickening. On the glans penis, algd’on the mucous membrane of the urethra near the outside orifigé, in mares on the mucous membrane of the vaginal opening and the vulva, spots freed from pigments may be observed, as:well as fine or thick radiating shrunken cicatrices. The lymph glands, especially those in the region of the genital organs; are swollen, soft, and show on the cut surface a moist glistening appearance. The muscles, espgéially those of the croup and of the pos- terior extremities are pale red, in places intermixed with butter- yellow stripes and hémorrhages, or with blackish-red or yel- lowish-red areas. The capsular ligaments of some joints are reddened, the cartilages of the epiphyses are ulcerated, while the synovial fluid appears cloudy and reddish-gray in color. The intra- and intermuscular connective tissue shows serous infiltration or may be changed in places into cicatricial tissue. The internal organs show pronounced anemia and edema- tous infiltration, sometimes a hypostatic pneumonia or mani- festations of a general septic infection. In cases which have had a rapid course, an acute swelling of the spleen and of the lymph glands may also be present. Frohner describes a thrombosis of several peripheral arteries by masses of leuco- cytes as a rare lesion. According to the descriptions of older authors portions of the spinal cord, especially in.the lumbar section, contain softened areas in the gray substance, besides small punctiform hemorrhages; as a matter of fact however changes visible with the naked eye may be entirely absent, even in cases with fatal termination. The meninges of the spinal cord may in parts contain smeary, friable masses. The larger nerve branches, especially those of the extremities, are either serously infiltrated or changed into connective tissue cords, which are strongly adherent to the intra- or intermuscular connective tissue. The histological examination of the nervous system (Marek) in the chronic cases shows in the extra-spinal nerve trunks, and most pronounced in the nerves of the posterior extremities, sometimes also in some of the cerebral nerves (V., VII. pair) a cellular infiltration, degeneration and atrophy of some of the nerve fibres, and an increase of nuclei of the endoneurium. These changes reach the highest degree near the sensory ganglia and in the facial nerve in the Fallopian canal. The nerve cells of the inter-vertebral ganglia in general, especially in the lumbar portion of the spinal canal, show an atrophy, chromatolysis, sclerosis, and peripheral displacement of the nuclei, while the connective tissue of the nerve fibres, which shows round cell infiltration, has partially disappeared. The peri- and endoneéural 822 Dourine. nuclei, however, are increased. The cellular infiltration extends also to the sensory roots of the entering zone of implantation, while the degeneration of some of the nerve fibers may be followed into the posterior trunks of the spinal cord, and up to the nuclei of the medulla. The other trunk, as well as in general also the nerve cells, are intact in the spinal cord, as well as in the medulla, otherwise, however, the chronic cases which have been examined manifested no changes, with the exception of some perivascular, inflammatory foci in the gray substance of the spinal cord. This, however, does not exclude the occurrence of intensive inflammatory changes in other cases. A fatty degeneration of the muscle fibers, also perivascular cellular infiltra- tion of the intramuscular connective tissue, the intensity of which varies in different parts of the body, is present in the muscles. It is most pronounced in the muscles of the croup and the posterior extremities (Fig. 143). Marek failed to find spe- cial changes either in the corium, or in the subcutaneous connective tissue, corre- sponding with the location of the dollar spots, whereas he met a focal cellular infiltration under the mucous membrane of the vagina, even in chronic cases. Fig. 148. Transverse section through the N. cruralis of a horse affected with dou- rine. a pronounced, 6 slight absence of nerve fibres; ¢ distended nerve sheath; d and ¢ epineural cell infiltration. (Marek.) Symptoms. In the appearance of the symptoms two stages must be distinguished, for which essentially different symptoms are characteristic, and which moreover are separated from each other by shorter or longer, apparently normal periods. The symptoms of the first stage affect principally the genital organs and differ from each other according to the sex of the animals, while in the second stage the symptoms predominate which point to an affection of the nervous system and which are not influenced by the sex of the patient. The characteristic symptoms of the first stage develop sub- sequently to the infectious coitus, after an incubation of from 5 to 6 days up to one month, sometimes however apparently after several months, as in some cases the disease is manifested only by moderate febrile attacks which may be unnoticed. Symptoms. 893 Prince & Lafosse observed after the infectious coitus an incubation of 7-60 days, Hertwig 2-8 days (?), Rodloff 8-14 days. Schneider & Buffard, also Baldrey, LEA bs pe “ alos amt infections the development of the first symptoms, or at leas e first febrile attacks after 8-20 days, B fter 40-45 ys, M aa ys, Buoy after 40-45 days, Marek Trypanosomes may sometimes be demonstrated in the urethral or vaginal secretion as early as 4-5 days after the infection; in spite of this, however, except- ing the rise of temperature, the local symptoms may not develop for months (according to Kern sometimes only after 9 months). In stallions the disease usually commences with an edema- tous infiltration of the sheath, which gradually extends from one place over the entire skin of the part, and especially to the anterior pendulous portion. The swollen sheath does not Fig. 144. Dourine. Swelling of the sheath and the lower chest; plaques on the croup and on the neck of a stallion. , feel warmer and is not painful. It is of doughy consistence, resembling somewhat a fat bag, only that the skin is stretched and not wrinkled (Fig. 144). The swelling spreads along both folds which pass from the orifice of the sheath to the abdomen and forwards and backwards to the scrotum. At the same time the glans penis also swells and the animal protrudes a longer or shorter portion of this organ from the sheath. The glans proper shows hardly any perceptible changes, excepting the edematous swelling which however may also be very slight, and a grayish transparent, or yellowish-gray mucus oozes out 824 Dourine. from the urethra. In infrequent cases the swollen glans appears of higher temperature and more sensitive. The border of the urethral opening is also frequently swollen, slightly reddened and the mucous membrane protrudes slightly: (especially in jacks). Later lentil to pea-sized, yellowish-red nodules on an infiltrated base develop, sometimes singly, at other times in groups, on the mucous membrane of the urethra in the vicinity of the urethral opening, also on the glans and on the body of the penis, and change into round, flat ulcers in 12 to 36 hours; these usually heal after a time, leaving behind roundish white spots. In some cases however they may persist for a long time, and even enlarge, after which their base is lardaceous, their borders raised, and on final healing prominent scars re- main. During the development of these changes the animals mani- fest a continuous desire to urinate, but they pass only small quantities of urine and nervously raise one of the hind legs or arch their backs. Besides this frequent erections of the penis are observed and the animals usually show an increased sexual desire. In mares the first manifestations consist in an edematous swelling of the vulva, discharge from the vagina, also redden- ing and inflammatory swelling of the vaginal mucous mem- brane. The labia of the vulva usually appear swollen on both sides, frequently however not uniformly; at the same time they are dense, elastic, not painful, and frequently covered with non-pigmented spots, similar to those sometimes occurring in the vicinity of the reetum (so-called toad spots). Sometimes the clitoris is swollen, so-that it protrudes from the lower gaping opening in the vulva. The mucous membrane of the vagina is loosened, shows dark red spots on a reddish-yellow base and is sometimes thickened into gelatinous, quivering, - longitudinal pads. The mucous follicles are also swollen, especially in the superior commissure, and in the vicinity of , the clitoris gelatinously translucent, and may be felt as millet- seed-sized, rarely larger nodules. The nodules may later break down, whereupon in their place small round ulcers, with sharp borders and yellowish bases appear. The ulcers finally heal, either without leaving any trace, or in their places light yellow spots may remain for a time (proliferated epithelium) (Fig. 145). Besides the nodules, pea-sized vesicles may develop ex- ceptionally on the mucous membrane of the vagina and on the vulva, in rare cases also in the surrounding portions of the skin, these contain a yellow serous fluid, and similar small ulcers develop after they burst. In severe cases the ulcerations increase in size, their bases becoming covered with necrotic tissue and the dark red borders showing an elevated swelling. They heal very slowly, and in their places round, smooth scars remain for a long time. Meanwhile the discharge from the vagina increases; first it Symptoms. 895 is white or yellowish and slimy, later more tenacious and finally purulent, dirty yellow, or reddish, dries on the lips of the vulva to dirty brown crusts and glues the hairs of the tail together. The edematous swelling may extend to the udder and the abdomen, as well as to the thighs. During the development of the local changes the mares manifest oestrum-like behavior, they shift their feet restlessly, swing their tails, strain frequently to urinate, sometimes passing only a little mucus and at other times a small quantity of urine after which they arch the back. The symptoms do not always reach so high a degree that atten- tion may be attracted to their pres- ence. Cases are relatively frequent in which the characteristic changes are only observed in the later stages, when by subsequent careful examination the traces of the pre- existing ulcerative processes may be found on the genitals in the form of white scars. If however nodules and ulcers develop only on the mucous membrane of the urethra, as sometimes occurs in stallions, not even traces of the local affec- tion may be found on the genital organs. The initial symptoms are Fig. 145. Dourine. Unpigment- . ¥ i ; ed spots on the lips of the vulva; sometimes unnoticed, especially in _ pronounced emaciation. mares in breeding establishments, but carefully watched stallions may direct the attention to the affection by the appearance of the nervous symptoms. The ulcers on the vaginal mucous membrane are described by all authors, with the exception of Rodloff, who never observed them. Mares observed a discharge from the vagina only in 17 out of 197 affected mares. In the second stage, which, as a rule, follows the first after several weeks, and sometimes after a temporary improvement, exceptionally however without any period of transition, symp- toms appear which indicate an affection partly of the skin, partly of the peripheral nerves and the intervertebral ganglia. The so-called