dh Ge toi ee N H ‘ Perest tits eat Ae weay Par trey B02 te 00 De ee Rs ate rl eeataent 140 88 Ce ' Tay: Fine eed ae iva ouverts te ta tt A be 5 Nts OEE te AC cata s ACR TOY LD ek Meter ne ESSE Meade ser Oe irite ‘ ‘ eer elie? nar er 20st ae ees ee eiee PP Ss Pe eee Ge eae es ‘ were AE De Sch Sate oer o* ws tyiaaters datotgesee atte Nala ne feprceranes erti ht, rye - ae ee rere ale ppt are trp me bye ty ROUT T. Tide ole Dhebl Chere sulk Yo ye ay ee As + TORONTO OF joy ‘ re to eb ini Sapper pst ten eid Beak UNIVERSIT Ih 1761 Hewes 34 aed a Digitized by the Internet Archive in 2008 with funding from Microsoft Corporation http://www.archive.org/details/animalparasiteshOOchanuoft ANIMAL PARASITES AND HUMAN DISEASE BY ASA C. CHANDLER, M.S., Px.D. INSTRUCTOR IN ZOOLOC x¥, OREGON AGRICULTUR CORVALLIS, OREGON FIRST THOUSAND NEW YORK JOHN WILEY & SONS, Inc. Lonpon: CHAPMAN & HALL, LimitTEep 1918 CopyricuT, 1918 BY Asa C, CHANDLER KE a as T> % > ~~ LZABRAPSNS / \ . w “s * j \\ ( RARD 4N0Cr }) {| MAR 22-1965 I} OZ » . -no0* / iTy oF TO) ¥ 999411 Stanbope [press F. H.GILSON COMPANY BOSTON, U.S.A. To MY MOTHER WHOSE SELF-DENYING LOVE AND UNFAILING DEVOTION MADE MY SCIENTIFIC EDUCATION POSSIBLE PREFACE Ir is the belief of the writer that one of the most pressing needs of the present time is the education of the people as a whole in the subjects of vital importance with which this book deals, and an increased interest in this field of scientific work. Scien- tists are the leaders of the world, and should constantly endeavor to keep a little ahead of the lay population who follow them. It is, however, important that the leaders should not only blaze the trail, but should make it sufficiently easy to find so that the followers may not fall too far behind. In the intense fascination of exploring the trail, and the eager impulse to press on to newer and ever newer fields, the scientist is in danger of forgetting the handicaps of his followers, and of leaving them hopelessly in the rear. Popular ignorance of many important facts of parasitology and preventive medicine, even facts which have been common bases of operation for scientists for many years, is deplorable. To a large extent, however, the scientists themselves are to blame, for in their enthusiasm for discovery they have forgotten to make it possible for the laity to reap the benefits of their investigations. There is even a tendency to belittle the efforts of those workers who devote their energies toward assisting the general public to keep in touch with scientific progress. - A book or paper which collects the work of others, models it into a connected whole, and makes readily available what before was widely scattered and accessible only to a skilled “library-prowler,” is stigmatized by the term ‘mere com- pilation.”” It is the firm belief of the writer that this is not only unjust but unwise. No less mental and physical energy, if not perhaps even more, is necessary for efficient ‘‘ mere com- pilation ”’ than for the addition of new facts to scientific knowl- edge, and the value to civilization, which must be the ultimate criterion by which all scientific work is judged, must be equally as great, if not greater. The value of connecting related facts is twofold: it helps to keep the world in general somewhere nearly abreast of the times, and it is a distinct aid to further Vv vi PREFACE progress. Having the courage of his convictions along these lines, the writer has spent much time which he might other- wise have spent on original research in the compilation and popu- larization of the subject matter of this book. It is the aim of this volume to present the important facts of parasitology, as related to human disease, in such a manner as to make it readable and useful not primarily to the parasi- tologist, but to the public health and immigration service officers; to the physicians who are concerned with something more than their local practice; to teachers of hygiene, domestic science or other subjects in which health and preventive medicine are im- portant; to college and high school students; to the traveler; and to the farmer or merchant who is interested in the progress of science and civilization. It is the hope of the author that this book may not only be a means of making available for the laity facts which may and probably will be of direct importance to them at one time or another, but that it may also be instru- mental in arousing the interest of more students in this branch of science, to the ultimate end of enlisting a larger number in the ranks of its workers. No attempt has been made in the following pages to give detailed descriptions of parasites, or to go further into their classification than seemed necessary to give a correct conception of them. Likewise discussions of correct scientific names and synonymy have been entirely omitted, since, important and interesting as they may be to a parasitologist, they are of no interest to the lay reader. An attempt has been made to use scientific names which are most generally accepted as correct, except that in cases of disagreement between American and European usage, the American name has been used. In cases where some other name than that adopted in this book has been or is still in common use, it is given in parenthesis to afford a clue to the literature associated with it. The endeavor to avoid repetition in the discussion of certain parasites in one chapter, and of their transmitting agents in another, has often presented difficulties, since some facts might - equally well be included in either place. As far as possible these facts have been given in the place where the author has felt that they would most often be sought, but mistakes have undoubtedly been made, and furthermore what one reader would PREFACE Vii search for under “ malaria,” for instance, another would seek under “ mosquitoes,” and vice versa. For this reason frequent cross-references are given. As far as has seemed advisable, without too greatly encumber- ing the text with round-about phrases, scientific terms have been omitted or if used have been explained. It is difficult to keep constantly before one the unfamiliarity with even everyday scientific terms of many readers for whom this book is intended, but an earnest attempt to do so has been made. In the text the author has purposely refrained from citing references and from mentioning more than a few names of in- vestigators. It obviously would be impossible to give refer- ences, or even to mention more than a small per cent of the thou- sands of contributors to the material here assembled without making the text cumbersome and unreadable, especially for the readers for whom the book is especially prepared. Only a few of the leading figures in the history of each group of parasites have been mentioned; other citations would have meant a more or less arbitrary selection of a few from among many, which must inevitably result in injustice. For similar reasons no bibliography is given. Instead, the author has prepared a list of “‘ Sources of Information ”’ which includes the names of all the leading periodicals in which im- portant articles on parasitology have appeared or are likely to appear, and a list of books which cover all or a portion of the field of parasitology in a comprehensive manner. In these books will be found bibliographies; most of the references cited in these bibliographies will be found in the magazines or papers listed in “‘ Sources of Information ”’ and this list will aid any- one interested in pursuing the subject farther to keep in touch with the new work which is constantly appearing. The author has felt that more real value would attach to such a list than to a list perhaps 50 times as long and yet inevitably incomplete, containing exact references to particular articles. The illustrations, with two or three exceptions, have been drawn by the author either from specimens or from illustrations of other authors. Pen and ink drawings have been used con- sistently in place of photographs since it is believed that such drawings, if carefully done, are far more valuable for scientific purposes than are photographs. The trained eye is able by Vill PREFACE voluntary concentration on certain parts, and inattention to others, to see much more than can a camera, which has no such power of adjustment. A pen and ink drawing can, therefore, represent more accurately what can be seen by the eye than can a photograph. The author has received valuable advice re- garding the illustrations from Mr. A. J. Stover, scientific il- lustrator at the Oregon Agricultural College, and wishes to take this opportunity to express appreciation for it. Deep appreciation is felt for the invariable willingness with which authors, editors and publishers of scientific papers and books have given permission to copy illustrations. Special mention should be made, however, of the generosity of Sir Patrick Manson and of the American publishers of his “‘ Tropical Diseases,” Wm. Wood and Co.; of Dr. A. Alcock, author of “ Entomology for Medical Officers”’; of Professor Wm. A. Riley and Dr. Johannsen, authors of ‘‘ A Manual of Medical Ento- mology,” and of Dr. A. W. Sellards, who, in the absence of Dr. Strong, lent photographs taken in Peru by the Harvard School of Tropical Medicine. The illustrations taken from the journal Parasitology have been especially numerous, and mention should, therefore, be made of the unreserved permission to use them given by the editor, Professor G. H. F. Nuttall. Many illus- trations of worms have been taken from the work of two of the real pioneers in the study of helminthology, Professor Karl Leuckart of the University of Leipzig, under whom many of the present parasitologists were trained, and Professor Arthur Looss of the University of Cairo in Egypt. It is a high tribute to the work of Professor Leuckart that many illustrations published by him in the first comprehensive work on the animal parasites of man, in 1863, are still the best available ones and will be found reproduced in the majority of modern works on the subject. Particular appreciation is felt for the assistance received from three publications which contain reviews of current literature in particular phases of medical zoélogy, namely, the Tropical Diseases Bulletin, which reviews practically all current work on protozoan parasites and helminthology, the Review of Applied Entomology, Series B, containing abstracts of nearly all work on medical and veterinary entomology, and the Journal of the _ American Medical Association, which gives references to all PREFACE _ ix articles in the leading medical journals of all countries, and reviews many of them. Any of these periodicals will be lent by the Association library, at the average cost of postage, to any member of the Association. These three publications, on account of their scope and thoroughness, are of inestimable value to anyone who attempts to keep pace with the progress of the medical sciences. There are, however, few if any of the journals or books listed under ‘‘ Sources of Information ”’ which have not been drawn upon either for illustrations or infor- mation or both. All of these, collectively, have made this book possible, and to them, and to the workers who contribute to them, are due, therefore, not only the thanks of the author but also the thanks of everyone who may profit in any way by this book. The writer is very deeply indebted to the authorities who have been kind enough to read the manuscript, and who have freely given the benefit of helpful suggestions and criticisms. Pro- fessor Gary N. Calkins, Professor of Protozodlogy at Columbia University, Dr. B. H. Ransom, Zodlogist of the U.S. Bureau of Animal Industry, and Dr. L. O. Howard, Chief of the U. S. Bureau of Entomology, have helped materially to round off the rough corners, and fill in the chinks, of the sections on Pro- tozoa, “‘ worms,” and arthropods, respectively. Hearty thanks is also due my wife, Belle Clarke Chandler, for the invaluable assistance she has given by her constant and efficient codperation in the editorial part of the work. TABLE OF CONTENTS Cuap. Paces NERBIIN TROD UCTION Tas Veit asc cts sess ccs ui chee. eae 1-11 LRPPARASTORSEIN (GENERAL. ...2..-.5...050...0-..05.0.. 12-25 PART I. PROTOZOA TiS IincRODUCTION TO) PROTOZOA........:........:4-50..: 26-37 WW ARR SETR OCHIANDE Seite yeu cinc setae ceces-s cols vondi he noolecs oon cacy 38-73 Eve lens MM CVCl meger sts e208 Sf. o\ 0d vials ake eO 42-48 SAOLOILNS ool ciidate "es Scr cache ee 48-62 WERE LS :S'o oS 6 BS LAS Ce re, tee te ay aia 63-65 inieCHOUS JewinehGas 5454 soos oomeoboudaeamesssesne 65-69 at DItepUCVeCIMM ane feo sce Mb ae ed 69-70 WtheropirochssterDiseases. .-... ... kaos aces eto. 70-73 V. LrisHMan Bopies AND LEISHMANIASIS................ 74-92 alla azar mean srteohs, Toss macs Sy ton Sei) cee 77-82 Intantl emtallaravanters 5 of an inch) in length, and thus being visible to the naked eye. Its body is oval and en- tirely covered with cilia, and at the anterior end there is a gash- like slit leading to the mouth or ‘ cytostome ” (Fig. 34, cyt.). The large bean-shaped nucleus (Fig. 34, n.) lies near the middle of the body and near each end is a pulsating cavity or contractile vacuole (Fig. 34, c¢.v.) which excretes waste matter. These parasites multiply by transverse division, often so rapidly that the animals do not have time to grow to full size and so become very small. When ready to leave the body they form an oval cyst about themselves. Sometimes two occupy a single cyst (Fig. 34B), and later fuse together. Since the ciliated bodies of the protozoans can be seen, under a microscope, inside the large transparent cysts, their identification is not difficult. The cysts can exist outside the body for a long time, awaiting an opportunity for reinfection. BALANTIDIUM COLI 127 Balantidium swims about in the contents of the large intestine devouring particles of fecal material. As long as the animal confines its activities to this, no ill effects result, but it also has the power, like Endameba histolytica, of invading the tissues and causing ulceration, perhaps after an injury from some other cause has given an opening for invasion. Although many in- fected persons do not show any dysenteric symptoms, these are likely to appear at any time. When they do appear, they are of a very serious nature, and cause a high mortality. On post mortem examination the large intestine is often found in a hor- rible condition, ulcerated from end to end, with shreds of muti- lated or dead tissue hanging from the walls. Unfortunately there is no specific treatment for balantidial dysentery as there is for the amebic disease. In some cases emetin and alcresta ipecac (see p. 135) have caused a disap- pearance of the parasites, but these are not reliable remedies. Salvarsan and methylene blue have also been recorded as suc- cessful in some cases. Organic compounds of silver seem to have some value in destroying Balantidium, and there are other drugs and herbs of much local fame which are undoubtedly sometimes effective. Rest and care of the general health are always required. Prevention of balantidial dysentery consists not only in the sanitary disposal of human feces, as in the case of other human intestinal protozoans, but also in the proper care of hogs, since Balantidium is a common parasite of these animals, and is probably normally a hog parasite. A large proportion of hogs are infected in almost all warm and temperate countries, and it is nearly always in hog-raising countries, and in places where there is too close association between hogs and man, that balantidial dysentery occurs. Around Manila, where the disease is fairly common, the majority of the hogs are infected and pass encysted parasites in their feces almost constantly. In Colombia the disease is found only in those altitudes where hogs are raised and among those who raise them. CHAPTER VIII AMEBZ: Toss of us who have had an opportunity, in studying micro- scopic life in water, to observe the restless movements of the tiny bits of naked protoplasm which we call amebe, having watched them slowly creep along the surface of a slide, extending a portion of the body as a finger-like projection or ‘ pseudo- podium ” and then allowing the rest of the body to flow up to the new position; having seen them creep up on tiny protozoans or other single-celled organisms and devour them by merely wrapping themselves around them, thus engulfing them in an improvised stomach; and having seen them propagate their kind by simply constricting in the middle and dividing in two; — those of us who have observed these acts on the part of such tiny and simple animals have come to be fascinated by them and to like them, and find it hard to realize that certain species are ‘nstrumental in causing some important human diseases. Amebz are found almost everywhere in water, soil and carrion. They have even been found recently to exist in large numbers in the sunbaked sands of the Egyptian deserts, lying dormant in their cysts which protect them from evaporation, ready to emerge and resume an active life when they become moistened. In view of the wide adaptability of these animals it is not surprising to discover some living as parasites, finding congenial surround- ings in the bodies of higher animals. Classification. — Amebe are protozoans belonging to the sub- class Sarcodina, a group characterized by a body without a cuticle, though sometimes protected by a shell or cyst wall, and by their peculiar method of locomotion. In the adult form they have neither flagella nor cilia, but simply outgrowths of proto- plasm, called pseudopodia. In the amebe and their close rela- tives the pseudopodia can be projected anywhere on the surface of the body, now here, now there, though the number, form and activity of the pseudopodia are quite different in different species. 128 PARASITIC SARCODINA 129 The life history also varies in the different species, many possess- ing a flagellated stage. On the basis of life history and habits the old genus Ameba has been broken into a number of genera, seven according to Calkins. Of these only three occur as para- sites of man. The amebe which are especially adapted to live as parasites in the bodies of animals belong to at least two distinct genera, Endameba and Craigia (or Parameba). Endameba includes amebz of large size which are not readily distinguishable from the free-living genera except in their parasitic manner of life and by the fact that they will not grow in pure cultures. Craigia includes parasitic species of amebze which, like some free-living forms, pass through a stage in which they possess flagella and resemble true flagellates. In addition to these, the genus Vahlkampfia includes species which may tempo- rarily live as parasites in man if accidentally swallowed. They are minute in size, nor- mally free-living, and have no flagellated stage of devel- opment. A few species are Fic. 35. Chlamydophrys stercorea, show- true parasites of eold-blooded ing portion of protoplasm of body (prot.) 2 : and slender anastomosing pseudopodia (ps.) animals. Belonging to the protruding from transparent shell (sh.); n., Sarcodina also, but not nucleus. x 300. (After Schaudinn, from ? Doflein.) closely related to the amebe, is a peculiar parasite, Chlamydophrys stercorea (Fig. 35), found in freshly passed feeces of a number of animals, including man. It has a transparent glassy shell of pseudochitin, through the mouth of which it protrudes its slender pseudopodia. The number of distinct species of Endameba which live in the human body is still a matter of dispute. Due largely to the work of Darling in disentangling the species of amebe only two are now usually recognized as habitually inhabiting the human intestine. One of these, EH. coli, is a very common but ap- parently harmless resident, while the other, EF. histolytica, is a bandit of the first order, and the cause of amebic dysentery and liver abscess, diseases of great importance in tropical countries. 130 AMEB Possibly Endameba coli will prove to be a group of related species instead of a single species. In Brazil, for instance, Aragaéo has described an ameba very similar to £. coli in some respects, but with certain constant differences, which he named E. brazilien- sis. A small ameba, Vahlkampfia lobospinosa (Fig. 36), usually supposed to be identical with the free-living fresh water species, is often found in the large intestine and in feces, probably having been ingested in cyst form with food. It does no damage whatever. In our mouths several species find a congenial environment, and one, E. gingivalis (buccalis), is very common and is thought by most workers to be at least indirectly connected with pyorrhea, which, next to decaying teeth, is probably Fic. 36. Vahlkampfia : ese lobospinosa (whitmorei), the commonest human disease. FE. gingivalis ce. v., contractile vacu- also attacks the tonsils, and is probably ole; n., nucleus. X 1300. -_ j. : : : (After Whitmors) indirectly the cause of certain kinds of goitre. Another species of ameba, which has only rarely been found, is LZ. mortinatalium. It has been observed in various organs such as the liver, kidneys and lungs of syphilitic infants and in two eases in the parotid glands of non-syphilitic infants. Syphilis seems to serve as a favoring circumstance for this species. On account of its rarity this ameba is not of such importance to the human race as FE. histolytica or E. gingivalis, though apparently very destructive when it does occur. Another species, 2. wrogenitalis, has occasionally been found in the urogenital tract, being voided with the urine. Two species of Craigia live as intestinal parasites of man, and cause a type of dysentery closely resembling that caused by L. histolytica. Amebic Dysentery Importance. — One of the most serious menaces in the tropics is dysentery; people who have always lived in temperate countries have no conception of the severity of this ailment. In many tropical countries dysen ery ranks next only to malaria as a cause of death, and very often it finishes the work of such diseases as malaria, kala azar, and other fevers. When the American troops occupied Vera Cruz in 1914 they found dysentery one of the chief causes of death among the Mexican population. The occu- TYPES OF DYSENTERY 131 pation of the Phillipine Islands was accompanied by a frightful epidemic of dysentery among the American soldiers, and until the city of Manila was cleaned up it was a veritable pest hole for the disease. There are many different types of dysentery, especially in the tropics, each showing somewhat different symptoms and having to be treated in different ways. Some cases of dysentery’ are due merely to improper diet, some to disturbances of the digestive tract due to other diseases, and the majority to intestinal para- sites of some kind, either bacteria, protozoans, or worms. Ina restricted sense the term “‘ dysentery ”’ is used for intestinal dis- eases caused either by bacteria or protozoans. The diseases caused by protozoans other than amebz are discussed in the chapter preceding this. “ Bacillary Dysentery ” is a bacterial disease and need not be discussed here except in comparison with the other types of dysentery. It occurs in temperate as well as in tropical countries and is very common in epidemic form in armies, prisons and asylums. Amebic dysentery, on the other hand, is uncommon outside of warm climates but is endemic in local areas in almost all tropical and subtropical countries. In some districts 85 per cent of all dysentery is caused by amebxe. Amebic dysentery is common on the Gulf Coast of the United States, and endemic cases probably occur throughout the United States, since numbers of cases are on record from such northern states as Minnesota and Iowa, though apparently not introduced directly or indirectly from more southern localities. Since the beginning of the European war amebic dysentery has become fairly common in France. The so-called ‘trench diarrhea” is often amebic dysentery. Unlike the bacterial disease it does not give rise to extensive epidemics in places where it is not normally found. The role played by amebe in dysentery was in doubt for a long time. The presence of amebe in perfectly healthy indivi- duals, and the fact that amebz grown in artificial cultures would never cause dysentery experimentally, confused the problem. As said before there are species of ameba, especially Endameba coli, which, though closely resembling the real villain, H. histo- lytica, live in the human intestine apparently without doing the slightest damage. Neither ZH. coli nor E. histolytica will grow on cultures, the cultured amebe being distinct from either, and quite incapable of damaging the intestine. Walker and Sellards 132 AMEB® ‘arried on a long series of experimental feedings with amebe of various species and largely as a result of their work the true facts of the case have been unraveled. They proved the harmlessness of Endameba coli and also showed that E. histolytica and E. tetragena, long considered distinct species, are really two phases of a single species. The Dysentery Ameba. — The dysentery ameba, F. histolytica (Fig. 37), is large and active, 25 to 40 u (qolog to gto Of an inch) in diameter, with a rather trans- parent appearance and blunt pseudopodia. The distinct clear outer layer of protoplasm and very indistinct eccentri- cally placed nucleus, together with the presence in the body of vacuoles and particles of red blood corpuscles in process of digestion, are its distinguishing Fic. 37. Endameba_ histolytica, living characteristics. A comparison specimen showing ectoplasm and endo- of the vegetative form with plasm, and several ingested blood corpus- = coe E cles. x 1000. that of EH. coli is shown in Fig. 388A and B. There are two stages in the life history of this ameba, the vegetative and the cystic. As long as conditions in the intestine are favorable for their growth and development, the amebe con- tinue in their active vegetative condition, multiplying by simple division of the body into two. When conditions have become unfavorable for them, however, as in later stages of the disease, they decrease in size down to seven or eight pw (about 3x55 of an inch) in diameter, become round in form, and begin to develop a tough cyst wall around themselves. This is known as the pre- cystic stage (Fig. 39). From this stage they pass rapidly into the cystic stage by the completion of the cyst wall and the divi- sion of the nucleus into four daughter nuclei, thus forming the well-known “‘ tetragena”’ cysts (Fig. 38A’), long supposed to belong to a distinct species. Examined under a microscope they look like tiny globules with a mother-of-pearl reflection. These cysts can readily be distinguished from those of Endameba coli in that the latter usually have eight nuclei instead of four (Fig. 38B’). The cysts may remain in the intestine for a long time, MODE OF INFECTION 133 but they are eventually passed out with the feces. Unlike amebe in the vegetative stage, the encysted amebe are resistant to drying and may live for at least a month in dried or partially dried feces if not exposed to direct sunlight. They are not, how- Fic. 38. Comparison of Hndameba histolytica and E. coli. 1500. A, EB. histolytica, vegetative stage; note small indistinct nucleus (n.), clear ectoplasm (ec.), ingested red corpuscles (c.) and contracticle vacuole (c. v.). B, E. coli, vegetative stage; note large distinct nucleus (n.), indistinctness of ectoplasm, com- mon absence of ingested food materials and of contracticle vacuole. A’, E. histo- lytica, cyst; note small size (10-14 yw), four nuclei (n.), and ‘‘chromidial body”’ (chr.). B’, EH. coli, cyst; note large size (15-20 uw), and eight nuclei (n.). ever, so resistant to drying as are the cysts of many free-living amebe. In this condition the amebe may be blown about by the wind, may contaminate garden vegetables where ‘ night-soil”’ is used as fertilizer, or may be carried on the feet of flies. If by any of these or other means they reach human food or water and thus Fic. 39. _ Preeystic : A stage of EH. histolytica, secure entrance to the digestive tract, the .jmetimes mistaken for cyst wall is dissolved by the pancreatic juice, 2 distinct species and and four little amebz, each containing one of ue ee ee the daughter nuclei which were formed when Penfold.) the cyst first developed, are set free in the intestine and begin to grow and multiply. The active vegetative amebe from an acute case of dysentery are destroyed in the stomach if swallowed, and cannot reach their feeding grounds in the large intestine; 134 AMEB only the parasites in the encysted stage, with an enclosing capsule to protect them from being digested, can reach the intestine and cause disease. The Disease. —In the experiments made by Walker and Sellards in feeding ameba-infected material to animals and human volunteers, dysentery symptoms appeared in from 20 to 94 days, averaging about two months. The most marked symptom is an acute diarrhea in which the stools consist largely of blood and mucus. In a typical case from Alabama a patient passed as many as fifteen or twenty stools in an hour. This condition had been going on for years, recurring about three or four times a year, lasting a month at a