THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA PRESENTED BY PROF. CHARLES A. KOFOID AND MRS. PRUDENCE W. KOFOID THE SCIENCE SERIES 1. The Study of Man. By A. C. H ADDON. Illustrated. 8° 2. The Groundwork of Science. By ST. GEORGE Mi- VART. 3. Rivers of North America. By ISRAEL C. RUSSELL. Illustrated. 4. Earth Sculpture ; or, The Origin of Land Forms. By JAMES GEIKIE. Illustrated. 5. Volcanoes; Their Structure and Significance. By T. G. BONNEY. Illustrated. 6. Bacteria. By GEORGE NEWMAN. Illustrated. 7. A Book of Whales. By F. E. BEDDARD. Illustrated. 8. Comparative Physiology of the Brain, etc. By JACQUES LOEB. Illustrated. 9. The Stars. By SIMON NEWCOMB. Illustrated. 10. The Basis of Social Relations. By DANIEL G. BRINTON. xi. Experiments on Animals. By STEPHEN PAGET. 12. Infection and Immunity. By GEORGE M. STERNBERG. For list of works in preparation see end of this volume. ITbe Science Series EDITED BY professor 3. Acfteen Cattell, flD.H., pb.S). AND jf . £. INFECTION AND IMMUNITY Infection and Immunity With Special Reference to The Prevention of Infectious Diseases By George M. Sternberg, M.D., LL.D. Surgeon- General U. S. Army (Retired) Ex-President of the American Medical Association, and of the American Public Health Association ; Honorary Member of the Epidemiological Society of London, of the Societe* Francaise d'Hygiene, of the Royal Academy of Medicine of Rome, etc. G. P. Putnam's Sons New York and London Cbc fsntcherbocfcer pre$3 1903 COPYRIGHT, 1903 BY G. P. PUTNAM'S SONS Published, October, 1903 Ubc Untcherbocfeer preee, f*ew PREFACE I N this volume the writer has attempted to state the main facts, so far as they have been established, with reference to infection and immunity, with the practical object in view of indicating the measures necessary for the prevention of infectious diseases. As the work is intended for non-medical readers, I have avoided technical terms as far as practicable, and when it has been necessary to use these have endeav- oured to explain them. I have thought it best not to enter upon a discussion of the theories of im- munity, or to attempt to give an account of the re- sults of recent investigations with reference to the " antitoxins," " agglutinins," " precipitins," " bacterio- lysins," etc. This line of investigation has, during the past few years, been so prolific in surprising re- sults, and so many new technical terms have become necessary for the designation of the newly discovered bodies of this class and for the understanding of Ehrlich's " side-chain theory," which attempts to ex- plain their mode of action, that this subject does not, iii 1KS63B18 iv PREFACE at present, seem suitable for popular treatment. In my opinion, a knowledge of the well established facts in this field of investigation should constitute an es- sential part of a liberal education ; and the diffusion of such knowledge cannot fail to promote the sanitary interests of the people. The general statement may be made that all infec- tious diseases are preventable diseases, and at the present time it is possible to indicate the necessary measures of prevention for nearly all of these dis- eases. That they continue to prevail, and to claim hundreds of thousands of victims annually, is largely due to the fact that the public, generally, has not yet been educated upon these subjects. It would seem that so important a matter should receive special attention in our high schools and col- leges, and the writer hopes that this volume may, to some extent at least, serve as a text-book, suitable for the use of students, and as a manual of ready reference for those who are responsible for the sani- tary welfare of the inmates of homes, schools, public institutions, etc. In Part Second the most important infectious diseases are considered in special chapters, and an attempt has been made to indicate the manner in which each one is propagated, its importance as a factor in our mortality statistics, and the best methods of restricting its extension. I have been strongly PREFACE v tempted to write an additional chapter upon venereal diseases, but have refrained from treating this un- savoury topic. I may, however, be permitted to quote here from the concluding paragraph of my " Lomb Prize Essay," upon Disinfection and Personal Prophy- laxis against Infectious Diseases, published by the American Public Health Association in 1886 : " This chapter might be greatly extended, but, having passed in review the principal measures of individual prophylaxis against those infectious diseases which are most fatal, we shall not dwell upon precautions to be taken in other contagious diseases. These precautions will not differ from those already recommended in the cases of smallpox and scarlet fever. So, too, in regard to the infectious skin diseases. These are communicated by personal contact, and rarely occur except among those who neglect per- sonal cleanliness as well as other sanitary laws. Soap and water will generally suffice for individual prophylaxis. By avoiding filthy persons as well as filthy places, the danger of contracting these and certain other unmentionable infectious diseases will be reduced to a minimum." G. M. S. 2144 CALIFORNIA AVENUE, WASHINGTON, June /o, 1903. CONTENTS PART FIRST CHAPTER I PAGE GENERAL REMARKS UPON INFECTION ... 3 CHAPTER II DISEASE GERMS CHAPTER III CHANNELS OF INFECTION 14 CHAPTER IV SUSCEPTIBILITY TO INFECTION 23 CHAPTER V DISINFECTION 28 CHAPTER VI TESTS OF DISINFECTION 32 CHAPTER VII DISINFECTION BY HEAT 43 CHAPTER VIII • SUNLIGHT AS A DISINFECTANT 48 CHAPTER IX DISINFECTION BY GASES 51 CHAPTER X VARIOUS CHEMICAL DISINFECTANTS 57 viii CONTENTS CHAPTER XI PAGE NATURAL IMMUNITY 63 CHAPTER XII ACQUIRED IMMUNITY 73 CHAPTER XIII ANTITOXINS 82 PART SECOND CHAPTER I BUBONIC PLAGUE 89 CHAPTER II ASIATIC CHOLERA no CHAPTER III TYPHOID FEVER 126 CHAPTER IV DYSENTERY, CHOLERA INFANTUM, ETC 140 CHAPTER V RELAPSING FEVER 145 CHAPTER VI TYPHUS FEVER 154 CHAPTER VII TUBERCULOSIS 159 CHAPTER VIII LEPROSY .181 CHAPTER IX DIPHTHERIA 191 CHAPTER X INFLUENZA 199 PNEUMONIA WHOOPING-COUGH SMALLPOX SCARLET FEVER MEASLES . MALARIAL FEVERS YELLOW FEVER WOUND INFECTIONS TETANUS . HYDROPHOBIA . INDEX CONTENTS CHAPTER XI CHAPTER XII CHAPTER XIII CHAPTER XIV CHAPTER XV CHAPTER XVI CHAPTER XVII CHAPTER XVIII CHAPTER XIX CHAPTER XX IX PAGE 2O5 211 214 228 234 252 264 272 279 289 ILLUSTRATIONS FIGURE PACK i. — BACILLUS OF BUBONIC PLAGUE .... 101 2. — SPIRILLUM OF ASIATIC CHOLERA ("COMMA BACIL- LUS OF KOCH") 121 3. — BACILLUS OF TYPHOID FEVER 136 4. — SPIRILLUM OF RELAPSING FEVER, AS SEEN IN THE BLOOD 149 5. — BACILLUS OF TUBERCULOSIS, AS SEEN IN THE SPUTUM OF A PATIENT HAVING PULMONARY CONSUMPTION . 160 6. — BACILLUS OF LEPROSY, AS SEEN IN A THIN SECTION OF A LEPROUS NODULE * . 182 7. — BACILLUS OF DIPHTHERIA ..... 193 8.— BACILLUS OF INFLUENZA 200 9. — MICROCOCCUS OF PNEUMONIA 206 10. — MICROCOCCUS OF PUS-FORMATION .... 266 ii. — MICROCOCCUS OF ERYSIPELAS, ETC 267 12. — BACILLUS OF TETANUS 273 PART FIRST INFECTION, DISINFECTION, AND IMMUNITY CHAPTER I GENERAL REMARKS UPON INFECTION J\ A UCH confusion exists in the popular use of the * " term " infection." By many it is supposed to be synonymous with contagion. But this is not in ac- cordance with established usage among well-informed physicians. It is a far more comprehensive term ; for, while all contagious diseases are infectious, not all infectious diseases are contagious. A contagious disease is one which may be transmitted by personal contact, as, for example, smallpox, measles, scarlet fever. These diseases may also be communicated, indirectly, through the medium of objects which have been in contact with infected individuals, such as clothing, bedding, etc. (" fomites "). While the con- tagious diseases mentioned and others which are gen- erally recognised as liable to be contracted by contact with the sick are also infectious, there are numerous diseases which are infectious but not contagious. As examples of this class we may mention the malarial 3 4 INFECTION AND IMMUNITY fevers, yellow fever, and trichinosis. Still others, such as cholera, typhoid fever, and dysentery are only transmitted by personal contact under very excep- tional circumstances. The word " infection," from the Latin verb inficio, means literally to put or dip into anything ; but in its accepted technical sense the putting of non-living particles into a living body does not constitute in- fection. A man who receives a load of bird-shot in the muscles of his thigh is not infected with bird-shot or with lead. But when a living micro-organism is introduced into the body of a living animal and multi- plies there, the animal is infected. This infection may be localised, as in the case of a carbuncle, an abscess, a pneumonia, a pleurisy, etc., or it may be a general blood infection, as in relapsing fever, yellow fever, or the malarial fevers. In cholera and dysen- tery the infectious agent is in the alimentary canal, and penetrates to a greater or less extent the mucous membrane of the intestine. In typhoid fever it in- vades the glands of the intestine and mesentery, and the spleen. In diphtheria the mucous membrane of the throat and posterior nares is the usual seat of the infection. Certain infectious diseases have their seat in vari- ous favourite localities upon the external portion of the body. These are the infectious skin diseases, GENERAL REMARKS UPON INFECTION 5 which are also contagious for evident reasons. The fact that the infecting parasite must penetrate the body of its living host is well illustrated by the in- fectious skin disease known popularly as " itch " (scabies). The itch insect deposits its ova and rears its family in burrows beneath the epidermis, and thus becomes the agent in the production of an infectious skin disease. Certain other parasites, known as pediculi, infest the surface of the body, especially in localities covered with hair. As these do not pene- trate the skin, their presence does not constitute an infection. The fact that a disease may be transmitted through a series of individuals either by contagion or in some other way — by inoculation, by contaminated drink- ing-water, etc. — is evidence that it is due to a living disease germ of some kind and that it is consequently infectious. An individual who has been stung by a wasp or bitten by a rattlesnake is not infected but poisoned. The symptoms resulting from such a bite cannot be reproduced in another individual by inocu- lation of blood or other material from the body of the person bitten. But the bite of a rabid dog gives rise to an infectious disease — " hydrophobia "-—which may be transmitted by inoculation through a series of men or dogs or other susceptible animals. The poison introduced by a wasp or rattlesnake 6 INFECTION AND IMMUNITY does not multiply in the body of the individual bitten and the symptoms produced bear a direct relation to the amount injected. Moreover, the symptoms fol- low very closely after the bite. On the other hand, an infectious disease resulting from inoculation, or con- tracted in any other way, is not developed at once ; but after the introduction of the infectious material a certain interval elapses, technically known as the "period of incubation," before the symptoms char- acteristic of the disease are manifested. In the case of hydrophobia, resulting from the bite of a rabid animal, this so-called period of incubation may be greatly prolonged. It is seldom less than two weeks and may be six months or more. But, as a rule, the period of incubation is quite definite for each infectious dis- ease, although differing greatly in different diseases. Thus it is usually less than three days in scarlet fever and diphtheria ; from two to five days in yellow fever and influenza ; from seven to ten days in whooping- cough ; eleven or twelve days in smallpox ; fourteen days in measles ; and from seventeen to twenty-one days in mumps. In wound infections, resulting from the introduction of certain well-known disease germs into wounds produced by the surgeon's knife or other- wise, the period of incubation is comparatively short, and erysipelas or " blood-poisoning " may be developed within a few hours after the inoculation occurs. GENERAL REMARKS UPON INFECTION 7 What has already been said will, it is hoped, make the following definition of an infectious disease quite clear. An infectious disease is one which is caused by the introduction of living disease germs within the body of a susceptible individual. This definition in- cludes the idea of the reproduction — that is, multipli- cation within the body — of the specific disease germ, which must be living and thus capable of reproduc- tion in order to produce an infectious disease. More- over, it must find conditions favourable for its reproduction within the body or it will not give rise to any disease process — that is, the individual must be susceptible. CHAPTER II DISEASE GERMS TTAVING ascertained that infection results from * * the introduction of living " disease germs " into susceptible individuals, it will be well to give some consideration to these agents of infection. The term disease germ is a popular one and is used to desig- nate any micro-organism capable of giving rise to an infectious disease. The word micro-organism, which I shall have frequent occasion to use, may require a little explanation. By an organism we mean an or- ganic structure which has been built up by vital pro- cesses. It may be a plant or an animal, it may be complex or simple, large or small, but it must, at one time at least, have been endowed with life. A micro- organism is simply a microscopic organism, and being microscopic it is an organism of very simple structure, usually consisting of a single cell (" unicellular micro- organism "). When using the word micro-organism with reference to a disease germ, we must use an 8 DISEASE GERMS 9 adjective to indicate that the particular micro-organism under consideration is capable of producing disease, for there are numerous micro-organisms which are en- tirely harmless. The word pathogenic literally means disease-producing ; a pathogenic micro-organism is therefore a microscopic organism capable of produc- ing disease. This sounds a little more scientific than " disease germ," and it has seemed to me necessary to spend a little time in explaining the meaning of the term, as I may have occasion to use it from time to time, although it is my intention to avoid the use of technical terms as far as possible. When we say that a certain infectious disease is due to a pathogenic micro-organism we have not committed ourselves as to the characters of this dis- ease germ. It may belong to the animal or the vege- table kingdom ; it may be round or oval or spiral in form ; it may be large or small, although microscopic. But when I speak of the micrococcus of pneumonia or the bacillus of typhoid fever, I am using terms which convey much more definite information with reference to the disease germs referred to, and before proceeding any farther it will be desirable to make the reader acquainted with the principal characters of some of the best-known pathogenic micro-organisms. Some of these belong to the animal and some to the vegetable kingdom. Although so very minute and io INFECTION AND IMMUNITY simple in structure, consisting, as a rule, of a single cell, they may be differentiated by the expert without great difficulty, and classified as animal micro-organ- isms ("Protozoa") or as vegetable micro-organisms (" Protophyta "). By far the greater number of known disease germs are recognised as vegetable micro-organisms belonging to the class known as Bacteria. This class includes a large number of harmless species, which abound especially in surface waters and in the upper layers of the soil. The bacteria are classified with reference to their form. Those which are spherical are called micro- cocci / those which are longer in one diameter than in the other — oval, rod-shaped, or filamentous — are called bacilli ; those which are elongated and spiral in form, like a corkscrew, are called spirilla (singu- lar— micrococcus, bacillus, spirillum). The germs of pneumonia, of erysipelas, of boils and abscesses, of Malta fever, of cerebro-spinal meningitis, and some others are micrococci, all having distinct specific char- acters by which they can readily be recognised by an expert bacteriologist. The germs of typhoid fever, of tuberculosis, of influenza, of diphtheria, of dysen- tery, of bubonic plague, of tetanus, and of several infectious diseases of the lower animals (hog cholera, swine plague, anthrax, glanders) are bacilli. As in the case of the pathogenic micrococci, these all have DISEASE GERMS n specific characters by which they can be differentiated one from the other, independently of the fact that each gives rise to a specific infectious disease. The germs of Asiatic cholera and of relapsing fever are spirilla. All bacteria multiply by binary division — that is, one cell divides into two, each resembling in form and dimensions the parent cell, and each in its turn dividing in the same way. The rapidity of multipli- cation by binary division varies greatly in different species, and depends upon circumstances relating to temperature, moisture, and suitable nutrient material. Under favourable conditions bacilli have been ob- served to divide in twenty minutes, and, as each daughter cell is equal in size to the mother cell, it is evident that an amount of nutrient material has been assimilated during this time equal to the quantity contained in the original cell. As a result of this rapid development, " colonies " containing millions of bacilli may be developed from a single cell in twenty- four to forty-eight hours. A simple calculation will show what an immense number of cells may be pro- duced in this time as a result of binary division oc- curring, for example, every hour. The progeny of a single cell would be at the end of twenty-four hours 16,777,220. During the process of multiplication by binary division, the bacterial cells often remain attached to each other, and we may see them under 12 INFECTION AND IMMUNITY the microscope grouped in pairs, or in chains, or in irregular masses. Some of the bacteria multiply not only by binary division but also by the formation of spores, which correspond, so far as the preservation of the species is concerned, to the seeds of higher plants. The growing cells are delicate plants which are easily killed by heat and by various chemical agents (dis- infectants). But the spores resist a much stronger solution of germicidal agents and a much higher temperature. They also resist desiccation, and may retain their vitality for months or years until circum- stances are favourable for their development, when, under the influence of heat and moisture, they repro- duce the minute microscopic plant — bacillus or spiril- lum— and multiplication by binary division again occurs. It is fortunate that comparatively few patho- genic bacteria produce spores, for if this were the case it would be a much more difficult task to arrest the progress of an epidemic of such diseases as typhoid fever, bubonic plague, cholera, or diphtheria. The only infectious disease of man in which spores have been demonstrated to be formed is tetanus, or lockjaw. As this disease is not likely to be com- municated by the sick to those associated with them, either directly or indirectly, the formation of spores by the tetanus bacillus is not so serious a matter. DISEASE GERMS 13 As to the structure of the bacterial cells but little can be said, except that these simple, unicellular plants consist of a transparent protoplasm enclosed in a cel- lular envelope or membrane. The very varied char- acters which distinguish different species of bacteria make it evident that there are essential differences in the living cell contents, or protoplasm, although these differences are not revealed by chemical analy- sis or by our optical appliances. CHAPTER III CHANNELS OF INFECTION l^vISEASE germs gain access to the bodies of sus- •— ^ ceptible individuals, giving rise to infectious diseases, through various channels. The most im- portant of these are doubtless the alimentary and respiratory tracts, to which access is obtained through the mouth and nasal passages. It is sometimes diffi- cult to ascertain whether infection has occurred as a result of the deposition of germs contained in inspired air upon the mucous membrane of the respiratory passages or by reason of their having been taken into the stomach with food or drink. Germs suspended in the air would be to a consid- erable extent deposited upon the moist mucous mem- brane of the mouth and nasal passages, and would be carried thence to the stomach rather than to the lungs. However, in certain diseases, infection no doubt results from the deposition of germs in the bronchial tubes. This is true of pulmonary consumption, of u CHANNELS OF INFECTION 15 influenza (la grippe), of the pulmonic form of bubonic plague, of " wool-sorter's disease " (pulmonary an- thrax), and of pneumonia. In diphtheria the initial infection commonly occurs upon the surface of the tonsils. This is also, no doubt, true in the various forms of tonsillitis and possibly in scarlet fever. In- deed there is good reason to believe that the ton- sils constitute the avenue through which infection occurs, occasionally at least, in a considerable number of diseases of this class, including tuberculosis. The exact knowledge which has been gained during the past twenty years has made it evident that infection through the medium of the air is by no means as common as was formerly believed. We now know that malarial fevers and yellow fever are not con- tracted in this way, but that they result from inocula- tions made by infected mosquitoes. Some disease germs are quickly killed by desiccation and exposure to sunlight. These are not likely to be carried through the air in a living condition, and consequently the diseases produced by them are not propagated in this way. This is true of Asiatic cholera and to a con- siderable extent of typhoid fever, which diseases are recognised as being essentially water-born. How- ever, the bacillus of typhoid fever resists desiccation for some time, and when the surface of the ground becomes contaminated with the discharges of typhoid- 1 6 INFECTION AND IMMUNITY fever patients the bacillus may be carried by the wind, with dust, and deposited upon the moist mucous membrane of the mouths and nasal passages of indi- viduals who breathe this dust-laden air. This is also true of the bacillus of bubonic plague, and to a still greater degree of the bacillus of tuberculosis. The bubonic-plague bacillus, contained in the ex- creta of infected individuals and of rats, which are very susceptible to the disease, may retain its vitality for a considerable time when deposited upon the ground, and it is in this way that insanitary localities become centres of infection. The tubercle bacillus, which is contained in the matter coughed up from the lungs by persons suffering from pulmonary con- sumption, may retain its vitality and infecting power for a long time after the expectorated material con- taining it has been dried and pulverised. It is evident that such dust is likely to be carried by currents of air and deposited in the lungs of per- sons who are compelled to live in localities where such insanitary conditions prevail. No doubt this is the usual way in which pulmonary consumption is contracted. Again, the dust deposited in the mouth and nasal passages may be swallowed and other forms of tubercular disease result — tubercular peritonitis, tubercular meningitis, tubercular joint disease, tuber- culosis of the vertebral column. CHANNELS OF INFECTION 17 In smallpox, scarlet fever, and the " eruptive fevers" generally infectious material is given off from the sur- face of the body of the sick person. This is associ- ated with cast-off epithelium, pus cells, etc., and constitutes a kind of dust which abounds in the sick- room and clings to the clothing and bedding of the patient and of those in attendance upon him. In influenza and whooping-cough the patient forcibly ejects small masses of mucus which soon become desiccated and are likely to make up a portion of the dust in apartments occupied by such patients. Evi- dently the great danger from infection in these dis- eases results from visiting the sick-room or handling clothing which has been exposed to contamination by infectious material coming from the body of the sick person. In typhoid fever, Asiatic cholera, and dysentery the infectious material coming from the sick person is contained in the discharges from the bowels and is usually quickly removed from the sick-room. The great danger as regards the spread of these dis- eases consists in the possibility that ignorant or care- less persons may throw these discharges upon the ground or dispose of them in some way which makes it possible for the germs to be washed into a well or a running stream from which water is used for drink- ing purposes. But this is not the only way in which 1 8 INFECTION AND IMMUNITY disease germs may find their way from the excreta of the sick to the stomachs of healthy persons. If thrown upon the ground, flies alighting upon the foul material may subsequently visit a near-by kitchen and there walk over the food prepared for the family meal, leaving numerous typhoid bacilli in their tracks ; or they may fall into the milk, or in some other un- suspected way convey the deadly microscopic germs to some article of food or drink. Again, articles of clothing soiled by the discharges of the sick may be the means of conveying infection to laundresses, who in handling such articles are liable to soil their hands or in some indirect way to introduce the pathogenic bacteria into their mouths. This mode of infection is liable to occur in any disease in which the germ is present in the discharges from the bowels, and es- pecially in Asiatic cholera. In Oriental countries, where human excreta con- stitutes a very common fertilising material, green vegetables, which are eaten raw, are believed to serve as the medium through which the germs of dysentery and cholera are occasionally conveyed to the stomachs of persons partaking of such articles of food. There is also considerable evidence in favour of the view that typhoid fever may be con- tracted by eating oysters which have been grown in sewage-polluted waters. The infectious disease known CHANNELS OF INFECTION 19 as trichinosis is contracted by eating pork containing living trichinae. As these parasitic worms are promptly killed at a comparatively low temperature, cooked pork is quite harmless, so far as this disease is con- cerned. Infection through wounds is far less common at the present day than was the case before aseptic sur- gery and the antiseptic treatment of wounds became established as a standard method of surgical proced- ure. Formerly epidemics of septicaemia, erysipelas, and hospital gangrene were of frequent occurrence, and the cleanest and best regulated hospitals were not exempt from these visitations. But in the light of our present knowledge such epidemics are no longer excusable and the infection of surgical wounds is extremely rare. Accidental wounds may, however, become infected at the time they are inflicted or be- cause of failure to apply proper surgical dressings. Jagged and penetrating wounds which do not bleed are especially liable to be infected by the lodgment of germs in the deeper portion of the wound. It is in this way that tetanus or lockjaw is commonly pro- duced. The tetanus bacillus forms spores which may retain their vitality for years. These are found in soil which has been enriched by manuring and in the dust of streets. Bubonic plague is another disease which is com- 20 INFECTION AND IMMUNITY monly contracted through accidental wounds. In countries where it prevails, it has been observed that the natives, who do not wear shoes and stockings, are much more liable to infection than Europeans, and it seems to be well established that infection may occur through insignificant wounds, such as scratches or abrasions of exposed parts of the body. We have also satisfactory evidence that tuberculosis may be transmitted to man by the accidental inoculation of an open wound. Malignant pustule, or anthrax, is communicated in the same way, and it sometimes happens that the inoculation is effected by flies which have been in contact with the infectious material escaping from the body of an animal having the dis- ease or recently dead as a result of it. It is well known that surgeons when operating upon an infected wound and pathologists when performing autopsies, in certain cases, are liable to a severe and sometimes fatal attack of "blood-poisoning" as a result of infection through a slight scratch or abra- sion upon the hand, or through an accidental punc- ture made by a surgical needle. The germ which is most frequently concerned in this blood-poisoning, or septicaemia, is well known and is the usual cause of puerperal fever, erysipelas, and a considerable propor- tion of the cases of peritonitis. It is, therefore, in treating or making autopsies upon cases of this nature CHANNELS OF INFECTION 2 1 that physicians run the greatest danger of accidental infection. The question whether infection may occur through the unbroken skin has been studied and an affirma- tive result obtained. The liability to infection in this way is, however, comparatively slight. When it does occur, it appears that the germs penetrate through the hair follicles. Infection may occur through mu- coiis membranes, and it is in this way that infectious conjunctivitis and various other specific inflamma- tions of mucous membranes are propagated. Infec- tious skin diseases, such as scabies (itch), ringworm, barber's itch, etc., may, no doubt, be contracted by susceptible persons, when conditions are favourable, independently of any wound or abrasion, especially in those who do not indulge in frequent bathing and thus give the germs time to penetrate the epidermis. Researches made during the past few years have demonstrated that malarial fevers and yellow fever are communicated to man through the bites of in- fected mosquitoes. Certain infectious diseases of lower animals are also transmitted by insects. Thus it has been shown that ticks are responsible for the propa- gation of a fatal disease of cattle known as Texas fever, and an infectious disease of horses, which has recently prevailed extensively in the Philippine Islands, is communicated by a biting fly, which 22 INFECTION AND IMMUNITY transmits the parasite from diseased to healthy animals — " surra disease." The tsetse-fly disease of Africa is transmitted in the same way and is very fatal to horses and also to the ox, the dog, the ass, and the sheep, but not to wild animals indigenous in the region where the tsetse fly is found. The parasite is present in great numbers in the blood of infected animals, and the fly simply acts as a carrier of this parasite from diseased to healthy animals. CHAPTER IV SUSCEPTIBILITY TO INFECTION TT has long been known that certain infectious dis- eases prevail only or principally among animals of a single species, while others are communicable to several species, including man himself. Thus typhoid fever, cholera, and relapsing fever are diseases of man, and during their epidemic prevalence none of the domestic animals contracts any 'of these diseases. On the other hand, the lower animals are subject to various infectious diseases which may prevail as fatal epidemics but which are never communicated to man — for example, chicken cholera, hog cholera, swine plague, rinderpest, foot-and-mouth disease. Again, several species, including man, may be sus- ceptible to a disease while other animals have a natural immunity to it. Thus tuberculosis is com- mon to man, to cattle, to apes, and to the small herbivorous animals (by inoculation), while the carni- vora, as a rule, are immune ; anthrax may be 23 24 INFECTION AND IMMUNITY communicated by inoculation to man, to cattle, to sheep, to guinea-pigs, rabbits, and mice, but the rat, the dog, carnivorous animals generally, and birds are immune ; glanders, which is essentially a disease of horses, may be communicated to man, to the guinea- pig, and to field-mice, while house-mice, rabbits, cattle, and swine are to a great extent immune ; smallpox is essentially a disease of man, but a modified form of the disease may prevail among cattle (cowpox). Susceptibility to infection also depends to a con- siderable extent upon conditions relating to the indi- vidual. It is well known that an attack of certain infectious diseases protects the individual from subse- quent attacks. This subject will receive attention in the chapter devoted to " Acquired Immunity." But in the absence of any such acquired immunity the susceptibility of individuals of the same species dif- fers considerably, and the same individual may be more susceptible to infection at one time than at another. Certain families or races are especially sus- ceptible to infection by certain disease germs. Thus the negro race is less susceptible to yellow fever and to the malarial fevers than the white race ; on the other hand, smallpox is exceptionally fatal among negroes and dark-skinned races. In general it may be said that when an infectious disease is first intro- duced among primitive races, who, by reason of their SUSCEPTIBILITY TO INFECTION 25 isolation, have been previously exempt from it, it is apt to be exceptionally fatal. This is no doubt due to the fact that there has been no opportunity for the operation of the laws of