rfr*Jr**f*F0 CORNELL UNIVERSITY. L THE THE GIFT OF ROSWELL P. FLOWER FOR THE USE OF THE N. Y. STATE VETERINARY COLLEGE. 1897 CORNELL UNIVERSITY LIBRARY 3 1924 057 010 559 The original of this book is in the Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924057010559 THE PATHOLOGY <«*■ DIFFERENTIAL DIAGNOSIS INFECTIOUS DISEASES OF ANIMALS By VERANUS ALVA MOORE, B.S., M.D. Professor of Comparative Pathology, Bacteriology and Meat inspection, New York State Veterinary College, Cornell University, Ithaca, N. Y. WITH AN INTRODUCTION BY DANIEL ELMER SALMON, D.V.M. Former Chief of the Bureau of Animal Industry, United States Department of Agriculture. SECOND EDITION REVISED AND ENLARGED ILLUSTRATED ITHACA, N. Y. TAYLOR & CARPENTER 1906 T PRESS OF JOURNAL JOB DEPARTMENT ITHACA, N. Y. Ho. i as© Copyright, 1906. By Veeanus Alva Moore. Sf 7*/ TO DANIEL ELMER SALMON LARGELY THROUGH WHOSE LABORS THERE WAS ES- TABLISHED IN THE UNITED STATES DEPARTMENT OF AGRICULTURE THE BUREAU OF ANIMAL INDUSTRY WHICH HAS MADE POSSIBLE EXTENSIVE INVESTIGA- TIONS INTO THE NATURE OF EPIZOOTIC DISEASES IN AMERICA AND WHO FOR TWENTY-ONE YEARS DIRECTED THESE INVESTIGATIONS THIS VOLUME IS DEDICATED. PREFACE. The time that has elapsed since the publication of the first edition of this volume has been fruitful of results in the study of the various infections of animals. A number of dis- eases have been more thoroughly investigated and consequently much new subject matter has been made available. With the rapid accumulation of new knowledge of the nature of the infectious diseases of animals, the preparation of a text-book suitable for student use becomes more and more difficult. In this revision the general plan of arrangement of subject matter and the system of classifying diseases that were adopted in the first edition have been retained. A continued study of these affections has strengthened the conviction of the writer that the most natural grouping of these maladies for purposes of study and instruction is in accordance with their etiological factors. I desire to express my full appreciation of the kind recep- tion given the first edition and the helpful reviews and criti- cisms that were accorded to it. It is hoped that this edition will be of greater aid to both student and practitioner than the former one. My thanks are especially due to Dr. S. H. Burnett for helpful suggestions and for assistance in reading proof. V. A. M. PREFACE TO THE FIRST EDITION/ The literature on infection and the etiology and morbid anatomy of infectious diseases of animals is exceedingly rich in the results of new discoveries and important investigations. However, students just beginning this study and following a prescribed curriculum have not the time nor are they prepared to read with profit the detailed records of original research. Such publications seem to be better adapted for those doing advancd or graduate work. Furthermore many of these publications are out of print and are only available for consultation. For these reasons it is believed that a volume containing the rudiments of the subject will be of use to the student and an aid to the teacher. It is also believed that such a work will be of assistance to practitioners. In preparing this volume the aim has been to bring to- gether in a concise form the fundamental facts in the path- ology of the more common infectious diseases of animals, especially those existing in the United States, with which sanitarians and the practitioners of comparative medicine must contend. To this end the current literature, the reports of the investigations made at various Institutions and Experi- ment Stations, as well as the standard works on comparative pathology have been freely drawn upon to all of which full acknowledgment is hereby made. In order to bring into consideration the clinical value of a knowledge of morbid anatomy a few of the symptoms or ante- mortem manifestations have been included. It is hoped that this correlation of symptoms and lesions will stimulate a deeper VI PREFACE interest in the study of comparative pathology and thus render it of more permanent and practical value for those entering into the practice of veterinary medicine. In selecting the subject matter care has been taken to avoid, as far as possible, the introduction of results concerning which there are controversies. It has seemed best to deal with those facts about which at the present time there is little or no doubt. After the discussion of each disease a few refer- ences to the literature are appended. These are intended sim- ply to bring the attention of the student to a few publications respecting the cause and morbid anatomy, considered in the light of modern etiology, of the disease in question and to a few articles containing the results of original research. In order not to complicate or unnecessarily expand this text, a knowledge of general pathology and the principles of bacteriology has been taken for granted. The difficulties involved in the preparation of such a text are both numerous and obvious. The indication of errors or omissions with any other criticisms that will tend to better the volume and increase its efficiency for the student will be thankfully received. V. A. M. TABLE OF CONTENTS. PAGE List of Illustrations x List of Reference Books xiii Introduction x iv CHAPTER I. general consideration of etiology, infection and specific infectious diseases. Etiology i Infection 2 Channels of Infection .' 5 Wound infection 6 A specific infectious disease 9 The differential characters of a specific infectious or epizootic disease 10 Dissemination of infectious diseases 12 Cause for variations in the course of an infectious disease 13 Classification or grouping of infectious diseases 14 Migula's classification of bacteria 16 CHAPTER II. DISEASES ATTRIBUTED TO WOUND INFECTION. Botryomycosis 19 Omphalopleblitis 21 White scours in calves 22 Infectious suppurative cellulitis. 25 Fistulous withers and poll-evil 27 Infectious mastitis 28 Miscellaneous infections 31 CHAPTER III. DISEASES CAUSED BY BACTERIA-GENUS STREPTOCOCCUS. General discussion of streptococci 33 Strangles 39 Equine contagious pleuro-pneumonia 44 Apoplectiform septicemia in chickens 52 Streptococcus mastitis 54 Vlll CONTENTS CHAPTER IV. DISEASES CAUSED BY BACTERIA-GENUS MICROCOCCUS. Takosis 57 CHAPTER V. DISEASES CAUSED BY BACTERIA — GENUS BACTERIUM. Pasteurelloses 63 Swine plague 65 Hemorrhagic septicemia in cattle 87 Fowl cholera 98 Goose septicemia 104 Infectious leukemia in fowls 106 Swine erysipelas 115 Anthrax 121 Glanders 141 Tuberculosis 160 Avian tuberculosis 185 Ovine caseous lymph-adenitis 209 Asthenia in fowls and pigeons 216 Diphtheria in calves and swine 217 CHAPTER VI. DISEASES CAUSED BY BACTERIA — GENUS BACILLUS. Hog cholera 219 Tetanus 238 Blackleg 248 Foot-rot in sheep 257 Special infections 259 CHAPTER VII. DISEASES CAUSED BY BACTERIA — FAMILY SPIRILIvACE^B. Animal diseases caused by spirilla 261 CHAPTER VIII. DISEASES CAUSED BY FUNGI. Actinomycosis 263 Actinobacillosis 279 leeches 283 Pneumonomycosis 294 Epizootic lymphangitis 302 CONTENTS ix Farcy in cattle 30 r Mycotic stomatitis ^ c Blastomycetes infection in horses 306 CHAPTER IX. DISEASES CAUSED BY PROTOZOA — GENUS PIROPI.ASMA. Texas fever goy Ictero-hematuria in sheep 325 Equine malaria 326 Canine malaria 328 CHAPTER X. DISEASES CAUSED BY PROTOZOA — GENUS AMEBA. Infectious entero-hepatitis in turkeys 331 CHAPTER XI. DISEASES CAUSED BY PROTOZOA — GENUS TRYPANOSOMA. Classification of Trypanosoma 344 Surra 351 Dourine 362 Mai de caderas 370 Nagana 373 CHAPTER XII. INFECTIOUS DISEASES FOR WHICH THE SPECIFIC CAUSE IS NOT YET DETERMINED. Rinderpest 377 Contagious pleuro-pneumonia in cattle 388 Foot and mouth disease 400 Rabies 405 Diphtheria in fowls 428 Iufluenza 440 Dog distemper 446 Infectious cerebro-spinal meningitis 453 Cornstalk disease in cattle 457 Infectious abortion 462 Variola in animals 468 Epithelioma contagiosa 471 Infective sarcomata in dogs 473 Fowl pest 474 X ILLUSTRATIONS CHAPTER XIII. IMMUNITY AND PROTECTIVE INOCULATION. Natural immunity 47& Artificial immunity 47^ Hemolysins 4§3 Protective inoculation 4&5 Prevention 49° CHAPTER XIV. DISINFECTION. Disinfection 493 Disinfection of stables 497 ILLUSTRATIONS. PLATES. Bacteria, fungi and protozoa I Tuberculous bovine heart II Tuberculous and healthy spleens, pig III Tuberculosis of lung, pig IV Fungus associated with leeches V Aspergillar pneumonia VI Map showing Texas fever line VII Diphtheria in pigeons VIII Diphtheria in chickens IX FIGURES IN TEXT. PAGE 1. Purulent infiltration 6 2. Abscess in partially immunized rabbit 15 3. Streptococcus of mastitis 28 4. Section of cow's udder 30 5. Morphology of streptococcus 34 6. Micrococcus caprinus 58 7. Bacterium of swine plague 66 8. Lung showing emphysema in interlobular spaces 71 9. Right lung of pig showing areas affected with swine plague. 72 10. Portion of lung showing hemorrhagic interlobular infiltration 75 11. Hemorrhagic kidney, pig 76 12. Hemorrhagic heart, cow 93 13. Bacterium sangninarium 106 14. Bacterium sanguinarium in the liver 107 15. Temperature chart of fowls affected with leukemia 108 16. Diseased blood in infectious leukemia no ILLUSTRATIONS xi 17. Congested liver in infectious leukemia in 18. Phagocytic action of leucocytes on the red blood corpuscles. 112 19. Bacterium of swine erysipelas 116 20. Anthrax bacteria from an impression preparation 122 21. Cover-glass preparation from anthrax blood 123 22. Bacterium anthracis, in blood 127 23. Bacterium mallei 143 24. Nasal septum, glanders 146 25. Glandered lung 148 26. Section of glandered nodule 150 27. Farcy, cutaneous glanders 152 28. Bacterium tuberculosis 164 29. Lymph glands on side of cow's head 167 30. Dorsal aspect of bovine lungs 169 31. Bovine tracheal and bronchial lymph glands 170 32. Posterior mediastinal glands 171 33. Section of very young tubercles 173 34. Tuberculous focus in cow's lung 175 35. Section of tuberculous lung, \ cow 176 36. Tubercular pleura 177 37. Tubercles on mesentery 178 38. Tubercles on omentum 179 39. Tuberculous ulcers, intestine, cow 180 40. Section of a tuberculous ulcer 181 41. Tuberculous spleen, pig 183. 42. Avian tubercle bacteria 186 43. Culture of avian tubercle 187 44. Tuberculous liver, fowl 190 45. Tuberculous mesentery, fowl 191 46. Tuberculous skin, fowl 192 47. Section of a tubercle, fowl 193 48. Chart showing the effect of cold water on temperature 202 49. Non-tubercular temperature reaction 203 50. Chart showing tuberculin reaction 204 50. Bacterium of Preisz 210 51. Caseous nodules on leg of rabbit 211 52. Bacterium, asthenics 216 53. Bacillus of hog cholera 222 54. Ulcerated intestine inhog cholera 227 55. Spleen of pig, normal and with hog cholera 228 56. Bacillus tetani 238 57. Bacillus of blackleg 250 58. Bacillus necrophorus 257 59. Necrotic area, liver, rabbit 258 60. Spirochaete anserina 261 61. Ray fungus 265 62. Actinomycosis, head of steer 267 63. Young actinomycotic growth 269 64. Actinomycotic jaw, cow 270 65. Section of actinomycotic jaw 271 66. Actinomycosis of upper jaw 272 67. Actinomycosis in tongue 273 68. Actinobacillosis 280 69. Leeches, lesions in lip of horse 286 70. Leeches, lesions in lip of horse 287 71. Isolated nodule from lesion 288 72. Club-like ends of hyphae fungus, "leeches" 289 Xll ILLUSTRATIONS 73. Section through nodule,; "leeches" 290 74. Aspergillus fumigatus 295 75. Necrosis, kidney of rabbit 3 00 76. Piroplasma bigeminum 3 10 77. Coccus form of Piroplasma bigeminum 311 78. Texas fever parasite in blood of kidney 311 79. Coccus form of Texas fever parasite in kidney 312 80. Invasion of corpuscles with Piroplasma bigeminum 312 81. Adult male tick, Boophilus anmtlatus 313 82. Bull suffering from Texas fever 314 83. Adult female tick, Boophilus annulatus 315 84. Eggs and young tick, Boophilus annulatus 315 85. Ameba meleagridis 333 86. Ceca of turkey with lesions of entero-hepatitis 336 87. Cecum showing ulcers, in entero-hepatitis 337 88. Liver of turkey affected with entero-hepatitis 338 89. Early lesions in entero-hepatitis 340 90. Trypanosoma Brucii 345 91. Tripanoplasma Borrelli 345 92. Trypanosoma Lewisi 346 93. Map showing distribution of trypanosomiasis 349 94. Trypanosoma Evansi 352 95. Trypanosoma of surra ; 353 96. Trypanosoma Equiperdum 363 97. Trypanosoma of dourine 364 98. Negri bodies 408 99. Section of normal plexiform ganglion, dog 423 100. Section of plexiform ganglion from a case of rabies 423 101. Diphtheria in fowls, eye 430 102. Diphtheria in fowls, sinus 431 103. Diphtheritic exudate, throat of pigeon 433 104. Diphtheritic exudate, larynx, fowl 434 105. Diphtheritic exudate, larynx and trachea, fowl 434 106. Epithelioma contagiosa, fowl 472 107. Ehrlich's figures, complement 484 108. Ehrlich's figures, various receptors 484 109. Ehrlich's figures, free receptors 484 no. Ehrlich's figures, antibody 484 A LIST OF REFERENCE BOOKS. Boui,EY ET Reynal. — Nouveau Dictionaire pratique de M£decine de Chirurgie et d'Hygiene Veterinaires. Cadeac. — Encyclopeclie V£terinaire. Dieckerhoff. — Lehrbuch der speciellen Pathologie und Therapie fiir Thierarzte. EnENBERGER, SchuTz und Baum. — Jahresbericht iiberdie Leistungen auf dem Gebiete der Veterinar-Medicin. Fleming. — A manual of veterinary sanitary science and police. Friedberger und frohner. — Lehrbuch der speziellen Pathologie u. Therapie der Haustiere. Gai/tier. — Traitd des maladies contagieuses et de la police sanitaire des animaux domestiques. HuTyra und MarEk. — Spezielle Pathologie und Therapie der Haustiere. KlTT. — Lehrbuch der pathologischen Anatomie der Hausthiere. Kolle und Wassermann. — Handbuch der pathogenen Mikroorgan- ismen. Law. — Veterinary Medicine. (Especially Vol. IV.) Nocard ET Leclainche. — Les maladies microbiennes des animaux. LubarSCH und OSTERTAG. — Ergebnisse der allgemeinen Pathologie und Pathologischen Anatomie des Menschen und der Tiere. OSTERTAG. — Handbook of meat inspection. Authorized translation by E. V. Wilcox. REynal. — Traits de la Police Sanitaire des Animaux Domestiques. Schneidemuhx. — Lehrbuch der vergleichenden Pathologie und Ther- apie des Menschen und der Hausthiere. Wauev. — The four bovine scourges. For bibliography on all medical subjects, see Index-catalogue of the Library of the Surgeon-General's office. Annual reports, Special Reports and Bulletins on Animal Diseases issued by the Bureau of Animal Iudustry, U. S. Department of AgricuL ture, Washington, D. C. Proceedings of the American Veterinary Medical Association. The Bulletins on Animal Diseases issued by the various State Agri- cultural Experiment Stations. INTRODUCTION. An elementary treatise on the pathology of the infectious diseases of animals — a treatise that states briefly, clearly and comprehensively all that is known, and excludes all that is not known — has long been needed not only by the students who are beginning this interesting subject, but by members of the veterinary profession who, as practitioners, investigators or teachers, wish to learn in the shortest time the present con- dition of our knowledge. A work which supplies this need will be welcomed and appreciated. There are few subjects more important to Americans than a thorough comprehension of the infectious diseases of animals. An enormous amount of money is invested in the domesticated animals in the United States, and the security of this invest- ment depends very largely upon our ability to protect these animals from infectious diseases. There are many diseases of this class which spread among animals as smallpox, bubonic plague or cholera spread among mankind ; and it requires a thorough knowledge of all the characteristics of such diseases to guard against them, to recognize them when they appear or to control them. For a period already too long, exact knowledge of these diseases has been confined to a comparatively small number of men ; but with the great property interests at stake it is ex- tremely desirable that this information should be distributed, that not only responsible officials but every practitioner should share it. With not far from three thousand million dollars worth of farm animals in this country, and with a single disease ■that sometimes destroys a hnndred million dollars worth of INTRODUCTION XV property in a year, it is not difficult to see the value of that precise knowledge which is required to deal promptly and efficiently with these plagues. It is a narrow and incorrect view to hold that the farmer who owns these animals is the only one who suffers from the ravages of the diseases which destroy them. Animal products constitute a large part of the national food supply. If this food supply is diminished, made dearer and more difficult to obtain, want, misery, disease and death among mankind increase. At first the effects of a scarcity of the food supply may be almost inappreciable and felt only by the very poor ; but as the con- ditions of famine are approached, suffering is multiplied and intensified until whole communities are prostrated or destroyed. An abundant supply of wholesome and nutritious food is there- fore an essential condition of the welfare and prosperity of a people. The great commercial operations of nations also depend to a great extent upon the good condition of animals. When all of the horses are disabled by an epizootic, as they have been on rare occasions by influenza, the delivery of purchased goods has nearly ceased, the shipments of flour, iron, machinery and other products have been temporarily arrested and busi- ness has been almost at a standstill. Again, it should be re- membered that we export annually from the United States forty million dollars worth of live animals, one hundred million dollars worth of meats, fifty-five million dollars worth of lard, tallow and other animal fats, and nine million dollars worth of dairy products. Let this traffic be stopped by the shortage of supplies or by prohibitive orders of other nations on account of the unrestrained prevalence of infectious diseases, and the earnings of steamships, and railroads, and banks, and com- mission houses, are at once diminished ; men employed in these XVI INTRODUCTION enterprises are discharged, and in innumerable ways the wel- fare of people who have no part in the ownership of any of these animals or their products is affected. Finally the most serious of all is the case in which the animal plague, in addition to being destructive to animal life, is communicable to and fatal to man, as is true of anthrax, rabies and tuberculosis. Such diseases destroy property, dis- turb business, lessen the food supply, and directly threaten human life. What more is needed to impress upon the reader the supreme importance of studying and understanding the infectious diseases of animals ? The pathology of these diseases is in itself a large subject. Investigations concerning it have extended over more than a century of time and the literature of the subject is enormous. To concentrate this knowledge, to select the truth and discard the errors, and to develop a concise and systematic treatise is a task of great magnitude and one which has required much labor and thought. The writer has not seen the manuscript, but, from his long and intimate acquaintance with the author, he feels sure that the work has been patiently, carefully, intelli- gently and thoroughly done, and that it will be favorably received. D. E. Salmon. CHAPTER I. GENERAL. CONSIDERATION OF ETIOLOGY, INFECTION AND SPECIFIC INFECTIOUS DISEASES. S i. Etiology. The development of the science of bac- teriology, together with a knowledge of the parasitic protozoa, has already demonstrated that a large number of the infectious diseases are the direct result of the invasion of the animal body by certain species of microorganisms. A specific etiology which teaches that for each of the various epizootics we have a single, definite cause has become recognized and accepted by all pathologists. Although there are a number of distinct diseases for which such a specific agent has not been found, the evi- dence in the very nature of the maladies is conclusive that for each of these such an etiological factor exists. In studying the pathology of infectious diseases the idea of a definite and adequate cause should be kept in mind. It is no longer justifiable to attribute them to an unfavorable environment, poor hygiene, or improper sanitation, conditions which may aid the specific cause but which cannot supplant it. It is often a troublesome task to differentiate between the morbid affections, often fatal in their results, brought about by improper care and food, and the maladies dependent upon a specific cause. The reason why many of the former theories accepted unsanitary conditions, certain kinds of food or other similar agencies as the etiology of distinct, infectious diseases, is found in the fact that the infectious microorganisms were and still are often transmitted to the individual through such channels. It is important, therefore, that the limitations of both the exciting cause and the environment should be fully taken into account. Although for certain diseases such as rinderpest and rabies we do not know just what the specific cause is, the fact that its location in the body of the diseased 2 ETIOLOGY animal is known, that with these morbid tissues the diseases can be produced in healthy animals and that without these definite infections, no matter what the conditions are, they cannot be made to develop, argues against extraneous conditions as exciting causes. The mysteries which formerly surrounded the origin, the course and the disappearance of animal plagues have in a large degree been cleared away ; and in their place we are con- fronted with the problems involved in the life history and the possibilities of invading microorganisms. In fact during the last few years the biological sciences have been brought into immediate use by the pathologist. Etiology has become per- manently linked to microbiology so that in seeking for the specific cause of an infectious disease we look for some spe- cies of organic life which may belong either to the animal or to the vegetable kingdom. The fact that certain animals and plants have become, if they were not in the beginning, para- sitic on other larger and higher forms of life has long been recognized ; but the idea came later, that the various infections giving rise to a wide series of phenomena, known as symptoms and morbid anatomy, were actually and simply the results of the invasion of the individual with living microscopic plants '(bacteria) or animals (protozoa). It is likewise true that for many of the disorders consisting of changes recognized in the terms of general pathology, the cause may be found in the ^conditions of life under which the individual has been forced to exist. Etiology, therefore, in a broad sense, includes both the infecting microorganisms that produce the specific infectious diseases, and poor hygienic, unsanitary conditions and physical forces which may produce non-specific morbid changes often sufficient to cause death. § 2. Infection. The term infection has come to be gen- erally understood to mean the entrance into the animal body, from without, of living microorganisms capable of multiplying within the living tissues and of producing in consequence thereof a local or a general diseased condition and possibly the death of the individual. The invading microorganisms may belong to any one of the three great grongs of microscopic INFECTION 3 life, namely, bacteria, higher fungi, or protozoa. It is cus- tomary and convenient, if not altogether logical, to limit the term microorganisms to these forms, excluding altogether the entozoa and other animal parasites, most of which are not microscopic in size. A diseased condition produced by substances not capable of reproducing themselves as, for example, organic or inorganic chemical compounds, is an intoxicative process. In an infec- tion, the immediate cause of the symptoms and morbid changes in the tissues is an intoxication due to the action of the meta- bolic products (toxins) of the invading microorganisms. The theories of their mechanical interference with the normal func- tions of the body or that they absorb the nutriment thus depriving the tissues of necessary food, wait for demonstration. The results of infection vary in their manifestations. If the invading organisms remain at the point of entrance and produce local tissue changes, the condition is spoken of as a wound infection. If the invading bacteria become widely distributed in the circulation and tissues, the condition is known as septicemia or bacteriemia. If the infecting bacteria remain at the point of entrance and multiply there, elaborating a toxin which is absorbed and which causes symptoms and possibly death, the condition is a toxemia. If there is a febrile condition, resulting from the absorp- tion of the products of putrefaction caused by saprophytic bacteria, the condition is called sapremia. If the invading organism is one possessed of definite pathogenic properties, such as the bacterium of anthrax, giving rise to a definite series of symptoms and lesions, the affection is designated a specific, infectious disease. Through the agency of metastasis, invading microorgan- isms may be carried from the point of introduction to other parts of the body, where they may become localized, multiply, and give rise to any one of many forms of lesions. It may happen that the point of entrance is so obscure that the resulting morbid changes are not easily traced to an external 4 INFECTION infection. There are many illustrations of this in comparative pathology, such for example as suppurative cellulitis. For convenience in discussion, infections may be divided into two clinical groups, namely, wound infections and specific infectious diseases although in certain instances they cannot be separated. In arriving at a clear understanding of the nature of in- fections, it is well not to be too closely circumscribed by classifications. It is better to look upon them as a series of processes going on in the animal world due to the activities of infecting or parasitic microorganisms. In other words, the lesions following an infection, are simply the results of parasitism. In the study of the various forms of infection in the lower animals, lesions have been found to contain, apparently as their causative factors, bacteria which suggest at least that certain of the supposed saphrophytic organisms may, under certain con- ditions, become parasitic and cause infections resulting in more or less local or general disturbance. Many lesions seem to be produced by bacteria which are harbored normally upon the skin. When these organisms are introduced by accident into the living tissues they multiply and acquire, if they did not already possess it, the power to produce tissue changes. We cannot, therefore, dismiss the subject of infection without a passing consideration of the possible etiological significance, under certain conditions, of many species of bacteria ordinarily considered harmless with which the animal body is con- stantly surrounded. In the search for the cause of many le- sions supposed from their nature to be infectious, or in apply- ing methods for their prevention, it is well to take into consid- eration all microorganisms which might possibly be the caus- ative factors and not limit the search to the detection of the already recognized pathogenic species. Recent investigations point to the conclusion that domesticated animals frequently suffer as the result of the invasion of bacteria at present not listed among the pathogenic microorganisms, and what is true in this regard for bacteria, may be hypothetically applied to the higher fungi and to the protozoa. CHANNELS OF INFECTION 5 §3. Channels of infection. There are a number of ways by which microorganisms may be introduced into the living tissues of the animal body. The more common of these are as follows, namely : 1. Through the digestive tract. Bacteria gain entrance into the tissues from the digestive tract where they have been brought with the food or water. It is not clear in all cases how the invading organisms get into the tissues from the intestine. It has been demonstrated that tubercle bacteria will pass through the mucosa with fat globules in the process ol digestion and absorption. 2. Through the respiratory tract. Bacteria are taken into the lungs where they are brought with the inhaled atmosphere. Pulmonary tubercular affection is often brought about in this way. 3. Through abrasions of the skin or i?itestinal mucosa. The wide distribution of bacteria in nature renders it highly probable that in all wounds of the integument microorganisms will reach the fresh tissues. They may come from the cutting or tearing implement, the particles of dirt which may fall into or upon the cut surface, or from the ducts of the glands of the skin itself. It may happen that the fresh tissues thus exposed are infected with one or with several species of bacteria. It may be that one or more of these species may be destroyed by the living juices of the body or by the leucocytes, or again it is possible that, from their saprophytic nature, they may not be able to multiply in this new environment ; in either case the infection is of no significance and clinically would not be recognized. It may happen that only one species of the in- fecting bacteria multiplies and produces the morbid changes. This would be a single infection. If, however, two or more species cooperate in the production of the lesions, it is called a mixed infection. This term is often used to designate the condition where one species may be responsible for the tissue changes, although other bacteria are present but only in an accidental or passive way.. 4. Through the generative organs. Infection of the re- productive organs takes place in certain instances where they 6 WOUND INFECTION are the seat of the disease. This is especially true in case of maladie dit coit. 5. Through the agency of insects. Some insects carry the virus of certain diseases from the infected and introduce it into the susceptible individuals. Thus the mosquito carries the Plasmodium of human malaria, the cattle tick the piroplasma of Texas cattle fever and flies are often the introducers of pathogenic bacteria, such as those of anthrax. In certain instances, as with malaria, a part of the life cycle of the micro- organism takes place in the body of the carrying insect. 