time. In the intervals between these attacks the symptoms were mild and the patient passed only two or three stools a day. Sometimes the attacks are more regularly chronic, or may recur at long intervals. Often the dysentery is accompanied by evening fever and anemia from loss of blood in the bowels. Instead of producing ulcers on the mucous surface of the large intestine such as occur in bacillary dysentery, the amebe work deeper into the muscular linings of the intestines. Local swellings first appear, followed by an ulceration of the mucous membrane. This produces a portal for the entrance of the amebe to the tissue underlying the mucous membrane, and here they make extensive excavations. The lesions are most common in the upper half of the large intestine but can be found from the lower part of the small intestine to the rectum. The exposed ulcera- tions vary from the size of a pinhead to that of a silver dollar, their ragged edges tending to roll into the crater-like areas. Often the tunnel-like excavations under the mucous membrane connect with one other. Liver abscess is a common result of infection with Hndameba histolytica. Often these abscesses are of large size, filled with a slimy and somewhat bloody chocolate-colored pus. Over a quart of such pus has been removed from an amebic liver abscess. The parasites are found at the edges of the abscess, eroding more tissue and enlarging the pus cavity. How they reach the liver to do their damage is not certainly known, but it seems probable that they bore into bloodvessels in the walls of the diseased large intestine and are carried by the portal vein to the liver, where they find a fertile feeding ground. TREATMENT OF AMEBIC DYSENTERY 135 Treatment and Prevention. — One of the greatest discoveries in the field of medical treatment since the production of salvar- san by Ehrlich is the discovery of emetin as a specific poison for amebe. Emetin is an alkaloid substance prepared from ipecac, the extract of the roots of a Brazilian herb. It was long known that ipecac sometimes had a very marked effect on dysentery, but since amebic dysentery has only recently been differentiated from other forms very variable results were obtained from its use. Ipecac has a decided disadvantage in that it causes violent vomiting, but its alkaloid, emetin, in the form of emetin hydro- chloride, while possessing all the amebicidal properties of ipecac, can be used in the form of injections into the veins, and therefore does not cause vomiting. Experiments with cultural species of amebe showed that emetin (emetin hydrochloride) is destructive to amebe when diluted 500,000 times, and the intestinal amebe on a microscope slide become round and motionless and ap- parently dead when subjected to this very dilute solution. Emetin is given in hypodermic injections. Almost without exception the effect of the drug on the disease is certain and rapid. Severe cases which have been running on for years can be cured in four or five days by this simple treatment. One of the chief disadvantages is that the treatment is often discontinued too soon. The dysenteric symptoms disappear as if by magic and the patient is often not willing to be subjected to continued drug injections until every trace of the amebe has disappeared. Emetin is powerless against encysted amebe and an apparently cured patient may continue to harbor and scatter these dangerous microscopic particles of living matter for some time, thus en- dangering other members of the community. It is probable that self-infection from the remaining cysts is the cause of the fre- quent cases of recurrence of amebic dysentery after inadequate treatment. Under continued treatment the cysts gradually dis- appear from the intestine, but their exodus is hastened by purges. Bismuth subnitrate has been used with good success in con- junction with emetin, the bismuth acting as a sedative on the intestine and aiding in the healing of the lesions, and also as an amebicide. Another aid to the efficiency of emetin is a daily enema of saline salt solution, since this tends to eliminate the bac- teria which are apparently necessary for the welfare of the amebe. Another preparation of emetin, alcresta ipecac, is effective 136 AMEB against dysentery amebz, though not so certain in its action as the hydrochloride. It has an advantage in that it can be taken in the form of tablets when a physician is not available and the apparatus for hypodermic injection is not at hand. Some doc- tors in southern United States have advocated the use of extract of a common southern plant, Chaparro amargosa, to destroy in- testinal amebx. This extract is very cheap and entirely devoid of danger in ordinary doses, but its use in place of emetin has not yet been sufficiently justified. Walker and Emrich have recently (1917) reported the suecess- ful use of oil of chenopodium for treatment of mild cases of amebic dysentery, and especially of “ carriers.”’ It is pointed out that emetin in its various forms is often inefficient in treatment of carriers on account of its powerlessness against encysted amebz and its inability to eliminate them. These investigators em- phasize the importance, before giving the oil, of a preliminary purgation with Epsom salts (magnesium sulphate) sufficient to produce fluid bowel movements, the purpose being both to re- move excess feecal matter from the intestine and to bring the amebe out of their protective cysts and subject them in the unencysted condition to the action of the chenopodium. The treatment found most effective by Walker and Emrich is as follows: (1) magnesium sulphate, from one-half to one ounce, at 6 a.m.; (2) oil of chenopodium, 16 minims in gelatine capsules (to obviate disagreeable odor and taste), at 8 A.M., 10 A.M. and 12M., and (3) castor oil, one ounce, containing 50 minims chloroform, at 2 p.m. This or any other treatment should be followed by examination of the feeces at intervals for some weeks after treat- ment, to make certain of the cure. The keynote to the prevention of dysentery whether it be caused by amebe or other protozoans or bacteria is sanitation. The efficacy of sanitary measures was well illustrated by the fact that during the first month of the occupancy of Vera Cruz by the Americans in 1914 there were four times as many cases of dysentery as during the second month when sanitary measures had been taken and were enforced. The fact that only the en- cysted parasites as found in the fresh or dried feces of infected individuals can cause disease suggests a simple remedy in the proper disposal of infected feeces. In tropical countries, however, such a preventive measure is not so simple as it sounds. In CRAIGIASIS 137 many districts where amebic dysentery is endemic the first rudiments of sanitation are unknown and every possible method of transmission of amebic dysentery is given full opportunity. Polluted drinking water, uncleanliness, transmission by flies, and the almost universal use of “ night-soil’’ (human feces) for fertilizer, all help the cause of dysentery and account for its prevalence. The segregation and cure of dysentery patients, and the care- ful disposal of their feeces, is not enough to eradicate the disease entirely since there are many immune carriers of the disease who, though apparently well, harbor the encysted amebe in their feces and thereby constitute a source of danger to the community. It is estimated that in the tropics about ten per cent of infected persons show no marked symptoms. Thorough sanitation throughout the community is the only preventive measure which is adequate. Still another factor in the distribution of dysentery amebz is the rat. Dr. Lynch of Charleston, S. C., discovered that in that city rats suffered from amebic dysentery as well as man. The fact that rats became infected by eating infected human feeces, the frequent occurrence of the disease in rats in houses where human amebic dysentery has occurred, and the ready transmission of the disease from rat to rat indicate that the rat infection is identical with that in man, and is not due to the ameba peculiar to rats, H. muris, and that rats may play an important role in the spread of the human infection. It may be that rat destruction will prove to be an important preventive measure against amebic dysentery. Craigiasis Closely related to amebic dysentery in cause, symptoms, treatment and prevention is a form of dysentery caused by amebe of the genus Craigia (or Parameba), and hence called “ craigiasis.”” The parasite of this disease was discovered by Captain C. F. Craig, of the United States Army, in the Philip- pines a few years ago, and named by him Parameba hominis, a name which was later changed to Craigia hominis. A nearly allied species, C. migrans, was discovered by Barlow in natives of Honduras. Cases of infection with one or the other of these parasites have also been reported from southern United States, 138 AMEBZ and it is not improbable that they will prove to be of wide geo- graphic distribution, and often mistaken for Endameba or flagel- lates, according to the phase of existence in which they are observed. The Parasites.— As already remarked, Craigia resembles some of the free-living soil amebe in that it passes through a flagellated stage, but it differs from them in having only a single flagellum instead of two. Briefly the life history of Craigia hominis (Fig. 40A to F) is as follows: the adult form (Fig. 40E), resembling a typical ameba, is about half the size of the dysentery Fia. 40. Life cycles of Craigia. C. hominis (A to F). A, swarmer just escaped from cyst; B, young flagellated form; C, mature flagellated form; D, same, dividing; #, amebie form before encystment; F, cyst with swarmers. ; C. migrans (G to L). G, swarmer just escaped from cyst; H, young flagellated form; J, mature flagellated form; J, amebic form developed by transformation from J, without any multiplication; K, mature amebic form, ready to encyst; L, eyst with swarmers (note larger size and smaller number of swarmers than in C. hominis). 1000. (After Barlow.) ameba (10 to 25 pu (zz'59 tO too Of an.inch) in diameter), and when moving exserts several blunt pseudopodia. In addition to the nucleus it possesses a structure, possibly a parabasal body, which appears as a bright glistening object in the living animal and stains deeply with nuclear stains. The animal multiplies by simple division for a time, but eventually encysts, rotating on its axis during the process of forming the double-walled cyst. When fully developed the cysts (Fig. 40F) are considerably larger than those of the dysentery ameba (15 u (y/o of an inch) in diameter) and contain about 40 round refractive bodies, which CRAIGIASIS 139 later escape from the cyst and develop into little flagellated or- ganisms called “ swarmers”’ (Fig. 40A and B). These grow to several times their original size (Fig. 40C), multiply a few times by simple division (Fig. 40D), and finally lose their flagellum and pass again into the ameboid stage. C. migrans (Fig. 40G to L), as described by Barlow in Honduras, where C. hominis also exists, differs in that each flagellate on attaining full development passes directly into the ameboid form without first multiplying. The swarmers (Fig. 40H) are larger and fewer in number than are those of C. hominis, and the adults (Fig. 40K) average a slightly larger size. . The Disease. — Barlow describes craigiasis as he found it in Honduras as more insidious in its development than amebic dysentery and not so distressing in its early stages, but ulti- mately quite as dangerous a disease. The symptoms — diar- rhea with bloody and mucous stools, loss of appetite, abdominal pain, etc.,— are quite similar to those of amebic dysentery. In Barlow’s experience liver abscess is even commoner in craigi- asis than in amebic dysentery. The disease is looked upon as more dangerous to the community than amebic dysentery because of the larger per cent of healthy carriers, who, though showing no marked symptoms for years, may be a constant means of spread- ing the infection. The usual source of infection is believed to be polluted water. Treatment. — Although emetin is as destructive to Craigia as it is to other amebe, injections of the hydrochloride are not so effective as in amebic dysentery since only the tissue-dwelling ameboid forms are reached by the emetin in the blood, while the free-swimming flagellated forms escape. Complete and rapid cure is best effected by combined treatment with emetin injected into the blood and ipecac taken by mouth, accompanied by occasional flushing of the bowels with saline laxatives or enemas to remove the cysts. The same preventive measures used against amebic dysentery are applicable to craigiasis. The Mouth Amebe The fact that our mouths are inhabited by amebz of several species has been known for many years, but only recently has much interest centered in them, this interest being due to the 140 AMEB® belief of a number of investigators that the common ameba of the mouth, Endameba gingivalis (buccalis), has a pathogenic effect, and is the cause of pyorrhea. Although amebe have not yet proved to be the direct cause of any diseased condition of the mouth, yet this direct relation has been shown recently to be by no means impossible, and an indirect relation is very probable. Pyorrhea, or Rigg’s disease, in some stage afflicts the majority of all adult people, and over 50 per cent of all permanent teeth which are lost are lost as the result of pyorrhea. The apparent relation between this disease and the presence in the mouth of the above-mentioned ameba, E. gingivalis (buccalis), was first demonstrated in 1914 by Barrett, and since then the relation- ship between the disease and the amebz has been so well estab- lished that there can be little doubt of it, except as to whether the amebze cause the disease directly by destroying the tissues or in- directly by injuring the tissues and facilitating the entrance of bacteria. The prevalence of amebe in the mouth, even in young children, is well shown by a recent investigation by Anna Wil- liams of the mouths of over 1600 school children in New York City. Of the children between five and seven years of age 35 per cent were found infected, while of those between five and 15 years 60 per cent were infected. The ameba, EH. gingivalis, which does the damage can be ‘shown up” by placing a bit of the pus from a tooth pocket on a microscope slide. Here the villains will be found in the midst of their wreckage. They are from one to three times the diameter of the pus cells, usually from 12 to 20 uw (gol5m to ys'y0 Of an inch) in diameter, and have a granular appearance; the nucleus is rela- tively very small. Often when stained they show dark bodies inside of them which are probably the nuclei of other organisms or of semi-digested pus cells. When living the amebe prowl about sluggishly, pushing out a blunt pseudopodium now on one side of the body, now on the other, then drawing up the body, and pushing out more pseudopodia, thus slowly working their way about between the pus cells and fragments of tissue. The outer layer of the body, or ectoplasm, which serves as a sort of protect- ing envelope, like the rind on a melon, is clear and transparent but is not readily distinguishable except when the animal is moving. The pseudopodia are always formed first out of this clear ectoplasm, the more granular, grayish inner substance or AMEB OF THE MOUTH 141 endoplasm pouring out into it later. The reproduction of these little animals is by a simple division of the body into two when they have grown large enough to feel cumbersome as single individuals. Although cysts are formed for protection against Fie. 41. Common shapes of Endameba gingivalis, from human mouth. x 650. (After Bass and Johns.) an unfavorable environment, no multiplication within the cysts has been observed such as occurs in Endameba coli or E. histolytica. The cysts, which are rarely found, usually measure from eight to ten yp (5/99 tO gsyo Of an inch) in diameter, and are perfectly spherical with a thin wall. Some investigators have suggested the possible identity of E. gingivalis and E. histolytica, but, as pointed out by Craig, the sluggish movements, small nucleus, absence of certain changes in form of the nucleus observed in the dysentery ameba, formation of cysts with a single nucleus, inability to produce dysentery when swallowed and other characteristics all indicate that without doubt the mouth ameba is quite distinct from the in- testinal amebe. Other species besides EH. gingivalis have been found in the human mouth, but little is known about them. Z£. kartulisi is large with very distinct ectoplasm; it is said to occur only rarely. Recently Craig has described another ameba of small size, which he has provisionally named EF. confusa on account of the likelihood of confusing it with small specimens of LE. gingivalis. 142 AMEB Endameeba gingivalis and Disease. — As intimated above, although the presence of amebez in the mouth has been known for many years, these parasites attracted little interest until 1914 when several investigators called attention to an apparent relationship between the ameb and the presence of pus pockets between the teeth and gums, a disease known to dentists and physicians as ‘‘ pyorrhea alveolaris.”” The amebe do not thrive on exposed surfaces in the mouth, but find a congenial environ- ment in any little secluded pockets between the teeth and gums, in crevices between close-fitting teeth, or where a bit of food forms a protected spot for them. Stowed away in such places, and invariably accompanied by bacteria and often spirochetes, they multiply rapidly. That they feed largely on other organisms cannot be doubted, but that they prey also on the living tissue cells is practically certain. Eventually the delicate peridental membrane surrounding the roots of the teeth (Fig. 42), correspond- ing in a general way to the periosteum of bones, is eaten away and becomes ulcerated. The eating away of the living membranes Sketch of Fic. tooth showing peridental 42. membrane, which is the tissue attacked by Enda- meba gingivalis and the seat of pyorrhea, peri- dent., peridental mem- brane; periost., perios- LEHI! Crs) “CrOWwn:) 1, root; p. pulp. (After Bass and Johns.) of the teeth and gums is accompanied by a constant formation of pus, and a marked proneness for the gums to bleed, often with- out provocation. The swallowing and ab- sorption of the pus and of the poisonous waste products generated by the parasitic organisms are probably the cause of the more or less noticeable constitutional symptoms which accom- pany the disease. These may consist of feverishness, dis- ordered digestion, nervous troubles, rheumatic pains in the joints, anemia, or various combinations of these ailments. We have long known that unhealthy mouths were the cause of gen- eral bad health, but we never until recently had any definite clue to the reason why. As the ulceration of the membrane continues, the tooth is gradually loosened from the gum. Just as meadow mice girdle fruit trees, so these amebe, or the bacteria or spirochetes which accompany them, eat away the living “ bark” of the teeth and AMEBA AND PYORRHEA 143 gums, eventually causing the teeth to fall out. As already stated, over 50 per cent of all permanent teeth which are lost fall out as the result of pyorrhea. Whether the formation of the pus pockets is initiated by the amebe or by other organisms is not known, but certain it is that Endameba gingivalis is almost without exception found in the lesions, and at the very bottom of them, often burrowing into the inflamed tissues to a depth of several times its own diameter, devouring cells and transporting bacteria. The belief in the réle of the amebe is based on these facts and on the fact that often, - though not always, the disease is greatly improved by treatment with emetin, which has a specific action on amebe. Some in- vestigators, notably Craig, consider it, to quote from Craig, “more than doubtful that Endameba gingivalis is the cause of pyorrhea alveolaris, this conclusion being based upon the follow- ing facts: the occurrence of the parasite in a large per cent of healthy mouths and in the material that can be scraped from healthy teeth and gums; the occurrence and persistence of the parasite in patients treated with emetin, even when marked improvement in the clinical symptoms have occurred; the ab- sence of the parasite in some typical cases of pyorrhea; the lack of improvement with emetin shown in numerous instances of the disease, although the endamebe may disappear; and the fact that emetin acts upon other organisms as well as upon endamebe and the possibility that the improvement that often follows its administration may be due to such action or to a favorable action on the tissue cells.” That these facts argue against the causa- tion of pyorrhea by amebe alone is unquestionable. These facts, however, are not only not opposed to the possibility of amebe being partly or indirectly responsible for the disease, but may be interpreted as being in support of such a view. It is entirely in accord with the known facts about the disease to suppose that the pus pockets may be initiated or enlarged by the action of amebz, the damage being then continued by bacteria which have been given a portal of entry. This would account for the occasional absence of amebe in typical cases of pyorrhea and for the occasional cases of the disease which are not improved by emetin. It is further quite conceivable that the amebze may live for a long time in crevices in the mouth without doing any damage, and yet be capable of causing or aggravating pus pockets 144 AMEB under suitable conditions. Perhaps some slight injury to the membranes or the combined action of the amebe and certain bacteria is necessary to start the process. Parallel cases of parasites which may live for a long time as harmless messmates and then, under favorable conditions, become pathogenic are well known; one of the best examples is the intestinal ciliate, Balantidium coli. This would account for the presence of Endameba gngivalis in healthy mouths. It is significant that in her investigation of school children in New York, Anna Williams -found only 30 per cent of apparently healthy mouths, and 94 per cent of mouths with spongy and bleeding gums, infected. As to the statement that amebe still exist in pus pockets after treatment with emetin, even when there is marked improvement in clinical symptoms, there is no doubt but that the number of amebe is greatly reduced, and those on the frontier where the most damage is done are undoubtedly killed, since they are most exposed to emetin in the blood. The ineffectiveness of emetin against amebe which are not directly in the tissues has been demonstrated in the case of the free-swimming stages of Craigia (see p. 139). Again, were the improvement following treatment with emetin due to favorable action on the tissue cells, such im- provement would invariably follow. That emetin affects other organisms besides amebz is true, but it is more active against these protozoans than against any other organisms, as far as is known. The complete cure of pyorrhea which emetin sometimes effects, the almost invariable improvement shown after its use, and the occasional failure of it, all point to the instrumentality of amebze in causing or aggravating the disease, but indicate that they may be aided and abetted, or entirely replaced, by bacteria or other organisms. There is some evidence that chronic tonsilitis also is often caused by EF. gingivalis, since this parasite is found in the ma- jority of diseased tonsils, irritating the tissues and opening the road for bacteria. An indirect relation of this same mouth ameba to certain types of goitre also has been shown to be very probable. Evans, Middleton and Smith found that diseased tonsils and nasal passages and enlarged thyroid glands (goitre) are frequent com- panions in the goitre belt of Wisconsin. They believe that the amebe injure the tissues sufficiently to give ample opportunity TD PREVENTION AND TREATMENT OF PYORRHEA 145 for bacteria to enter and multiply in enormous numbers, and that certain of these bacteria produce poisonous substances which exert a stimulative effect on the thyroid glands, thus causing goitre. The effect of the presence of amebe, indirect as it is, can be fully demonstrated by destroying them with emetin. In 18 out of 23 cases of goitre treated with emetin the size of the thyroid mass was obviously reduced. Prevention and Treatment.— Ordinary cleanliness of the mouth by frequent brushing of the teeth, rinsing of the mouth, and care of imperfect teeth is the most important factor in keep- ing the gums healthy and free from an injurious degree of amebic infection. In the investigation of school children in New York already mentioned the number of ameba-infected mouths was reduced one-half by ordinary cleanliness and care. Such methods, however, are of little value if the amebze have estab- lished themselves in a pus pocket, since in such situations they cannot be reached by the usual methods of mouth cleansing. In the New York investigation it was found that mouths could almost always be freed of amebe by using a mouth wash with a weak solution of emetin, the latter being a valuable preventive measure. In older people, however, where the amebe have often already succeeded in stowing themselves away in little crevices and pockets where mouth washes cannot reach them, some other method must be employed. The ideal method is to open up and thoroughly clean out any pus pockets which can be found. This should be followed by a hypodermic injection of emetin, repeated on a few successive days to destroy all amebz, wherever situated. All amebe disappear in 90 per cent of cases in from one to three days, while after six days of treatment, amebe disappear in at least 99 per cent of cases. Usually with the death of the parasites the soreness ceases, the pus formation stops, the gums stop bleeding and the general health rapidly improves. Of course it takes time for the injured tissue to heal and the part destroyed is never replaced. There is also constant danger of reinfection and the already eroded pocket forms an excellent place for fresh amebz to take up a claim and begin their destruc- tive work. Furthermore there are cases of pyorrhea which do not respond to treatment with emetin, probably because the work begun by the amebe is continued by bacteria. Emetin, diluted 200 to 400 times in alcohol and applied with a tooth brush, 146 AMEB® is usually sufficient to kill recently implanted amebic infections. A thorough mouth rinse with a drop or two of emetin in half a glass of water is an excellent protective measure but even with the use of these means of prevention some apparently cured cases of pyorrhea get reinfections within a few months. The form of emetin known as “‘ alcresta ipecac,” in tablet form, is often useful. Two of these tablets taken three times a day for from four to six days is fairly certain to destroy amebe and has the advantage of being easily taken without the aid of a physi- cian. It sometimes causes a little abdominal discomfort and looseness of the bowels, but usually has no marked bad effects. As intimated before, the prevention of infection with En- dameba gingivalis is largely a matter of ordinary mouth hygiene. Infection can be avoided to a large extent by care in eating and drinking. One should never eat or drink with the same articles that have been used by other people. The practice of promis- cuous kissing is, of course, a ready means of transmission for these parasites as for many others. Occasional infection with the parasites of pyorrhea is, however, almost inevitable. If the mouth is kept scrupulously clean and in as near perfect condition as possible, the amebze may find no congenial place to settle down, but in the vast majority of mouths there is an abundance of fertile ground for them. Once they are established in a pocket or crevice the injection of emetin, or the taking of ipecac tablets, is the only safe method of getting rid of them. The mouth wash described above, consisting of a drop or two of extract of ipecac in half a glass of water every evening is a fairly safe means of prevention. Tooth pastes containing emetin are now upon the market, but few physicians place much con- fidence in them. CHAPTER IX MALARIA Importance. — Of all human diseases there is none which is of more importance in the world today than malaria, and this in spite of the fact that we have a very full knowledge of its cause, the manner of its spread, its cure, and means of prevention. It has been estimated to be the direct or indirect cause of over one- half the entire mortality of the human race. Sir Ronald Ross says that in India alone it is officially estimated that malaria kills over one million persons a year, a greater number of deaths than was caused by the great European war in the first two years of its existence. When there is added to this the thousands from the rest of Asia, Africa, Southern Europe, South and Central America, and the southern part of our own country who are annually sacrificed on the altar of the malarial parasite; the millions of others who are broken in health, incapacitated for work and made easy victims of other