dollar spots appear first, usually on the sides 8°26 Dourine. of the chest and on the croup, more rarely on the neck, shoulder, withers or on other parts of the body (Fig. 146). They are either round or semi-circular, or again irregular in shape. The former have a diameter of 4-8-15 cm., and may be recognized in that their periphery is formed by a ring 1-3 cm. broad, over which the hair stands erect or disarranged as a result of an edematous infiltration of the capillary bodies, on account of which the ring appears darker and less glistening. Within the ring the skin is not swollen, the hair is smooth, and therefore this portion appears sleek and glistening like the skin outside of the ring. The second eategory of the dollar spots is a very irregular, zigzag-shaped form, fre- quently extending 15-20 em. in one direction, and covered with roughened hair. Besides these spots, lentil to bean-sized nod- ules develop on the skin, over which the hair is also rough; such nodules are mostly observed on the inner surface of the thighs, in the flanks, and more rarely on the sides of the thorax and on the shoulders. The fourth form resembles urticaria Fig. 146. Dowrine. Plaques on the left side and the designation of of the abdomen. “‘dollar spots’’ is really appropriate only for this form of eruption. Sometimes on the inner surface of the thigh, sometimes in the flanks, lentil to dollar-sized, uniform protuber- ances appear, over which the hair appears rough and dull. The number of the dollar spots may be considerable, even exceeding one hundred. They usually persist for 1 to 8 days, when they disappear without leaving a trace, whereupon however fresh plaques soon appear on other parts of the body. All forms of eruptions are painless, are not of a higher temperature, and are not associated with itching. Strausz in Mezohegyes observed besides the dollar spots a severe vesicular and crustaceous eczema on the abdomen, on the chest, also on the croup, and at the base of the tail. The intensely itching eruption (‘‘iteh disease’’) which caused the patients to rub and scratch severely, resisted all treatment, but after a time it was arrested of its own ac- cord, and finally healed! later however hair failed to grow on the hair- less spots, and if in these places the pigment of the skin had disappeared the affected part of the body showed a variegated appearance. Symptoms. 897 Kern observed in some cases persistent perspiration and sub- a alopecia, Fréhner saw white hair appear on the rump of a stallion. ; Hyperesthesia either over the entire body surface or only in the region of certain nerve trunks, may be established either simultaneously with the appearance of the dollar spots or later. Ie On account of the increased sensitiveness of the skin, some- times a slight touch or a slight prick on the skin causes the animal to offer opposition, while stroking the back with the fingers causes the patients to groan and depress the back. | At the same time an increased sensitiveness of certain nerve trunks may be ascertained; thus the animal manifests sharp pains on pressure or stroking over the N. ischiadicus and peroneus, the Nn. intercostales, the N. medianus and infraor- bitalis. As the contraction of certain groups of muscles press or stretch the nerves lying between them a disturbance in their movements results owing to their sensitiveness. The walk of the patients is stiff, they hold one or the other leg more flexed, especially on trotting and galloping, also during quick turns and therefore evince lameness. If the animal stands still it periodically raises a foot spasmodically, as if tortured by lancinating pains, and holds it high for a while. trembling. Similar manifestations are observed when the animal starts to move and during passage of the bowels. These spasms occur more frequently during nighttime than during the day and are sometimes observed when the animal is lying down. In some animals a sudden lameness sets in, which however disappears after a few days. On account of the sensitiveness of the inter- costal nerves the respiration is accelerated and superficial, while owing to irritation of the vagus nerve, the patients cough periodically. The increased sensibility gradually passes into a hyperes- thesia, exceptionally into a complete anesthesia, and as a rule paralysis of certain motor nerves appears in the meantime. This is observed in almost every case in the hind extremities, quite fréquently in some of the facial nerves, especially the N. facialis, while the nerves of the anterior extremities, and those in other parts of the body are but rarely affected. The symptoms of paralysis are usually not even on both sides of the body. On the head they are almost invariably unilateral. As a result of paralysis of the nerves on the pos- terior extremities, the animals show a staggering gait, which is noticeable while walking in a straight direction, but more so while walking in a circle. On trotting they hold the hind legs spread apart or drag them with the flexed hock on the ground; when halted they usually knuckle (Fig. 147). The paralyses of certain nerves of the head are manifested in cor- responding disturbances of motion and in distortions. Accord- ing to Lorenz and Fréhner a peripheral recurrens-paralysis 828 Dourine. occurs frequently sometimes in spite of its long existence with- out leading to a demonstrable atrophy of the posterior muscles. The sphincter muscles of the anus and the bladder are not paralyzed. The superficial reflexes are increased over the region of the hyperesthesia, but they hecome weaker after the appearance of the muscular paralysis and finally disappear entirely. The tendinous reflexes, corresponding to the affected nerves, are diminished from the beginning or entirely absent, especially the patellar reflex. The electrical irritability of the nerves and muscles is likewise reduced in the regions of the paralysis or a partial and even a total degeneration reaction may be established (Marek). The symptoms of paralysis diminish sometimes consider- ably after several weeks and may disappear entirely, even a ee Fig. 147. Dourine. Paraparesis in an affected mare. (Snapshot.) when a degeneration reaction had previously been ascertained. In other cases they become more aggravated, the withering muscles become markedly atrophied, and finally the paralysis of the hind parts reaches such a degree that the animals are no longer capable of rising from the ground. Frequently affections of certain joints and tendons become associated with the nervous symptoms. The hock joint, more rarely the fetlock joints, or some articulations of the front legs, swell from day to day, together with the corresponding {endinous sheaths. The swellings are produced by the ac- cumulation of a large quantity of fluid in the synovial cap- sule or in the tendinous sheath, but at the same time there are no inflammatory symptoms perceptible. On palpation they show fluctuation, at the same time they are not warmer or pain- ful. Besides they may retrogress as rapidly as they develop and recur again after a cer- tain time. The respira- tion is quiet and slower than nor- mal, but even after short exer- cise it becomes very much accel- erated, calming down only grad- ually. Toward the end of the dis- ease a catarrh of the air passages or broncho-pneu- monia may de- velop. The heart action is mostly normal, only the heart is more easily excited, as even after short exercise accelera- tion, and some- times also an ar- rhythmic pulse may develop. The superfi- cial lymph glands, most frequently the inguinal, sometimes also the submaxillary glands, occasion- ally become swol- len, when they feel soft, elastic and painless or only moderately sensitive. nal March 38 2 7 Feb. 271 28 January ri yi Na 101 717 72] #3[ 4] 75] 16 771 181 79] 20] 271 221 23] 24] 25 z] December T.| P| 8. [22] 23] 2s] 25] 26] 27] 28] 20] So] 37 7 > =) of ST wo} Sf 8] SIF Ss] TS] 7s S} Ss} SB} SOR St 8) 8] SP Sys Sr ayo; USP UmSrPCUSTCUST:COST TT S):CUST TS & EEE EE BE ed ky al of al al of of slfal Ss] o Sto ~ | miles 59 AT Fever curve of a mare which received on December 22 urethral mucus from an infected stallion into the vagina. 829 : Fig. 148. Dourine. ‘Trypanosomes were first found in the vaginal secretion on December 31, and from then on in varying numbers until death, while in the. blood In the period between January 26 and From January 16, swelling of the lips of the vulva. they were demonstrated only once, on March 2d. “ebruary 26, absence of fever. 830 Dourine. The number of red blood corpuscles in the blood may diminish to one-tenth of the normal, while white corpuscles may increase 10 to 30 times. In many cases a pronounced eosinophilia may also be demonstrated (Marek, Frohner). The daily quantity of the urine fluctuates within normal limits; its specific gravity is 1,023 to 1,060 and on an average it is lower than in healthy horses. Of the normal constituents the quantity of phosphoric acid is markedly increased in about 70% of the cases (up to 4-5 gm.); besides the quantity of urea is also increased (Liebermann; according to Roger the urine contains glucose). In the eyeground the papillae and their surroundings ap- pear congested in some cases, and in time blood pigment is deposited in the tissues surrounding them. These changes may later reduce the vision and even result in blindness. Conjunc- tival catarrh is a frequent symptom, in some cases however also an exudative iritis develops which finally leads to atrophy of the bulbus. Fréhner observed in one case a unilateral con- traction of the pupil. The body temperatures show a periodical rise of remittent character (Fig. 148). In the later course a continuous fever may set in, probably produced in part by suppurative processes, especially in the genital organs, but towards the termination of the disease also by the gangrene of the sores from constant lying down. With the temporary febrile attacks, fresh plaque eruptions develop frequently, but the course of the disease may continue without fever even for months. _ Mares which are impregnated by an infected stallion fre- quently abort during the second or third month of pregnancy. The affected animals become greatly emaciated during the paralytic stage of the disease, although the appetite remains good almost to the end. Besides the paralysis, the weakness brought on by the emaciation contributes to the inability of the animals to rise in the later stages of the disease. The im- mediate cause of death is either a hypostatic pneumonia or a septicemic affection in association with the gangrene caused by the pressure sores. Course and Prognosis. In northern regions dourine usually runs a chronic course. After the local affection of the genital organs, several weeks or even months usually elapse before the nervous symptoms are markedly perceptible, while the dollar spots may appear earlier, sometimes simultaneously with the swelling of the sheath. After the appearance of the nervous symptoms the disease may in unfavorable cases take a rapid course, so that the animal succumbs in 3 to 4 weeks, completely exhausted, or—and this is more frequently the case—the disease extends over several months, frequently from 1 to 2 years. In such cases more or less pronounced improvement may be noticed periodically, which is however only temporary, and Course and Prognosis. 