6. Transmission of the virus fro?n the parent to the fetus. Occasionally the young of diseased parents are born infected with the disease with which one or both of its parents were suffering. In these cases the specific bacteria were transmitted either from the sire at the time of coition, or later to the fetus in the uterus from the dam. It is important not to confuse these rare cases with those in which the offspring are born uninfected but subsequently contract the disease. Many of the so-called hereditary diseases are the result of post-natal infection. § 4. Wound Infection. Wound infections are the direct results of the entrance of certain microorganisms into trau- matisms and operative incisions. They fall very naturally into two classes. 1 . Those infections producing local, acute or more chronic- inflammatory processes usually leading to suppuration and finally healing by „, *»«•*£*&„ *— l "'*°* ,„.,S j \ primarily brought about by me- ® "'MM:'- 0< ^* *» f'mi- chamcal injuries which render o o ^' { '*'' / "?•' possible the entrance into the °0n ^•"•••£^" fresh tissues of the bacteria of the O Jifc: skin or of the milk ducts. Other /••*•"• ..• / 00 cases may be due to infection Fig. 3. Streptococcus from a through the teat of bacteria capa- case of infectious mastitis. \,\ e f producing, by means o, their metabolic products, the inflammatory condition without a distinct injury to the mucous membrane. The former view that there was a sphincter muscle near the base of the teat which closed the duct sufficiently to prevent the entrance of bacteria to the secreting portions of the gland was not well founded upon anatomical facts (Fig. 4). The acute and more chronic inflammatory affections of the udder fall very naturally into two groups, namely, (1 ) those in which the parenchyma is most affected and (2) those in which the stroma or fibrous tissue is involved. The form of mastitis more frequently encountered as an infectious (transmissible) disease is characterized by very marked changes in the milk, accompanied by the usual symptoms of parenchymatous in- flammation of the gland itself. The discharge from the udder usually contains flaky masses held in suspension in the clear or perhaps cloudy serum. The color varies, and occasionally the fluid is blood-stained. The microscopic examination shows the presence of agglutinated fat globules, pus cells and often red blood corpuscles. INFECTIOUS MASTITIS 29 A number of bacteria* considered of more or less etiological value has been found associated with lesions of doubtful spe- cific origin. The results of Kitt, Nocard, Mollereau, Guille- beau, Zschokke, Bang and still others, in which a Bacterium, a Micrococcus, a Staphylococcus, and a Streptococcus have been found and reported as standing in a causal relation to the trouble, indicate that a variety of microorganisms are active in producing those affections which are frequently grouped with- out distinction as infectious mastitis. The review of much of the literature on this subject, shows that a number of cases re- ported as infectious were isolated or sporadic ones, i. e., they were in dairies where the disease did not spread to other ani- mals. While these may be truly infectious in their nature they should be differentiated from the rapidly spreading phlegmons which are easily recognized as infectious (contagiousj. If we take into account the variety of anatomical changes which have been described in the various udder affections, we can reasonably admit that different agencies ma3' have been instrumental in their production. The various species of bacteria which have been isolated from the udder lesions may very likely have been of etiological importance in their respective cases. Already the facts have been pointed out, that the udder is normally more or less extensively invaded with bacteria and that certain species of bacteria seem to persist in the milk ducts of the glands when once they become lodged there. If these results apply to cows generally as rigidly as they did to those examined, an explanation for the presence of a variety of bacteria in the affected udders is not difficult to find. Whether these particular organisms, under certain conditions, would become primarily responsible for udder disease is not known. The evidence suggests that a number of the bacteria, heretofore described as the cause of mammitis, were in the affected glands by virtue of their presence in the normal udder. Concerning these points additional investigations are much needed. *Among the bacteria which have been found in udder trouble and described as the possible or perhaps the more probable cause the follow- ing species may be mentioned : Bacterium phlegmasia uberis, Strep 3° INFECTIOUS MASTITIS tococcus agalactia contagiosa, Staphylococcus mastitidis, Galactococcus versicolor, G.fulvus, G. albus. Fig. 4. Section of a quarter of a cow's udder through one teat ; (a) cistern, (b) larger milk ducts, (c) secreting portion of mammary gland. 2, drawing of secreting portion of gland, enlarged. INFECTIOUS MASTITIS 3 1 The writer has examined the milk secretions from the affected cows in two quite serious outbreaks of mastitis. In the first, the milk was drawn in sterile bottles after the udders and the hands of the milker had been thoroughly washed in a 1 to 1000 solution of corrosive sublimate. In all, there were eight samples of miik taken from as many different cows. In six of the eight specimens streptococci appeared in pure cul- ture. In the other two cases micrococci were associated with the streptococcus. In the second outbreak, the milk from four diseased udders was drawn with aseptic precautions directly into tubes containing slant agar and promptly sent to the laboratory, where it was carefully examined. From two cases pure cultures of streptococci were obtained, while those from the others were impure. The streptococci obtained from the twelve cases appeared to be identical and the clinical aspect of the disease in the different animals was the same. In a dairy that was under close observation by Ward, one cow was found to be troubled in one quarter of the udder with an inflammatory process which produced thickened masses in the blood-stained milk. From this milk a streptococcus was isolated in pure culture. It could not be differentiated from the one isolated from the cows in the outbreaks mentioned. Another cow in this herd was found to have her udder per- manently infected with a streptococcus. Another animal in the same dairy suffered repeatedly from acute streptococcus mastitis. There are a large number of morbid conditions more or less frequently encountered in domesticated animals, which seem to be due to infection of some kind but which are not demonstrated to be of such an origin. These will continue to be attributed by some to infection and by others to various gen- eral causes until the truth concerning their etiology is revealed. VII. § 18. Miscellaneous infections. Attention should be called to the many morbid conditions, resulting from infection, that are encountered in different species of animals and 32 INFECTIOUS MASTITIS are liable to be attributed to other agencies. Usually such lesions are referred to general pathological conditions, but a more careful inquiry will reveal the presence of infection' Among these, may be mentioned pericarditis in cattle, so fre- quently associated with punctures by foreign bodies. The ex- tensive exudative inflammations in these cases are frequently associated with micrococci. The same has been true of certain cases of localized endocarditis resulting in the formation of fun- goid, purulent, or necrotic masses about the valves of the heart. When one considers the possibilities of infection from acci- dental causes, as well as from surgical interference, together with the agency of metastasis, it is not difficult to understand how such a variety of morbid conditions can come about. In- fection, therefore, forms an important part of pathology, out- side of those specific organisms that cause epizootics of greater or less severity. REFERENCES. i. Bollinger. Mycosis der Lunge beim Pferd. Archiv fur pathol. Anat. Bd. XLIX (1870) S. 583. - 2. Gay. A bacteriological study of fistulous withers, botryotny- cosis and infected wounds in the horse. Amer. Vet. Review. Vol. XXIV (1901) p. 877. 3. DkJong. Untersuchungen iiber Botryomycer. These de Gies- sen 1899. 4. Johne. Zur Actinomykose des Samenstranges. Deutsche Zei- schr.fi'ir Thierm. Bd. XII (1885) S. 73. 5. Frohner. Ein Fall von generalisister Botryomykose. Monat- sheftefiir Thierheilk. Bd. VIII (1897) p. 171. 6. Lucet. Ann. de V Institut Pasteur. Vol. VI (1893) p. 324. 7. M'Fadyean. Metastatic lesions in Discomycosis The Jour. Compr. Path, and Ther. Vol. XIII (1900) p. 337. 8. Migula. System der Bacterien. 1897. «^-v 9. Moore. Suppurative cellulitis in the limbs of cattle due to streptococcus infection. Amcr. Vet. Review. June, 1898. __ 10. Nocard. A New Pasteurellose : White scours and lung disease of calves in Ireland. Amer. Vet. Review. Vol. XXV (1901) p. 326. 11. Smith and Dawson. Injuries to cattle from swallowing pointed objects. Ann. Report U. S. Bureau of Animal Industry. 1893-4 p. 78. 12. Ward. The invasion of the udder by bacteria. Bulletin No. 178 Cornell Univ. Agric. Exp. Station. 1900. CHAPTER III. DISEASES CAUSED BY BACTERIA GENUS STREPTOCOCCUS. § 19. General discussion of streptococci. The con- fusion which exists concerning species in this group of bacteria and the variety of antistreptococcic serums on the market, ren- der a summary of the present knowledge concerning this group of bacteria somewhat desirable. The genus Streptococcus is based, according to Migula, on its method of reproduction or division. Streptococci are spherical bacteria that divide in one plane. The segments do not separate but are held together in short or longer chains, although the divisions seem to be com- plete. Just how the segments are held together is not fully determined. According to older and more commonly encoun- tered classifications, a streptococcus is simply a number of micrococci (spherical bacteria) united in the form of a chain. In some of the supposedly different species the segments are oblong and vary in size. Frequently, however, the segments vary in size and form in the same chain. The more usually observed cultural characters and bio- chemic properties of different streptococci are quite similar, although it is difficult to obtain two cultures that will exactly agree in all of their manifestations when grown on a large number of media. Their disease-producing powers, however, vary within wide limits. While variations in the physio-, logical properties and pathogenesis are true for different cul- tures (species?), it has been found that there is a possibility of much variation in the subcultures of the same species. As with certain other bacteria, their virulence is the first to suffer; change. In differentiating species, therefore, the fact must not be overlooked, that the existing characters and properties 34 STREPTOCOCCI possessed by the streptococcus in hand, may have been more or less influenced by its conditions of life. When, for example, two streptococci appear to be identical under the majority of tests, a slight deviation in a single property cannot be considered of great differential value especially if this particular manifesta- tion is among those most subject to change. A fundamental difficulty in differentiating species among streptococci seems to be a lack of information concerning the possible variations brought about by different environments. The further diffi- culty of identifying any of the very large number of forms which have been assigned specific names is due to the brevity of their description and the failure of the author to mention any character or property, or combination of the same, which / v :• • •. ••• •• v •• • Yf 1. 2. 3 .-fry..-' • „* •%••'*" •••• \ • • • •.." ••• • ••••• 4. 5. 6. Fig. 5. Six forms of streptococci. 1. Long chains consisting oj small segments arranged with equal spaces between them. 2. Long and shorter chains in which the segments are arranged in pairs. The size of the individual segments is considerably larger than those in the long chains. 3. Short and longer chains where the segments are oval with the long diameter perpendicular to the long axis of the chain. 4. Long interlacing chains. 5. Short and longer chains with one or more seg- ments very mnch larger than the others. 6. Chains showing divisions in two planes. This form of division has been observed in a few cases. The dividing in two planes is an exception which is not satisfactorily explained. X about 1000. CLASSIFICATION OP STREPTOCOCCI 35 -would distinguish it from others. However, such deficiencies ■cannot well be avoided in the time of rapid accumulation of •observations and the evolution of methods. § 20. Classification of streptococci. A few investi- gators have tried to eliminate the confusion concerning species T>y classifying streptococci according to distinct morphologic characters and pathogenic properties. Of these classifications the following may be mentioned : I. The classification of von Ling elsheim. This author di- vides all streptococci into two groups, or species, namely : — (a) Streptococcus brevis — which is non-pathogenic. (6) Streptococcus longus — which is pathogenic. This is a combination of pathogenesis and morphology which the author thought applicable to the entire genus. He ■worked very largely, however, with the streptococci from the human mouth and throat. II. The classification of Kurth. Kurth worked largely with the streptococci from cases of scarlatina. His system is practically the same as that of von Lingelsheim, with the ex- ■ception that he does not include pathogenesis as necessarily belonging to either group. The divisions are as follows : (a) Streptococcus rigidi — Streptococci growing in short chains, imparting a uniform tubidity to bouillon. (b) Streptococcus fiexuosi — Streptococci which grow in long interlacing chains forming flocculi in bouillon, leaving the liquid clear. III. The classification of Pasquale. Pasquale worked with thirty-three streptococci, including nearly all of the then known species. His work was quite exhaustive, but he had to deal with cultures of various generations. He divides them into four groups, as follows : (a) Short saphrophytic streptococci. (b) Long non-virulent streptococci. (c) Long pathogenic streptococci. (a?) Short highly infectious streptococci. Group (d) pertains largely to bacteria which are no longer recognized as streptococci, for examble, the diplococcus {Micro- coccus lanceolatus) of pneumonia. It is now known that strep- 36 STREPTOCOCCI tococci which grow in short chains are often virulent. This is especially ^rue of the pyogenic forms. The study of streptococci from various sources, more especially from tissues of diseased animals, suggests the desira- bility of delaying a further classification until more definite data are obtained concerning the natural history, not only of these, but also of the species normally present on the mucous membranes of animals and in nature generally. The specific name is, pathologically or even biologically speaking, of little moment unless we can attach a certain definite meaning to it concerning the morphologic characters, cultural manifestations- and the degree of disease-producing power possessed by the organism designated. In a group of twenty-eight streptococci previously studied, the writer found the pathogenic forms, i. e., those able to produce disease in rabbits, guinea pigs, or mice, about equally divided between the long and short chains. Of the twenty-eight, nine possessed a certain amount of virulence for one or more of these animals. § 21. Distribution of streptococci in nature. The fact has been pointed out in many publications that strepto- cocci are quite widely distributed in nature. The results of the bacteriologic examinations of normal mucous membranes show that they are frequently included in the bacterial flora of the mouth, throat, nares, intestines, vagina, and in a few cases they have been found in the bronchioles of the horse and rab- bit. They are also present in greater or less numbers on the skin, especially in the deeper layers, presumably in the ducts of the sweat and sebaceous glands and along the hair shafts, and follicles. They exist in soil and in water, and occasionally these forms are quite as delicate in their morphology and equally as sensitive to the influence of environment as those isolated from diseased animal tissues. In view of this wide distribution, the presence of a streptococcus in any abnormal condition cannot be considered necessarily a specific inftcticn from a previous case of the same kind. In many affections where the specific organism has been demonstrated, such for example as diphtheria, tuberculosis and hog cholera, strepto- cocci frequently appear in the lesions. In these cases, they are DISTRIBUTION OF STREPTOCOCCI 37 considered as accidental or secondary invaders, although in some of these maladies, such as tuberculosis, they are believed to be of more or less secondary importance. When, however, the specific cause of the disease is not positively known, and streptococci which possess certain pathogenic powers for ex- perimental animals are constantly present and seem to stand in a causal relation to the disease, the pathologist is confronted with a puzzling problem in trying to determine the source and the etiological importance of the organism in hand. In cases of infection leading at once to septicemia, peritonitis or sup- puration, the explanation is more simple than in the epizootic ■diseases, such as Brustseuche, where the constant presence of streptococci in the lesions can be quite as easily explained on the ground of their invasion of the parts affected from a normal habitat as on the hypothesis of a specific infection. It is in these instances that we are seeking for the crucial test. We have found in a few test experiments that when certain of the delicate streptococci which exist (are found) in external nature (soil or water) are introduced within the tissues of cer- tain animals they become, by reason of their activities, a source of irritation which causes local tissue disturbances. In a few cases they have produced septicemia with fatal results. In cases of infection resulting in septicemia, or in those where the disease is more localized, as in strangles or mastitis, and possibly in others where the affection spreads more or less rapidly, we cannot well escape from the feeling that the strep- tococci, present in such large numbers, must either stand in a causal relation to the disease or be accounted for by their rapid proliferation in native soil made favorable for their excessive increase by the conditions produced by the true etiological fac- tors. Their natural distribution is so wide and their virulence so capricious that a secondary invasion, which seems always to be possible, renders the fixing of etiological responsibility upon a streptococcus isolated from any diseased tissue a somewhat difficult task. The problems in this connection which concern us most and which need more extended investigation pertain (1) to the determination of the parasitic possibilities of strepto- cocci existing in nature, i. e. , those ordinarily considered as sap- 38 STREPTOCOCCI rophytes and (2) to the distinction, if it exists, between strep- tococci that are able to produce local inflammatory processes- leading to suppuration and those which produce highly infective and rapidly spreading diseases, such as erysipelas and. strangles. In view of the confusion respecting species in this genus, the identity of streptococci isolated from the lesions in the various diseases which have been attributed to streptococci is, at the present time, a matter of some uncertainty. There is- also considerable skepticism concerning the primary etiological, significance of the streptococci in a number of diseases in which they have, heretofore, been assigned as the cause. Recent in- vestigations, especially those of Ljgnieres, tend to the conclu- sion that they are often secondary invaders in certain of these- diseases. Petruschky has pointed out analogous cases in human infections in showing that streptococci play an impor- tant role as secondary invaders in human diphtheria, scarlatina and tuberculosis. Pathogenesis. In the absence of verified results to prove the non-specific relation of streptococci to the diseases which have with reasonable certainty been attributed to the activities of this genus of bacteria, these affections are tentatively in- cluded among the specific streptococcic maladies. It is very important, especially when the use of antistreptococcic serums are in question, to take into account the apparently large number of forms, or species, commonly included in the general statement of a streptococcus disease or infection. In 1897, Van.de Velde, in a very exhaustive series of experiments, showed that one streptococcus antitoxin will not immunize against another, save to a very slight degree. Better results- are reported by the use of polyvalent serums. There are a number of acute local disorders, such as vaginitis in cows, that have been attributed to this genus. REFERENCES. 1. Klein. Seventeenth Annual Report of the Local Government Board. Supplement containing report of Medical Officer. London. 1887, p. 256. HISTORY OF STRANGLES 39 2. Kurth. Arbeiten a. d. Kaiserlichen Gesundheitsamte, Bd. VII (1891), S. 389. 3. Moore. Bulletin No. 3. U. S. Bureau of Animal Industry. Washington, D. C. 1893, p. 9. 4. Pasquale. Beitrdge zur path. Anat. u. zur allgemeinen Path- ologie, Bd. XII (1893), S. 433- 5. Petruschky. Zeitschrift f. Hygiene, Bd. XVII, S. 59. 6. von Lingelsheim. Zeitschrift/. Hygiene, Bd.lX (i89i),S.33l. 7. Welch. The Amer. four, of Med. Sciences, Vol. CII (1891), P- 439- STRANGLES. Synonyms. Coryza contagiosa equorum, Distemper, Gourme (Fr. ), Druse (Ger.) § 22. Characterization. Strangles is an infectious dis- ease of horses, asses and their hybrids occurring sporadically and in epizootics. It is characterized principally by a fever, followed by an acute catarrh of the mucosa of the upper air passages especially of the nares, and a suppurative inflamma- tion of the lymph glands of the submaxillary and pharyngeal regions. The lesions, however, are not restricted to these parts. It is a disease of young animals. § 23. History. Strangles was among the first equine diseases to be recognized. In 1664, Solleysel gives an account of it and points to the fact that it had been known for a long time. Its infectious (contagious) nature was determined ex- perimentally in 1790 by Lafosse and since that time by a num- ber of other investigators. In 1873, Rivolta found in the pus of the abscesses a micrococcus which appeared in chains of from three to five segments. Baruchello, in 1887, described as its cause an organism, which he designated as Bacillus adenitis equi. Strangles has been thought by some, to be identical with scrofula and measles. Sacco and Nasbot con- sidered it as horse pox. Viborg and Toggia and more recently Nasbot advocated the inoculation of horses with the lymph of horse pox as a prophylactic measure against strangles. Dela- motte demonstrated that this procedure was of little or no pre- ventive value. The supposed specific cause {Streptococcus equi) of strangles was described first by Schiitz and later by Sand 4<3 STRANGLES and Jensen in the same year (1888). The discovery has been confirmed by Poels, L,upka and others. More recently Lig- nieries has discovered a "coccobacillus" which he believes to be the primary cause. He considers the streptococcus of Schiitz as a secondary invader of no specific value. His con- clusions do not appear to have been confirmed. § 24. Geographical distribution. Strangles is a wide spread disease among horses. It appears to stand in equine pathology very much as measles do in human medicine, — a disease of early life and consequently more prevalent where there are more young. It seems to exist in all countries where the horse kind are raised and to be more prevalent in breeding districts than elsewhere. § 25. Etiology. Strangles is caused by Streptococcus equi, first described by Schiitz in 1888. With pure cultures of this organism Schiitz was able to produce the disease in healthy horses. It is fatal to mice, a maximum virulent virus destroying life in three days. In the writer's experience streptococci only have been found in the abscesses. The period of incubation varies, from four to eight days is the most usual time. § 26. Symptoms. The first indication of this disease is a rise of temperature. There is loss of appetite, depression, and often great weakness. The general symptoms may con- tinue for a few days before the localization of the lesions is apparent. The first local manifestation consists usually in a catarrh of the nasal mucosa or swelling of the submaxillary and pharyngeal lymphatic glands. The nasal discharge is at first serous and somewhat viscid, but in from 3 to 5 days it be- comes purulent and of a yellowish-green color. The catarrhal condition may exist in one or both nostrils. It may extend into the pharynx, larynx, trachea and even to the bronchi. In most cases, swelling of the sub-maxillary glands appears con- currently with the purulent nasal catarrh. The spreading of the inflammation to the connective tissue which surrounds the glands, and the stasis of the lymph in the efferent lymph vessels, often cause the development, from the sub-maxillary lymph glands, of very extensive swellings tnat may occupy MORBID ANATOMY 41 the entire inter-maxillary space, and may spread even to the outer side of the maxilla. Abscesses form in most cases. In exceptional cases, strangles may present catarrhal symptoms without suppuration of the lymph glands. Jensen states that it may first assume the form of pharyngitis, purulent pneumonia, and pleuritis without any well marked morbid affection of the lymph glands. The urine generally remains alkaline ; it frequently contains a considerable quantity of al- bumen. At times, strangles is accompanied by a cutaneous exan- thema which takes the form of an eruption of wheals, nodules, vesicles and even pustules ; these may appear, chiefly on the sides of the neck, shoulders and sides of the chest. These ex- anthemata are characterized by their sudden appearance, and often by their equally rapid disappearance. An eruption of vesicles may break out on the nasal mucous membrane. The contents of the vesicles is at first limpid, but later it becomes purulent. Rabe states that the streptococcus of strangles can produce ulcers on the nasal mucous membrane. § 27. Morbid anatomy. The lesions in strangles are interesting from the fact that in the beginning the disease is general but later in its course it becomes a series, exceedingly variable in different individuals, of localized morbid foci. The lymphatic glands seem to suffer most, although any organ may be involved. As indicated by the symptoms, the lesions in most cases are characterized by an acute inflammatory pro- cess followed by suppuration. The glandular swellings about the head usually terminate in suppuration, the pus discharging either externally or into the oral cavity. In other cases, the pus undergoes caseation. Frequently the inflamed glands become confluent, resulting in a single large abscess. Small abscesses may occur under the pharyngeal mucosa. The inflammation may extend to the superficial lymph vessels of the skin, especially of the head, resulting in the for- mation of a large number of small abscesses.' This may be followed by a diffuse phlegmonous swelling of the parts. Metastatic abscesses are liable: to occur in a great variety of 42 STRANGLES organs. The metastasis seems to take place through both lymph and blood vessels although the lymphatic glands are most often affected. Suppurating foci have been described in nearly every lymphatic gland in the body. The discharge of pus from the bronchial, mesentric or other glands, within or adjacent to the pleura or peritoneal cavities, may give rise to a fatal pleuritis or peritonitis. There is no organ of the body free from possible suppurative lesions as a result of metastasis. Strangles may become chronic, especially when the nasal catarrh extends into the sinuses of the head, in the guttural pouches, or pharyngeal cavity. In these cases the animal be- comes emaciated. The lesions in these cases resemble some- what those of chronic glanders. Many complications are liable to arise. Mixed infections and secondary lesions often occur. The prognosis, however, is favorable. Death from strangles is caused usually by either septi- cemia, pyemia, pleuritis, peritonitis or suppurating (metas- tatic) pneumonia. The duration of the disease varies according to its severity and the localization of the lesions. In mild cases convalescence begins in a few days, but in other cases restoration may re- quire weeks and even months. The mortality, according to available statistics, does not exceed three per cent. § 28. Differential diagnosis. Strangles is to be differ- entiated from : 1 Purulent nasal catarrh. In this affection, there is rarely suppurating sub-maxillary glands, although occasionally these glands may be swollen. 