diseases; the valleys, countries, and even continents which have been barred from full civilization and development by this more than by any other cause; then only can we get a glimpse of the real meaning of malaria to man. Ross argues convincingly that the downfall of the great Greek empire and the present poverty-stricken blighted condition of many parts of Greece is probably due primarily to the invasion of that country, not by burning and devastating armies of men, but by the malaria parasite, an in- finitely more terrible though unseen foe which destroyed the new- born infants, undermined the health of the children or killed them outright, rendered the richest agricultural lands uninhabi- table, and, in a word, sapped the vitality of the people until the boasted power and glory of Greece is but a mocking memory. Though historians and economists have failed to recognize it, the réle of malaria and other endemic diseases must have played an enormous part in the history of the world and in the progress of nations. Malaria and its powerful accomplice, the hook-~- 147 148 MALARIA worm, are largely responsible for the present deplorable condition of some parts of our own South. Dr. Howard estimated in 1907 that there were nearly 12,000 deaths a year in the United States from malaria. This, however, is probably almost inconsiderable when the amount of damaged health and weakened resistance to other diseases is taken into consideration. Dr. Von Ezdorf, of the U.S. Public Health Service, in a recent attempt to estimate the prevalence of malaria in the United States, obtained data, based on morbidity reports, which indicate that at least four per cent of the population of eight southeastern states — 1,000,000 people — is affected by the disease annually, and found by 13,526 blood examinations that over 13 per cent harbored malarial parasites in their blood, the percentage being much higher in negroes than in whites. Dr. Howard thinks that an estimate of 3,000,000 cases of malaria a year in the United States would not be too high. Millions of acres of fertile land in this country are rendered useless or only imperfectly cultivable. Taking everything into consideration, Dr. Howard makes the astounding but well- founded statement that the annual financial loss to the United States from malarial diseases is not less than $100,000,000. This is the condition in the United States, a large portion of which is relatively free from malaria, and in no part of which is the dis- ease so prevalent or so destructive as in the tropical portions of Asia, Africa and South and Central America. In a broad way one-third of the population of highly malarial countries suffer from the disease annually. According to Ross the number of deaths from malaria in India must reach 1,300,000 every year. Obvi- ously the importance of this disease to mankind is not likely to be overestimated. History. — “ Malaria ’’ means bad air, and was therefore ap- plied to a number of fevers which were commonly associated with the bad air of swampy regions. The idea that malaria is caused by bad air, unwholesome odors, damp night winds, or impure drinking water is even yet adhered to not only by some of the populace but even by a few unenlightened medical men. Ross says that it takes ten years for the world to grasp a new idea, but his estimate is far too low; it is now (1917) 37 years since the organism causing malaria was discovered and 19 years since its transmission by mosquitoes was experimentally proved. It was in 1880 that Laveran, a French army surgeon in Algeria, ’ MALARIAL PARASITES 149 ‘ , discovered a parasitic ‘‘ germ ”’ which he proved to be the true cause of malarial fevers. Dr. King, of Washington, in 1883 suggested the probability of malaria parasites being spread by mosquitoes, adducing much circumstantial evidence in support of his views. It was not until 1898, however, that Sir Ronald Ross, an Englishman in the Indian Medical Service, experiment- ally proved that the malaria parasite is absolutely dependent upon certain species of mosquitoes for its transmission from man to man. Only six years ago (1911) the parasites of malaria were first successfully cultured outside the human body by Bass and Johns at New Orleans, a feat which will eventually lead to new and valuable discoveries. Other workers deserve no less credit, perhaps, for suggestive ideas, or for additional facts concerning the life and control of the malarial parasites. The ultimate results of their discoveries have only begun to be felt, but al- ready such enterprises as the building of the Panama Canal have been rendered possible. The Canal could never have been built under the old régime of medical ignorance. Statues of the pioneers in the work of unraveling the truths about malaria and yellow fever might well have occupied conspicuous places at the Panama Pacific International Exposition at San Francisco. Malarial Parasites. — Malarial fevers, of which there are several different kinds, we now know to be caused by protozoan parasites which live at the expense of the red blood corpuscles, and are injected into the human body and transmitted from person to person only by the bite of certain species of mosquitoes. The malarial parasites belong to the protozoan class Sporozoa, or spore animals, so called from their habit of reproducing by breaking up into a number of small parts or spores, instead of simply dividing into two as do most of the Protozoa. All of the Class Sporozoa are parasitic and have no organs of locomotion when full grown. Although there are many different kinds which live as parasites in other animals, very few normally attack man and only the malarial parasites, belonging to the genus Plasmodium, are of primary importance. There is still consider- able disagreement as regards the classification of the human malarial parasites. Nearly all workers on the subject agree that there are at least three well-defined species of Plasmodium causing human malaria, and there is some evidence that distinct subspecies or varieties of some of these occur. The commonest 150 MALARIA and most widely distributed species is Plasmodium vivax, which causes tertian malaria. Of somewhat more limited geographic range, being confined to tropical and subtropical countries, but of infinitely more importance on account of the deadly nature of its attacks, is Plasmodium falciparum, the cause of the exstivo- autumnal type of malaria, also called malignant tertian or subter- tian fever. During the hot part of the year in the tropics 96 per cent of malarial cases are of the estivo-autumnal type. The third species, Plasmodium malaria, causing quartan malaria, is relatively uncommon, though more frequent in temperate than in tropical countries. These three species of malarial parasites differ from each other in a number of important details of structure and life history and in the diseases which they produce. Life History of Plasmodium falciparum; Human Cycle. — The life history of malarial parasites may well be exemplified by that of the malignant zstivo-autumnal parasite, Plasmodium falciparum, as diagrammatically shown on Fig. 43. When first injected into the human blood by a mosquito the animal is exceedingly minute (Fig. 43A). It immediately enters or at- taches itself to a red blood corpuscle, where it grows until it occupies one-half or two-thirds of the corpuscle, meanwhile un- dergoing a number of different forms. It first goes through a ‘signet ring” stage (Fig. 48B), the ringlike appearance being due to the presence of a transparent area occupying the middle of the parasite, while the tiny round nucleus occupies a position at one side of the parasite, simulating the setting in a ring. As the parasite grows larger it becomes irregular in shape (Fig. 43C) and quite active, constantly changing its form, thrusting out little clublike processes or pseudopodia, now here and now there. Although it has been taken for granted that malarial parasites penetrate the blood corpuscles and live inside of them recent investigations by Mary R. Lawson (Mrs. Johnson) indi- cate that this may not be the case at all, but that the parasites may attach themselves to the surface of the corpuscles, squeezing up little mounds of the substance of the corpuscles and encircling these mounds with their bodies, just as a bit of skin might be squeezed up between the fingers. Sometimes several parasites attach themselves on top of each other around a single mound. A number of facts give support to Mrs. Johnson’s theory: it affords a logical explanation for the ring forms of the parasite; it 1 1 LIFE HISTORY 5 CsSLOyyNe SNOWeA UOAy suorjsosong) “OOS X ‘X-Y ‘OOO X ‘M-py ‘“poorq uvuiny oyUT e1ods jo uonoafur ‘xy :spurls Arearpes oyu sorods jo sureajoued ‘44, {AjtAwo Apoq oyui saaods SUTPBIOGIT pojysanq ojpnsdvo ONYBUL "4s YOBULO}S S,O}INDsour Jo [[BM JoJNO UO sfnsdvo pel[y o1ods jo yueudoyoeAop ut sosvys ‘Q puv yp ‘Ss SyoRutoys $,OJINDsouL Jo ][BAN suljyeioued ‘s50 pozytytofy wiory podojoAop ‘Apoq oylpu10M FuNoA ‘Y -uoMneztiqydey (7) [ayA00jouIes o[BUl WOT; SoJOUIvS o[RUL JO UOISNA}Xo “av ,‘Apoq poyeyjosey,, JO UoTwVUIo; ‘YF soyoulVs opRUIey oANyRUt ‘Cy ‘yO poysosip soposndaos pooyq jo sjuvumot !oyIMbsour Jo Youuwojs ut ‘oumes ‘Ay pue py Sureedjs poolq ut ‘AjOATJOOdSaI (SoyADOJOUNLS) S[[oo o[BUL pUB o[BUlos ‘7 pu YW ‘ojo ‘UOTyB[NAOds ‘YyMOIS JO UOTYTYOdO. ‘7 pue ‘7 ‘FY :oposndioo Mou jo youqye puv soyisvavd sunod Jo uorjeroqy ‘H ‘7 {(sefnuvas yuouIsId jenprisear o}0U) uoryeyn1o0ds wWodI, Surjpnsos ‘ojosnd1oo ur soyseaed Sunok ‘yy ‘oyeyniods 0} Aptos oyisvaed y[npe ‘gq ‘eBRjs proqoure s9zR] ‘9 ‘oBR4s sult,, SUNOA ‘g foposnd.a09 poolq pot SurtojUo OJMbHsou Jo puvps Arvaryes wioay o10ds ‘py !(uwnuiodvwppf wnripowusy)g) oyisewed BIIe[BUL JO ALOJSTY OFT "EH “SY No (s2}2udouy)y Papafur buyysng opn eA Aq apow uafsunay “poojq oyu! vAr;Dg fo uByoafui “GY apow safouns an ‘opin bsoyy 242 152 MALARIA explains the occasional distinct projection of the parasites at the periphery or edge of the corpuscles (Fig. 44); and it accounts for the ease with which the parasites may be distorted in making B Fig. 44. Blood corpuscles showing malaria parasites at periphery. B shows two para- sites resting one above the other. blood smears. Another argument in favor of this theory as opposed to the intracorpuscular theory is that the hemoglobin in the corpuscles is believed to be in a more or less solid state, and would therefore make it difficult for the parasites, if situated inside, to indulge in such active movements as they do. The majority of protozodlogists, however, have not accepted Mrs. Johnson’s conclusions. As the parasite develops there is a distinct tendency for the affected corpuscles to clump together, thus clogging the tiny capillaries which are large enough to allow the passage of only a single corpuscle at a time. In this way the capillaries of such organs as brain, spleen, bone marrow and others may be obstructed to a fatal degree. Three-fourths of the life cycle of the parasites is usually passed in the plugged capillaries so that only during one-fourth of their cycle can they be found readily in the circulating blood. After about forty hours the nucleus of the parasite divides into a variable number of fragments, usually from ten or 15 to as many as 32, 7.e., under favorable conditions it may split five times, into two, four, eight, 16, and 32 parts. The rest of the body divides itself into portions, one surrounding each fragment of the nucleus, thus forming a little heap of “ spores ” (Fig. 43E) ready to burst apart and leave the corpuscle on which the parent parasite had been feeding. In the center of the heap can be found a little mass of coal-black pigment granules, the waste products resulting from the digestion of the oxygen- carrying red substance of the blood, hemoglobin. When the parent parasite bursts the young parasites formed by this rapid process of multiplication are set free (Fig. 43F) in the blood where each enters a new corpuscle and repeats the process of growth and reproduction. The pigment and other waste products which are left behind when the parasite multiplies are released into the blood stream where they are carried to all parts of the (Sketches from mi- crophotographs by Mary Lawson [Mrs. Johnson].) NUMBERS OF PARASITES 153 body and deposited in the spleen or other organs or under the skin, causing the sallow color so characteristic of malarial patients. It is at the time of the bursting of the corpuscles and release of the waste matters which act as poisons that the characteristic chills and fever of malaria are felt. Since the cycle from one generation to the next is usually about 48 hours in the estivo- autumnal parasite the attacks of ague are felt at these intervals. In the malignant type of malaria the bursting of all the para- sitized corpuscles and release of poisonous waste matter does not occur so nearly simultaneously as it does in the other species, the result being that the paroxysms of chill and fever are drawn out over many hours. A “quotidian ”’ type of malignant malarial fever in which agues occur every 24 hours is occasionally met with, the parasites of which are thought by some authors to constitute one, or even two, distinct species. The majority of cases of malaria with daily-recurring fevers are due to double or triple infections, the different broods maturing on different days. This rapid process of multiplication in the human blood re- sults in a short time in an enormous number of parasites, some- times many billions. The actual quantity of parasites in a human body in a ease of severe exstivo-autumnal malaria has been estimated at 600 cc., or over one pint. It may or may not mean more to the reader to know that such a quantity of ma- larial parasites would number 3,000,000,000,000. A better con- ception of the real meaning of such a number may perhaps be gained when it is realized that to count off this number at the rate of 100 per minute day and night without cessation would require 30 times the period of time that has elapsed since the birth of Christ. Eventually, however, either the parasite kills its host, which very commonly happens with this particular species, or the host, by the development of a temporary immunity in his body, kills or, as it more often happens, suppresses the parasite. Such a course of events unaltered, would lead to a very early and complete extermination of the parasite. There is a second chapter in the life history of Plasmodium which saves it from such an early death. After the parasites have been developing in the blood for about two weeks or more there are developed special sexual forms or gametocytes, male and female, in the form of sausage-shaped 154 MALARIA crescents (Fig. 43K and L). Just as in the case of other kinds of animals and plants, nature has adapted these animals to cope with their environment. As long as the blood of their host forms a suitable environment they continue to multiply in the normal manner, but when conditions due to the formation of antibodies become unfavorable they produce these sexual crescents in large numbers and patiently await rescue at the hands, or rather the beak, of a mosquito. The crescents may persist in the blood for several weeks, gradually disappearing after all other symptoms of infection have vanished. Only slight differences can be seen between the male and female gametocytes, the female being more granular in appearance, and with the pigment particles arranged in a more regular triangular manner (Fig. 48K and L). Mosquito Cycle. — When sucked into the digestive tract of the mosquito these gametocytes begin a complex developmental cycle, providing conditions of temperature -are favorable. The most favorable temperatures are between 75° and 85° F. The digestive fluids dissolve the remnant of the blood corpuscles, but the crescents resist digestion (Fig. 43M and N) and become more obviously sexually differentiated. The male gametocyte de- velops into a “ flagellated body ” (Fig. 43P), a little sphere from which several long slender filaments project. These are very active, constantly lashing to and fro, and ultimately break loose and wriggle about in the stomach of the mosquito like little spermatozoa, which, in effect, they are. The female gameto- cyte develops into an inactive sphere or gamete (Fig. 430) and one of the filaments from the flagellated male enters to fertilize it (Fig. 43Q). How perfectly the process simulates the act of fertilization of an egg by a spermatozoan in the higher animals! The result of the union of the filament from the flagellated body with the inactive female gamete is a body which corre- sponds in every way to a fertilized egg of a higher animal. This new individual, the beginning of a new generation, grows, elon- gates, and becomes quite like a little worm (Fig. 43R). It now wriggles and worms itself about in the stomach of the mosquito and penetrates the wall, lodging itself between the inner and outer linings of the stomach (Fig. 488). Here more rapid growth takes place and a heavy capsule develops, protruding on the outer surface of the mosquito’s stomach like a wart (Fig. 45). Mean- while the contents of the capsule undergo important changes, A oe ——— as DEVELOPMENT IN MOSQUITO 155 dividing into daughter cells (Fig. 43T) from each of which slender spindle-shaped bodies project like the “ stickers’ on a chestnut burr (Fig. 43U). Ultimately the cells lose their identity and the entire capsule or cyst becomes crammed full to the bursting point with myriads of these spindle-shaped bodies which have now developed into spores (Fig. 43V). Such a capsule may contain over 10,000 spores, and there may be as many as 500 capsules on a single mosquito’s stomach (Fig. 46). About Te ot ieee" 12 days or more, according to temperature, tion of stomach of after the infected blood was swallowed by the sal icas ioe OF mosquito, the capsule becomes mature and subtertian malaria. bursts, releasing the spores into the body cavity {Pout 80 After of the mosquito. From here the little parasites make their way to the three-lobed salivary gland (Fig. 46, sal. gl.) lying in the fore part of the thorax and connecting with the sucking beak. They assemble in the cells lining the salivary Fig. 46. View of digestive tract of Anopheles, showing spore-filled capsules of malaria parasites on wall of stomach. pal., palpi; prob., proboscis; ant., antenn; ph., pharynx; ces., cesophagus; sal. gl., salivary glands; f. res., ventral food reservoir; d. f. res., dorsal food reservoirs; prov., proventriculus; st., stomach; malp. tub., malpighian tubules; int., intestine. x 10. glands (Fig. 43W) and remain there perhaps for weeks, until the mosquito bites. When this happens the parasites flow with the poisonous saliva into the puncture made by the mosquito and, ‘should the prey of the mosquito be a human being, the whole 156 MALARIA process of asexual multiplication in the human blood corpuscles begins over again. Since it takes ten or 12 days for the sexual cycle to be completed in the case of sxestivo-autumnal malaria, an infected mosquito is not dangerous for at least this length of time after biting a malarial patient. However, once the new generation of spores has been developed, the mosquito remains dangerous for several weeks and may infect many persons, as not all the parasites are poured out of the salivary glands at one biting. It is commonly believed that malaria parasites not only do not develop but cannot live in the mosquito at a temperature below 60° F. but Dr. King has recently shown that the tertian parasite, Plasmodium vivax, can survive several days in Anopheles quadri- maculatus at temperatures slightly below freezing, and can with- stand a mean temperature of 46° F. for 17 days. The estivo- autumnal parasite, P. falciparum, though more closely confined to the tropics than the other species, was found to survive a temperature of 35° F. for 24 hours. This clearly shows that the malaria parasites can readily pass the winter in the mosquito hosts even in places where the mean temperature may fall con- siderably below 60° F. for some time. Other Species. — The other species of malarial parasites dif- fer only in minor details of their structure and development. The tertian parasite, Plasmodium vivax, during the early stages of its development in the blood corpuscles is extremely active. Its unceasing restless changing of shape is fascinating to watch under the microscope and one feels that it was very appro- priately named ‘ vivax.” Unlike the malignant parasites of estivo-autumnal malaria, the tertian parasites do not tend to clump together, and so do not become plugged in the capillaries but remain constantly in the circulation. To this fact, as will be shown later, is due the ‘‘ benign ”’ nature of this and also of the quartan parasite. The tertian parasites have the peculiarity of growing very large and of causing the corpuscles which they parasitize to enlarge and become unhealthy in appearance. The number of spores which result from the sporulation every 48 hours ranges from ten to 25. According to Ross the normal number of splits of the nucleus is four, which would result in 16 spores. One of the most striking points of difference from the “malignant ”’ parasites is the fact that the gametocytes SPECIES OF PLASMODIUM 157 are not in the form of crescents, but instead resemble mature parasites ready to sporulate. A comparison of Fig. 47A, A’ and A” with B, B’ and B” and C, C’ and C” brings out the prin- cipal differences among the three species of parasites as regards size at maturity (A, B, C), number of spores (A’, B’, C’) and form of gametocytes (A”, B’’, C’’). Fic. 47. Comparison of three species of malaria parasites < 2000 (figures selected largely from Manson). A, A’ and A’, Plasmodium vivax; B, B’ and B”, Plasmodium malarie; C, C’ and C’’, Plasmodium falciparum. A, B and C, mature parasites in red corpuscles. A’, B’ and C’, segmented parasites ready to leave corpuscles. A”, B” and C’ , mature gametocytes. The quartan parasite more closely resembles the tertian para- site in flexibility of body and form of gametocytes (Fig. 47C”’), but it differs in that it does not cause the corpuscle to enlarge (Fig. 47C) and is never active in movements. It produces only from five to ten spores, the nucleus normally undergoing three splits. The spores form a very regular rosette or ‘ daisy-head,” ar- ranging themselves petal-like around the dark mass of pigment in the center (Fig. 47C’). Unlike either of the other parasites this one causes ague by its sporulation once in 72 hours instead of in 48 hours. A comparison of certain phases of this parasite with the same phases of the others will be found in Fig. 47. Propagation. — As remarked above infection with malaria is now known to take place exclusively through the bites of certain species of mosquitoes, all belonging to the genus Anopheles (in- cluding its subgenera). While over a hundred species of Anoph- 158 MALARIA eles have been described, less than one-third have been proved to be carriers of malaria. Some species will carry certain types of malaria and not others (see p. 489). A knowledge of the malaria-transmitting ability of various species of mosquitoes and their habits is of the utmost importance in any attempt to exterminate malaria by exterminating mosquitoes. The knowl- edge that A. malefactor of Panama, breeding in cavities of stumps and trees, was not a malaria carrier saved several hundred thou- sand dollars in the anti-malarial campaigns in the Canal Zone. The distinguishing characteristics of Anopheles and a_ brief account of a few of the more important malaria-carrying species will be found on pp. 439-441. Reports of malarial outbreaks have occurred which were said to be due to some other cause than mosquito transmission, but when completely investigated there has always been found to be a “leak”? somewhere. Sometimes the presence of mosquitoes was unsuspected, sometimes other fevers have been mistaken for malaria, and sometimes the malarial parasites have been harbored for weeks or months in “latent” form. This is a phase of malaria which is little understood, but it is a well-known fact that long after symptoms of the disease have disappeared, and the parasites can no longer be found in the blood, a fresh outbreak may occur, coincident with some loss of vitality, or some physiological shock on the part of the host from some other cause. Often a mere change of climate and environment is sufficient to precipitate “latent ” malaria. It is highly probable that the ordinary blood parasites are carried in the meantime in such small numbers as to be practically impossible to find. Ross has pointed out that if 1000 parasites in the body were able to withstand the unfavorable conditions and existed there during the “latent” stages, a man working 12 hours a day searching blood smears would have a chance of finding one only once in five years. Some authors have advanced the theory that the gametocytes, suddenly stimulated by some unknown cause, develop by parthenogenesis, 7.e., without the ordinary sexual mosquito cycle, and thus cause the relapse. This idea has been widely accepted but there seems to be little ground for it and some positive evidence against it. The parasites naturally thrive best when their host is weakened by some other influence which then acts as an accomplice for them. Such influences are ex- COURSE OF DISEASE 159 posure to sudden changes in climate, fatigue, dissipation and other sickness. Even educated people often come to believe that malaria is directly caused by these conditions. Suffice it to say that many experiments, carried out with the utmost care and accuracy, and checked by numerous repetitions, have proved beyond doubt that the mosquito is the necessary - transmitter and intermediate host of malarial parasites. A few investigators think it possible that other animals besides man may serve as hosts for the malarial parasites, so that malaria may occur even in uninhabited regions. Although many para- sites are able to live in a number of different kinds of animals, this does not seem to be true with the malarial parasites, and all attempts to infect even monkeys have so far failed. Until some definite proof of the réle of some other animal as a host for human malarial parasites has been brought forward we may look upon this as very improbable. Possibly the alleged presence of malaria in uninhabited regions may be explained by the malarial parasites in the mosquito passing into the eggs of the mosquito, and thus being carried on generation after generation. Though the germs of some diseases are known to do this in their insect hosts, experiments with hereditary transmission of ma- larial parasites in mosquitoes have so far been unsuccessful. The Disease. — Malaria as a disease is extremely variable. A “typical” case of malaria, in the tropics at least, is a rather unusual thing. As we have seen, there are at least three different kinds of malarial parasites, each of which produces a somewhat different disease. While ordinarily all the parasites of a brood mature at regular intervals, a person in a malarial district may be infected with two or more broods maturing at different times, and the case may be farther complicated by a “ mixed ” infec- tion, that is, by more than one species of malaria at a time. Varying degrees of immunity, the effects of insufficient quinine or other drugs, the, presence of complicating diseases and the virulence of the particular strain of parasites all have a hand in modeling the effects produced by “ malaria.’”’ It is little wonder that in some places practically every ailment or feeling of ‘‘ ma- laise”’ is attributed to malaria. In the tropics such a diagnosis would be correct in a great many cases. However, the habit of attributing any indisposition which cannot be accounted for otherwise to malaria has been transplanted into non-malarial 160 MALARIA places, and it is not uncommon to hear of a person having a “touch of malaria ’’ when in reality he has only indigestion, a cold or a light case of la Grippe.