natural selection, by " sur- vival of the fittest." But under the operation of these laws, in process of time, a certain degree of race immunity is likely to be established. Individual susceptibility depends to some extent upon age. As a rule, young animals are more sus- ceptible to infection by inoculation than adults of the same species. In the human race we recognise certain diseases as especially liable to prevail among children — scarlet fever, whooping-cough, etc. It is also known that the tendency to tubercular infection diminishes with advancing years. Tubercular menin- gitis and tubercular joint diseases are most common in children, and pulmonary consumption in young adults. Again, the susceptibility of individuals de- pends to a considerable extent upon conditions re- lating to their general ,health. Various depressing agencies increase the susceptibility to infection. Most prominent among these are insufficient food, insani- tary surroundings, great fatigue, and mental worry — grief, fear, etc. The fact that pestilence and famine are likely to go hand in hand has long been known. Whether the prevailing epidemic be cholera, bubonic plague, relapsing fever, typhus, or smallpox, the 26 INFECTION AND IMMUNITY influence of insufficient food is most marked, and in times of distress, due to failure of the food supply, any infectious disease is liable to exhibit a malignancy and fatal character, although under ordinary conditions it may be comparatively harmless. Insanitary sur- roundings, by vitiating the air, insufficient ventilation and overcrowding of dwellings, factories, school- houses, etc. — all have a tendency to lower the vital resisting power of individuals subjected to such in- fluences and to increase the susceptibility to infec- tion. Debility resulting from loss of blood or the exhaustion following great fatigue also increases the susceptibility to various infectious diseases. Clinical observation shows that a similar result follows the ex- cessive use of alcoholic drinks. Localised infectious processes are not only more liable to be established in individuals whose vital energy is reduced by any of the causes mentioned, but also as a result of causes which reduce the resist- ing power of the tissues at the point of invasion. Thus a carbuncle or an abscess may develop in tis- sues that have been bruised or injured in any way ; and the congestion or inflammation of the fauces which is so common as a chronic or acute condition —a "sore throat"-— no doubt increases the suscepti- bility to diphtheritic infection in this locality. It is well known that pneumonia often follows attacks of SUSCEPTIBILITY TO INFECTION 27 measles, of influenza, or of bronchitis, in which dis- eases there is a catarrhal inflammation of the bron- chial tubes which appears to favour infection by the specific micrococcus which is the usual cause of pneu- monia. The victims of chronic alcoholism are es- pecially subject to pneumonia. Certain occupations increase the susceptibility to certain infectious diseases. Thus pulmonary con- sumption is more likely to be developed in those who lead an indoor life, whose occupation has a tendency to prevent full expansion of the lungs — tailors, seam- stresses ; and in persons who are compelled to breathe a dust-laden atmosphere — factory hands, grinders, etc. Susceptibility to pneumonia, influenza, tonsil- litis, and diseases of the air passages generally is increased by living in over-heated apartments. Ex- posure to cold, per se, is not likely to increase the susceptibility to such infections in individuals who are habituated to living in the open air, such as sail- ors, hunters, soldiers living in tents, etc. CHAPTER V DISINFECTION '"THE object of disinfection is to prevent the exten- sion of infectious diseases by destroying the specific infectious agent (germ) which gives rise to them. This is accomplished by the use of disin- fectants. The writer, as chairman of the Committee on Dis- infectants of the American Public Health Associa- tion, in 1885, defined a disinfectant as "an agent capable of destroying the infecting power of infec- tious material." In the preliminary report of this Committee the following general statements with reference to disin- fection and disinfectants are also made : "There can be no partial disinfection of such material [that is, material containing disease germs] ; either its infecting power is destroyed or it is not. In the latter case there is a failure to disinfect. Nor can there be any disinfection in the absence of infectious material. " Popularly, the term disinfection is used in a much broader 28 DISINFECTION 29 sense. Any chemical agent which destroys or masks bad odours, or which arrests putrefactive decomposition, is spoken of as a disinfectant. And in the absence of any infectious disease it is common to speak of disinfecting a foul cesspool, or a bad-smell- ing stable, or a privy vault. " This popular use of the term had led to much misapprehen. sion, and the agents which have been found to destroy bad odours — deodorisers, — or to arrest putrefactive decomposition — antiseptics, — have been confidently recommended and extensively used for the destruction of disease germs in the excreta of patients with cholera, typhoid fever, etc. " The injurious consequences which are likely to result from such misapprehension and misuse of the word disinfectant will be appreciated when it is known that recent researches have demon- strated that many of the agents which have been found useful as deodorisers, or as antiseptics, are entirely without value for the destruction of disease germs. " This is true, for example, as regards the sulphate of iron, or copperas, a salt which has been extensively used with the idea that it is a valuable disinfectant. As a matter of fact, sulphate of iron in saturated solution does not destroy the vitality of disease germs, or the infecting power of material containing them. This salt is, nevertheless, a very valuable antiseptic, and its low price makes it one of the most available agents for the arrest of putre- factive decomposition. " Antiseptic agents also exercise a restraining influence upon the development of disease germs, and their use during epidemics is to be recommended when masses of organic material in the vicinity of human habitations cannot be completely destroyed, or removed, or disinfected. " While an antiseptic agent is not necessarily a disinfectant, all disinfectants are antiseptics; for putrefactive decomposition is due to the development of * germs ' of the same class as that to which disease germs belong, and the agents which destroy the latter also destroy the bacteria of putrefaction, when brought in contact with them in sufficient quantity, or restrain their develop- ment when present in smaller amounts. 30 INFECTION AND IMMUNITY " A large number of the proprietary ' disinfectants ' so-called, which are in the market, are simply deodorisers or antiseptics of greater or less value, and are entirely untrustworthy for disinfect- ing purposes." The offensive gases given off from decomposing organic material are no doubt injurious to health ; and the same is true, even to a greater extent, of the more complex products known as ptomaines, which are a product of the vital processes attending the growth of the bacteria of putrefaction and allied organisms. It is therefore desirable that these pro- ducts should be destroyed ; and, as a matter of fact, they are neutralised by some of the agents which we recognise as disinfectants, in accordance with the strict definition of the term. But they are also neu- tralised by other agents — deodorants — which cannot be relied upon for disinfecting purposes, and by dis- infectants, properly so-called, in amounts inadequate for the accomplishment of disinfection. Their form- ation may also be prevented by the use of antiseptics. From our point of view, the destruction of sulphur- etted hydrogen, of ammonia, or even of the more poisonous ptomaines, in a privy vault, is no more dis- infection than is the chemical decomposition of the same substances in a chemist's laboratory. The same is true as regards all of the bad-smelling and little- known products of decomposition. None of these DISINFECTION ,. 31 is " infectious material," in the sense in which we use these words ; that is, they do not, so far as we know, give rise directly to any infectious disease. Indirectly they are concerned in the extension of the " filth diseases," such as cholera, bubonic plague, and typhoid fever. This because persons exposed to the foul emanations from sewers, privy vaults, and other receptacles of filth have their vital resisting power lowered by the continued respiration of an atmo- sphere contaminated with these poisonous gases, and are liable to become the victims of any infectious dis- ease to which they may be exposed. CHAPTER VI TESTS OF DISINFECTION \ \ 7 HAT means have we of proving that the infect- ing power of infectious material has been de- stroyed ? Evidence of disinfection may be obtained : (a) from the practical experiments — experience — of those en- gaged in sanitary work ; (f) by inoculation experi- ments upon susceptible animals ; (c) by experiments made directly upon known disease germs. (a) It is a matter of common experience that, when a room has been occupied by a patient with an infec- tious disease, such as smallpox, scarlet fever, or diphtheria, susceptible persons are liable to contract the disease weeks or even months after the patient has been removed from it, unless in the meantime it has been disinfected. If a second case does occur from exposure in such a room, it is evident that it has not been disinfected. But the non-occurrence of sub- sequent cases cannot always be taken as evidence 32 TESTS OF DISINFECTION 33 that the means of disinfection resorted to were effi- cient. Negative evidence should be received with great caution. In the first place, the question as to whether susceptible individuals have been fairly ex- posed in the disinfected room must be considered. Then it must be remembered that susceptible persons do not always contract a disease, even when they are exposed in a locality known to be infected. A further difficulty in estimating the value of evidence obtained in practice arises from the fact that in connection with the special means of disinfection resorted to, such as fumigation, hanging up cloths saturated with a disinfecting solution, etc., it is customary to resort to additional precautionary measures, such as wash- ing surfaces with soap and hot water, whitewashing plastered walls, and free ventilation. It is apparent that under these circumstances it would be unsafe to accept the fact that no other cases occurred in a room treated in this way as evidence that the particular disinfectant used is efficient for the destruction of the infectious agent of the disease in question. The fond mother who attaches a charm to her child's neck to protect it from evil also takes the precaution of guard- ing it from contact with other children who are sick with any infectious disease. If her child fortunately grows to manhood or womanhood without having suffered an attack of scarlet fever or diphtheria, she 34 INFECTION AND IMMUNITY may imagine that her charm has protected it ; but the evidence upon which her faith is founded is not of a nature to convince those who are familiar with scientific methods of demonstration. " Well edu- cated " persons are often ready to testify in favour of methods of disinfection or of treatment upon evid- ence which, from a scientific point of view, has no more value than that which the fond mother in ques- tion has to offer in favour of the little bag containing camphor or assafcetida or some other charm of equal value which she has attached to her child's neck to keep it from catching scarlet fever or diphtheria at school. On a par with these charms, so far as disin- fection is concerned, we may place the saucer of chloride of lime, which it was formerly the fashion to place under the bed of a patient sick with an infec- tious disease, the rag saturated with carbolic acid or chloride of zinc, suspended in the sick-room, and even the fumigations with burning sulphur, as sometimes practised by those who are unfamiliar with the evid- ence as to the exact value of this agent and the conditions necessary to insure successful disinfection with it. Chloride of lime, sulphurous-acid gas, and carbolic acid are among our most useful disinfecting agents ; but disease germs cannot be charmed away by them any more than by a little bag of camphor. TESTS OF DISINFECTION 35 Having pointed out the fact that negative evidence, in a restricted field of observation, must be accepted with great caution in estimating the value of disin- fectants, we hasten to say that the combined experi- ence of sanitarians, derived from practical efforts to restrict the extension of infectious diseases, is of the greatest value, and that this experience is, to a great extent, in accord with the results of exact experi- ments made in the laboratory. (6) Inoculation experiments upon susceptible ani- mals, made directly with infectious material which has been subjected to the action of a disinfectant, have been made by numerous observers. The proof of disinfection in this case is failure to produce the characteristic symptoms which result from inoculation with similar material not disinfected. Thus, Davaine found that the blood of an animal just dead from the disease known by English writers as anthrax or splenic fever, inoculated into a healthy rabbit or guinea-pig, in the smallest quantity, infallibly pro- duces death within two or three days ; and the blood of these animals will again infect and cause the death of others, and so on indefinitely. This anthrax blood therefore is infectious material, which can be utilised for experiments relating to the comparative value of disinfectants. Davaine made many such experiments, not only with the blood of anthrax, but also with that 36 INFECTION AND IMMUNITY of a fatal form of septicaemia in rabbits, which is known by his name. Other investigators have fol- lowed up these experiments upon infectious material of the same kind, and also upon material from other sources — the infectious material of glanders, of tuber- culosis, of symptomatic anthrax, of fowl cholera, of swine plague, etc. It has been proved that the infectious agent in all of the diseases mentioned is a living germ, and that disinfection consists in destroying the vitality of this germ. But in experiments made with blood or other material obtained directly from diseased animals, the results would be just as definite and satisfactory if we were still ignorant as to the exact nature of the infecting agent. The test shows the destruction of infecting power without any reference to the cause of the special virulence, which is demonstrated to be neutralised by certain chemical agents in a given amount. All of the experiments made with the above-mentioned kinds of virus have been made upon the lower animals ; but there is one kind of material which it is justifiable to use upon man himself, and with which numerous experiments of a very satisfactory character have been made. This material is vaccine virus. Fresh vaccine, when inocu- lated into the arm of an unvaccinated person, gives rise to a very characteristic result — the vaccine vesi- TESTS OF DISINFECTION 37 cle. The inference seems justified that any agent which will neutralise the specific infecting power of this material will also neutralise the smallpox virus. In these experiments the more careful investigators have taken the precaution of vaccinating the same person with disinfected and non-disinfected virus from the same source. A successful vaccination with the non-disinfected virus shows that the individual is susceptible and the material good ; failure to produce any result is evidence that the potency of the disin- fected virus has been destroyed by the chemical agent to which it was exposed. (c) As already stated, it has been demonstrated that the infectious diseases of the lower animals, which have furnished the material for experiments upon disinfectants by the method of inoculation, are "germ diseases," and that the infectious agent is in each case a living micro-organism, belonging to the class known under the general name of Bacteria. The bacteria are vegetable organisms, which, by reason of their minute size and simple organisation must be placed at the very foot of the scale of living things ; but they make up in number and in rapidity of development for their minute size. Many of these disease germs are now known to us, not only by microscopic examination of the blood and tissues of infected animals, but also by " culture 38 IXFECTION AND IMMUNITY experiments." That is, we are able to cultivate them artificially in suitable media, and to study their mode of 'development in the laboratory, quite independently of the animals from which our " pure cultures " were obtained in the first instance. The culture fluids used are prepared from the flesh of various animals ; and when to one of these a certain quantity of gela- tine is added, we have a "solid culture medium," upon the surface of which some of these germs will grow most luxuriantly. To start such a " culture," it is only necessary to transfer, with proper precautions, a minute quantity of the infectious material to the surface of our culture medium, or into a fluid which has been found to be suitable for the growth of the particular organism which we desire to cultivate. A second culture is in the same way started from the first, and so on indefinitely. Now it is evident that these pure cultures furnish us a ready means for testing the power of various chemical agents to destroy the vitality of known dis- ease germs, as shown by their failure to grow in a suitable culture medium after exposure for a given time to a given percentage of the disinfectant. Very many experiments of this nature have been made. We may say here, that the experimental data on record indicate that those agents which are efficient for the destruction of any one of the pathogenic TESTS OF DISINFECTION 39 organisms upon which experiments have been made, or of harmless species of the same class, are efficient for the destruction of all, in the absence of spores. There is, it is true, within certain limits, a difference in the resisting power of different organisms of this class to chemical agents. This is not, however, suffi- ciently marked to prevent the general statement that a disinfectant for one is a disinfectant for all, in the absence of spores. The last clause of the above statement calls for an explanation, and certain details with reference to the mode of reproduction of disease germs. All of the bacteria multiply by binary division ; that is, one in- dividual divides into two, and each member of the pair again into two, and so on. The spherical bac- teria, known as micrococci, multiply only in this way, but some of the rod-shaped bacteria, or bacilli, also form spores. These spores correspond with the seeds of higher plants. They are highly refractive, oval or spherical bodies, which, under certain circumstances, make their appearance in the interior of the rods, which cease to multiply by binary division when spore formation has taken place. The point of special in- terest with reference to these spores is, that they have a resisting power to heat, and to the action of chem- ical disinfectants, far beyond that which is possessed by micrococci, or by bacilli without spores. The 40 INFECTION AND IMMUNITY difference may be compared to the difference between a tender plant and its seeds to deleterious influences, such as extremes of heat and cold. Thus the spores of certain species of bacilli withstand a boiling tem- perature for several hours, while a temperature of 150° Fahr. quickly kills most bacteria in the absence of spores. A similar difference is shown as regards the action of chemical agents. Certain agents, — e. g., sulphurous-acid gas and carbolic acid, — which are extensively used as disinfectants, have been proved by exact experiments to be quite impotent for the destruction of spores. This being the case, it is advisable, in practical disinfection, always to use an agent which has the power of destroying spores, in those cases in which the exact nature of the disease germ has not been demonstrated. The cholera germ of Koch does not form spores ; and there is good reason to believe that the same is true as regards the germs of yellow fever, of scarlet fever, and of small- pox, which have not yet been demonstrated. This inference is based upon evidence obtained in the prac- tical use of disinfectants, and upon certain facts relat- ing to the propagation of these diseases. A second general statement, which is justified by the experimental evidence on record, is, that agents which kill bacteria in a certain amount prevent their multiplication in culture fluids, when present in quan- TESTS OF DISINFECTION 41 tities considerably less than are required to completely destroy vitality. An agent, therefore, which in a certain proportion and in a given time acts as a " germicide," in a smaller quantity may act as an antiseptic — i. e., may prevent putrefactive decomposition by restraining the devel- opment of the bacteria of putrefaction. Antiseptics also prevent or retard the development of pathogenic bacteria. It follows from this that germicides are also antiseptics ; but the reverse of this proposition is not true as a general statement, for all antiseptics are not germicides. Thus alcohol, common salt, sul- phate of iron, and many other substances which are extensively used as antiseptics, have scarcely any germicide power, even in concentrated solutions, and consequently would be entirely unreliable as disinfectants. Practically, antiseptics may accomplish the same result in the long run as we obtain in a short time by the use of disinfectants. If, for example, we pre- vent the development of the germs of cholera, or of typhoid fever, in an infected privy vault, by the continued use of antiseptics, these germs will in time lose their ability to grow, when introduced into a suitable culture medium. But in the meantime there is always the possibility that some of them may escape, with the fluid contents of the vault, into the 42 INFECTION AND IMMUNITY surrounding soil, and contaminate some well or stream from which drinking-water is obtained. For this reason privy vaults, cesspools, and sewers should never be allowed to become infected. All infectious material, such as the dejections of patients with cholera or typhoid fever, should be destroyed at its source, in the sick-room ; or, if it is ascertained that such material has been thrown into a privy vault, the entire contents of the vault should be promptly disin- fected. The same rule applies to infectious material thrown upon the ground, or wherever it may be. CHAPTER VII DISINFECTION BY HEAT TT is hardly necessary to say that burning of in- * fectious material, infected clothing, etc., is an effectual method of disposing of it. This method of disinfection is always to be recommended, when practical and consistent with a due regard for econ- omy and the rights of individuals. As a rule, arti- cles of little value, which have been soiled with infectious material, had better be burned ; and this is especially true of old clothing and bedding. But we have other efficient methods of disinfection, which make it unnecessary to sacrifice articles of value ex- cept under unusual circumstances. While all disease germs are readily killed by ex- posure for a short time to the temperature of boiling water, many of the most important pathogenic bac- teria are quickly destroyed by a much lower tempera- ture than this — that is, when exposed in a liquid or in a moist condition. When in a desiccated condition, 43 44 INFECTION AND IMMUNITY or exposed to the action of hot, dry air, a much higher temperature is required. This fact must constantly be kept in view in carrying out practical measures of disinfection, and for this reason the disinfection of clothing, blankets, etc., by dry heat is rarely employed. At quarantine stations and municipal disinfecting sta- tions disinfection by steam is relied upon to a great extent, and has been proved by experience to be su- perior to all other methods. The disinfection of bandages, instruments, and dressings of all kinds for the " aseptic " treatment of surgical wounds is also accomplished by exposure to moist heat (steam or boiling water). In considering the value of heat as a disinfectant, we must take account of the very great difference in the resisting power of growing bacteria and of the reproductive elements formed by some of them, which are known as " spores." The spores of certain bacteria found in surface water and in the soil may resist the temperature of boiling water or of live steam for several hours, but fortunately the spores of known disease germs have far less resisting power. In experiments made nearly twenty years ago, I found that the spores of the anthrax bacillus did not grow after exposure to the temperature of boiling water for four minutes. As already stated, bacteria which do not form DISINFECTION J3 Y HE A T 45 spores are quickly killed by a temperature consider- ably below that of boiling water. The exact thermal death-point of a considerable number of the most important disease germs was determined by the writer in a series of experiments made in 1885. The cholera germ and the micrococcus of pneumonia were the least resistant of all those tested, and were de- stroyed by ten minutes' exposure to a temperature of 130° Fahr. The typhoid bacillus was killed in the same time by a temperature of 140°. In general the statement may be made as a result of my own experi- ments and those of other investigators, that patho- genic bacteria which do not form spores are killed by ten minutes' exposure to a temperature of 140° Fahr. (moist heat), with the exception of the tuber- cle bacillus, which requires a somewhat higher tem- perature (160° Fahr.). The list of known disease germs which are killed by ten minutes' exposure to a temperature of 140° Fahr. (60° C.) includes the bacillus of typhoid fever, of diphtheria, of bubonic plague, of glanders, the micrococcus of pneumonia, of erysipelas and puerperal fever, of boils and ab- scesses, the spirillum of cholera and of relapsing fe- ver. In addition to these known germs it has been determined that the same temperature destroys the infecting power of vaccine virus, and presumably of smallpox virus, of hydrophobia virus, and of certain 46 INFECTION AND IMMUNITY other kinds of infectious material in which the spe- cific germ has not yet been demonstrated. While dry hot air is, as a rule, unreliable for the de- struction of disease germs, certain bacteria are quickly destroyed by desiccation. This is true of the cholera spirillum and of the micrococcus of pneumonia. On the other hand, the bacillus of typhoid fever, the bacil- lus of diphtheria, the bacillus of tuberculosis and the bacillus of bubonic plague may retain their vitality for weeks, or even months, when in a desiccated condi- tion. This is true also of the virus of smallpox and of scarlet fever. Low temperatures do not destroy bacteria. They have been exposed to a temperature of— 87° C., ob- tained by the evaporation of liquid carbonic acid, but when again brought under favourable conditions showed no diminution in their capacity for develop- ment. Repeated freezing and thawing has, however, a deleterious action. The typhoid bacillus may be killed in cultures which are frozen and thawed out at intervals of three days, by repeating the operation five or six times. The facts stated in this chapter make it evident that heat constitutes the most generally useful agent for the destruction of infectious material. Any arti- cle of food or drink which has been recently brought to a temperature approaching that of the boiling- DISINFECTION B Y HE A T 47 point is surely free from living disease germs dan- gerous to man. All articles of clothing which have been subjected to the ordinary operations of the laundry are safely- disinfected. Vessels containing the infectious discharges of per- sons suffering from cholera, typhoid fever, etc., if thoroughly treated with boiling water may be disin- fected, together with their contents. To make sure of this the quantity of boiling water used should be three or four times greater than the contents of the vessel, and from ten to twenty minutes should be given for the disinfecting action of the hot water. Articles of bedding and clothing which would be injured by immersion in boiling water may be disin- fected by exposure to steam in a properly constructed disinfecting chamber or " steriliser." Clothing may also be disinfected by dry heat if freely exposed in a closed chamber to the action of hot dry air, at a temperature of 125° C. for two hours. CHAPTER VIII SUNLIGHT AS A DISINFECTANT \ A 7 HAT has been said in the preceding chapter with reference to the germicidal value of heat and desiccation would indicate the utility of exposing infected articles to sunshine in the open air, as has long been the custom in domestic sanitary practice. But it has been ascertained by carefully conducted experiments that such exposure has an additional value on account of the disinfecting action of the sunlight per se. As long ago as 1877 two English experimenters (Downes and Blunt) in a communica- tion made to the Royal Society of London presented evidence showing that sunlight has an injurious effect upon bacteria, and that sterilisation of cultures in liquid media could be effected by prolonged exposure to direct sunlight. Since then many experiments have been made by different observers and the fact has been fully confirmed. Even the spores of cer- tain bacilli are destroyed by long exposure to sun- 48 SUNLIGHT AS A DISINFECTANT 49 light. The distinguished German bacteriologist, Dr. Robert Koch, reported, some years since, the results of his experiments with the tubercle bacil- lus. He found that the time required to kill this bacillus varies from a few minutes to several hours, depending upon the thickness of the layer exposed. Even diffused daylight exerts a certain germicidal action, although the time of exposure is very much longer — five to seven days for the tubercle bacillus. In the writer's experiments made in 1892 it was found that two hours' exposure to direct sunlight was fatal to the cholera spirillum suspended in a liquid medium. The electric light, and even gas-light, have also a germicidal action upon certain disease germs, al- though very much less in degree than sunlight. It has been ascertained that the rays at the violet end of the spectrum have the greatest disinfecting power, while the red rays are comparatively inert. The facts stated fully sustain the popular idea that the exposure of infected articles of clothing and bed- ding in the sun is a useful sanitary precaution. Re- peated and prolonged exposure will, however, be necessary to ensure safety. In the case of such dis- eases as smallpox, diphtheria, and scarlet fever more speedy and reliable measures of disinfection will be required. Exposure to the sunlight is nevertheless a 50 INFECTION AND IMMUNITY most useful and economical procedure and is to be commended as a routine practice in domestic sanita- tion, and also as an additional and supplementary precaution when infected articles have been subjected to the action of other disinfectants. CHAPTER IX DISINFECTION BY GASES TT is impracticable to disinfect the atmosphere of an occupied apartment ; for any gaseous or volatile agent which would destroy disease germs suspended in the air would render it irrespirable. Moreover the air of the sick-room should be constantly renewed by ventilation, and there is far less reason for disinfect- ing it when the patient has been removed than while it is occupied, for then the air may be quickly re- newed by opening doors and windows. As is well known, particles of dust suspended in the air of a room have a tendency to settle upon the floor, upon window ledges, etc., and infected particles from the patient's body will constitute a portion of this dust in such diseases as smallpox and scarlet fever, while in tuberculosis, diphtheria, influenza, and pneumonia expectorated material may become desiccated and constitute a portion of the dust. Every effort should be made to prevent a room 51 52 INFECTION AND IMMUNITY occupied by patients sick with an infectious disease from becoming infected. Carpets, stuffed furniture, curtains, and other articles difficult to disinfect should be removed at the outset. Indeed, nothing should be left in the room which is not absolutely required, and all furniture and utensils should be of such a character that they can be readily disinfected by washing with boiling water or with a disinfecting so- lution. Abundant ventilation and scrupulous cleanli- ness should be maintained, and a disinfecting solution should always be at hand for washing the floor, or articles in use, the moment they are soiled by infectious discharges. Daily wiping of all surfaces — floors, walls, and furniture — with a cloth wet with a disinfecting solu- tion is to be recommended. For this purpose a solution of chloride of lime (2 per cent), or of car- bolic acid (2 per cent), or mercuric chloride (1:1000), may be used. By such precautions the infection of the sick-room may be prevented, especially in those diseases, such as cholera and typhoid fever, in which the infectious agent is not given off from the general surface of the body of the sick person. If a complete disinfection of the room is required it is indispensable that it be first vacated. It will then be practicable to use certain gaseous disinfectants. DISINFECTION BY GASES 53 The various so-called disinfectants which are often recommended to purify the air of the sick-room are, at the most, simply deodorisers of greater or less value, and are entirely unreliable for the destruction of disease germs under the conditions existing in an occupied apartment. Disinfection of the vacated room consists in the destruction of all infectious particles which remain attached to surfaces, or lodged in crevices, in inter- stices of textile fabrics, etc. The object in view may be accomplished by thorough washing with a reliable disinfecting solution, but many sanitarians think it advisable to " disinfect the room " with a gaseous disinfectant, such as formaldehyd or sulphur dioxid. If " fumigation " with sulphur dioxid is resorted to, the directions given by the Committee on Disinfectants of the American Public Health Association should be followed : that is, three pounds of sulphur should be burned for every thousand cubic feet of air-space. At the end of from twelve to twenty-four hours, doors and windows should be opened, and the room freely ventilated. After this fumigation, all surfaces should be washed with a disinfecting solution (chloride of lime 2 per cent., carbolic acid 2 percent., or mercuric chloride 1:1000), and afterwards thoroughly scrubbed with soap and hot water. Plastered walls should be whitewashed. 