2 Glanders. In glanders, the tissue changes are more persistent and the skin lesions, if they exist, do not heal as rapidly as in strangles. In chronic cases, the diagnosis is quite difficult. Here animal inoculations must be resorted to. Mice inoculated subcutaneously with the nasal discharge suc- cumb to the streptococcus of strangles but they are resistant to the bacterium of glanders. Guinea pigs inoculated in a like manner will, in case of glanders, develop that disease from the lesions of which pure cultures of Bacterium mallei may be obtained. PREVENTION 43. 3 Paroiditis . In this affection the swelling is localized and suppuration does not often occur. 4 Abscesses due to pyogenic bacteria. The cases are rare where there would be any question as to diagnosis. The bac- teriological examination including the inoculation of animals- would give positive aid unless the pyogenic organism hap- pened to be a virulent streptococcus in which case a differen- tiation "might be difficult. § 29. Prevention. Isolation of the infected and removal of healthy animals from place where the diseased animals came down. If in stables the stalls should be thoroughly disin- fected before being used for well animals. REFERENCES. 1. L,ignie;res. The etiology of equine influenza as infectious- pneumonia. Jour. Compr. path, and Ther. Vol. XI (r8p8),',p. j/2. Translated from Recueil de Med. Vet. Vol. IV (1897). 2. Poi fowl cholera and Wildseuche are of swine -blague. , , , . , . .. closely related to it. The pathogenic organism associated with the lesions in certain forms of broncho-pneumonia in cattle differs very slightly from this. In human pathology, we find a striking resemblance in Micrococcus lanceolatus to the swine- plague bac- terium, especially in its manifold and varied pathogenic possi- bilities and its frequent presence in normal saliva. The fact should be recognized that experimentally the different varieties or forms of this group {Bacterium septi- cemiae hemorragicae Hiippe, Pasteurel/aTrev.) are not inter- changeable in their pathogenesis except for the rabbit. Thus an epizootic form of fowl cholera has not been produced with the swine-plague or rabbit septicemia organism. Further, it has been shown that in the upper air passages of healthy swine, cattle, horses, cats and dogs* there are bacteria not dis- *The investigations thus far made show these bacteria to be present in 48 per cent, of healthly swine, 80 per cent of cattle, 50 per cent, of sheep, 16 per cent, of horses, 90 per cent, of cats, and 30 per cent, of dogs. ETIOLOGY 67 "tinguishable in their cultural characters and their effect upon rabbits from the swine-plague bacterium. The presence of this organism in the trachea of healthy pigs has been sug- gested as the source of the cause of sporadic cases of swine plague. It explains the frequent association of this bacterium with hog cholera and other maladies. What the conditions are by which this organism is enabled to produce disease in its host have not been clearly pointed out. If the rabbit is taken as the animal on which to test the pathogenesis of the bacteria belonging to the swine plague group, we find that those from different sources are very simi- lar. In nature, the bacteria of swine plague, rabbit septicemia, fowl cholera, and those located in the normal upper air pas- sages of the various species of animals mentioned exist, pos- sessed of marked variation in virulence, that is, there are those that will kill a rabbit in from 16 to 24 hours when inoculated rsubcutaneously with a pure culture and those that require from 3 to 10 days, or even weeks, to destroy life. With the variations in the time period, we have corresponding differ- ences in lesions. The virulent forms produce septicemia while the attenuated varieties excite a severe purulent infiltration about the place of inoculation and exudates on one or more of the serous membranes. Conversely, it has been shown that rabbits possessed of a certain amount of natural or artificially produced resistance will, when inoculated with a virulent cul- ture, die after the same period of time and with lesions similar to those prodnced by the attenuated virus in the susceptible rabbit. The fact that this organism is not frequently described in our works on bacteriology and because of some confusion existing concerning it and the bacillus of hog cholera, it is deemed best to insert a short description of it here. § 68. Brief description of the bacterium of swine plague. * ■ Morphology.— A non-motile, rod-shaped organism varying from 0.8 to 2.0 microns in length and from 0.4 to 1.2 microns in breadth. The ends are oval, and the shorter forms resemble micrococci. The size depends upon the medium and the stage of development of the individ- ual bacteria. A capsule has not been demonstrated, although often 68 SWINE PLAGUE there appears to be one in preparations made directly from tissues. It i& not observed in cultures. Spores have not been seen. Involution forms- are not uncommon in old cultures. They are especially numerous in the organs of a rabbit when it is allowed to lie for some hours after death before it is examined. It exhibits, when stained in cover-glass, preparations made directly from animal tissues, a light center with deeply stained extremities (polar stain). In preparations made directly from cultures this character is much less marked. It stains readily with the basic aniline dyes. It does not retain the coloring matter when stained after Gram's method. Cultural and biochemic properties.— -This organism is less hardy than the bacillus of hog cholera, and on certain of the media used it grows very feebly or not at all. It requires a temperature of about 37 C. although it develops very slowly at the room temperature. Agar. — The growth on this medium is not vigorous. It is of a neutral grayish color, with a glistening, moist appearing surface. It is slightly viscid and adheres to the agar surface. Isolated colonies vary from 1 to 2 mm. in diameter, nearly round, convex, with smooth and sharply-defined margins. The condensation water becomes faintly clouded with a grayish sediment which becomes viscid. Within the agar the colonies appear as minute grayish dots. In agar, especially in plates (Petri dishes), it emits a peculiar, disagreeable, pungent odor. Gelatin. — Ordinarily it does not grow in gelatin. (Dr. Theobald Smith found that certain cultures 'grew in this medium. ) Potato. — It does not grow on potato. Bouillon. — Alkaline, peptonized bouillon becomes uniformly clouded in 24 hours when kept at a temperature of 36° C. Occasionally cultures are obtained in which the growth appears in the form of floc- culent masses, but usually after a few generations these disappear and the liquid becomes uniformly cloudy. If the bouillon contains any dextrose or muscle sugar, its reaction becomes acid in 24 to 48 hours, owing to the fermentation of the carbohydrate. With the virulent cul- tures the liquid clears within a few days. The small amount of grayish sediment becomes viscid after some days, and upon agitation it is forced up, appearing as a somewhat twisted, tenacious cone, with its apex at or near the surface of the liquid. Frequently a thin, grayish, somewhat viscid band composed of bacteria is found on the sides of the tube at the surface of the liquid. It will not grow in acid bouillon. If the bouillon contains from 1 to 2 per cent, glucose, the growth is slightly more vigorous. Effect on sugars. — In the fermentation tube, alkaline bouillon con- taining sugars becomes uniformly clouded in both branches. Gas is not produced. In bouillon containing dextrose and saccharose the reaction becomes strongly acid in 24 hours, but the reaction of alkaline bouillon containing lactose is not changed. Milk. — Milk inoculated with this organism remains unchanged in ETIOLOGY 69 appearance for several weeks. When boiled, after this period, the casein is not coagulated. Indol. — This organism grows feebly in Dunham's solution ; some cultures have given a decided indol reaction, but others have not. The production of indol is reported to be one of the properties of the German swine plague. Smith* obtained only a trace of indol in one out of four cultures of swine-plague bacteria. Phenol. — This was found by Lewandowski's f method in all of the cultures tested by Smith. I have failed to obtain the reaction in a few cultures, but usually it appears. Thermal death point. — This organism is destroyed in bouillon at 58 C. in ten minutes. A temperature of 56 C. for this time did not destroy its vitality. Effect of drying. — These bacteria cannot stand drying. The bacte- ria in a drop of bouillon dried on a cover-glass and kept at the room temperature are destroyed in 24 to 36 hours. In similar preparations made from agar cultures they resist drying from five to eight days. The difference in the time between the two cultures is probably due to the thicker layer in case of the agar preparations. Persistence of vitality in water and soil. — Experiments to deter- mine the length of time this organism will live in water and in the soil show that it is destroyed in water in test tubes in from nine to eleven days. In the soil it was not found after eight days. Dr. Smith states that it is destroyed in the soil after four days. Power to resist disinfectants. — The bacterium of swine plague is very sensitive to the action of disinfectants. A large number of these agents have been tested. The following are among the more important : Commercial sulphuric acid, i/n per cent, kills in 30 minutes. Commercial hydrochloric acid, % per cent, kills in 10 minutes. Lime, lime water kills in 1 minute. Lime, 0.015 per cent, kills in 30 minutes. Carbolic acid, }i per cent, kills in 60 minutes. Carbolic acid, 1 per cent, kills in 5 minutes. Carbolic acid, 2 per cent, kills in 1 minute. Formalin, solution 1:2000 kills in 5 minutes. Trikresol, yi per cent, kills in 5 minutes. Pathogenesis. — This organism is pathogenic for rabbits, guinea pigs and mice among the smaller experimental animals and for swine. With the virulent form rabbits inoculated either subcutaneously or in the vein with very small, 0.001 c. c. doses, die of septicemia in from 16 to 24 hours. Guinea pigs are slightly less susceptible. When inoculated subcutaneously with 0.1 to 0.2 c. c. of a bouillon culture, they die in * Special report on swine plague, 1891, p. 89. t Deutsche med. Wochenschrift, 1890, s. 1186. 70 SWINE PLAGUE from 30 to 72 hours. Mice succumb in about 24 hours when inoculated with a drop of the culture. Pigs inoculated intravenously usually die from acute septicemia in from 18 to 36 hours. If they live longer there may be decided lung lesions. (See report on swine plague, Smith.) § 69. Symptoms. It is frequently difficult to recognize symptoms distinctive of swine plague. The peculiarities of swine render it exceedingly difficult to obtain evidence on physical examination of lung disease. Sometimes this affec- tion runs a very rapid course, the animal dying of septicemia. Usually it is more protracted, lasting from a few days to a week or longer. Animals affected with the more chronic form,, where there are lung lesions, eat very little or refuse food altogether. They cough considerably, especially when forced to run. The back is usually arched and the groins sunken. The whites of the eyes are reddened. The skin over the ventral surface of the body, nose and ears is frequently flushed. The cough, however, is the most reliable indication we have of swine plague ; but in some cases of hog cholera the coexist- ence of broncho-pneumonia also causes the animal to cough when forced to move rapidly. §70. Morbid anatomy. There are many known varia- tions in the appearance of the internal organs of hogs which have died of swine plague. The characteristic lesions are, as previously stated, to be found in the lungs. Frequently the abdominal viscera appear to be normal, although a careful examination will usually reveal slight changes. In the lungs, however, the disease is ordinarily obvious. The variety of lesions produced by the inoculation of swine- plague bacteria is not so great as that observed in the naturally contracted disease. While there are outbreaks in which con- siderable uniformity is observed, there are others in which each animal is a surprise to the pathologist. In general it may be stated that the lungs and the digestive tract are the chief seats of the disease, though other organs, notably the lymphatic glands, are secondarily involved. The disease is localized in the lungs and in the digestive tract most likely because the bacteria gain entrance through the respiratory and digestive passages. MORBID ANATOMY 71 The lungs have been found diseased in nearly every out- break which has been investigated. In some outbreaks the lung lesions predominated and pneumonia was the direct cause of death. In individual cases, pneumonia is absent but pleuritis and interlobular edema are generally present. In a few instances interlobular emphysema of the lungs has been observed. With pneumonia the seat of the lesions varies : usually the ventral lobes are first attacked, then the cephalic and azygos, and lastly the principal lobes. This movement of the disease seems to depend on gravity, inasmuch as the dis- eased parts are marked off from the healthy portion by a nearly horizontal line. In other words, the most dependent portions of the lungs are the ones affected first, and as the disease pro- gresses upwards only a small portion of the principal lobe directly under the back of the animal, remains pervious, pro- FlG. 8. Portion of a pig's lung showing emphysema. vided the life of the animal is maintained up to this point. In cases where disease is caused by lung worms or by embolism, the pneumonia involves portions of the principal lobes not con- tiguous to the ventral lobes. 7 2 SWINE PLAGUE Two kinds of pneumonia are encountered, namely, lobar and catarrhal or broncho-pneumonia. In the former the vesi- cular portion of the lung substance is chiefly affected ; in the latter the smaller bronchioles are primarily attacked and the alveoli secondarily. In croupous-pneumonia, there is, follow- ing the stage of congestion, an emigration of red blood cor- puscles some leucocytes, and an exudate of fibrin into the air spaces. These elements are firmly matted together by the coagulating fibrin, making the diseased lung firm to the touch. In broncho-pneumonia the catarrhal condition of the smaller air tubes makes them impervious to air. The lung tissue which they supply is gradually emptied of air and assumes the Fig. 9. Right lung of pig. The stippled portion is usually in- volved in cases of infections pneumonia or swine plague, (b) ventral lobe, (c) cephalic lobe, {a) principal lobe. The ventral lobe is usually the seat of the more advanced disease and consequently the first to become hepatized. The cephalic portion of the principal lobe (.1-) is usually hepatized and the remaining portion deeply reddened. appearance of red flesh, owing to the collapse of the walls of the alveoli and the distended condition of the capillary net- work. Subsequently the inflammation extends into the alveoli, which then become distended with cellular masses. MORBID ANATOMY 73 The nature of the lung disease will depend more or less upon the mode of entrance of the virus. If it enters only by way of the air tubes it will appear perhaps as a broncho- pneumonia. If it enters the lung tissue through the circu- lation we may have more or less scattered centers of hepatiza- tion (embolic pneumonia.) If it enters by way of the pleura, the virus will creep along the interlobular and peribronchial tissue before it invades the parenchyma proper. In natural infection of swine plague, bacteria seem to «nter the lung tissue chiefly by way of the air tubes. At the same time it is not improbable that occasionally they may ■enter the serous cavities first, i. e. , invade the pleural cavities and thence the lungs. This probability is shown by inocula- tions in which intravenous injections produced exudative pleu- ritis and pneumonia of the most dependent portions of the lungs covered by the pleural exudate. It is not improbable that even in the natural disease the bacteria which have gained access to a portion of the lung tissue by way of the air tubes reach the pleura covering this portion, and may then by this route invade other portions of the lungs. It may be that in this way a pneumonia originally single may become double. It has been observed that the first pneumonic infiltration of the principal lobe was at the point of contact with the dis- eased ventral lobe, and that the resting of a lobe against an inflamed serous surface, such as the pericardium, caused a pneumonic infiltration at the point of contact. The character and seat of the lung lesions are somewhat variable. It is difficult to find two lungs exactly alike so far -as gross appearances go. This to be sure may be due largely to the fact that animals die in different stages of the disease. Yet there are differences evidently not dependent on this fact, -which must be left for special pathological investigation. In general the cephalic (anterior) half of a swine-plague lung is hepatized, of a dark-red or grayish-red color and firm to the touch. The pleura is more or less thickened and opaque, and possibly covered with easily removable, friable, false membranes. In the more recently affected regions a faint but quite regular, delicate mottling with yellow is 74 SWINE PLAGUE observed to shine through the pleura when not thickened. These minute hazy, yellowish dots usually occur in groups of four. Occasionally whitish or yellowish patches varying much in size are seen, perhaps more frequently in the ventral lobes. These correspond to homogeneous dead masses of lung tissue. When such lungs are cut open, the section presents much the same appearance, both as regards color and mottling, as- when viewed from the surface, excepting that the details are less distinct. In some cases, in the most recently invaded territories in the principal lobe and nearer the dorsum in the other lobes, the dark or grayish- red cut surface shows grayish lines usually arranged in curves and circles. These, so far as determined, represent the cut outlines of the interlobular and peribronchial tissue infiltrated with cells. It has already been stated that these lines may represent the paths along which the swine-plague bacteria invade the lungs from the pleural surface. The cut ends of the bronchi of the ventral lobes are fre- quently occluded with thick, whitish pus ; in the other lobes a reddish froth is usually present. Rarely they also contain thick glairy mucus in which particles of dry pus and lung worms are imbedded. The contents of the air tubes in the ventral lobes may have been derived from the overdistended alveoli, or else a broncho-pneumonia may have preceded the swine-plague pneumonia. In microscopic sections of diseased lung tissue the alveoli and smallest air tubes are found distended with cell masses consisting chiefly of leucocytes. Usually there is very little fibrin and very few red corpuscles in the alveoli, even in cases, in which the disease was quite recent. It may be that the stage represented in ordinary croupous-pneumonia by the pres- ence of fibrin in connection with the cellular elements is very brief, and that it is speedily replaced by large numbers of leu- cocytes. The large predominence of these elements in some portions of the lungs, as well as beginning fatty degeneration, is probably the cause of the regular mottling of the lungs, as seen from the surface. The little yellowish hazy dots represent alveoli surrounded by the hyperemic walls. MORBID ANATOMY 75. The necrotic and caseous changes so frequent in swine plague are most interesting. The latter are usually quite small and disseminated in large numbers over the diseased lobes. The former represent larger masses from a marble to a horse- chestnut in size. They represent tissue which has ;been de- stroyed by the rapid multiplication of swine-plague bacteria in particular localities. Hence they are found in all stages of the pneumonia. The large caseous masses may be considered as the result of a slow death of larger areas of lung tissue, due primarily to the gradual overdistention of the tissue by leuco- cytes, and hence the gradual cutting off of the blood supply. One is a rapid death due directly to highly virulent bacteria, the other a slow death, or a kind of dry suppuration in the later stages of the pneumonia, characteristic of the pig, and due indirectly to the irritation of perhaps more attenuated races of bacteria. In some cases there are extensive hemorrhages in the interlobular connective tissue. Hemorrhage in the interlobular tissue of a swine plague- lung : [a) hemorrhage, (b) hepatized lobules. The inflammation of the pleura frequently extends to the pericardium. This membrane is opaque, thickened and its vessels distended. It may be glued to the contiguous lobes of the lungs and covered by a false membrane, smooth or rough- 7 6 SWINE PLAGUE ■ened, which extends upon the large vessels emerging at its base. Disease of the digestive tract in a considerable proportion of animals inoculated with swine-plague cultures consisted in a severe catarrhal inflammation of the lining membrane of the stomach. The hyperemia was very intense, border- ing on hemorrhage. Occasionally the extension of the peri- tonitis, produced by intra-abdominal inoculation along the mesentery causes a severe inflammation, with exudation on the mucosa of the small intestine. A case is reported where all the Peyer's patches of the small intestine were in a hyper- emic, and partly hemorrhagic condition. In the naturally contracted disease extensive hyperemia of the mucosa of the large intestine, bordering on a hemorrhagic condition, has been observed. In other cases a peculiar croup- ous exudation appeared, which seemingly resulted from the effect of swine-plagne bacteria in the large intestine. Fig. ii. Kidney from a case of acute swine plague, showing pun- ctiform hemorrhages, The production of intestinal disease by swine-plague bac- teria may be supposed to go on as follows : the bacteria first attack the lung tissues and there produce more or less hepatiza- tion. The blood through the lungs finds its path partly ob- structed. This reacts on the blood in the right side of the heart and the venous blood entering it. Hence there may be MORBID ANATOMY 77 more or less stasis of blood in the portal circulation which in turn impairs the digestive functions of the stomach. The swine-plague bacteria in the lungs in the later stages of the pneumonia may be coughed up in the contents of the bronchial tubes, swallowed and passed through the impaired stomach unharmed into the intestines. The stagnation of the feces in the large intestine furnishes the bacteria an opportunity to cause inflammation with exudation of the mucous membrane. The tendency of swine-plague bacteria to cause fibrinous in- flammatory deposits on serous membranes may serve to explain such action on mucous membranes. There is general congestion with resulting degeneration of the parenchyma of the spleen, kidneys and liver in the acute septicemic forms of the disease. In these cases the specific bacterium is easily obtained from the abdominal organs. In brief, the lesions of swine plague as they appear in various outbreaks may be summarized in four classes, namely : 1. The acute septicemic form in which the lesions are characterized by a general hyperemic condition of the serous membranes and parenchymatous organs. Not infrequently hemorrhages, especially the punctiform variety, occur. No localized lesions. 2. Cases of pneumonia with or without pleuritis. The other organs remained normal in appearance. 3. Cases where either in addition to, or possibly in the absence of, the lung lesions there are marked anatomical changes in the mucosa of the digestive tract and possibly in the lymphatic glands. 4. Cases of mixed infection, especially with hog cholera, where in addition to the swine-plague lesions which may be more or less modified, there are those, especially of the digestive tract, characteristic of the accompanying disease. In order to present as clear a picture as possible of the findings in a case of this disease, the published autopsy notes of one animal are appended. "Pig died yesterday, put on ice. Weight about 30 pounds. Skin on ventral aspect of body more or less reddened ; over the sternum a few excoriations. The enlarged inguinal glands show as lumps under 78 SWINE PLAGUE the skin. On section they present a mottled gray and red surface, the red limited chiefly to the cortex. Edema of the subcutis over right knee. "False membrane covers the left half of the mass of intestines and the spleen ; consists of an elastic, rather firm yellowish white layer. Spleen firmly glued to the surrounding intestines, slightly enlarged, dark, softened. liver firm, cut with considerable difficulty. Kidneys in condition of parenchymatous degeneration. One hemorrhagic spot in medullary portion of the kidney. Pelvis contains a whitish glairy liquid. "Digestive tract. Two superficial necroses on the inner surface of lower lip in front, one on the upper lip and on edge of tongue near tip. Stomach contains a little deeply bile-stained fluid. Mucosa sprinkled with red spots of a washed-out appearance, most numerous in fundus and near pyloric valve. Hyperemia of duodenum begins sharply at pyloric valve. From the opening of bile duct a few drops of thick bile can be expressed. Remainder of small intestine not markedly changed. The Peyer's patch in lower ileum has some of its follicles enlarged from which caseous masses can be expressed. "Large intestine contains much sand and gravel. Mucosa of caecum of a dark slate color. The summit of the folds of a purplish hue. Free edge of valve bordered by a thin slough. On Peyer's patch near valve areas of necrotic tissue of a yellowish color, resting on a firm, yellowish- white base three-sixteenths of an inch thick. Upper colon has its mucosa of the same dark slate color, merging into a wine red. Two ulcers one-eighth of an inch in diameter observed. In lower colon con- gestion slight and gradually disappearing towards rectum. A small number of circular whitish erosions, apparently associated with the solitary follicles. "Thorax. On the left lung, the ventral and cephalic lobes are in- terspersed with small regions of collapse. The remainder of the lobes very emphysematous and hyperemic. Of the right lung, the anterior half (i. e., including cephalic, ventral, and adjacent portion of principal lobes) hepatized, covered by a thin false membrane, gluing the various lobes lightly to each other and to chest wall. The diseased lobes show the regular mottling in the upper, dorsal portion. As we proceed to- wards the ventral portion the mottling is less distinct, the tissue firmer and interspersed with small, irregular, necrotic foci. The smaller bron- chi contain a thick, whitish pus. In ventral lobe a portion of the par- enchyma as large as a marble completely converted into a grayish- yellow homogeneous mass. Of the principal lobe about one-third or one-fourth hepatized. The mottling of surface very regular. On sec- tion grayish, circumscribed areas one-half an inch in diameter inter- spersed. Over these masses the pleura is converted into a wrinkled, roughened, hide-like membrane. "Trachea and bronchi contain small quantities of foamy liquid in- MORBID ANATOMY 79 termingled with yellowish particles. Bronchial glands barely enlarged, firm ; some lobules pale, others reddened. "Bacteriological notes. At the autopsy an agar tube was inoculated with a platinum loop lightly rubbed over the pleural exudate. On the following day a thin grayish growth with condensation water clouded. Examination of hanging drop and stained cover-glass preparations shows only swine plague germs. "In cover-glass preparations of hepatized lung tissue a large number of germs resembling swine-plague bacteria were seen. "With a bit of hepatized lung tissue, a rabbit was inoculated subcu- taneously at 2 p. M. The rabbit was dead next morning at 8 A. M., i. e„ in less than 18 hours. In spleen, liver, and blood preparations numer- ous polar-stained swine-plague germ9 present. An agar culture from heart's blood contained only swine-plague germs. "From the peritoneal exudate of pig, consisting of cells and fibrin and numerous bacteria of several varieties, two agar plate cultures were made. On Plate A one large colony of spore-bearing bacilli and one small colony of swine-plague germs. Plate B, completely overgrown by the spore-bearing bacillus. "A bouillon culture from the exudate contains streptococci and swine-plague bacteria. Agar plate cultures were made therefrom and both germs isolated. "At the same time a large rabbit was inoculated subcutaneously with a bit of the exudate. Dead in 18 hours. Stained