- It is largely due to this fact that malaria is looked upon in non-malarial districts as of such small consequence. The early stages of all types of malaria are similar except that the quartan type produces the intermittent fevers on every third, instead of every second, day. During the incubation period of the disease there is a feeling of ennui with headache and perhaps slight fever. After about a week, when the parasites have mul- tiplied to 150,000,000 or more, the regular intermittent fevers set in. Each attack begins with a shivering chill, sometimes accompanied by convulsions, so severe that the teeth chatter and goose-flesh stands out all over the body. Yet the tempera- ture will be found to be several degrees above normal, and still going up. In the wake of the chill comes a burning and weak- ening fever, with violent headache and vomiting and a tempera- ture from six to eight degrees above normal. The fever stage in turn is followed by a period of sweating, so profuse that the clothes or bedding may become wringing wet. The sweating gradually subsides, the temperature drops rapidly, often below normal, and the patient, after from six to ten hours in the case of benign infections and about 20 hours in malignant infections, rests fairly easy until the next attack. The fact that the attacks most commonly occur between midnight and noon, instead of in the evening, is often useful in distinguishing malaria from other intermittent fevers. In the case of “benign” (tertian and quartan) infections after these agues have recurred for about ten days or two weeks, the symptoms gradually subside and the patient experiences a rally. From this point either he may recover completely (even if untreated) or he may suffer a relapse with all the old symptoms of regular agues. Then comes another rally and a second relapse, this continuing for months or years, aided, perhaps, by constant reinfections. During all this time general symptoms of emaci- ation, sallowness, anemia and enlarged spleen constantly in- crease at a diminishing rate with each elapse, and decrease at a similarly diminishing rate with each rally, so that eventually a fairly constant state of spleen-enlargement, emaciation, anemia, sallowness and general run-down condition is arrived at — the BLACKWATER FEVER 161 well-known condition of chronic malaria, or malarial cachexia, common especially in children. The spleen enlargement is the most readily recognizable symptom of chronic malaria and there- fore the ‘“‘ spleen rate,” 7.e., the percentage of enlarged spleens in a community, gives a fairly accurate measure of the prevalence of malaria to which some degree of immunity has been developed. Usually, unless the weakened condition has given some other disease a chance to put an end to it all, a general improvement ultimately begins. This is especially true in children, so that by the time they reach adult life they are in fairly good health and immune to malaria. In the case of exstivo-autumnal or malignant malaria the course of the disease is often not so light, and early death is not a rare occurrence. The fact that the bodies of the malignant parasites clump together and plug the capillaries, thus preventing the proper flow of blood in the vital organs, is probably the chief cause of their malignant nature. One of the most certain symp- toms of a malignant attack of malaria is a total loss of conscious- ness or coma, due to a plugging of the capillaries in the brain. Indeed, 50 per cent of the deaths from malaria are said to be caused by a plugging of the brain capillaries. The type of brain disease Which may be caused is very variable but some mental disturbance almost always occurs, and may take place at almost any time during the course of the disease, though it never occurs during the first fever fit, probably because the parasites are not yet numerous enough to do any great damage. In connection with malarial fevers there must be mentioned a much dreaded and little understood condition known as “ black- water fever.’ This is a disease in which something destroys the red blood corpuscles in large numbers, causing the coloring matter of the blood, hemoglobin, to be liberated, eventually to be voided with the urine, giving the latter a very dark color. At the same time there is a more or less irregular fever, bilious vomiting and severe aches. In a great many cases it results in death. This disease has usually been considered as an outcome of severe malaria, since it always occurs in malarial countries and usually follows or accompanies an attack of malaria. It is not uncommon in southeastern United States, some parts of tropical Africa, southern Europe and many parts of tropical Asia and the East Indies. In many other malarial districts it 162 MALARIA is entirely absent. It is suggested by Manson that the fever is caused by a distinct organism, and that malaria is merely a predisposing cause. Immunity and Epidemics. — Absolute immunity to malaria is rarely if ever acquired but, as already remarked, oft-repeated infections especially in childhood tend to build up a high de- gree of tolerance to the effects of the parasites and a diminution in the number of parasites in the body. The protection afforded by a single infection is very slight, and is retained for only a short time in the absence of reinfections. Even the cumula- tive effect of numerous infections disappears rapidly in the course of a few years. Some authors divide malaria into two types. There is a “ tropical ”’ form, occurring in places where reinfections can occur practically throughout the year on account of the continued warm temperature. The other, a “subtropical”? form, is found in regions where cold weather causes an annual seasonal interruption of infection by a cessation of breeding on the part of Anopheles, and by a discontinuance of growth on the part of the parasites in the mosquitoes. In tropi- cal malaria a fairly constant degree of immunity is maintained, and epidemics are rare if they occur at all. In Java and other tropical places, according to Robert Koch, nearly every native child, under four years of age, has his blood teeming with ma- laria parasites from which he suffers little inconvenience. These parasites gradually become scarcer in older children and are often practically absent in adults who, however, have been shown to be passive ‘‘ carriers’ of small numbers of the parasites and therefore a source of danger to the community. The “ carriers,” though relatively immune to the more acute symptoms of the disease, are left in the run-down condition of malarial cachexia. As pointed out by Gill, there is a striking analogy between the confirmed opium-eater and the malarial cachectic. Both have purchased their immunity at a heavy price. In the former the emaciated frame, sallow complexion and other signs of debility proclaim the victim of a drug habit; in the latter the enlarged spleen, the lack of physical and mental energy, and the shrunken body bear witness to the havoe wrought by long-standing ma- laria. In the case of neither does death often take place as the direct effect of their respective poisons, but both readily fall victims to intercurrent affections. In subtropical malaria, on ce TREATMENT 163 the other hand, the average tolerance of the community to the disease suffers an annual relapse, and may constantly decrease for a number of years. When the immunity of the community as a whole becomes quite low, and there is a sudden increase in the probability of infection by a great increase in number of mosquitoes, accompanied possibly by an influx of infected people, ‘an epidemic of the disease may occur of such extraordinary se- verity as to involve almost the entire population, and to cause a mortality of several hundreds per thousand. Such devastating epidemics, probably of the subtertian type of malaria, have been termed “fulminant malaria’’ and are believed to occur quite extensively in malarial countries lying just outside the region of “ tropical’ malaria. Fulminant malaria in especially severe form occurs periodically in parts of India and in Italy. It was formerly thought that considerable racial immunity protected the negro races, but it has been shown that in many cases, at least, the immunity has been acquired by constant exposure to the disease, and that it disappears upon removal from infected regions. The whites in southern United States are said to suffer markedly more from malaria than do the negroes though the latter are more frequently parasitized, but this may be due, in part at least, to the more permanent residence of the latter in the malarial districts. As said before, individual resistance to the effects of the disease is variable. Occasionally there is found a fortunate individual who is naturally absolutely immune, but this is a very rare occurrence. Treatment. — It is one of the greatest blessings in the world that we have for malaria a definite and specific cure as near to being a “sure cure”’ as has been discovered for any disease. Quinine has been found absolutely destructive to malarial para- sites. While a dose of quinine given during a fever attack will not act quickly enought to cut it short, it will, if given immediately after an attack, prevent the next one, or at least alleviate it. Meanwhile the organisms disappear from the circulation. It is usually supposed that they are directly killed by the quinine, which acts as a virulent poison for them, though this is doubted by some workers. The methods of administering quinine must, of course, vary with the age and condition of the patient, and the state of the disease. Sometimes very speedy action is needed, and it is not safe to wait for quinine to be slowly absorbed from 164 MALARIA the stomach. Many a patient has died from malaria with enough quinine in his stomach to have saved his life had it been properly given. In such cases injections into the muscles, or still better, directly into the veins, is necessary. In malignant malaria quinine does not reach the parasites plugged in the capillaries and therefore can destroy them only as they sporulate and get back into the circulation. Since the parasites of this type often sporulate at irregular intervals a constant supply of quinine at a killing concentration must be kept in the blood. However, overdosing with quinine is not an uncommon fault with physicians. Quinine poisoning in some respects resembles malarial symptoms and the physician, thinking the latter are not abating, gives still more quinine until the patient succumbs ty *\. Not a few malarial deaths are really due to excessive .e. Malarial specialists, such as Professor Bass of New say that it is never necessary to give more than ten or “os ioly fifteen grains of quinine at a time, if given as the case ~ures it. Twenty grains of quinine sulphate a day taken by ».outh in several doses for a period of two weeks is said by Bass to disinfect anyone. Quinine must be avoided during or immedi- ately following an attack of blackwater fever, since the symptoms of this malady are intensified by its use. In case of severe malarial cachexia, the only safe course is for the patient to leave the malaria-infected country in which he has been living, and stay away for an extended period of time. He should take regularly small doses of quinine to kill any lurk- ing parasites which may remain in his body, and do everything possible to build up his general health and to regain his lost vitality. Prevention. — The prevention of malaria is a problem that should be solved not by individuals but by civie effort. Ross says: ‘It (malaria) is essentially a political disease — one which affects the welfare of whole countries; and the prevention of it should therefore be an important branch of public administration. For the state as for the individual health is the first postulate of prosperity. And prosperity should be the first object of scientific government.” Since the malarial parasites have two hosts, man and mosquito, the possibility of exterminating them in either host presents itself. Stephensport, in New Guinea, was practically cleared of malaria PREVENTION 165 in a few months by destroying the parasites in man by whole- sale ‘‘ quininization.”” In most places, however, the difficulties connected with this method of extermination are even greater than those associated with its alternative, the destruction of malarial mosquitoes. The relation of partially or entirely im- mune “ carriers’ to the spread of malaria is of extreme impor- tance and is usually greatly underestimated. The number of such apparently healthy carriers in malarial districts is astonish- ingly large. Eradication of malaria by attacking it in man would entail the persistent and thorough quinine treatment of all these carriers as well as of patients. Undoubtedly in practically every case, if accompanied by as extensive a use of quinine as is possible, eradication of malarial mosquitoes is the most effective and most permanent preventive measure. A discussion of methods of reducing and controlling such mosquitoes will be found on pages 455-462. Complete extermination of malarial mosquitoes is not necessary to reduce or even to eradicate malaria entirely. Ross has shown by mathematical computation that a relatively high number of malarial mosquitoes per person is necessary in a community to propagate malaria successfully. A small deviation above or below a certain number of malarial mosquitoes, probably between 40 and 60 per person during a month, a deviation too small to be detected readily, will mean the difference between an ulti- mate extermination of the disease and its permanent establish- ment. Ross also shows that the relation between the amount of malaria in a given region and the number of malarial mosqui- toes is so definite that it can be mathematically computed. These facts are of importance in the fight against malaria since they demonstrate to us that we do not have to exterminate totally even the malaria-carrying species of Anopheles in order to exterminate malaria, and our task becomes much less difficult. By this partial extermination some of the most malarial districts in the world have been practically freed. Up to 1900 over 16,000 deaths a year from malaria occurred in Italy; now they may be counted in hundreds. One of the first demonstrat ons of what could be accomplished by mosquito extermination was made by Major Ross in 1902 at Ismailia on the Suez Canal where from 1100 to 2500 cases of malaria occurred annually in a population of less than 10,000. Four years later not a single new case 166 MALARIA occurred there. The same thing on a much larger scale was accomplished in the Canal Zone at Panama by Surgeon-General Gorgas and his staff. On this relatively large malaria-infested area the death rate for the total population of about 100,000 was reduced 64 per cent in four years. The deaths from malaria were reduced about 85 per cent in less than four years, and yellow fever was totally eradicated. Similar feats have been accom- plished at Havana, Staten Island, and other places. One of the most recent examples of what can: be done was furnished by the American occupation of Vera Cruz in 1914. The American troops were severely attacked by malaria of all three types, and an anti- mosquito campaign was immediately inaugurated. It cost the Sanitary Department $5000 a month to oil the pools, drain the low parts of the city and its environs, and dispose of the standing water in street gutters, refuse heaps, etc., but in a few months Vera Cruz, one of the most deadly malarial districts in the world, was practically freed from Anopheles, and danger of malaria reduced to almost nothing. Obviously the wholesale reduction or extermination of malarial mosquitoes can be accomplished only by communities or by government aid. San Antonio has freed itself of mosquitoes and mosquito-borne diseases by enlisting the services of the school children. In our southern states, where there are 65,000,000 acres of swamp land, and where the chief malarial mosquitoes are swamp breeders, malaria can never be destroyed until state and federal governments are willing to invest money as readily to take water off the land in these parts of the country as they now invest it to put water on the land in the arid western parts. Much can be done toward reduction of malaria in selecting dry brushless sites for houses and in constructing them in mos- quito-proof fashion. The houses one sees in the American Government settlements on the Canal Zone, built well up off the ground and with open sleeping porches, wide verandas and airy windows, all carefully screened, are ideal for tropical dis- tricts where malaria and other insect-borne diseases are common. They present a happy combination of airiness, sanitation, and complete protection from insect pests. In well-known malarial districts it is a good personal safeguard to use screens as much as possible and to take regular doses of QUININIZATION 167 quinine at all times as a preventive measure. In the pine swamps and along the coasts of Florida malaria is practically absent on account of the effectiveness of screening necessitated by the abundance of non-malarial mosquitoes. Three to five grains of quinine daily, or ten to fifteen grains once a week, is an almost certain malaria preventive. Quinine, however, is apt to cause abortion in pregnant women, though less so than is a severe attack of malaria. Some people are naturally very susceptible to quinine and cannot take it; such people should carefully avoid malarial districts. Tea, coffee and other mild stimulants are also said to be beneficial, but the safest course is always the same — quinine, CHAPTER X OTHER SPOROZOA, AND OBSCURE OR INVISIBLE PARASITES ALTHOUGH the class Sporozoa includes a very large number of species, all of which are parasitic, and many of them the cause of fatal diseases in vertebrate as well as invertebrate animals, yet very few other than the malaria parasites, already discussed, are normally parasitic in man, and none of these can be looked upon as of prime importance in the causation of human disease. Of greatest importance, perhaps, are the Coccidiida or coccidians, which in lower animals are frequently the cause of fatal diseases and have been known to be fatal to man, though in some cases causing very little inconvenience. Another sporozoan parasite which is of importance where it occurs is Rhinosporidium, which produces tumors in the nose. A group of muscle-dwelling Sporozoa, the Sarcosporidia, occur accidentally or sporadically in man. There is another group of Sporozoa, the Piroplasmata, related to the malaria parasites, which are the cause of some of the most fatal diseases of domestic animals, including Texas fever and East Coast fever of cattle, biliary fever of horses, etc. These diseases are invariably, as far as known, transmitted by ticks. There is one human parasite, Bartonella bacilliformis, the cause of Oroya fever of Peru, which is thought to belong to this group of organ- isms. There is a possibility that Rocky Mountain spotted fever and the related Japanese disease, kedani, may also be caused by Piroplasmata, though the parasites have not yet been discovered. There are a number of other diseases, some of them of great importance, of which the ‘‘ germ ” either has never been seen or is of obscure nature. It is not always possible to guess at the nature of such undiscovered parasites but in some cases we can get a fairly accurate conception of them from a study of the course of the diseases they cause, the conditions under which they thrive and their means of dissemination. One by one the villains be- 168 OBSCURE AND INVISIBLE PARASITES 169 hind the screens are brought to light, experimented with, and brought under control but there are still some which have defied the most ardent researches of modern science and have never yet been discovered. The fact that many of them are able to pass through filters of certain kinds, as shown by the infectiveness of fluids containing them after having been passed through the ‘filters, demonstrates that at least in some stages of their de- velopment they are actually too small to be visible under the highest power of the microscope. However, in the case of some of these unseen parasites we have sufficient knowledge of their habits and life histories to wage a fairly intelligent war against them, at least as regards prevention. The parasite of yellow fever, for instance, has never been seen with certainty. Yet we know almost beyond question that it is a protozoan, we know its full life history in a general way, and to a large extent we know how to combat it, far better, in fact, than we know how to combat some of the well-known parasites. There are two other diseases, dengue and phlebotomus fever, which are quite certainly caused by parasites related to that of yellow fever, but which have not yet been discovered. Until recently typhus fever was included in the list of possible proto- zoan parasites but Plotz in 1914 discovered a bacillus which is now quite generally believed to be at least partially the cause of that disease. Rocha-Lima and others have found certain minute bodies in typhus-infected lice which they suspected might be of protozoan nature, and Rocha-Lima has named them Rickettsia prowazeki.* American investigators are inclined to look upon these bodies as forms of the bacillus discovered by Plotz. Several other diseases, some of them of prime importance, of which the parasites are of obscure nature, are believed by some workers to be caused by Protozoa: such are hydrophobia or rabies, trachoma, smallpox, verruga peruviana (not Oroya fever), foot-and-mouth disease, measles, scarlet fever and a few others. The parasites or parasite-like bodies which are associated with these diseases are in some cases minute, in other cases, e.g., hydrophobia, of relatively large size. In most of these diseases the ‘“‘ germ” or virus is capable of passing through ordinary bacterial filters, as shown by the infectiveness of filtered material. It is also evident from this that the viruses live out- * See footnote on p. 73. 170 OTHER SPOROZOA side the cells or blood corpuscles, at least during part of their life history. On the other hand, in these diseases there have been discovered bodies of various kinds within the cells, inter- preted by some workers as true parasites, by others as reaction products of the cells. These bodies have received zodélogical names, e.g., the Negri bodies of hydrophobia were named Neuro- ryctes hydrophobie, the cell inclusions in smallpox Cytoryctes variole, and soon. It is now a commoner belief that these bodies consist of material extruded from the nucleus of the cell into its cytoplasm where it surrounds one or many of the minute or- ganisms during the intracellular portion of their life history. For these problematical organisms, minute in size, of uncertain life history, and apparently enshrouded in a mantle of extruded nuclear material during their intracellular life, the name Chlamy- dozoa (meaning mantle animals) has been given. Whether these bodies have been correctly interpreted as described above and whether they should be considered Protozoa is open to question. Their animal nature has not been sufficiently demonstrated to warrant more than brief mention of them and the diseases they cause in a treatise on animal parasites. In the following paragraphs the sporozoan parasites and ob- scure or invisible parasites which have been briefly mentioned above will be discussed in a little more detail in the following order: (1) coccidians, (2) Rhinosporidiuwm, (3) Sarcosporidia, (4) Oroya fever, (5) the yellow fever group, (6) the spotted fever group, (7) Chlamydozoa. Coccidians There are a number of serious diseases of animals which are caused by parasites of the class Sporozoa known as coccidians. These are very small animals, without distinct organs of lo- comotion, which have both an asexual and a sexual phase in their life history (Fig. 48). The asexual phase is not unlike what takes place in the asexual phase of malaria parasites, ex- cept that the parasites live inside of cells lining the intestine instead of in the blood. Like the malaria parasites, a coccidian, within the epithelial cell in which it is living (Fig. 48A—C), di- vides into two, four, eight, sixteen, or perhaps twenty or more daughter cells, arranged somewhat like the segments of an orange (Fig. 48D). The young coccidians, escaping from the COCCIDIANS 171 host cell which has been preyed upon and destroyed, invade fresh cells, multiply again, and thus eventually destroy large portions of the lining of the digestive tract. The daughter coccidians are not adapted for withstanding conditions outside the intestine In intestine. Fig. 48. Life history of Himeria avium. A, infection of epithelial cells of in- testine by sporozoites ingested with food or water; B, growth inside cell; C and D, sporulation and formation of young spores; # and G, formation of female gamete; F and H, formation of male gametes; J, fertilization; J, fully developed odcyst as passed out with feces; K, L and M, formation of four sporocysts; N, complete development of sporocysts, each containing two sporozoites; O, same, ingested by susceptible animal; P, sporocyst liberated from oédcyst in alimentary canal; Q, liberated sporozoite ready to infect epithelial cell, as shown in A. of the host, and therefore the parasite would be exterminated with the death of its host were it not protected in some manner against this calamity. The sexual phase of its life history serves 172 OTHER SPOROZOA this important purpose. Probably stimulated by reactions against them on the part of the host certain coccidians, instead of multiplying in the usual manner, differentiate into sexual forms, some transforming into large immobile egglike female individuals or macrogametes (Fig. 48E and G), others dividing into numerous very active flagellated spermlike male individuals or microgametes (Fig. 48F and H). One of the spermlike in- dividuals penetrates an egglike individual and fuses with it (Fig. 481), in precisely the same manner as a spermatozo6n fertilizes an egg in higher animals. The fertilized individual develops a thick resistant cyst wall and is then known as an “odeyst”’ (Fig. 48J). The parasite is now ready to hazard the dangers of an exit into the outside world, and is passed out with the feces. Eventually, sometimes within a few days, the con- tents of the odcyst divide into several parts, each known as a “ sporoeyst ” (Fig. 48K, L and M). Each sporocyst in turn develops within itself a number of ‘ sporozoites” (Fig. 48N), each capable of infecting a separate cell in a new host. The odcysts with their contained sporocysts and sporozoites can exist in soil or dust for a long time, : awaiting an opportunity to enter a new ion Oaenn ior Tacs victim with food or water. spora from British soldier Infection with coecidians has not often See ok ee been observed in man but it is pos- sporocysts, each with four sibly more prevalent than is commonly a * 1000. (After thought. A few cases have been re- ported of human infection with a coc- cidian very similar to Eimeria stiede, which infests the intestine and liver of rabbits; some workers believe these cases to have been caused by this very species, and that infection ‘probably resulted from eating infected livers of rabbits. Recently Wen- yon has reported the not uncommon occurrence of odcysts of two species of coccidians in the feces of British soldiers returning from Gallipoli. The cysts of the commoner species, of the genus Isospora, contain a single mass of protoplasm when first passed, but in three or four days they become fully developed and con- tain two sporocysts, each with four sporozoites (Fig. 49). The cysts of the other species, referred to the genus Eimeria, differ in producing four sporocysts, each with two sporozoites (Fig. RHINOSPORIDIUM 173 50). Little is known of the symptoms produced by these para- sites, but since they live inside epithelial cells of the intestine or liver they must be injurious. Wenyon has recently reported dysenteric symptoms in a case in which no intestinal parasites except Isospora o were present. Coccidians are un- es}}) \ oogyst doubtedly spread by means of water or food polluted by mud and dirt, by unsanitary habits, and by flies. ~"-" Sporocyst resco Sporozoite Rhinosporidium, a Parasite of the Nose In natives of India there is occasion- —yyg, 50. Odeyst of Himeria ally observed a peculiar infection of the containing four sporocysts, each nose in which a red tumor, flecked with “!t2 *¥° sporozoites. whitish spots, and likened by some authors to a raspberry, grows out from the partition or septum of the nose, remaining attached by a narrow stalk. The tumors are not very painful, but they tend to block the nasal passages. It has been suggested that this disease, known as nasal polypus, may have the same in- fluence on the intellect of children that other impediments of the nose and throat are known to have. When the tumor is cut the white spots visible on the surface are seen to be scattered throughout the tissue and to be of very variable size. Microscopic examination shows them to be the cysts of a protozoan parasite in various stages of development. The parasite has been named Rhinosporidium kinealyi, and is classified as a member of the group of Sporozoa known as Hap- losporidia. The cysts in the tumor are filled with great numbers of spherical or oval bodies, the pansporoblasts, each of these in turn contain- ing from one to a dozen closely-packed spores (see small portion of a cyst in Fig. 51). The manner of development of the cysts and of the tumor can readily be discovered from the various stages of development of different cysts and parts of cysts which can be observed in a single tumor. The youngest cysts are small granular masses of protoplasm, more or less irregular in shape. As one of these minute animals grows there are developed within it small bodies with definite shape which are destined to become the pansporoblasts already mentioned. However, the proto- 174 OTHER SPOROZOA plasm at the periphery of the animal continues to grow, constantly becoming differentiated into new pansporoblasts. The young pansporoblasts (Fig. 51, yg. pansp.), at first simple masses of protoplasm, soon form within themselves one, two, four, and ultimately as many as 12 spores, tightly clumped together so as to resemble little mul- —=—= —__ berries (Fig. 51, mat. DoS 900" pansp.). From the mode of development of the cysts it is clear that the older pansporoblasts are the ones near the center of the cyst, the younger ones those toward the periphery. | When _ the cysts have reached a certain size the growth of the periphery ceases, ° all the pansporoblasts ma- Fic. 51. Portion of fully developed cyst of Rhinosporidium; ec. w., eyst wall; yg. pansp., ture and the cyst ruptures, young pansporoblasts; mat. pansp., fully de- liberating the spores into veloped pansporoblasts containing spores, sp. : ° xX about 100. (After Fantham and Porter.) the surrounding tissue, each to develop into a new cyst. How the parasites are transmitted to new hosts is not known. A similar disease was found some years ago in South America and a parasite, then named Coccidiwm seeberi, has been described from the tumors. It is possible that this may be the same organism as that of Indian nasal polypus, but according to Fan- tham, who was one of the original describers of Rhinosporidium, there are a number of differences between them. CC. e-— a yg. pansp.