831 finally the disease passes into the aggravated condition which leads to a fatal termination. In southern regions the disease appears to run a more acute course, so that the patients may die after 1 to 2 months and even inside of 6 to 8 days (Monod). At the same time the febrile attacks are more conspicuous following each other in more rapid succession, and the paralytic symptoms also de- velop more rapidly, therefore there are no marked, and es- pecially no chronic interstitial changes of the nerves in the dead animals. _The termination of the disease varies in different outbreaks. While sometimes about half of the affected animals die (in India, according to Pease, the mortality amounts to 70-80%), in other cases the loss is much smaller (thus for instance in A.-Vadasz and vicinity, out of 30 mares in which the disease. was established with certainty only two died). Recovery is possible even after the appearance of the nervous symptoms, dollar spots and paralysis, and such animals may then perform hard work for years. It is probable that in some cases only the local changes of the genitals develop after an infection, which definitely heal without the later development of nervous symptoms. Some authors are of the opinion that the disease develops more rapidly in stallions and that it runs a more unfavorable course than in mares, and in Algeria it is supposed to limit itself in asses in the majority of cases to a local affection of the genital apparatus. Diagnosis. In northern regions where dourine apparently represents the only trypanosome affection of solipeds, the diagnosis is definitely established by the demonstration of trypanosomes; but this is associated with considerable difficulty, as the parasites are present but rarely in the blood, and even then only in very small numbers. Their occurrence in the serous fluid of the dollar spots, especially immediately after these appear, is more constant, as is also the case in the edema- tous swellings in the vicinity of the external genital organs, but even here the examination requires great patience. Their demonstration in the mucous secretion of the urethra and vagina is much easier (Fig. 149), but even there it is to be remembered that they may disappear periodically from the secretion. A sufficient quantity of secretion is obtained from the vagina by scraping the mucous membrane with a scalpel or with a glass slide. In stallions the penis is drawn out with the left hand, and then a long-handled, bean-shaped, oval spoon with dull edges is introduced into the urethra, with which the mucous membrane is seraped off. F . In doubtful cases blood may be injected subcutaneously into dogs. In the swellings which subsequently develop trypanosomes are always present in great num- bers (Buffard & Schneider). Mice may also be used for this purpose. Since the material is frequently non-pathogenic for test animals, even from horses positively affected with dourine (see p. 817), only a positive result’ of the inoculation has a diagnostic significance. 832 Dourine. As the ring and semi-circular dollar spots have been ob- served in northern regions only in dourine, they may be con- sidered as characteristic for the disease, or at least accepted as suspicious in a high degree. Their repeated appearance for weeks and months, and frequently also their persistence for several days, distinguish them from the ordinary urticaria. In tropical regions the differentiation of dourine from nagana, surra and Mal de caderas may evidently cause diffi- culty, but as according to the reports so far available, trypano- somes in the secretions of the genital organs are found only in dourine, their presence there would clear the diagnosis; like- wise an infection which may be shown to have been trans- mitted by coitus speaks for dourine. Fig. 149. Vaginal secretion of a mare affected with dourine. a trypanosomes; 6b epithelial cells from the deeper, d from the superficial layer of the mucous membrane; c leucocytes; e erythrocytes. After a fresh, unstained preparation. According to Baldrey the disease may be distinguished from surra in that the latter usually occurs in epizooties, geldings and unbred mares become affected, the body temperatures reach high degrees and last longer, and trypanosomes are present in the blood in great numbers at the beginning of the fever. According to Davison, Bursattee (see p. -739) also resembles dourine as it also is associated with a swelling of the genitals and inflammation of the skin; these however are very painful. , At times where there exists no suspicion of infection, the initial stage of dourine is sometimes mistaken for a traumatic ix. dJammation of the genitals ; however, the traumatic origin may Diagnosis, Treatment. 833 easily be excluded by the absence of a visible injury, or on the ground of the torpid character and persistent presence of the edematous swelling. The coital, vesicular exanthema can readily be taken for dourine, as both affections develop after coitus with quite similar symptoms. In the coital exanthema however the eruptions disappear much more rapidly and are almost invariably benign; further the vaginal mucous mem- brane is reddened, the affected parts are painful, the usually numerous ulcers heal within a few days and with this the dis- ease terminates, that is, no nervous symptoms develop with the local affection. Glanders may also come into consideration, as in its later course edematous swellings may result on the sheath and on the abdomen, but a mistake is prevented by the other symptoms, which are usually present. The swelling of the submaxillary lymph glands may readily be distinguished by its soft elastic consistency from the glandular swelling of the glands. The weakness of the hind parts is only characteristic of dourine when associated with the other nervous symptoms. From other diseases in which similar weakness of the hind parts occurs, the paralysis of the musculus quadratus lumborum muscle, and the tearing of the lumbo-sacral articulation should be mentioned, in which however the animal is not capable of backing up at all, while a horse with dourine is capable of per- forming this function, although with difficulty and staggering. Paralysis of the facial nerves from other causes may be dis- tinguished from dourine by the absence of edematous swelling of the genitals and the plaques as well as other symptoms of paralysis. Besides frequent accessory conditions, the affection of several animals in association with coitus, and the multiplicity of the symptoms in different animals are as a rule sufficient points for establishing the diagnosis of the disease in question. _ Experiments by Uhlenhuth & Woithe, Manteufel, also Zwick & Fischer, with the complement fixation, the precipitation, the agglomeration, as well as the cutaneous ‘and ophthalmo tests for the diagnosis of dourine, gave negative results throughout. : ; Treatment. Recently arsenical preparations have been used frequently in treatment, Trélat having obtained satisfac- tory results from the internal administration of arsenious acid (3-6 gm. daily), Arkhangelsky & Novikoff from subcutaneous injections (0.01-0.05 gm. in increasing doses). Uhlenhuth & Woithe found atoxyl very effective on small animals in labora- tory experiments. In horses the conditions for such a treat- ment are rather unfavorable, as the large doses required at the beginning of the disease are badly tolerated by these ani- mals, also on account of the presence of the parasites in the secretion of the genitals, in the edematous fluid of the swell- ings and in cavities of joints, where they may elude the destruc- Vol. 1—53 834 Dourine. tive action of the remedy. Nevertheless there are reports which appear to indicate the possibility of a recovery of the disease processes following such treatment. Uhlenhuth & Woithe succeeded in keeping an artificially infected horse in good strength for one year by increasing doses of atoxyl (0.3-5.0 gm. intravenously), its blood, however, contained trypanosomes throughout the entire period in vary- ing quantities, and it suddenly died from acute septicemia with extensive intestinal hemorrhages. Rennes obtained better results in an artificially infected horse, which he injected at intervals of 3-4 days, alternately with 4 gm. of atoxyl subcutaneously and 3 gm. kalium tartaricum intravenously; after the administration of 32 gm. atoxyl and 21 gm. kal. tart. the horse was permanently cured. Yakimoff treated 10 horses by injecting atoxyl ten times in succession, either subeutaneously (4-8 gm.) or intravenously (0.5-3.0 gm.), in increasing doses, and this treatment was repeated. The results were good, as a relapse was observed in only one case. Monod also is supposed to have succeeded in permanently curing an affected stallion with similar treatment (first 0.5 gm. intravenously, then every second day an increase of 0.1 gm. until the maximum dose of 1.0 gm. was reached). The atoxyl solution must be freshly prepared at each application by boiling on a water-bath. Of other arsenical preparations, Miessner found in one case arsenophenylglycin very effective, in which the nutritive condition and strength of an already greatly weakened animal was materially improved by two injections of the remedy (dose?) and the edematous swellings retrogressed. Fréhner, on the other hand, not only failed to observe an improvement in one case after an intravenous injection of 24 gm. atoxyl, but even noted severe symptoms of intoxication, such as marked psychic irritation, severe colic and on the second day nephritis. Finally Monod reported lasting results in three stallions, which in part were treated with arsen-trisulfid alone (15-30 gm. per os), the others alternately receiving atoxyl. The local treatment of the swellings with astringent washes and the suppuration of the testicles or lymph glands in accord- ance with the rules of surgery are only of subordinate im- portance. Prevention. Stallions and mares should be examined before coitus as to their health, and horses with inflammatory changes on the genital organs should be excluded from coitus on general principles. Besides this it is advisable to wash the penis of the stallion after every covering with a sponge dipped in clean water. — Veterinary Police. The veterinary police measures depend on the principle that horses affected with dourine should be excluded from breeding once and for all. Such measures appear to be justified in spite of the possibility of a complete recovery, by the frequent relapses and also by the fact that trypanosomes may be present for months in the genital organs of apparently recovered animals.’. Accordingly affected stallions should be castrated, while affected mares should receive a distinctive branding. The relatively late development of the: symptoms Prevention, Veterinary Police. 835 characteristic of the disease, as well as the possibility of a healthy stallion transmitting the disease from an affected mare to a healthy animal, appear to justify an action requiring that healthy stallions which have covered mares affected with dourine should be considered the same as those affected. Literature. Hertwig, Mag., 1842. VIII. 269; 1847, XIII. 373, — Rouget, A. P., 1876. 717. — Schneider & Buffard, Ree., 1900. 81; J. vét., 1902. 144; A. P., 1905, XTX. 715. — Marek, Z. f. Tm., 1900. 1V. 401; D. t. W., 1909. 121. — Kern, 2. f. Tm., 1905. IX. 259. — Lingard, Cbl. f. B., 1904. XX XVII. 537. — Baldrey, J. of comp. Path., 1905. XVIII. 1. — Sieber & Gonder, A. f. Schiffs- u. Trophyg., 1908. XII. 246. — Uhlenhuth & Woithe, Arb. d, G.