54 INFECTION AND IMMUNITY Experiments made during the past twenty years have shown that fumigation by burning sulphur is not by any means so reliable a method of disinfection as was formerly supposed. It has very little value un- less the articles to be disinfected are in a moist con- dition. This may be effected by introducing steam into the room together with the sulphur fumes. There is a class of diseases, however, in which sulphur fumi- gation is a most valuable method of disinfection : I refer to yellow fever and the malarial fevers, in which diseases the infectious agent is transmitted by mos- quitoes. Such mosquitoes, after filling themselves with blood from the sick person, hang about the room, attached to the ceiling, to window-curtains, etc., for the purpose of digesting their meal and supplying themselves with another when occasion offers. The room is infected because of the presence of these infected mosquitoes, which with the blood of the patient have taken in the disease germs present in such blood. Disinfection in such a case consists in the destruction of the infected mosquitoes, and this is very readily accomplished by means of sulphur fumi- gation. Owing to the superior germicidal power of formaldehyd and its non-toxic properties, this gas has to a considerable extent taken the place of sulphur fumigation for disinfecting purposes. Formaldehyd is generated either by the application DISINFECTION B Y GASES 55 of heat to an aqueous solution of the gas (formalin) or by the oxidation of wood alcohol. In making practical use of this agent a suitable apparatus will be required. For the disinfection of a room with its contents, freely exposed for surface disinfection, one pound of formalin should be volatil- ised for each thousand cubic feet of air-space — the time of exposure to the disinfecting action of the gas being not less than twelve hours. In the absence of any apparatus satisfactory results have been obtained by the Department of Health of the city of Chicago, as follows : " Ordinary bed sheets were employed to secure an adequate evaporatory surface, and these, suspended in the room, were simply sprayed with a forty per cent, solution of formalin through a common watering-pot rose-head. A sheet of the usual size and quality will carry from one hundred and fifty to one hundred and eighty cc. of the solution without dripping, and this quantity has been found sufficient for the disinfection of one thousand cubic feet of space. Of course, the sheets may be modified to any necessary number. . . . Surface disinfection was thorough, while a much greater degree of penetration was shown than that secured by any other method." Formalin may also be used in the disinfection of rooms and their contents by spraying all exposed surfaces. Experiments made by Kinyoun and others show that formaldehyd gas does not injure the colour or textile strength of fabrics of wool, silk, cotton or linen 56 INFECTION AND IMMUNITY and that it has no injurious action upon furs, leather, copper, brass, nickel, zinc, polished steel or gilt work. Iron and unpolished steel are attacked by the gas. As is the case with sulphur dioxid the germicidal power of formaldehyd is increased by the presence of moisture. Other volatile and gaseous disinfectants have been used, but from a practical point of view those men- tioned are the best. Chlorin is a powerful germi- cide in the presence of moisture, but its irritant and corrosive properties interfere with its usefulness as a disinfecting agent. CHAPTER X VARIOUS CHEMICAL DISINFECTANTS TT is my intention in the present chapter to refer briefly to some of the most useful chemical dis- infectants. The most potent germicide is not always the best disinfectant for practical use. Questions of cost, poisonous properties, injurious effects upon tex- tile fabrics, etc., must be considered in selecting an agent for any special purpose. The mineral acids are all active germicides when used in solutions of proper strength, and a one-per- cent, solution of sulphuric, nitric, or hydrochloric acid will quickly destroy pathogenic bacteria in the absence of spores. Such a solution could be safely used to disinfect the excreta of patients suffering from cholera or typhoid fever. Among the vegetable acids it is only necessary to mention citric acid, which has been recently recommended, in the form of lemon juice, for destroying typhoid bacilli in drinking-water. The idea that the addition of a spoonful of lemon-juice to 57 58 INFECTION AND IMMUNITY a glass of water, just before drinking it, will be suf- ficient to ensure the destruction of typhoid bacilli present in the water is not well founded. Exact ex- periments show that the bacillus of typhoid fever is killed, in five hours' time, by a solution containing one-half of one per cent, of citric acid. But the time element must not be overlooked. However, the ex- perimental evidence supports the view that the typhoid bacillus or the cholera spirillum would not retain their vitality very long in a strong lemonade, containing one per cent, or more of citric acid. The addition of sulphurous acid to water is still more effective, espe- cially as regards the cholera germ, which is very sens- itive to the action of acids. The addition of this acid to drinking-water during the prevalence of cholera has been recommended and practised, apparently with good results. It has been shown by carefully con- ducted experiments that one part in five hundred will destroy the cholera spirillum in the course of a few hours. The caustic alkalies all have considerable germicidal value. Potash soap containing an excess of alkali will destroy the typhoid bacillus in six-per-cent. so- lution within thirty minutes ; and the scrubbing of floors, articles of furniture, etc., with such a solution, especially when used hot, is a most reliable method of disinfection. Solutions of potash — common lye — VARIOUS CHEMICAL DISINFECTANTS 59 or of soda are extremely valuable for certain purposes in domestic sanitation, and scientific researches fully justify the cleansing methods with these agents which have long been popular with good housewives. A hot solution of caustic soda or potash in the propor- tion of one part to two hundred of water will quickly destroy the germs of cholera, of typhoid fever, of diphtheria, or of glanders. Caustic lime is also an excellent disinfectant and has the advantage of being comparatively cheap. For this reason it is one of the best agents for the disinfec- tion of masses of filth in vaults or cesspools and upon the surface of the ground. Milk of lime, made by slaking fresh quicklime with water and mixing the resulting hydrate of lime with eight parts of water may be used for this purpose and also for the dis- infection of liquid excreta in the sick-room. Lime wash applied to surfaces is a reliable disinfectant, as has been proved by experiment, thus giving scientific confirmation of the value of a method which has gained popular favour as a result of experience — that is, of the sanitary value of whitewash freely and fre- quently applied to outbuildings, cellar walls, etc. Various coal-tar products have been proved to be valuable germicides, and on account of their compar- ative cheapness have been largely used in practical disinfection. Among these the most useful are 60 INFECTION AND IMMUNITY carbolic acid, creolin, cresol, and lysol. A five-per-cent. solution of either of these may be used for the disin- fection of the liquid discharges of patients with cholera, cholera infantum, dysentery, or typhoid fever ; also for the expectoration of those suffering from pulmon- ary tuberculosis, pneumonia, diphtheria, influenza, scarlet fever, measles, or whooping-cough. It must be remembered, however, that time is an element in the accomplishment of disinfection, and after adding the disinfecting solution to the material to be dis- infected an interval of an hour or more should be allowed before the contents of the vessel are thrown into a vault or sewer. A two-per-cent. solution of one of the above mentioned disinfectants may be used for washing floors, articles of furniture, leather, etc. Such a solution may also be used for the disinfec- tion of pocket-handkerchiefs, bed-linen, underclothing, and other articles which require disinfection before sending them to the laundry. The articles to be dis- infected should be completely immersed in the dis- infecting solution, contained in a suitable receptacle, and left for at least an hour before removal from the sick-room or its immediate vicinity. Chlorinated lime (" chloride of lime," " bleaching powder ") is a valuable disinfectant and also a prompt deodoriser. It may be used for the disinfection of excreta in the sick-room, in open pits, etc., and for VARIOUS CHEMICAL DISINFECTANTS 61 infected sputa. A solution containing six ounces of good bleaching powder to the gallon of water will be suitable for ordinary use. By exposure to the air the chloride of lime rapidly deteriorates in quality. It should therefore be kept in air-tight receptacles, and only so much of the disinfecting solution made as is required for immediate use. Owing to its bleaching properties and injurious action upon fabrics of all kinds the chlorinated-lime solution is seldom used for the disinfection of bed-linen and articles of clothing, but it may be employed for washing floors and other woodwork. Many of the metallic salts have decided germicidal value, and some of them have been largely used in practical disinfection. Among these the bichloride of mercury, or " corrosive sublimate," has a prominent place. In very dilute solutions this salt is fatal to all known disease germs, and in the proportion of i : 500 it will destroy the spores of pathogenic bacteria (an- thrax, tetanus). For ordinary use a standard solu- tion of one part in one thousand parts of water may be used. This will be suitable for washing surfaces and for the disinfection of bed- and body-linen. But owing to the fact that the bichloride of mercury combines with albuminous substances, and is thus rendered practically inert, this salt is not a reliable disinfectant for excreta or expectorated matters. The 62 INFECTION AND IMMUNITY very poisonous nature of this salt must be constantly kept in mind by those who make use of it for disinfect- ing purposes. The solution is colourless, and a fatal dose might easily be mistaken for water. To avoid such accident it is customary to colour the solution with indigo or an anilin dye. Sulphate of copper has been used to some extent, especially in France, for the same purposes as the salt last mentioned (corrosive sublimate). Its germ- icidal value is considerably less, but in solutions con- taining from two or five per cent, it is reliable for the destruction of pathogenic bacteria not containing spores. Like the bichloride of mercury its germicidal action is neutralised to a considerable extent by the presence of albuminous material. It is therefore not to be selected for the disinfection of sputa and excreta. With reference to the various proprietary disinfect- ants which are in the market and largely used, I would say that many of them are deodorants of more or less value and are entirely unreliable for the de- struction of disease germs. Others contain germ- icidal agents of value ; but, as a rule, they are not economical in use, as compared with heat, carbolic acid, formaldehyd, and other disinfectants of estab- lished value referred to in the present volume. CHAPTER XI NATURAL IMMUNITY IT is hardly necessary to explain that absence of susceptibility to an infectious disease constitutes what is known as immunity for or against the disease in question. Now this immunity may be natural or acquired — that is, due to inheritance or developed in a susceptible individual subsequent to birth. We have said in a preceding chapter that man is immune as regards certain infectious diseases of the lower ani- mals, and that many of the infectious diseases to which he is subject are not transmitted to the domes- tic animals with which he is most closely associated. This natural immunity is not, however, in all cases absolute and complete. For example, the white rat possesses a remarkable immunity against anthrax, a disease which may be communicated by inoculation to sheep, cattle, rabbits, guinea-pigs, mice, and to man himself. But it has been shown that this natural im- munity of the white rat may be overcome by giving 63 64 INFECTION AND IMMUNITY it an exclusively vegetable diet. Again, natural im- munity may in some cases be overcome by the de- vitalising agencies mentioned in the chapter on sus- ceptibility to infection (starvation, great fatigue, etc.). Infection also depends upon the comparative virul- ence of the infecting agent, or germ, and to some extent upon the number of germs introduced. Immunity, therefore, whether natural or acquired, often has only a relative value, and may be overcome as a result of circumstances favourable to infection. Thus it has been found that germs having very little pathogenic virulence, and harmless under ordinary conditions, may kill guinea-pigs when injected into the muscles of the thigh after they have been bruised by mechanical violence. Pasteur found that fowls, which have a natural immunity against anthrax, be- come infected and die if they are subjected to artificial refrigeration after inoculation. Pigeons have a natural immunity against anthrax, but if they are enfeebled by lack of food they succumb to inoculations with the anthrax bacillus. The pathogenic power of known disease germs also varies greatly as a result of conditions relating to their development. In general it may be said that cultivation in the bodies of susceptible animals in- creases the virulence of disease germs. Attenuation of virulence may be effected by several methods, all NATURAL IMMUNITY 65 of which depend upon subjecting the germs to preju- dicial influences of one kind or another — long exposure to oxygen, exposure to a temperature a little short of that which would completely destroy their vitality, exposure to various chemical agents. Attenuated germs may cause infection in very sus- ceptible animals, and may gain in virulence as a re- sult of their growth in such animals. After passing through a series of susceptible animals they may finally acquire such pathogenic virulence that they can overcome the resisting power of animals having a considerable degree of natural immunity. Apply- ing the facts ascertained by experiments upon the lower animals, we can understand how the earlier cases in an epidemic may occur in the most suscept- ible individuals, and are often comparatively mild ; but, as a result of its transmission through a series of individuals, the germ gradually increases in vir- ulence and the epidemic in malignancy. Thus the earlier cases in an epidemic of diphtheria or of scarlet fever are often mild, while later cases prove to be extremely difficult to manage and show a high rate of mortality. Infection also depends to some extent upon the number of germs introduced. The resources of na- ture, upon which immunity depends, may be suffi- cient to dispose of a few typhoid bacilli or diphtheria 66 INFECTION AND IMMUNITY bacilli ; while a larger number introduced at one time may overwhelm the resisting power of the individual. The essential difference between a susceptible and immune animal depends upon the fact that in one the pathogenic germ, when introduced by accident or experimental inoculation, multiplies and invades the tissues or the blood, where, by reason of its nutritive requirements and toxic products, it produces changes in the tissues and fluids of the body which constitute disease and may result in death. On the other hand, in an immune animal multiplication of the germ and consequent disturbance of vital functions does not occur, or is restricted to a local invasion of limited extent, in which the parasitic invader soon succumbs to the resources of nature. This essential difference evidently depends upon conditions favourable or un- favourable to the development of the germ ; or upon its destruction by some active agent present in the tissues or fluids of the body of the immune individ- ual ; or upon a neutralisation of its toxic products by some substance in the body of the animal which resists infection. Among the unfavourable conditions which may be supposed to prevent the development of disease germs in animals which have a natural immunity against infection by them, we may mention, first, the temperature of the animal. It is well known that NATURAL IMMUNITY 67 the constant body temperature of mammals varies considerably for different species. Birds, as a rule, have a higher temperature than mammals, and rep- tiles are " cold-blooded animals." A disease germ, like the tubercle bacillus, for example, which requires for its development a temperature not very different from that of a healthy man, may fail to infect a pigeon because of its comparatively high, or a frog because of its low, temperature. Certain experiments which have been made by bacteriologists give sup- port to this view. This is the explanation offered by Pasteur of the immunity of fowls against anthrax — a disease of sheep and cattle ; and in support of this view he showed by experiment that when chick- ens are refrigerated by being immersed in cold water, after inoculation, they are liable to become infected and to die. Again, the composition and especially the reaction of the blood and other body fluids may perhaps be the determining factor. Some germs do not grow readily in an alkaline medium ; and some animals — for example, the white rat- have a highly alkaline blood. Experiments made by the German bacteriologist, Behring, seem to show that the natural immunity of the white rat against anthrax infection is lost when the animal is given food which reduces the alkalinity of its blood. It is probable, also, that the presence or absence of 68 INFECTION AND IMMUNITY various substances favourable or unfavourable to the development of particular disease germs may, in cer- tain cases, be the fundamental cause of race immun- ity. It has been shown by experiment that natural immunity may be overcome in certain animals by inoculating them with disease germs mixed with certain chemical substances — or with sterilised cult- ures of various bacteria. The susceptibility of the victims of chronic alcoholism to infection by various pathogenic bacteria is well known. Whether this is due to the presence of alcohol or to chemical changes in the body fluids resulting from its use is not de- termined. A complete knowledge of the facts would probably show that immunity, natural or acquired, in the ultimate analysis, to a large extent has a chemical basis — that is, it depends upon the presence of some substance which exercises a deleterious influence upon the germ or neutralises its toxic products. That the blood-serum of healthy animals contains substances which have a decided germicidal effect has been demonstrated by experiments made with blood withdrawn from the circulation. This property belongs to the clear serum which is obtained after coagulation of the fibrin and separation of the clot containing the red and white blood corpuscles. When the blood-serum is kept for some time it loses its germicidal activity. This is also destroyed by heat, NATURAL IMMUNITY 69 but not by freezing. The blood of different species differs considerably in this regard, and that of the same species may show a decidedly greater germ- icidal action for one disease germ than for others. That the presence of these germicidal substances con- stitutes a most important element in natural immun- ity can scarcely be doubted. According to Behring the blood of the rat and of the frog, which an- imals have a natural immunity against anthrax, is especially fatal to the anthrax bacillus. The numer- ous experiments which have been made show that the germicidal action of blood-serum, which is very promptly manifested, is limited as to the number of bacteria which may be destroyed by a given amount. When the number of bacteria is excessive only a limited number are destroyed, and after an interval those not destroyed multiply abundantly in the blood- serum, which, in the absence of its germicidal con- stituent, is an excellent culture medium for many pathogenic bacteria. It would appear from this that the element in the blood to which the germicidal action is due is neu- tralised in exercising this power — in other words, that the effect is the result of a chemical reaction. These germicidal substances in the blood of healthy animals are complex nitrogenous compounds, which belong to the group of organic bodies known to 70 INFECTION AND IMMUNITY chemists as proteids. They are sometimes spoken of as " defensive proteids," because they appear to serve as a provision of nature for defence against disease germs. Possibly the increased susceptibility to infection resulting from starvation, great fatigue, and other devitalising agencies is due to a diminution in the quantity of these defensive proteids present in the blood. These germicidal substances differ from the " antitoxins," of which I shall speak in a subse- quent chapter, in the fact that their power to destroy pathogenic bacteria is destroyed by a comparatively low temperature (140° Fahr.). Independent re- searches made by several different investigators seem to show that the defensive proteids of the blood have their origin in the leucocytes, or white blood-cor- puscles, and that an alkaline condition of the blood is favourable, if not essential, to the formation of such germicidal substances, or at least to their release from the leucocytes. The number of leucocytes increases in certain infectious diseases, and this increase, together with an increased alkalinity of the blood, which has been noted, may be a provision of nature for overcoming infection when it has already occurred. A more direct role has been ascribed to the leu- cocytes as defenders of the living body against invasion by pathogenic bacteria. NATURAL IMMUNITY 71 In my chapter on " Bacteria in Infectious Diseases," in Bacteria, published in the spring of 1884, but placed in the hands of the publishers in 1883, I say : "Jf we add a small quantity of culture fluid containing the bacteria of putrefaction to the blood of an animal, withdrawn from the circulation into a proper receptacle, and maintained in a culture oven at blood-heat, we shall find that these bacteria multiply abundantly, and evidence of putrefactive decomposition will soon be perceived. But if we inject a like quantity of the culture fluid, with its contained bacteria, into the circulation of a living animal, not only does no increase and no putrefactive change occur, but the bacteria introduced quickly disappear, and at the end of an hour or two the most careful microscopical examination will not reveal the presence of a single bacterium. This difference we ascribe to the vital properties of the fluid as contained in the vessels of a living animal, and it seems probable that the little masses of protoplasm known as white blood-cor- puscles are the essential histological elements of the blood, so far as any manifestation of vitality is concerned. The writer has elsewhere (1881) suggested that the disappearance of the bacteria from the circulation, in the experiments referred to, may be effected by the white corpuscles, which, it is well known, pick up, after the manner of amoebae, any particles, organic or inorganic, which come in their way. And it requires no great stretch of credulity to believe that they may, like an am&ba, digest and assimilate the pro- toplasm of the captured bacterium, thus putting an end to the possi- bility of its doing any harm. " In the case of a pathogenic organism we may imagine that, when captured in this way, it may share a like fate if the captor is not paralysed by some potent poison evolved by it, or over- whelmed by its superior vigour and rapid multiplication. In the latter event the active career of our conservative white corpuscles would be quickly terminated, and their protoplasm would serve as food for the enemy. It is evident that in a contest of this kind the balance of power would depend upon circumstances relating 72 INFECTION AND IMMUNITY to the inherited vital characteristics of the invading parasite and of the invaded leucocyte." This explanation is now very commonly spoken of as the " Metschnikoff theory," although, as shown, by the above quotations, it was clearly stated by the writer several years (1881) before Metschnikoff's first paper (1884) was published. Metschnikoff has, how- ever, been the principal defender of this explanation of acquired immunity, and has made extensive and painstaking researches, as a result of which many facts have been brought to light which appear to give support to this theory. The recorded experimental evidence leads us to the conclusion that natural immunity is partly due to germicidal substances present in the blood-serum, which have their origin in the leucocytes, and are soluble only in an alkaline medium ; that local infec- tion is usually resisted by an afflux of leucocytes to the point of invasion, which to some extent serve to protect the individual from disease germs, by their direct action as " phagocytes"-— that is, by picking up and destroying the invading parasites. These agencies, together with conditions relating to body temperature, and the chemical constitution of the fluids and tissues of the body constitute the principal factors upon which natural immunity depends. CHAPTER XII ACQUIRED IMMUNITY IT is well known that in certain infectious diseases a single attack protects the individual from subse- quent attacks. In some cases such protection lasts during life, while in others it is more or less temporary. The protection afforded by an attack not only varies in different diseases, but in the same disease differs greatly in individual cases. Thus second or even third attacks of smallpox occasionally occur, although, as a rule, a single attack is protective. In certain diseases second attacks are not infre- quent. This is true of pneumonia, Asiatic cholera, diphtheria, and especially of influenza. But there is usually a considerable interval between two attacks of any of these diseases, and the inference is that temporary immunity results from each attack. In the malarial fevers, which are due to infection by a blood parasite of a different class, no immunity is afforded by an attack of the disease, in its usual form 73 74 INFECTION AND IMMUNITY at least — chills and fever. On the other hand, the debility resulting from an attack seems to constitute a predisposition to subsequent attacks. As showing the liability to two or more attacks from certain infectious diseases, I give below a table compiled from the literature, as given in medical journals, which was published several years ago (Maiselis). Second Third Fourth attacks. attacks. attacks. Smallpox 505 9 o Scarlet fever 29 4 o Measles 36 i o Typhoid fever 202 5 i Cholera 29 3 2 These figures support the view generally enter- tained by physicians, that second attacks of measles are comparatively rare, while second attacks of small- pox are not infrequently observed. Considering the large number of cases of typhoid fever which occur annually in all parts of Europe and America, the number of second attacks reported is comparatively small, and in this disease it may be stated that, as in smallpox and scarlet fever, a single attack usually protects during life from subsequent attacks. The second attacks of cholera recorded are not numerous, but an investigation made in the countries where this disease prevails annually, or frequently, would probably show that two or more attacks of the ACQUIRED IMMUNITY 75 disease in the same individuals are not of infrequent occurrence. That immunity may result from a comparatively mild attack as well as from a severe one is a matter of common observation in the case of smallpox, scarlet fever, yellow fever, measles, and other infec- tious diseases. And it not infrequently happens that such mild attacks are not recognised. In that case the protection afforded during sub- sequent epidemics is often ascribed to natural im- munity. This is no doubt the true explanation of the immunity of natives of Havana, and other cities where yellow fever has prevailed for many years, to this disease. An unrecognised attack suffered during childhood has resulted in immunity which is supposed to be due to inheritance. The popular idea that natives are exempt from this disease is an additional motive for calling it by some other name, especially as the attacks are usually extremely mild in native- born children. The production of immunity by protective inocula- tions was for a long time limited to a single disease — smallpox. Inoculations with virus, obtained from a pustule on a smallpox patient, were extensively prac- tised before the discovery of vaccination by Jenner. These inoculations gave rise to a mild attack of the disease, followed by immunity, which was apparently 76 INFECTION AND IMMUNITY as complete as that following a more severe attack contracted in the usual way. This method seems to have been practised by Eastern nations long before it \vas introduced into Europe. It was extensively em- ployed in Turkey early in the eighteenth century, and was introduced into England through the influence of Lady Mary Wortley Montagu. No doubt the mortality from smallpox was greatly diminished by these inoculations ; but they were attended by the disadvantage that the disease was propagated by them, inasmuch as inoculated individuals became a source of infection for others. Inoculation was still practised in England for some time after the demon- stration of the protective value of vaccination, but in 1840 it was prohibited by an act of Parliament. There is some evidence that vaccination as a pro- tection against smallpox was practised to a limited extent prior to the time of Jenner. Thus Humboldt has stated that it was known at an early period to the Mexicans. But its introduction as a reliable method of protecting against smallpox is due to the patient researches of the renowned English physician, whose attention was first attracted to the subject in 1 768, although it was not until 1796 that he made his first vaccination in the human subject. His first public institution for the practice of vaccination was estab- lished in 1799, and the following year the practice ACQUIRED IMMUNITY 77 was introduced into France, Germany, and the United States. In the infectious disease of cattle known as pleuro- pneumonia, protective inoculations were successfully made some time before the demonstration by Pasteur of the efficacy of such noculations in anthrax and chicken cholera (1880). Various methods have been employed. The natives of the banks of the Zam- beze cause animals to swallow a certain quantity of the liquid from the pleural cavity of an animal re- cently dead, and thus give them immunity. The virus has been injected into the circulation by some experimenters, and others have proposed to attenuate it by heat. But the method which has been most extensively employed is that discovered by the Dutch settlers at the Cape of Good Hope (the Boers), and consists in inoculating animals in the tail with serum from the lungs of an animal recently dead, or with a virus obtained from the tumefaction produced by such an inoculation in the tail. This is also the method most extensively employed in Australia, into which country infectious pleuro-pneumonia was intro- duced in 1858. Toussaint, a pioneer in researches relating to pro- tective inoculations, has a short paper in the Comp- tes rendus of the French Academy of Sciences of July 12, 1880, entitled "Immunity from Anthrax 78 INFECTION AND IMMUNITY ('charbon') Acquired as a Result of Protective In- oculations." In this communication, he reports his success in conferring immunity upon five sheep by means of protective inoculations, and also upon four young dogs. We must, therefore, accord him the priority in the publication of experimental data demonstrating the practicability of accomplishing this result. But it