--=—- Sarcosporidia, Parasites of the Muscles Brief mention should be made of a group of Sporozoa known as the Sarcosporidia which develop relatively enormous cysts in the muscles of vertebrate animals, especially in mammals. These parasites are usually found in the striped muscles but they also occur in other muscles. Infected muscles (Fig. 52B and D) appear to have white streaks or patches in them, sometimes SARCOSPORIDIA WA; several inches in length. Microscopic examination shows that these patches are cysts containing thousands of tiny spores, segregated into chambers (Fig. 52A) which correspond to the pansporoblasts of Rhinosporidium. The spores (Fig. 52C), es- caping from the cyst, ultimately develop into new cysts in much i Wotes, fs, ee A aT oA mt (a MALL ays (MI rea Hf eee Mutiny et oe ee is tie { ask Eat = ie 7 (eT IL pt sth D Fie. 52. Sareosporidia. A, Sarcocystis blanchardi of ox, longitudinal section of infected muscle fiber (m. f.) showing spores (sp.) in chambers of compartments (comp.); n., nucleus of muscle fiber, x 265. (After von Eecke from Wasilewsky.) B, cross section of sarcocyst from human larynx, probably S. tenella, « 200. D, same, longitudinal section. (After Baraban and St. Remy.) C, spore of S. tenella of sheep. (After Laveran and Mesnil.) the same way as is the case with the nose parasite. Although the muscle parasites have been known to parasitologists for many years there are portions of the life history which are not yet known. Darling and others have suggested that these pe- culiar protozoans may be “ side-tracked varieties of parasites of invertebrate animals.” We have no definite knowledge of the normal means of transmission although a number of possible methods are known. It has been found that infections can be spread by cannibalism, and that the feces of infected mice can infect other mice; it has also been stated that spores occur in the circulating blood, which would mean that blood-sucking ar- thropods may be instrumental in the transfer. Fleshflies may also play a part in dispersing the spores. Erdmann has shown that when spores of Sarcosporidia de- velop in the intestine a very powerful toxin, called sarcocystin, is discharged and destroys the neighboring epithelial cells of the intestine and thus breaks a way for the young parasite into the 176 OTHER SPOROZOA lymphaties and ultimately into the muscles. Crawley has re- cently described in Sarcocystis muris of mice what he interprets as sexual differentiation of the spores and fertilization within 18 hours after the spores have been ingested by mice. Crawley believes the Sarcosporidia to be closely allied to the Coccidia, and suggests that there may be an unrecognized stage of development in a carnivorous animal. It is quite evident from the various hypotheses and speculations mentioned above that there is much yet to be learned about these enigmatic parasites. Only a few scattered cases of Sarcosporidia in man have been recorded, and these may be looked upon as purely accidental. The parts affected have been the muscles of the heart and larynx. Many speculations as to how these infections occurred have been made, but nothing definite is known about it. It is probable that the human infections are due to Sarcocystis muris, a species which produces a very fatal disease in mice, and infections may have been due to contamination of food or water with the ex- crement of infected mice. The use of meat of Indian buffaloes infected with another species, Sarcocystis tenella bubali, seems to have no injurious effect on man, but ingested spores cause ir- regular fever. Oroya Fever The Disease. — Since at least the time of the Incas, Peru has suffered from a strange disease which has swept over the country from time to time in the form of frightful epidemics, some of which have cost thousands of lives. One of the severest recent outbreaks occurred among the workmen building the Peruvian Central Railway between Lima and Oroya and it is estimated that at least 7000 individuals died in it. In 1906 at least one- tenth of 2000 workmen employed building tunnels and bridges on the Central Railway died of the fever, and one bridge in par- ticular, which was the scene of a great many deaths from the dis- ease, has come to be known as the Oroya Fever Bridge (Fig. 53). The disease is at present endemic in the deep cleft canyons or quebradas (Fig. 53) characteristic of the west face of the Andes, at an elevation of between 2500 and 8000 ft., but it is probable that it has a wider distribution than is now supposed. It shows a marked seasonal prevalence, most of the cases occurring from January to April, especially toward the close of the warm, rainy season. OROYA FEVER Li Fic. 53. Above, a typical ‘‘quebrada”’ or canyon on the west slope of the Andes where Oroya fever abounds. Below, the famous *‘ Oroya Fever Bridge’’ on Peruvian Central Railway where hundreds of lives were lost from Oroya fever. (Photos kindly lent by Harvard School of Tropical Medicine, previously published by Strong et al.) 178 OTHER SPOROZOA Oroya fever has been constantly confused with other diseases and it was not until the South American expedition of the Harvard School of Tropical Medicine, under the leadership of Dr. R. P. Strong, made an investigation of the disease that some order was brought out of the confusion. Malaria, para- typhoid, and particularly verruga peruviana are the diseases which have been most frequently confused with Oroya fever. Mixed infection of these diseases and others such as yaws and tuberculosis with true Oroya fever has still further complicated matters. From the time of the Incas verruga peruviana and Oroya fever have been associated and regarded as different phases of the same disease, and this view is still held by some inyesti- gators. The fact that the characteristic nodules of verruga were usually associated with a very mild form of fever and sometimes with none at all, while oroya fever was of very severe type caus- ing very high fatality, raised some question as to the distinctness of the diseases. To settle this point a Peruvian medical stu- dent, Daniel Carrion, vaccinated himself with blood from a verruga nodule. Five or six weeks later he died of a severe fever, and the question of the identity of the disease was ap- parently settled, and the fever was called ‘“ Carrion’s Fever ”’ in his honor. The notes regarding Carrion’s illness have been lost and it is now believed that he may have died of some other disease or that the patient from whom he inoculated himself may have been suffering from some other disease in addition to verruga. As a result of their own studies, Dr. Strong and his colleagues believe that the diseases are quite distinct. They have shown that Oroya fever is caused by a very minute parasite living in the red blood corpuscles and multiplying in the endothelial cells, and that it cannot be inoculated into animals; verruga peruviana, on the other hand, is caused by a virus which is ultra-microscopic, probably related to the smallpox virus, and can be successfully inoculated into laboratory animals. It is easy to understand how the two diseases were confused, since to a large extent their ranges overlap and a visitor to endemic regions would be likely to contract both. Verruga, being less quickly contracted and having a longer incubation period, would tend to appear later than Oroya fever, and would therefore be looked upon as a later stage of the same disease. The native belief that a general erup- BARTONELLA BACILLIFORMIS 179 tion was favorable to recovery, a belief undoubtedly based upon the benign nature of verruga, leads to the adoption of all sorts of methods to invoke a breaking out of the skin, such as applications of turpentine, rubbing with irritant leaves, etc., and undoubtedly a great many cases of eruptions following Oroya fever are really only the eruptions caused by the artificial irritation of the skin. Oroya fever, after an incubation period of about 20 days, begins with a general ‘feeling of malaise and aches in the Joints, followed by chills and fever, which last irregularly for many weeks. The fever is accompanied by a rapid pernicious anemia, the red blood corpuscles being reduced in some cases to one-fifth, or even less, of their normal number. This causes severe prostration and in a large per cent of cases death results within three or four weeks. The skin assumes a yellowish waxy color, and there are often slight hemorrhages of the mucous membranes and various internal organs, as demonstrated by post mortem examinations. The liver and spleen become moderately enlarged, and the lymph glands are swollen. The Parasite. — The true parasite of Oroya fever was first discovered by Barton, of Lima, Peru, in 1905 and confirmed by him in 1909, at which time he suspected that it might be a protozoan. The parasites were more thoroughly studied by the Harvard expedition in 1913 and 1914 and named Barton- ella bacilliformis. Dr. Strong and his colleagues describe them as minute rods or, more Fic. 54. Bartonella bacilliformis, liv- . ley Herieiaeds _ ing. A, Band C, successive drawings of rarely, rounde odles OCCUT- 4 single red corpuscle showing movements ring inside the red blood cor- of parasite within it; D, F and F, corpuscle 1 Fi al a 55 containing two rod-shaped and four round puscies ( igs. 9 an 5). parasites, showing migrations of the rod- These parasites, the rod form shaped individuals. : 4 z D5. (After Katsurada) in water with certain species of snails, particularly Melania liber- tina, the miracidia swarm about the snails and burrow into them, shedding their cilia as they go. The entire cycle of development in the snail has not been worked out but it is probably very similar to that of Schistosoma. Sporocysts of various sizes occur in the liver and other tissues of the snail, and it is probable that these produce the cercarie directly. Nakagawa discovered the encysted cercarie of this species, proved to be such by experimental infection of animals, in three 222 THE FLUKES species of crabs in Formosa, and Yoshida, another Japanese in- vestigator, acting on the discovery of his countryman, found the larve in a fourth species of crab in Japan. The crabs most com- monly infected are Potamon obtusipes, a coarse-shelled, chestnut- colored crab about one and a half inches in diameter, and P. dehaanii, a slightly smaller species, grayish black or red- dish in color. Both these crabs bound in the shallow waters of mountain streams, and the former species is sometimes used as food. An- Fic. 72. A common fresh-water crab Other implicated species, of Japan, Brioche Japonious, which serves. Erigcheir japonicus (Fig. 72), is abundant in all plains rivers in Japan and is a common article of diet throughout the country. It is a larger crab, reaching a diameter of three inches, and has large hairy claws. The fourth species, Sesarma dehaani, is of medium size, dark in color with light reddish claws, and inedible. Miyairi has shown that in Korea another crab, Asiacus japonicus, is the intermediate host. The lung fluke cerearize encysted in these crabs (Fig. 73A) were found chiefly in the liver while young, but when older they Fia. 73. A, encysted cerecaria of human lung fluke, Paragonimus ringeri, from gill of crab; B, larva emerging from cyst. o0.s., oral sucker; int., intestine; ex. v., excretory vesicle; v. s., ventral sucker. 50. (After Yoshida.) occur in the gills. They vary in number from a few to several hundred. In some localities a very high per cent of crabs are infected, Nakagawa reporting that practically 100 per cent are infected in one district in Formosa where the lung fluke is very common. The cysts containing the cercarie are nearly round, 0.5 mm. (5 of an inch) or less in diameter, and have relatively EEE —E—— Tare - re a > ——" or tail tee ts ey a Fy, "ww LUNG FLUKES 223 thick walls. The enclosed cercaria lies straight, unlike most encysted cercarie, and the body is entirely covered by short spines. In fully-developed specimens the suckers, digestive tract and other parts of the anatomy of the enclosed cercarie can be seen (Fig. 73A). While still in the cysts the cercariz are fairly resistant to unfavorable environmental influences, but are easily destroyed after hatching. When an encysted cercaria is swallowed by a susceptible ani- mal the cyst wall is dissolved off in the intestine, the active liberated larva (Fig. 73B) bores through the intestinal wall, wanders about in the abdominal cavity for some time, then bores through the diaphragm into the pleural cavity, whence it eventually penetrates the lungs from the outer surface. It becomes mature in about 90 days. Occasionally the worms apparently get lost and bore through the abdominal wall and muscular connective tissues. It is probably in this way that other organs than the lungs are penetrated by the flukes. There are two ways in which man may become infected, namely, by eating infected crabs which are not thoroughly cooked, or by drinking water containing cysts discharged from infected crabs. As already remarked, the mature cysts make their way to the gills, whence they can easily be removed, and whence they probably escape readily under natural conditions, thus becoming free in the water. Here they may remain alive for some time, probably 30 days or more. Yoshida states that the cysts sink to the bottom, in which case human infection could occur only rarely if ever from infected water. Nakagawa, how- ever, observed that 20 per cent of the larve when freed float on the surface of the water. Prevention of infection, in Japan at least, obviously consists in abstinence from raw crabs as food and in avoidance of water for drinking which may possibly be infected. Whether or not other animals may serve as hosts for the cercariz is unknown, but if the allied Paragonimus kellicotti is truly endemic in the United States, where no fresh-water crabs are found, some other animal must serve as an intermediate host, possibly certain species of crayfish. The fact that the lung fluke is not known as an en- demic human parasite in this country suggests that the inter- mediate host may be an animal which is not used as food and the habits of which give little opportunity for the parasites to gain 224 THE FLUKES access to the human body. The disease is said to have increased in Peru, having been introduced there by Japanese and Chinese laborers. If this is true some Peruvian animal, probably a fresh-water crab, must serve as an intermediate host. This suggests that the disease if once intro- duced might flourish in other countries, especially where fresh-water crustaceans are eaten. Lung fluke infection is evidently another disease for which a quarantine should be established. Liver Flukes Although the liver fluke of the sheep, Fasciola hepatica, and other flukes of herbivorous animals are occasionally found in man, they cannot be looked upon as usual human parasites. Adult liver flukes are sometimes accidentally eaten with raw liver, in which ease they attach themselves to the mem- branes of the throat, causing irritation, congestion, a buzzing in the ears, difficult breathing, and other quite alarming symptoms. Vomiting to ex- Fic. 74. The Chinese fluke, pe] the worms usually gives immediate Opisthorchis sinensis. X 33. ; m., mouth in oral sucker; ph., relief. pharynx; gen. p., genital pores; There are several species of flukes, v. s., ventral sucker; sh. gl., so- . called vittelline or yolk glands, however, which are apparently espe- really shell glands; ut., coiled Gially adapted for parasitizing carnivo- egg-filled uterus; int., intestine; : i sp. d., sperm duct; ov., ovary; Tous animals, and which are common sem. ree., seminal receptacle, hyman parasites in *some countries. where sperms for fertilizing eggs ; WF Nea are temporarily stored; t.,testis; Japan, China, the Philippines and other exe. ¢., exeretory canal; exe. P-» oriental countries are especially afflicted excretory pore. (After Stiles.) : : by these flukes. The commonest species in man is the Chinese fluke, Clonorchis sinensis (Fig. 74) which is found in all of southern Asia from India to Korea. In some parts of Japan about 60 per cent of the population are said to harbor it in their livers, sometimes in hundreds or even thousands. Leiper found it common in both dog and man in the vicinity a er ee ee as HUMAN LIVER FLUKES 225 of Shanghai. It is also found in the liver ducts of cats, hogs, and probably other flesh-eating animals. It is from one-half to three-quarters of an inch in length, and nearly four times as long as wide. . The ventral sucker is very small, and is situated on the anterior third of the body. Some authors believe that a small variety of this fluke found in Japan constitutes another species, C. endemicus, but this view is assailed by recent investigations. In Europe there occurs a species, Opisthorchis felaneus. (Fig. 775A); which is very common in domestic cats and dogs and is by no means uncommon in man; there is one record of its having been found in eight or nine out of 124 post mortem examina- tions in Siberia. A very closely related species, O. pseudofelineus (Fig. 75B), has been found in cats and coyotes in the central parts of the United States. From its similarity to the Old World species it would not be surprising to find it occasionally parasitic in man. ; : Fia. 75. A, Cat fluke, Opisthorchis felineus; The European SPeCcles, B, American cat fluke, O. pseudofelineus. Abbre- Opisthorchis felineus, is viations as in Fig. 74. x about 5. (A, after usually a litflesiescothan Stiles and Hassall; B, after Stiles.) half an inch in length, and shaped very much like Clonorchis sinensis. The American QO. pseudofelineus is somewhat longer and slenderer than the European species. Another species of the same genus, O. noverca, occurs commonly in pariah dogs in India, and occasionally in man. It differs from the Euro- pean species chiefly in having the skin thickly beset with spines. 226 THE FLUKES Little is known of the life history of any species except the Chinese fluke, C. sinensis. The eggs (Fig. 76A) are of charac- teristic shape, and hatch in water into miracidia (Fig. 76B). The encysted cercarie of this fluke (Fig. 77A) have been found in the subcutaneous tissues and muscles of 12 different species of fresh-water fish. The cysts, which are very small, measuring only about 0.14 by 0.10 mm. (+45 by zo of an inch), are usually more abundant in the superfi- Fic. 76. Egg and ciliated em- cial than in the deeper tissues. Fe Seg Cakes Reeateiad Although cysts can be found in fish throughout the year, the younger ones are more frequently met with in late summer and early autumn. When infected fish are eaten, according to experiments re- cently made with animals by Kobayashi, the larval flukes escape from the cysts (Fig. 77B) within three hours, and in fifteen hours they may; already have reached the bile duct and gall bladder. The parasites reach maturity and eggs are found in the feeces of the host within 26 days. The young flukes have a spiny cuticle until nearly mature, but the spines finally disappear. a The first intermediate host Fic. 77. Larve of Chinese fluke; A, : : -y- cercaria encysted in fish; B, larva freed into which newly hatched cili- from cyst; m., mouth in oral sucker; v. s., ated embryos penetrate is not ventral sucker; ex. v., excretory vesicle; : ph., pharynx; int., intestine. certainly known yet, but Kobayashi believes it is one or more of the several species of snails of the genus Melania, especially Melania libertina. These snails have been found to harbor cercarie which bear a distinct resem- blance to the young encysted larve of the Chinese fluke, and they are abundant in rivers and swamps of regions where the liver infection prevails. It is probable that the European liver fluke, O. felineus, and its Indian and American allies all have histories very similar to that HUMAN LIVER FLUKES Pea | of the oriental species. Their occurrence in man in countries where fresh-water fish is a common article of diet, and their frequency in animals which eat raw fish, strongly suggest fishes as intermediate hosts. These liver flukes, like the sheep fluke, live chiefly in the gall _ bladder and bile ducts where they often cause much mechanical obstruction on account of their large numbers. Severe infec- tions such as occur in countries like Japan where raw fish is commonly eaten cause symptoms of a very serious nature. One of the most prominent of these is enlargement of the liver ac- companied by more or less bloody diarrhea; the latter becomes more and more constant as time goes on. The liver sometimes becomes painful, and jaundice is a frequent symptom. The patient becomes anemic, emaciated and weak, and is ready prey for other diseases. There are often periods of partial recovery followed by relapses, probably due to reinfections, and the patient ultimately becomes exhausted and succumbs to a cold, an attack of malaria, or other ailment from which one would ordinarily recover readily. There is no specific treatment for the disease. The only measures that can be taken are to remove the patient from any possible source of reinfection and to keep him in the best possible general health, with wholesome diet, good air and proper ex- ercise. How long the flukes persist in the liver is not known. Means of prevention of the disease are suggested by what is known of the life history of the parasites. The most important measure is unquestionably the suppression of the habit of eating uncooked fish in places where the disease is endemic. Kobayashi has shown that while the larve of C. sinensis are killed at once on exposure to a boiling temperature and in a short time when exposed to considerably lower temperatures, they are not destroyed by exposure to vinegar for five hours, nor by re- frigeration. A second measure, which is far less reliable, is the prevention of contamination of water in which fish live. It is impossible to prevent some contamination of water by the lower animals which carry the infection, and it is nearly as difficult to prevent con- tamination by human feces. The almost universal use of night soil (human feces) for fertilizer in oriental countries is a serious hindrance to the sanitary disposal of such infected material. 228 THE FLUKES Leiper suggests that this problem may be solved by a chemical treatment of night soil which would destroy all parasite eggs or cysts and yet not injure its value as a fertilizer. Intestinal Flukes There are several species of flukes which appear to be common parasites of the human intestine in certain parts of the world, especially in the oriental countries where the other human flukes abound the most. Many of these flukes are very small, but they may occur in great numbers, producing practically the same effects as do tapeworms, — anemia, emaciation and general debility. Many species are probably only accidental human parasites, normally living in some other host but occasionally finding their way into the human intestine with food or water and establishing themselves there. The smallest fluke known to be parasitic in man is Yokagawa yokagawa, named after a Japanese parasitologist. It is widely distributed in Japan, Korea, Formosa, parts of China, and probably other oriental countries. It infects mice and dogs as well as man. The whole life history is unknown but the encysted cercariz are known to occur in the “ ayu,” a Japanese fresh-water fish which is commonly eaten raw, and in a number of other kinds of fish. The cysts are most numerous in the connective tissue under the skin and about the fins, especially early in the season, indicating that the fish become infected by free-swimming cer- earie which bore through the skin, and not by cercarize eaten with another host. The encysted cercariz closely resemble those of Clonorchis sinensis. The development in the final host is said to take only from seven to ten days. Y. yokagawa inhabits the upper portion of the small intestine, sometimes in consider- able numbers, but it never seems to do enough damage to cause more than a slight intestinal catarrh. It is remarkable for the lack of a ventral sucker and is only about 1 mm. (about 3; of an inch) in length, and about half as broad. Its body is covered with a great many microscopic spines. ; A very similar fluke, Heterophyes heterophyes (Fig. 62), only slightly larger, occurs in a variety of animals from Egypt to Japan, and occasionally parasitizes man. Two species of Echi- nostoma normally parasitic in other animals occur occasionally INTESTINAL FLUKES 229 in man in the Malay countries. They are distinguished from other flukes by the crown of spines around the mouth sucker. One species, H. zlocanum, about one-fifth of an inch long, was found endemic among some Filipinos in a prison in Manila. The other, H. malayanum, about two-fifths of an inch long, oc- casionally parasitizes man in the Malay countries. Gastrodiscoides hominis (Fig. 78) is a species which is character- ized by the expansion of the posterior end of the body into a great Fic. 78. Gastrodicoides hominis. A, ventral view, showing disc-like .expansion and posterior position of ventral sucker; B and C, dorsal views; D, lateral view; E, eggs. A-D, X 3; E, x65. (After Lewis and McConnell.) concave dise. It is a small reddish brown parasite a little over one-fourth of an inch in length, which inhabits the cecum and large intestine of hogs, and occasionally of man, in India. 