cover-glass pre- parations of blood from heart, spleen, and liver tissue show polar- stained swine-plague germs. An agar culture from the blood contains only swine-plague germs. "From the spleen, after thoroughly scorching through the exudate, two agar plate cultures and a bouillon culture were made with bits of spleen pulp. The bouillon culture contained only swine-plague germs. "The swine-plague bacteria were thus obtained from lungs, pleura, spleen, and peritoneal exudate, while hog-cholera bacilli, which were looked for with the greatest care, could not be found." (Smith, Re- port on Swine Plague, p. 62.) The course of the disease varies in acute cases from one to three weeks. In chronic or complicated cases it is indefinite. The prog7iosis in swine plague is very unfavorable. Most of the affected animals die, and those that recover are usually not thrifty. § 71. Differential diagnosis. In sporadic cases, swine plague is to be differentiated from broncho-pneumonia due to other causes than the swine-plague bacterium. Pneumonia of a non-specific nature is often associated with deaths due to 80 SWINE PLAGUE dietary or other causes. It frequently causes death in chronic cases of other diseases (terminal pneumonia). In epizootics or outbreaks, it is to be distinguished from hog cholera when there is accompanying catarrhal pneumonia. To make a positive diagnosis, it is usually necessary to depend upon the results of the bacteriological examination. Pneumonia resulting from lung worms, (Strongylus para- doxus) can be distinguished by a careful examination of the contents of the bronchioles. In case of coexistence of hog cholera and swine plague a bacteriological examination is necessary to determine the pres- ence of the two diseases, owing to the possibility of an accom- panying or terminal pneumonia with hog cholera. The question has arisen as to whether the presence of Bad. septicemiae hemorrhagicae in the hepatized lung constitutes a diagnosis of swine plague. As understood at the present time it would seem that the presence of this species of bacteria would indicate the nature of the disease. It must be remembered, however, that bacteria not readily distinguishable from the swine-plague organism exists in the normal upper air passages, from whence it could be brought into the diseased lung and in such a case it might appear as a secondary invader only, or it might have been primarily the cause of the lesions. It is not improbable that epizootics may start from these sporadic cases, although conclusive proof of this is still wanting. It seems, however, that the presence of this organism in the lung tissue of a sporadic case should be considered in the light of the dis- tribution of these organisms and not necessarily as the starting of an epizootic. §72. Prevention. Recent investigations show that out- breaks of swine plague are much more extensive than hereto- fore supposed. The present knowledge of this disease indi- cates that the adoption of measures for its prevention is quite as important as for hog cholera. In general the measures to be adopted and followed and the rules to be observed in the prevention of epizootic swine plague are practically the same as those for the prevention of hog cholera. It will be seen from a comparison of the two species of bacteria that the SPECIFIC TREATMENT 8 I bacillus of hog cholera is a more hardy organism than that of swine plague. Thus the swine-plague bacterium is destroyed more rapidly by drying and will live a much shorter time in the soil. However, the channels through which it may gain access to a herd are practically the same, and every precaution suggested in reference to hog cholera, is applicable to swine plague. It is believed that the time during which a field, hog yard or pen should be kept free from swine after the appear- ance of the disease can, with safety, be shorter after swine plague than after hog cholera. In any case several months should elapse before the yards or pens are reoccupied. If the disease appears, the well animals should be promptly separated from the sick and placed in suitable pens or yards — protected against subsequent infection, and given an abundance ot wholesome food and water. It is well to remove the sick animals to other pens. The thorough disinfection of the infected pens should be insisted upon before they are again occupied. § 73. Specific treatment. For a number of years in- vestigations have almost constantly been under way in the United States Bureau of Animal Industry, for the purpose of finding some method by which the disease could be success- fully and specifically treated when introduced into a herd. Drugs and medicines have been tried, preventive inoculations and injections of toxins have been made. The serum therapy which has affected relief in certain other diseases has been and is now being tested with somewhat favorable results, yet we do not see that a specific therapeutic agent has been demonstrated. In view of this, it becomes necessary to apply with renewed zeal our present knowledge of the nature of the malady and endeavor to prevent its occurrence or reappearance by keeping the animals under the best possible conditions. Prevention of the disease is more promising than treatment. § 74. The effect of swine-plague bacteria in rabbits. In 1894, Smith and Moore described the appearance of the effect of swine-plague bacteria in rabbits and also the effect of resistance on the part of the rabbit on the form of the resulting lesions. As this disease is caused by a bacterium belonging 82 SWINE PLAGUE to the septicemia hemorrhagica group, it seems desirable that the results above referred to should be restated. The appended paragraphs are taken from the report of these investigations. Among the forms of disease observed after the subcu- taneous inoculation of rabbits with swine-plague bacteria from different sources (epizootics) are the following : Septicemia. Peritonitis. Pleuritis (usually with pericarditis). Pleuritis (usually with pericarditis and peritonitis). L,ocal lesion only. In septicemia, death ensues within eighteen or twenty- four hours. The local lesion produced at the seat of inocula- tion is slight. Bacteria are abundant in the parenchyma (blood vessels) of the various organs. In the form character- ized by peritonitis death ensues in three to seven days. The local lesion, which in all these forms of diseases increases in •extent with the prolongation of the life of the animal, is here characterized by' more or less suppurative infiltration of the skin and the subcutis. The peritonitis in its earlier stages is •characterized by punctiform hemorrhages on the cecum and a. fibrinous or cellular exudate. It always contains immense numbers of bacteria. When pleuritis is also present the exu- date usually involves the pericardium as well. It varies in amount according to the duration of the disease and is essen- tially the same as the peritoneal exudate. The form characterized by pleuritis and pericarditis with- 'Out peritonitis is interesting in so far as the seat of inoculation does not explain the localization, for, in every case, the inocu- lation was made in the region of the abdomen. The lungs may become hepatized secondarily through invasion from the pleura if the animal lives long enough. Lastly, the form of disease in which the only localization is a very extensive suppurative infiltration associated with hemorrhage and edema of the subcutaneous tissue is not common. It should be stated that the cultures from the same out- break continued to produce the same form of disease in rabbits MODIFICATIONS 83 until modified by age. The maintenance of a certain uniform virulence for years is well exemplified by a variety isolated in the summer of 1890. This variety was fatal to rabbits within twenty hours when first isolated and this degree of virulence has maintained itself up to the present, a period of nearly four years. § 75. Modifications of the septicemic type by in- creasing the resistance of rabbits. By the injection of steril- ized cultures which increase the resistance of rabbits, Smith and Moore were able to produce nearly all the pathological variations which follow the inoculation of natural races of swine-plague bacteria as isolated from outbreaks. This modi- fication of the septicemic type is not fortuitous, for among the large number of rabbits inoculated during the past three and one-half years with the culture employed, none have survived twenty to twenty-four hours. Whenever the course of the inoculation disease in rabbits departed from this rapidly fatal type, it was due to some preliminary treatment of the rabbit. The degree of resistance determined quite regularly though not invariably the form of the disease. This degree was measured by the relative quantity of the protective ma- terial (sterilized cultures, sterilized blood, and blood serum) injected. The grades of disease induced range themselves in the following order : 1. No resistance — acute septicemia. 2. Slight resistance — peritonitis. 3. Increased resistance — pleuritisand pericarditis with or with- out secondary pneumonia. 4. Higher degree of resistance — pleuritis and peritonitis. 5. Still greater resistance — irregular lesions in the form of ab- scesses, subcutaneous and subperitoneal. 6. Nearly complete immunity. Very slight reaction at the point of inoculation. Most of the cases cited below as illustrating these modified forms of the septicemic type belong to the series of immuniz- ing experiments of the preceding article. To this the reader is referred for additional illustrations. First degree of resistance — peritonitis. — Rabbit No. 12 re- ceived 7 cc. of bouillon culture of swine-plague bacteria steril- 84 SWINE PLAGUE ized by heat. Subsequently with a control rabbit it was in- oculated with a minute dose of swine-plague bacteria under the skin. The control died within eighteen hours, the treated rabbit in three days. The macroscopic changes were limited to the point of inoculation and the peritoneum. At the former there was a purulent infiltration of the subcutis, 1.5 cm. in diameter, with dilatation of surrounding blood vessels. The peritonitis was characterized by an exudate of a slightly viscid character covering liver, spleen, and cecum, and made up of fibrin, leucocytes and immense numbers of bacteria. Second degree of resistance — pleuritis and pericaj-ditis. — Rab- bit No. 38 was treated before inoculation with 4.5 cc. of a sterilized suspension of agar cultures of swine-plague bacteria in 3 doses. Together with a control rabbit, it received under the skin the equivalent of 0.001 cc. of a fresh bouillon culture of swine-plague bacteria. The control died in twenty hours. The treated rabbit died six days after inoculation. At the point of inoculation there was a purulent infiltration of the sub- cutis 3 cm. in diameter. The abdomen and abdominal viscera were free from macroscopic changes. In the thorax, the pleural cavity was lined with a grayish, friable exudate consisting of round cells and bacteria. Lungs hj'peremic and only partly collapsed. Pericardium also covered with a slight exudate. Third degree of resistance — pleuritis {pericarditis) and peri- tonitis. — Rabbit No. 15 received in the ear vein a total of 12 cc. of a sterilized bouillon culture of swine-plague bacteria. It was inoculated subcutaneously with virulent swine plague bacteria May 26, and died June 3, eight days later. The control rabbit died within eighteen hours. The following changes were observed : A purulent infiltration into the subcutaneous tissue at the point of inoculation extending over an area 6 cm. in diameter. The superficial layer of the subjacent muscle discolored. Surrounding the area of infil- tration the blood vessels were injected. The cecum and liver were cov- ered with a very thin grayish exudate, which also appeared on and between the coils of the intestine. Spleen not enlarged. The right lung and chest wall covered with a thin grayish exudate. In the cephalic lobe, two small areas of consolidation ; principal lobe hyperemic. The left pleural cavity lined with a quite thick membran- RESISTANCE IN RABBITS 85 ous exudate, which covered the entire surface of the lung. On the dor- sal surface of the principal lobe a mass of lung tissue 2 cm. in diameter, firm and of a yellowish-gray color. The remaining portion of the prin- cipal lobe hyperemic ; cephalic lobe in a state of collapse. Pericardium covered with a thin cellular exudate. Higher degrees of resistance . — None of the treated animals which have come under our observation have succumbed to a mere extension of the lesion produced at the point of inocula- tion as is occasionally observed after inoculation with certain varieties of swine-plague bacteria found in nature. There have been noticed, however, certain peculiar localizations resem- bling those produced in the subcutis after inoculation, and in a few cases the local lesion persisted a considerable length of time. It was quite severe in all fatal cases in which the disease was prolonged several weeks after inoculation, although the real cause of death was due in all such cases to localizations on one or more of the serous membranes. The peculiar forms of disease may be grouped as follows : {a) Persistence of local lesions. — Rabbit No. 50 received in the abdominal cavity 3.5 cc. of the sterilized suspension of agar culturesin 3 doses. It was subsequently inoculated beneath the skin with 0.001 cc. of a bouillon culture of swine-plague bacteria which produced a large local swelling. On February 25, 1892, nearly eight months after its inoculation it was chloroformed. The only lesion fonnd was in the subcutaneous tissue. At the point of inoculation the skin was sloughed over an area 3 cm. in diameter. The denuded surface was covered with a thick scab. The subcutis beneath the scab and surrounding the ulcer was infiltrated with pus. A stained cover-glass preparation showed swine-plague bacteria. No other lesions were found. (b) Sub-peritoneal abscess.— Rabbit No. 16 was injected intraven- ously with 16 cc. of sterilized bouillon cultures of swine-plague bacteria. After some days it was inoculated beneath the skin with 0.001 cc. of a fresh bouillon culture of virulent swine plague bacteria. The control rabbit died within twenty hours. Rabbit No. 16 showed no ill effect from the inoculation for several months when it was noticed that it was becoming emaciated. It died June II, 1892, one year and six days after its inoculation, with a subperitoneal abscess. (c) Multiple abscesses under the skin.— Rabbit No. 439 received into the ear vein in three injections 4 cc. of sterilized blood from a swine plague rabbit. Later it was inoculated subcutaneously with 0.001 cc. of a bouillon culture of>irulent swine-plague bacteria. The control rabbit died within twenty hours. Two months after the inoculation it was ft^v 86 SWINE PLAGUE noticed that this rabbit with others was suffering from a large number of subcutaneous abscesses." REFERENCES. 1. DE SchwEiniTz. Serum therapy. Proceedings Society for the Promotion of Agricultural Science, 1896, p. 47. 2. be SchweiniTz. The serum treatment of swine plague and hog cholera. Bulletin No. 23. U. S. Bureau of Animal Industry ■, 1899. 3. LoEFFi/ER. Arbeiten a. d. Kaiserlichen Gesundheitsamte , Bd. I (1885), S. 51. ^J 4. Moore. Pathogenic and toxigenic bacteria in the upper air passages of domesticated animals. Bullet in No. 3. U. S. Bureau of Animal industry, 1893. " ? 5. Moore. Concerning the nature of infectious swine diseases in the State of New York with practical suggestions for their prevention and treatment. Report of the New York State Commissioner of Agriculture, 1897. S 6. Smtttt. Preliminary investigations concerning infectious pneu- monia in swine (Swine plague). Ann. Rpt. Bureau of Animal In- dustry, U. S. Dept. of Agriculture. 1886. p. 76. * 7. Smith . Special report on swine plague. Bureau of Animal Industry, U. S. Dept. of Agriculture, 1891. 1/ 8. Smith and Moore. Experiments on the production of im- _ munity in rabbits and guinea pigs with reference to hog cholera and swine plague bacteria. B ulletin No. 6 , Bureau of Animal Industry, U. S. Dept. of Agricultnre, 1894. p. 65. 9. WELCH and Clements. Remarks on hog cholera and swine plague. First International Congress of America. Chicago. 1893. HEMORRHAGIC SEPTICEMIA 87 HEMORRHAGIC SEPTICEMIA IN CATTLE. § 76. Characterization. Hemorrhagic septicemia in cattle is determined by an acute attack usually running a rapid course and terminating fatally. The lesions consist largely of hemorrhagic areas more or less widely distributed throughout the body and due to the presence of a specific microorganism. §77. History. In 1879, Bollinger described under the name of Wild-und Rinderseuche an epizootic disease which killed a large number of wild boars and deer in the Royal game preserves of Munich. After the disease in these animals had died out, the domestic cattle in the neighborhood began to die of the same or a very similar affection. He reports it to be sudden in its onset and rapidly fatal in its course, with a mortality of 90 per cent. Death occurred in from 12 hours to a few days after the appearance of symptoms. An exanthematous and a pectoral form are described. In the exanthematous form there are large and small hemorrhages disseminated throughout the muscles and viscera. The intes- tines exhibit large numbers of ecchymotic areas, while the submucous tissue is infiltrated with a serous exudate. Large hemorrhagic tumors infiltrated with serum are abundant in the subcutaneous tissue, often extending into the muscles. The mucous membranes of the tongue, larynx and pharynx, and the lymphatic glands of these regions, are swollen and infiltrated with more or less bloody serum. In the pectoral form, there is a hemorrhagic lobular pneumonia, with considerable infil- tration into the interlobular tissue of a serofibrinous exudate. The pleura is infiltrated and inflamed and covered with a fibrinous exudate. The pleural cavities contain from two to twenty-five litres of liquid. At the same time there exist a eertain degree of hemorrhagic enteritis and the widely dissem- inated hemorrhagic lesions common to the preceding form. In 1885, Kitt studied an epizootic disease in cattle and swine in Sincbach. From this disease he isolated a short, polar staining, non-motile, rod-shaped organism, fatal to cattle^ horses, pigs, sheep, goats, dogs and rabbits. In the following 88 HEMORRHAGIC SEPTICEMIA year Oreste and Armanni reported a destructive disease of young buffaloes in Italy with symptoms and lesions similar to those reported by Bollinger and Kitt. This disease had been known in Italy for a century or more, where in certain districts it is reported to have recurred with great regularity, destroying both old and young animals. In the same year {1885) Poels described a septic pleuro-pneumonia in calves which prevailed in the vicinity of Rotterdam. It was of a septicemic nature. From the organs he obtained an organism belonging to the Bacillus septicemiae hemorrhagicae group of bacteria. In 1889, Jensen described a similar disease affecting calves in Jutland. In the same year Piot reported the presence of "barbone" in the buffaloes and domestic cattle in Egypt. In some districts 40 per cent, of the horned cattle are said to have died in a single year. It is reported as being more prevalent in the wet season. In 1890, Van Ecke described a hemorrhagic septicemia in cattle in Dutch India, particularly in Java, the lesions of which were similar to those first described by Bollinger. The specific organism was virulent for rabbits, mice, turtle doves, calves, horses and swine ; sheep and asses were almost immune. In the following year Galtier described the same disease imported from Algiers to Lyons. A number of other investigators have studied and reported cases of this disease. In 1890, Nocard isolated from cases of broncho-pneumonia in American cattle landed at La Villette, France, an organism similar to that described as the cause of septicemia hemor- rhagica. In 1896, Smith called attention to a similar organism which he found in cases of sporadic pneumonia in cattle ; he does not think, however, that this organism was primarily the cause of the disease, giving it a secondary place in the eti- ology. As early as 1891, Smith published the discovery of the presence of an organism morphologically and in its cultural characters identical with that of swine plague in the upper air passages of healthy swine. The same year Moore reported the presence of a like organism in the upper air passages of cattle, horses, sheep, dogs and cats. The following year, Fiocca de- HISTORY 89 scribed a pathogenic bacterium resembling that of rabbit septi- cemia in the saliva of healthy cats and dogs. Hueppe proposed the name Bacillus septicemiae hemor- rhagicae for this group of organisms and septicemia hemor- rhagica for the disease they produce. Lignieres has designated the diseases caused by this group as Pasteurelloses. While there may be objections to this unifying name, there seems to be no serious reason for not accepting it as a working hypoth- esis. In 1898, Fennimore described under the name of "Wild and Cattle Disease" a malady occurring in Eastern Tennessee. Its serious nature caused an investigation to be made by the Tennessee Agricultural Experiment Station. Norgaard, who assisted in this investigation, recognized it as the same disease -as that described by Bollinger in 1878. Fennimore states that it has occurred to a considerable extent in his practice. In 1901, it was carefully studied by Wilson and Brimhall for the Minnesota State Board of Health. They report 60 cases of this affection which they have examined in cattle in the state of Minnesota. In 1903, Reynolds described an investi- gation into several outbreaks of this disease in the same state. It is from the two latter reports that we draw very largely for the symptoms and morbid anatomy of this disease in cattle. § 78. Geographical distribution. It will be seen from the history that this disease is a wide spread malady occurring in nearly every country. It appears to be quite prevalent in the western and northern parts of the Mississippi valley. It occurs in other localities more rarely. § 79. Etiology. Septicemia hemorrhagica in cattle is caused by an organism belonging to the group of bacteria •designated by Hueppe as the hemorrhagic septicemia group and specifically named Bacillus bovisepticus by Kruse. This, according to Migula's classification, should be Bacterium bovisepticum. A brief description of the organism as given by Wilson and Brimhall is appended. "The organism has a strong tendency to show polar staining in tis- sues and to form chains of much shortened individuals in liquid media, which causes it to be mistaken in examinations of a single specimen for a diplococcus or a streptococcus. Sometimes in cover-glass preparations 90 HEMORRHAGIC SEPTICEMIA from solid organs and very frequently in those from body fluids and liquid cultures, the bacteria were found in chains of three to twelve individuals. In cover-glass preparations the bacteria are from o.6/< to 0.8/1 broad and from 1.0 to 1.5/u in length. In tissues which have been fixed in 96 per cent, alcohol, they are somewhat smaller. In cultures, especially in fluid media, they are apt to be much smaller and approach diplococci in appearance. The ends are rounded. In stained preparations directly from the tissues most of the bacteria have the ends intensely stained and the central portion but faintly so. In some chains in rapidly grow- ing broth cultures this is not the case, many of the individual bacteria being evenly stained throughout and somewhat pointed at the ends. They do not retain the stain by Gram's method. The organism is non- motile. It is aerobic, but prefers the depths rather than the surfaces of the media. It grows best at the body temperature and more slowly at room temperature. In plain and dextrose broth a heavy growth appears in 24 hours. In Dunham's solution a small amount of indol is formed in 48 hours. No coagulation of milk. On I/ofHer's blood serum, direct from the diseased tissues, it failed to grow well. On potato no appreci- able growth has been obtained. In gelatin plates small, granular, white to slightly yellowish colonies appear after 48 hours. In gelatin stab cultures a light growth occurs on the surface, while along the needle tract numerous colonies like those in the deep portions of the plate cultures develop. The bacteria are destroyed in fluids at 58° C. in 7 or 8 minutes, by 1 to 5,000 mercuric chloride in one minute, and by a solution of lime water as weak as 0.04 per cent, almost immediately." The period of incubation is supposed to be very short. The method of infection is not known. § 80. Symptoms. There is little opportunity to deter- mine the symptoms. The animals observed at the onset of the disease by Wilson and Brimhall appeared to be dumpish and out of sorts. There is sudden stopping of the milk secretion in milch cows. As a rule the affected animals refuse food. Of the few that make an attempt to eat, those with affected throats are unable to swallow except with much difficulty. These cases also breathe very heavily. The animals show marked dis- inclination to move and when incited to do so, exhibit stiffness, and in some instances actual lameness. Animals have been observed to drop to the ground and die in a short time, ap- parently without pain. Other animals live for several hours in great pain as indicated by groans and spasms of the muscles. The paroxysms of pain are apparently intermittent. There is SYMPTOMS 91 extremely rapid loss of flesh in the animals that are sick for any length of time. Reynolds has observed the symptoms in a few cases. He describes three stages. First, (24-36 hours) general dullness and checking of milk secretion. Second, diarrheal discharge dark in color, and of disagreeable odor. The breath was noticed to be offensive. In some cases nervous symptoms de- veloped. The temperature remained about normal during this period. Third, in this stage the eyes are wild, there is grinding of the jaws, convulsions of the face and neck muscles followed by a period of intense restlessness and activity. He also records the observation that the cases that ap- peared to be the worst in the beginning lived longer than those that appeared to be mild. Opportunities for the accurate determination of tempera- ture at the beginning of the disease have been very few. An initial temperature of 105.6° F. followed by a rapid decline has been observed. Painful edematous swellings about the legs, shoulders and under the throat are noted as early symp- toms. The intestinal discharges are often streaked with blood. In other cases the feces are black, tarry or of a bloody, serous nature. Bloody urine and a bloody serous discharge from the nose have been present in some cases. The vaginal and rectal mucous membranes are intensely congested. The marked swelling of the face, stomatitis, glossitis, and convulsive movements of the jaws in the pneumonic form of the disease, described by European writers, more especially Bollinger, were not observed by Wilson and Brimhall or by Reynolds. The duration of the disease is short. Often the animals are found dead. The prognosis is unfavorable. The mortality is placed at from 80 to 90 per cent, of the animals affected. §81. Morbid anatomy. The characteristic lesions of the disease are widely distributed areas of hemorrhage, vary- ing in size from a pin point to several centimeters in diameter. They vary in color from light red to almost black. They are frequently accompanied with a sero-fibrinous exudate, usually 92 HEMORRHAGIC SEPTICEMIA yellow, but occasionally dark red in color. The hemorrhagic areas in the animals just dead are not so dark as those in animals that have been dead for some hours. The large areas, some centimeters in diameter, are apparently due, in some instances at least, to single hemorrhages, infiltrating an exten- sive mass of tissue, and in others to a number of minute hem- orrhages closely placed and partially coalescing. Gas is not present in the subcutaneous connective tissue except in cases where extensive post-mortem changes have occurred. There is extensive fullness of the vessels of the subcu- taneous connective tissue in the acute cases, especially in those animals which are not killed by bleeding. In animals which live until emaciation is marked, there is no engorgement of the vessels. Reynolds reports one outbreak in which meningitis in- volving the spinal cord, brain or both of these organs were invariably present. All cases show some hemorrhagic areas in the subcu- taneous tissue, though the number and size of these vary greatly in the different cases. Some animals show not over a dozen areas between two and three centimeters in diameter, though many minute ones are present. In other animals, on removing the skin, hemorrhagic areas are found in great num- bers and so extensive that a large fraction, possibly one-eighth, of the body surface appears to be involved. The large hemor- rhages in the subcutaneous connective tissue appear to be of the composite type noted above. The location of the superficial lesions varies in different animals. In most cases the parts about the shoulder are most affected. A few animals show marked lesions in the gluteal and inguinal regions. At first sight the muscle tissue in some cases seems to be much involved. A closer examination, however, usually shows that while some of the minute hemorrhages are in the