-A., 1908. XXIX. 403 (Lit. on ee — Froéhner, Monh., 1909, XX. 385. — Zwick. D. t. W., 1910. Nr. 9 eibl. (d) Mal de Caderas. History. The etiology of the disease (Mal de caderas—hip disease) was cleared up by Elmassian, when in 1901 he found trypanosomes in the blood of horses at Argentine. Voges, Zabala and Ligniéres con- firmed the finding, and furnished further contributions on the etiology as well as symptomatology of the disease. Occurrence. Until the present time the disease has been diagnosed exclusively in the sub-equatorial countries of South America: Brazil, Argentine, Bolivia and Paraguay, as well as on some islands of the delta of the Amazon River. According to Lacerda the disease is supposed to have been introduced from the islands of Marajo, westward and southward, and resulted. in some localities of Brazil in a complete annihilation of the horses. There are marshy localities in Argentine in which up to 25% of the horses die, and it is stated that a cavalry regiment lost 100 out of 600 newly purchased horses within half a year (Voges). Etiology. The trypanosoma equinum (Th. Elmassiani) is similar to the parasite of nagana, with the only difference that its blepharoplast, is very small and can be stained only with difficulty (Ligniéres; Fig. 150). Ruminants and hogs are only slightly susceptible to artificial infec- tions; other animals have about the same susceptibility as for the organ- ism of nagana. In horses infected = subcutaneously with blood, disturb- Fig. 150. Trypanosoma equi- ances in locomotion develop in the [yim Himassani. | Guinea Dig later stages of the disease in a strik- sky-Zieman. ing manner (similarity with dourine). The disease cannot be reproduced, even in susceptible animals, by feeding fresh blood containing numerous parasites (Zabala). Animals immunized against nagana or surra are still suscep- tible to caderas and vice versa. ‘4 ‘ae - “grime tontains albumen and frequently some blood, the latter 836 Mal de Caderas. The natural mode of infection has not yet been elucidated. At first it was thought that stinging flies were the transmitters of this disease, especially the stomoxys brava (Mosca brava) and tabanidae as well as possibly also mosquitoes (Ligniéres-& Zabala, Voges); according to the observation of HElmassian & Migone, however, horses which are separated from affected ani- mals only by a fence remain healthy in spite of being swarmed by stomoxys flies. Later the last-named authors connected a rodent with the appearance of the disease (Hydrochoerus capibara, vulg. Carpincho), observing that these animals sometimes die in great numbers, and that hunting dogs which have eaten their flesh also become affected, whereupon the disease soon breaks out among horses. Anatomical Changes. These consist usually in an acute swelling of the spleen and the lymph glands, accumulation of sero-fibrinous exudate in the serous body cavities and in the joints, hemorrhagic nephritis, parenchymatous degeneration of the internal organs, besides hemorrhages and serous infiltra- tion of the muscles of the croup. Symptoms. A weakness of the hind parts is noticeable from the onset of the disease, as the animals show a staggering gait, bringing forward the hind legs, dragging them on ‘the ground, and frequently knuckling in the tarsal joints. With the rapidly progressing emaciation, the paraparesis reaches a very high degree, so that the patients rise from the ground with difficulty, after which they stand with legs spread apart, and ean not be made to move. Finally they are unable to rise, and then the sphincter ani becomes relaxed and the rectum fills with balls of feces or defecation becomes involuntary. The body temperature shows a febrile elevation atypical in character, urticaria-like swellings appear on the skin which beeome covered with small crusts; subcutaneous edemas are observed but rarely, and then only on the lower abdomen, while swelling of some of the joints is frequently observed. The sometimes in great quantities. Inflammation of the conjunc- tivae and.cornea is a frequent complication. The appetite re- mains good until the end. ’s- 'The course is always unfavorable. After the appearance of the disturbances in locomotion the animals usually succumb in’ 1 to 2 months, but there is also a chronic form of the affec- tion (known in Paraguay as Baacy-poy=slow emaciation), which develops very gradually, so that the emaciation and weak- ness of the hind parts becomes apparent only after months. Trypanosomes are found in the blood only in acute cases in considerable numbers, while otherwise their demonstration is successful only by inoculation of test animals (mouse, rat). The disease runs under similar manifestations in mules and asses. Symptoms, Treatment and Prevention. 837 Treatment and Prevention. Ehrlich & Shiga found trypan red effective in experiments on mice against the trypanosomes of Mal de caderas. For practice however no satisfactory method of treatment is known. In consideration of the fact that the mode of natural in- fection is still-unknown, no certain preventive measures can be established. Nevertheless keeping the solipeds from marshy pastures, and the destruction of affected horses, may prove beneficial. Literature. Elmassian & Migone, A. P., 1903, XVIT. 241 u. 1904, XVIII. 587. — Voges, Z. f, Hyg., 1902. XXXIX. 323. — Ligniéres, Bull., 1903. 51. Other Trypanosome Diseases. Besides the affections considered above other diseases of domestic animals have been described, the classi- fication of which however is at present still doubtful. The most im- portant will be set forth briefly in the following: : i. Gambia Fever of Horses. This is caused by the trypanosome dimorphon discovered by Dutton & Todd in Senegambia. It occurs in the blood of horses shortly after infection in a short tadpole form, and in the latter stages in a longer, more slender form, in both of which the plasma extends almost to the anterior end of the flagella. The clinical symptoms resemble those of nagana, only subcutaneous edema is absent (for treatment see p. 802). The transmission of the parasite is supposed to oceur by the Clos- sina palpalis. In recent times the same trypanosome has been demon- strated in different localities of Africa, not only in horses, but also in other domestic animals, as the cause of an affection which is mostly chronic (Laveran & Mesnil, C. R. 1904. CX XXVIII. 732). 2. Zousfana. Observed by Szewezyk and Rennes in Algeria in solipeds, and attributed to a particular trypanosome similar to the Tr. sudanense. The disease runs a chronic course, with symptoms. of anemia and hemoglobinuria, but without edema. Possibly identical with nagana cr surra. (Szewezyk, Bull., 1903. 220.—Rennes, Ibid., 1907. 298.) 3. Soumaya (Souma). Described by Cazalbou as a disease of horses in the French Sudan and supposed to occur also among mules, cattle and sheep in the upper valley of the Niger and the adjoining territories. Its cause, the Trypanosoma Cazalboui, was described as a new species, its nucleus being placed near the rounded posterior end. Dogs and small test animals are not susceptible. According.to Buffard it is also virulent for cattle, and is transmitted by stomoxys flies. Symp- toms in horses are anemia, swellings of the skin and weakness of the hind parts. The course is sometimes acute, covering about 50 days, at other times it may extend over a year. Thiroux & Teppaz reported good results from treatment with atoxyl and auripigment, or with auripig- ment alone. (Cazalbou, Acad. de méd., 1904.—Laveran, A. P., 1907, XXI., 325.—Buffard, Soc. biol., 1907, 71—Thiroux & Teppaz, C. R., 1908, CXL, 651.) 4, Baleri. Occurs quite frequently among solipeds in certain lo- ealities in the Sudan, with symptoms of fever, infiltration of the skin, anemia, emaciation, and muscular weakness, Its course is from 3-4 838 Trypanosome Diseases. months. The Trypanosoma Pecaudi, named by Laveran, resembles the Tr. dimorphon, and is, according to Buffard, said to be transmitted by the Glossina palpalis. Dogs are also susceptible. Thiroux & Teppaz found the auripigment effective. (Cazalbou, Rev. gén., 1907, IX, 564.— Bouffard, A. P., 1908, XXII, 1.) 5. Mbori and El Debab of Camels. (Maladie de la mouche.) The Sergent brothers in Algeria, and Cazalbou in Timbuctu, have described this as an independent affection, but according to Laveran it is supposed to be identical with surra. The camels become affected with symptoms of anemia and emaciation, also turning the head and neck to the side, while edema and disturbances in locomotion are not usually observed. About 10% of the dromedaries are supposed to be affected in Algeria. (Laveran, Acad. de méd., 1904.—Sergent & Ledoux, Soc. de’Path. exot., 1908, 22.) Other Trypanosomes. Besides those described, other species of trypanosomes have recently been found in domestic animals; some of these will be briefly described in the following: Trypanosoma Theileri; first demonstrated by .Theiler in cattle in South Africa, later by Schilling in Togo, Szewezyk & Rennes in North Africa, Sander on the Island of Mafia of the German-East African protectorate, Valladares in Madras, Luhs in Trans-Caucasia, Pease found it in India also in buffaloes. It is characterized by its considerable size (30-70 » long, 2-5 » broad, and a long flagella. First it was con- sidered by Theiler as the cause of gall sickness (see p. 783), but it appears to be a harmless habitant of the blood of cattle. (Theiler, Comp. Path., 1903, XVI, 192.—Mayer, Z. f., Infkr., 1909, VI, 46 [Lit.].) A similar trypanosome was found by Frank in great numbers in the blood of German cattle in Stein-Wingert (Wiesbaden), and named by Frosch Tryp. Frank. Further Knuth, Rauchbaar & Morgen- stern succeeded in demonstrating trypanosomes of the same type by inoculation of defibrinated cattle blood into sterile beef bouillon; in the District of Oberwesterwald in 7 out of 25, in another stable 10 out of 17, and in a third 6 out of 9 otherwise healthy cattle, which originated from various localities of Germany. (Z. f. Infkr., 1909, V. 313.—B. t. W., 1910, 539 u. 610.) Also very similar is, according to Lingard, the Tryp. himalayanum and the Tryp. indicum, further the Tryp. muktesari, this however somewhat. smaller, and with shorter flagella (C. R., 1908, 452), also the Tryp. americanum, which was by Crawley found frequently in healthy cattle in North America (An. Ind. Bull. 119, 1909). Broden described the Tryp. congolense as a, special species, which frequently causes disease in the Congo especially among horses, but also among other domestic animals and has also been found in the northern part of Rhodesia. It is smaller than the nagana trypanosome, has no free flagella, and otherwise resembles the small form of the Tryp. dimorphon. (Laveran, A. P., 1910, XXIV, 81.) This closely resembles the Tryp. nanum, which was demonstrated by Theiler in Zambesia and in Limpopo in cattle, and in Zuzuland in a horse. (Soc. de pathol. exot., 1909.) Mathis & Léger observed a trypanosome in a chicken, which they named Tryp. Calmettei. (Soc. biol. 1909, LXVI, 452.) (See also Lithe, Handb. d. Tropenkrkh., 1906, III, 124, u. Doflein, “Lehrb. d. Protozoenkunde, 1909, 390.) Trypanosome Affections in Man. 839 Trypanosome Affections in Man. By the findings of Nepveu (1898), Dutton (1902) and Castellani (1903), as well as by numerous subsequent confirmations, it was established that the so-called sleeping sickness of the negroes is caused by a blood parasite, the Trypanosoma gambiensis. It greatly resembles the parasite of nagana, and is also transmitted into the healthy body of man by the tsetse fly, especially by the Glossina palpalis. The disease, which occurs in tropical Africa, manifests itself in the first stage (Trypanosome fever) in irregular fever, transitory edema, and erythema, also swelling of the lymph glands and spleen. If the patients survive, symptoms of the sleeping sickness proper develop in a few months. Fatigue with frequent head- aches, subcutaneous edema, diminution of the intelligence, and finally symptoms of a severe meningitis, especially conspicuous somnolence, whereupon the patients die in a deep comatous condition. Good results were obtained in the treatment with arsenical preparations, especially with atoxyl. (S. Mense, Handb. d. Tropenkrankh., 1906, III, 617.