5 of an inch) in length. The mother worms usually burrow into the walls of the intestine far enough so that the young can be deposited directly into a 290 TRICHINA WORMS lymph or bloodvessel rather than into the lumen of the intestine. “The larve are carried in the blood or lymph stream, and are distributed to nearly all parts of the body. They leave the capillaries in the striped muscles and penetrate into the fibers. Although young migrating larve may accidentally be carried to other tissues, and have even been found in the cerebrospinal fluid and in the mammary glands and milk of a nursing woman, they are apparently incapable of developing in any tissue except — mt Hm TT) Been een OD St Fic. 120. Larve of trichina worms burrowing in human flesh before encyst- ment. From preparation from diaphragm of victim of trichiniasis. X 75. voluntary muscle. They may settle in the heart muscle, but degenerate there without continuing their development. . The muscles particularly favored by the worms are those of the dia- phragm, ribs, larynx, tongue and eye, which, as noted by Staubli, are among the most active uncles: and ‘the muscles with the richest blood supply and largest amount of oxygen. According to Flury frichine have a high glycogen content, and probably subsist on the glycogen stored in the striped muscles; in fact the abundance of glycogen may account for their location in these muscles. FORMATION OF CYSTS 291 When the larvee have arrived at their destination in the muscles they thread their way between the fibers towards the ends of the muscles (Fig. 120), ultimately penetrating the individual fibers where they coil up into loose spirals, constantly coiling and un- coiling as much as their close quarters will permit. When worms which are still boring are teased out of the flesh and warmed to - blood heat, they can be seen constantly tightening and loosening their coiled form, reminding one of a fist being alternately clenched and unclenched. After entering muscle fibers the worms grow rapidly in size to a length of one mm. (,'5 of an inch), ten times their original size, and become sexually differentiated. The inflam- mation caused by the movements and waste products of the animals results in the degeneration of the enclosing muscle fibers and in the formation, beginning about a month after infection, of connective tissue cysts around the young worms. The cysts (Fig. 118), which are completely developed in from seven to nine weeks, are lemon-shaped, from 0.25 to 0.5 mm. (y45 to 5 of an inch) long, lying parallel with the muscle fibers. As a rule only one or two worms are enclosed in a cyst but as many as seven in a cyst have been observed. When first formed the cysts are very delicate and can only be seen by careful focusing with the microscope, but they gradually grow thicker and more conspicuous, and after seven or eight months there begins a deposit of chalky calcareous matter (Fig. 12VAS, this process Fic. 121. Stages in calcification of trichina; : 3 A, ends calcified; B, thin layer of calcareous ultimately results in the material over whole cyst, worm beginning to entire cyst becoming hard- degenerate; C, complete calcification. (After ened into a_ calcareous as dish nodule (Figs. 121B and C), and even the enclosed worm, which usually degenerates and dies after some months, becomes calcified after a number of years. There are cases, however, where the trichina worms do not die and disintegrate so soon, and the calcification process is much slower. There are records of these worms found living in cysts in hogs 11 years after in- fection-and in man 25 to 31 years after, though it is doubt- ful whether in some of these cases a fresh infection did not 292 TRICHINA WORMS occur unknown to the patient or to the observers who made the records. The larval worms, which, as pointed out by Ransom, on account of their advanced stage of development are comparable with the nymphs rather than the larve of arthropods, when encysted in the flesh of some susceptible animal never develop further until eaten by another susceptible animal. If they are eaten the cyst is dissolved off*in the intestine of the new host, the larve are set free in the digestive tract, and within three days be- come sexually mature and copulate, to begin the performance all over. Obviously man usually if not always becomes infected from eating infected pork, whereas hogs may be infected not only by eating scraps of raw pork but also by eating the bodies of infected rats and mice. The latter animals are infected in a similar manner. The number of trichina worms which may be harbored by a single host is almost incredible. According to the writer’s investigations, the sausage which was the cause of a recent epidemic in Portland, Oregon, contained over 2,000,000 larve to the pound at a very conservative estimate, and in a bit of human muscle from the diaphragm of an Italian who fell victim to the disease the number of worms was even greater. The Disease. — The disease caused by trichina worms is more fatal to man than to any other animal, the fatality sometimes rising to 30 per cent or more of the cases.. Even in man the worms, if eaten only in small numbers, produce no serious or even noticeable effect. When eaten in great numbers, however, as would always happen in eating heavily-infected raw or under- done pork, the worms produce symptoms so much like typhoid fever that the disease is undoubtedly often diagnosed as such. The course of the disease, as described by Ransom, is somewhat as follows: the first symptoms of the disease — diarrhea, ab- dominal pains and intestinal catarrh — are the result of irritation of the intestine by the adult worms, especially the females, which burrow deep to deposit their young. Except in very light cases, a sort of general torpor is noticeable, accompanied by weakness, muscular twitching, ete. A very striking symptom, which ap- pears in about a week and lasts for a few days, is a marked puffi- ness or edema of the face and especially of the eyelids. As pointed out by Ransom, the gravity of the case cannot be judged SYMPTOMS 293 from the severity of the first symptoms. In some of the worst cases the first symptoms are very mild. Ms In nine or ten days or longer the second stage of the disease appears, accompanying the period of migration of the larve. This is the period which is frequently fatal. The most_pro- nounced-symptoms_are intense muscular pains and rheumatic aches, with disturbances in the particular muscles invaded, in- - terfering with the movements of the eyes, mastication, respira- tion, etc., the respiratory troubles becoming particularly severe in the fourth and fifth weeks of the disease, in fact sometimes so severe as to cause death from dyspnea or asthma. Profuse sweating and more or less constant fever, though sometimes occurring in the first stage also, are particularly characteristic of the second stage. The fever is commonly absent in children. The third stage, accompanying the encystment of the parasites, begins about six weeks after infection. The symptoms of the second stage become exaggerated, and in addition the face again becomes puffy, and. the arms, legs and abdominal walls are also swollen. The patient becomes very anemic, skin eruptions occur, the muscular pains gradually subside and the swollen portions of the skin often scale off. Pneumonia is a common compli- cation in the third stage. ~ Trichinella is unique among worms in causing constant fever. It is probable that the fever as well as certain changes in the blood corpuscles and chemical changes in the invaded muscles is due both to poisonous substances given off by the worms and to poisonous substances resulting from destroyed muscle tissue. Such substances have been found by Flury and Groll and others in cases of Trichinella infection. They are substances which act on the muscles themselves, on the nervous system, and on the bloodvessels. It is quite evident, as pointed out by Herrick, that with the invasion of the blood and tissues by millions of larvee and with the breaking down of large amounts of muscle tissue a constant inoculation of the infected person with poisonous protein material is taking place, a condition which always gives rise to fever. Certain volatile acids are produced by the muscle degeneration, and these are considered by Flury to account for the muscular pains. Other toxic substances account for most of the other symptoms of the disease, e.g., the marked increase in certain kinds of white blood corpuscles, the eosinophiles. 294 TRICHINA WORMS The duration and final outcome of the disease is variable, according to the heaviness of the infection. Death, as remarked before, may frequently result, and according to Ransom most commonly occurs from the fourth to the sixth week. It rarely occurs before the end of the second week or after the seventh. Recovery usually does not occur in less than from five to six weeks after infection, and often not for several months. Re- current muscular pains and weakness may continue for years and a stiffness may persist indefinitely in the invaded muscles. Com- monly cases in which a copious diarrhea appears early in the disease are of short duration and mild in type. Young children, due either to smaller quantities of pork eaten or to greater tend- ency to diarrhea, are likely to recover quickly. Treatment and Prevention. — The search for a specific remedy for trichiniasis has so far been futile. Even the adult worms in the intestine are much more difficult to dislodge or destroy than _ are other intestinal worms, since they bore so deeply into the intestinal walls that the ordinary drugs do not affect them. Even were it possible to drive out the adults readily, this often could not be done in time to prevent disease or death, since the infection is seldom recognized before the larve are already produced and are migrating throughout the bedy. This is the critical stage of the disease; if the system can endure the irritation and inflam- mation produced by the burrowing of millions of worms and can withstand the effects of the toxins produced both from the worms themselves and from the destroyed tissues during the first and heaviest onslaught of the newly produced larve, the danger is past. The fever, the muscular pains, amounting to agony for a time, and the intestinal disorders continue for weeks but gradually subside. The treatment employed during all this time can only be systematic and of general nature — efforts to reduce the fever, to permit sleep, to keep the digestive system in as good order as possible and to do all that can be done to keep up the vitality and general health. It is possible that if the trichina worms could be isolated and ground up, and injected into the blood, an active immunity could be built up as in the case of typhoid vaccinations. Passive immunity by injection of serum from a convalescent has been stated by Salzman to have some curative as well as preventive value, but this work needs confirmation. The disease, however, PREVENTION 295 is not so prevalent or so difficult to prevent by other means as to make promiscuous immunization justifiable, even if possible. A more hopeful though so far unproductive line of research regarding the treatment of the infection lies in experiments with drugs or serum to kill either the adult worms in the intestine or the larve before they begin destroying the tissues. Personal preventive measures against trichiniasis are easy and consist simply in abstinence from all pork which is not thoroughly cooked. Many experiments have been performed, and are still in progress, by the U. 8. Bureau of Animal Industry regarding the temperature necessary to destroy trichina worms. Boiled pork must be cooked for a length of time proportionate to its weight in order to insure the permeation of heat to the center. Experiments show that at least 30 to 36 minutes should be al- lowed to each kilogram of meat (2 lbs.). Hurried roasting does not destroy the parasites as long as red or raw portions are left in the center. Cold storage for 20 days or more at temperatures below 10° F. has been shown by Ransom to be destructive to trichine. The regulations of the U. 8. Bureau of Animal In- dustry, relative to pork products customarily to be eaten without cooking, require freezing for 20 days at a temperature of not higher than 5° F., or curing in accordance with certain specified pro- cesses. Temperatures above 10° F. are more or less uncertain in their effects. Salting and smoking are not efficacious unless carried out under certain conditions. Thorough salting is effec- tive, provided the meat is left for some time for the salt to per- meate it. Large pieces of pork placed in brine have been known to contain living trichine for over a month. The parasites in sausages are destroyed in 24 hours by hot smoking whereas they resist cold smoking for three days. Prevention of trichiniasis by meat inspection methods is at best only partial, and, while meat inspection might help to lessen the chances of the disease, it should not be implicitly relied upon. Probably in an ordinary meat inspection all heavy infections would be found, provided the inspector has been doing his work properly. The inspection usually consists in the microscopic ex- amination of a bit of muscle from tongue and diaphragm; if the examination is negative, the hog is passed. Obviously light infections must frequently escape notice, and the false sense of security which is the result of knowledge that meat has been 296 TRICHINA WORMS “inspected”? may do much damage. There is no inspection for trichine in force in the United States at the present time. Much could be done to prevent the prevalence of trichina in- fection in pork by preventing hogs from eating food which might be infected. Hogs should never be allowed access to the car- casses of other hogs or to the dead bodies of rats and mice, or to waste scraps of pork. Dead hogs or waste pork, if there is any possibility of their being infected, should not be thrown where rats and mice could prey upon them. If, these principles were carefully followed out, there is no doubt but that trichiniasis could be reduced to a much greater extent than it has been. The symptoms of trichina disease in hogs are much less evident than in man, and there is no certain diagnosis of it in living ani- mals except by microscopic examination of the muscles for the detection of the larve. When heavily infected, hogs show severe intestinal disorders, abdominal pains and stiff muscles, but there is nothing diagnostic in these symptoms. A farmer who drives sick hogs to market, however, in order to get rid of them, with- out giving proper warning of their condition which might make possible the discovery of trichina infection if present, should be considered guilty of criminal negligence, and punished in accordance with the damage done by this negligence. This is particularly true if he feeds his hogs waste containing raw meat, or allows them to feed upon dead animals —a very common practice. As has recently been pointed out by Stiles, there is no prac- tical or proper method of inspecting meat by which the absence of Trichinella can be guaranteed, and it is therefore unjust to hold a butcher responsible for cases of trichiniasis which may result from the eating of pork sold by him. ‘There are laws which pro- vide that ‘‘ diseased meat ” shall not be sold and that an implied warranty of fitness for food goes with any sale of food. Neither of these laws, however, can be unreasonably enforced. Techni- cally all meat is diseased, since there are no market animals which are not parasitized in some way. As to the “ implied warranty,” this can go only with an implied guarantee on the part of the buyer that the food will be properly prepared before being eaten. Clams in the shell, unhusked corn and uncooked beans are guaranteed as being fit for food only when properly prepared. In like manner pork is sold with the understanding FITNESS OF PORK FOR FOOD— 297 that it will be properly prepared, 7.e., thoroughly cooked. Raw pork, since it is likely to contain Trichinelle which may cause disease, and since the absence of these worms cannot be guaran- teed by any practical inspection now known, is unfit for food and therefore cannot be guaranteed if eaten raw. As Stiles has pointed out, great and unjustifiable loss may result from too _ stringent enforcement of the laws mentioned above. CHAPTER XVII FILARIZ AND THEIR ALLIES — General Account. — One of the most interesting and_ puzzling groups of human parasites are the members of the nematode genus Filaria. They are extremely common parasites in all tropical countries; (Have a unique and extraordinary life history, are associated with many serious pathological conditions and have figured prominently in the history of medical science. Sir Patrick Manson first discovered these worms swarming in human blood, while working on tropical diseases in India. They had previously been observed in various bodily excretions but only in rare cases and in small numbers. Manson found them in enormous numbers in the blood, but only at night. The worms were evidently larve and since they only rarely and ap- parently accidentally escaped from the body with excretions, the thought occurred to Manson that they must be liberated from the blood by some nocturnal blood-sucking insect. Man- son and others later proved this theory to be correct, and thus took the first step toward our present knowledge of the biologi- cal transmission of disease by insects, a step which marked the beginning of a new era in modern medicine. Many species of Filaria from human blood have been described, some of which undoubtedly are not valid species. Some species apparently produce no pathological conditions whatever, while others are associated with, and are usually considered to be the direct cause of, a large number of diseased conditions. Some of the species are of limited geographic distribution while others are of world-wide range, probably due to differences in the ex- tent of the distribution of the intermediate host. In some tropical localities 50 per cent or more of the population are para- sitized by these animals. In South China ten per cent of the entire population is said to be infected and in some South Sea Islands over half of the inhabitants are infected. Recently in an exam- ination of 949 natives from the Congo-Cameron country of 298 LIFE HISTORY OF FILARIA BANCROFTI 299 Africa, about 74 per cent of the men, 79 per cent of the women and 33 per cent of the children were found to be filariated. The blood-dwelling filariz which are readily observed are, as remarked above, only larvee, the adults being much larger, long, slender worms which live in the lymphatic vessels, connective tissue or other tissues of the body. It is to these adult worms and not to the larve that the so-called “ filarial diseases’ are supposed to be due; the blood-living worms apparently cause no serious symptoms. The larve have been termed ‘ micro- filariz ’’ to distinguish them from the adult worms. _Filaria bancrofti The most widespread species and most important from a medical point of view is Filaria bancroftt. This nematode occurs more or less abundantly in all warm climates of the world, north to southern United States and southern Europe and Asia, and south to southern Qo) Australia and Patagonia. Life History. — The adult Filarie g Ss were_ re_not discovered for many years Hie 199) AdultsoePaara after ‘the larve had been found in the bancrofti, female () and . Natural size. blood, since they occur in the deep- (iter Se as a seated 'lymphatie. vessels where they could _ “be observed only on post mortem examinations. They are very long, s slender nematodes (Fig. 122), the females three or four inches in length and hardly greater in diameter than a horsehair, and the males about half this size. In their normal habitat in the lymph vessels the males and females live coiled up to- gether, sometimes several pairs of them Fig. 123. Microfiluria of in a knot. The male worms, in addition eles ial varent. cer, t0 their smaller size, may be distin- rounded by delicate mem- guished from the females by the coiled Dene ecu tail which reminds one of a vine tendril. The greater part of the body of the female is occupied by a pair of uteri, which in the adult are always filled with eggs. The eggs (Fig. 123) usually hatch before they are laid so that living young swarm forth from the parent worm, but in excep- tional cases the eggs are deposited before hatching. The young DEPARTR.EN ‘4 Ur 300 FILARILZ AND THEIR ALLIES worms reach the blood by way of the lymph stream and these grow to about 300 yu (a little over 745 of an inch) in length. They are delicate colorless worms (Fig. 124A), blunt at the anterior end and tapering to a slender point at the tail end, and are entirely enclosed in a remarkably delicate transparent sheath, which, although it fits as tightly as a glove over a finger, is too long for the animal and can be seen projecting at either end. The sheath may be looked upon as a wonderful adaptation to prevent the worms from being able to bore through the bloodvessels and escape from the blood, in which case they would miss their chance for ‘ salvation.” The internal organs are in a very rudimentary condition. The most remarkable cir- cumstance connected with the life of these microfilariz is the periodical appearance and dis- appearance of them in the blood of the peripheral vessels. If the blood of an infected person is examined during the day few if any worms can be found, but as evening ap- Ses proaches they begin to appear Fic. 124. Comparison of microfilarie; and continue to increase until fa, amore (ge ith sheath): # about midnight, after which C, mf. loa (large, with sheath); D, mf. they decrease again until Zunees (demarquat email shar ti, 2° morning, During the night when they are most abun- dant there may be as many as 500 worms in a single drop of blood. If the parasites are assumed to be evenly distributed throughout the peripheral circulation, this would imply the presence of several million worms in the body. The periodic appearance and disappearance of microfilarie in the blood is not invariable. When an infected person is made to sleep in the daytime instead of at night, the appearance and disappearance of the parasites in the peripheral bloodvessels can be reversed, implying that the distribution of the parasites may be dependent FILARIA BANCROFTI IN MOSQUITOES 301 on some physiologic condition of the host. Still stranger is the fact that in many of the South Sea Islands, Samoa, the Fiji Islands and the Philippine Islands, the microfilariz show no periodic disappearance, although if a person infected in a place where the parasites do show periodicity be transferred to one of the above-named islands, the periodic phenomena still persist. As stated before, Manson, the great English parasitologist, with characteristic ingenuity, suspected that this parasite, so abundant in the blood, must make use of some blood-sucking insect as a means of transmission, and further concluded that the night swarming of the parasites in the peripheral circulation might be an adaptation to the nocturnal habits of an intermediate host. Working on this hypothesis, he discovered that certain mosquitoes acted as the liberating agents for the parasites. The fact that in those islands where no periodicity is shown the usual inter- mediate host is a diurnal mosquito A édes (or Stegomyia) pseudo- cutellaris, certainly bears out the adaptation hypothesis. On the grounds of the apparently distinct habits and different adaptation, the non-periodic microfilarize have been separated into a distinct species, or at least subspecies, to which the name Filaria philip- pinensis was applied by Ashburn and Craig in 1906. Zodlogists are coming more and more to realize the importance of physio- lologic as well as morphologic characteristics as a basis for sepa- rating species and subspecies. The case of these filariz is by no means unique in the organic world. Physiologic and biochemical reactions are the main basis for the classification of the Bacteria, and some Protozoa can be distinguished better by their patho- genic effects and biochemical reactions than by their morphology. To continue their development the larval worms must be sucked up by the females of certain species of mosquitoes. A considerable number of species of mosquitoes of several different genera, including Anopheles, Aédes and Culex, may serve as intermediate hosts for F'. bancrofti (see p. 449). The commonest and most widespread transmitting agent is the house mosquito of the tropics, Culex quinquefasciatus (fatigans), a species which also transmits dengue. A few hours after being swallowed by a susceptible mosquito the microfilaria (Fig. 125A) become rest- less and endeavor to escape from their sheaths. This they eventually accomplish by butting against the anterior end, having gained as much impetus as their close quarters will allow. 302 FILARL® AND THEIR ALLIES Once free, the little larve (Fig. 125B) move actively about in quite a different manner from the ineffective wriggling in which they indulged while enclosed in the sheath, and by means of which they were unable to ‘ get anywhere.” The active liberated worms make their way to the thoracic muscles of the mosquito, where they le between the muscle fibers and par- allel with them. The body, growing rapidly, by the fourth to tenth day becomes thick and sausage-like (Fig. 125C), with a short, pointed tail, but it later Fic. 125. Development of Filaria bancrofti in IMcreases g reatly In mosquito; A,as withdrawn with blood (first 24 hours) leneth and decreases in stomach; B, form found in tissues just outside ~~ 8 3 : stomach (48 to 72 hours after ingestion); C, form slightly in thickness, found in muscles on fourth day; D, AEE larval thus becoming long and form, ready for transmission, in proboscis (two or : : more weeks after ingestion). 150. (After Lewis Slender again (Fig. Tee inal) 125D). Meanwhile the internal organization of the animal undergoes a great change. The central core of cells gradually becomes differentiated into a digestive tract, separated from the body wall by a true body \ \ Fie. 126. Mature larve of Filaria bancrofti in thoracic muscles and proboscis of mosquito. (After Castellani and Chalmers.) cavity. By the time the larva has reached its full size — about 1.5 mm. (~, of an inch) in length — the digestive tract is a com- plete tube with both mouth and anal openings. While these changes are taking place, the larval worm, though capable of activity, remains at rest between the muscle fibers (Fig. 126), FILARIAL DISEASES 303 but it now becomes active again and migrates into the connective tissue of the anterior parts of the body of its host, and ultimately into the proboscis (Fig. 126). Here the worms lie in pairs, or several pairs together, awaiting an opportunity to re-enter a human host. The length of time required for the metamorphosis and de- _velopment in the mosquito varies from about two weeks under ideal conditions to several weeks under less favorable circum- stances. When the infected mosquito bites a human being, the worms emerge from ‘the proboscis and bore through the skin in the immediate vicinity of the wound, though not directly through the puncture. _ Experiments have shown that the larve can not be deceived into entering vegetable tissue, such as a banana, even though for many days they have been at the tip of the proboscis, ready to emerge when the mosquito bites into warm-blooded flesh. It is possible that these parasites may occasionally find entrance to the human body by other paths than the mosquito’s bite but this has not yet been proved. The popular belief that bad water is the cause of filarial infection is probably due to the effect of stagnant water on the abundance of mosquitoes, and not to the emergence of the larve from the bodies of mosquitoes into water. Bahr has shown that the larve will live in water only seven hours. Once back in a human body from this period of ‘‘ purgatory ”’ in the body of a mosquito the larve migrate to the lymphatic vessels, there to attain sexual maturity, copulate and reproduce. The larve of the next generation escape again to the blood as microfilariz, and the cycle is complete. The adult worms may live for many years and even the microfilarie are able to live for a considerable time, as shown by their continued presence after the death of the parents. Filarial Diseases. — The disease symptoms which are _asso- ciated with Filaria bancrofti can all be traced to interference with the lymphatic system. In many cases there are no ill effects of the infection felt for many years, or perhaps never, though sooner or later there is usually produced anemia, en- largement of the spleén and fever. More serious are the effects produced by obstruction of the lymphatics. This causes great “enlargement of the lymph vessels and the diversion of the lymph 304 FILARLE AND THEIR ALLIES pote its normal_channel, and results in varicose lymph glands _ (Fig. 127C) and ee and in distended lymph sacs which may burst into the kidneys, bladder or body cavity. Often the microfilarie disappear from the blood, probably on account of the death of the parents, but the obstruction of the lymphatics continues to exist, as do the evil effects resulting therefrom. Fic. 127. A few extreme cases of elephantiasis; A, of legs and feet; B, of scrotum; C, varicose groin gland; D, of scrotum and legs; #, of mammary glands. (A and B sketched from photos from Castellani and Chalmers; C, D and # from Manson.) One of the most frequent results of a blocking of the lymph vessels is an enormous enlargement of the part of the body in which the blocking occurs, known by the suggestive name, ‘“elephantiasis ”’ (Fig. 127). In most cases the lower limbs and_— scrotum are the parts affected, though almost any portion of —————————— — — ~ OE a ee —— TT FILARIAL DISEASES 305 the body may occasionally become enlarged. In some South Sea Islands 50 per cent or more of the population are thus affected. The disease begins by repeated attacks, at intervals of from a month to a year, of “ elephantoid ” or filarial fever in which chills and high fever accompany a painful swelling of the parts affected. These attacks, also known as lymphangitis, end in an emission of lymph .and a partial subsidence of the swelling. But each attack leaves a little more permanent tissue, so that in time the growth, which is hard and unyielding, develops to enor- mous proportions. Sometimes an affected leg may reach a diam- eter of several feet. In one case recorded by Manson, a scrotum affected by elephantiasis reached a weight of 224 pounds, though it must be admitted that this is unusual. Another condition resulting from filarial infection is the escape of the contents of lymph vessels into the kidneys or bladder, a condition technically known as “‘ chyluria.”” The urine is milky and coagulates after standing a short time. This condition lasts for a few days or weeks, then ceases and returns at irregular intervals. It produces severe anemia and a general feeling of ennul, and saps the vitality. Occasionally the presence of dead filarize in the body leads to the formation of abscesses which sooner or later discharge. If on any of the appendages, no further trouble results, but such abscesses in the internal regions of the body may have serious or fatal effects. Though very probably some of these so-called ‘ filarial dis- eases’ are caused directly by the filaria, the exact relation of F. bancrofti to all of the pathological conditions associated with its presence in the body ts far from settled. Dutcher and Whit- marsh, of the United States Army, in investigations of filarial diseases in Porto Rico recently obtained pure cultures of a certain type of bacterium from the blood or serum of 15 patients, all but one of whom was affected by some form of filarial disease, whereas in unaffected individuals, with one exception which was looked upon as a “ carrier,” the cultures from the blood remained uniformly sterile. In a few cases in which filarial diseases were present the bacterium was not found but it was believed that either the infection was so light that the cultures did not happen to become contaminated, or