is especially to the experimental researches of Pasteur that we are indebted for the development of practical methods, which have been extensively employed in protecting cattle, sheep, and swine from the fatal effects of various infectious maladies, and man from hydrophobia as the result of the bite of a rabid animal. Pasteur's inoculations are made with an " attenu- ated virus " — that is, with a culture of a pathogenic micro-organism which has a diminished degree of virulence and which whei introduced into a suscep- tible animal induces a non-fatal and comparatively mild attack. The researches of Pasteur and of his followers in this line of investigation show that pathogenic viru- lence may be attenuated by prolonged exposure to oxygen ; by exposure to a temperature a little below that which would completely destroy vitality ; by the action of certain chemical agents ; and, in some ACQUIRED IMMUNITY 79 cases, by passing through a series of non-susceptible animals. As a general rule, pathogenic virulence is increased by successive inoculations in susceptible animals and diminished by cultivating the pathogenic micro-organ- ism in artificial media outside of the animal body, or by passing it through animals having but slight sus- ceptibility to its pathogenic action. As pathogenic virulence depends, to a considerable extent at least, upon the formation of toxic substances during the active development of the pathogenic micro-organism, we infer that diminished virulence is due to a dimin- ished production of these toxic substances. An important step was made in the progress of our knowledge in this field of research when it was shown that animals may be made immune against certain infectious diseases by inoculating them with filtered cultures containing the toxic substances just referred to, but free from the living bacteria to which they owe their origin. The first satisfactory experimental evidence of this important fact was obtained by Sal- mon and Smith in 1886. These bacteriologists suc- ceeded in producing an immunity in pigeons against the pathogenic effects of the bacillus of hog cholera, which is very fatal to these birds, by inoculating them with sterilised cultures of the bacillus mentioned. Similar results were reported by Roux in 1888, from 8o INFECTION AND IMMUNITY the injection into susceptible animals of sterilised cultures of the anthrax bacillus. More recently (1890) Behring and Kitasato have shown that animals may be made immune against the pathogenic action of the bacillus of tetanus or the bacillus of diphtheria by the injection of filtered, germ-free cultures of these bacilli. In Pasteur's protective inoculations against hydro- phobia, it is probable that the immunity which is de- veloped after infection by the bite of a rabid animal is due to the toxin of this disease present in the emulsion of spinal cord which is used in these in- oculations. We have also experimental evidence that animals may acquire an artificial immunity against certain poisonous substances of animal and vegetable origin. By inoculations with minute and gradually increas- ing doses, animals may be made immune against rattle- snake venom, and there is reason to believe that persons who have been repeatedly stung by poison- ous insects — mosquitoes, bees — acquire a considerable degree of immunity from the distressing local effects of their stings. Professor Ehrlich, of Berlin, in 1891, published the results of some researches which have an important bearing upon the explanation of acquired immunity, and which show that susceptible animals may be ACQUIRED IMMUNITY 81 made immune against the action of certain toxic pro- teids of vegetable origin, other than those produced by bacteria, — one, ricin, from the castor-oil bean, the other, abrin, from the jequirity bean. The toxic po- tency of ricin is somewhat greater than that of abrin, but both are far more poisonous than strychnin. A small quantity of a solution containing one part in one hundred thousand parts of water will quickly kill a mouse. But when injected into these animals in still smaller and non-fatal doses, or given to them with their food, immunity may be established to such a degree that they resist subcutaneous injections of two hundred to four hundred times the quantity re- quired to kill a non-immune animal. In a later paper (1892), Ehrlich has given an account of subsequent experiments which show that the young of mice, which have an acquired immunity for these vegetable poisons, acquire immunity from the inges- tion of their mother's milk ; and also that immunity from tetanus may be acquired in a brief time by young mice through their mother's milk. These results have been confirmed by other observ- ers and show that some substance upon which ac- quired immunity depends is present in the milk of an immune animal. CHAPTER XIII ANTITOXINS \ A 7"E have seen in the preceding chapter that, in certain cases at least, acquired immunity is due to the presence of substances developed in the body of the immune animal which may escape in the milk of a nursing female and give protection to its young. Such protective substances are called " anti- toxins," because it is evident that they, in some way, neutralise the toxins of various disease germs and the animal and vegetable poisons referred to — abrin, ricin, snake-venom. The German chemists, Brieger and Ehrlich, have succeeded in separating the antitoxin of tetanus from the milk of a goat which had been made im- mune by repeated inoculations with the toxic pro- ducts of the tetanus bacillus. A precipitate obtained from the milk by chemical processes proved to be from four hundred to six hundred times as active as the milk itself, as shown by its power to neutralise 82 ANTITOXINS 83 the tetanus toxin. But the usual source from which antitoxins are obtained for practical purposes is the blood of animals which have been rendered immune. The diphtheria antitoxin, which is now extensively and successfully employed for the cure of diphtheria, is obtained from the blood of horses which have been immunised by repeated inoculations with the toxic products of the diphtheria bacillus. A most interesting question presents itself in con- nection with the discovery of the antitoxins : Is the animal which has been immunised against any par- ticular toxin also immune for other poisonous sub- stances of the same class ? This question has been definitely answered in the negative by experimental investigation. In other words, each specific toxin causes the development in the body of the immune animal of a specific antitoxin which has no neutralis- ing action upon any other toxin than that which gave rise to its production. An animal which has been immunised against the toxic action of ricin is poi- soned by the usual fatal dose of abrin. The tetanus antitoxin affords no protection against the poisonous products of the diphtheria bacillus and vice versa. The antitoxins protect susceptible animals from in- fection when introduced by inoculation at the same time or in advance of the disease germs against which they have a specific action. They may also, in 84 INFECTION AND IMMUNITY some cases, be successfully used in the cure of infec- tious diseases, when these have not advanced too far. The remarkable success attending the use of the diphtheria antitoxin for this purpose is well known and a certain degree of success has attended the efforts of physicians in the treatment of other dis, eases by the same method — tetanus, erysipelas, pneu- monia. But specific treatment by antitoxins is still in its infancy and much careful experimental work and clinical experience will be necessary in order to determine the practical value of this method in the diseases mentioned and in other infectious maladies. Enough is known at present, however, to lead to the hope that when methods have been devised for obtaining these various antitoxins in a pure and con- centrated form they will constitute a most valuable addition to our resources for the treatment of infectious diseases. Indeed the only hope of specific medication for such diseases appears to lie in this direction. In the present volume I shall not attempt to dis- cuss the questions connected with the origin of the antitoxins in the bodies of immunised animals, the chemical nature of these substances, or the mode of their action in neutralising the toxins. These are questions which would involve a considerable amount of technical knowledge on the part of the reader for ANTITOXINS 85 an understanding of the most advanced views regard- ing them, as expounded by Ehrlich and others — Ehr- lich's "side chain theory." In a popular treatise a simple statement of well ascertained facts will, I hope, be appreciated, while an exposition of theories still under discussion might prove wearisome. It has been shown that the antitoxins when mixed with toxins in a test-tube exhibit their specific neutral- ising action as shown by the innocuousness of the mixture when injected beneath the skin of a sus- ceptible animal. The antitoxin of snake poison, which has been suc- cessfully used in India for the cure of persons bitten by the deadly cobra, when mixed with cobra venom in proper proportion completely neutralises the poi- sonous properties of this venom. Such a mixture injected beneath the skin of a small animal is without effect. But if the mixture is heated to 70° C. the antitoxin is destroyed and by inoculation experiments the toxin is found to be still present and active. The facts stated show that in certain infectious diseases acquired immunity depends upon the forma- tion of antitoxins in the bodies of immune animals. But these antitoxins have no power to destroy specific disease germs. They neutralise the toxic products of these germs without exhibiting any germicidal action upon the germs themselves. As, 86 INFECTION AND IMMUNITY however, the power of the germs to overcome the resources of nature and invade the blood or tissues depends upon the toxic products developed by them, they are deprived of their power to multiply in the bodies of living animals when these poisonous sub- stances are neutralised. Practically they become as harmless as the common "saprophytic bacteria" which surround us on all sides, and are swallowed in count- less numbers with every glass of unsterilised water we drink. But there is another class of substances, developed during certain diseases, which exhibit specific germi- cidal activity and have no antitoxic value. Such sub- stances are found in the blood of animals which have been made immune to the pathogenic action of the cholera spirillum, the typhoid bacillus, and the bacillus of hog cholera. The writer, some ten years ago, obtained experi- mental evidence which indicates that smallpox im- munity probably depends upon a substance which destroys the smallpox germ, rather than upon an antitoxin. Further details with reference to the antitoxins will be found in Part Second of this volume, in which questions relating to infection, disinfection, and im- munity will be discussed in connection with the more important infectious diseases, considered separately. PART SECOND SPECIFIC INFECTIOUS DISEASES 87 CHAPTER I BUBONIC PLAGUE T^HE history of bubonic plague extends back to a remote antiquity. Greek physicians of the second and third century before the Christian era have left a record of a pestilential malady character- ised by the formation of buboes, which prevailed in Libya, in Egypt, and in Syria ; and two Alexandrian physicians, Dioscorides and Poseidonios, who were contemporaries of Christ, have given a description of the disease which leaves no doubt as to its identity with the plague of more recent times. It may be well to explain at this point that the buboes charac- teristic of the disease are enlarged and inflamed glands in the groins, in the armpits, and elsewhere, which in chronic cases may suppurate and discharge a virulent pus by which the disease is propagated. We now know that the germ of the disease is found not only in these suppurating buboes but also in the blood of an infected individual. 90 INFECTION AND IMMUNITY Three forms of the disease are recognised by modern authors — one a mild or abortive form, in which there is little pain or fever and in which the buboes rarely suppurate. In this form the enlarged glands in the groin, armpit, and neck usually disap- pear in about two weeks. In its usual form the disease is ushered in with chilly sensations, fever, lassitude, and pain in the back and limbs. The bu- boes are quickly developed and the general symp- toms soon assume a grave character. If the patient lives for a week or more, the buboes usually sup- purate and carbuncles and boils are often developed. In the third or fulminant form of the disease, death may occur within a few hours from the outset of the attack and in advance of the development of the characteristic buboes. These cases could scarcely be recognised were it not for the fact they occur during the epidemic prevalence of the disease among per- sons who have been exposed to infection. From the first to the sixth centuries of the Christian era we have no authentic accounts of the prevalence of bubonic plague, but there is no reason to believe that it had entirely disappeared from those countries in which it had previously prevailed. During the sixth century, however, its ravages were greatly ex- tended and it prevailed as a devastating epidemic in many parts of the Roman Empire, both of the East BUBONIC PLAGUE 91 and of the West; indeed, in the time of Justinian it extended far beyond the limits of the Roman Em- pire. The origin of this extensive epidemic which raged for more than half a century appears to have been in Lower Egypt in the year 542 ; thence it ex- tended in one direction along the north coast of Africa, and in the other into Palestine and Syria. The following year it invaded Europe, which at the time was in a state of political disturbance and war- fare, and during this and subsequent years it de- vastated many sections of the country, depopulating towns and leaving the country in some instances nothing more than a desert inhabited by wild beasts. The accounts given of this widespread epidemic in- dicate that other infectious maladies, which at the time had not been clearly recognised as specific diseases, were associated with the plague and contributed to the general mortality. During the middle ages epidemics continued to occur, but the accounts of the nature of the prevail- ing " pest " are usually confused and unsatisfactory, and it was not until nearly the middle of the four- teenth century that the horrible epidemic known as the black death devastated Europe and caused the death of more than 25,000,000 of its inhabitants. There has been considerable difference of opinion among the best authorities as to whether the black 92 INFECTION AND IMMUNITY death of the fourteenth century was identical with bubonic plague. It presented some features which seem to distinguish it from subsequent epidemics, and it had its origin from a different quarter of the globe. While bubonic plague has usually invaded Europe from Egypt, the black death is believed to have originated in Northern China. It is not known exactly when or where this epidemic had its origin, but it is known to have reached the Crimea in 1346 and Constantinople the following year. The same year it was conveyed by ships to several seaports of Italy both on the Mediterranean and the Adriatic, and also to Marseilles on the French coast; in 1348 it extended to the interior of these countries and to Spain ; also to England, Holland, and the Scandi- navian peninsula. The following year it completed the invasion of Europe. The disease first appeared in London in Novem- ber, 1348, and it continued to prevail in various parts of England for a period of eight or nine years. In 1352 the epidemic prevailed in the town of Oxford to such an extent that this town lost two-thirds of its academic population. The plague again invaded England in 1361 and 1368. As a result of these devastating epidemics in England, as well as in other parts of Europe, large parts of the country remained for a time uncultivated, and owing to BUBONIC PLAGUE 93 the lack of labourers there was a great increase in wages. The following graphic account of the ravages of this pestilence is by a writer of the period : "Wild places were sought for sheiter; some went into ships and anchored themselves far off on the waters. But the angel that was pouring the vial had a foot on the sea as well as on the dry land. No place was so wild that the plague did not visit — none so secret that the quick-sighted pestilence did not discover — none could fly that it did not overtake. For a time all com- merce was in coffins and shrouds, but even that ended. Shrift there was none; churches and chapels were open, but neither priests nor penitents entered — all went to the charnel-house. The sexton and the physician were cast into the same deep and wide grave; the testator and his heirs and executors were hurled from the same cart to the same hole together. Fire became ex- tinguished, as if its element had expired, and the seams of the sailorless ships yawned to the sun. Though doors were open and coffers unwatched, there was no theft; all offences ceased, and no cry but the universal woe of the pestilence was heard among men." That the " black death" of the fourteenth century was in fact the same disease which subsequently pre- vailed in Europe under the name of " the plague," and more recently known as " bubonic plague," can scarcely be doubted. But the epidemic was character- ised by an unusually large number of cases of the pulmonary form of the disease, in which it seems probable that the lungs are the primary seat of infec- tion, while in the bubonic form the bacillus effects a 94 INFECTION AND IMMUNITY lodgment through some superficial wound or abra- sion, or possibly through the bites of insects, and it first invades the lymphatics, producing inflammation of the nearest lymphatic glands. General invasion of the blood appears, from recent investigations, to be a secondary phenomenon which only occurs in very severe and usually fatal cases. The pulmonic form of the disease, which was so prominent in the epidemic known as black death, is extremely fatal and is known to occur at the present day. Bubonic plague continued to prevail in various parts of Europe at the end of the sixteenth century, and early in the seventeenth century (1603) an epidemic occurred in London which caused the death of 38,000 of its inhabitants. It continued to prevail in this city and in various parts of England, Holland, and Ger- many, and six years later caused a mortality of 1 1,785 in the city of London. During the year 1603 a most disastrous epidemic occurred in Egypt, which is said to have caused a mortality of at least a million. After an interval of ten or fifteen years, during which there was a marked diminution in the number of cases and the extent of its distribution in European countries, it again obtained wide prevalence during the year 1620 and subsequently, especially in Germany, Hol- land, and England. The epidemic in the city of B U BO NIC PLA GUE 95 London in 1625 caused a mortality of more than 35,000. In 1630 a severe epidemic occurred in Milan, and in 1636 London again suffered a mor- tality of over 10,000, while the disease continued to claim numerous victims in other parts of England and on "the continent." Later in the century (1656) some of the Italian cities suffered devastating epi- demics. The mortality in the city of Naples was in the neighbourhood of 300,000, in Genoa 60,000, in Rome 14,000. The smaller mortality in the last- named city has been ascribed to the sanitary meas- ures instituted by Cardinal Gastaldi. Up to this time prayers, processionals, the firing of cannons, etc., had been the chief reliance for the arrest of pesti- lence, with what success is shown by the brief his- torical review thus far presented. This enlightened prelate inaugurated a method of combating the plague and other infectious maladies which, with in- creasing knowledge and experience in the use of scientific preventive measures, has given us the mas- tery of these pestilential diseases, and has been the principal factor in the extinction of bubonic plague from the civilised countries of Europe. But it was long after the time of Cardinal Gas- taldi before sanitary science was established upon a scientific basis and had acquired the confidence of the educated classes. Indeed the golden age of 96 INFECTION AND IMMUNITY preventive medicine has but recently had its dawn, and sanitarians at the present day often encounter great difficulty in convincing legislators and the public gen- erally of the importance of the measures which have been proved to be adequate, when properly carried out, for the prevention of this and other infectious maladies. We have now arrived in our review at the period of the " great plague of London." For some years this city had been almost if not entirely free from the scourge, but in the spring of 1665 it again appeared and within a few months caused a mortality of 68,596 in a population estimated at 460,000. This, how- ever, does not fairly represent the percentage of mortality among those exposed, for a large pro- portion of the population fled from the city to escape infection. Upon the continent the disease prevailed exten- sively, especially in Austria, Hungary, and Germany. The epidemic in Vienna in 1679 caused a mortality of 76,000. In 1 68 1 the city of Prague lost 83,000 of its inhabitants. During the last quarter of this cen- tury the disease disappeared from some of the prin- cipal countries of Europe. According to Hirsch, it disappeared from England in 1679, from France in 1668, from Holland about the same time, from Ger- many in 1683, and from Spain in 1681. In Italy it B U BON 1C PL A GUE 97 continued to prevail to some extent until the end of the century. At the beginning of the eighteenth century bubonic plague prevailed in Constantinople and at various points along the Danube ; from here it extended in 1704 to Poland, and soon after to Silesia, Lithu- ania, Germany, and the Scandinavian countries. The mortality in Stockholm was about 40,000. The dis- ease also extended westward from Constantinople through Austria and Bohemia. In 1720 Marseilles suffered a severe epidemic, probably as a result of the introduction of cases on a ship from Leghorn. The mortality was estimated as being between 40,000 and 60,000. From Marseilles as a centre it spread through the province of Provence, but did not invade other parts of France. In 1743 a severe outbreak occurred on the island of Sicily. A destructive but brief epidemic, which is estimated to have caused a mortality of 300,000, occurred during the years 1770 and 1771 in Moldavia, Wallachia, Transylvania, Hungary, and Poland. At the same time the disease prevailed in Russia, and in 1771 caused the death of about one-fourth of the popula- tion of the city of Moscow. Early in the nineteenth century (1802) bubonic plague appeared at Constantinople and in Armenia. It had previously prevailed in the Caucasus, from 98 INFECTION AND IMMUNITY which province it extended into Russia. In 1808 to 1813 it extended from Constantinople to Odessa, to Smyrna, and to various localities in Transylvania. It also prevailed about the same time in Bosnia and Dalmatia. In 1812 to 1814 it prevailed in Egypt, and, as usual, was conveyed from there to European countries. During the same year it prevailed extens- ively in Moldavia, Wallachia, and Bessarabia. In 1831 it again prevailed as an epidemic in Constanti- nople and various parts of Roumelia, and again it appeared in Dalmatia in 1840 and in Constantinople in 1841. Egypt, which for centuries had been the principal focus from which plague had been intro- duced into Europe, continued to suffer from the disease until 1845, when it disappeared from that country. The last appearance of Oriental plague in Europe, until its recent introduction into Portugal, was the outbreak on the banks of the Volga in 1878-79. The disease had previously prevailed in a mild form in the vicinity of Astrakhan and was probably intro- duced from that locality. An interesting fact in con- nection with this epidemic is that in Astrakhan the disease was so mild that no deaths occurred, and that the earlier cases on the right bank of the Volga were of the same mild form, but that the disease there in- creased rapidly in severity, and soon became so ma- B UBONIC PLA G UE 99 lignant that scarcely any of those attacked recovered. This is to some extent the history of epidemics else- where, and not only of plague, but of other infectious diseases, such as typhus fever, cholera, and yellow- fever. In all of these diseases the outset of an epi- demic may be characterised by cases so mild in char- acter that they are not recognised, and during the progress of the epidemic many such cases may con- tinue to occur. These cases are evidently especially dangerous as regards the propagation of the disease, for when they are not recognised no restrictions are placed upon the infected individuals, although they may be sowing the germs broadcast. The termination of an epidemic in the pre-sanitary period depended to a considerable extent upon the fact that those who suffered a mild attack acquired thereby an immunity, and that when the more sus- ceptible individuals in a community had succumbed to the prevailing disease there was a necessary termi- nation of the epidemic for want of material. Another factor which, no doubt, has an important bearing upon the termination of epidemics is a change in the virulence of the germ as a result of various natural agencies. Time will not permit me to dis- cuss this subject in its scientific and practical aspects, but the general fact may be stated that all known disease germs may vary greatly in their pathogenic ioo INFECTION AND IMMUNITY virulence, and that in every infectious disease mild cases may occur, not only because of the slight sus- ceptibility of the individual, but also because of the "attenuated" virulence of the specific germ. In the eighteenth century, the beginning of sanitary science, isolation of the sick, and seaboard quarantines came to the aid of these natural agencies, and did much in the way of arresting the progress of this pestilential disease. At the present day these measures, together with disinfection by heat or chemical agents, are relied upon by sanitarians with great confidence as being entirely adequate for the exclusion of this disease or for stamping it out if it should effect a lodgment in localities where an enlightened public sentiment permits the thorough execution of these preventive measures; but when the disease prevails among an ignorant population which strenuously ob- jects to the carrying out of these measures, the con- test between the sanitary officer and the deadly germ is an unequal one, and the stamping out of an epi- demic becomes a task of great magnitude, if not entirely hopeless. This is illustrated by the experi- ence of the English in their encounter with bubonic plague in their Indian Empire. Plague seemed to be almost a thing of the past and no longer gave any uneasiness in the countries of Europe which had formerly suffered from its rav- B U BON 1C PLA GUE i o i ages, when in February, 1894, it made its appearance in the city of Canton, China, and three months later in Hong Kong. The disease is known to have been epidemic in the province of Yunnan, which is about nine hundred miles distant from Canton, since the year 1873, but it attracted little atten- FIG. i. Bacillus of bubonic plague. A, magnified rooo diameters ; B, more highly magnified to show li end-staining." tion until the lives of Europeans living in the city of Hong Kong were threatened by the outbreak of an epidemic among the Chinese residents of that place. Many thousands of deaths occurred in Can- ton during the three months which elapsed after its introduction to that city before it effected a lodgment in Hong Kong. Fortunately this outbreak gave the opportunity 102 INFECTION AND IMMUNITY for competent bacteriologists to make scientific in- vestigations relating to the specific cause of this scourge of the human race and to the demonstration that it is due to a minute bacillus. This discovery was first made by the Japanese bacteriologist, Kita- sato, who had received his training in the laboratory of the famous Professor Robert Koch, of Berlin. This discovery was made in the month of June, 1894, in one of the hospitals established by the English officials in Hong Kong. About the same time the discovery was made, independently, by the French bacteriologist, Yersin. From this time the study of the plague has been established upon a scientific basis and very material additions have been made to our knowledge with reference to the prevention and treatment of the disease. That the plague bacillus has not lost any of its original virulence is amply demonstrated by the high death-rate among those attacked, and we are justified in ascribing its restricted prevalence to the general improvement in sanitary conditions in civilised coun- tries and to the well directed efforts of public health officers in the various localities to which it has been introduced during recent years. In the Philippine Islands, where it prevailed to a considerable extent when our troops first took possession of the city of Manila and where the conditions among the natives BUBONIC PLAGUE 103 are extremely favourable for its extension, it has been kept within reasonable bounds and, indeed, the latest reports indicate that it has been practically extermin- ated by the persistent efforts of the medical officers of our army, charged with the duty of protecting the public health in those islands. The monthly report of the Board of Health for the city of Manila for September, 1902, the last at hand, records but one death from plague during that month. During the same period there were ten deaths from typhoid fever, thirty-five deaths from dysentery, and seventy-six deaths from " the great white plague," pulmonary tuberculosis. Bubonic plague, cholera, and typhoid fever have long been classed as " filth-diseases," and in a certain sense this is correct, although we now know that the germs of these diseases not only are not generated by filth, but do not multiply in accumulations of filth. They are' present, however, in the alvine discharges of the sick, and when this kind of filth is exposed in the vicinity of human habitations or gains access to wells or streams, the water of which is used for drinking, the germs are likely to be conveyed to the alimentary canals of susceptible individuals, and thus the disease is propagated. Until quite recently the attention of sanitarians was so firmly fixed upon the demonstrated transmission of cholera and typhoid 104 INFECTION AND IMMUNITY fever through the agency of contaminated water or milk that certain other modes of transmission were overlooked, or at least underrated. I refer to the transmission by insects, or as dust by currents of air. I have for many years insisted upon the part played by flies as carriers of infectious material from moist masses of excreta from cases of cholera and typhoid fever. There is good reason to believe that the bacillus of bubonic plague may be transmitted in the same way. Certain of the lower animals, including rats and mice, are very susceptible to infection, and they play an important part in the propagation of the disease. The germs are found not only in the blood and in pus from suppurating buboes, but also in the dis- charges from the bowels of the sick and of infected rats. This being the case it can readily be seen how important a strict sanitary police is in arresting the spread of an epidemic. Dr. James A. Lowson, who has written an excel- lent account of the epidemic in Hong Kong, says : " Filth and overcrowding must be recorded as two of the most important factors. The district of Torpingshan supplied these factors in a marked degree at the beginning of the out- break, the majority of the houses being in a most filthy con- dition, as, owing to the uncleanly habits of the people, the amount of what is generally termed rubbish accumulates in a Chinese house in a crowded city to an extent beyond the imagi- BUBONIC PLAGUE 105 nation of civilised people. When to a mixture of dust, old rags, ashes, broken crockery, moist surface soil, etc., are added fecal matter and the decomposing urine of animals and human beings, a terribly insanitary condition of affairs prevails." The period of incubation in bubonic plague — the time which elapses between exposure to infection and the development of the disease — is usually from three to six days. From the report of Dr. Lowson of cases treated in the various hospitals of Hong Kong, under the con- trol of English physicians, it appears that the mortal- ity was much greater among natives of Hong Kong than among the foreign residents of that city. The mortality among Europeans (i i cases only) was 13.2$; among Japanese (10 cases), 60 % ; among Portuguese (18 cases), 66$; among Chinese (2619 cases), 93.4$. To a considerable extent, no doubt, this difference in mortality was due to the unfavourable surroundings of the natives and their lack of proper nursing and medical attendance, many of them being brought to the hospital in a dying condition. Experiments upon rats and other animals show that they become infected when cultures of the plague-bacillus are deposited upon the mucous mem- brane of the nose. During the epidemic prevalence of the disease these animals die in large numbers, and there is good io6 