— Koch, Beck & Kleine, Arb. d. G.-A., 1909, XX XI, 1, H.) Chagas found in a child in Brazil a trypanosome (Tr. Cruzil), which supposedly is transmitted by the Cinorrhinus insect. The symp- toms were similar to those of the African trypanosome fever. (A. f. Schiffs, u. Tropenhyg., 1909, XIII, 351.) ‘3. Spirochaetosis of Fowls. Spirochaetosis avium. (Spirillosis or Spirochaetosis of Chickens; Spirillosis gallinarum et anserum.) Spirillosis represents usually a fatal septicemia of chickens, geese and ducks, caused by a screw-shaped blood parasite, the Spirochaete gallinarum. History. Spirillae were first demonstrated as disease producers by Sakharoff (1891) among geese in Trans-Caucasia, later by Marchoux & Salimbeni (1903) in Brazil. At first it appeared as if two different diseases were concerned, but Williamson (1908) and Galli-Valerio (1909) have established the identity of their causative agents. In the meantime Levaditi, Borrel & Marchoux, Neufeld & Prowazek and Nuttall have contributed to the etiology, Uhlenhuth and his co-workers, then Levaditi & McIntosh, Dschunkowsky & Luhs to the atoxyl treat-_ ment of the disease. Occurrence. The disease occurs frequently as a dangerous plague among chickens in the most varied localities, while in geese and ducks it has been found only sporadically. Outside of Brazil the chicken spirillosis has been met with to the present time in Bulgaria (Gareitschnoff), in Roumania (Mezinescu), in Cyprus (Williamson), in Egypt (Dreyer, Balfour, Bitter), in Tunis (Galli-Valerio, Comte & Bouquet), in South Africa (Johnsohn, Bevan, Mohr), in Australia (Cleland), and in India (Greig, Montgomery, Rainey) ; the spirillosis of geese, outside of Trans-Caucasia (Sakharoff, Dschunkowsky & Luhs) only in Tunis (Ducloux). 840 Spirillosis of Fowls. Etiology. The causative agent of the disease (Spirochaete gallinarum, Sp. anserum) is a blood parasite, probably belong- ing to flagellated protozoa, which closely resembles the cause of recurrent fever of man (Spirochaete Obermeieri) which has been known for several decades. It occurs in fine threads, 10-20 » long, formed similarly to the spiral thread of a screw, supplied with one or more cilia (Borrel) which move actively be- tween the blood corpuscles in the blood of living ani- Fig.151. Spirochaete anserina. Goose 3 2 blood. (After Cantacuzene. ) mals affected with the dis- ease (Fig. 151). They dis- appear from the blood shortly after death and in drawn blood they remain alive at best only for 2 to 3 days. Dschunkowsky & Luhs are reported to have succeeded ‘in cultivating the spiro- chaete of geese in blood plasma of geese by means of reed sacks in the body of a rabbit up to the third generation; later indications of degeneration became ine ae on the threads, but the fluid possessed a protective action against artificial infections. The disease may be produced easily by subcutaneous in- jection of blood containing spirillae from geese to geese, from ducks to young chicks, but only with difficulty to grown chickens, while the transmission from affected chickens to chicken species, as well as to water fowl is readily accomplished (it was not possible to infect monkeys with the spirilla of chickens). After a subcutaneous infection in chickens a considerable number of parasites appear on the second day independently of the quan- tity of inoculated blood which continue to increase until the fifth day, and in the meantime clump together, forming great agglomeration masses. On the sixth day after the temperature has fallen rapidly, they disappear from the blood, whereupon death ensues or the animal gradually recovers. The artificial infection is also successful by placing infected ticks upon the birds (see lower down), further by feeding blood containing spirillae, as well as by cohabitation of affected with healthy chickens. Brumpt described the Sp. Nicollei from Tunis, also the Sp. Neveuxi as varieties of the chicken spirochaete, which are also transmitted to chickens by the Argas persicus; between this and the chicken spirochaete only immunizing differences exist. : The natural infection is in chickens transmitted principally by the Argas miniatus tick, more rarely by the Argas persicus and reflexus, further by the Ornithodorus moubata. These ticks exist freely in the bushes at the borders of forests, etc., attach Etiology, Anatomical Changes, Symptoms. 841 themselves at night to chickens and suck their blood. If the blood contains spirochaetes, they are found for 3 to 4 days in the digestive canal of the ticks, whereupon they disappear from there, but they may remain infectious for a longer time, according to Nuttall even after six months. If they are kept at 35° C., the parasites multiply in their bodies, and after 4 to 5.days they may be found in the excretory duct of the salivary gland of the ticks (Borrel & Marchoux). : _ Anatomical Changes. In birds dead with the disease the spleen is considerably enlarged and swollen, the liver swollen, showing fatty degeneration and focal necrosis; the heart muscle also shows at times fatty degeneration and the epicardium is ae ae fibrinous membranes. No spirillae are found: in e blood. Symptoms. The incubation is in chickens 7 to 9 days after placing infected ticks upon them; spirochaetes may however be demonstrated in the blood as early as from the fifth day on (Marchoux & Salimbeni, Uhlenhuth & Gross). The symptoms consist in inappetence, rise of temperature as high as 42.5-43° C., marked weakness and somnolence, pale- ness of the comb, diarrhea and emaciation, with which in some cases paralysis of the legs becomes associated. (Mohn observed, even before the appearance of spirochaetes in the blood, the feet swollen and the toe turned under and backwards.) After the somnolence has reached a high degree, the crisis sets in 1 to 2 days later, the comb taking on a bluish-red colora- tion, the temperature falls, and soon death follows, usually under severe convulsions or recovery commences. Sometimes however this is only apparent, as the paralysis of the legs in- creases and gradually extends to the wings, the birds become greatly emaciated, and finally die with a few rare exceptions (chronic form). 7 According to Nuttall the spirochetes are totally or mostly destroyed by bactericidal and agglomerating substances after having multiplied for a time in the blood. The more resistant, and therefore the surviving parasites are then the cause of the supervening chronic affection. Serum of ‘birds which have recovered from one attack, destroys in test tube experiments the spirochetes of the first attack, but not those of later’ attacks. The appearance of parasiticidal substances in great quantities in the blood before the crisis is reached has also been demonstrated by Gabritschewsky and Uhlenhuth. By microscopical examination spirochaetes may be demonstrated in great numbers in fresh blood preparations made with physiological salt solution until the appearance of the crisis, but later, and also in animals dead of the disease, they are no longer present. The duration of the disease in the more frequent acute cases is mostly 4 to 5, in the chronic cases 8 to 15 days. 842 Spirillosis of Fowls. Treatment. According to the experiments of Uhlenhuth & Gross, which were later confirmed by Levaditi & McIntosh, three subcutaneous injections of 0.05 gm. each, likewise two adminis- trations of 0.1 gm. atoxyl per os, protected chickens against a simultaneous or an immediately preceding or subsequent sub- cutaneous virulent infection, and chickens treated in this man- ner apparently acquired a lasting immunity. Affected chickens, which have already harbored spirochetes in their blood for 2 to 3 days, but which are not yet severely affected, recover from a single intra-muscular injection of 0.05 gm. atoxyl, when the parasites disappear from the blood after 34 hours and the animals survive. In the internal application of the remedy double doses (0.1 gm. per os) appear to have the same action. ; Uhlenhuth & Manteufel found atoxylate of mercury more effective than atoxyl; by its intra-muscular application (in sus- pension with olive oil and gum arabic), in doses of 0.1 gm., it produced recovery even at the height of the blood infection, and in earlier stages it prevented a fatal termination even in doses of 0.04-0.06 gm. Such recovered chickens remain immune against later infections. Dschunkowsky & Luhs obtained good results in geese with 2 or 3 subcutaneous injections of 0.1-0.15 gm. each of atoxyl, per kilogram of body weight. Finally, according to the favorable results in the treat- ment of the human recurrent fever and syphilis, Ehrlich’s amidoarsenobenzol may also prove effective. Immunization. Blood drawn from infected chickens is no longer infectious after 48 hours, and if injected subcutaneously into healthy chickens produces an immunity against a virulent affection. Fresh blood heated for five minutes to 55° C. has a similar action, whereas when heated for 10 minutes at that temperature it no longer produces immunity (Marchoux & Salimbeni). An active immunity may further be produced in geese with emulsion from organs of geese dead of tthe disease, also with atoxyl and a simultaneous injection of virulent blood, as well as with blood from infected geese which have been kept on ice for some time (Dschunkowsky & Luhs). Blood serum from geese and chickens, which after recovery from the disease were treated with blood containing spirillae, protects in quantities of 2 ec. against virulent infection. Finally horses produce serum after repeated injections with blood containing spirillae which in a quantity of 3-5 cc. renders ineffec- tive in geese an inoculation made 24 hours previously (Sakharoff). Injections of immune serum in the blood circulation of affected birds results in death, as it produces an agglomeration of the spirochaetes and thereby thrombosis of the blood vessels (Levaditi). Literature. See also literature in Uhlenhuth & Gross, Arb. d. G.-A., 1907. XXVII. 231. — Further: Sakharoff, A. P., 1891. V. 564. — Gabritschewsky, Chl. f. Bakt., 1898. XXIII. 365. — Cantacuzéne, A. P., 1899. XIII. 529. — Borrel & Marchoux, Soe. biol., 1905. 362. — Borrel, ibid., 1906. — Levaditi, A.'P., 1906, XX. 924, — Levaditi & McIntosh, Soe. biol., 1907, XLII. 1090. — Neufeld & Prowazek, Arb. 7. G.-A., 1907. XXV. 494, — Uhlenhuth & Manteufel, Z. f. Immf., 1908. I. 108. _ Dschunkowsky & Luhs, Kongr. Haag 1909. — Brumpt, Soe. path. exot., 1909. ITI, Spirochaetes in Mammals. 