muscle proper, the larger ones are in the intermuscular con- nective tissue. They are usually accompanied by a consider- able quantity of yellowish or blood stained serous exudate. MORBID ANATOMY 93 The intermuscular connective tissue appears to be quite as much involved as the subcutaneous connective tissue. The lymphatic glands are frequently though not uniformly nor constantly enlarged. Those that are enlarged are edematous and often hemorrhagic. The cervical and prescapular glands are most seriously affected. Fig. 12. Photograph showing hemorrhages beneath the endocar- dium of the right ventricle {Reynolds). The nasal mucous membrane in some cases is congested, and a bloody serous discharge from the nostrils is present. <54 HEMORRHAGIC SEPTICEMIA The tissues around the larynx are hemorrhagic and infiltrated with blood-stained serum. The mucous membranes of the larynx and trachea are more or less congested and covered with a frothy mucus, sometimes streaked with blood. In some instances no lesions are observable in these organs. The lungs are in general almost free from evidence of disease. Occasion- ally there are a small number of hemorrhagic areas, pyramidal in shape with their bases on the pleura. In most cases the parietal pleura is studded with small hemorrhages. The •diaphragm sometimes contains very large hemorrhagic areas. The pericardial sac usually shows small, sometimes very numerous, hemorrhages in the walls, and in many instances contains a blood-stained serum. The heart walls, with but few exceptions, contain ecchy- moses and petechiae. These sometimes extend deep into the muscle. Similar areas of hemorrhage are also visible in the ■endocardium. The heart usually contains post-mortem blood clots. The blood, in animals just dead, is said to be somewhat lighter than normal in color. When post-mortem changes set in, the blood is darker in color, but reddens on exposure to the air. The spleen shows on its surface a few small hemorrhagic areas. It is usually normal in size, color and consistency, except where post-mortem changes have taken place. Stomatitis and glossitis are rarely observed. The pharynx is usually congested. The stomach walls contain few or many hemorrhagic areas. These are sometimes extremely large, especially on the third stomach. As a rule the larger hemorrhages penetrate the entire thickness of the walls. The smaller ones are confined to the subserous or mucous coats. The stomach contents are apparently normal. The intestinal walls are constantly affected. Hemorrhagic areas involving all the coats are frequently present. Smaller ones, visible only from the inner or outer surface, are always present. General enteritis and peritonitis are constantly observed. Localized enteritis is frequent. MORBID ANATOMY 95 The bowel contents are in some cases dark and tarry ; in others the feces are apparently normal in color and consistency but streaked with bloody mucous. The kidneys are usually but slightly affected. When lesions are present they are hemorrhages but pin point in size and mostly confined to the cortical substance, though a few are found in the walls of the pelvis and ureters. The urine is bloody in some instances. The vaginal mucous membrane is congested in many cases. Wilson and Brimhall saw one animal that was four months pregnant which exhibited small hemorrhagic areas in the placental membranes. The udder is congested in some cases. It may be hemorrhagic. The central nervous system occasionally shows hemor- rhages in the dura. A few cases are reported of hemorrhages on all of the joint surfaces. Brimhall recently reported an outbreak where the autopsies showed very few hemorrhagic areas in the subcutis and internal organs. There were lesions in its spinal cord. The spleens were enlarged. In nine out- breaks Bad. bovisepticum was present. Wilson and Brimhall fixed portions of the subcutaneous tissue, skeletal muscles, lymphatic glands, lung, heart wall, stomach wall, and spleen in 95 per cent, alcohol and in 4 per cent, formaldehyde solution and stained by various methods. In general, the lesions found were enormous extravasations of blood, some recent and some showing coagulation of fibrin. In the areas of less recent hemorrhage, the surrounding tissues showed varying degrees of ordinary coagulation necrosis. This was particularly marked in the affected muscles, lymph gland and portions of the lungs. In the borders of such necrosed areas leucocytic infiltration was not infrequent. In the spleen in which the hemorrhagic areas were neither num- erous nor large, there was in some instances an apparent destruction or shrinkage of the parenchyma. A very important feature in this disease has been brought out, namely, that it is necssary, in order to obtain cultures of the bacterium producing it, that the media should be inocu- Q6 HEMORRHAGIC SEPTICEMIA lated at once. It is evident from the literature, that with this precaution cultures should invariably be obtained. § 82. Differential diagnosis. Septicemia hemorrha- gica in cattle must be differentiated from anthrax, sympto- matic anthrax, and the affection known as "corn-stalk dis- ease." Death from this disease must also be distinguished from those due to certain accidental causes, poisoning, or the effect of over eating of grain or green fodder (hoven). The suddenness with which the animals may die from all of these causes renders the symptoms, should they be observed, of very little value in making a diagnosis. It is necessary, therefore, that in all casses, especially with the first animals to die, careful post-mortem and bacteriological examinations should be made. In case of septicemia hemorrhagica, the cultures will usually reveal the presence of Bad. bovisepticum . The lesions will be hemorrhagic in nature. In case of the "cornstalk disease" the lesions may consist of small hemorrhages (petechise) especially of the serous membranes and heart. The cultures will be negative. With anthrax and symptomatic anthrax, their specific bacteria will be found. § 83. Prevention. When this disease occurs it is im- portant to remove the unaffected animals to other fields or enclosures. It is well to divide them into small groups if possible. The carcasses of animals that die should be burned or buried deeply with a good covering of a disinfectant, such for example, as quick lime. Should death occur in a stable, all contaminated litter should be burned and the floors, mangers and walls thoroughly disinfected. Experiments directed towards protective inoculation have been made, but thus far the results have not been sufficiently satisfactory to warrant the recommendation of the methods. REFERENCES. 1. Bollinger. Ueber eine neue Wild-und Rinderseuche. Miinchen. 1878. J Brimhall. Haemorrhagic septicemia in cattle. Amer. Vet. Rev. Vol. XXVII (1903-4), p. 103. REFERENCES 97 2. Fennimore. Wild and cattle disease. Jour, of Comp. Med. and vet. Archiv. Vol. XIX (1898), p. 625. 3. Gai/Tier. Nouveaux faits tendant a etablir que la pneumo- enterite infectieuse existe sur les grands et les petits ruminants en algerie. Recueil de tried, vet., 7 serie, Vol. VIII (1891), p. 97. 4. HueppE. Ueberdie Wildseuche. Berlin, klinisch Wochenschrift, 1886, p. 753. 5. KiTT. Uebereine Experimentelle,der Rinderseuche (Bollinger) ahnliche Infectionskrankheit. Sitzungsberichte der Gesellschaft fiir Morphologie und Physiologie in Mimchen, I. 1885, p. 240. 6. PiOT. Le Barbone du Buffle. Bulletin d V Instut. Egyptian, 1889. 7. Poels. Septische Pleuropneumonie der Kalber. Fortschr. d. Med. 1886, p. 388. 8. Reynolds. Hemorrhagic Septicaemia. Bulletin No. 82. Minn. Agric. Experiment Station, 1903. \/ V 9. Wilson and Brimhall. Sixty cases of hemorrhagica septi- cemia in cattle due to bacillus bovisepticus. Report State Board of Health of Minnesota, 1901. (Very full bibliography.) v 11. Woolsey and Jobling. A report on hemorrhagic septicemia in animals in the Philippine Islands. 1903. No. 9. Bureau of Govern- ment Laboratories, Manila, P. 1. 98 INFECTIOUS DISEASES FOWL CHOLERA. § 84. Characterization. This is an infectious disease of fowls caused by bacteria, and transmissible by cohabitation and inoculation. It is determined by a high fever, great weakness and prostration, and usually terminates in the death of the affected bird. It is reported that it attacks all varieties of domesticated poultry (chickens, ducks, geese, pigeons, tur- keys), and caged birds such as parrots and canaries.. It also attacks some species of wild birds. It is communicable by inoculation to rabbits and mice. Guinea pigs are not very susceptible. §85. History. This disease is mentioned in some of the oldest works treating of the diseases of animals. Fowl cholera was studied by Chabert in 1782, who regarded it as a form of anthrax. Since 1825, it has been frequently observed in France where it caused enormous losses in 1830, in 1850 and in i860. About 1830, it became known in Russia, Bohemia and Austria. In 1851, Benjamin considered it to be a con- tagious disease but remarked that people and dogs might con- sume with impunity the meat of affected fowls. Delafond observed that it might be transmitted to birds and rabbits by ;using blood, secretions, and portions of the flesh. It was also recognized that the excrement plays an important part in the dissemination of the virus. During recent years it has been observed in nearly all of the countries of Europe as well as in the United States. It has been reported from many places in the United States, but its presence seems to have been determined by scientific investigation in but a very few of these. Salmon investigated it in South Carolina in 1879-80, and Higgins in 1898 reported it from Canada. Salmon gave special attention to vaccination and the effect of disinfectants in destroying the virus. In 1904, Ward reported an outbreak in California. Perroncito was among the first to describe the specific cause of the disease. This was followed by the contributions of Pasteur, who, in 1880, cultivated the bacterium in chicken broth and showed that its virulence might be reduced to such an extent that it could safely be used for vaccination. This ETIOLOGY 99 is the first case in which a virulent organism was successfully modified in a laboratory and made to act as a vaccine. It was the forerunner of the preparation of vaccines for a number of diseases, more particularly for anthrax, black quarter, and rabies. § 86. Geographical distribution. Fowl cholera seems to be widely distributed in Europe and it has been found in a few localities in the United States and in Canada. § 87. Etiology. Fowl cholera is caused by a specific bacterium which is not distinguishable morphologically or in its cultural manifestations from the other members of the group of bacteria of which Bad. septicemiae hemorrhagicae is the type. In this group are the bacteria of rabbit septicemia, swine plague, and Wilds euche . It is a small, slightly elongated organism with rounded ends. In stained preparations from the tissues it exhibits a pronounced polar stain. The period of incubation is placed by European writers at from 18 to 48 hours. In the case of 40 fowls inoculated by Salmon, it varied from 4 to 20 days, the average period being 8 days. Ward fed viscera of dead fowls to 10 healthy ones. They died in from 24 hours to 6 days. § 88. Symptoms. The symptoms described for this disease in Europe differ somewhat from those reported by Salmon. Usually the appetite is lessened. Occasionally they continue to eat almost to the time of death. The earliest indication of the disease is a yellow coloration of the urates. In health, these are a pure white though they are frequently tinted with yellow as the result of disorders other than cholera. Occasionally the first symptom is a diarrhea in which the excrement is passed in large quantities and consists almost entirely of white urates mixed with colorless mucus. Very soon after the first symptoms appear the bird sepa- rates itself from the flock, it no longer stands erect, the feathers are roughened, the wings droop, the head is drawn down towards the body and the general outline of the bird becomes spherical or ball shaped. At this period there is great weakness, the affected bird becomes drowsy and may sink into a sleep which lasts during the last day or two of its life and from which it is almost impossible to arouse it. IOO FOWL CHOLERA The crop is nearly always distended with food and appar- ently paralyzed. There is in most cases intense thirst. If the birds are aroused and caused to walk, there is at first an abundant discharge of excrement followed at short intervals by scanty evacuations. With the beginning of diarrhea the body temperature rises to 109 to no° F. Ward states that in advanced stages it ranges from 109 to ii2 u F. The comb loses its bright hue and becomes pale and bloodless. In Europe, the comb is described as dark blue, purple, or black, and some writers in the United States have referred to it in the same terms. Salmon reports that he never observed it. Diseased birds rapidly lose in weight. They become so weak that they walk with great difficulty, a slight touch causes them to fall over. The fowls become very much emaciated. Death may occur without a struggle or there may be convulsive movements and cries. This disease may run rapidly through a flock destroying the greater part of the birds in a week, or it may assume a more chronic form, spreading slowly, and remain upon the premises for several weeks or months. § 89. Morbid anatomy. The comb is pale and blood- less. The superficial blood vessels usually contain but little blood. The liver is usually enormously enlarged, softened, and the blood vessels are engorged. The gall bladder is distended with thick, dark bile. The crop is usually distended with food. The stomach often presents externally a number of circular discolorations, about three millimeters in diameter, which on section are found to be extravasated blood. The small intestines are congested. The rectum and cloaca usually present deep, red lines upon their mucous membrane, evidently the first stage of inflammation, which results, in chronic cases, in thickening of the walls, especially of the rectum, the desquamation of the mucous membrane and the formation of large ulcerated surfaces. MORBID ANATOMY IOI The mesentery is generally congested, often greatly thickened and reddened, and rendered opaque by inflamma- tion. The ureters are distended with yellow urates ; the kidneys seem engorged, and on section accumulations of the tenacious, yellow urates are frequently seen. The spleen is generally normal in size and appearance, though frequently enlarged and softened. The pericardium is sometimes distended with effusions, in which case there is noticeable hyperemia of the surface of the heart. The lungs are often, though not generally, engorged with dark blood ; they are seldom, if ever, hepatized. The blood vessels are sometimes filled with a firm clot, and contain but little liquid ; at other times the blood does not coagulate at all. It seems to be those cases in which the duration of the disease is longest, that the blood loses its power to coagulate. Ward has summarized the morbid anatomy in the fowls examined by him as follows : "At death, or some hours previous, the comb frequently takes on a dark purple color, but this does not always occur. Very often the comb is pale and bloodless. The skin of the breast and abdomen is frequently reddened. "In post-mortem examinations a congestion of the blood vessels of the liver, kidney, mesentery, or intestines is noticeable to some degree in all cases. Punctiform hemorrhages are found upon the heart with almost absolute uniformity. The liver is very frequently marked with punctiform whitish areas of necrosis. Stained sections show these necrotic foci throughout the substance of the liver, and besides reveal a congestion of the blood vessels of that organ. The next most striking lesions occur in the first and second duodenal flexures. The mucosa is deeply reddened and studded with hemorrhages varying in size, but seldom exceeding one millimeter in diameter. These involve the in- testinal coats to an extent that makes them distinctly visible on the peritoneal surface. The contents of the duodenum consist of a pasty mass, more or less thickly intermingled with blood clots. The intestinal contents sometimes consist of a cream-colored pasty mass, or may be brownish red or even green in color. Lesions are very rarely observed in other portions of the intestines. The ureters are noticeable in practically all cases by reason of the yellow-colored urates that they contain. The nasal cavity, pharynx and oral cavity frequently contain a viscous mucous fluid, probably regurgitated from the crop. "The field notes on twenty-one post-mortem examinations refer to 102 FOWL CHOLERA hemorrhages in the heart in twenty-one cases ; punctiform necroses in the liver, fifteen cases ; hemorrhages in duodenum, seven cases ; the dis- coloration of the skin in six cases. The presence of a gelatinous exudate within the pericardium was noted twice. A fibrinous exudate in the pericardium occurred the same number of times. Hemorrhages in the peritoneum other than those visible through the mucosa of the duode- num occurred but twice. In one case hemorrhages were abundantly scattered throughout the muscles of the trunk and legs. "Fowls inoculated subcutaneously with cultures exhibit on post- mortem examination the punctiform hemorrhages on the heart and the hemorrhages in the mucosa of the duodenum exactly as in cases infected naturally. ' ' BLOOD COUNTS OF FOWLS INFECTED BY INGESTION AND INFECTED NATURALLY. Fowl. White. Red. Remarks. Temperature. No. 3 23,000 2,290,000 per cmm. 3 days after exposure to infection 44-6° C. No. 3 20,000 2,800,000 " " 4 " " " " " 43-7° C. No. 6 37,000 3,930,000 " 3 " " " " " 43-3° C. No. 8 87,000 4,490.000 " " 3 " " " " " 42. S° C. No. 8 101,000 2,960,000 " ' 4 " " " " 42.2° C. A ___ 58,000 1,710,000 " " Naturally infected 42.8 C. B __. 45,000 1,925,000 " ' " " 2.980,000 per cmm 2,987,000 " " 3,II5,O00 " " 3,980,000 " " 3,920,000 " " 2.380,000 " " 2,620,000 " BLOOD COUNTS OF APPARENTLY HEALTHY FOWLS. Fowl. White. E No. II 24,000 No. 12 26,300 No. 14 36,000 No. 15 52,000 No. 16 61,000 No. 17 30,000 No. 18 24,000 The duration of the disease varies from a few hours to several days. The prognosis is unfavorable. The mortality is very high, often 100 per cent. § go. Differential diagnosis. Fowl cholera is to be differentiated from : 1. A number of dietary disorders which cause the death of a large number of fowls. Such cases are often thought to be chicken cholera and so reported by the owners. A diagnosis is to be made in the findings of a bacteriological examination. PREVENTION 103 2. Fowl cholera is to be differentiated from infectious leukemia. There are a number of resemblances in the clinical history of the two diseases but there are marked differ- ences in both the morbid anatomy and etiology. For a com- parison of the lesions and specific bacteria of these two diseases see infectious leukemia. § 91. Prevention. Pasteur introduced a preventive inoculation or vaccine for this disease. Kitt has found that the eggs of fowls unknown to this disease possessed a sub- stance somewhat similar to antitoxin. He immunized fowls by injecting them simultaneously with from four to eight cubic centimeters of the white of such eggs. While exceed- ingly interesting this method does not seem practicable. More recently he has obtained a horse serum that promises to be of immunizing value. Good sanitary conditions, isolation of the well from the sick fowls and thorough disinfection seems to be the most satisfactory procedure. It is important not to introduce the disease with newly purchased fowls or to expose healthy ones to the disease either at or in transportation to various poultry exhibits. REFERENCES. 1. HigginS. Notes on an epidemic of fowl cholera and upon the comparative production of acid by allied bacteria. Jour, of Experi- mental Medicine, Vol. Ill (1898), p. 651. 2. Kitt. Die Serumimpfung gegen Gefliigelcholera. Monatshefte fiir praktische Tierheilk. Vol. XVI (1904), S. 1. 3. PERRONCITO. Arch, fur wiss.prackt. Thierheilkunde ', 1879, p. 4. 4. PaSTEDR. De l'attenuation du virus du Cholera des poules. Comptes Rendus des Seances de V Academie des Sciences, Vol. XCI (i88o),p. 673. . ti 5. Pasteur. Sur les maladies virulentes, et en particulier sur la maladie appalSe vulgairement cholera des poules. Ibid. Vol. XC (1880), p. 239. 6. Salmon. Annual Reports of the U. S. Commissioner of Agri- culture, 1880-82. 7. Salmon. The diseases of poultry. Washington, D. C. 1889,. p. 232. 8. Ward. Fowl cholera. Bulletin No. 156. College of Agric. Calif. Agric. Exp. Station, 1904. 104 INFECTIOUS DISEASES GOOSE SEPTICEMIA. § 92. Characterization. The disease is an acute sep- ticemia causing the death of the infected goose in a few hours after there are evidences of sickness. § 93. History. In 1902, Curtice described this disease as causing considerable loss in Rhode Island. The following note by T. Smith, dated October 31, 1900, quoted by Curtice, is significant in explaining the condition under which the disease appeared : "Geese born in April and May and collected during the summer and fall for fattening, kept in open yards, crowded together but able to move about ; about 500 in a pen. Fed on a mixture of corn meal and meat and beef scraps. Epidemic began in midsummer. Deaths up to twenty a day (one workman says sixty one day); about 3,000 lost to date." § 94. Etiology. The cause of this disease is a bacterium belonging to the septicemia hemorrhagica group. It is stated to have "the characters of the fowl cholera type." It killed rabbits when they were inoculated with 0.2 cc. of a bouillon culture. § 95. Symptoms. The symptoms are indefinite. In the outbreak described the geese were often found dead. The description of the disease by Curtice is appended. ' Few symptoms ot disease were seen, those noted pertaining mainly to the death struggles. Very few that died were noticed to be sick more than an hour or two before death, and, as the experimental investigation demonstrated, the dis- ease could not have lasted, in the majority of the geese, more than thirty-six hours. An uncertain gait, a burrowing of the head into the dirt, twisting it around, or actions indicating spasms of the throat, were the earliest symptoms. Some geese were observed to die within five minutes or after the first seizure." There are few chronic cases and recoveries are not recorded. Some show no other symptom than being slower in action, and separating themselves somewhat from the flock. However, this sign is quite important when the wild nature and gregarious habit of the goose is taken into account. MORBID ANATOMY IO5 § 96. Morbid anatomy. The tissue changes, as given by Curtice, are as follows : "There was considerable mucus in the throat and mouth, and a very tenacious mucus in the nose. The veins of the head were usually congested, as though the animal had died of asphyxia. This, together with spasm of the throat, indi- cates a spasmodic closure of the glottis. The digestive tract was found to be full of food in nearly all stages of digestion. In some cases the catarrhal products of the intestines contained petechiae. Sometimes these points were collected in more or less extensive patches. Perhaps more than half of the livers showed yellow spots of from a pin point to a pin head in size. These discolorations were found on section to extend into the substance of the liver, and were evidently dead tissue, or necroses. In one example the heart disclosed severe inflam- mation, both epicarditis and pericarditis being present. In one •case the lungs were affected. In all, fifteen cases were exam- ined, and from these this composite description of the post mortem appearances is drawn." Hemorrhages on the serous membranes and punctate ne- croses in the liver seem to be quite characteristic lesions. Post mortem notes. — These are a few taken from Curtice's publication. "Goose No. 1. Died last night ; quite fat. Right lung, ventral portion quite firm, whitish. Some flocculi of exudate in peritoneal cavity. Liver shows numerous point-like necrotic foci. Blood thick, blackish, and tarry. Mucus, glassy on dusky mucosae of nose and throat. "Goose No. 2. Died last night. Somewhat thinner than No. I. Ecchymoses on fat in abdomen and gizzard and on heart muscle ; necrosis in liver. Blood thick, tarry. Mucus in nasal passages. "Gander No. 7. Died last night ; now cold. No well marked hem- orrhagic lesion in pleuroperitoneal cavity. Whitish points in liver. Hemorrhagic or extremely hyperemic condition of duodenum. Jeju- num, or second coil of intestine, filled with a glairy mucous fluid in which are suspended shreds and patches of food (?). Few if any necroses in liver." §97. Differential diagnosis. The disease here described is caused by Bacterium septicemiae hemorrhagicae which re- sembles that of fowl cholera and other members of that group of bacteria. A diagnosis, therefore, is made positive by finding this organism in the tissues of the sick and dead geese. 106 INFECTIOUS LEUKEMIA IN FOWLS M'Fadyean has described a disease under this title causing the death of many geese in which he found the blood swarm- ing with bacteria suggesting Bad. septicemiae hemorrhagica? but morphologically different, but which he could not induce to grow on any of several media in cultures under both aerobic and anaerobic conditions. It appears that this is a different disease from that described by Curtice. § 98. Prevention. The procedure that can be suggested at present is isolation of the well from the sick, repeating the separations as often as new cases appear. The infected pens- should be thoroughly disinfected before being reoccupied. REFERENCES. 1. Curtice. Goose septicemia. Bulletin No. 86. R. I. Agr. Exp^ Station, 1902. 2. M'Fadyean. A remarkable outbreak of goose septicemia. Jour. Compar. Path, and Ther. Vol. XV (1902), p. 112. INFECTIOUS LEUKEMIA IN FOWLS. Synonym. Fowl typhoid. § 99. Characterization. A specific leukemia of fowls- caused by a bacterium. It is not known whether or not other species of domesticated birds are susceptible. § 100. History. This disease was first briefly described but not named, by Moore in 1895. At that time it had been, studied in but a few fowls and these the last to die in their respective flocks. In the following year other fowls were examined very carefully from two out- breaks of the disease and it is upon the data obtained in their investigation to- gether with those procured from many produced cases ., . ,, , . .. , ., Fig. 13. Bacterium saneuinarium that the description of the disease is based. It was found by Smith in 1894, on Block ETIOLOGY 107 Island, R. I. In 1898, Dawson found it to be the cause of very serious losses among poultry near Baltimore, Md. In all of the outbreaks studied, the owners of the fowls first reported the disease as chicken cholera. In 1902, Curtice investigated an outbreak in Rhode Island which was described under the heading of fowl typhoid. §101. Geographical distribution. It was first studied in fowls taken from an outbreak in Virginia. Since then, it has been identified in Maryland, the District of Columbia, and the State of Rhode Island. There is good evidence in the numerous reports of destructive fowl diseases to believe that it is quite widespread in the United States. Thus far, there seems to be no reports of its existence in other countries. § 102. Etiology. Moore isolated ,. y* and described a pathogenic bacterium . \j » /3 which he designated Bacterium san- -£3fef (^BSciilv guinarium. With this organism the ■'■'■$$$!{■.$ fofo|S\ disease has been produced in healthy '5%, ''" ■■(Ko^^y ■ :i- fowls both by feeding cultures and by " ' Z^^-^'f^ intravenous injections. Its etiological '"^~* '" / '-W*r' relation to the disease is, therefore, ? m .u. AchimpofBad. quite clearly established. It is possible sangvinarium in a blood that certain accompanying conditions s P ace *'« the liver < (much may be necessary in conjunction with en arge >' the organism to cause the disease to spread rapidly in a flock. Experimentally it did not spread from diseased (inoculated or fed) to healthy fowls when kept in the same yard. §103. Symptoms. From the statement of the owners of the diseased fowls in the different outbreaks and from the appearance of those in which the disease was artificially pro- duced, little can be positively stated concerning the early symptoms. There is a pronounced anemic condition of the mucosa of the head. An examination of the blood shows a marked diminution in the number of red corpuscles and an increase in the number of white ones. In the disease pro- duced artificially by feeding cultures of the specific organism there is, in most cases, a marked drowsiness and general debility manifested from one to four days before death occurs. io8 INFECTIOUS LEUKEMIA IN FOWLS The period during which the prostration continues varies from a few hours to two days. The mucous membranes and skin about the head become pale. There is an elevation of from i to 4 degrees in temperature. The fever is of a con- tinuous type, as shown in the appended temperature chart of two fowls in which the disease was produced artificially. FAHR. & 6 7 e t /o // /z / 3 '/2 J// K -^. ,^ Urn ad. ) \ /,-' '"'-' v __ - ■/□'jd, , V>' ^~- -/ ' r 1 \ £^ .-■> / '\ -^.