INFECTION AND IMMUNITY reason to believe that they play an important part in the propagation of the malady. It has been sug- gested that infection may be carried from rats to man through the agency of fleas which swarm upon these rodents and desert them when they die. The Japanese physician, Aoyoma, who was associ- ated with Kitasato, and who contracted the disease but recovered, is of the opinion that in a great major- ity of the cases, and perhaps in all, infection occurs through an external wound. He calls attention to the fact that physicians and nurses in attendance upon cases of the disease rarely become infected, and states that during the epidemic of 1894 in Hong Kong only three Japanese and one Chinese physician be- came infected, while all of the nurses escaped ; also to the fact that of three hundred English soldiers who volunteered to clean and disinfect the Chinese pest- houses during the prevalence of the epidemic, only ten contracted the disease. The greater liability of the lower class of natives to contract the disease, he ascribes not only to the insanitary surroundings in which they live, but also to the fact that they seldom wear shoes and stockings, and thus are very liable to infection through insignificant wounds, scratches, or abrasions, both of the feet and hands. In this con- nection it is well to call attention to the fact that in former epidemics physicians have suffered severely, BUBONIC PLAGUE 107 and that whatever immunity they enjoy is due to the observance of sanitary precautions, the importance of which has become apparent as we have acquired a more exact knowledge of the etiology of the disease. During the past few years a number of prominent bacteriologists have been engaged in researches re- lating to the prevention and cure of bubonic plague by means of an antitoxic serum, obtained by the same method and in accordance with the same funda- mental scientific principle as in the case of the anti- toxic serum which is now so successfully employed in the treatment of diphtheria. The experiments thus far made have apparently been attended with a consider- able degree of success. Professor Calmette reports that the serum of Yersin prepared at the Pasteur Institute in Paris proved to be curative in a con- siderable proportion of the cases treated during the recent outbreak at Oporto, and that protective inocu- lation conferred a temporary immunity, which, how- ever, did not last longer than twenty days. The mortality in cases not treated by Yersin's serum was 70 %, in those treated with it 13 %. The inoculations made by Haffkine in Bombay appear to have been quite successful. In his first experiment 8142 persons were inoculated. Of these, 1 8 subsequently contracted the disease and 2 died. Among 4926 persons inoculated a single time at io8 INFECTION AND IMMUNITY Dharwan 45 were subsequently attacked and 15 died ; while among 3387 persons in whom a second inoculation was made, only 2 were attacked. Haff- kine uses in his inoculations a sterilised culture of the plague-bacillus. The inoculation is followed by slight fever and enlargement of the nearest lymphatic glands. All symptoms disappear at the end of two or three days. The plague-bacillus is very easily destroyed by disinfectants. Dr. Lowson reports that a i % solu- tion of carbolic acid kills the bacilli within an hour, a 2 % solution almost immediately. Quicklime was almost as prompt in its action. Exposure to fresh air for three or four days usually destroys the vitality of the bacillus, and exposure to direct sunlight destroys it in three or four hours. Kitasato and Yersin both arrived at the conclusion that the disease may be contracted by inoculation, through a wound or abra- sion ; by way of the respiratory tract when the bacillus is present in dust carried by the inspired air ; or by way of the stomach when food or drink taken con- tains the bacillus. What has been said indicates very clearly the proper preventive measures, and when these are en- forced with energy and intelligence there need be little fear of the epidemic extension of the disease. For the prevention of this and other filth diseases, BUBONIC PLAGUE 109 our main reliance must rest upon isolation of the sick, disinfection of all infectious material, and gen- eral sanitary police of infected localities. The de- struction of rats in localities infected, or likely to become so, is also a measure of prime importance. Protective inoculations will hardly be necessary if the measures above referred to are vigorously en- forced, and in the opinion of the writer it is only under exceptional circumstances that such inocula- tions need be practised on a large scale. Those whose duties require them to care for the sick or visit infected localities may be given such protection as is afforded by Haffkine's inoculations. But the im- munisation of entire communities by inoculation in anticipation of a possible plague epidemic hardly seems necessary in the present state of sanitary knowledge. CHAPTER II ASIATIC CHOLERA A SI AT 1C cholera has its permanent home in In- *~* dia, and especially in the thickly populated region occupied by the delta of the Ganges, the principal city of which is Calcutta. Here it prevails through- out the year, with a period of maximum intensity in the hot and comparatively dry month of April. Heavy rains have a salutary sanitary influence in this and other regions where the disease is prevalent. From the infected area referred to, the disease spreads almost annually to other parts of India and neighbouring Asiatic countries, and at intervals has extended its ravages to Africa, Europe, and America. These widespread epidemics are, however, of com- paratively recent origin. After a devastating epidemic in India during the years 1816 to 1819 the disease extended to Mauritius and the east coast of Africa, to Farther India and the islands of Sumatra, Java, and Borneo, and to China. no ASIATIC CHOLERA in Two or three years later the disease prevailed in Syria and Palestine, and for the first time, so far as is known, appeared in a European country, in Astrakan. A second great epidemic, beginning in India in 1826, reached Astrakan in 1830. Thence it extended as far north as St. Petersburg. The fol- lowing spring it invaded Poland and extended from Austria into Germany. At the same time it had been carried by way of Persia, Mesopotamia, Arabia, and Palestine into Egypt. Hungary, Austria, and Turkey were invaded during the same year (1831), and it finally reached Great Britain, where in 1832 it obtained wide prevalence. In this year also France, Belgium, and Holland were invaded. In 1832 it reached the United States by way of Canada, where it was carried by Irish immigrants. It spread rapidly along the St. Lawrence and the shores of Lake Ontario. By an independent import- ation it was brought in the same year to New York and spread thence southward and westward, invading the States of Pennsylvania, Virginia, Maryland, Ken- tucky, Ohio, Indiana, and Illinois, and in October first appeared in the city of New Orleans. The fol- lowing summer it broke out afresh in this city and rapidly spread through the southern, central, and western States. It also invaded the Indian Territory and California. In 1834 it reappeared in the eastern 1 1 2 INFECTION AND IMMUNITY States, and in 1835 was reintrodueed from Cuba to the city of New Orleans. In the meantime Mexico had been invaded, and subsequently the disease ob- tained a limited prevalence in Central America and the Gulf coast of South America. Simultaneously with this widespread epidemic in America the disease spread in Europe to Sweden and Norway in the north and to Italy, Spain, and Portugal in the south. The disease died out during the winter of 1837-38, and for the ten following years Europe, Africa, and America remained free from this scourge of the human race. In 1846 the disease, which had pre- viously shown increased epidemic extension in India, obtained ^wide prevalence in Persia, thence it ex- tended to Arabia, and the following year reached Constantinople. In 1848 it spread through Turkey, Hungary, Asia Minor, Syria, and Egypt. In the meantime it had been introduced into Russia (in 1847), and early in the summer of 1848 reached Germany. In the autumn of this year it was intro- duced into England and Scotland, and the following year obtained wide prevalence in the British Isles. Holland and Belgium were invaded at the same time, and in 1849 France and Austria suffered severe epi- demics. Northern Italy also suffered from the disease, which indeed prevailed in all parts of Europe, with the exception of Spain and Portugal, which countries ASIA TIC CHOLERA 1 13 remained exempt. In December, 1848, cholera was brought from Europe, by emigrant ships, both to New York and to New Orleans. From the last- named city it spread northward to Memphis and westward into the State of Texas, and during the year 1849 nearly all of the States east of the Rocky Mountains suffered to a greater or less extent, es- pecially those located in the valleys of the Ohio and Mississippi rivers. It continued to prevail during the following year (1850), and in October was car- ried to San Francisco by way of the Isthmus of Pan- ama. During this epidemic the West Indies suffered severely, especially the islands of Cuba and Jamaica. It also prevailed in Mexico, and to some extent in South America. The epidemic did not terminate in the Western Hemisphere until the end of the year 1854, but in Europe it had practically ceased to pre- vail, except in a few localities in northern Europe, by the close of the year 1850. In the spring of 1852 another widespread epidemic was inaugurated. The disease appeared almost at the same time in Persia, Mesopotamia, and Poland, apparently as a survival from the previous epidemic, and extended to adjacent countries. In Russia it continued to prevail to some extent during a period of ten years, the years 1853, 1855, and 1859 being notable as marking its widest extension and the ii4 INFECTION AND IMMUNITY greatest mortality. This was also the case in north- ern Germany. In 1855, Austria and Italy suffered severely. The disease was brought to England from Germany in 1853 an<^ extended to various parts of the island during this and the following year. France also suffered severely from the disease at this time (1853-54), and also Spain and Portugal, where it prevailed during the period from 1853 to J86o. In North America the disease was introduced into Canada in 1853, and obtained wide extension through- out the United States in 1854. The disease disap- peared from the countries of North America the following year, but in Central America and in South America it prevailed to some extent for several years subsequent to this date, although the year 1855 was that of greatest extension and fatality. Another epidemic period is that embraced between the years 1865 and 1875. As usual, the epidemic extension of the disease in Europe was preceded by a period of increased fatality in its native haunts, in the lower basin of the Ganges, and also by its exten- sion to other eastern countries — China, Japan. I shall not attempt to follow the progress of the dis- ease through the countries of Europe, but, as show- ing its fatal character, will give some mortality statistics. The epidemic of 1867 in Italy was at- tended by a mortality of 130,000. In Prussia, during ASIATIC CHOLERA 115 the year 1866, 114,683 deaths were reported. In England the disease, in 1865 and the next year, caused a mortality of 14,378, nearly half of the deaths occurring in the city of London. In Belgium a mort- ality of 32,812 occurred during the year of greatest prevalence (1866). In North America the disease was introduced in 1866 by three independent importations, to New York, New Orleans, and Halifax. The following year it obtained wide extension, especially in the western States and in Texas. Again cholera invaded Europe during 1871-73, and again it was introduced into the United States by way of New Orleans, and thence spread to some extent in the valley of the Mississippi, and along its principal tributaries. The epidemic of 1872 is esti- mated to have cost 120,000 lives in Russia, and the previous year the mortality was still greater. In Hungary the disease claimed 190,000 victims during the years 1872 and 1873. In Prussia the number of deaths in 1873 was 28,790. Cholera disappeared from Europe and America in 1873, and the next great epidemic was inaugurated in 1884, when it reached the shores of France and Italy. According to Dr. Shakespeare,1 this epidemic "cost France 15,000 of its inhabitants in 1884, J885, 1 Report on Cholera in Europe and India, by E. O. Shakespeare, M.D. (1890). n6 INFECTION AND IMMUNITY and 1886; Spain, 180,000 in 1884 and 1885 ; Aus- tria-Hungary, 4000 inhabitants in 1886; Italy, about 50,000 inhabitants in 1884, 1886, and 1887." In Japan, the epidemic of 1885 was attended with a mortality of 109,434. In 1891 cholera prevailed extensively in India, Syria, Arabia, Siam, and Japan, and was introduced into Austria by way of Persia. By November, 1892, it is estimated that half a million cases had occurred in Russia with a mortality of at least 50 per cent. A severe outbreak of the disease occurred in the city of Hamburg during the month of August of this year, resulting in 8005 deaths. From Hamburg the disease was brought to New York harbour on sev- eral ships carrying immigrants, but owing to the vigorous measures adopted by the local health author- ities, assisted by the Marine Hospital Service, the disease was arrested at the threshold of the country and an epidemic was averted. The success obtained at this time shows what can be accomplished by sani- tary measures based upon an exact knowledge with reference to the specific cause of the disease (cholera germ) and its mode of transmission. The extension of cholera from its home in India to the countries of Europe and America, which first occurred during the nineteenth century, was no doubt due to the increased facilities for rapid transit, especially by steamboats ASIATIC CHOLERA 117 and railroads. Infected individuals leaving the lo- calities where they had contracted the disease, would fall by the way, or recover before travelling any great distance, if restricted to the methods of transportation available before the introduction of steam as a motive power for ships and railroad coaches. The fact that cholera is carried from place to place by men, follow- ing routes of travel, is well stated by the German physician Griesinger. He says : " Cholera has never advanced like a broad stream inundating entire countries at one time, bringing disease to all regions lying parallel with each other, over a wide extent, but it always ad- vances in relatively narrow lines from which usually, but not always, lateral offshoots arise. In countries with a small popu- lation we see constantly that this district corresponds with the great lines of travel. If the disease oversteps high mountains, if it passes through a desert, if it crosses the ocean, it always fol- lows the lines of human intercourse, the post and military routes, the caravan and sailing routes, etc. If it has broken out on an island, then the first cases have always been in a seaport, never in the interior." We now know definitely that the cholera germ is carried from place to place by cholera-infected in- dividuals, who harbour this deadly spirillum in their intestines and leave it wherever the discharges from their bowels are deposited. Mild cases of " choleraic diarrhoea" are even more dangerous as regards the propagation of the disease than severe and fatal cases, for the infected individual may not suspect the nature u8 INFECTION AND IMMUNITY of a malady which he considers trivial, and, instead of being isolated and properly treated as he should be in his own interest and that of the public gener- ally, he goes from town to town or from country to country distributing cholera germs by the way. Cholera is contracted only by the introduction of cholera germs into the intestinal canal by way of the mouth and stomach. The spirillum is easily destroyed by acids, and consequently does not multiply in the healthy human stomach, and, under ordinary condi- tions, probably does not survive to reach the intes- tine, owing to the germicidal action of the acid gastric juice. But any derangement of the digestive process predisposes to an attack of the disease. Excesses in eating or drinking cause the individual to be more susceptible to infection. In Germany it has been noted that an increase in the number of cases is likely to occur on Sunday, because of the indulgence of the labouring classes in wine and beer during this day of rest and recreation. Invalids, and especially those subject to disorders of the stomach and bowels, are especially liable to contract the disease during its epidemic prevalence. But it is safe to say that no one will contract cholera unless living cholera germs are introduced into the intestinal canal. This usually occurs as a result of drinking cholera-infected water, or partaking of food ASIATIC CHOLERA 119 which in some way has become infected and which has not been sterilised by heat. The cholera spiril- lum is so easily destroyed by heat that the prevention of the disease is a comparatively simple matter. Any article of food or drink which has been subjected for a few minutes to a temperature of 140° Fahr. (60° C.) is absolutely safe, unless it has been reinfected after such exposure. Such reinfection might occur if the sterilised food or liquid is exposed to contamina- tion by infected flies. These insects, without doubt, not infrequently act as carriers of infection from ex- posed cholera excreta — on the ground or in shallow pits — to articles of food or drink which they light upon or fall into. When the water supply of a town becomes infected as a result of contamination by cholera excreta, a general epidemic is almost sure to occur, unless those using the water are sufficiently intelligent and well informed to take the precaution of sterilising, by heat, all water used for drinking purposes. When this is done there is little liability to infection through other channels, with the excep- tion of the milk supply — which should also be steril- ised by heat — and the danger from flies already referred to. This latter source of infection is to be guarded against by a strict sanitary police, by which all exposed excreta are covered with earth or dis- infected, and by the use of fly screens and other 120 INFECTION AND IMMUNITY methods of getting rid of these dangerous domestic pests. But the most important sanitary precaution consists in the immediate disinfection of all cholera excreta. This should be effected so far as possible in the sick-room or its immediate vicinity. And the dangerous mild cases of choleraic diarrhoea should be looked for and placed under treatment, an important part of which will be complete rest and isolation under conditions which admit of the necessary meas- ures of disinfection. A channel of infection not yet mentioned, is through the soiled underclothing or bed linen of cholera patients. Laundresses have not infrequently contracted the disease as a result of handling such infected articles. For this reason disinfection by im- mersion in boiling water or a suitable disinfecting solution should be carried out in the sick-room, or an adjoining apartment. The cholera germ, which was discovered by the German bacteriologist, Dr. Robert Koch, in 1884, is usually seen in the form of slightly curved rods, re- sembling somewhat a comma, and was first spoken of as " the comma bacillus of Koch." But these slightly curved rods may grow out into longer or shorter spiral filaments, and the so-called comma bacillus is described in systematic works upon bacteriology as a "spirillum" (Spirillum cholera Asiatics). It is con- ASIATIC CHOLERA 121 stantly found in the excreta of persons suffering from cholera, in the mild cases of choleraic diarrhoea as well as in the severe and fatal form of the disease. Fortunately for the human race, this cholera spirillum is a tender exotic which has not succeeded in estab- lishing itself permanently in Europe and America. Although not killed by cold, its epidemic extension is I'/ i . ( ^i to *' s ^ ' * - '_«• A - + tf** c n, , 'J » V ^ ^ V ' ti v' > * i, * °» ,»T?; § FIG. 2. Spirillum of Asiatic cholera (" comma bacillus of Koch ") ; magni- fied jooo diameters. arrested upon the approach of winter ; and our brief historical review of its prevalence, outside of its home in India, shows that after a period of longer or shorter duration the disease dies out and does not occur again independently of a fresh importation. Under favourable conditions as to temperature, the cholera spirillum multiplies in well or river water, 122 INFECTION AND IMMUNITY especially if this contains a certain amount of organic impurities. It has been shown by experiment that it will multiply abundantly in distilled water to which from two to three per cent, of bouillon has been added, also that it may preserve its vitality in steril- ised well or river water for several months. Koch found in his early investigations that rapid multipli- cation may occur upon the surface of moist linen. In a moist condition the cholera spirillum may retain its vitality for months. It is therefore evident that there is danger of its being carried to remote local- ities in bed linen or underclothing soiled by cholera discharges, if such articles in a moist condition are packed up, without disinfecting, to be transported with other personal effects of immigrants. Exposure to a temperature of 140° Fahr. (60° C.) destroys the cholera spirillum very promptly. It is also quickly killed by desiccation and by exposure to direct sunlight — two to four hours' exposure. Experiments made in Dr. Koch's laboratory show that it is killed in two hours by sulphuric acid or hydrochloric acid diluted in the proportion of one part to 1300 parts of water; by carbolic acid 1:400 ; by lysol i : 500 ; by corrosive sub- limate 1:10,000; by sulphate of copper 1:500. Solu- tions of this strength would disinfect soiled linen, but in practice it will be best to use the agents mentioned in much stronger solutions — one-per-cent. solutions ASIATIC CHOLERA 123 of carbolic acid, lysol, or sulphate of copper, or one part of corrosive sublimate to 1000 of water. For the disinfection of cholera excreta, milk of lime is to be recommended (see page 59), or a five-per-cent. solution of carbolic acid or lysol, or a two-per-cent. solution of chloride of lime, or boiling water. Sanitarians no longer have any great apprehension with reference to the extension of this Asiatic plague in European countries or in America The measures for its prevention are simple and easily applied, and it is only in localities where ignorance or prejudice stands in the way of the execution of these means that the deadly spirillum is likely to establish itself in civilised countries. The measures referred to may be summed up briefly as follows : Isolation of the sick, including all cases of choleraic diarrhoea ; disin- fection of excreta ; sanitary police of infected locali- ties ; boiling of drinking water ; exclusion of flies from dwellings, and especially from kitchens. The last-mentioned sanitary precaution is perhaps the most difficult of execution. But, fortunately, it is not essential when the measures previously men- tioned have been carried out, especially the disinfec- tion of excreta. Indeed all other measures might be neglected as superfluous if we could be assured of the complete destruction of all cholera germs in the excreta of infected individuals. And if this could be i24 INFECTION AND IMMUNITY accomplished in the countries where the disease has its permanent habitat, there is every reason to believe that its complete extinction would soon be effected. The prevention of cholera by " protective inocula- tions " has been tested on a large scale in Spain, during the epidemic of 1885, a°d more recently in India, by the method of Haffkine. Unfortunately the evidence relating to the value of these protective inoculations is not very satisfac- tory. The evidence, however, is in favour of the view that a partial and temporary immunity may be conferred by the subcutaneous injection of cultures of the cholera germ. We should not expect such inoculations to confer an absolute immunity, inas- much as this does not result from an attack of the disease. That repeated attacks may occur in the same individual is well established, and this may hap- pen during a single epidemic, as was observed in the last Hamburg epidemic. That the inoculated are not exempt from attack is shown by Haffkine's statistics with reference to in- oculations made by him in India (1895). Five hun- dred inoculated individuals gave a mortality of 19, or 3.8 percent., while among 1735 non-inoculated, under similar conditions, the mortality was 6.5 per cent. In our opinion inoculation as a method of prevention should not be employed on a large scale in anticipa- ASIATIC CHOLERA 125 tion of an epidemic, as it is far less reliable than the preventive measures heretofore referred to — disinfec- tion of excreta, boiling of drinking water, etc. But for individuals who are required, for any reason, to remain in an infected locality in India or elsewhere, it is perhaps worth while to further test the value of this method of prevention. CHAPTER III TYPHOID FEVER DUBONIC plague, Asiatic cholera, and dysentery ^ are filth diseases which appertain especially to the populous countries of the Orient. In the present chapter we shall consider a filth disease which prevails in all parts of the civilised world, and which continues to claim its annual quota of victims notwithstanding the fact that we know its specific cause (germ), its mode of transmission, and the preventive measures which if thoroughly carried out would soon lead to its extinction. According to the last census return, there were 35,379 deaths from typhoid fever in the United States during the census year 1900. The increase in mortality over the num- ber in 1890 (27,056) is out of proportion to the increase in population, notwithstanding the general improvement in the sanitary condition of towns and cities. This is no doubt due to the continued pollu- tion of water supplies and to the extension of this infectious disease in rural districts. 126 TYPHOID FEVER 127 As the typhoid bacillus is contained in the excreta of the sick, no single agency is more important for the prevention of this, and of other filth diseases, than the use of properly constructed sewers for the reception of excreta and its removal from the vicinity of human habitations. Disease germs contained in human excreta, when this is conveyed, by flushing or otherwise, to properly constructed sewers, are no longer dangerous to the community where these sewers are located. But they may be capable of doing serious harm to other communities if the sewers empty into a stream the water of which is used for drinking purposes. Sewers had come into use and had the warm endorsement of sanitarians long before the discovery of the germs of the infectious maladies under con- sideration, and before it was positively known that the infectious agents in these diseases are contained in the discharges from the bowels. But now that we have an exact knowledge of the causes of these diseases, the reason for the beneficent results attend- ing the use of sewers, in connection with an ample and pure water supply, is apparent. It may be safely asserted that a city or town having a complete and satisfactory sewer system and a pure water supply is practically immune from epidemics of cholera or typhoid fever, provided, of course; that the sewers 128 INFECTION AND IMMUNITY are used for the purpose for which they are in- tended, and that streets and back yards no longer serve as receptacles for filth, as was usual during the presanitary period, even in great cities like London and Paris. The axiom tout a /' tgout now governs the practice not only in Paris but wherever the fun- damental principles of sanitation are understood and sewers have been constructed. Unfortunately, the cost of sewer construction, the reluctance of taxpayers to part with their money, and the ignorance or indifference of municipal authorities have conspired to prevent the accomplishment of this fundamental sanitary measure in very many towns in the United States, and our endemic plague — typhoid fever — continues to claim a large annual quota of victims in such localities. Even in the national capital our sewer system is incomplete, and in many out-of- the-way places, especially in the densely populated alleys of the city, shallow box privies are in use as receptacles for human excreta. The typhoid-fever rate, owing to this and other causes, is disgracefully high. Mortality rates in towns and cities throughout the civilised world depend to a large extent upon the purity of the water supply and the efficiency of the system of sewage disposal ; and the constant im- provement which is shown by the mortality statistics TYPHOID FEVER 129 of England and other countries which have made the most progress in this direction is undoubtedly largely due to these two factors. This is well illustrated by the mortality statistics of armies. In the German army, the annual death-rate in 1868 was 6.9 per thou- sand, a decade later it was 4.82, in 1888 it had fallen to 3.24, and in 1896 to 2.6. In our own army, the death-rate during the period of peace just prior to the Mexican War (1848) was about three and one-half times as great as durmg the five years preceding our recent war with Spain ; and since the year 1872 there has been a diminution of the death-rate of nearly forty per cent. In the British army at home stations, the mortality rate during the decade end- ing in 1884 was 7-2 Per thousand, in 1889 the rate had fallen to 4.57, and in 1897 to 3.42. In the Italian army there has been a gradual and progres- sive reduction from 13.3 per thousand in 1875 to 4-2 in 1897. The mortality in the French army was a little over 21 per thousand during the five years ending in 1825. In 1890 it had fallen to 5.81 per thousand. According to the best estimates, the average of human life in the sixteenth century was somewhat less than twenty years ; at the present time it is more than twice as long ; and during the past twenty- five years the average duration of life has been '3° INFECTION AND I MM UNITY lengthened about six years. During the first thirty- five years of the past century, the vital statistics of the city of London showed a mortality of about 29 per thousand. At the present time the mortality in that great city has been reduced to from 17 to 19 per thousand. No doubt a considerable proportion of this reduc- tion in the rate of mortality in London and in other large cities in this country and in Europe is due to a diminished typhoid-fever rate. Indeed, sanitarians at the present day depend largely upon this factor of the general mortality rate of cities as an index of their sanitary condition. The following table showing the typhoid death-rate of cities, compiled by the Register of Vital Statistics of the New York Health Depart- ment, is given in a recent publication. AMERICAN CITIES POPULATION. DEATHS. DEATH-RATE PER 10,000 INHABI- TANTS. Washington 278,7l8 161 «5.78 Chicago i.6o8,s;7q 500 3.00 Boston • C7"Z,C7Q 142 2.48 Philadelphia 1. 3 21 408 444 Vl6 Providence 178.000 47 2.04 New York i ci6.qi7 727 2.06 St. Louis coS ooo 108 7. -2 I San Francisco 360 ooo 70 I. Q4 TYPHOID FEVER FOREIGN CITIES POPULATION. DEATHS. DEATH-RATE PER 10,000 INHABI- TANTS. Belfast •5C I 08"? "?4O 9O4 St Petersburg oO *»W**O I 24.8 64.3 o^y I 060 •VT- 8 4.0 Cairo 608 QIO 48^ "•T-y 7 06 Glasgow 764. 467 108 2 c;o Liverpool 686 41:4 i y«j i6c *O!r 2 41 Dublin 376 081 ivj 1 04 2 77 London 4.^44 08^ 54-8 121 Paris 2 660 £\ ^Q ?A-2 I 2Q Berlin •^""^OOV I 80 1 QOO JT-O 88 j .^y O 47 Vienna I 7?C 740 76 O 44 Munich CO"? OOO 24 0 48 0>-'O»w^ w.