843 Spirochaetes in Mammals. Parasites resembling the spirochaetes of fowls morphologically occur sometimes also in mammals, . their etiological part however is at present not yet cleared up, as they were met with either in healthy animals or in such as are infected with piroplasma or trypanosomes. Transmission experiments have not given conclusive results. The available findings are therefore described only very briefly in the following: 1. Spirochaete (Spirillum) Theileri. First demonstrated by Theiler (1902) in the Transvaal in febrile animals together with piro- plasma and trypanosomes. They are 20-30 » long, spiral-shaped bodies. The first experiments of transmission were without results, later how- ever Theiler reported that he succeeded in transmitting the parasite from cattle to cattle and to sheep, and Dodd also found that they may be transmitted from animal to animal. According to Theiler the natural infection is transmitted by the Boophilus decoloratus and the Rhipicephalus Evertsi, and Laveran & Vallée succeeded in infecting a cow at Alfort, by placing larvae of the .first-named species, which originated from ticks taken from cattle in the Transvaal. In this case spirochetes appeared in the blood between the fifteenth and the nineteenth day without the development _of perceptible symptoms. Nevertheless Theiler believes that these parasites are independently capable of producing a disease, the autopsy findings of which. resemble those of piroplasmosis. Evidently the same spirochetes were found by Ziemann in Kamerun in a calf, by Heanley in two Chinese buffalo calves, and by Koch in Daressalam in cattle. 2. Spirochaetes Tschischir, demonstrated by Djatschenko in Kuban (Russia) in the blood, spleen and liver of cattle which were affected with symptoms of an infectious hemoglobinuria. The parasite has the form of a comma or of an ‘‘S’’ and ean te cultivated artificially (Vibrio?). Transmission experiments were negative. 3. Spirochaete Ovina, found by Martoglio & Carpano in Erythtaea simultaneously with endoglobular parasites in a sheep affected with febrile symptoms. It forms threads 10-20 # long, with 4-10 spiral windings; artificially they could not be transmitted. Theiler also reports finding spirochaete in sheep in the Transvaal, and Zie- mann in Kamerun (Dodd considers them identical with the Sp. Theileri). 4, Spirochaete Suilla, found by Dodd in Pretoria in the tissue of superficial ulcers of the skin, which extended over the entire body of hogs (10-14 # long, with 2-6 spiral windings). Material from the ulcers rubbed into the scarified skin of healthy hogs produced a similar skin affection, which under progressive emaciation usually led to death. Similar parasites were found by Cleland in West Australia in fibrous nodules of castration wounds. 5, Spirochaete Equina. Stordy in East Africa found spirillae in very great numbers in the blood of a horse which showed a fatal affection with symptoms of high fever, swelling of the subcutis and emaciation. A similar finding is reported by Stordy in a severely 844 Spirochaetosis in Man. affected pony, whose blood transmitted the parasite to horses, cattle and sheep, and he considers them identical with the Sp. Theileri. Literature. Theiler, J. of Comp. Path., 1904. XVII. 47; Bull. P., 1905. IT. 617. — Djatschenko, Chl. f. Bakt., 1904. XXXV. 737. — Martoglio & Carpano, Ann. d’Igiene sperim., 1904. XIV. 577. — Laveran & Vallée, C. R., 1905, CL. 1515. — Ziemann, Obl. f. Bakt., 1905, XXXVIII. 447. — Dodd, J., of Comp. Path., 1906. XIX. 318. — Heanley, ibid., 8. 322. — Stordy, ibid., S. 226. — Titze, Z. f. Infkr., 1908. IV. 139. (Review with literature). — Knuth, ibid., 1910. VII. 149 (recent lit.). Spirochaetosis in Man. Recurrent fever (Febris recurrens) is known as a spirochetosis and is caused by the Spirochaete recurrentis s. Obermeierei discovered by Obermeier (1868). The affection is mani- fested by severe febrile attacks lasting from 3 to 12 days, and recurring after 2 to 11 days. In most cases lasting recovery results after several febrile attacks. The natural transmission appears to result through the agency of blood-sucking arthropodes, possibly also by insects and lice. According to the most recent observations of Iversen in Russia the disease may be cured quickly and permanently with Ehrlich’s Amidodrsenobenzol. A similar affection in the tropics, the African recurrent fever, or ‘tick fever,’’ is produced by the Spirochaete Duttoni (according to. Koch identical with the above), and is transmitted to healthy man by a tick (Arnithodorus moubata). (Schilling, Mense’s Handb. d. Tropen- krankheiten, 1906, III, 668.) Since the discovery by Schaudinn of fine spirochaetes (Sp. pallida, Treponema pallidum) in the syphilitic organs, syphilis is also con- sidered as a spirochetosis. This view has received material support by the splendid results of Ehrlich’s chemotherapy. Besides a spirochete (Sp. pertenuis) was found by Castellani, as a probable cause of the disease in Framboesia tropica, a skin affection of the tropies which clinically resembles syphilis. (A. f. Schiffs- u. Tropenhyg., 1907, XJ, 22.) STS te Diseases of the Blood and Blood- Producing Organs 1. Anemia. Anaemia... The name anemia designates the absolute diminution of the hemoglobin in the blood without a visible affection of the blood-producing organs and without symptoms of abnormal leucocytes in the blood. These pathological conditions may depend either upon a more or less uniform diminution of all of the constituents of the blood (Oligemia), on the diminution. of red blood corpuscles (Oligocythemia), or on a simple dimi- nution of the blood-coloring matter in the presence of otherwise normal numbers of red blood corpuscles (Oligochromemia). In the majority of cases Oligemia and Oligocythemia are present simultaneously, and in severe cases the water contents of the blood is considerably increased at the expense of the other constituents (Hydremia). Etiology. After profuse losses of blood a severe anemia may develop in a short time, sometimes even in a few minutes (Anemia acuta); thus after phlebotomy, epistaxis, after injury of larger blood vessels, after bursting of aneurysms, after very profuse parenchymatous bleeding (hemoglobinuria, intestinal hemorrhages, ete.), also after severe hemoglobinemia. In the majority of cases the development of the anemia. oceurs slowly and gradually (Anemia chronica). Thus re- peated losses of blood may in time produce anemia. A con- tinuously insufficient nutrition has an important part in the ctiology of anemia. The unfavorable action of the food may become manifested either as a result of an insufficient quantity by feeding foods deficient in proteids or iniron. The effect of a qualitatively insufficient nutrition may be assumed in anemia of sheep (the so-called chlorosis, Cachexia aquosa), which develops when the animals are pastured in marshy moorland pastures, or after failures of crops if the animals are fed in winter in- sufficiently on poor food-stuffs such as beet leaves, ete. In cattle a continuous feeding on food lacking in nutritive ma- terial may also cause severe anemia (Hydremia). Thus the 845 846 Anemia. affection results with relative frequency in cattle kept near alcohol distilleries or sugar refineries (Jost, Hildebrandt, Arloing), where the principal food consists of the very watery (up to 95%) slops, beet shavings or the syrup-like fluid remain- ing after the refining of the sugar. The affection attacks preferably working oxen, which must utilize a part of the other- wise insufficient nutritive substances for the execution of their work; also because they have less opportunity after satiating themselves with food substances abounding in water, to partake of additional solid fodder (Roloff). Horses, sheep and goats become affected from the same cause much more rarely. In this form of anemia toxic substances and acids which form during the storing of these foods apparently have an accessory action. (Arloing attributes the development of the disease exclusively to the action of these substances.) Werner observed anemia and hydremia in hogs in connection with the feeding of watery food. The anemia of sheep and cattle previously mentioned is considered by various authors as an independent affection under the name of chlorosis of sheep, or as hydremia of cattle. This does not appear well founded on account of the fact that these conditions are differentiated from the other forms of anemia only by special etiological factors, the pathological changes corresponding with those of other forms. _ The investigations of, Carré & Bigoteau appear to show that the chronic intoxication of sheep produced by the bacillus pseudo-tuberculosis ovis (Preisz) may result in a hydremic condition of sheep. The keeping of animals in poorly ventilated places as well as lack of exercise, may in itself produce anemia, as is some- times observed in fattening hogs, in milch cows, house dogs, ete. Anemia may develop as a regular symptom in chronic affections with disturbances of appetite or of digestion, or in affections with great loss of proteids (long Jasting suppuration, albuminuria, persistent diarrhea, effusion of copious transudate, exudate, helminthiasis, ete.), or in increased splitting up of proteids (fever, action of bacterial toxins in various chronic infectious diseases, mineral poisons, malignant tumors). Blood parasites may be mentioned as another cause of anemia (piroplasma, trypanosomes, Filaria immitis). The anemia of sucking pigs and young hogs, which has been ob- served by Braasch in Schleswig-Holstein and which caused great losses in some localities, is not yet sufficiently cleared up. This very severe anemia which appears already in the first weeks of life, may be the result of an unnatural keeping of the breeding hogs, but the action of an infectious substance (bacillus pyogenes) cannot be excluded with: certainty. Guittard reported on a disease in chicks which appeared in some localities of France as an infectious anemia with symptoms of severe anemia and weakness, developing soon after hatehing, and resulting in death in a few days. The occurrence of chlorosis in animals is not yet proven. In human medicine a disease is designated by this name, which usually occurs during the period of Etiology, Anatomical Changes, Symptoms. 