-ju 4 0b * - - ,-" Fig. 15. Temperature chart of two cases of infectious leukemia arti- ficially produced in fowls. Although the course of the disease in different fowls is usually constant, there are many variations. The time required for fatal results is from two to three weeks, but ordinarily death occurs in about eight days after feeding the cultures. The rise in temperature can be detected about the third day and external symptoms about the fifth or sixth, occasionally not until a few hours before death. The symptoms observed in the cases produced by feeding correspond with those described by the owners of affected flocks. As indicated in the inoculation experiments, the symp- toms following the intravenous injection of the virus were, as would be expected, considerably modified from those fowls which contracted the disease by the ingestion of cultures of the specific bacterium. § 104. Morbid anatomy. The only constant lesions found in the fowls which contract the disease naturally, as well as in those fed upon the virus, are in the liver and blood. The liver is somewhat enlarged and dark colored. A close in- spection shows the surface to be sprinkled with minute grayish areas. The microscopic examination shows the blood spaces MORBID ANATOMY I09 to be distended. The hepatic cells often stain very feebly. Not infrequently the cells are isolated and their outlines indis- tinct. Occasionally foci are observed in which the liver cells appear to be dead and the intervening spaces infiltrated with round cells. The changes in the hepatic tissue are presumably secondary to the engorgement of the organ with blood. The rareness with which the intestinal tract is affected in both the natural and artificially produced cases is exceedingly interesting and important for the differential diagnosis. There is in most cases a hyperemia of the mucous membrane of the colon, but this condition is not uncommon in the healthy indi- vidual. The kidneys are generally but not uniformly pale. They are streaked with reddish lines, due to the injection of blood vessels. In section the tubular epithelium appears to be normal. The kidneys seem to be, from the number of bacteria in the cover-glass preparations, especially favorable for the localization of the specific organism. The spleen is rarely dis- colored or engorged with blood. The lymphatic glands were not appreciably enlarged in any individual examined. The lungs except in chronic cases are normal. The brain and spinal cord are unaffected. The heart muscle is usually pale and sprinkled with gray- ish points, due to cell infiltration and necrosis. These lesions are so common that it seems safe to consider them character- istic manifestations. Death usually occurs in systole, the auricles containing very little thin, unclotted blood. The most important alterations are found in the blood. These consist, in the progress of the disease, of the gradual disappearance of the red corpuscles and increase in the number of white ones, as determined by blood counts made daily or every other day, from the time of inoculation, or of feeding the virus, until the day of death. The diminution in the number of red corpuscles and the increase in the number of white ones are illustrated in the blood count of two cases of artificially produced disease. In carefully heated cover-glass preparations of healthy fowls, blood stained with methylene- blue and eosin, the nuclei are colored a deep blue, and the cellular protoplasm surround- no INFECTIOUS LEUKEMIA IN FOWLS ing the nucleus is stained by the eosin. In similar prepara- tions made from the blood of the affected fowls there are a greater or less number of , .......... ..._, I v*-* 9 % ,0- « M#9*s» cells which do not take the ■eosin stain. These were ■called spindle cells by Van Recklinghausen, blood plates by Bizzozero, and he- matoblastsby Hyem. More recently Dekhuyzzen has called them thrombocytes. In these the portion of the cell body surrounding the nucleus remains unstained ■or becomes slightly tinted with blue. Occasionally they contain one or more vacuoles, and the margin is frequently broken . The ap- parent dissolving away of the red corpuscles has been frequently observed and corpuscles showing the intermediate stages are readily detected in carefully prepared specimens. These must be differentiated from the blood plates'. The cause of the destruction of the red corpuscles is not satisfactorily explained. In his report on fowl cholera, Salmon illustrates leucocytes surrounding the red corpuscles, but the marked diminution of the red cells was not determined. He speaks, however, of the pale color of the blood. In fresh preparations of the blood, portions of red cells may be seen within the leucocytes, those containing spindle shaped granules. The determination of the extent of this mode of destruction -of the red corpuscles necessitates further investigation. :J Fig. 16. Blood from a well advanced case of infectious leukemia showing red corpuscles, blood plates and in- crease in the number of leucocytes. MORBID ANATOMY TABLE SHOWING CHANGES IN THE NUMBER OF CORPUSCLES. Fowl No. 82, inoculated in the wing vein, February 6. Number of Number of Date Tempera- red cor- white cor- ture (°F.) puscles puscles Remarks per c. mm. per c. mm. Feb. 6 107.4 3,744,444 21,222 Well. 7 109 3,417.391 26,087 Apparently well. 8 108.2 2,784,700 55.000 Do. 9 10S 4 2,807,692 76,925 Do. 11 107.4 3,481,818 90,909 Feathers ruffled ; refuses food. *3 110.2 2,133,333 100,000 Very quiet ; comb pale.. H 108 2,530,000 140,000 Fowl died later in the day. Fowl No. 501, fed culture March 26. Number of Number of Date Tempera- ture (°F.) red cor- puscles white cor- puscles Remarks per c. mm. per c. mm. Mar. 26 106,2 3,535,ooo 18,940 Well. 28 no 2,430,000 70,000 Fowl eats very little. Apr. 2 110.6 1,684,210 80,000 Blood very pale; fowl weak; refuses food. 3 106 1,745,000 245,000 Very weak ; many red corpuscles at- tacked by leucocytes. 4 In fresh preparations of the blood of affected fowls examined in Toisson ' s fluid, red corpuscles which take the violet stain more or less intensely throughout are frequently observed. In the blood of poultry two distinct classes of white corpuscles are conspicuous. The first which predomin- ates in numbers, contains nuclei with from one to four lobes, and the cytoplasm is sprinkled with a variable number of round, elongated, or spindle-shaped bodies. In the fresh condition they are highly refractory. They stain with eosin, and if the preparations are heated sufficiently they will retain certain of Fig. 17. Section of chicken's liver showing blood engorgement. INFECTIOUS LEUKEMIA IN FOWLS the aniline dyes. The other class consists of round or nearly round cells which take the blue stain feebly. Usually it is difficult to detect the nucleus, although it is occasionally dis- tinct. Between these two types there are many varieties. The leucocytes containing the spindle-shaped bodies appear to be the phagocytes, as they were the only ones which were observed to engulf the red corpuscles. Bacteria have not been demonstrated in these cells, although their presence has, in several cases, been suspected. From the appearances ob- served in the red blood corpuscles it seems highly prob- able that phagocy- tosis plays a com- paratively large part in their des- truction. Another hypothesis is also suggested, namely, that a toxin pro- duced during the multiplication o f the specific organ- ism has this effect In the fresh preparations we can ob- In the stained Fig. 18. The phagocytic action of the white blood corpuscles upon the red ones in case of advanced leukemia. The changes represented front i to 9 took place in 35 minutes. on the red corpuscles. serve the phagocytes attacking the red cells. ones, mutilated red corpuscles and free nuclei are present. The hypothesis is suggested that the leucocytes partially digest certain of the red corpuscles in their attack upon them. Whether these changes are entirely attributable to the phagocytes is an open question. In the blood from healthy fowls it is comparatively rare to see one of the white corpuscles engulfing a red one. As the disease progresses, however, this warfare becomes very con- spicuous, owing perhaps to the increased number of the colorless cells. Up to the present the study of these corpuscles DIFFERENTIAL DIAGNOSIS "3 has not been extended beyond the observation of the general appearance of these structures, and no attempt is made to ex- plain the apparently marvelous increase in the number of the leucocytes. It is an interesting and as yet unexplained fact that the increase in the corpuscles is apparently restricted to those containing the spindle-shaped bodies. § 105. Differential diagnosis. Intestinal disturbances, especially diarrhea and fowl cholera, are the diseases liable to be mistaken for infectious leukemia. A comparison of the important changes in the morbid anatomy in fowl cholera, as described by European writers, and in the disease under consideration, can be made from the appended columns, in which their more characteristic lesions are contrasted : Lesions in fowl cholera. 1. Duration of the disease from a few hours to several days. 2. Elevation of temperature. 3. Diarrhea. 4. Intestines deeply reddened. 5. Intestinal contents liquid, mucopurulent, or blood stained. 6. Heart dotted with ecchy- moses. 7. Lungs affected, hyperemic or pneumonic. 8. Specific organisms appear in large numbers in the blood and organs. 9. Blood pale (cause not deter- mined) . 10. Condition of leucocytes not determined. Lesions in infectious leukemia. 1. Duration of the disease from a few hours to several days. 2. Elevation of temperature. 3. Diarrhea not common. 4. Intestines pale. 5. Intestinal contents normal in consistency. 6. Heart usually pale and dotted with grayish points, due to cell infiltration. 7. Lungs normal, excepting in modified cases. 8. Specific organisms compara- tively few in the blood and organs. 9. Blood pale, marked diminu- tion in the number of red corpuscles. 10. Increase in the number of leucocytes. Attention should be called to the fact that as yet there seems not to have been a careful study of the condition of the blood in fowl cholera. Salmon observed many changes which may have been similar to or identical with those herein recorded. Ward found an increase in the number of white ii4 INFECTIOUS LEUKEMIA corpuscles and in some cases a decrease in the number of red ones in cases of fowl cholera. The difference between the specific organism of these two diseases can be readily appreciated by a comparison of the more diagnostic properties of each ; they are arranged in parallel columns, as follows : Bacterium of fowl cholera. Bacterium short, with oval ends. It usually appears singly in tissues. Ordinarily it exhibits a polar stain (from tissue). 4. Grows feebly or not at all on gelatin. 5. It does not change milk. 6. Resists drying from one to three days. 7. Kills rabbits inoculated sub- cutaneously in from eigh- teen to twenty-four hours. 8. It kills fowls when injected subcutaneously in small quantities. Bacterium sanguinarium Bacterium short, with ends oval or more pointed. It usually appears in pairs united end to end or in clumps in tissues. It gives a light center, with uniformly stained per- iphery (from tissue). Rarely a polar stain is observable. Decided growth on alkaline gelatin. Saponifies milk. Resists drying from eight to twelve days. Kills rabbits inoculated in- travenously in from three to five days. Rabbits in- oculated ■subcutaneously remain well or die in from six to ten days. It does not kill fowls when injected subcutaneously in small quantities. While there are many similarities in the symptomatology of these two diseases, there are pronounced differences in the morbid anatomy and in the specific microorganisms. These facts render positive differentiation dependent upon a care- ful bacteriological and pathological examination. In fowl cholera the course of the disease is more rapid than in leukemia. § 106. Prevention. Prompt isolation of the well from the sick fowls and thorough disinfection of the houses and yards. SWINE ERYSIPELAS 115 In reference to preventing its introduction, Curtice makes the following observation : "Inasmuch as one possible method of introducing the disease is through purchases, it will always be necessary for purchasers to enquire into the history of the flocks from which additions are to be made, and especially to examine into the condition of the fowls. It is better in any case to keep new purchases by themselves for some weeks or until it is apparent that they are healthy." REFERENCES. 1. Curtice. Fowl typhoid. Bulletin 87. Agr. Exp. Station of the R. I. College of Agric. and Mech. Arts. 1902. 2. Dawson. Infectious leukemia. Annual Report of the Bureau of Animal Industry, U. S. Dept. Agric. 1898. 4. Moore. A study of a bacillus obtained from three outbreaks of fowl cholera. Bulletin No. 8, U. S. Bureau of Animal Industry. 1895. 4. Moore, Infectious leukemia in fowls — A bacterial disease frequently mistaken for fowl cholera. Ann. Report of the Bureau of Animal Industry, 1895-96. SWINE ERYSIPELAS. Synonyms. Red fever of swine, Rouget (Fr.), Rotlauf (Ger.) §107. Characterization. This disease, peculiar to swine, is determined by a rise of temperature, cerebral disturbances and pronounced reddening of areas of the skin. It is a disease of adult life. It is stated that pigs are rarely attacked under three months or over three years of age. Lydtin and Schot- telius found some differences in the degree of susceptibility of certain breeds of swine. The common country pig was least susceptible. § 108. History. This disease has been known in Europe for many years. Smith found a bacterium in rabbits inocu- lated with the organs of pigs that had died of an undetermined disease in Minnesota, which was either the bacterium of swine erysipelas or of mouse septicemia. The latter organism had Il6 SWINE ERYSIPELAS been recorded on two previous occasions from pigs in this country. § 109. Geographical Distribution. Swine erysipelas is an infectious disease that occurs enzobtically and in epi- zootics in most of the countries of Europe. It was formerly restricted in Bavaria to the districts along the Danube, and was entirely unknown in southern Bavaria (Kitt) . It is stated that the disease tends to become enzootic chiefly in valleys and low-lying plains which have slow-flowing streams and heavy, damp, clay soil ; and that sandy and granite soils are comparatively free from it. It occurs chiefly during the months of July, August and September, although it appears sporadically during the winter months. It has not been described from the United States. § no. Etiology. I^oeffler and Schiitz pointed out in 1885 that swine erysipelas was caused by a very slender bacterium 1 to 2/t long and 0.3 to 0.4/i broad, straight or slightly curved, ends not rounded and in cultures often appearing in filaments. It is very closely related to the bacterium of mouse Fig. 19. Bacter- septicemia described by Koch in 1878. In i™ of swine ery- « , ., 1 t • r ..- sipelas, showing Europe, where the bacterium of mouse septi- , w f ' r free organisms cemia is quite common, swine erysipelas pre- and also their vails. There is much uncertainty concerning presence within the relationship of the bacterium of mouse ifie cells - septicemia to that of this disease. Smith has suggested that possibly the bacterium which has been found in this country may gain virulence sufficient to produce epizootics, if such is not already the case. It is exceedingly important that careful search be made for this organism in the outbreaks among swine where the nature of the disease is not clearly determined. House mice and pigeons are susceptible to the bacteria of swine erysipelas ; guinea pigs and fowls are immune. Rabbits suffer from erysipelatous swellings when inoculated subcutane- ously in the ear. The bacterium of swine erysipelas is to be differentiated from that of mouse septicemia. SYMPTOMS 1 1 7 The period of incubation is stated to be at least three days. It is apparently longer than that in many cases. § in. Symptoms. The disease usually begins sud- denly and violently. The animal refuses food, makes efforts to vomit, has a rise of temperature, manifests severe nervous disturbance, is very weak, torpid and indifferent to its surround- ings. When approached it tries to hide itself under its bed- ding. The hind quarters become weak and paralyzed. Mus- cular spasms and grinding of the teeth are sometimes observed. At first there is constipation, the conjunctiva is of a dark red or brownish-red color, and the eyelids are sometimes swollen. Usually a day or two after the first symptoms develop or, per- haps, from the first attack, reddish spots appear on the thin parts of the skin, such as the region of the navel, lower surface of the chest, perineum, inner surface of the thighs, ears and throat. These spots, which at first are bright red and.'about the size of a man's hand, become, later on, dark red or purple, and soon unite into large, irregularly-shaped patches. As a rule, they are neither paiuful to the touch or prominent, but sometimes they show a slight inflammatory swelling. The skin of the red spots, especially of the ears, may suffer from an eruption of vesicles and may even slough. The reddening of the skin may be very slight in severe cases, or may appear only immediately before, or even after death. Death takes place usually on the third or fourth day. In the very severe form, the animal may die in twenty-four hours, otherwise the disease requires a week or longer to run its course. Jensen considers that this disease, instead of being uniform in its clinical aspects, manifests itself in the following forms, which differ from each other by well-marked peculiarities. The forms recognized as varieties of this disease but more generally considered as distinct maladies and known by different names are as follows : i. True erysipelas. Swine urticaria. Erysipelas without redness of the skin. Diffuse necrotic erysipelas of the skin. Endocarditis of erysipelas. Il8 SWINE ERYSIPELAS He also maintains that there may sometimes be transitional forms between the respective varieties which he enumerates. Different forms of epizootic erysipelas have also been described by Cornevin, Hess and others. § 112. Morbid anatomy. In the ordinary form of epi- zootic erysipelas there is a septicemic condition without any well marked morbid changes of separate organs. In less acute cases the septicemia may give way to hemorrhagic and diph- theritic gastro-enteritis, considerable swelling of the lym- phatic system, hemorrhagic or parenchymatous nephritis, and hepatitis, acute swelling of the spleen and myositis. The hemorrhagic gastro-enteritis consists at first of excessive inflammation of the mucous membrane of the stomach in the region of the fundus. The mucosa shows a dark-red discoloration which is partly diffuse and partly in spots. The cells suffer from cloudy swelling and the mucous membrane is covered with a viscid layer of mucus. The intestinal mucous membrane is swollen, especially on the top of the folds and in the neighborhood of Peyer's patches. It is infiltrated with blood and sometimes shows superficial scabs. Less frequently, circumscribed parts of the mucosa of the cecum and of the anterior parts of the colon suffer from a diphtheritic affection. The solitary follicles and Peyer's patches appear as prom- inently raised patches. Sometimes they are infiltrated with blood and surrounded by a reddish band. There is ulceration and cicatrization of the solitary and agminated follicles. The mesenteric glands become more swollen than the other glands of the body, of a dark red color, and show softening. The surface of fresh sections is dun-colored with interspersed dark- red areas. The paraglandular tissue is hyperemic and infil- trated with blood. The kidneys are enlarged, the cortex of a grayish-red and the medullary portion of a very dark- red color. Frequently catarrhal nephritis occurs as a complication. The acute swelling of the spleen arises in consequence of an acute hyperemia, with an increase of the cellular constitu- ents of the pulp, in which case the organ is enlarged, but not softened as in anthrax. The pulp is of a purple color, moder- ately soft and free from hemorrhages. MORBID ANATOMY II9 There is cloudy swelling and enlargement of the liver. The surface of sections has a grayish-brown color, and the acini are widened. The muscles are gray in color, soft, flac- cid, watery, glistening and sometimes they are sprinkled with hemorrhages. They give the general appearance of boiled flesh. The myocardium shows similar spotted changes, and punctiform hemorrhages beneath the endocardium. In the abdominal and thoracic cavities and pericardium, there may be found small quantities of an orange-colored, clear fluid, which may be mixed with flaky coagula. Many English veterinarians regard the occurrence of more or less luxuriant vegetations on the valves of the heart to be so common that it is to be considered almost diagnostic. It would appear from the literature that this endocarditis is not nearly so common in continental Europe. The lungs remain unchanged, or at most exhibit a post mortem edema. By microscopic examination, the specific bacteria are found every- where in the body, especially in the spleen and kidneys, and to a less extent in the blood. The duration of the disease varies from 1 to 10 days. In types of moderate severity it runs from 3 to 4 weeks. The prognosis is unfavorable. There is from 20 to 80 per cent mortality. § 113. Differential diagnosis. Swine erysipelas is to be differentiated from : 1. Hog cholera and swine plague. The frequent red- dening of the skin in these diseases together with the modified lesions so frequently observed may cause confusion. The bacteriological examination will enable the positive diagnosis to be made. (See hog cholera and swine plague.) 2. Anthrax, which is very rare in swine. Here, too, the bacteriological examination discloses the true nature of the disease. 3. Erythemata due to various dietary causes. The significance of a deep reddening of the skin about the head, abdomen and thighs of pigs is not fully determined. It is clear, however, that such a condition often occurs in the absence, so far as present knowledge goes, of a specific infec- 120 SWINE ERYSIPELAS tion. It is frequently found in pigs suffering from digestive troubles, or poisoning from eating decomposed offal. § 114. Preventive inoculation. Pasteur's preventive inoculation was until recently the chief prophylactic means employed against epizootic erysipelas. Metschnikoff found that the blood of immunized rabbits was antitoxic, and Lorenz maintains that the serum of swine that have recovered from swine erysipelas is also antitoxic, and will produce immunity in other animals. The treatment introduced by Lorenz is to inject the immunizing serum in the proportion of 1 cc. to every 10 kilogrames of the body weight of the animal. Two days afterward 0.5 to 1.0 cc. of virulent culture is injected, and after twelve days the dose is doubled. The use of the im- munizing serum is reported to be very successful. REFERENCES. 1. Bang. Ueber Rotlauf-Endocarditis bei Schweinen. Deutsche Zeitschr.f. Thiermed. Bd. XVIII (1891), S. 27. 2. Jensen. Die Aetiologie des Nesselfiebers und der diffusen Hauttiekrose des Schweines. Deutsche Zeitschr. f. Thiermed, 1892, S. 278. 3. Loeffler. Experimentelle Untersuchungen iiber Schweine- Rotlauf. Arbeiten aus d. Kaiserlichen Gesundheitsamte. Bd. I (1885), S. 46- 4. Lorenz. Die Schutzimfung gegen Schweinerotlauf mit An" wendung eines aus Blutseaum immunisirter Thiere hergestellten Imp ' fstoffes. Deutsche Zeitschr f. Thiei mod, Bd. XX (1894), S. I. 5. Lorenz. Die Veterinarpolizeiliche Behandlung des Schwein- erothlatifes und die Schutzimfung. Berliner thierarz. Wochcn, 1897, S. 574- 6. Lorenz. Schutzimfungen gegen den Rotlauf der Schweine. Ibid, 1897, S. 109. 7. Moore. Mouse septicemia bacilli in a pigs spleen with some observations on their pathogenic properties. Jour, of Comp. Med. and Vet. Archives, Vol XIII (1892), p. 333. 8. Pastuer ET Thuillier. La vaccination du rouget des pores a. Paide du virus mortel attenue de cette maladie. Comp. Rendus. Acad, des Sciences, Vol. XCVII (1883), p. 1163. 9. SchuTz. Ueber den Rotlauf der Schweine und die Impfung mit demselben. Arbeit a. d. Kaiserlichen Gesundheitsamte, Bd. I (1885), S. 56. 10. Smith. An Examination of Pasteur's Vaccine for Rouget. Annual Report U. S. Bureau of Animal Industry, 1885, p. 187. 11. Smith. Swine efysipelas or mouse septicemia bacilli from an outbreak of swine disease. Ann. Rept. U. S. Bureau of Animal Industry, 1895-96, p. 166. INFECTIOUS DISEASES 121 ANTHRAX. Synonyms. Splenic fever, splenic apoplexy, wool sorters' disease, malignant pustule, anthracemia, mycosis intestinalis, ■chctrbon (Fr.), Milzbrand (Ger.) § 115. Characterization. Anthrax is an infectious disease occurring sporadically and in epizootics in herbivora and omnivora and communicable to nearly all warm-blooded animals, and to man. It is characterized by the presence in the diseased tissues or liquids of Bacterium anthracis, by an enlarged spleen, blood extravasations and by local gangrene. It usually occurs in the acute form. § 116. History. Anthrax is among the oldest of the known infectious diseases of animals. Descriptions of epi- demics and epizootics of this disease are given by Homer, Plutarch, Livy and other writers before the Christian Era. The Arab physicians designated it as "Persian Fire." Exten- sive outbreaks are mentioned in the literature of the fifteenth, sixteenth, seventeenth, eighteenth and nineteenth centuries. Chabert pointed out in 1780 that the various kinds or forms of disease, which had previously been described as independ- ent affections, were all one disease. As late as 1805, Kausch gave a good description of anthrax but denied its contagious- ness. Delafond and Gerlach thoroughly investigated ovine anthrax in 1S54 and its contagiousness was experimentally shown by Gerlach. In 1850., Heusinger published a very comprehensive treatise on anthrax which deals at length with its history and geographical distribution. Much new information concerning the nature of anthrax -was acquired during the fifth decade of the last century. In 1855, Pollander announced the discovery, which he first made in 1849, of minute unbranched rod shaped bodies in the blood of cattle dead of anthrax. Davaine observed similar bodies in 1850. Then followed a long series of observations and some- what controversial discussions on the bacterial origin of the disease, culminating in 1875 by Robert Koch's careful descrip- tion of the morphology of its specific organism including the spore formation. Cohn, however, seems to have been the 122 ANTHRAX first to have called the organism a Bacillus and to have sus- pected the existence of spores. Toussaint, in 1880, and Pasteur in 1881, published results of investigations directed toward protective inoculation. Since that time, the literature on the cause, morbid anatomy and prevention of anthrax has become very extensive. §117. Geographical distribution. Anthrax is a widely disseminated disease. The continent of Europe has perhaps suffered most from its ravages. It occurs, also, in Northern, Eastern and Central Africa, where in recent years it has become a great plague. In Siberia, it has caused fearful destruction, and in that country it is still known as the "Siberian Plague." It has frequently appeared in England. Russia, India and Australia are also infected. In the United States it has been reported from at least fifteen states and territories. In fact there are very few, if any, countries where this disease has not been found. In the eastern part of this country it exists to a greater or less extent. A knowledge of its specific cause, with the methods of properly disposing of dead animals, isolation and disinfection, as well as the preventive inoculations now in vogue, have made it possible to prevent wide- spread epizootics. In America it is looked upon as a comparatively rare dis- ease, excepting in certain infected districts. § 118. Etiology. An- thrax is due to the presence of a microorganism known as Bacterium anthracis. This organism is found in the diseased tissues and organs FlG - 20. Anthrax bacteria in an im- of affected animals. On ac- Passion preparation made from a col- count of its spores, it is 0Hy °" an a S^ plate culture. very resistant to the normal destructive agencies in nature. Consequently when it is once introduced into a locality it tends ETIOLOGY 123 to remain there for many years, possibly causing from time to time a few cases of anthrax or serious epizootics or epidemics. The spores are also frequently carried in the wool, hair, hide, hoofs and horns taken from animals sick or dead of anthrax. Thus the affection has been introduced into far distant localities. Bacterium anthracis is a rod-shaped organism varying in length from 1 to 4 /1, but having a quite uniform breadth of about one micron. In a suitable medium it grows out in long flexible filaments which combine to form thread-like bundles. When examined, the ends of the rods seem to be square cut. In preparations from animal tissues there appear sometimes to be slight concavities in the ends of the segments when two of them are united. In cultures spores are formed. These are oval, highly refractive bodies held within the cellular envelopes of the filaments, but later they are set free by the dissolution of this membrane. It stains readily with the aniline dyes and also by Gram's method. The bacterium of anthrax itself is not an especially hardy organism. On the contrary it is easily destroyed by weak Fig. 21. Anthrax bacteria in a cover-glass preparation of blood, showing chains and capsules. disinfectants and it has a low thermal death point. Its spores, however, are among the most hardy of bacterial life to resist chemical and thermal agents. They resist drying for months 124 ANTHRAX or years and often boiling for a half hour or longer does not destroy them. On this account it is very difficult to eliminate the virus from infected pasture lands, especially if they are wet or marshy. As the spores may remain on the soil in a dormant condi- tion for many years, it sometimes happens that the disease does not appear until long after the introduction of the virus. Anthrax has been known to break out among cattle grazing on a field in which the carcasses or hides from affected animals were buried many years before. Through some means the spores seem to be able to get to the surface and contaminate the grass. The virus may be introduced with blood or bone fertilizers, hides, hair or wool from infected countries. When the extent of this traffic is realized, it is easy to understaud how anthrax has been brought to this country and why it occasion- ally appears here and there over a large part of the continent. Many outbreaks, as well as isolated cases, illustrating this common method of dissemination are on record. The period of incubation is very short. In inoculated animals it ranges from i to 5 days. § 119. Animals attacked. Nearly all animals suffer from anthrax. The herbivora and rodents are most susceptible. Horses and mules often suffer from it. M'Eadyean has reported outbreaks aggregating 54 cases, of which 49 were oattle, 4 horses and 1 pig. He states also that for a period of 5 years there had been reported 192 cases in horses and 3,390 in cattle. It is interesting to note that the Algerian race of sheep are immune. A satisfactory explanation for this striking exception has not been recorded. It has been stated that a single bacterium introduced into the subcutaneous connective tissue of a guinea pig or mouse is sufficient to kill. Cats, tame and wild rabbits and hares are the next most susceptible species. It is stated that dogs, pigs, and foxes are very slightly susceptible. Rats, fowls and pigeons are reported to be immune. Fish and. amphibia are rarely attacked. §120. Channels of infection. Three common modes of infection are recognized for anthrax, namely : through the digestive tract, by the skin and by the lungs. In cattle the CHANNELS OF INFECTION 1 25 infection seems to be largely through the alimentary canal ; in horses and sheep by the skin or digestive tract ; in men through wounds of the skin and the respiratory tract. Al- though these are the usual methods there are many exceptions with each species. 