^. while among the vaccinated it was only 3.40$. The gradual loss of immunity after vaccination is established by the well-known fact that revaccination after a longer or shorter interval is successful in a considerable pro- portion of the cases. This is therefore to be recom- mended whenever smallpox is prevalent. As a result of neglect of vaccination an epidemic occurred in Sheffield, England, some years ago. Statistics collected during this epidemic (1887-88) show that among children less than ten years of age the vaccinated were attacked in the proportion of SMALLPOX 217 5 per thousand, and the unvaccinated in the pro- portion of 101 per thousand. The death-rate among the vaccinated was about one-tenth of one per cent, and among the unvaccinated 44 per cent. Similar and even more favourable statistics could be pre- sented from other parts of England and from all countries where vaccination is systematically practised. The total number of deaths reported from small- pox, in the United States, during the last census year was 3484. If the mortality had corresponded with that of England and Wales before the introduc- tion of vaccination it would have amounted to more than 210,000. The practical stamping out of smallpox in the Dis- trict of Holguin, Cuba, and in the island of Porto Rico, since the Spanish-American War, by the vac- cination of all the inhabitants, under the direction of the military authorities of the United States, is a matter of record in my annual reports as Surgeon- General of the Army for the years 1899 an<^ 1900. In my report for 1899 I say : " It is understood that the occurrence of smallpox among our troops in the Philippines gave rise in England, where the pro- tective influence of vaccination was under discussion at the time, to the claim that, as vaccination was compulsory in the United States Army, and carried out under military rules, the presence of the disease among our soldiers showed the inefficiency of the process. This claim of the opponents of vaccination is not well 2i8 INFECTION AND IMMUNITY taken. On the contrary, the history of vaccination and of small- pox in the United States Army suffices in itself to demonstrate that protection from the disease is proportioned to the care with which vaccination is performed. . . . Although this disease has prevailed in many parts of the United States during the past fifteen years (1883 to 1897), and frequently with epidemic vio- lence, among the civil population in the immediate vicinity of military posts, there occurred only 20 scattered cases, of which 4 were fatal, in a mean strength of 25,000 men." The cases which occur in various parts of the coun- try, from time to time, are for the most part among unvaccinated individuals. For example, in the city of Chicago, the Bulletin of the Health Department for the month ending May 31, 1903, says : " During the month forty- five cases of smallpox were discovered and removed to the Isolation 'Hos- pital. Of these thirty-nine never had been vaccinated ; six had old, imperfect marks, said to be from vaccina- tion in childhood. Fifteen were unvaccinated child- ren under six years of age." It is unnecessary to give any further facts in support of the protective value of vaccination, which, since the discovery of Jenner in 1796, has been established by unimpeachable statistical data in all parts of the civilised world. But there are certain persons whose minds are not penetrated by the logic of facts, or who have not taken the pains to make themselves familiar with these facts, who still oppose vaccination on the ground that it has no value as a preventive measure. SMALLPOX 219 Recent researches seem to prove that the small- pox germ multiplies in the epithelial cells of that portion of the skin which is involved in the pustules which are characteristic of the disease. This germ is extremely minute and it has not been cultivated in artificial media. It does not belong to the same class as the germs of typhoid fever, cholera, diphtheria, etc. (the bacteria), but to the protozoa. It is generally recognised that smallpox patients must be isolated and cared for by immune attendants, and that clothing and all articles exposed to infection must be thoroughly disinfected. This is especially important, as the infectious agent or germ is given off from the general surface of the body, attached to epithelium, pus cells, etc. This infectious agent may retain its capacity for harm (vitality) for months in spite of desiccation. An instance is given by Dr. Buck, of New York, in which an unvaccinated infant, when two months - old, contracted smallpox in the room in which it was born and in which a case of smallpox had occurred two years previously. The danger of infection from a patient before the eruption has developed is very slight if any and it is chiefly through pus and scabs which are formed at a later stage of the disease that the malady is propa- gated. The time which elapses after exposure before the first symptoms of the disease are manifested is 220 INFECTION AND IMMUNITY usually twelve days and the duration of the disease in cases ending in recovery is about three weeks. That the smallpox virus may be carried a considerable dis- tance through the air by currents of wind, and the disease thus be propagated, seems to be well estab- lished by the observations of certain English authori- ties upon the subject. But it is not certain whether it is directly, as dust carried by the wind, or indirectly, attached to the feet of flies which have been in con- tact with the pustules on the body of a smallpox pa- tient, that the disease has been conveyed in the instances which have been recorded. The extreme limit to which the disease is likely to be commun- icated in this way probably does not exceed a mile. The disinfection of the room occupied by a small- pox patient, and all its contents, calls for the most careful, intelligent, and thorough measures. Only absolutely necessary articles should be left in the room and it is well to have screens in the windows to exclude flies. Abundant ventilation is important. While oc- cupied by the patient, floors, window-ledges, and all places where dust is liable to accumulate should be frequently wiped with a cloth wet with a suitable dis- infecting solution (5 % solution of carbolic acid or i : 1000 solution of corrosive sublimate). All washable articles which have been in contact with the sick per- son or in use in the sick-room should be immersed in SMALLPOX 221 a disinfecting solution in the room or in an adjoining room. Subsequently they are to be subjected to the action of steam or of boiling water. Woollen clothing, carpets, curtains, etc., are best disinfected by steam. But the room and its contents, after the patient has left it, may be disinfected with formaldehyd gas or by fumigation with burning sulphur. This disinfection should, however, be attended to by an expert and is to be followed by thorough washing of all surfaces with a disinfecting solution, and subsequent scrubbing with hot soap-suds, whitewashing of plastered walls, free ventilation, and exposure of clothing, bedding, etc., in the open air to direct sunlight. With reference to vaccination, which is our chief reliance for preventing the spread of the disease, we recommend the vaccination of infants and revaccina- tion at the age of ten or twelve, as practised in Ger- many. After this tests of the immunity of persons of any age should be made, by revaccination, when- ever smallpox is prevalent, or when the individual is about to travel in countries where this preventive measure is neglected or carried out in an indifferent manner. Chicken-pox is a highly contagious disease which fortunately is mild in character and does not contribute to our mortality statistics. The fact that mild cases of smallpox have not infrequently been mistaken for 222 INFECTION AND IMMUNITY varicella, or chicken-pox, should be borne in mind. This mistake has been responsible for the spread of smallpox in numerous instances and is to be guarded against by the isolation of the sick and the measures of disinfection heretofore recommended for prevent- ing the extension of that disease. The period of incubation in chicken-pox is fourteen days. The germ of this disease has not been discovered, but it has been demonstrated that it is present in the " lymph " contained in the vesicles which are charac- teristic of the disease. CHAPTER XIV SCARLET FEVER OCARLET fever is widely prevalent in the coun- ^ tries of Europe and in North and South America, but is scarcely known in Asia and in Africa. It is said to occur occasionally in China, but to be un- known in Japan. It is impossible to say how long it has prevailed in Europe, but the first to clearly recognise it as a distinct specific disease was the famous English physician Sydenham (1685). It was not introduced to North America until about the year 1735 and first appeared in South America about 1830. The germ of scarlet fever has not been demon- strated but, as is well-known, the scarlet fever patient gives off from the surface of his body infectious material by means of which the disease may be com- municated, either directly or indirectly, to other sus- ceptible individuals. This consists essentially of cast-off (" desquamated ") epithelium, to which the 223 224 INFECTION AND IMMUNITY infectious agent, or germ, is attached, and which may retain its infecting power for many months. The sputa of scarlet fever patients also contains the germ and by some physicians is believed to be to a large extent responsible for the spread of the dis- ease. As the mucous membrane of the mouth and throat is involved in the eruption which is character- istic of the disease and is in fact the locality where this eruption, followed by desquamation of the epi- thelium, may first be observed, it is evident that all expectorated material must contain the infectious agent. The disease may be communicated by the scarlet fever patient at any time during the period of desquamation, which may last for a month, or more. The period during which the patient should be isol- ated, dating from the outset of the attack, is gen- erally fixed at six weeks. The infection may persist in clothing and bedding, in use during the period of desquamation, or exposed in the sick-room, for a year or more. Certain persons seem to have a natural immunity to scarlet fever and escape the disease although re- peatedly exposed to it. In some instances, no doubt, this failure to contract the disease is due to a pre- vious mild and unrecognised attack rather than to an inherited immunity. The protection afforded by an attack of the disease, however mild, is almost abso- SCARLET FEVER 225 lute. That is, second attacks are extremely rare, although not unknown. The fact that adults rarely contract the disease is to a large extent due to the protection afforded by an attack during infancy or childhood. That adults may suffer fatal attacks of the disease is amply proved by the mortality statistics of this and other countries. The greatest number of cases, however, occur between the ages of two and ten years. In the United States the mortality from this dis- ease during the census year 1900 (6333) was some- what less in proportion to the population than during the previous census year. The proportion to 1000 deaths from all causes was 6.3 in 1900 and 7.1 in 1890. These rates are considerably below the rates in England and Wales, where during the year 1899 scarlet fever caused 11.7 in every 1000 deaths. The mortality rate is higher in cities than in the country. The States of New Jersey and Massachusetts show the highest mortality rate and the State of Vermont the lowest (this applies only to the registration States, viz. : Connecticut, District of Columbia, Maine, Massachusetts, Michigan, New Hampshire, New Jersey, Rhode Island, New York, Vermont). Scarlet fever is a disease in which the evil influ- ences of overcrowding and insanitary surroundings 226 INFECTION AND IMMUNITY are not so apparent as in many other diseases. In- deed some authors assert that the children of the rich suffer even in greater proportion than those of the poor. In the United States the mortality among the coloured population is considerably less than among the whites — 12 deaths in 1000 from all causes among whites and 2.6 per 1000 among coloured. More deaths occur during the winter than during the sum- mer months. This is no doubt partly due to the unfavourable influence of exposure to cold in the development of some of the most fatal complications which are likely to occur during the progress of the disease — nephritis, pneumonia. For the prevention of scarlet fever we must de- pend entirely upon isolation of the sick and the dis- infection of all infectious material, inasmuch as no method of protecting by inoculation is known, The general directions given with reference to the disin- fection of the sick-room and its contents on page 220 apply equally to scarlet fever. Special care must be taken with reference to the sputa of the patient, which should be disinfected by the same methods recommended for tuberculosis (p. 171) and other diseases in which the infectious agent is present in secretions from the mucous membrane of some por- tion of the respiratory tract. The advantages attending the removal of scarlet SCARLET FEVER 227 fever patients to special " contagious-disease hos- pitals " have been amply demonstrated. Dr. Hope, Medical Officer of Health for the city of Liverpool, refers to this in his report for the year 1901, as follows : " Want of hospital accommodation goes far to explain the in- crease in the number of cases of scarlet fever. The reduction in the number of cases of this disease, which had been noted in 1900, ceased immediately the removal of patients to hospitals was stopped, although the total removed was but 6 % lower than in the previous year. This happened during the annual cleaning of some of the wards. " When to this is added the economy to householders if saved from a complete disinfection and renovation of houses, after two or three months' presence of scarlet fever, and the yet greater value to wage-earners of being able to go from their houses to continue their work, instead of loss of time through a forced quarantine, it will be apparent that nowhere, whether in a large city or in the country, can there be any question as to the advisability of having first cases of scarlet fever, like smallpox, removed to hospitals or a temporary building or tent, with, if necessary, the mother to act as nurse." In the city of London, in 1891, 18,381 cases of scarlet fever were reported ; of these 14,539 (78 %) were treated in hospitals, with a mortality of 542 (3-73 50- CHAPTER XV MEASLES DEFORE the time of Sydenham (1685) measles ^ and scarlet fever were not, as a rule, recognised as distinct diseases and both of these eruptive fevers were commonly confounded with smallpox. Indeed it not unfrequently occurs even at the present day that cases of smallpox are diagnosed as measles at the outset of the attack ; but the development of the characteristic eruption of smallpox soon makes it evident that a serious mistake has been made. The period of incubation in measles is from ten to twelve days, and the eruption usually appears on the third day after the initial symptoms are developed. These consist of fever and catarrhal symptoms, attended with cough and a watery discharge from the con- gested mucous membrane of the eyes and nose. Measles, like scarlet fever, is a disease which has not been materially influenced by modern sanitary measures. The sanitary statistics of England and 228 MEASLES 229 Wales show an increased mortality from this disease during the decade ending in 1890, over the previous ten years (2.57 per 1000 deaths under five years of age in 1871-80 and 3.13 in 1881-90.) In the United States the total number of deaths from measles re- ported during the census year 1900 was 12,866. The number of deaths in 1000 from all causes was 12.9 while in 1890 the proportion was u.i, showing a decided increase in this country also. More deaths occur in proportion to the population in cities (18.2 per 100,000) than in the country (9.9 per 100,000). The greatest mortality occurs among infants less than a year old (i 52.8 per 100,000) and among young child- ren. After the age of five the mortality rate is greatly reduced (under five years 106.5 ; from five to fourteen years 7.4). The death-rate among the coloured popula- tion was somewhat greater than among native whites. " The greatest proportions of deaths from measles occurred in the South-west Central region (51.7), the South Mississippi River belt (40.7), and the Southern Interior plateau (22.7); and the least in the Pacific Coast region (2.1), the Ohio River belt (6.3), and the Prairie region (6.5)" (Census Reports, 1900). The mortality from measles is to a large extent due to pulmonary complications, which are especially liable to occur in young children. The influence of external conditions in giving rise to these fatal complications 23o INFECTION AND IMMUNITY (broncho-pneumonia, diphtheria) is shown by the fact that the greatest mortality occurs during the months of February, March, April, and May, and the least during the summer and autumn months, also by the very low mortality of the Pacific Coast region. The combined influence of an unfavourable climate and density of population is shown by the statistics relating to the State of Rhode Island, which has the highest death-rate from this disease of any of the registration States (47.6). The lowest rate in the re- gistration States was in Vermont (6.1). Patients having measles may communicate the dis- ease from the very outset of the attack and it is prob- able that the germ is present in the abundant secretion from the bronchial and nasal mucous mem- branes, as well as in the desquamated epithelium from the surface of the body after the eruption has de- veloped. When convalesence has been established, if the patient's body and clothing have been disinfected he can no longer communicate the disease. The period during which isolation should be insisted upon, to prevent the extension of the disease, is about three weeks from the date of the first appearance of the eruption. The infectious material is not so tenacious of vitality as in smallpox and scarlet fever and the disease is not so likely to be conveyed by means of infected clothing and other articles exposed in the MEASLES 231 sick-room, if an interval of two or three weeks has elapsed since infection. This fact, however, should not lead to a neglect of the usual measures of dis- infection heretofore recommended (see p. 220 and p. 171). Free ventilation of the sick-room, after thorough scrubbing of surfaces with hot water and soap will, as a rule, ensure its disinfection. But it will be prudent not to allow susceptible children to enter such a room for at least fourteen days. The following directions, published by the Board of Health of the city of Glasgow, set forth very forcibly the importance of preventing the spread of measles and the fact that isolation of the sick must be relied upon as the principal measure of prevention: "Measles is a dangerous disease, one of the most dangerous with which a child under five years of age can be attacked. It is especially apt to be fatal to teething children. It tends to kill by producing inflammation of the lungs. It prepares the way for consumption. It tends to maim by producing inflammation of the eyes and ears. " In Glasgow, during the last five years, measles has caused three deaths for every one which has been caused by scarlet fever ; only one infectious disease has been more destructive to life, viz.: whooping-cough. Measles has carried off more than four times as many persons as enteric fever (typhoid). "It is therefore a great mistake to look upon measles as a trifling disease. " The older a child is the less likely is it to catch measles; and if it does, the less likely is it to die. " If every child could be protected from measles until it had 232 INFECTION AND IMMUNITY passed its fifth year, the mortality from measles would be enorm- ously decreased. "It is therefore a great mistake — because, as a rule, children sooner or later have measles — to say * The sooner the better,' and to take no means to protect them, or even deliberately to expose them to infection. " It is wrong for mothers with children in arms to go into houses where measles exists. "Every child with measles ought at once to be put to bed and kept warm. The mildest cases may be made serious by a chill. Measles is for this reason most dangerous in winter and spring. "A case of measles continues infectious for at least three weeks after the appearance of the rash. During that time separ- ation from the healthy ought to be secured either by removal of the sick to hospital or by isolation at home. " Isolation means not merely a separate room for the sick, but the withdrawal of apparently healthy children from school (day and Sunday) and the exclusion of strange children from the house. " The isolation, as far as possible, from other children of all children belonging to the same family is more necessary in the case of measles than of any other infectious disease, because of this peculiarity—/^ days before the rash comes out, the child is highly infectious. " School teachers, especially, ought to be familiar with the appearance of children in this stage of measles. "The eyes are watery, glistening, and sensitive to light; there is a ringing cough, sneezing, and running from the nose, with flushed face; in short, all the signs of a bad cold in the head. " No child showing these symptoms ought to be allowed to go to school. " Any child observed at school with these symptoms ought to be sent home at once. Such children are to be looked for more particularly in the Infant Department. " DR. J. B. RUSSELL. " Sanitary Office, " Montrose Street, Glasgow, "January, 1897." MEASLES 233 Second attacks of measles are comparatively rare, even more so than second attacks of smallpox or of scarlet fever. The apparent exemption of adults from attacks of measles is largely if not altogether due to the fact that they have usually suffered an attack during childhood. It has been noticed that regiments of soldiers recruited in cities are less sub- ject to measles than regiments raised in rural districts. This is no doubt due to the greater prevalence of the disease among children in cities, where few escape attack during infancy or the age of going to school. During a severe epidemic in the Faroe Islands in 1 846 scarcely any one escaped except those old enough to have passed through the previous epidemic in 1 781. German measles (Rubella) is a distinct disease from measles, but its specific character was not gen- erally recognised by physicians until the last half of the nineteenth century. An attack of this disease does not protect the child from the far more danger- ous disease, measles. The mortality from German measles is practically nil. Its prevention is therefore of much less importance, but is to be effected by the same measures, viz.: isola- tion of the sick and disinfection of all clothing and other objects which have been exposed in the sick-room. The period of incubation in this disease is quite variable, but as a rule it is longer than that of measles. CHAPTER XVI MALARIAL FEVERS HTHE discovery of the malarial parasite may justly be considered one of the greatest achievements of scientific research during the nineteenth century. We owe it to Laveran, a surgeon in the French army, who made the discovery in 1880 while sta- tioned in Algeria. His painstaking microscopical researches convinced him that the blood of patients suffering from malarial fever contains living amoe- boid parasites which in one stage of their develop- ment invade the red blood corpuscles and lead to their destruction. Subsequent researches in various parts of the world have made it evident that this blood parasite is in fact the malarial germ and the cause of the phenomena which characterise fevers of this class. It has also been demonstrated that the disease is transmitted to man by mosquitoes of the genus Anopheles, in the bodies of which the para- site passes through certain stages of development, 234 MALARIAL FEVERS 235 resulting in the formation of a multitude of minute spore-like bodies which are found in the salivary glands of the insect. Twenty-five years ago the best-informed physicians entertained erroneous views with reference to the nature of "malaria" and the cause of the malarial fevers. Observation had taught them that there is something in the air in the vicinity of marshes in tropical regions, and during the summer and autumn in semitropical and temperate regions, which gives rise to periodic fevers in those exposed in such localities ; and the usual inference was that this something was of gaseous form — that it was a special kind of bad air (malaria) generated in swampy localities under favourable meteorological conditions. It was recognised at the same time that there are other kinds of bad air, such as the offensive emanations from sewers and the products of respira- tion of men and animals ; but the term malaria was reserved for the kind of bad air which was supposed to give rise to the so-called malarial fevers. In the light of our present knowledge it is evident that the term is a misnomer. There is no good reason for believing that the air of swamps is any more dele- terious to those who breathe it than the air of the sea-coast or that in the vicinity of inland lakes and ponds. Moreover, the stagnant ponds, which are 236 INFECTION AND IMMUNITY covered with a " green scum " and from which bub- bles of gas are given off, have lost all terrors for the well-informed man, except in so far as they serve as breeding-places for mosquitoes of the genus Ano- pheles. The green scum is made up of harmless algae and the gas which is given off from the mud at the bottom of such stagnant pools is for the most part a well-known and comparatively harmless com- pound of hydrogen and carbon — methane or " marsh gas." In short, we now know that the air in the vicinity of marshes is not deleterious because of the presence of any special kind of bad air in such local- ities but because it contains mosquitoes infected with the malarial parasite. The discoveries referred to, as is usual, have had to withstand the criticism of conservative physicians, who, having adopted the prevailing theories with reference to the etiology of periodic fevers, were naturally skeptical as to the reliability of the observa- tions made by Laveran and those who claimed to have confirmed his discovery. The first contention was that the bodies described as present in the blood were not parasites, but deformed blood corpuscles. This objection was soon set at rest by the demon- stration, repeatedly made, that the intra-corpuscular forms underwent distinct amoeboid movements. No one witnessing these movements could doubt that he MALARIAL FEVERS 237 was observing a living micro-organism. The same was true of the extra-corpuscular flagellate bodies, which may be seen to undergo very active move- ments, as a result of which the red blood corpuscles are violently displaced and the flagellate body itself dashes about in the field of view. The first confirmation in this country of Laveran's discovery of amoeboid parasites in the blood of ma- larial-fever patients was made by myself in the path- ological laboratory of the Johns Hopkins University in March, 1886. In May, 1885, I had visited Rome as a delegate to the International Sanitary Conference, convened in that city under the auspices of the Italian Government, and while there I visited the Santo Spirito Hospital for the purpose of witnessing a demonstration, by Drs. Marchiafava and Celli, of that city, of the presence of \heplasmodium malarice in the blood of persons suffering from intermittent fever. Blood was drawn from the finger during the febrile attack, from individuals to whom quinine had not been administered. The demonstration was entirely satisfactory, and no doubt was left in my mind that I saw living parasitic micro-organisms in the interior of red blood corpuscles obtained from the circulation of malarial-fever patients. The mo- tions were quite slow, and were manifested by a gradual change of outline rather than by visible 238 INFECTION AND IMMUNITY movement. After a period of amoeboid activity of greater or less duration, the body again assumed an oval or spherical form and remained quiescent for a time. While in this form it was easily recognised, as the spherical shape caused the light passing through it to be refracted, and gave the impression of a body having a dark contour and a central vacuole, but when it was flattened out and under- going amoeboid changes in form it was necessary to focus very carefully and to have a good illumination in order to see it. The objective used was a Zeiss's one-twelfth inch homogeneous oil immersion. Very properly, skepticism with reference to the causal relation of these bodies to the disease with which they are associated was not removed by the demonstration that they are in fact blood parasites, that they are present in considerable numbers during the febrile paroxysms, and that they disappear during the interval between these paroxysms. These facts, however, give strong support to the inference that they are indeed the cause of the disease. This in- ference is further supported by the evident destruc- tion of red blood corpuscles by the parasite, as shown by the presence of grains of black pigment in the amoeba-like micro-organisms observed in these corpuscles and the accumulation of this insoluble blood pigment in the liver and spleen of those who MALARIAL FEVERS 239 have suffered repeated attacks of intermittent fever. The enormous loss of red blood corpuscles as a result of such attacks is shown by the anaemic con- dition of the patient and also by actual enumeration. According to Kelsch, a patient of vigorous constitu- tion in the first four days of a quotidian intermittent fever, or a remittent of first invasion, may suffer a loss of 2,000,000 of red blood corpuscles per cubic millimetre of blood, and in certain cases a loss of 1,000,000 has been verified at the end of twenty-four hours. In cases of intermittent fever having a dura- tion of twenty to thirty days the number of red blood cells may be reduced from the normal, which is about 5,000,000 per cubic millimetre, to 1,000,000 or even less. In view of this destruction of the red blood cells and the demonstrated fact that a certain number at least are destroyed during the febrile parox- ysms by a blood parasite which invades the cells and grows at the expense of the contained haemo- globin, it may be thought that the causal relation of the parasite should be conceded. But scien- tific conservatism demands more than this and the final proof has been afforded by the experiments of Gerhardt and of Marchiafava and Celli — since confirmed by many others. This proof consists in the experimental inoculation of healthy individuals 240 INFECTION AND IMMUNITY with blood containing the parasite and the develop- ment of a typical attack of periodic fever as a result of such inoculation. After such an inoculation a period varying from four to twenty-one days elapses before the occurrence of a febrile paroxysm. This is the so-called period of incubation, during which, no doubt, the parasite is undergoing multiplication in the blood of the inoculated individual. The dura- tion of this period depends to some extent upon the quantity of blood used for the inoculation and its richness in parasites. It also depends upon the particular variety of the parasite present, for it has been ascertained that there are at least three distinct varieties of the malarial parasite — one which pro- duces the quartan type of fever, in which there is a paroxysm every third day and in which, in experi- mental inoculations made, the period of incubation has varied from eleven to eighteen days ; one in which the paroxysm occurs every second day (ter- tian), in which the period of incubation is from nine to twelve days; and one, denominated the aestivo-autumnal type, in which the period of incuba- tion rarely exceeds five days. The parasite associated with each of these types may be recognised by an expert, and there is no longer any doubt that the difference in type is due to the fact that different varieties or " species " MALARIAL FEVERS 241 of the malarial parasite exist, each having a dif- ferent period of development. Blood drawn dur- ing a febrile paroxysm shows the parasite in its different stages of intra-corpuscular development. The final result of this development is a segment- ing body, having pigment granules at its centre, which occupies the greater part of the interior of the red blood corpuscle. The number of seg- ments into which this body divides differs in the different types of fever, and there are other points of difference by which the several varieties may be distinguished one from the other, but which it is not necessary to mention at the present time. The im- portant point is that the result of the segmentation of the adult parasites contained in the red corpuscles is the formation of a large number of spore-like bodies, which are set free by the disintegration of the remains of the blood corpuscles and which con- stitute a new brood of reproductive elements, which in their turn invade healthy blood corpuscles and effect their destruction. This cycle of development, without doubt, accounts for the periodicity of the characteristic febrile paroxysms ; and, as stated, the different varieties complete their cycle of develop- ment in different periods of time, thus accounting for the recurrence of the paroxysms at intervals of forty-eight hours in one type of fever and of three 242 INFECTION AND IMMUNITY days in another type. When a daily paroxysm oc- curs, this is believed to be due to the alternate de- velopment of two groups of parasites of the tertian variety, as it has not been possible to distinguish the parasite found in the blood of persons suffering from a quotidian form of intermittent fever from that of the tertian form. Very often, also, the daily paroxysm occurs on succeeding days at a different hour, while the paroxysm every alternate day is at the same hour, a fact which sustains the view that we have to deal, in such cases, with two broods of the tertian parasite which mature on alternate days. In other cases there may be two distinct paroxysms on the same day and none on the following day, indicating the presence of two broods of tertian parasites maturing at different hours every second day. The hypothesis that malarial infection results from the bites of mosquitoes was advanced and ably sup- ported by Dr. A. F. A. King, of Washington, D. C, in a paper read before the Philosophical Society on February 10, 1883, and published in the Popular Sci- ence Monthly in September of the same year. In 1894 Manson supported the same hypothesis in a paper published in the British Medical Journal (De- cember 8th), and the following year (1895) Ross made the important discovery that when blood containing the crescentic bodies was ingested by the mosquito MALARIAL FEVERS 243 these crescents rapidly underwent changes resulting in the formation of motile filaments, which become detached from the parent body and continue to ex- hibit active movements. In 1897 Ross ascertained further that when blood containing crescents was fed to a particular species of mosquito, living pig- mented parasites could be found in the stomach walls of the insect. Continuing his researches with a parasite of the same class which is found in birds, and in which the mosquito also serves as an inter- mediate host, Ross found that this parasite enters the stomach wall of the insect, and, as a result of its development in that locality, forms reproductive bodies (sporozoites), which subsequently find their way to the veneno-salivary glands of the insect, which is now capable of infecting other birds of the same species as that from which the blood was obtained in the first instance. Ross further showed that the mosquito which served as an intermediate host for this parasite could not transmit the malarial parasite of man or another similar parasite of birds (Jialteri- diuni). These discoveries of Ross have been con- firmed by Grassi, Koch, and others, and it has been shown that the mosquitoes which serve as inter- mediate hosts for the malarial parasites of man be- long to the genus Anopheles, and especially to the species known as Anopheles claviger. 