847 puberty, especially in girls, and is associated with a diminution of the hemoglobin contents of the red blood corpuscles. It subsides after a systemic administration of iron. The affection of sheep designated under this name is, as already men- tioned, not identical with this disease. Anatomical Changes. All organs of animals which have died as a result of hemorrhage are characterized by a con- spicuous paleness and by the absence of blood; this is most readily recognized in the lungs, which appear pale pink in color. At the same time the heart and the large blood vessels con- tain only small amounts of loose blood coagulum. In chronic anemia blood is frequently found in nearly normal amount in the heart and in the blood vessels, but it appears paler, more watery, stains the hand only slightly and contains only little loose gelatinous coagulum. Fatty degeneration of the parenchy- matous organs, especially of the heart muscles and of the kidneys is not infrequent. Dropsieal development is almost constantly found in chronic fatal anemia. Symptoms. The symptoms of acute anemia develop in ac- cordance with the severity of the hemorrhage, sometimes very rapidly, at other times somewhat more slowly. The animals become much depressed, perspire profusely, stagger and sway in walking. The mucous membranes become gradually more and more pale, finally even porcelain white; the heart action is throbbing, the pulse at first frequent, tense and small, later however soft and empty. The respiration is accelerated and labored; a conspicuous cooling off develops in the peripheral parts of the body; there is also muscular trembling. If the animal has lost great quantities of blood within a short time its entire behavior expresses great anxiety, it sways, finally falling to the ground, becomes unconscious and dies in con- vulsions if the bleeding continues. . The symptoms of chronic anemia develop much more slowly and persist for a longer time. The mucous membranes appear very pale, pink colored, in severe cases almost milky or porcelain white. There is languor, easy fatigue even on quiet walking; after prolonged exercise the animals commence to sway and sometimes even fall to the ground. At rest they appear somnolent and indifferent and lie down a great deal. The frequency of the heart action increases considerably, even on very slight external causes. The heart sounds sometimes become imperceptible or indistinct owing to the false sounds; the pulse is at the same time weak. In severe cases slight hemorrhages appear in various organs. Further symptoms of severe anemia are diminished appetite, irregular movement of the bowels, accelerated and superficial respirations, lusterless hair, in sheep dryness and dullness of the wool. The nutrition is at first, and sometimes also in the later stages satisfactory, the anemia however which is caused by organic affections or insufficient feeding causes emaciation. 848 Anemia. Corresponding to the intensity of the affection the blood appears lighter, its hemoglobin content diminished (in the determination with Fleischl’s or Gower’s hemoglobinometer under 70°, in very severe cases even between. 30-40°). The number of red blood corpuscles is diminished and may fall to 3,000,000 to 2,000,000 per cubic millimeter. Besides in severe cases the red blood corpuscles may show a poikilocytosis; that is they are smaller or larger, angular, elongated, supplied with projections, club or biscuit-shaped. Not infrequently, especially in an anemia which has developed rapidly nucleated red blood corpuscles may be found (erythroblasts) in suitably stained preparations (with hemotoxylin-eosin), further in some of the red blood corpuscles basophilic granules, the remains of broken- down nuclei of the erythroblasts are observed. The number of white blood corpuscles is, as a rule, increased on account of the increase of polynuclear leucocytes (in one of the authors’ cases 180,000 white blood corpuscles could be counted per cubic milli- meter of blood). Through these, also as a result of the diminu- tion of the red blood corpuscles, the numerical relation of the two becomes much closer (in one case of anemia caused by the Filaria immitis, the authors observed the relation of red blood corpuscles to the white as 18:1), so that the examination of unstained blood preparations may cause confusion with leukemia. ; As the clinical methods of blood examination give only relative values of a certain volume, the degree of anemia cannot always be established from the number of red blood corpuscles or from the hemoglobin content, especially so since the proportional values may be normal in spite of the present anemia, for instance in the oligemia which occurs exceptionally without qualitative changes of the constituents of blood, as well as in all those cases of anemia in which the animal lost either too much water or had not taken any water, and in which a thickening of the blood resulted in consequence (Wetzl). After a time edematous swellings appear on different parts of the body, on the lower abdomen, lower chest, in the sub- maxillary space, at the lower part of the extremities, being not sharply circumscribed, but flat swellings of doughy consistence. The eyelids may show a pad-like swelling and an effusion may take place into the body cavities. The edematous swellings are especially extensive and prominent after feeding very watery food stuffs, thus in anemias of cattle in sugar factories the swelling may increase to such an extent that it renders the movement of the animal entirely impossible. In this stage of the disease the animals are usually affected with diarrhea, by which they are weakened still more, finally they are unable to stand up and succumb. Jost, Hildebrandt and Moussu have described other peculiar mani- festations in hydremia of cattle in sugar factories. Sometimes the affected animals suddenly collapse during walking, others dic after.a sickness lasting but a few days in the course of a few hours as if struck : by apoplexy. Some are entirely incapable of passing feces as a result, ue Symptoms, Course, Prognosis. 849 of the weakness of the abdominal and body muscles. There is polyuria, in which a very pale watery urine of low specific gravity is passed; sometimes profuse salivation is present. In acute cases the autopsy may reveal a gastro-intestinal inflammation. Course. Great losses of blood may produce death inside of a few hours, or even in a few minutes, while the duration of chronic anemia may extend to several months and even years. This occurs especially in anemia which develops in association with chronic diseases. Ascites of sheep and cattle lasts at least from 3 to 6 months or even longer, but some animals may die in a shorter time. The last mentioned short course may re be only apparent if the first indications escape de- tection. Diagnosis. The recognition of anemia causes, as a rule, no difficulty. It may be confounded, especially on a single examination, with pronounced weakness of the heart and a general collapse of the blood vessels which result also in a conspicuous paleness of the peripheric parts of the body. Simple anemia is distinguished from pseudo-leukemia or from leukemia by the normal condition of the blood-forming organs, and also by the condition of the white blood corpuscles. Fur- ther the milder cases may be distinguished from pernicious anemia by the normal appearance of the blood corpuscles, on the other hand from the severe cases by the absence of giganto- cytes and gigantoblasts, as well as by the severe general affec- tion. In horses infectious anemia should also be taken into consideration. In all cases of anemia however it should be aimed to de- termine the fundamental affections, the recognition of which is of great value from a prognostic and therapeutic standpoint. Prognosis. The acute anemia which develops after great losses of blood terminates with suitable nutrition of the animal almost without exception in a relatively short time in recovery. By the ingestion of large amounts of water the blood attains within a few days its original quantity, the salts and the proteids being rapidly replaced from the food. Only the replacement of the red blood corpuscles requires a longer time, up to several weeks; after exceedingly large losses of blood the recovery may require even several months, and may not follow at all even after suitable treatment. If the animal has lost at least half of the normal quantity of its blood within a short time, there exists no longer any hope for its improvement, The prognosis of chronic anemia depends on the nature of the fundamental affection. In the independent forms how- ever the prognosis depends, not only upon the degree of anemia, ‘but also upon the condition that the cause of the disease ig capable of removal, although under favorable conditions the disease usually terminates in recovery, the course of an already Vol. 1—54 850 . Anemia, existing dropsy can no longer be influenced in spite of suitable care and treatment. Treatment. In acute anemia, if bleeding still continues, the hemorrhage should first of all be arrested; in external hemor- rhage by surgical measures, internal bleedings by the adminis- tration of hemostatic remedies. Most satisfactory are Ergot (15-25.0 or 0.5-2.0 gm. of the extract; 5-10.0 or 0.2-1.0 gm. per os; the extract may also be used subcutaneously in half doses), Ergot i in (1-2.0 or 0.02 to 0.2 gm.) Extractum hydrastis_ (10-15.0 gm. subcutaneously for horses) ; very good results may further be obtained by intravenous injections of adrenalin or suprarenin (1-5 cc. of a solution of 1:1000 per 100 kg. body weight). The transfusion of blood from a healthy animal of the same species can hardly be accomplished in practice, while the infusion of physiological salt solution into the veins (combined with adrenalin or suprarenin), or into the rectum is frequently carried out and may be a life saver. In cases developing less suddenly an increased partaking of water may increase the fallen blood pressure, the ingestion of water should however be permitted only after the cessation of the hemorrhage. Berger always obtained good results by infusions of salt solutions into the rectum (10-20 liters of a 0.6% solution for horses and cattle). The infusion should be made slowly and the rubber tube of the irrigator should be introduced far into the rectum. Flatten, Dorn and Frick constructed suitable appliances for the application of intravenous injections of physiological salt solution, but the infusion may ke carried out in emergency with the aid of a simple rubber tube and funnel. The solution should be sterilized by boiling and then cooled down to body temperature. Albrecht repeatedly injected defibrinated blood drawn from healthy horses under the skin of affected horses. The blood, which was kept at 40° C., was injected in quantities of 80 cc. with the aid of a syringe of suitable size into various parts under the skin of the abdomen and facilitated the absorption by mas- saging the place of injection. In this manner he succeeded in injecting 1% liters of blood under the skin of the abdomen in 3 short time. In all cases of anemia special care must be taken in regulat- ing the diet. The necessary substances for the formation of blood (proteids and nutritive salts) should in the first place be given in increased amounts. Best adapted are nutritious food stuffs (oats, barley, legumin, good hay, meat, ete.), in very weakened animals yolks of eggs, milk, strong bouillon mixed with eggs, in the absence of appetite the animals should be drenched with this food. In primary anemia with normal digestion the purely dietetic treatment alone frequently pro- duces an improvement progressing from day to day and even complete recovery may result in a relatively short time. The food should be given in small rations but frequently. In anemia brought on by feeding food stuffs lacking in nutritive qualities, above all substances saturated with water, recovery may be obtained in such cases which are not very severe, by a suitable change in food, particularly by the substitution of dry foods. An edema which may be present does not require any special treatment. Treatment. 