1. Infection through the alimentary canal. This is the more common mode of infection in cattle. The resulting disease has been designated by various names, among which are "intestinal anthrax," "fodder anthrax," "spontaneous anthrax," internal anthrax," "anthrax fever," and anthrax without external manifestations. In these cases the infecting organisms, either the spores or the vegetating bacteria them- selves, are taken into the body with food or drinking water. M'Fadyean has recently shown that infected food stuffs are often responsible for the infection. It is stated that the in- fection takes place in most cases in the small intestine, the mucosa of which, it is stated, need not necessarily be injured. It is highly probable that the gastric juice destroys most of the bacteria while the free spores are not injuriously affected by it. In the infected districts, the spores exist at or upon the surface of the soil and possibly on the blades of grass from which they are easily taken up by grazing animals. In lands thus infected, the specific organism has been introduced at some previous time either by the burying of anthrax animals in these fields, by the use of infected tannery or slaughter house refuse as fertilizers, by flooding from infected streams, or by the bringing of the organism in the droppings of birds or other small animals which have fed upon anthrax carcasses. It is reported that the spores will find their way to the surface even when the dead animals have been buried at a considerable depth. There has been some controversy in the writings of Pasteur, Koch and Bollinger concerning the method by which the spores reach the surface. Pasteur supposed that they were brought by earth worms from the buried carcasses. Koch believed this impossible because of the low temperature of the ground at the depth at which the animals are buried. Bol- linger has shown experimentally the possibility of Pasteur's views. Karliniski and others have found that the spores of 126 ANTHRAX anthrax may be disseminated by slugs, insects and larvae which are found on untanned infected skins. 2. Infection through the skin. In animals, this mode of infection occurs less frequently than in man. Anthrax produced in this way is usually characterized by local mani- festations known as "carbuncle disease," or "malignant pus- tule." In this mode of infection the bacteria penetrate through wounds in the skin and exposed mucous membranes, into the living tissues by means of infected utensils, the use of infected instruments, and insects, especially the house fly (Musca domestica). Dalrymple has called attention to the spread of this disease among animals in the lower Mississippi Valley by means of the horse fly ( Tabanidae') . In man many cases of the disease occur from the injuries or cuts made at the post-mortem of anthrax animals or by the infection of skin wounds while handling infected hides or wool. Malignant pustule is reported to be quite common among the employes of certain tanneries and upholstering establishments where hides and hair imported from infected districts or countries are used. 3. Infection through the respiratory tract. Faser, Buch- ner, Lemke, and other writers have shown experimentally that the disease can be produced by the inhalation of spores. In man this form of infection is quite common among the wool sorters. In Great Britain , where much foreign wool is handled, it has been reported as causing as many as 500 deaths annually. It is known as "wool-sorter's disease." § 121. Symptoms. In anthrax, the symptoms vary not only in different species of animals but also in different in- dividuals according to the location of the disease. Again, there is often considerable variation when the lesions are ap- parently the same. The most characteristic features of the disease are the suddenness of the attack, the grave general disturbances, high elevation of temperature, a tendency to ecchymoses of the mucous membranes and local manifestations, such as carbuncles and edema of the skin, digestive disturb- ances, brain complications or difficult respiration. Anthrax has been classified according to its course asper- acute, acute and subacute. It has also been divided accord- SYMPTOMS 127 ing to the site of its manifestations as anthrax with visible localization and anthrax without visible localization. Anthrax without visible localization. This form is gener- ally due to ordinary infection presumably by spores. It in- cludes the peracute, acute, and subacute. 1. The peracute or apoplectic anthrax gives rise to symptoms of cerebral apoplexy. The animal becomes sud- denly ill, staggers about for a brief period and falls. There is often a bloody discharge from the mouth, nostrils and anus. Death usually ensues in from a few minutes to an hour. '■&-'■ -4, Fig 22. y4 camera lucida drawing of a field in a preparation of blood from a case of acute anthrax, much enlarged {Burnett). Usually there are convulsions. Sheep and cattle suffer most frequently with this form of the disease. They are often found dead. This is especially true in the beginning of an epizootic. 2. In the acute form, the disease runs a somewhat slower course, lasting usually not to exceed twenty-four hours. The 128 ANTHRAX temperature rises rapidly to from 105 to 108 F. With this there are signs either of congestion of the brain or of the lungs. If the brain is affected the animal becomes restless, excited, stamps the ground, rears in the air, bellows, runs to and fro and finally goes into convulsions followed by stupor and death. If the lungs are congested there is difficulty in breathing, more or less wheezing, panting, groaning, palpita- tion of the heart, small and frequent pulse, cyanosis of the mucosa of the head, bloody discharges, hematuria, staggering and finally convulsions and death from suffocation. Occasion- ally there is a partial remission of the symptom, followed by relapse. It has been observed that occasionally there are pre- monitory symptoms preceding the acute attack, consisting of slight digestive disturbances and diminished vivacity. Burnett found the anthrax bacteria in large numbers in the blood dur- ing this stage. He likewise found them to be present in the blood of the more chronic cases during the febrile period. 3. The subacute form is known as anthrax fever or in- termittent anthrax. The symptoms are the same as in the other forms, except that they are more sharply defined and the course is longer. The disease lasts from one to seven or eight days, the average being about forty-eight hours. The high temperature, the congestion of the lungs or brain complicated with intestinal disturbances, especially colic, are usually well marked. In epizootics where the peracute or acute form ushers in the disease, the later cases usually are of the subacute variety. Anthrax with visible localization. These forms usually re- sult from infection of the skin and mucous membranes. The lesions are spoken of as carbuncles and often there is marked local edema of the skin. This form is common in many horses and sometimes it occurs in cattle. It is reported to occur in other species. The carbuncles are circumscribed, cutaneous swellings which are at first hard, hot and painful. Later they become cold and painless, with a tendency to become gangren- ous. The edematous tissue becomes doughy, cold to the touch and painless. Frequently fluctuating swellings of the skin occur. The duration of this form of the disease varies from SYMPTOMS 129 four to fifteen days. Ordinarily it is not so fatal as interna anthrax. When the infection is on the mucous membrane the animal suffers from fever, dyspnea, difficulty in swallowing and cyanosis, together with the immediate local effects. Death occurs much sooner than when the disease is located on the skin. It is stated that dogs and swine suffer from this form more than from the acute types. In horses, anthrax usually runs an acute or subacute course. The first symptom is rise of temperature with a rapid, feeble pulse. There may be chills and muscular spasms. The mucosa of the head becomes cyanotic and lacrymation is often present. The animal has a dull, stupid look, appears to be stunned and walks with a staggering gait. In some cases there are symptoms of cerebral congestion, such as restlessness or convulsions. Colic is a very characteristic symptom in the horse, otherwise the symptoms are the same as in cattle. Infec- tion of the skin usually occurs on the hypogastrium, lower part of the breast, inner surface of the fore and hind quarters. Swelling of the hind quarters often causes lameness. Car- buncles of the mucous membrane of the tongue is said to be rare in this species. In sheep and goats the disease is usually of the acute or apoplectic form. The animals appear as if suddenly stricken with apoplexy. If death does not occur within a very short time, symptoms already described for this form of the disease may be recognized. Subacute anthrax is said to be very rare in sheep. In swine, anthrax is ordinarily characterized by local lesions on the mucous membrane of the larynx and pharynx. The animals have a rise of temperature and the intermaxillary space is generally swollen. The swelling may spread along the trachea, giving rise to difficulty in swallowing, hoarseness, cyanosis of the mucosa of the mouth, dyspnea and rapid breathing. The animal shows signs of paralysis. Death occurs from suffocation. Frequently the tongue becomes the seat of the disease. Carbuncles occurring on the skin, especially of the back, have been described in this species. I30 ANTHRAX In dogs and cats, the disease usually runs a very rapid course. The fact that they are usually infected by eating the meat of animals dead of anthrax causes them to suffer largely from the intestinal form. It has been stated that probably much of the so called anthrax in dogs was simply cases of ptomaine poisoning. It is reported that in birds anthrax usually runs a very rapid and usually fatal course. Toward the end they stagger, tremble, or go into convulsions and die with bloody discharges from the mouth, nostrils and anus. From the first the birds are depressed, weak, and their feathers ruffled. There is evidence of dyspnea. Carbuncles are said to appear on the comb, wattles, conjunctiva, tongue and extremities. It has been stated that the milk from cows suffering with anthrax contains Bad. anthracis. The writer found in the examinations made in one epizootic that the anthrax bacteria were presnt in considerable numbers in the milk just before or immediately after death, but they were not found in the milk of animals in the earlier stages of the disease. § 122. Morbid anatomy. The nature and extent of the tissue changes depend upon the course of the disease. When experimentally produced it is ordinarily a septicemia. It often occurs in domesticated animals when they contract the disease naturally. The more common anatomical changes, except in the most acute cases and in the strictly localized lesions or carbuncles, are : Hemorrhages varying in amount from petechiae to blood extravasations, with more or less serous, gelatinous and hem- orrhagic infiltration of the submucous, subserous and subcuta- neous tissue. The capillaries are distended and frequently there are hemorrhages beneath the epidermis. The subcutis is sprinkled with ecchymoses. Frequently there are gelatinous effusions of a rather firm consistency and of varying size. The color also differs, ranging between a deep yellow and a yellowish brown. Often these edematous areas are sprinkled with hem- orrhagic foci. A simple serous edema may occur. The lymphatic glands may be hemorrhagic, edematous MORBID ANATOMY 131 or both. An edema of the connective tissues of the neck or about the trachea is often very marked. The muscles vary in color but usually they are darker than normal, and like the skin, they often become sprinkled with ecchymoses. The heart muscle suffers from parenchy- matous changes. In the larger cavities of the body, a sanguinolent fluid is found in moderate quantities. Blood extravasations of differ- ent sizes are seen under the serous membranes, particularly on the mesentery and mediastinum. The subserous connective tissue, especially on the mesentery, anterior mediastinum and in the neighborhood of the kidneys, is often infiltrated with a gelatinous substance. On this account the neighboring lymph glands are considerably swollen, filled with serum and sprinkled with hemorrhages. The internal organs contain a large quantity of blood. All the larger veins and the heart are filled, while the surrounding tissues show sanious imbibition. The spleen is considerably enlarged (two to five times its normal size), either uniformly or by prominent tumor-like protuberances. The pulp is soft, more or less fluid, and stained a dark red color. The capsule is always very tense. It is frequently sprinkled with ecchymoses. The liver and kidneys are highly congested and somewhat enlarged. The parenchyma contains areas of blood infiltration and the cells themselves manifest various kinds of degenera- tion. The portal lymph glands often appear to be enlarged, and the retroperitoneal tissue may be infiltrated with a serous, gelatinous fluid. The subperitoneal tissue of the intestines and of the abdominal walls may be similarly affected. The nature of the lesions of the intestinal canal varies according as the disease is intestinal anthrax, or anthrax caused by inoculation. In cases of inoculation anthrax, the intestine is frequently normal. In other cases there may be submucous and subserous hemorrhages, or swelling of the mesenteric glands. The principal changes in intestinal anthrax are always found in the small intestine, chiefly in the duo- denum. In the milder cases of intestinal anthrax the mucous 132 ANTHRAX membrane is affected, by circumscribed or diffuse swellings. The bacteria are often found in very large numbers on the surface of the mucous membrane. Necroses and ulcers appear in those parts where the bacteria are most thickly congregated. In very severe cases, the abomasum or the true stomach may be affected with a gelatinous and sanious infiltrations of the mucous membrane. The mucosa of the abomasum, and es- pecially of the duodenum, is, in consequence of excessive hyperemia, dark red or almost black, and is covered with erosions and ulcers or necroses, which may exttend down to- to the submucosa. The contents of the intestine are bloody, and the submucosa is infiltrated with a serous, gelatinous, or hemorrhagic exudate, so that the mucous membrane often projects, in the form of large tumors, into the lumen of the intestine. On the site of Peyer's patches and the solitary fol- licles we may find flat or prominent nodules, the surface of which are covered with diphtheritic crusts. The lungs are greatly congested, edematous and show areas of ecchymoses. The entire respiratory mucous mem- brane is considerably reddened and ecchymotic. The mucous membrane of the pharynx and opening of the larynx is often so edematous that stenosis of the larynx takes place. The contents of the trachea and the bronchi consist mostly of bloody froth or mucus. The brain is often studded with ecchymoses. The surface of its membranes often exhibits hemorrhages with an accumu- lation of sanious serum in the ventricles. Extravasations of blood sometimes occur in the anterior chamber of the eye and under the retina. All the other organs may contain hemor- rhages, and the urine frequently contains blood. The blood is usually dark. It has a tarry or varnish-like lustre, and shows little tendency to coagulate. It does not as- sume its normal red color when exposed to the air. Burnett studied the blood of a few cases of anthrax in 1904. The ap- pended tables give the results of his examinations. MORBID ANATOMY RESULT OF THE EXAMINATION OF THE BLOOD OF FIVE ANTHRAX IN CATTLE. 133 CASES OF Cow No. 8 First symptom observed July 8 Date of Exam- ination S3 Hemo- globin per cent Red Corpuscles per c.mm. Leuco- cytes per c. mm. Remarks 107-5° Anth. bact. in blood " 8 July 9 I06.6 60 4,072,000 20,000 Died July 9 " 4* " 4 " 4 " 4 " 6f " 6 " 6 " 6 " 6 July 10 July 11 " 13 I06.2 56 5,471,000 4,814 IO3.O 38 3,400,000 3,444 July 7 " J 9 56 2,086,000 9,876 Recovered Anth. bact. in blood July 9 " 11 I04.O 50 3,876,600 8,222 60 3,954,000 5,2io " 13 " 14 101.8 101.2 47 3,484,000 5,666 Apparently recovered. Died of Anthrax Nov. 4 " 6 " 6 " 3 " 3 June 29 " 19 " 24 July 14 54 1,980,000 8,777 63 3,132,000 11,888 101.2 57 4,168,000 5,222 Recovered July 15 July 16 103.8 53 2,324,000 8,111 " 17 IOI.O 58 2,632,000 5,333 " 18 102.0 8,163 — " 19 " 24 5,940,000 1 1 ,000 61 10,767 Recovered *Temperature July 8, 102. i°. -(■Temperature July 8, 107.4° Temperature July 10, ioo.o ' Temperature July 9, 103.0 . 134 ANTHRAX THE DIFFERENTIAL COUNT OF THE LEUCOCYTES IN FIVE CASES OF ANTHRAX IN CATTLE. Cow Date 1 M 1 j I Leucocytes | Q per c. mm. Lympho- cytes Large Mono nuclear Polynuc- lear Eosino- philes Mast Cells No. 7080 % No. 2200 341 261 273 % No. % 35-6 No. 3520 548 75 636 5i8 432 430 % 17.6 2 8 11. 4 2.2 6.4 6-3 8-3 7.8 7.6 No. 80 48 7 11 4i 36 62 % 04 0.2 1.0 0.2 0.2 0.5 0.7 0.7 1.1 0.4 0.7 0.2 0.8 0.7 0.5 0.8 Soper No. 8 Tuly 9 35-4 27.4 II. 7120 " 4 " IO 5-2 2200 64.8 45-7 " " " II 4814 1670 34-7 7.1 It (I " 13 3444 9876 I43 2 4257 41.6 7.6 1667 4696 3436 2115 2221 2800 3120 48.4 47-5 41.8 40.6 47-2 39-2 « .< " 19 43-i 2.7 " 6 " 9 8222 5210 5666 393° 2287 2833 3747 6033 3352 47.8 296 3.6 " " " 11 43-9 338 6.5 ( ( ( t " 13 40.1 4.0 " " " 14 50.0 119 263 2.1 " " " 19 8777 1 1888 42.7 3-o 5-8 31-9 26.2 1930 1946 146 22.0 16.3 2.8 35 89 10 " " " 24 50.7 64.2 698 261 154 " 3 " 14 5222 8111 5333 8163 5-o 1451 3033 1568 27.8 Bradish No. i " 16 3528 2832 6375 6611 59 11 43-5 1.9 37-4 29.4 11. 2 23-5 20.3 1330 640 734 1496 2099 16.4 12.0 9.0 13.6 J 9-5 65 36 55 86 < < ii " 17 53-i 256 138 4.8 it it " 18 78.1 1-7 914 2585 ii it " 19 1 1000 10767 60.1 253 484 2 -3 ii ii ,, 24 54-9 4-5 2186 He found that the number of red corpuscles and the per- centage of the hemoglobin are reduced. In the chronic cases they tend to return to the normal condition. There was an in- crease in the number of lymphocytes and a decrease in the number of poly nuclear leucocytes. In some cases there was a marked increase in the number of eosinophiles. No change MORBID ANATOMY 1 35 from the normal was noted in the large mononuclear leucocytes or in the mast cells. The bodies of animals which have died from anthrax are often well nourished. Rigor mortis is absent and they decom- pose quickly. Very frequently blood flows from the natural openings of the body, and the rectum is sometimes prolapsed. All the foregoing lesions may be absent in very acute apoplectic cases. The specific organism is, however, always present in the cadaver. It is important to note that occasionally the usual changes indicated by the symptoms and the duration of the disease are not found on post-mortem examination. In one epizootic, the writer saw an animal dead from sub-acute anthrax in which the blood and tissues were teeming with anthrax bacteria, yet the organs examined macroscopically appeared to be normal. Other animals in the same outbreak exhibited the more usual anatomical changes. The period of duration varies from a few hours to a week or even longer. The prognosis is unfavorable. In some herds the mor- tality is 100 per cent, while in others a number of animals may recover. The average mortality is placed at about 70 per cent in animals. In the human species many persons re- cover from its local form (malignant pustule). M ' Fadyean has reported this disease in 39 consecutive out- breaks in which a total of 54 animals died. In New York the disease existed in 1904 in 15 herds in one locality. There were more than 30 deaths. In one herd of 21 animals, 20 had the disease, 16 died and 4 recovered. In another dairy 4 out of 7 died, but in the others one or two animals in each was affected. These facts are interesting in showing that the disease does not always cause heavy losses. It is, however, a serious malady. § 123. Differential diagnosis. It is important not to confuse anthrax with a number of non-specific disorders and accidental causes of death. The suddenness of the attack, and in very virulent cases, the short duration of the disease may tend to the mistaking of it for poisoning, cerebral apoplexy, pul- monary congestion, heat apoplexy, death from lightning, or 136 ANTHRAX acute gastrointestinal inflammation. The affection known as corn-stalk disease is not infrequently taken for anthrax and vice versa. In all of these cases the doubt following the post- mortem can be easily settled by a bacteriological examination which, with genuine anthrax, will reveal the presence of Bac- terium anthracis. It is believed by those who have dealt most with antrax, that the specific organisms are always in the cir- culating blood before death. The putrefactive organisms that resemble Bad. anthracis morphologically, do not appear in the cutaneous blood as quickly after death as they do in the organs. There are, however, certain specific diseases from which anthrax must be differentiated. The most important of these are symtomatic anthrax (black leg), malignant edema, and septicemia hemorrhagica. Rabies is not infrequently taken for anthrax. If the diagnosis cannot be determined by the anatomical changes (which can be relied upon only in some- what typical cases) the positive diagnosis can be made only with the finding of the anthrax bacteria. In animals just dead, where decomposition has not begun, these organisms can usually be found in properly stained cover-glass preparations made directly from the blood or tissues. After decomposition begins to take place, a putrefactive organism, that is not easily distinguished from that of anthrax, often appears in the tissues. It is, therefore, necessary in such cases to resort to culture methods before a positive statement can be made. As the bacilli of malignant edema and symptomatic anthrax are anaerobes, they will not develop in aerobic cultures, such as on slant agar or in bouillon. The bacterium of septicemia hemorrhagica, being a small oval organism, is easily told from that of anthrax. It is important to recognize the possi- bility of error, if the conditions restrict the examination to the study of the microscopic preparations. Differential Stain. M'Fadyean has described a peculiar staining reaction which he considers of value for the micro- scopic diagnosis of this disease. The reaction is in evidence when films of blood, exudates, or tissue juice containing the bacteria are stained with a simple aqueous solution of methy- lene blue. The method as applied to blood is as follows : DIFFERENTIAL DIAGNOSIS 1 37 Place a drop of the blood on a clean slide. The size of the drop should be about 2 mm in diameter. It is spread quickly with a plantinum needle until it covers an area about 12 mm in diameter. Protect from dust and allow the slide to remain until all evidence of moisture has disappeared. When dry, heat the preparation by lowering it film upwards into the flame of a Bunsen burner or an alcohol lamp for a second. Repeat this three times or until the glass is too hot to be borne by the skin in the palm of the hand. Allow the slide to cool and then cover the film with 1 per cent, aqueous solution of methylene blue. After a few seconds pour off the free stain and wash the slide thoroughly in tap water. Dry the slide by pressing it gently between two layers of bibulous paper, and then more thoroughly by holding it in the current of hot air above the Bunsen flame. Finally, mount in Canada balsam. The microscopic examinations (x 800 to 1000) will show an occasional leucocyte and the anthrax bacteria. There will appear no other visible formed elements. The nuclei of the corpuscles generally exhibit a greenish-blue tint, the anthrax rods are stained blue. The intensity of the stain depends upon the length of time after death before the films were made. Usually the segment character of all but the shortest rods will be apparent. If they are deeply stained this is not very dis- tinct. The peculiarity in the reaction lies in the color of the amorphous material which is present between and around the bac- teria. This material presents itself under the form of coarse or fine granules of a violet or reddish-purple color, which is in sharp contrast to the tint of the bacteria or cell nuclei, espec- ially with brilliant lamp or gas light. These violet granules differ a good deal in form and size ; sometimes they are very minute, and at others coarsely granular. When the bacteria are arranged in clumps the violet material is often in greatest amount about them. Free-lying anthrax rods will be sur- rounded by a thick envelope of the same substance. M' Fad- yean states that he has never found this reaction in animals dead from other diseases. The peculiar coloring, he states, in some cases may be observed without the aid of the microscope. 