244 INFECTION AND IMMUNITY The question whether malarial fevers can be con- tracted in any other way than through inoculation by infected mosquitoes, or direct experimental inocu- lation with the blood of one suffering from malarial infection, has been submitted to experimental investi- gation, and the answer is in the negative. Formerly it was believed by many physicians that malarial fevers might be contracted by drinking surface water obtained in malarious localities, but there is no ex- perimental evidence in favour of this hypothesis. The first experiment of the nature indicated was made in the summer of 1900, and the results were reported by Manson in September of that year. Five healthy individuals lived in a hut on the Roman Campagna since early in the month of July. They were protected against mosquito bites by mos- quito-netting screens in the doors and windows and by mosquito-bars over the beds. They went about freely during the daytime, but remained in their pro- tected hut from sunset to sunrise. At the time Man- son made his report all these individuals remained in perfect health. It has long been known that labourers could come from the villages in the mountainous re- gions near the Roman Campagna and work during the day, returning to their homes at night, without great danger of contracting the fever, while those who re- mained on the Campagna at night ran great risk of MALARIAL FEVERS 245 falling sick with fever, as a result of " exposure to the night air." What has already been said makes it ap- pear extremely probable that the " night air/'/^r se, is no more dangerous than the day air, but that the real danger consists in the presence of infected mosquitoes of a species which seeks its food at night. As pointed out by King, in his paper already referred to, it has repeatedly been claimed by travellers in malarious regions that sleeping under a mosquito-bar is an effectual method of prophylaxis against intermittent fevers. An experiment on a larger scale has since been made by some medical officers of the Japanese army on the island of Formosa, where two companies of soldiers were stationed in a very malarious locality. The men of one company were carefully protected from the bites of mosquitoes and did not suffer attacks of malarial fever, while those of the other company, who were not protected from mosquito bites, suffered severely. The geographic distribution of the malarial fevers is coextensive with the conditions favourable for the development of the mosquito which serves as an inter- mediate host of the parasites to which the disease is due. Accordingly we find that these fevers prevail in tropical regions, where there is abundant moisture, in all parts of the world ; and in temperate regions, 246 INFECTION AND IMMUNITY during the summer months, wherever there are suit- able breeding-places for mosquitoes of the genus Anopheles. The more severe and fatal forms of malarial infec- tion are found especially in low-lying regions in the tropics. In the United States malarial fevers are common along the Gulf and South Atlantic coasts, and in the valleys of rivers throughout the Southern and South-western States. There is considerable malaria along the shores of lakes Ontario and Erie, but fevers of this class are rare in the vicinity of lakes Superior and Michigan. The disease prevails in a mild form in some portions of the States of New York and Pennsylvania but is extremely rare in New England and is almost unknown on the Pacific Coast. Many localities in the United States which furnished numerous cases of malarial fever when first settled have since become comparatively healthy as a result of agricultural operations by which marshy lands have been drained and reclaimed. The seasonal prevalence differs in different regions, but in the temperate zone is usually greatest during the summer and early autumn. A considerable rain- fall during the spring and summer months leads to the formation of stagnant pools and marshes which serve as breeding-places for mosquitoes, but an ex- cessive rain-fall, by which swamps and ponds are kept MALARIAL FEVERS 247 full of water, is not favourable for the multiplication of mosquitoes and it has long been known that malarial fevers are less prevalent under such circumstances. The total number of deaths from malarial fever during the census year 1900 was 14,874 and the proportion per 1000 deaths from all causes was 14.9. The proportion during the census year 1890 was considerably greater (22. i). The popular idea that the negro is less susceptible to malarial fever than the white man does not appear to receive sup- port from the census returns as the mortality among the coloured was 59.8 per 100,000 of population and among whites 6.5 per 100,000. But it must be re- membered that the coloured population of the United States is located to a much greater extent than the whites in the more malarious regions of the country. Another factor which probably vitiates the statistics to a considerable extent is the fact that many deaths ascribed to malarial fever are doubtless due to typhoid fever. This mistake in diagnosis has frequently been made in all parts of the world and is especially liable to occur among an ignorant population. The mortal- ity from malarial fevers does not, however, fairly re- present the mischief accomplished by malaria-infected mosquitoes. The forms of malarial fever commonly encountered in the United States are rarely fatal, especially if 248 INFECTION AND IMMUNITY proper treatment is resorted to ( the administration of quinine). But the infection is very persistent, re- lapses are frequent, and in malarious regions many individuals often suffer for years from chronic mala- rial infection and finally succumb to some chronic or- ganic disease resulting from repeated attacks of fever, or from some acute disease for which a predisposition has been established as a result of continued ill-health and the anaemia which is characteristic of chronic malarial poisoning. The greatest proportional num- ber of deaths from malarial fever, within the limits of the United States, during the census year 1900 oc- curred in the "South Mississippi River belt" (88.8 per 1000 deaths from all causes) ; the next greatest in the "South Atlantic Coast region" (61.7) ; the next greatest in the "South-west Central region " (57.9) ; next in the " Gulf Coast region " (47.9) ; next in the "Southern Interior plateau" (43.8). The least mor- tality occurred in the region of the " Great Northern Lakes" (2.2); next in the "North Atlantic Coast region" (2.3); next in the "Central Appalachian region " (2.6) ; next in the " Northeastern hills and plateaus" (2.8); next in the "Pacific Coast region" (2.9). Now that we know the life history of the malarial parasite and the manner by which it gains access to the human body, the proper preventive measures are MALARIAL FEVERS 249 apparent. In general these consist in destroying the breeding-places of mosquitoes when practicable, in destroying the ova and larvae in marshes and pools of stagnant water, and in avoiding the bites of the insects. In bodies of water containing minnows and other small fish the larvae of mosquitoes are promptly dis- troyed, as they serve them as food. Frogs also feed upon mosquito larvae. Mosquitoes do not, as a rule, deposit their eggs in running streams and a perfectly smooth surface of water is required for the exit of the adult mosquito from the puparium. It is said that this may be effectually prevented by agitating the surface of the water with a water-wheel put in motion by a wind-mill. There are various temporary exped- ients by which the larvae may be killed in the breed- ing-places of mosquitoes, but evidently the most effectual remedy is to destroy the breeding-places by filling up stagnant pools, filling or draining marshes, and removing all small receptacles of water from the vicinity of dwellings. Rain-water barrels, bottles, tin cans, street catch-basins, etc., all serve as breed- ing places, especially for mosquitoes of the genus Anopheles which serve as the intermediate host of the malarial parasite. As a temporary measure the use of petroleum is to be especially recommended. This quickly spreads out over the surface of bodies of 250 INFECTION AND IMMUNITY stagnant water, whether large or small, and destroys the larvae, which are obliged to come to the surface from time to time for air. An ounce of oil is said to be sufficient for fifteen square feet of surface, and an application of this amount to be effective for about two weeks. The destruction of adult mosquitoes near dwellings may be to some extent accomplished by placing lighted lamps, in plates containing petroleum, at a little dis- tance from the house. The mosquitoes fly about the lamps and many of them are likely to fall into the petroleum, which quickly kills them. The task of kill- ing mosquitoes inside of a house is, however, far eas- ier than that of destroying those on the outside. Their entrance should as far as possible be prevented by the use of window and door screens. Those which pass these barriers should be destroyed by burning, in the closed apartments, pyrethrum powder, or by fumigation with formaldehyd gas or sulphur dioxid (formed by burning sulphur). It is especially import- ant that all mosquitoes should be killed in the autumn in houses located in malarious regions. Otherwise they are likely to hibernate and the females will serve in the spring to start a new generation of annoying and possibly dangerous pests. They are to be found not only in bedrooms, but in cellars, kitch- ens, closets, and attics. MALARIAL FEVERS 251 For the protection of individuals from the bites of mosquitoes, infected or otherwise, a mosquito-bar at night and a suitable veil of mosquito-netting in the daytime will be the most reliable resource. Various substances which are obnoxious to the insects may also be rubbed upon exposed portions of the body. Of these oil of eucalyptus is perhaps the most effica- cious. The following prescription is said to serve a useful purpose when applied to the hands and face : Ether and alcohol, of each five parts ; cologne water and oil of eucalyptus, of each ten parts ; tincture of pyrethrum fifteen parts. This is to be diluted, be- fore it is used, with four or five parts of water to one of the mixture. An infusion of quassia is also said to be useful for the same purpose. If by the measures heretofore referred to the bites of infected mosquitoes can be avoided no other pro- phylaxis will be required. But those who are unavoid- ably exposed in malarious regions and who, with all possible precautions, are unable to escape the bites of these insects will do well to take quinine in doses of six to ten grains during the day at intervals of four or five days. This is believed to be better than a daily dose of a smaller amount. CHAPTER XVII YELLOW FEVER WELLOW fever is an infectious disease which has a comparatively restricted geographic range. Occasional epidemics have occurred in North Amer- ica in every one of our seaport cities as far north as Boston and on the Mississippi River as far north as St. Louis, but it has never established itself as an endemic disease within the limits of the United States. The cities of Havana, Vera Cruz, and Rio de Janeiro have been the principal foci of the disease for many years, and from these cities it has been car- ried to the seaports of North and South America and of the West Indies. It has also prevailed for many years on the west coast of Africa, which by some authorities is regarded as the original source of this pestilential malady, while others believe that it already existed in the West Indies at the time of the discovery of these islands. The disease has never reached the east coast of Africa, and is unknown in 252 YELLOW FEVER 253 Asia. In Europe its ravages have been restricted to Spain, to which country it has several times been introduced by means of ships coming from the West Indies. In the United States several severe epidemics oc- curred in the city of Philadelphia during the latter part of the eighteenth century (1793, 1797, 1798), but since that time the ravages of the disease have, for the most part, been confined to more southern localities. During the first sixty years of the past century it prevailed almost annually in one or more of the Southern seaports of the United States and not infrequently it extended its ravages to the interior towns in one or more of the Southern States. So frequently did it prevail during the summer months in New Orleans and Charleston that the permanent residents of those cities commonly regarded it as a disease of the climate and a necessary evil which it was folly to attempt to combat by quarantine restrictions. In the great epidemic of 1853, yellow fever pre- vailed extensively in the States of Florida, Alabama, Louisiana, Mississippi, Arkansas, and Texas. The epidemic of 1867 was limited to the States of Louisi- ana and Texas. Those States again suffered severely in 1873, and the States of Florida, Alabama, and 254 INFECTION AND IMMUNITY Mississippi were also invaded. A still more extended and deadly epidemic occurred in 1878, causing a mor- tality of 15,934 out of a total number of cases exceed- ing 74,000. In this epidemic the disease followed the Mississippi River to the very suburbs of St. Louis, and the State of Tennessee suffered severely as well as the States south of it. The city of Memphis alone had a mortality from the disease of about five thousand. These repeated epidemics not only cost the lives of thousands of citizens and paralysed business of all kinds during their prevalence, but apprehension with reference to the recurrence of the disease very materi- ally interfered with the growth of many Southern cities and retarded greatly the development of those por- tions of the country most liable to invasion. All this is now changed ; public health officials are no longer filled with apprehension upon the approach of sum- mer by the thought that any ship arriving from Havana may introduce the deadly pestilence to our shores ; commerce is no longer subjected to the seri- ous restrictions formerly considered necessary for the exclusion of the disease ; and the public generally have been made aware that the fangs of this threat- ening monster have been drawn by the scientific de- monstration of its mode of attack and the simple measures which have been proved to be effective in preventing its propagation. YELLOW FEVER 255 The demonstration that yellow fever is propagated from man to man by mosquitoes of the genus Ste- gomyia was made by a board of medical officers of the United States army, which was appointed upon the recommendation of the present writer, and which prosecuted its researches in Cuba during the years 1 900 and 1 90 1 . This board consisted of Major Walter Reed, Surgeon U. S. A. ; Dr. James Carroll, Con- tract Surgeon U. S. A. ; Dr. A. Agramonte, Contract Surgeon U. S. A. ; and Dr. Jesse W. Lazear, Con- tract Surgeon U. S. A. In a " Preliminary Note," read at the meeting of the American Public Health Association, October 22, 1 900, the board gave a report of three cases of yellow fever which they believed to be the direct result of mosquito inoculations. Two of these were members of the board, viz., Dr. Jesse W. Lazear and Dr. James Carroll, who voluntarily submitted themselves to the experiment. Dr. Carroll suffered a severe at- tack of the disease and recovered, but Dr. Lazear fell a victim to his enthusiasm in the cause of science and humanity. His death occurred on September 25th, after an illness of six days' duration. About the same time nine other individuals who volunteered for the experiment were bitten by infected mosqui- toes— i. e., by mosquitoes which had previously been allowed to fill themselves with blood from yellow 256 INFECTION AND IMMUNITY fever patients — and in these cases the result was negative. In considering the experimental evidence thus far obtained, the attention of the members of the board was attracted by the fact that in the nine inoculations with a negative result, " the time elapsing between the biting of the mosquito and the inoculation of the healthy subject varied in seven cases from two to eight days and in the remaining two from ten to thirteen days, whereas in two of the three successful cases the mosquito had been kept for twelve days or longer." The inference drawn by Dr. Reed and his asso- ciates, from the experiments thus far made, was that yellow fever may be transmitted by mosquitoes of the genus Stegomyia, but that in order to convey the infec- tion to a non-immune individual the insect must be kept for twelve days or longer after it has filled itself with blood from a yellow-fever patient in the earlier stages of the disease. In other words, that a certain period of incubation is required in the body of the insect before the germ reaches its salivary glands, and consequently before it is able to inoculate an individ- ual with the germs of yellow fever. This inference, based upon experimental data, received support from other observations, which have been repeatedly made, with reference to the introduction and spread of yel- low fever in localities favourable to its propagation. YELLOW FEVER 257 When a case is imported into one of our Southern seaport cities from Havana, Vera Cruz, or some other endemic focus of the disease, an interval of two weeks or more occurs before secondary cases are developed as a result of such importation. In the light of our present knowledge this is readily understood. A certain number of mosquitoes having filled themselves with blood from this first case, after an interval of twelve days or more, bite non-immune individuals living in the vicinity, and these individuals, after a brief period of incubation, fall sick with the disease ; being bitten by other mosquitoes they serve to trans- mit the disease through the " intermediate host " to still others. Thus the epidemic extends, at first slowly from house to house, then more rapidly, as by geometrical progression. The results reported by Dr. Reed and his associates have since been fully confirmed by their subsequent experiments and by independent investigations made in Cuba and also in Brazil. Before the discovery that yellow fever is trans- mitted by mosquitoes, this disease was generally re- garded as one of the filth diseases, although there were many facts opposed to this view. In the light of our present knowledge we can no longer class it with typhoid fever, cholera, bubonic plague, and dys- entery, in which diseases the germ is known to be 258 INFECTION AND IMMUNITY present in the alvine discharges of the sick, and which are, consequently, well named filth diseases. We now see clearly, however, why in certain par- ticulars relating to its etiology it resembles the mala- rial fevers. It is limited as regards its prevalence to comparatively warm latitudes or to the summer months in more temperate regions and is dependent, to a certain extent, upon rainfall or the proximity of standing water, because these conditions are neces- sary for the propagation of mosquitoes. It is evident that in view of our present knowledge relating to the mode of transmission of yellow fever, the preventive measures which have heretofore been considered most important — i. e., isolation of the sick, disinfection of clothing and bedding, and municipal sanitation — are either of no avail or of comparatively little value. It is true that yellow-fever epidemics have resulted, as a rule, from the introduction to a previously healthy locality of one or more persons suffering from the disease. But we now know that its extension did not depend upon the direct contact of the sick with non-immune individuals and that isolation of the sick from such contact is unnecessary and without avail. On the other hand, complete isolation from the agent which is responsible for the propagation of the disease is all-important. In the absence of a yellow-fever patient from which to draw YELLOW FEVER 259 blood the mosquito is harmless, and in the absence of the mosquito the yellow-fever patient is harmless — as the experimental evidence now stands. Yellow-fever epidemics are terminated by cold weather, because then the mosquitoes die or become torpid. The sanitary condition of our Southern seaport cities is no better in winter than in summer, and if the infection attached to clothing and bedding it is difficult to understand why the first frosts of autumn should arrest the progress of an epidemic. But all this is explained now that the mode of transmission has been demonstrated. Insanitary local conditions may, however, have a certain influence in the propagation of the disease, for it has been ascertained that the species of mos- quito which serves as an intermediate host for the yellow-fever germ may breed in cesspools and sewers, as well as in stagnant pools of water. If, therefore, the streets of a city are unpaved and ungraded and there are open spaces where water may accumulate in pools, as well as open cesspools to serve as breed- ing-places for Stegomyia fasciatus, that city will pre- sent conditions more favourable for the propagation of yellow fever than it would if well paved and drained and sewered. It will be remembered that the malarial fevers are contracted as a result of inoculation by mosquitoes 260 INFECTION AND IMMUNITY of the genus Anopheles, and that the malarial para- site has been demonstrated not only in the blood of those suffering from malarial infection, but also in the stomach and salivary glands of the mosquito. If the yellow-fever parasite resembled that of the ma- larial fevers it would no doubt have been discovered long ago. But as a matter of fact, this parasite, which we now know is present in the blood of those sick with the disease, has thus far eluded all re- searches. Possibly it is ultra-microscopic. Individuals of every race and of all ages, who are exposed to infection for the first time, during the epidemic prevalence of the disease, are subject to be attacked. But there is a wide difference in the de- gree of this susceptibility among races, and among individuals of the same race. It has been 'asserted that the negro race has a con- genital immunity from yellow fever, but this is a mistake. The susceptibility of the negro is, however, much less than that of the white race, and among those attacked the mortality, as a rule, is small. Immunity is acquired by suffering an attack of the disease ; this acquired immunity is not, however, absolute. Second attacks no doubt occasionally occur, al- though this has been denied by some authors. The proper measures of prophylaxis are given in YELLOW FEVER 261 the following circular, which was submitted for my approval by the chief surgeon, Department of Cuba, and was published by the commanding general of that department. " CIRCULAR ) " HEADQUARTERS DEPARTMENT OF CUBA, " No. 5. ) " Havana, April .27, 1901. *' Upon the recommendation of the chief surgeon of the depart- ment, the following instructions are published and will be strictly enforced at all military posts in this department: "The recent experiments made in Havana by the Medical Department of the Army having proved that yellow fever, like malarial fever, is conveyed chiefly, and probably exclusively, by the bite of infected mosquitoes, important changes in the meas- ures used for the prevention and treatment of this disease have become necessary. " i. In order to prevent the breeding of mosquitoes and to pro- tect officers and men against their bites, the provisions of General Orders No. 6, Department of Cuba, December 21, 1900, shall be carefully carried out, especially during the summer and fall. " 2. So far as yellow fever is concerned, infection of a room or building simply means that it contains infected mosquitoes, that is, mosquitoes which have fed on yellow-fever patients. Disin- fection, therefore, means the employment of measures aimed at the destruction of these mosquitoes. The most effective of these measures is fumigation, with either sulphur, formaldehyd, or insect powder. The fumes of sulphur are the quickest and most effective insecticide but are otherwise objectionable. Formalde- hyd gas is quite effective if the infected rooms are kept closed and sealed for two or three hours. The smoke of insect powder has also been proved very useful; it readily stupefies mosquitoes, which drop to the floor and can then be easily destroyed. ** The washing of walls, floors, ceilings, and furniture with dis- infectants is unnecessary. " 3. As it has been demonstrated that yellow fever cannot be 262 INFECTION AND IMMUNITY conveyed by fomites, such as bedding, clothing, effects, and baggage, they need not be subjected to any special disinfection. Care should be taken, however, not to remove them from the infected rooms until after formaldehyd fumigation, so that they may not harbour infected mosquitoes. " Medical officers taking care of yellow-fever patients need not be isolated; they can attend other patients and associate with non-immunes with perfect safety to the garrison. Nurses and attendants taking care of yellow-fever patients shall remain isolated, so as to avoid any possible danger of their conveying mosquitoes from patients to non-immunes. " 4. The infection of mosquitoes is most likely to occur during the first two or three days of the disease. Ambulant cases, that is, patients not ill enough to take to their beds and remaining unsuspected and unprotected, are probably those most responsi- ble for the spread of the disease. It is therefore essential that all fever cases should be at once isolated and so protected that no mosquitoes can possibly get access to them until the nature of the fever is positively determined. " Each post shall have a ' reception ward ' for the admission of all fever cases and an 'isolation ward ' for the treatment of cases which prove to be yellow fever. Each ward shall be made mosquito-proof by wire netting over doors and windows, a ceil- ing of wire netting at a height of seven feet above the floor, and mosquito-bars over the beds. There should be no place in it where mosquitoes can seek refuge, not readily accessible to the nurse. Both wards can be in the same building, provided they are separated by a mosquito-tight partition. " 5. All persons coming from an infected locality to a post shall be kept under careful observation until the completion of five days from the time of possible infection, either in a special de- tention camp or in their own quarters; in either case their tem- perature should be taken twice a day during this period of observation, so that those who develop yellow fever may be placed under treatment at the very inception of the disease. " 6. Malarial fever, like yellow fever, is communicated by mos- quito bites and therefore is just as much of an infectious YELLOW FEVER 263 disease and requires the same measures of protection against mosquitoes. On the assumption that mosquitoes remain in the vicinity of their breeding places, or never travel far, the pre- valence of malarial fever at a post would indicate want of proper care and diligence on the part of the surgeon and commanding officer in complying with General Orders No. 6, Department of Cuba, 1900. " 7. Surgeons are again reminded of the absolute necessity, in all fever cases, to keep, from the very beginning, a complete chart of pulse and temperature, since such a chart is their best guide to a correct diagnosis and the proper treatment. " BY COMMAND OF MAJOR-GENERAL WOOD. " H. L. SCOTT, "Adjutant-General." The practical execution, in the city of Havana, by Major1 Gorgas, Surgeon U. S. A., chief sanitary offi- cer of the city during its occupation by our troops, of the measures indicated in the above circular was attended with entire success. For more than two years this city has been entirely free from cases of yellow fever, while for many years prior to the date when Major Gorgas inaugurated his war upon in- fected mosquitoes the disease had prevailed to a greater or less extent annually and a certain number of deaths had occurred every month in the year. 1 Now Colonel Gorgas, by special act of Congress, as a reward for his services. CHAPTER XVIII WOUND INFECTIONS /CERTAIN of the diseases heretofore considered ^-^ may be communicated to man by inoculation and are occasionally contracted by the accidental inoculation of wounds or abrasions. Thus we may have a tubercular infection of the skin (" lupus") ex- tending sometimes to adjacent lymphatic glands, or a localised diphtheritic process, upon any portion of the surface of the body. But in the present chapter we propose to consider certain localised or general infectious diseases which as a rule have their origin through the accidental introduction of pathogenic bacteria into an open wound or upon an abraded surface. Before the days of antiseptic surgery such accidental inoculations were much more frequent than at present. Erysipelas, hospital gangrene, suppura- tion, septicaemia (" blood-poisoning "), and tetanus were of frequent occurrence and the mortality from certain surgical operations which are now almost free 264 WOUND INFECTIONS 265 from risk was often excessive. These facts are well known to the public and it is also generally known that when a wound made by the surgeon, or the result of accident, suppurates or gives rise to fever, it is because it has become infected. The germs which usually give rise to wound infection have been care- fully studied by bacteriologists and are now well known. The two most common species, which are responsible to a large extent for the suppuration of wounds, for erysipelatous inflammation, and for "blood- poisoning," are widely distributed and are commonly found upon the surface of the body and of mucous membranes in healthy persons. One of these is a micrococcus which, when cultivated in artificial media, is recognised by the fact that it forms masses of a golden-yellow colour. These masses are made up of minute spherical cells which adhere to each other in irregular grape-like bunches — hence the technical name Staphylococcus pyogenes aureus. The other is also a micrococcus in which the spherical cells are united in chains, like strings of pearls. This is called Streptococcus pyogenes. This latter is also called the streptococcus of erysipelas because it has been demon- strated to be the cause of erysipelatous inflammations. These two species of pathogenic bacteria give rise to a great variety of infectious processes. Both are found, either separately or associated, in the pus of 266 INFECTION AND IMMUNITY abscesses, in boils and carbuncles, in suppurating wounds, in puerperal fever, in peritonitis, in suppur- ative disease of the ear, in general blood-poisoning, etc. As in other infectious diseases infection by these pathogenic micrococci (so-called " pus cocci ") depends upon three factors, viz. : the virulence of the germ ; FlG. 10. Micrococcus of pus-formation {Staphylococcus pyogenes aureus) ; magnified 1000 diameters. the vital resistance of the tissues invaded ; and the number of germs introduced into an open wound. The virulence of the germs is much greater when they come from a suppurating wound, from a case of erysipelas or of puerperal fever, or, in short, from any infectious process in the body, than when they come from the mouth or the surface of the body where they WOUND INFECTIONS 267 have been living a saprophytic existence. Here it may be necessary to explain that a saprophytic bac- terium is one which exists independently of a living host and which obtains its supply of nutriment from dead animal or vegetable material, while a parasitic bacterium is one which invades the body of a living animal and receives its nourishment at the expense of FIG. II. Micrococcus of erysipelas, etc. {Streptococcus pyogenes) ; magnified 1000 diameters. the tissues and body fluids of its " host." But certain bacteria, like those at present under consideration, may live either as saprophytes or as parasites. Their ability to effect a lodgment in the tissues and multiply there, after having led a saprophytic life for some time, is favoured by a reduction in the vital resisting power of the individual as a result of various 268 INFECTION AND IMMUNITY depressing agencies — alcoholism, insufficient nourish- ment, loss of blood, etc.; or by a diminished vital re- sistance at the point of invasion as a result of injury to