851 Of the medicinal agents iron is first to be considered. The selection of the iron preparations is considerably influenced by its price, otherwise the iron preparation should be adminis- tered for a long time and in not too small doses. Of the numerous preparations employed Ferrum pulveratum (2-5 gm. for large animals, 0.5-1.0:gm. for sheep, 0.02-0.1 gm. for dogs, should be given for a dose three times a day), Ferrum sulfuricum (in same doses) may be mentioned. It is advisable to administer both with stomachics and salines. For drinking water the water in which the red hot pieces of iron are cooled in black- smith shops, may be given. For small animals Ferrum hydr. reductum (0.005-0.01 gm. with sugar in powder), Ferr. lacticum (0.02-0.1 gm.), or Tinct. Ferri pomati (10-20 drops), are suita- ble. In the presence of inappetence a small quantity of hydro- chloric acid should be added to the drinking water. Arsenic (of Fowler’s solution 10-30 gm. for large animals, 2-10 drops ‘for small; 0.1-0.3 gm. or 0.001-0.005 gm. of the arsenious acid) may also be administered, as according to experience it aids metabolism. In small animals the Tablettae ferri peptonati cum arseno sec. Bleyer may be conveniently administered (daily 1 to 3 tablets). Evers treats anemia with Damholid (100 gm. of a fresh solution: subcutaneously for large animals, for. small animals the same amount per os). Literature. Arloing, C. R., 1892. 776. — Berger, B. Mt., 1902. 8. — Braasch, Monh., 1891. II. 59. — Carré & Bigoteau, Rev. gén., 1908. XI, 433, — Dorn, B. t. W., 1906. 433. — Dralle, A. f. Tk., 1886. XII. 71. — Evers, B. t. W., 1905. 201. — Flatten, Ibid., 1906. 697 — Frick, D. t. W., 1904. 253. — Guittard, Pr. vét., 1897. 32. — Hildebrandt, Pr. Mt., 1857/58. 114; 1858/59. 120. — Jost, Ibid., 1857/58. 114. — Petzold, S. B., 1863. 86. — Pflug, W. f. Tk., 1857. 413, — Plate, B t. W., 1906, 713. — Pr. Vb., 1902. IT. 34. — Werner, W. f. Tk., 1897. 186. — Wetzl, Klinische Blutuntersuchungen, Diss. Budapest 1908. 2. Infectious Anemia of Horses. Anaemia Infectiosa Equorum. (Swamp fever of horses, Malarial fever of the horse, River bottom disease, Loin distemper; Infektidse Blutarmut der »Pferde [German]; Anémie infectieuse, Anémie per- nicieuse, Typho-anémie infectieuse du cheval [Carré & Vallée], Anémie pernicieuse ’ progressive, Anémie épizootique [French].) Infectious anemia is a specific infections disease of the horse species which is manifested sometimes as an acute, at other times as a chronic septicemia, and causes a destruction of great numbers of red blood corpuscles. It is caused by an ultra-microscopical microorganism. History. Originally it was without a doubt confounded with the idiopathic simple anemia. As an independent disease it was first de- scribed by Lignée (1843), and almost simultaneously by Charlier (1843) 852 Infectious Anemia of Horses. and Dénoe (1843), and was associated with conditions of feeding, the more so as later Delafond (1851) failed in its artificial transmission. Its infectious nature was first indicated by Anginiard (1859). Later Zschokke (1883) reported several cases of pernicious anemia observed by him in Switzerland, which in part developed as an outbreak, and clinically as well as anatomically completely corresponded with the infectious anemia, the same as the cases observed somewhat later by Fréhner (1886) and Ostertag (1890) in Germany. As a matter of fact Fréhner considered the pernicious anemia of horses even at. that time as an infectious disease. The nature of the disease was cleared up in all details by Carré & Vallée (1904-1906) ; further contributions on the disease were furnished by Ostertag (1907), Marek (1907) and Hempel (1909). Ekwall (1895) described an enzootic anemia of horses in Sweden, which also corresponded with the infectious anemia clinically and anatomically, but its identity with infectious anemia cannot be estab- lished positively for the reason that Brickmann recently (1904-1906) demonstrated parasites in the blood in a similar affection of horses. Occurrence. The disease is observed among horses, al- though other solipeds may be infected artificially, and it is probable that they may here and there become also affected by natural infection. It appears in more or less circumscribed localities, in the first place in marshy places, usually as a disease confined to single or several adjoining premises, and causes considerable economic loss because the disease as a rule leads sooner or later to death. Sporadic cases of the disease may also be observed, namely, through the introduction by newly purchased affected or infected horses, which then under certain conditions may alone become affected, while the other animals of the premises may be spared. In France infectious anemia prevails in the northeastern territories, above all in the entire valley of the Meuse, further in the districts of Aube, Marne, Céte-d’Or, Meurthe-et-Moselle, and was recently observed by Dupas also in Chalons, In some of the localities it causes very great losses, which according to Vallée are estimated for the Department at 200,000 frances annually. ; In Germany the disease occurs less extensively than in the adjoining terri- tories of the infected French districts, especially in Lorraine (Képke, Jarmatz, Ostertag), further in the district of Trier. Hochstein observed it in a horse stable in Bavaria. -In Hungary the disease was established by Marek upon three premises in three different counties. From what was already said it appears that the disease occurs also in Switzerland and probably in Sweden. It was likewise observed in Mexico. To all appearances infectious anemia of horses has a far greater geographical distribution than appears from the data mentioned, only it is frequently confounded with other internal diseases. Thus in certain cases the so-called skalma is probably as a matter of fact an infectious anemia. Etiology. The fundamental investigations of Carré & Vallée, the results of which were later fully confirmed by Oster- tag and Marek, showed that the contagion of infectious anemia belongs to the ultra-microscopical microorganisms. The virus passes the porous (Chamberland-Berkefeld) porcelain filters and cannot be demonstrated by staining methods or by cultiva- tion. Etiology, Pathogenicity, Natural Infection. 8d3 The virus is present in the blood, in the urine and in the feces of the affected, also of the apparently recovered animals. The saliva has no infectious properties (Ostertag). Whether there exists any kind of a relation between infectious anemia and horse pest has not been decided (see p. 286). Tenacity. The virus loses its virulence entirely when heated to 58° C., dry- ing at room temperature does not influence it; thus dry blood serum was found harmless only after seven months (Carré & Vallée). In storing the blood without drying it loses its infectiveness only after three months. The virus resists putre- faction for a long time, even in strongly ammoniacal substances (urine, manure). Thus Carré & Vallée found urine of an infected horse, kept in a manure pit, virulent even after 214 months. : Pathogenicity. The disease may be produced artificially in horses by intravenous or subcutaneous administrations of virulent blood or blood serum, immaterially whether larger quantities (up to 750 ec.) or very small quantities (1 cc.) are injected (Carré and Vallée). The disease of the test animals is indicated by a febrile rise of the temperature, which according to Carré and Vallée always occurs within 5 to 9 days; in one of Marek’s cases however the incubation lasted for 18 days. The disease in test animals rarely develops with the same characteristics as in animals from which the blood has been procured. To produce a successful infection per os, larger quantities (at least 15 cc.) of virulent blood or urine are necessary according to Ostertag, and in such cases the incubation also extends over a longer time, 15 to 24 days. The incubation period may however be shortened by the repeated administration of great quantities of virulent material. Donkeys cannot always be infected (Carré & Vallée, Marek), while other domestic animals, also small test animals are entirely resistant (Carré & Vallée, Ostertag, Marek). Man also resists the in- fection. The experiments of Ostertag. and Marek proved that, after an intestinal as well as subcutaneous or intravenous infection, the disease in test horses not infre- quently runs a chronic course, and aside from periodical rises in temperature, for a long time causes no noticeable disturbances, a condition which deserves notice in transmission tests. Natural infection may occur indirectly through the inges- tion of food or drinking water contaminated by urine or with -feces of affected animals. As the urine and feces always con- tain the virus, but especially. during the febrile attack, and as it is very resistant against outside influences, there is an ample opportunity afforded for indirect infection. The virus is taken up either with the bedding or with the grass in the pasture, or the food may become contaminated by attendants or in other ways, especially in insanitary stables. With the ichor, or more directly with feces or urine, the virus may contaminate the drinking water, for instance by draining from the manure ‘pit or in the pasture. On the other hand a direct transmission does not appear to occur. Carré & Vallée failed in demonstrat- 854 Infectious Anemia of Horses. ing an intermediate action by any parasitic insects. Contrary to this Ries asserts that the infection is transmitted by the larvae of gad-flies or mosquitoes. He failed however to sub- stantiate his contention by experimental proof. Infection only results when either large quantities of viru- lent material are taken at one time, or from the taking of smaller quantities at frequent times. Accordingly the occasional in- gestion of a mouthful of contaminated hay or straw does not appear at all dangerous (Ostertag). Whether the affection which sometimes occurs in the suck- ing foals of affected mares, results from an intrauterine con- tamination or an infection through the milk cannot be decided. The introduction of the disease in previously uninfected premises invariably occurs through newly bought, affected or apparently recovered horses, whose blood however continues to retain its infectiousness (Marek). As long remissions are by no means rare in the chronic forms of the disease, and as in the cases of slow course only very few apparent symptoms are generally noticeable, it happens not infrequently that horses suffering with the disease are offered for sale. Anatomical Changes. The infectious anemia of horses is characterized by the anatomical changes of an acute or chronic septicemia, with visible changes of the blood, in which the changes depending on the duration of the disease may show very pronounced variations. The spleen in acute cases, or in animals which have died during a relapse of the disease, appears considerably enlarged, sometimes double or four times its size. Its capsule is tense and covered with hemorrhages, the pulp is blackish-red, dis- tended, mushy, sometimes even liquefied, as in anthrax. Some- times in the otherwise normal or more or less enlarged spleen, various sized nodulated protuberances are found, which repre- sent softened areas of a blackish-red color. The slower the course the less marked is, as a rule, the swelling of the spleen, while in a very protracted course it may be entirely absent, but in such cases the consistency of the organ is rather some- what increased. All of the lymph glands of the body show acute swelling and a hemorrhagic condition is noted in cases in which hemorrhages have occurred in the corresponding organs; in chronic cases however the lymph glands either fail to show an edematous swelling or it is but slight. Subserous hemorrhages are usually found. In chronic cases however they are not prominent. Hemorrhagic spots up to the size of a silver dollar are especially numerous under the peri- toneum of the cecum and colon, they occur also, but in smaller numbers in other parts of the peritoneum.