that the infection had died out. A number of other observers have obtained cultures of bacteria 306 FILARL£ AND THEIR ALLIES from blood and tissues of elephantiasis cases. Others, however, have found the blood quite sterile. It is worth noting in this connection that the number of cases of elephantiasis or other filarial diseases in which microfilariz are not present in the blood is considerably greater than those in which the larval parasites are present. This is usually explained by assuming that the parent filariz have died or that the larvee cannot reach the blood on account of a blocking of the lymph channels by fibrous growths. Cruickshank and Wright, for instance, in 130 cases of elephantiasis in Cochin, found only 12 with microfilarie in the blood. The observations recorded above are certainly significant and may revolutionize our ideas in regard to filarial diseases. However, even if some of the “ filarial diseases’ were found to be due to bacteria, the filariz might still be incriminated as carriers of the bacteria, and therefore as an indirect cause of the diseases. Treatment and Prevention. —So far there is no widely-ac-_ cepted treatment by which the parent filarie, and with them the microfilariz, can be destroyed. The number of the larve_is reduced, however, by injections of thymol, ichthyol and other drugs, and such injections might-prove to be a useful_preyentive measure. McNaughton has recently reported five cases of filarial infection successfully treated by injections of salvarsan; one case was of ten years’ standing. Usually the only course of the physician is to relieve as far as possible the abnormal conditions associated with the presence of the worms. Such relief, of course, varies greatly with the diverse pathological conditions which may arise. Varicose glands and vessels, un- less causing great discomfort, are usually left alone, since they are lymph channels substituted for the normal ones in the body which have been blocked, and it is therefore dangerous to inter- fere with them. In cases of elephantoid fever the only treat- ment is such as would tend to relieve the pain in the swellings and the fever, and perhaps in severe cases the pricking of the swollen part to allow the exudation of the collecting lymph. In chyluria the treatment consists in rest and in making the pelvic regions as comfortable as possible to prevent pressure which would tend to burst the lymphatics and force the lymph into the kidneys or bladder. Elephantiasis, the commonest expression of filarial disease, is seldom completely recovered from. Formerly the only treatment was temporary reduction FILARIA PERSTANS 307 of the swellings and prevention of further growth by care of the general health, avoidance of violent exercise, massage and tight bandaging. In severe cases of elephantiasis of the leg physicians sometimes cut off great masses of the elephantoid tissue, grafting on new pieces of skin to cover the parts operated on. Removal of enlarged growths of the scrotum can usually be accomplished successfully. Another method which has been used with some success is an operation for the draining of the lymph from the tissue all the way into the bone or even from the bone itself. Castellani has recently found a method of reducing elephantoid tissue which will probably supplant all of the above methods. This consists in the injection into the diseased tissues of a drug, fibrolysin, which, as its name implies, has the property of destroy- ing fibrous connective tissue. Elephantoid swellings are re- ported to have been cured by this method in a few months. Prevention of filarial diseases can best be accomplished by anti-mosquito campaigns. As far as is known at’ present mos- quitoes are the only means of transmission which the parasites have. The same preventive measures, therefore, which serve as preventives against malaria, serve also against Filaria ban- crofti, and since the former disease is found practically every- where that the filariz are found, it is possible to prevent the two diseases with one effort. People who carry filarize in their blood should be prevented, as far as possible, from exposing themselves to mosquitoes. In the places where the micro- filariz are periodic and the transmitting mosquitoes are nocturnal this should be perfectly possible, although in such localities as the Philippines and Samoa, where the intermediate host is largely diurnal, it would present almost insuperable difficulties. In places where Filaria is abundant and mosquitoes are not ex- terminated the carrying at night of a bottle of disinfectant, as alcohol or dilute lysol, for immediate application to mosquito bites would be well worth while. Other Species of Filaria There are, as previously stated, a number of other species of Filaria which inhabit the human body. Filaria (or Acantho- cheilonema) perstans is extremely common in the natives through- out Central Africa and also in parts of northern South America; 308 FILARL4 AND THEIR ALLIES ~ it is confined to regions of heavily forested tropical swamps. In some districts in Uganda it has been found in 90 per cent of the inhabitants. The microfilarie of this species (Fig. 124B) are smaller than those of F. bancrofti, have a blunt tail and lack the sheath which is so characteristic of F. bancrofti. Fur- thermore they show no tendency to disappear periodically from the peripheral vessels. The adult worm, which has rarely been found, is smaller than F. bancrofti (about three inches in length) and occurs in the connective tissue of the abdominal and peri- cardial cavities. The normal transmitting agent, probably some species of mosquito, is not certainly known. No disease symp- toms which ean be correlated with the presence of the parasite have yet been demonstrated. Another species, F. juncea (demarquaii), of which the larva (Fig. 124D) is small and without a sheath, as in F. perstans, but with a sharp tail, occurs in the West Indies and northern South America. It is not known to cause any diseased conditions. The adults live in the mesenteric tissues. In many Indians in British Guiana F. perstans and F. juncea occur together in the blood, and in some cases the presence of F. bancrofti compli- cates the matter still more. F. magalhtesi is another species about which very little is known. < 150. kedani _mite, a Trombidiid. (After Hirst.) x 40. (After Nagayo et al.) newly hatched six-legged larvee creep up on blades of grass or plant stems and await an opportunity to attach them- selves to an insect. If successful in finding a host, or rather in being found by a host, the mites gorge themselves with the juices of the insect, then drop to the ground, crawl to some snug hiding place and undergo a transformation. The whole inside of the body is remodeled, a fourth pair of legs is acquired, and after a few weeks the skin is shed and an adult trombidiid mite crawls forth. It is while the larval mites are hungrily awaiting the arrival of an insect upon which to feed that they attack human beings or animals which may pass their way. They are so small that they can easily pass through the meshes of ordinary clothing and reach the skin, where they set up a severe irritation and Se es ANNOYANCE FROM HARVEST MITES 2a) intense itching. Some authors claim that the mites burrow in the skin and produce inflamed spots, but ordinarily they do not go beneath the skin except sometimes to explore their way into the long tubes of the sweat glands. The habit of attacking warm-blooded animals is evidently abnormal, and the love of blood proves ruinous to those individuals which get an opportu- nity to indulge it, since they soon die victims of their own per- verted appetites. How like some human beings! The irritation caused by the mites is probably due to a spe- cific poison secreted by the mites rather than to any wounds that they make. The inflammation of the skin may not be felt for 12 or even 24 hours after infection by the mites. When the in- flammation does commence there appear large red blotches on the affected parts of the body which itch intensely and are made worse by scratching. After a day or so the red blotches blister and finally scab over. Red-bug rash is most frequent on tender- skinned people and on those parts of the body which are most exposed, though it may spread over the whole body and torment the victim unbearably. Laborers who are continually exposed to these mites seem to develop an immunity to the mite poison, and suffer little or none from them. Herrick states that one of the severest infestations he ever knew was contracted by a delicate-skinned person who-sat down on the ground for a few minutes on some golf links which had recently been laid out on an old pasture where there was still much long grass. This person’s body became covered with large inflamed spots even to the neck. The torture was intense for a week, and the infection persisted for a still longer period. A Mexican species, known by the Aztec name “ tlalsahuate,’’ meaning ‘‘ grain of earth,’’ shows a decided preference for the eyelids, armpits, groins and other thin-skinned portions of the body, where it induces itching and inflammation, and even ulceration when scratched. The “‘ béte rouge ’’ or ‘‘ colorado ”’ of the West Indies and Central America is a similar if not identical species. Sprinkling sulphur on the legs and inside the stockings is a necessary preventive measure for those who are seriously affected by red-bugs, and who have to walk through tall grass or brush where these pests abound. A hot bath shortly after infection, with soap or with soda in it, gives much relief. To allay the itch- ing weak ammonia or baking soda applied to the affected parts is 336 THE MITES good, and alcohol, camphor and other cooling applications are also useful. Since in many instances the adults are unknown, the larval harvest mites are, for the sake of convenience, placed in a col- lective group, Leptus, and the name is used in the manner of a generic name. The common red-bug of Europe, for instance, which is supposed to be the larva of Trombidiwm holosericewm is known as Leptus autumnalis. The most abundant species of red-bug in the United States is Leptus irritans. It occurs through- out the southern United States and as far north as New Jersey and the upper Mississippi Valley. An allied species, Leptus ° americanus, also occurs in many parts of southern United States. On the northern border of its range this mite does not appear until the latter part of June and becomes especially annoying during August, but its season becomes earlier and earlier the farther south it occurs. The European harvest mites, the commonest of which is Leptus autumnalis (Fig. 136), are well known pests throughout Europe, especially in Central and Western France, where they are known as the ‘“‘ bétes rouges”’ or “‘ rougets.’? They are said to attack small mammals, such as rodents, by preference. Unlike the American species, the European harvest mites become espe- cially abundant in the fall of the year. Japanese investigators have recently cast doubt on the commonly accepted belief that Trombidium holosericeum is the parent of Leptus autumnalis since in Japan the parent of the kedani mite (Fig. 137), which very closely resembles L. autumnalis, is quite different from 7. holo- sericeum, whereas an adult mite which very closely resembles the latter, produces larve quite different from L. autwmnalis. The Japanese harvest mite, larva of Trombidium akamushi, known locally as the akamushi (red-mite), tsutsugamushi (sick- ness mite) and kedanimushi (hairy mite), has been proven to be the carrier of a typhus-like disease known as kedani or flood fever. These larval mites occur in countless numbers on the local field mice, Micromys montebelloi, living especially on the inside of the ear. They frequently attack the farm laborers who engage themselves in harvesting and handling the hemp which is raised on the flood plains of certain Japanese rivers. It is among these people that the kedani or flood fever occurs, always following the bite of a mite. The bite, usually in the LOUSE-MITE San armpits or on the genitals, is at first painless and unnoticed, but the mite remains attached at the wound from one to three days before dropping to the ground to transform to the nymphal stage. The bite of the mite is said to develop into a tiny sore or inflamed spot in the region of which the lymph glands become swollen and painful and flood fever follows. The nymphs and _ adults of this mite have recently been found by Nagayo and his fellow-workers in Japan. The transmission of kedani by this mite is the only positive instance of human disease carried by Acarina other than ticks. Other Occasionally Parasitic Species There are many species of mites, of several different families, which under abnormal circumstances or by sheer accident may become troublesome parasites of man. Nearly all mites secrete salivary juices which have a toxic effect when injected into the blood; therefore any mite which will bite man under any circum- stances may become a pest: In nearly all cases the symp- toms of attacks by mites are similar —hivelike or rashlike eruptions of the skin, in- tense itching and in severe attacks fever. S Fic. 138. Louse-mite, Pediculoides ventri- Louse-Mite. — One of the cosus; 2, unimpregnated female; ¢, male, x 150. (9, after Brucker from Webster; most important of the occa- A sionally parasitic mites is the louse-mite, Pediculoides ventricosus (Fig. 138), belonging to the family Tarsonemide. This is a very minute species, barely visible to the naked eye, which is normally parasitic on grain-moth caterpillars and other noxious insects, and there- fore beneficial. These mites live in stubble, stored grain and beans, cotton seeds, straw, etc., attacking the various insects which infest these products and becoming numerous in pro- portion to the abundance of their prey. The female has the remarkable habit of retaining the eggs and young in her abdomen , after Banks.) 338 THE MITES until they have become fully developed males and females. Her abdomen in consequence becomes enormously distended so that the rest of the body appears as only a tiny appendage at one side of it. A gravid female (Fig. 139) fully distended may reach a diameter of 1.5 mm. (;!, of an inch) whereas normally she measures only 0.2 mm. (+4, of an inch) in length. Under the most favorable conditions only six days may elapse from the time the young females emerge from the mother before they reproduce a brood of their own. The brood varies in number from a few dozen to over 200. Like many other beneficial things, these predaceous little mites may become a distinct nuisance, and many _ serious outbreaks of infestation of human beings by them are on record, especially among the grain threshers of the central portion of the United States and among laborers who handle stored grains and other dry foods. In our Middle West Fic. 139. Louse-mite, gravid female. their attacks have often been ° x about 75. (After Brucker from gttributed to harvest mites. In Webster.) Italy the rash produced by louse-mites is called ‘ miller’s itch.” Several outbreaks have occurred in the United States due to the use of new straw mat- tresses. The transformation of all the grain-moth caterpillars into moths leaves the mites with their normal food supply cut off, and they are then ready to feed upon any flesh to which they may have access in an effort to prevent starving to death. The itching rash produced begins about 12 to 16 hours after exposure to the mites. At first they produce pale hivelike spots, which later become red and inflamed, and itch unbearably. Little blisters, the size of a pinhead or larger, appear at the sites of the bites and these later develop into little pustules. Scratch- ing results in the formation of scabs, and when these fall off dark spots which are slow to fade are left on the skin. The rash and itching normally disappear within a week unless fresh GRAIN MITES 339 detachments of mites are constantly acquired. In severe in- festations the irritation and poisoning is sufficient to cause constitutional symptoms such as fever, high pulse, headache, nausea, ete. Since the mites cannot thrive on human blood, and remain attached to the skin for only a short time, no treatment for destroying them is necessary. Remedies to relieve the itching, such as the application of soda or soothing ointments, or warm baths with a little soda, are called for. To prevent infection when handling infected produce, Dr. Goldberger, of the United States Public Health Service, suggested a greasing of the body, followed by a change of clothes and a bath after working with the infected material. Riley and Johannsen suggest the use of powdered sulphur as a preventive in view of its efficiency against harvest mites. Control of the mite consists largely in keeping grain and other dry produce as free as possible from the insects on which the mites feed. Burning stubble in winter and threshing wheat directly from the shock would tend to lessen the worms in stored wheat and with them the mites. Grain Mites. — The family Tyroglyphide, including many species of mites which normally feed on grain, flour, sugar, dried fruits, cheese and other foods, contains several species which become annoying to man and produce an itching rash on people who handle infested goods. According to Banks all the members of this family are pale-colored, soft-bodied mites, with prominent pincer-like chelicerz and no eyes. Their bodies are about twice as long as wide and are furnished with a few scattered long hairs (Fig. 140). | The life history of some members of the gee ree I Cra eee yroglyphus longior. X 30. family is quite remarkable in that there is (After Fumouze and added a phase of existence which does not stare: occur in other mites. All the species scatter their eggs haphazard over the infected material. Upon hatching the larve have six legs and acquire a fourth pair after moulting, in orthodox mite style. Some now develop directly into adults, while others go through what is called a “ hypopus”’ stage. The hypopus (Fig. 141) is very different from the nymph from which it develops: 340 THE MITES the body is hard and chitinous, there is no mouth or mouthparts, the legs are short and stumpy, and there is usually a raised area on the ventral surface with a number of tiny sucking discs. By means of these suckers the hypopus attaches itself to insects or other creatures and is thus transported to new localities, the entire object of the hypopus stage apparently being to secure passage to new breeding grounds. After dropping from its unwilling transporter the hypopus moults into an eight-legged nymph again, which, after feeding, develops into an adult. The Tyroglyphide are all quite similar Fie. 141. Hypopus or in appearance, and the characters which traveling stage of Tyro- : glyphus, ventral view. Separate the species, and even the genera, Po ee (After are few and minute. A considerable num- ber of species may attack persons who handle infested materials, and they are the cause of “ grocers’ itch.” This affliction is caused especially by various species of Glyciphagus and Tyroglyphus. Of historical interest is a case of dysentery apparently due to a Tyroglyphus, T. longior, (Fig. 140) which occurred in one of Linnaeus’ students. The mites were abundant in his feces, and were found to live and multiply in a juniper-wood cup which he used. As shown by Castellani, an itching rash known as “ copra itch,” occurring among the laborers in the copra mills of Ceylon where cocoanut is ground up for export, is caused by a variety of this mite, called T. longior castellanii. Copra itch occurs also among stevedores who handle copra in London. Another species, Glyciphagus buski, was taken from beneath the skin on the sole of the foot of a negro in England; it had caused large sores. The negro attributed the affliction to the wearing of a pair of shoes loaned him by a similarly affected negro from Sierra Leone, Africa. Another species, Rhizoglyphus parasiticus, which lives on roots, bulbs, etc., in India, produces a skin disease among coolies work- ing on tea plantations. It begins with blisters between the toes and spreads to the ankles, causing very sore feet. Other Species. — A few species of the family Tetranychide, including the ‘red spiders”? or spinning mites, occasionally become troublesome to man, although they are normally vege- SPECIES OCCASIONALLY ANNOYING 341 table feeders and may do much damage to cultivated plants. One species especially, Tetranychus molestissimus, which lives on the undersides of leaves of a species of cockle bur, Xanthium macrocarpum, in Argentina and Uruguay, attacks man during the winter months from December to February. It produces symptoms similar to those of the louse-mite, with intense itching “and some fever. The common “red spider,’ 7. telarius, an almost cosmopolitan species, also is reported to attack man oc- casionally. : The common chicken mite, Dermanyssus gallinae, belonging to the family Parasitide (Gamaside), frequently causes much irritation and annoyance to those who come in contact with it. Although it can thrive and multiply only on certain kinds of birds, it sometimes remains on mammals for some time, causing an eczema or rashlike breaking-out on the skin, attended, as in other mite infections, by intense itching. Except in cases of constant reinfection chicken mites are usually troublesome to man for only a few days at most. Since these mites can live for several weeks without feeding on their normal hosts, places formerly frequented by fowls may be infective after the removal of the birds. The mites normally remain on their hosts only long enough to fill up on blood, usually at night, spending the rest of the time in cracks and crevices in and about the coops. Various sprays of sulphur, carbolic solutions and oils are used to destroy them. An allied species, Holothyrus coccinella, living on geese and other birds on Mauritius Island, attacks man, causing burning and swelling of the skin, and frequently proves quite dangerous to children by entering the mouth. A very small mite, Tydeus molestus, belonging to the family Eupodide, attacks man in much the same manner as do the harvest mites. It is common on some estates in Belgium, ap- parently having been imported many years ago with some Peru- vian guano. It appears regularly each summer on grass plots, bushes, etc., in great numbers, disappearing again with the first frost. It causes great annoyance in red-bug fashion, not only to man but to other mammals and birds as well. 342 THE MITES Itch Mites The itch mites, belonging to the family Sarcoptide, are the cause of scabies or mange in various kinds of domestic and wild animals, and of “‘itch”’ in man. This disease is one which has been known for a very long time but was formerly supposed to be caused by ‘‘ bad blood” or other constitutional disorders such as cause the growth of pimples. Even at the present time the true cause of the disease is not understood by the majority of people. The Parasites. — The itch mites (Fig. 142) are minute whitish creatures, scarcely visible to the naked eye, of which the females Fic. 142. Human itch mite, Sarcoptes scabici; 9, female; ¢, male. X about 100. (Partly after Banks.) burrow beneath the skin and lay eggs in the galleries which they make. They are nearly round and the cuticle is delicately sculptured with numerous wavy parallel lines, pierced here and there by stiff projecting bristles or hairs. There are no eyes or trachezee. The cone-shaped mouthparts are covered over by the shieldlike upper lip. The legs are short and stumpy and are provided with sucker-like organs, called ambulacra, at their tips. In the female the two posterior pairs of legs terminate in a simple long bristle, whereas in the male only the third pair of legs terminates in bristles. The human itch mite, Sarcoptes scabiei, is only slightly distinguishable from the itch mites which cause scabies and mange in many of our domesticated animals. Each infected species of mammal has its own variety of itch ITCH MITES — LIFE HISTORY 343 mite, but many of them can be transferred readily from one host to another. In the common human species the male is only about 0.25 mm. (;}5 of an inch) in length, while the female is about 0.4 mm. (75 of an inch) in length. A variety of this mite, S. scabier crustose, causing the so-called ‘“‘ Norwegian itch,’’ is found in northern Europe and occasionally in the United States, but is always rare. The disease caused by it differs in some re- spects from ordinary itch. Still another species, Notoedres cati, which causes a very persistent and often fatal disease in cats, temporarily infests man, but is apparently unable to breed in human skin, since the infection dies out in the course of a week or two. The impregnated females of itch mites excavate tortuous tun- nels in the epidermis (Fig. 143) especially on such portions as Fig. 143. Diagrammatic tunnel of itch mite in human skin, showing female depositing eggs. X about 30. (Adapted from Riley and Johannsen.) between the fingers and toes, on the groins and external genitals, ‘and in the armpits, where the skin is delicate and thin. The tunnels are anywhere from a few millimeters to over an inch in length, and are usually gray in color from the eggs and excrement deposited by the female as she burrows. The eggs (Fig. 143) vary in number from 15 to 50. After they are all laid the female dies, having performed her duty in life. But there is no respite on account of her death, for in less than a week the eggs hatch into six-legged larvee. These live for about two weeks in the old burrow built for them by their mother, and during this time they indulge in three moults and undergo a metamorphosis which transforms them into nymphs similar in 344 THE MITES form to the parents, but not sexually mature. After a short time the nymphs moult again, and are then fully developed males and females. At this stage the mites, remaining hidden in the burrows or in any crevice in the skin during the day, wander about on the surface of the skin during the night and copulate there. The males do not burrow or enter the burrows made by the females, but merely hide under superficial dead cells of the epi- dermis. Since they die very soon after copulation, they are seldom found. The young impregnated females soon begin fresh excavations, and produce more eggs. Fifteen or twenty eggs each generation, of which approximately two-thirds are females, and a new generation about every four weeks, results in an enormous rate of increase. By working out the increase mathematically it will be found that in less than six months the progeny of one pair of itch mites theoretically would number several millions! The Disease. — The “‘ itch ”’ is a disease which in the past has swept over armies and populations in great epidemics, but it has decreased with civilization and cleanliness, and is fortunately comparatively rare at the present time, at least in civilized com- munities. As its name implies, the disease is characterized by itching of the most intense kind where the mites burrow in the skin. The itching is probably due only to a very slight extent to the me- chanical irritation in the skin, but is induced rather by poisonous substances secreted or excreted by the mites. Injection of fluid containing crushed mites produces an eruption and irritation similar to that caused by the burrowing of the living mites. The excretions of the mites as they feed in their burrows form little hard pimples, about the size of a pinhead or a little larger, containing yellow fluid. When these are scratched, as they are almost certain to be on account of the unbearable itching, they frequently become secondarily infected and may give rise to larger sores. Ultimately scabs form over them. Since the entire life history of the parasites is passed on a single host, generation after generation may develop from a single infection, and although the infection apparently may dis- appear temporarily, it persists recurrently for many years. Since the mites are sensitive to cold the infected areas of skin not only do not spread but may become restricted during the winter, to ITCH 345 spread with renewed vigor with the coming of warm weather. So persistent is the infection that it is doubtful whether it ever spontaneously dies out. ‘‘ Norwegian itch,” caused by Sarcoptes scabiei crustose, is even more persistent than ordinary itch, and, unlike the latter, may occur on the face and scalp as well as on other parts of the body. Infection can result only from the passage of male and female mites, or of an impregnated female, from an infected to a healthy individual. Normally this takes place by actual contact, rarely in the daytime on account of the secretive habits of the mites, but commonly at night, especially from one bedfellow to another. Gerlach experimented to determine how long the mites could live away from their hosts and found that in the dry warm air of a room they lost vitality so rapidly that they could not be re- vived after three or four days. In moist places, on the other hand, such as in the folds of soiled underwear or bedcloths, they survived as long as ten days. From this it is evident that in- fection may take place by means of bedding, towels, underwear or other cloth