the tissues by bruising, by burns, by various chemical agents, etc. When, however, these bacteria have been leading a parasitic life for some time they have a greatly increased virulence, as manifested by their ability to invade the tissues of healthy individuals whenever they find a portal of entrance. Under such circum- stances, also, infection may result from the introduction of a very small number of germs, whereas a compara- tively large number would be required in case the micrococci had for some time been leading a sapro- phytic existence. Fortunately for the human race the blood serum of healthy persons has the power of destroying a limited number of pathogenic bacteria of a low grade of viru- lence. But when these germs come directly from the seat of an infectious process, especially in the case of the streptococcus, a very small number may give rise to a rapidly extending and deadly blood infection - for example the blood-poisoning resulting from punc- ture of the skin with a needle during an autopsy of a case of erysipelas or of puerperal fever, or from a surgical operation upon a patient suffering from any form of streptococcus infection. Many pathologists WOUND INFECTIONS 269 and surgeons have suffered serious and often fatal results from such an apparently insignificant wound. Antiseptic surgery has for its object the destruction of all bacteria in wounds or attached to objects which are brought into contact with wounds, such as the hands and instruments of the surgeon, surgical dress- ings, etc. This is accomplished by the use of chem- ical agents of established germicidal value, which must be used in such a proportion as will insure the destruction of germs, and which will not have an injurious effect upon the vitality of the tissues and the healing process. The principal agents which have been used for this purpose are carbolic acid and corrosive sublimate (mercuric chloride) in solutions of proper strength. There are certain objections to the use of either of these agents in solutions strong enough to promptly destroy disease germs, especially when applied to wounds of considerable magnitude. For this reason antiseptic surgery has to a considerable extent been superseded by aseptic surgery^ which ac- complishes the same result without the application of chemical agents of any kind to the wound surfaces. Instruments and dressings are rendered sterile by heat, usually in a steam steriliser. The hands of the surgeon and the " field of operation " are thoroughly scrubbed with soap and water and then washed in an antiseptic solution to insure the destruction of germs 270 INFECTION AND IMMUNITY attached to the skin. Usually this is followed by washing with alcohol and sterile water to remove all traces of the antiseptic. Many surgeons at the pre- sent day prefer to wear india-rubber gloves while operating, as it has been found by experience that it is a difficult matter to thoroughly sterilise the hands. Such gloves are easily cleaned and sterilised. By the " field of operation " is meant the surface of the body in the vicinity of the incisions which are to be made in any surgical operation. This surface is cleaned as thoroughly as possible and other portions of the body are covered with a clean sheet or sterile towels. When the operating-room and its fixtures are " surgically clean " and all necessary precautions are taken with reference to instruments, dressings, the surgeon's hands, etc., an operation wound is ex- pected to heal promptly by adhesion of the wound surfaces, which have been brought together and re- tained by sutures or adhesive plaster, and bandages when necessary. Such wounds treated aseptically rarely suppurate. When they do it is because some of the bacteria which cause pus formation have found their way into the wound in spite of the precautions taken. It is more difficult to prevent suppuration in gunshot wounds and in extensive lacerations resulting from railway accidents, etc. The bruising of the tissues in WOUND INFECTIONS 271 such cases renders them less able to resist infection and less apt to unite by adhesion. It often happens, also, that the wound is infected at the time it is inflicted. Thus in a gunshot wound a portion of the clothing to which numerous germs are attached may be carried into the wound. Or the bullet itself may be infected, although this is no doubt of rare occurrence. Lacerated wounds are often inflicted with stones, pieces of wood, or other objects which have dirt adhering to them, which may contain various patho- genic bacteria, and which are liable to remain lodged in the wound. Such a wound may be cleansed and rendered aseptic by being thoroughly washed with sterile water (boiled or distilled), or it may be washed with an antiseptic solution and treated with antisep- tic dressings to prevent the development of any bac- teria which may chance to remain hidden away in the wound. CHAPTER XIX TETANUS A FORM of wound infection of special interest, be- cause of the very serious results which usually follow such infection, is that by the bacillus of tetanus, which gives rise to the disease commonly known as lockjaw. The bacillus of tetanus was discovered in 1884, by a student (Nicholaer) in the laboratory of Professor Fliigge of Gottingen. Having introduced small quan- tities of garden earth under the skin of mice and of guinea-pigs, some of these animals died with all the characteristic symptoms of tetanus. Subsequent re- searches have established the fact that in temperate and tropical regions the bacillus of tetanus is widely distributed and is commonly present in rich soil which has been manured. It is also present in the dust of city streets, and there is good reason to believe that its being found there is due to the fact that it is present in the intestinal contents of horses. 272 TETANUS 273 Formerly tetanus was supposed to be due to injury to the nerves, and the idea that it is an infectious disease, due to the introduction of a specific bacillus into a wound, had not been entertained prior to the demonstration that the symptoms which characterise this disease may be produced in the lower animals by inoculating them with garden earth or with a pure FIG. 12. Bacillus of tetanus ; magnified 1000 diameters. Spores are seen at the ends of some of the bacilli. culture of the tetanus bacillus. The nervous symp- toms are now known to be due to the fact that the tetanus bacillus produces a deadly poison (toxin) which has a special affinity for the nervous tissues. When a barefooted boy steps upon a rusty nail and, as a re- sult of the penetrating wound inflicted by it, develops tetanus, this result is not due to the fact that the nail 18 274 INFECTION AND IMMUNITY was rusty, or that a nerve had been injured, but to the introduction of earth containing the tetanus ba- cillus, which would more readily adhere to the rough surface of a rusty nail than to a new and clean one. The nature of the wound made is also favourable to in- fection, as the bruised tissues are not likely to bleed much, and the deep wound with a narrow orifice is well calculated to retain any foreign matter introduced at the time the injury was inflicted. Unlike the vari- ous pathogenic bacteria heretofore referred to, the tetanus bacillus will not grow in the presence of oxy- gen. It therefore cannot grow in open wounds exposed to the air, and is incapable of develop- ment in the blood of a living animal. It differs in another particular, also, viz., in the formation of "spores," which are developed in the rods — one at the end of each bacillus. These are spherical, highly refractive bodies, which resist desiccation, and may retain their vitality for months and probably for years when present in surface soil or in dust. A temperature of 212° Fahr. is required for their destruction. When a needle is dipped into a pure culture of the tetanus bacillus, and a mouse is inoculated with it, subcutaneously, the animal falls sick within twenty- four hours and dies of typical tetanus in two or three days. The tetanic symptoms are first developed in TETANUS 275 the vicinity of the point of inoculation. In inoculated animals, and in tetanus in man resulting from acci- dental infection, the bacillus may be obtained in the vicinity of the inoculation wound, but is not present in the blood or in the various organs of the body. The presence of the deadly tetanus toxin may, how- ever, be demonstrated by injecting the blood of a victim of the disease into a mouse, which dies with the characteristic tetanic symptoms after such an in- oculation. The fatal dose of this toxin is so small that, according to the Japanese bacteriologist Kita- sato, the amount of a culture, from which all living germs have been removed by filtration, which is re- quired to kill a mouse is not more than one hundred- thousandth of a cubic centimetre (o.ooooi c.c.). The tetanus poison is destroyed by five minutes' exposure to a temperature of 65° C. It is also destroyed by exposure to direct sunlight, but it may be kept inde- finitely in a cool dark place. The German chemists, Brieger and Cohn, have obtained the toxin in a pre- cipitated and comparatively pure state, in the form of yellowish transparent scales, which are readily soluble in water. They report that this purified toxin will kill a mouse in the dose of 0.00000005 gram, and they estimate that 0.00023 gram would be a lethal dose for a man. Comparing this with the most deadly vegetable alkaloids known, it is nearly six hundred 276 INFECTION AND IMMUNITY times as potent as atropin and one hundred and fifty times as potent as strychnin. It has long been known that persons who go bare- foot are more liable to contract tetanus than those who wear shoes. This is shown by the difference in the mortality between native soldiers and English troops in India. Statistics show that the mortality is higher among males than among females. This, of course, depends upon the fact that they are more out- of-doors and are more likely to receive accidental wounds. It is a rather remarkable fact that in the United States more deaths occur from tetanus in cities than in the rural districts. This is no doubt largely due to the considerable number of fatal cases of tetanus which occur among boys as a result of lacerated wounds of the hand made by toy pistols, which are so popular as a means of celebrating Inde- pendence Day. The use of these pistols has now been prohibited by several State Legislatures. Dr. Park of Buffalo, who has given special attention to the subject, re- ports that in Chicago during the month of July, 1881, sixty cases of tetanus occurred as a result of injuries inflicted by toy pistols. In New York City there were, from the same cause, 38 cases in 1899, 33 cases in 1900, and 27 cases in 1901. During our Civil War the total number of cases of TETANUS 277 tetanus reported, as a complication of gunshot wounds, was 505. This is about one case in every five hundred cases of gunshot injury. The proportion has been much greater in wars conducted by other armies in tropical countries. The total number of deaths from tetanus in the United States during the census year 1900 was 2259, of whom 1516 were males and 743 females. This includes the deaths from " trismus neonatorum" — tetanus of the new-born. Among the poorer classes in southern localities, and especially among the coloured population, tetanus not infre- quently results in the new-born from infection through the navel. In the registration area the high- est mortality from tetanus occurred in the States of Vermont and New Jersey. That the mortality re- ported is chiefly among new-born infants is shown by the fact that of the total number of deaths, 1 1 7. 7 per 100,000 were among children under one year of age, while the mortality between the ages of five to fourteen was only 3.7, and between fifteen and forty-four only 1.7 per 100,000 of these ages. The victims of the toy pistol are, for the most part, included in the group between the ages of five and fourteen. The deaths below the age of one year, constituting a large share of the total num- ber, may justly be classed as victims of dirt. The number of deaths among the new-born was still 278 INFECTION AND IMMUNITY greater in the non-registration area, which includes the Southern States — viz., 234.5 per 100,000 infants in cities. The death-rate among coloured infants was far in excess of that among whites — in the registra- tion area: 77.6 whites, 1233.4 coloured, per 100,000 children under one year of age. The facts stated indicate the proper preventive measures in this infectious disease : the thorough cleansing of all wounds and especially of penetrating and lacerated wounds and the use of antiseptic dress- ings by which the multiplication of the tetanus ba- cillus will be prevented, if by chance it has been introduced ; the banishment of the deadly toy pistol ; cleanliness and antiseptic dressings of the navels of new-born children ; and last, but not least, the educa- tion of the public generally as to the manner in which wounds become infected with the tetanus bacillus and the great danger attending such infection. CHAPTER XX HYDROPHOBIA A N OTHER fatal form of wound infection may ** result from the bite of a rabid animal — " hydro- phobia." The germ of this infectious malady has not been discovered, but it has been demonstrated by ex- periment that it is present in the saliva of rabid animals and in the nervous tissues — brain and spinal cord — of men and animals who succumb to the dis- ease. A considerable interval elapses after inocula- tion before the first symptoms of the disease are manifested. This period of incubation varies greatly in its duration, but is rarely less than two weeks or more than six months. By far the largest majority of the cases are developed within three months from the time the bite is inflicted. In the dog the period of incubation usually does not exceed two months. When numerous and severe lacerations have been inflicted, especially if these are upon the face, the disease is apt to develop at a comparatively early 279 280 INFECTION AND IMMUNITY date. Bites upon the extremities, especially when the teeth of the rabid animal have passed through the clothing, by which the virus is to some extent re. moved, are less likely to be followed by an attack of hydrophobia. Among the lower animals the following have been demonstrated to be susceptible to rabies : dogs, cats, cattle, sheep, horses, goats, swine, mice, rabbits, guinea-pigs, skunks. Man usually contracts the disease through the bites of dogs, cats, or wolves, and occasionally of skunks. A considerable proportion of those who are bitten by rabid animals may escape the disease, especially when the bites are upon the extremities and are not severe. Prompt cauterisation of the wound also has the effect of reducing the proportion of these attacks. The popular idea that dogs are especially liable to go mad in summer, during "the dog days," appears not to be well founded, as it may prevail at any season, and dogs do not go mad any more than men, unless they have been bitten by a rabid animal and the virus of the disease has been introduced into the wound ; or, as has occasionally happened, the infectious ma- terial has been introduced into an accidental wound inflicted in some other way. It has been claimed that certain parts of the world are free from rabies and that it does not prevail in HYDROPHOBIA 281 Egypt or in the city of Constantinople, which is noted for the number of its homeless dogs. But this is denied by other authorities and it is said to have been very prevalent in the city of Constantinople in 1839. Like other infectious diseases its prevalence varies greatly at different times and depends to a consider- able extent upon the measures taken to prevent its extension — such as the muzzling of dogs and the destruction of those without owners. In northern Europe rabies from the bite of a mad wolf is of not infrequent occurrence and the disease is also occasionally contracted as a result of bites inflicted by foxes, jackals, and ferrets. Wild animals during the excited stage of the disease lose their fear of man and are liable to run through frontier settlements and military posts, and to bite men and animals encoun- tered on their way. A most effectual way of resisting the spread of rabies is by the general muzzling of dogs allowed to run at large. The results of this preventive measure as applied in Great Britain are given below. Accord- ing to official reports the number of fatal cases of rabies in 1887 was 217; in 1888, 160; in 1889, 312- This increase in the number of deaths from hydro- phobia caused much alarm and led to the enforce- ment of regulations for the muzzling of dogs. As a result of this the number of cases fell to 129 in 1890; 282 INFECTION AND IMMUNITY 79 in 1891, and 38 in 1892. There was at this time much opposition to the muzzling ordinance and it was not enforced. As a result of this the number of cases again increased until in the year 1895 it reached high- water mark, 672 cases. Again the muzzling ordinance was enforced, with the result that the number of cases fell to 17 in 1898 ; 9 in 1899, and zero in 1900. The number of deaths from rabies in the United States is not shown in the census reports, the cases being no doubt included under the heading, " Other Causes." In the census of 1900, 33,776 deaths are included under this heading. It is unfortunate that we have no exact statistics with reference to this disease, inasmuch as its exist- ence has been denied by certain members of the medical profession. It is difficult to understand the mental operations of those who deny the existence of hydrophobia, the value of vaccination, and other well-established facts, except in the case of those who are ignorant. But for certain minds the logic of facts appears to have no weight as opposed to prejudice and preconceived theories. That there is an infectious disease, known to us as rabies, which is communicated from one ani- mal to others and from rabid animals to man, by the introduction of infectious material contained in the salivary secretions into a wound — usually inflicted by HYDROPHOBIA 283 the rabid animal's teeth — is as well established as any fact in medicine or in history. But fortunately the disease is rare and comparatively few physicians have been called upon to treat a case of it. It is reported that ninety-one persons have died of hydrophobia in the city of Chicago during the past ten years. The disease was known to the ancients and is very clearly described by Celus (B.C. 21). As long ago as 1813 the French physicians Magendie and Bouchet produced rabies in dogs by inoculating them with saliva obtained from a man suffering from hydro- phobia. But our exact knowledge of the disease dates from the researches of the famous French chemist, Pasteur (1881 to 1886). Pasteur first an- nounced his success in reproducing rabies in suscept- ible animals by inoculations with material from the nervous system — brain, spinal cord — in a communica- tion made to the French Academy of Sciences on May 30, 1 88 1. At the same time he reported his success in the discovery of " a method for consid- erably shortening the period of incubation in rabies and also of reproducing the disease with certainty." This was by inoculations, made after trephining, upon the surface of the brain, with material obtained from the brain of a rabid animal. Dogs inoculated in this way developed rabies in the course of two weeks and died before the end of the third week. In 284 INFECTION AND IMMUNITY a second communication (December n, 1882) Pasteur reported his success in communicating the disease by intravenous injections of virus obtained from the central nervous system of rabid animals ; also the experimental demonstration of the fact that all forms of rabies may be produced by the same virus ; also, that all parts of the spinal cord of rabid animals are virulent, as well as all parts of the brain ; also that an animal (dog) which had recovered from a mild attack after inoculation proved to be subsequently immune, and that "this observation constitutes a first step toward a discovery of the prophylaxis of rabies." In a subsequent communication (May 19, 1884) Pasteur presented evidence which demonstrated the fact that by successive inoculations in monkeys the period of incubation is prolonged and the virus of the disease attenuated ; that this attenuated (milder) virus from the monkey when inoculated into a dog no longer produces fatal rabies ; and that dogs so treated are subsequently immune. Having demonstrated these important facts Pas- teur determined to make a test experiment which should convince the scientific world of the truth and value of his discoveries. At his request a commission was appointed by the Minister of Public Instruction to determine the efficacy of his method as applied to the protection of dogs. In his address before the HYDROPHOBIA 285 International Medical Congress at Copenhagen (Au- gust 11, 1884) Pasteur gives the following account of the results of this test experiment. He says that he gave to the commission nineteen dogs which had been rendered immune against rabies by preventive inoculations. These nineteen dogs and nineteen control animals, obtained from the public pound, without any selection, were tested at the same time. The test was made upon some of the animals of both series by inoculations with virulent material from rabid animals, made upon the surface of the brain, by trephining ; and upon others by allowing them to be bitten by rabid dogs ; and upon still others by intra- venous inoculations. Not one of the protected ani- mals developed rabies ; on the other hand, three of the control animals out of six bitten by mad dogs developed the disease ; five out of seven which re- ceived intravenous inoculations died of rabies ; and five which were trephined and inoculated upon the surface of the brain died of the same disease. In a subsequent report the commission, of which M. Bouley was president, stated that twenty-three dogs, which had been protected, were bitten by mad dogs and that all remained in perfect health, while sixty-six per cent, of the control animals, bitten in the same way, developed rabies within two months. Evidently this method could be applied upon a 286 INFECTION AND IMMUNITY large scale for the prevention of rabies among dogs, and if these animals were thus protected, rabies would soon become practically extinct. The method is even more reliable than vaccination as a protection against smallpox. But its practical application on a large scale would be attended with great difficulties and would, no doubt, be opposed by a large proportion of the owners of dogs. There has, therefore, so far as I am informed, never been any attempt to apply this discovery of Pasteur's in a practical way for the prevention of rabies. But these preliminary experi- ments led to the discovery that animals and man may be rendered immune to the disease by protective in- oculations made after they have been bitten by a rabid animal. I shall not attempt to give an account of the experiments which led Pasteur to this im- portant discovery or of the methods employed for obtaining an attenuated virus, but will content myself with a summary statement of the results which have been attained in the practical application of this method of prevention. It is probably generally known that " Pasteur Insti- tutes" for the treatment of persons bitten by rabid animals have now been established in all parts of the civilised world. During the year 1891, 1564 persons were inoculated at the Pasteur Institute in Paris with a total mortality of 0.57 per cent. In 324 of HYDROPHOBIA 287 these cases the animal which inflicted the bite was proved to be rabid by experimental inoculations made in other animals — with an emulsion of the brain or spinal cord. This is now generally recog- nised as a conclusive demonstration that an animal, or man, from whom such virulent material has been obtained, was a victim of rabies. Perdrix (1890) in an analysis of the results obtained at the Pasteur Institute in Paris calls attention to the fact that the mortality among those treated has dimin- ished each year and ascribes this to improvements in the method employed. In the cases with severe wounds upon the head and face larger doses of the virulent material are used at more frequent intervals. Perdrix gives the following statistics with reference to the location of the bite as influencing the results of treatment. Bitten upon the head, 684; died, 12 = 1.75 Bitten upon the hands, 4396; died, 9 = 0.2 % Bitten upon the limbs, 2839; died, 5 = 0.17 # Recently the statistics of the Pasteur Institute in Paris for a period of sixteen years (1886 to 1901) have been published. During this period 112 deaths occurred among 25,986 persons inoculated — a mor- tality of 0.43 %. It is not claimed that all of the inoculated had been bitten by rabid animals. In many cases it is impossible to ascertain whether the 288 INFECTION AND IMMUNITY animal which inflicted the bite was really mad. But the cases in which satisfactory experimental proof has been obtained are considered separately in the statistics of the Pasteur Institute. Thus, in the year 1901, 171 persons were treated who had been bitten by animals proved to be rabid, and among these not a single death occurred. INDEX Acquired immunity, 73 Alcohol as an antiseptic, 41 Amoebic dysentery, 140 Anopheles, 235 Anthrax, 23 Antiseptic, definition of, 29 — surgery, 269 Antiseptics, 41 Antitoxin of diphtheria, 198 Antitoxins, 82 Aseptic surgery, 269 Asiatic cholera, 1 10 Attenuation of virulence, 64, 78 Bacilli, 10 Bacillus of bubonic plague, 101 — diphtheria, 193 — influenza, 200 — leprosy, 182 — tetanus, 273 — tuberculosis, 160 — typhoid fever, 136 Bacteria, 37 — multiplication of, II — structure of, 13 — spores of, 12 Bichloride of mercury, 61 Black death, 91, 93 Bleaching powder, 60 Blood-poisoning, 20 — germs of, 265—269 Blood serum, germicidal action 68, 268 19 of, Breathing exercises, 176 Bubonic plague, 89 — bacillus of, 101 — in Philippine Islands, IO2 — mortality from, 94-98 — period of incubation, 105 — prevention of, 108 — protective inoculations, 107 Carbolic acid as a disinfectant, 59 Caustic alkalies as disinfectants, 58 Channels of infection, 14 Chicken-pox, 221 Children, susceptibility of, 25 Chloride of lime, 60 Chlorin as a germicide, 56, Chlorinated lime, 60 Cholera, no — germs of, 120 — in America, ni-n6 — origin of epidemics, 117, 118 — predisposing causes, llS — protective inoculations, 124 — recent epidemics, 116 Cholera germ, description of, 120 — destruction of, 118, 122 — discovery of, I2O — infection by, 118, 119 Cholera infantum, 140 Citric acid as a germicide, 57 Climate in treatment of consumption, 177 Clothing, disinfection of, 47 289 290 INDEX Clothing, infection through, 18 Coal-tar products as germicides, 59 Cold, action of, on bacteria, 46 Colonies of bacteria, 1 1 Comma bacillus, 120 Contagion, definition of, 3 Corrosive sublimate as a disinfectant, 61 Creolin as a disinfectant, 60 Cresol as a disinfectant, 60 Culture experiments, 37 — fluids, 38 Cuspidors for consumptive patients, 171, 172 Deodorants, 30 Desiccation of bacteria, 46 Diphtheria, 191 — animals susceptible to, 192 — antitoxin of, 198 — bacillus of, 193 — disinfection in, 195 — mortality from, 194 — prevention of, 195 — propagation of, 191 Diphtheria bacillus, 193 — destruction of, 195 — discovery of, 192 — varieties of, 192 Disease germs. 8 — dates of discovery, 148 Disinfectant, definition of, 28 Disinfection, 28 — by gases, 51 — evidence of, 34 — in bubonic plague, 108 — in cholera, 122, 123 — of bed-linen, 60 — of clothing, 47 — of excreta, 47, 60 — of sick-room, 51-53, 174 — of sputa, 171 — tests of, 32 Dry heat as a disinfectant, 44 Dust, infection through, 16, 51 Dysentery, 140 — mortality from, 141 . Ehrlich's side chain theory, 85 Electric light, germicidal action of, 49 Epidemics, termination of, 99 Eruptive fevers, 17 Erysipelas, germ of, 266, 267 Excreta, disinfection of, 47, 60 Famine fever, 151 Filth diseases, 103, 126 Flies, as carriers of infection, 18 Fomites, 3 Formaldehyd as a disinfectant, 54 Fumigation, 53 German measles, 233 Glanders, 24 Heat, disinfection by, 43 Hospital gangrene, 19 Hydrophobia, 279 — mortality from, 282 — Pasteur's experiments, 283 — period of incubation, 279 — prevention of, 281 — protective inoculations, 283-288 — susceptible animals, 280 — transmission of, 284 Immunity, acquired, 73 — due to alkalinity of blood, 67 — due to body temperature, 66 — natural, 63 Infection, definition of, 4, 7 — general remarks upon, 3 Influenza, 199 — bacillus of, 200 — bacillus, destruction of, 204 — complications of, 200 — epidemics of, 200-202 INDEX 291 Influenza, incubation period, 2O2 — mortality from, 199, 200 — predisposing causes, 202 — prevention of, 203 Inoculation for smallpox, 76 Lepers, isolation of, 189 Leprosy, 181 — bacillus of, 182 — disinfection in, 190 — history of, 186 — in Great Britain, 187 — in India and China, 187 — in Norway, 188 — in United States, 189 — inoculation experiments, 182 — transmission of, 186 Leucocytes, phagocytic action of, 71 Lime as a disinfectant, 59 Lye as a disinfectant, 58 Lysol, 60 Malaria, 235 Malarial fevers, 234 — fevers, geographic distribution of, 245 — fevers, mortality from, 247 — fevers, period of incubation. 240 — fevers, prevention of, 249-251 — fevers, seasonal prevalence of, 246 — parasite, 237, 241 — parasite, discovery of, 234 — parasite, varieties of, 240-242 Measles, 228 — complications of, 230 — disinfection in, 230, 231 — mortality from, 229 — period of incubation, 228 — prevention of, 231 — second attacks, 233 Membranous croup, 194 Metchnikoff's theory, 72 Micrococci, 16 Micrococcus of erysipelas, 265, 267 — of pneumonia, 206 — of pneumonia, discovery of, 205 — of pneumonia, where found, 208 — of puerperal fever, 266 Micro-organisms, 8 Milk, antitoxins in, 82 — from tuberculous cows, 175 Mineral acids, as germicides, 57 Mortality of armies, 129, 143 Mosquitoes, infection by, 21 — malarial parasite in, 243 — transmission of yellow fever by, 255 Mucous membrane, infection through, 21 Natural immunity, 63 Oysters, infection by, 18 Pasteur Institute, statistics of, 287, 288 Period of incubation, 6 Phagocytosis, 71, 72 Plasmodium malariae, 237 Pneumonia, 205 — epidemics of, 209 — in Chicago, 207 — in United States, 206 — mortality from, 207 — predisposing causes, 206 — prevention of, 210 Pocket flasks for consumptives, 172 Potash as a germicide, 58 Protective inoculations, 75-78 — inoculations in bubonic plague, 107, 108 — inoculations in cholera, 124 — inoculations in typhoid fever, 139 Protophyta, 10 Protozoa, 10 Ptomaines, 30 292 INDEX Puerperal fever, germ of, 266, 267 Pulmonary consumption, mortality from, 160-162 Pure cultures, 38 Race susceptibility, 24 Rats as agents in spread of plague, 104 Relapsing fever, 145 — epidemics of, 146, 147 — germ of, 148 — in United States, 147 — predisposing causes, 151 — prevention of, 152 Salt as an antiseptic, 41 Sanitoria in treatment of tubercu- losis, 169 Saprophytes, 86, 267 Scarlet fever, 223 — history of, 223 — how communicated, 223 — mortality from, 225 — prevention of, 226 Second attacks of infectious diseases, 73-74 Septicaemia, 19 Sewers, sanitary value of, 127 Ship fever, 157 Sick-room, disinfection of, 51 Skin, infection through, 21 Smallpox, 214 — disinfection in, 220 — duration of, 220 — germ of, 219 — history of, 214 — mortality from, 215 — second attacks of, 74 Snake poison, antitoxin of, 85 Soda as a germicide, 59 Spirilla, 10 Spirillum of cholera, 121 — of relapsing fever, 149 Spores, 12, 39 — of tetanus bacillus, 273, 274 — resistance to heat, 44 Sputum, disinfection of, 171 Staphylococcus pyogenes aureus, 265 Steam as a disinfectant, 44 Streptococcus pyogenes, 267 Summer complaint, 140 Sulphate of copper as a germicide, 62 — iron as a germicide, 29 Sulphur fumigation, 53, 54 Sulphurous acid as a germicide, 58 Sunlight as a disinfectant, 48 Susceptibility, individual, 25 — due to alcoholism, 68 — race, 23 Surra disease, 22 Tetanus, 272 — bacillus of, 273 — mortality from, 276-278 — toxin, 273-275 Texas fever, 21 Thermal death-point of bacteria, 45 Ticks, infection by, 21 Tonsils, infection through, 15 Toy pistols, danger of, 276 Trichinosis, 19 Trismus neonatorum, 277 Tsetse-fly disease, 22 Tubercle bacillus, 160 — destruction of, 176 — discovery of, 159 — in milk, 175 Tubercular joint disease, 163 Tuberculosis, 159 — communication of, 159-163 — in Europe, 166 — in New York City, 161, 178 — influence of occupation, 165 race, 166 — mortality from, 160, 162 — of bowels, 163 — predisposing causes of, 164 INDEX 293 Tuberculosis, prevention of, 170 — susceptibility to, 164 — treatment of, 167 Typhoid bacillus, discovery of, 136 — description of, 136 — destruction of, 138 — in urine, 135 Typhoid fever, 126 — bacillus of, 138 — mortality from, 126-134 — preventive inoculations, 139 — second attacks of, 74 Typhus fever, 154 — causes of, 157 — epidemics of, 154-156 — in United States, 156 — mortality from, 158 Uncinaria Americana, 142 United States Army, mortality in, 143 Urine, typhoid bacilli in, 135 Vaccination, 76, 221 — discovery of, 218 — value of, 216-218 Vaccine virus, 36 Violet light, germicidal action of, 49 Water-born diseases, 15 Water supply, infection of, 133 Whitewash as a disinfectant, 59 Whooping-cough, 211 — mortality from, 212 — prevention of, 213 Wound infections, 19, 264 Yellow fever, 252 — board to investigate, 255 — epidemics in United States, 253- 254 — geographic range, 252-254 — prevention of, 258-265 — transmission of, 255 The Science Series Edited by Professor J. 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