which may come in contact with infected skin. The author once witnessed an epidemic of itch arising from the use of an infected wrestling mat in a college gymnasium. It is also possible for infection to be derived from mangy animals, though the mites, once adapted for several generations to a given host, do not survive a transfer to a different species of host more than a few days. Treatment and Prevention. — The treatment of itch before the nature of the malady was understood was considered very slow and difficult, and even at the present time it is looked upon by many people as a disease which can be recovered from only after prolonged treatment. The fact that the mites burrow beneath the skin to lay their eggs makes careless superficial treatment almost as inefficient as the internal medicine which was once taken to “ purify the blood.” The most effective treatment for the itch is as follows: the patient rubs himself vigorously with green soap and warm water for about 20 minutes, and follows this with a warm bath for half an hour or more, dur- ing which the soapy massage continues. In this manner the skin is softened, the pores opened and the burrows of the mites soaked so that the application of mite poison which is to follow will penetrate more readily. When the skin is thus prepared 346 THE MITES some substance for destroying the mites is applied. Sulphur ointment made by mixing one-half an ounce of sulphur to ten ounces of lard, is excellent; its virtue lies in the formation of hydrogen sulphide in contact with the skin, sulphur itself being inert. A still more efficient though more expensive remedy is a beta-naphthol ointment, prepared as follows: beta-naphthol, 75 grains; olive oil, 23 fluid grams; sulphur, 1 oz.; lanolin, 1 oz.; green soap, 1 oz. One of these applications, or some other, is unsparingly rubbed into the skin of the infected portions of the body, and of a considerable area around them. When rubbed in for 20 or 30 minutes the patient goes to bed, leaving the oint- ment on his body until morning when it is washed off with another bath. Meanwhile the soiled underwear, bedclothes or other possibly infected articles are sterilized by boiling or baking. Since this course of treatment does not destroy the eggs it is repeated in about ten days in order to destroy any mites which may have hatched in the meantime. For delicate-skinned individuals the treatment described above is too severe and may, of itself, give rise to inflammation of the skin not unlike that caused by the mites. In such case balsam of Peru may be used satisfactorily instead of sulphur ointment, but should be rubbed in several times at intervals of a few hours. It does not cause any irritation. Prevention of this annoying infection consists merely in avoid- ing contact with infected individuals, and of shunning public towels or soiled bed linen. A single infected individual in a logging or railroad camp may be a means of infecting the entire camp. Means should, therefore, be taken to guard against such individuals whenever possible, and to prevent the spread of infection from unsuspected individuals by care as regards the use of towels and bed clothes. Hair Follicle Mites The hair follicle or face mite, Demodex folliculorum (Fig. 144), of the family Demodecide, is a species which is most strikingly adapted for its parasitic life. It is a wormlike creature, very unmite-like in general appearance, which lives in the hair follicles and sebaceous glands of various mammals. In man it occurs especially on the face. HAIR-FOLLICLE MITE 347 The wormlike appearance of the adult mites is due to the great elongation of the abdomen which is marked by numerous fine lines running around it. The beak is short and broad, and the four pairs of legs, all similar, are short, stumpy, three-jointed append- ages. The female mites are .35 to .40 mm. long (about gy of an inch), while the males are a little smaller. The multiplication of these mites is slow. The eggs hatch into tiny six-legged larvee in which the legs are mere tubercles. It requires four moults to bring the larve to sexual maturity. In most cases these parasites cause no incon- venience whatever and their presence is not even suspected. In Europe a large proportion of people are said to be infected, but in Amer- ica, according to Riley and Johannsen, there is reason for believing that the infection is far less common than is usually supposed. Since generation after generation may be produced on a single host the infection is potentially | Fic. 144. Hair- indefinite in its duration. When the mites See eae ee become numerous in the hair follicles or 200. (After Meg- sebaceous glands they sometimes cause “black- ™2? heads” by causing a fatty accumulation to be produced, but they are not the only or even the usual cause of “ black-heads.”’ The skin disease known as “‘ acne’”’ has also been attributed to these mites, but probably erroneously. Follicle mites have been suspected also of spreading leprosy. The method of transmission of the mites to another host is not definitely known but it is probable that the adults wander on the surface of the skin at times, and may then be transmitted by direct contact or by towels, as are itch mites. In dogs, where the follicle mite, possibly a different species, causes a very severe and often fatal form of mange, transmission from dog to dog takes place in a very irregular manner, and there are frequent instances cited of infected dogs associating for a long time with uninfected ones without spreading the disease. Ex- periments with transmission of the canine follicle mite to man have invariably failed. Little is known about treatment of 348 THE MITES Demodex infection, but it is probable that sulphur applications in some form would reach and destroy them. Tongue-worms Related to the mites, but now placed in a distinct order, Lin- guatulina, are the tongue-worms. These animals have become so modified by parasitic life that the adults have lost nearly all re- semblance to the other members of their group, and have become so wormlike, both in form and life history, as to have been classified by older writers with the tapeworms (Fig. 146A). Only the larval = stage gives a clue to their real relationships. Their long bodies are either flattened or ee, cylindrical, and distinctly divided into rings or segments as in leeches. There is no dis- tinct demarcation between head, thorax and abdomen. On either side of the mouth are ve oe Head two hooks which can be retracted into grooves latus. x3. (After like the claws of a cat (Fig. 145). These are eerren) usually looked upon as the vestiges of some of the appendages. At the bases of the retractile hooks there open a number of large glands, the secretion of which is believed to have blood-destroying power. The internal organization of the body is degenerate in the extreme; there is no’ blood, no respiratory system, no special sense organs, no organs of locomotion; little more than the barest necessities of racial existence —a simple nervous system, a digestive tract and a reproductive system. The sexes are separate. The adult worms live in the nostrils, trache or lungs of ecar- nivorous reptiles and mammals, where they produce their myriads of eggs. The latter are voided with the catarrhal products of the respiratory system caused by the presence of the parasites. The egg-laden mucous excretions from the nose of an infected animal are dropped on vegetation and eaten by herbivorous ani- mals, whereupon the eggs (Fig. 146B) develop into larvee in the new host. These larve (Fig. 146C), hatched out in the stomach, are far more mitelike than the adults, inasmuch as they possess two pairs of rudimentary legs and primitive arthropod mouth- parts. The larve migrate to the liver, spleen or other organs . LINGUATULA RHINARIA 349 and there encyst (Fig. 146D). After a series of moults a second larval stage is entered upon, this time with a wormlike appear- ance much more like that of the adult (Fig. 146K). At this stage a ‘‘ wanderlust ” seizes the tongue-worm and it begins an active migration in an endeavor to reach a more satis- factory site for adult life. The mites may settle in the res- a2 See, - ee ece eget ecesege det irs eB Eee: sau ned EES re D («100) Fic. 146. Life history of tongue-worm, Linguatula rhinaria; A, adult female from nasal passage of dog; B, egg containing embryo; C, larva from sheep, man or other animals; D, encysted larva; E, 2nd larval stage, from liver of sheep or man. piratory tract of their original host, or may abandon their host by way of throat or anus to take chances on being snuffed up or taken into the mouth cavity of another animal. Having gained access to their final habitat in the nostrils or lungs, they attach themselves by their hooks, moult, copulate and reproduce. While both larval and adult stages of tongue-worms are oc- casionally found in man, the larve, as liver parasites, are more common. The tongue-worm most frequently observed in man is Lingua- tula rhinaria. The male of this species is a small worm, whitish in color, about three-fourths of an inch in length, whereas the female (Fig. 146A), which is yellowish or brownish due to the eggs in her body, reaches a length of from three to five inches. The adults occur most commonly in the nasal passages of dogs (Fig. 147). The eggs (Fig. 146B) are dispersed with mucus during the violent fits of sneezing to which the presence of the parasite gives rise. The swallowing of food or drink, especially grass or vegetables, soiled by this infective mucus, results in the access of the larva-containing eggs to the intermediate host, which is most frequently sheep, goats, rabbits, etc., but occasionally 350 THE MITES man. In the course of five or six months the larve (Fig. 146C), having migrated to the liver or lymph glands, transform to the second larval stage (Fig. 146E), reach a length of about one- Fie. 147. Head of a dog split in half to show three tongue-worms, Linguatula rhinaria, (a) in the nasal cavity. Reduced in size. (After Colin, from Hall.) fourth of an inch, and consist of from 80 to 90 rings or segments, each one with very fine denticulations on the hind margin. For a long time this larva was looked upon as a distinct species. L. rhinaria is nowhere abundant, even in its normal hosts, though in some parts of Europe about ten per cent of dogs are said to be infected. The majority of human cases reported have been in Germany. Another species which is occasion- ally found as a parasite in man dur- ing its larval stage is Porocephalus armillatus (Fig. 148). Unlike Lingua- tula, this worm has a cylindrical body, only about 18 to 22 rings of segments and a total length of about one-half faa Pyles nae inch. The segments have no fine latus; Q, female; ¢, male. denticulations as they have in Lingua- Natural size. (After Sambon-) ¢yJq, This species is said to spend its adult life in the lungs of the African python, the larve occurring occasionally in man, but more frequently in giraffes, monkeys and other African animals. Sambon thinks the eggs escape from the POROCEPHALUS Jo nostrils of pythons into water, and that infection occurs through drinking. The return of the larva from the intermediate host to the python probably takes place by the intermediate host being eaten. The larve as they occur in man or other animals may either be encysted or freely migrating in the tissues or body cavities. Such symptoms as emaciation, bronchitis, pleurisy and offensive discharges from the lungs may be present. From 75 to 100 larvee have been known to be expectorated by a single patient. A more slender species, P. moniliformis, bright yellow in color, occurs as an adult in pythons in southern Asia and the East Indies, and in two cases human infection has been reported. One case of human infection with a Porocephalus in Montana in 1876 is of interest, since, as pointed out by Sambon, it may have been the larva of P. crotali of rattlesnakes. CHAPTER XXI TICKS WHILE mites as a group are extremely annoying pests, with one exception they are not dangerous as disease carriers. The ticks, on the other hand, are not only annoying but dangerous. Several important diseases of domestic animals are transmitted solely by ticks, and several human diseases are likewise dependent on ticks for dissemination, especially African relapsing fever or “ tick fever’ and Rocky Mountain spotted fever. In addition to this, tick bites, at least those of some species, give rise to a serious form of paralysis, especially in children, which may end in death. Tick bites also frequently give rise to dangerous ulcerating sores which may result in fatal blood poisoning. The economic importance of ticks as parasites of domestic animals is not for consideration here, but it would not be amiss to state that the annual loss in the United States from cattle ticks alone is estimated at from $40,000,000 to $50,000,000. It is evident that ticks should be looked upon as worthy candidates for ex- termination wherever this is possible. Although the ticks constitute only one of several divisions of the order Acarina, they are so readily distinguishable and so well known that in the popular mind the ticks are looked upon as a group quite distinct from all other mites, and equivalent with them. They are of relatively large size and usually exceed all other Acarina in this respect even in their larval stages. Some species when full grown and engorged are fully half an inch in length. General Anatomy.— The body of a tick is covered by a leathery cuticle which is capable of great expansion in the fe- males as they engorge themselves on their host’s blood, filling the numerous complex pouches of the digestive tract (Fig. 149). When not engorged ticks are flat and oval or triangular in shape (Fig. 154), usually tapering to the anterior end, but after en- gorgement they resemble beans or nuts of some kind (Fig. 158). 352 GENERAL STRUCTURE 353 Fie. 149. Digestive tract of Argas persicus; an., anus; ch., chelicera; int. c., intestinal coeca; ces., esophagus; ph., pharynx; sal. gl., salivary glands; st., stomach. X about 20. (Adapted from Robinson and Davidson.) = SS > = i Ses = Mi SS B. Senee a Fic. 151. Tip of chelicera of a tick, much enlarged; cut. p., articulated Fic. 150. Head or capitulum of tick; cutting part; shaft, shaft; sh., sheath; hyp., hypostome; chel., chelicera; pal., fl. t., tendon of flexor muscle: ex. iter palpus; bas. p., basal piece. (Partly after tendon of extensor muscle. (After Banks.) Nuttall, Cooper and Robinson.) 354 TICKS Most ticks have a little shield or ‘‘ scutum ” on the dorsal sur- face, quite small in the females, but nearly or quite covering the back in the males (Fig. 156). Attached to it in front is a little triangular piece, the capitulum or ‘head’ which bears the mouthparts (Fig. 150). The latter consist of a quite formidable piercing organ, the hypostome, a pair of cheliceree or mandibles which are armed with hooks (Fig. 151), and a pair of blunt paipi which are probably tactile in function. The hypostome is a rasplike structure, beset with row after row of recurved teeth (Fig. 152). So firmly do these hold in the flesh into which the proboscis is inserted that forcible removal of a tick often results in the tearing off of the body from the capitulum which remains at- tached to the host. Like other Arachnida, ticks have four pairs of legs. These are quite conspicuous when the body is empty but are “Ey hardly noticeable after en- ne gorgement. The breathing ane Eee Gay as apparatus consists of a SMiee nymph; B, Argas persicus, adult; C, Ixodes tem of trachez which open paces female 2 fae, vale 2 bya paw ot ema male; G, Ornithodorus moubata, nymph; H, vicinity of the fourth pair Crsthororas smi eget ater Sal laces (elie ae plates which cover the spir- acles are sometimes used in distinguishing species. The ventral surface has two openings, the genital pore just back of the pro- boscis, and the anus some distance from the posterior end of the body (Fig. 154). Habits and Life History. — All ticks are parasitic during some part of their lives. The majority of them infest mammals, though many species attack birds and some are found on cold- blooded animals. A very decided host preference is shown by some species, whereas others appear to be equally content with any warm-blooded animal which comes their way. In many species the hosts or parts of hosts selected by the adults are not the same as those selected by the immature forms. are —_— we Was | LAA ON . | Eee So oe CAN LE LIFE HISTORY 355 The life histories of all ticks are more or less similar. After several days of mating the female ticks engorge and soon after drop to the ground and begin to lay their eggs (Fig. 153). These are deposited on or just under the surface of the ground. Some of the family Argaside engorge several times, laying a batch of from 20 to 50 eggs after each gluttonous repast. All of the - Ixodide, on the other hand, lay their eggs after a single engorge- ment. The eggs number from a few hundred in some species to upwards of 10,000 in others and are laid in rather elongate masses in front of the female. Each egg as it is passed out by the ovipositor is coated with a viscid substance by glands between the head and dorsal shield of the tick and is then added to the mass in front. The process of egg-laying occupies several days, as not more than several hun- dred eggs can be passed out and treated with the viscid coating in the course of a day. The eggs develop after an incubation period which varies with the temperature from two 4, 153. Texas or three weeks to several months. Eggs de- fever tick, Margaropus posited in the fall do not hatch until the fol- Renee ak lowing spring. The larval ticks which hatch from the eggs are much smaller than the adult ticks and have only six legs (Fig. 157B). They are popularly known as “seed ticks.”’ The seed ticks soon after hatching climb up on a blade of grass or bit of herbage and assume a policy of watchful waiting until some suitable host passes with- in reach. Seed ticks must be imbued with almost unlimited patience, since in many if not in the majority of cases long delays must fall to their lot before a suitable host comes their way like a rescue ship to a stranded mariner. The jarring of a footstep or rustle of bushes causes the ticks instantly to stretch out to full length, feeling with their clawed front legs, eager with the excitement of a life or death chance to be saved from starvation. If success rewards their patience, even though it may be after many days or weeks, they feed for only a few days, becoming distended with blood, and then drop to the ground again. Re- tiring to a concealed place they rest for a week or more while 356 TICKS they undergo internal reorganization. Finally they shed their skins and emerge as eight-legged but sexually immature ticks known as nymphs (Fig. 157C). The nymphs climb up on bushes or weeds and again there is a period of patient waiting, resulting either in starvation or a second period of feasting. Once more the ticks drop to the ground to rest, transform and moult, this time becoming fully adult and sexually mature. In this condition a host is awaited for a third and last time, copulation takes place, sometimes even before a final host is reached, and the females begin their final gluttonous feeding which results in distending them out of all proportions. In some species, especially those which live on hosts which return to fixed lairs, copulation takes place off the host. When this occurs, as in many species of Ixodes, the male is often not parasitic at all, and may differ markedly from the female in the reduced structure of its hypo- stome (Fig. 152C, E and F). In all species the males die shortly after copulation. This, in general, is the life history of ticks, but it is, of course, subject to considerable variation in different species. In many species there are two nymphal periods instead of one. In some species, as in the Texas fever tick, Margaropus annulatus, the moulting takes place directly on the host, thus doing away with the great risk of being unable to find a new host after each suc- cessive moult. In a few species the first moult is passed through on the host, but the second is passed on the ground. The most important asset of ticks to counterbalance the disadvantage of having to find new hosts is their extraordinary longevity. Larve of ticks have been known to live more than six months without food, and adults have been kept alive in corked vials for five years. There are two families of ticks, the Argaside and the Ixodide. The Argaside include the bird ticks and their allies, which are distinguished from the Ixodide by the absence of a dorsal shield and in having the head partially or entirely concealed under the overlapping anterior margin of the body (Fig. 154). The fe- males of this family do not become distended as do those of the Ixodide, but take more moderate though more frequent meals. They are chiefly inhabitants of warm countries. Both nymphs and adults feed at night, usually dropping off their hosts im- mediately after a meal, and thus seldom being carried from the TICK BITES aon lairs or abodes of their hosts. The Ixodidz, on the other hand, inhabit the hosts rather than their lairs, and frequently remain attached for several days, or even longer. In the less capacious Argaside the females lay their eggs in a number of installments 30 ° oN Ee La ecso900o ao oO ° o Fic. 154. Comparison of dorsal and ventral view of Ixodid and Argasid females; A, dorsal view of Ixodid 9; A’, ventral view of same; B, dorsal view of Argasid 9; B’, ventral view of same. An., anus; cap., capitulum; d. sh., dorsal shield; €.s., eye spot; gen. op., genital opening; sp., spiracle. after successive feeds, and the total number of eggs may be counted in hundreds instead of thousands. The reason for this difference is readily accounted for by the difference in habits in the two families, since the progeny of the Argaside, reared in the lairs of the hosts, have far better chances of finding a host and of surviving than do the progeny of the [xodidz which live on their hosts and may drop off to lay their eggs almost anywhere in the wanderings of the host. Tick Bites. — The status of ticks as human parasites, as stated before, is one not to be passed over lightly. Aside from the 358 TICKS transmission of diseases tick bites are dangerous to man in a number of ways. The wounds made by ticks, especially if the head is torn off in a forcible removal of the parasite, are very likely to become infected and result in inflamed sores or extensive ulcers, not in- frequently ending in blood poisoning. The author, as the result of the bite of a tick in northern California (probably Dermacentor occidentalis), suffered from an ulcerating sore on his arm, over half an inch in depth and three-fourths of an inch in diameter. Blood poisoning set in early causing a very high temperature and great pain in the arm, and it was only a timely return to civilization and hospital care that saved his arm if not his life. Sanitary removal of ticks and cleansing of the wounds, as described on p. 367, would be well worth the consideration of every inhabitant or traveller in a tick-infested country. Tick Paralysis. — More serious than the painful wound made by ticks is a peculiar paralyzing effect of tick bites, known as tick paralysis. This occurs especially from tick bites on the back of the neck or on the head; it affects the legs first, but spreads forward in a few days to the arms and neck and may result in death. Paralysis in man and animals from tick bites has been reported from South Africa and Australia and in North America from the parts of Oregon and British Columbia inhabited by the spotted fever tick. Sheep are especially subject to tick paraly- sis, to such an extent in British Columbia as to present a serious problem. This peculiar effect of tick bites has been reproduced experimentally in sheep in places where it has not been known to occur normally, by allowing a spotted fever tick, Dermacentor venustus (Fig. 156), to bite along the spinal column. ‘The bites of this tick are particularly likely to cause paralysis, though it is not yet known whether this is because of an especially toxic secretion produced by this species or because of its preference for biting along the spinal cord or on the head. There has been much controversy as to what really causes the paralysis, some authors believing that it is due to a microdrganism injected by the tick, since it is usually six or seven days after the attach- ment of the tick before the effect is felt. The fact, however, that no such organism can be discovered, that inoculations of blood and other parts of diseased animals into healthy ones does not result in transmission of the disease, and that the paralysis TRANSMISSION OF DISEASES 359 is usually accompanied by little or no fever, makes this seem unlikely. A single attack of tick paralysis seems to confer immunity and it is probable that many children are naturally immune. The most reasonable explanation is that the ticks secrete a toxic substance, especially when rapidly engorging, which has a specific action on the motor nervous system. Pos- - sibly the bite must pierce or come in contact with a nerve or nerve ending in order to produce the effect. Numerous cases of tick paralysis in children have occurred in British Columbia and in the Blue Mountains of Eastern Oregon. One doctor in the vicinity of Pendleton reported no less than 13 cases. The disease begins with paralysis of the legs and usually results in complete loss of their use; the paraly- sis ascends in the course of two or three days, affecting the arms and finally the thorax and throat. Unless the heart and respi- ration are affected, recovery follows in from one to six or eight days after removal of the ticks. The latter, often in pairs, are usually found on the back of the neck or along the middle line of the head, especially just at the base of the skull. If the ticks are not removed, the disease may result in death or in spon- taneous recovery after a few days or a week. Unfortunately in most of the cases of tick paralysis in chil- dren the ticks have not been identified, but it is well known that the spotted fever tick is the most frequent cause of paralysis in sheep and the only species by which such a disease has been reproduced experimentally. In South Africa, however, a similar paralysis in sheep results from the bites of Ixodes pilosus, and paralysis in children in Australia from the bites of other but undetermined species. The scrub-tick, Ixodes holocyclus, is said to be troublesome as a cause of paralysis in young stock in New South Wales. In the regions of Oregon and British Columbia where tick paralysis is especially prevalent there occur a number of different ticks, and there is no evidence that any tick which attacks man along the spinal cord or on the head may not cause paralysis. Ticks and Disease The réle of ticks as disease carriers has been well established since Dutton and Todd in 1905 proved that African relapsing fever was transmitted by a species of tick known as the tampan, 360 TICKS Ornithodorus moubata (Fig. 155). A year later Dr. Ricketts showed that spotted fever in the United Stated was dependent upon a tick, Dermacentor venustus, for its transmission. It is now known that ticks serve as intermediate hosts for a consider- able number of disease germs of two different groups, the spiro- chetes and the Piroplasmata. The various forms of relapsing fever of man are caused by spirochetes, and it is possible that all the different types of this disease may be transmitted by ticks, though in some of the types other arthropods act as the usual transmitters. Many diseases of domestic animals are caused by organisms of the group Piroplasmata (see p. 182), including Texas fever of cattle in North America, East Coast fever of cattle in Africa, biliary fever of horses in Asia and Africa, and similar diseases of sheep, dogs, rats and monkeys. The only human disease positively known to be caused by an organism of this group is Oroya fever of Peru, caused by Bartonella bacilli- formis (see p. 178). Whether or not a tick is instrumental in transmitting this disease is not yet known. Rocky Mountain spotted fever was at one time thought to be caused by a member of the Piroplasmata, but the parasite of this disease is still un- known. The fact that it is transmitted by a tick suggests that it may be found to belong either to the spirochetes or to the Piroplasmata. Ticks have also been suspected of carrying the East Indian form of kedani fever which in Japan is transmitted by a larval mite, but this has not been proved. Ticks and Relapsing Fever.— The fact that tick bites frequently give rise to serious fever and illness, now known as relapsing fever, which not infrequently result in death, has been well known in Africa for many years, in fact Livingston in his “ Darkest Africa ”’ speaks of this disease as resulting from tick bites. The implicated ticks, Ornithodorus moubata, known as “ tampans”’ or ‘“‘carapatos,’’ are very common pests in shaded places in the dirty thatched houses of the natives, and are difficult to avoid. They occur chiefly along the routes of travel, being readily carried and dispersed by caravans. They live also in the bur- rows of warthogs.