138 ANTHRAX §123. Protective inoculation. Toussaint was the first to make use of protective inoculations in anthrax. He heated defibrinated anthrax blood to a temperature of 50 to 55 C. for from 15 to 20 minutes then injected it as a protective agent. Pasteur, however, was the first to prove that immunity could be obtained by the use of cultures of attenuated bacteria. Several methods of attenuating the specific organisms have been proposed by Pasteur, Toussaint, Chaveau, Chamberland, Arloing and others. Pasteur's method consists in inoculating the animal with a small quantity of culture which has been grown at a high temperature — 42 to 43 C. — for several days. This deprives the bacteria of their virulence. To strengthen the resistance, the animals are again inoculated with a stronger virus. After the two inoculations, they are said to be protected against the most virulent anthrax ; but the immunity is of short duration. Chamberland reported in 1894 that a total of 1,988,677 animals had been treated by this method in France, and that the loss from anthrax had diminished from 10 per cent, in sheep and 5 per cent, in cattle to less than 1 per cent. Cope, in his report to the English Board of Agriculture, regards the conclusions of Chamberland as somewhat fallacious, because in order to prove that the animals inoculated received immunity, it should be shown that they were subsequently exposed to the risks of natural infection. The excellent work which has been done by Neal and Chester, at the Delaware College Experiment Station, has shown the possible efficiency of this method. Of the 331 cows which they vaccinated against anthrax, two died of the disease, giving a death rate of less than 1 per cent, and this in a territory so saturated with the virus that it was prac- tically impossible to keep cattle at all before its use. A more critical study of the reports on the use of this vaccine shows that while success can not be denied, failures must be admitted. It is reported both in England and Germany that the Pasteur vaccine has not been a marked suc- cess. In England, Klein, who tested the vaccine used in that country, found that if the animals did not die from the effect, of the vaccine, they did when exposed to the disease. The PROTECTIVE INOCULATION 1 39 German veterinarians and agriculturalists agree that the first vaccine is mild and harmless, but that the second vaccine, even in the hands of experts, is dangerous and often fatal. In the state of Illinois a number of cattle died of anthrax immediately after receiving the second vaccine for prevention and in Manitoba a large (about 500) number of sheep died after the second vaccine (Higgins). In a recent outbreak in the state of New York the animals that were vaccinated, but not carefully isolated from the infected pastures, continued to die of the disease after the second vaccination. The fact is reported to have been demonstrated by experiment that the virulence of the attenuated virus can be easily restored. Again, it has been shown by the investigations of Chester and Neal, of the Dalaware College Agricultural Experiment Station, that a vaccine which succeeded at one time subsequently proved fatal. The vital objection to this method is, that it requires the use of the living bacteria, which later may become virulent and consequently cause a subsequent outbreak. The scattering of pathogenic organisms, even in an attenuated condition, should be avoided if possible. It must be admitted, however, that Pasteur's method has done much good and helped to rob anthrax of much of its former terror, especially for the farmers of Europe. In America the spread of anthrax has been checked in many districts by its use. Dairy mple has pointed out its success in the lower Mississippi valley. Not- withstanding, it is highly probable that the spreading of a knowledge of the specific cause of this disease with that of the proper disposition of dead animals has also exerted much in- fluence for good in checking its ravages. In Germany and England the stamping-out system is con- sidered superior to vaccination. According to Crookshank, in England it is regarded as the only reliable means of sup- pressing the disease. To this end rigid laws have been enac- ted. In this country as rigid measures as possible for its eradication seem infinitely better than the general adoption of methods for establishing a tolerance for its existence. § 124. The simultaneous method. This method which consists in the injection of anthrax antitoxin or serum to- 140 ANTHRAX gether with a small quantity of virulent anthrax bacteria, has proven to be very satisfactory. It has the advantage of being administered at one time. This method of protec- tion against anthrax seems to have been first proposed by Sobernheim in 1899. Since that time Sclavo in Italy and others have published on this method. Sobernheim reports excellent results by the use of this method in immunizing cattle against anthrax in South America. The serum is now produced in large quantities in Germany. In this country, it does not appear to have been used. Prevention. In all cases the well animals should be re- moved from the barns or yards containing the sick ones and from pasture lands on which the sick became infected. The temperature of healthy and uninfected animals should be taken morning and evening for from one to two weeks after they are removed and all of those showing an elevation of temperature should be isolated. By careful isolation and safe disposition of the dead animals the spread of the disease can be checked. Animals do not, as a rule, spread the virus when the first symptom (rise of temperature) can be detected. All infected stables and yards should be thoroughly disinfected. The disposition of dead animals in an outbreak of anthrax is a matter of much importance. In all cases they should be burned if possible, if not, they should be buried deeply and covered with quick lime before the dirt is replaced. The ground over the place where they are buried should be fenced in to prevent other animals from grazing over it, and the surface should be burned annually for some years to destroy spores should they be brought to the surface. REFERENCES. 1. Chester. Anthrax, bacteriological work. Report Del. Agr. Expt. Station, 1895, p. 64. 2. Chester. Protective inoculation against anthrax. Proceedings of the Society for the Promotion of Agricultural Science, 1896, p. 52. 3. Davaine. Recherches sur les infusoires du sang dans la maladies connue sous le nom de sang de rate. Compt. Rend, de V Acad, des Sc.' 1863, 1864, 1865. GLANDERS 141 4- Dalrymple. Anthrax and protective inoculation in Louisiana. Proceedings of the Am. Vet. Med. Assn. 1901, p. 147. 5. Koch. Die Aetiologie der Milzbrand-Krankheit begriindet auf die Entwickelungsgeschichte des Bacillus Knth.ra.cis. Co hn's Beitr. zur Biol der Pftanzen, Bd. II (1876), p. 277. 6. M'Fadyean. Anthrax. Jour. Compar. Path and Ther. Vol. XI (1898), p. 51. 7. M'Fadyean. A peculiar staining reaction of the blood of animals dead of anthrax. Jour, of Compar. Path and Ther. Vol. XVI (1903)^. 35. 8. M'Fadyean. Extraneous sources of infection in outbreaks of anthrax. Jour. Compar. Path, and Ther. Vol. XVI, p. 346. 9. Moore. Report of an outbreak of Anthrax. Annual Report, Commissioner of Agriculture of the State of New York. 1897. 10. Pasteur, Chambesund et Roux. De l'attenuation des virus et de leur retour a la virulence. Camp. Rend, de I' Acad des. Sc. Vol. XCII (1881), p. 427. 11. Pasteur. La vaccin des charbon. Ibid. p. 666. 12. Russeli,. Outbreak of anthrax, fever traceable to tannery refuse. The\iyth annual report of the Wis. Agric. Exp. Station, 1889. 13. Sobernheim. Ueber das Milzbrandserum und seine praktische Anwendung. Deut. Med. Wochenschr. 1904. No. 26, u. 27. (First publication. Zeit. fur Hygiene, 1899, Bd. 31). GLANDERS. Synonyms. Malleus, farcy, morve (Fr.), Rotzkrank- heit (Ger.). § 125. Characterization. Glanders is one of the most important diseases of horses, asses and mules and when trans- mitted to man, one of the most fatal diseases of the human species. It runs an acute or chronic course attacking the lym- phatic system more especially in the upper air passages, lungs or skin. The disease is characterized by a strong tendency to the formation of small neoplasms or nodules which are likely to degenerate into ulcers from which exude a peculiar sticky discharge. In the very acute cases a considerable rise of tem- perature and general debility may accompany the formation of the lesions. Glanders of the skin is known as farcy. By direct inoculation several species of animals may be in- fected. Thus the disease has been reported in goats, rabbits, sheep, guinea pigs, field mice, and several of the wild animals, 14 2 GLANDERS. especially those of the cat tribe. Swine and pigeons are very slightly susceptible. Cattle, white mice, rats and domestic fowls seem to be immune. § 126. History. The theory of the contagiousness of glanders was much doubted at the beginning of this century. The view taken at the Alfort Veterinary College was that glanders might arise spontaneously from an attack of strangles. This view was far more widely accepted than the theory of its contagiousness, which was stoutly supported by the Veterinary College of Lyons. It was not until Rayer (1837) had demon- strated the transmissibility of glanders to man, and Chaveau (1868) had shown that the virus was contained chiefly in the firm component parts of the infective material, that the fact of the infectious nature of the disease was accepted. The theory of the spontaneous origin of glanders was widely accepted in Germany. Sixty years ago it was believed that glanders could be produced by the injection of pus, and that strangles could develop into glanders. Glanders was looked upon as a tubercular disease, scrofula, pyemia, diphtheritis, general dyscrasia and cachexia respectively. Virchow was the first to declare that the nodules of glanders were independ- ent, anatomical formations, which he placed under the head- ing of granulation tumors. Gerlach was the strong advocate for the exclusively infectious origin of the disease. Leisering appears to have been the first to give an accurate description of the lesions. The first biological researches into its nature were made in 1868 by Zurn and Hallier, who found a fungus which they believed to be its cause. In 1882, Loeffier and Schiitz suc- ceeded in finding the bacterium of glanders, in cultivating it, and in transmitting the disease to other animals by inoculating them with pure cultures of this organism. Their researches furnished the positive proof that glanders is a specific, in- fectious disease, produced exclusively by Bacterium mallei. § 127. Geographical distribution. Glanders exists in the greater part of the civilized world. It is more common in the temperate zones, where traffic in horses is active. In the United States it was largely confined to the Northern States ETIOLOGY 143 ■before 1861, but it spread over the South in connection with the civil war. It is said to have entered Mexico with the American cavalry in 1847. Similarly, Portugal is said to have been exempt until the invasion by Napoleon in 1797. Central Hindoostan was said to be free from it until the war with Afghanistan in 1878. In all these cases, the movements of •cavalry, artillery and of commissary trains were responsible for the introduction of the disease into new territory. In our own case the sale of horses and mules at the close of the civil war produced a very general diffusion of this disease, from which the country is still suffering. Insular places, especially if far from the main land and free from importation of horses, usually escape. Thus glanders is very rare in Iceland and in the Faroe islands. In Australia, Tasmania and New Zeland it is reported to be unknown. § 128. Etiology. Bacterium mallei, the -A&&-'- specific cause of glanders, was discovered '£$„. " >'^p''' v and isolated in pure culture almost at the ,ACi/' ? ' //Q° same time (1882) by Iyoeffier, Schiitz, Israel, V' O^-A'T* Bouchard, Charrm, Weichselbaum, Kauz- q ' \'y2£\ \ feld and Kitt. It is found in the recent °i ' ^ ' Q"^ ' * nodules, in the discharge from the nostrils, „ „ , ' ° ' Fig. 23. Bacter- pus from the specific ulcers, and occasionally ium mallei. in the blood of animals affected with glanders. Morphologically it is a small organism with rounded or pointed ends. It varies in breadth from 0.25/^ to 0.4/* and from 1.5/* to 3/j. in length. It is usually single but pairs, and long filaments, especially on potato cultures, are not rare. It frequently breaks into short, almost coccus-like elements. It stains with some difficulty. Of the aniline colors, the best results are obtained with the aqueous solutions, when they are made feebly alkaline. It is decolorized by Gram's method. It grows well, but slowly, at the body temperature on glycerine agar, in acid-glycerine bouillon, on blood-serum and on potato. Of the test animals, guinea pigs, and field mice are the most susceptible. In guinea pigs, subcutaneous injections are followed in four or five days by swelling at the point of inocu- 144 SYMPTOMS lation and sloughing of the skin, which are followed by the for- mation of a chronic, purulent ulcer. The lymphatic glands become inflamed and symptoms of general infection develop in from two to four weeks ; the glands suppurate and in males the testicles are involved. A purulent inflammation of the joints may occur. The formation of the specific ulcers upon the nasal mucous membrane, which foriins one of the characteristics of the disease in the horse, rarely occur in the guinea pig as a result of inoculation. The disease is often prolonged for sev- eral weeks or months. Guinea pigs succumb usually in from eight to ten days when injected into the peritoneal cavity with a virulent culture. In males, the testicles are invariably affected. The period of incubation is not generally known. It evi- dently varies from a few to many days. § 129. Symptoms. Two forms of glanders have been recognized, namely, acute and chronic. Acute glanders . Acute glanders is common in the ass and mule, but infrequent in the horse. After a short period of in- cubation the animal has a chill, elevation of temperature, a profuse muco-purulent, sticky discharge, sometimes mixed with blood, from the nose. Particles of food arrested in the pharynx occasionally appear in the nasal discharge. If uni- lateral the margin of the nostril swells, the mucosa is dark- red, infiltrated, marked with pea-like, yellowish elevations with red areolae, which in a few days become eroded, thus forming spreading ulcers. The submaxillary lymphatic glands on the affected side become enlarged. There may, however, be a uniform swelling of the intermaxillary space. The course is rapid and death ensues in from the sixth to the fifteenth day. The acute form rarely if ever becomes chronic. Chronic glanders. In the horse, this form of the disease may begin with a chill but usually the onset is very insidious. There may be a muco-purulent, sticky discharge, sometimes streaked with blood, from one or both nostrils. There may be intermittent or continued lameness, arthritis, edema of a limb, swelling of a testicle, cough, or epistaxis. There is usually a nodular but comparatively painless swelling of the submaxil- MORBID ANATOMY 1 45 lary lymph gland on the affected side. On palpation the swelling imparts a sensation suggestive of a number of peas. They are adherent to the adjacent structures. The nasal mucosa is congested, of a dark reddish color and sprinkled with superficial or deep ulcers either clean or covered with crusts. Rarely the submaxillary glands only are apparently dis- eased. In other cases, there is only a cough, the latent lesions being confined to the lungs. In still other cases, the lesions are restricted to one or both testicles, the spleen, or some other internal organ. Objective symptoms may or may not be present. Chronic glanders may terminate in the acute form. In chronic, cutaneous glanders, with or without edema of the limbs, there may be one or many nodules on the fetlock, or elsewhere on the line of the lymphatic vessels, with indura- tion of the lymphatics extending from it. The nodules may be suppurating and discharging, or they may be closed. § 130. Morbid anatomy. In chronic glanders, the most frequent locations of the lesions are on the respiratory mucous membrane, in the lungs, lymph glands and skin. M'Fadyean states that he has never seen a case of glanders in which the lungs were not affected if any lesions were found. Other or- gans are more rarely invaded. The mucous membrane of the upper respiratory passages is the usual seat of the lesions. Glanders occurs in two forms, ( i ) as circumscribed nodules with the formation of ulcers and cicatrices ; and (2) as diffuse or infiltrated lesions. In nodular glanders, which is the common form, the lesions are most frequently situated on the upper portion of the nasal septum and in the cavities of the turbinated bones. The affection begins with the appearance of nodules varying in size from a grain of sand to a millet seed. They are more or less translucent, of a roundish or oval shape, and of a dirty gray or grayish-red color. The nodules, which may attain to the maximum size of a pea, project somewhat above the sur- face of the mucous membrane. They are surrounded by a red- dish ring. Some of them are isolated and others are arranged in groups. Microscopically they consist of a large number of lymphoid cells, which disintegrate in the centre of'the nodule. 146 GLANDERS In consequence of the central fatty and purulent disintegra- tion, the nodules become yellowish in color, discharge and form Fig. 24, Photograph of a portion of a nasal septum showing ulcers in advanced glanders ; (a) perforations of septum, (6) ulcerated and ne- crotic tissue. ulcers. These ulcers are sometimes superficial, sometimes •deep, lenticular or crateriform, surrounded by a hard, indurated MORBID ANATOMY 147 •edge, and frequently becoming confluent, with irregularly ser- rated and eroded edges. They are sometimes covered with a brownish crust. The ulcers may increase in area or in depth and may even involve the underlying cartilage or bone, causing perforation of the septum nasi, and distensions of the maxillary or exostoses on the turbinated bones. The shallow lenticular ulcers may heal without leaving any visible changes ; but the deeper ones, after granulating, leave a radiating, star-shaped cicatrix which is either smooth or horny, and which, according to the shape of the ulcer, may be of an irregular, oblong form. The nasal septum is frequently covered with these scars. The ulcers and cicatrices are sometimes found in the maxillary and frontal sinuses, in the guttural pouches and in the eustachian tubes. They may also occur in the larynx, especially in the re- gion of the vocal chords. In the trachea and even in the bronchi, particularly on the anterior surface, numerous long, •oval ulcers or long, pointed, serrated scars are frequently found. In addition to the ulcers, a catarrhal inflammation of the mucous membrane is very apt to be present. Diffuse glanders manifests itself as a diffuse catarrh of the mucous membrane of the nasal and neighboring cavities, with superficial ulceration, thrombosis of the veins, inflammatory infiltration of the submucosa, considerable thickening of the mucous membrane and the formation of a peculiar, radiating cicatrix. Both the nodular and infiltrated forms are found in the lungs. In the nodular form, the lungs contain nodules* varying in size from a millet seed to that of a pea. They are gray by transmitted light, glassy and pearl gray by reflected light, and are surrounded by a congested or a hemorrhagic ring. The *Nocard showed that when glandered horses are treated with mallein, a certain proportion of them recover, in which case nodules that were present in the lungs cease to contain living bacteria, a fact he has fully- proved by inoculation. On post-mortem examination the nodules may be readily felt by passing the hand with firm pressure over the surface of the lung, which, when badly diseased, will feel like a bag full of shot or peas. 148 GLANDERS center of the nodules shows a pale yellow point inconsequence of caseation and disintegration of the innermost cells. These nodules are of different sizes, of varying numbers, and of different ages. The formation of a capsule by a connective tissue membrane is induced by a reactive inflammation in the tissue surrounding the nodule. The nodules may be of an FlG. 25. Drawing from a horse's lung containing glanders nodules. They appear on both the pleural and cut surfaces. embolic origin, situated principally in the periphery of the lung, their structure being the same as that of the nodules on the nasal mucosa. Sometimes the lung nodules represent lobular pneumonic foci, in which the alveoli are filled with red MORBID ANATOMY 1 49 and white blood corpuscles and with desquamated epithelium of the lungs. Central disintegration occurs very early. These areas are surrounded by a membrane resulting from a reactive inflammation which manifests itself and out of which a con- nective tissue capsule develops later on. There are two theories concerning the structure of the early nodules. One is, that the first cells are epithelial in nature, thus closely resembling a tubercle. The other is that the first stage of the nodules consists of air cells filled with leucocytes. M' Fad yean has called attention to the structure of the lung nodules, in which he finds a central part composed of leucocytes that have filled the air spaces, the walls of which have disappeared as if by liquefaction. This is surrounded by a zone of epithelioid cells. A third zone surrounds this, in which the walls of the air vesicles are recognizable. The walls are thickened. The fourth zone is composed ot air ves- icles filled with a fibrinous exudate, which entangles a few leucocytes. Frequently the exudate is free from red blood cor- puscles, but at times it contains much blood. In older nodules the third and outermost zone is composed of cirrhotic lung tissue, in which can be distinguished the remains of the air cells. This zone passes gradually into the normal tissue. In the last stage the central area shrinks and becomes calcified, while the other zones become converted into a distinct fibrous capsule. Other observers have not reported the calcification. It has not occurred in the writer's observation. The cell necrosis in glanders has been designated by Una chromatolais which consists in the disintegration of the nuclei before the destruction of the cell body and the retention of the staining property of the broken, nuclear chromatin. This gives the dark color in the central part of a stained nodule. Besides these nodules, there are often chronic bronchitis, peribronchitis, parabronchitis, atelectasis, inflammation of the tissue of the lung and less frequently circumscribed or exuda- tive pleuritis. Infiltrated glanders of the lungs form tumors from the size ■of a walnut to that of a child's head, consisting of a diffuse 15° GLANDERS glanderous infiltration of the alveoli and of the in- terstitial connective tissue. Frequently on section the infiltrated parts of the lungs resemble very closely a soft sar- coma. They are of a dirty white color, of a jj gelatinous, juicy consist- ency and irregular in shape. They may either become indurated so as to form hard, connective tis- sue like new growths (fibroma- like tumors of glanders, according to Gerlach), or they may be- come gangrenous. In Section of a glanders nodule in nodular and in infiltrated the lung ofahorse.{a)necroticcenter,{0 glanders of the lungs the zone of giant cells, (6) capsule surround , , . , , . . r A j , ,r.,-;» " bronchial glands, and fre- tng the nodule {ischutz) . quently the mediastinal glands become enlarged, indurated and studded with small foci of cell infiltration. In glanders of the skin (farcy) the nodules are found in the papillary layer, in the cutis and in the subcutaneous and superficial intermuscular tissue. The cutaneous nodules vary in size from a hemp seed up to that of a pea. They suppurate rapidly and form small ulcers. The nodules in the subcutis are inflammatory (metastatic) tumors from the size of a pea to that of a hen's egg. They change into large abscesses and discharge externally. In the region of the nodules the lym- phatic vessels are inflamed, swollen, and frequently resemble a rosary or knotted cord. Ulcers often develop from these secondary nodes. The neighboring lymph glands are at first swollen and soft, but later they become indurated by the growth of connective tissue and studded with dirty white nodules GLANDERS IN MAN 151 about as large as a pin's head, or with yellow foci of caseation. The capsule around the lymph glands becomes infiltrated with small cells and subsequently thickened. In rare cases second- ary chronic farcy occurs. It is marked by a large, diffuse new- growth of connective tissue with nodular thickening of the skin. This condition is termed glanderous elephantiasis or pachyderma. It chiefly affects the limbs and head. Of the abdominal organs, the spleen is most frequently at- tacked. It then contains embolic nodules, which vary in size and either suppurate, or become calcareous. Similar nodules occur, though not so often, in the liver, kidneys, testicles, brain, muscles, heart and bones. In the bones, the lesions consist of a cellular infiltration of the medulla and purulent breaking down of the osseous tissue. Ulcers are very rare on the mucous membranes of the eyes, stomach and vagina. The blood shows signs of slight leucocytosis. The specific bacteria are found in the blood only in cases of acute general infection. The anatomical changes in acute glanders consist chiefly in a disintegration of the respiratory mucous membrane, in a serous infiltration of the submucous, subcutis, and inter- muscular tissue, with inflammation and suppuration of the lymph vessels and lymph glands. There are also metastatic formations in the skin and lungs. The nasal mucous mem- branes are covered with rapidly spreading ulcers with consider- able infiltration into the submucosa. The mucous membrane of the larynx and pharynx may be swollen and covered with ulcers. The lungs are studded with purulent metastatic foci or fresh nodules. The skin is excessively swollen and covered with glanderous nodes. Sometimes diffuse gangrene of the skin occurs. § 131. Glanders in man. The symptoms of glanders in man are of much importance to the veterinarian. Although the susceptibility to the disease is usually not very great, cases of human glanders unfortunately occur, especially among veterinary surgeons and those having the care of horses. Human glanders is reported to be quite common in Russia. The parts usually first affected are the hands, nasal mucous 152 GLANDERS membrane, lips and conjunctiva. After a period of incubation of from three to five days the infected part becomes swollen Fig. 27. Photograph showing cutaneous glanders or farcy buds. {Photographed by Kelly) . and painful, with subsequent inflammation of the lymph ves- DIFFERENTIAL DIAGNOSIS J 53 sels and swelling of the glands. Fever is often the first symptom, and it is nearly always followed by a nasal dis- charge, ulcers on the nasal mucous membrane, pustules and abscesses in the skin, ulcers in the oral cavity, larynx, and conjunctiva, articular swellings, and grave general distur- bances. Sometimes there is intense gastro-intestinal trouble. Nodules occur in the lungs in some cases. As a rule, death takes place in from two to four weeks, and occasionally in a few days. In other instances, the disease becomes chronic, lasting for months or years. Bad. mallei has been found in the blood in cases of acute glanders. The positive diag- nosis depends on the possibility of infection having taken place, on inoculation in guinea pigs, or the proof of the presence of Bad. mallei. Treatment is usually of no avail. The only hopeful cases are those that are purely local in their manifestation. A few of these are reported to have been cured by applying deep cauterization. § 132. Differential diagnosis. Glanders is to be differ- entiated from a variety of nasal and lymphatic disorders more or less common in the horse kind. Before the discovery of the specific bacterium of glanders or of mallein, it was neces- sary to determine as closely as possible the differential anato- mical characters between glanders and those of other affec- tions, such as chronic nasal catarrh, strangles, lymphangitis, follicular ulceration of the nasal mucosa, cancer, sarcoma, actinomycosis, melanosis and the like. Strong has recently described a disease in the Philippine Islands, which first appears in nodules, that resemble those of glanders very closely. It is caused by a blastomyces. It occasionally attacks cattle as well as horses. Since the discovery of practically positive means of diag- nosis, it does not seem wise to speculate upon the chances of a correct differential determination by obscure clinical evi- dences. If the diagnosis of glanders can not be made from the symptoms and lesions in evidence or by the serum test two reliable courses are possible, although in most cases, but one •(mallein) is to be recommended for general use. These are animal inoculation and the use of mallein. 154 GLANDERS Serum-diagnosis. Rabieaux has found that the difference which exists between the agglutinating power of a serum from a glandered and from a healthy horse may be used as the basis of a method for diagnosing glanders. His method con- sists in collecting the serum as pure as possible, diluting it with sterile, distilled water to i in 10, or to i in 1500. The diluted serum is then mixed in a small sterile tube with an equal volume of a 24 to 72 hour culture of Bad. mallei in peptonized bouillon (without glycerine). The mixture is placed in an incubator at a temperature of 35" to 37° C. and examined at variable times under the microscope. In dilutions of from 1 in 10 to 1 in 50 the agglutination oc- curred in 20 minutes to 3 hours. In serum of a non-glandered horse from 2 to 6 hours were required to produce the agglutina- tion. In weaker dilutions the differences were more marked. Some observers find the serum test not entirely satisfac- tory for purposes of diagnosis. Schiitz and Miessner use the agglutination test for the diagnosis of glanders. Their method is to add the diluted se- rum to a test fluid, composed of a carbolized physiological salt solution and containing a cloudy suspension of the glanders bacteria. They find that the dead bacteria, killed by heating to a temperature of 60° C for 2 hours, agglutinate as readily as the living organisms. In applying the test they put 2 cc of the test fluid containing the bacteria in a small test tube, add the serum, and place the tube in an incubator at 37 ° C for from 24 to 30 hours. If the agglutination takes place, the upper part of the liquid is clear, with an irregular bordered sediment at the bottom of the tube. Upon gentle agitation the sediment falls in an irregular mass to the very bottom of the tube. The method is found to be very satisfactory and it is officially used in Prussia for the diagnosis of glanders. Sterile vials are fur- nished by the Pathological Institute, where the diagnosis is to be made, for the collection of blood from suspected cases of glanders. Animal inoculation. Male guinea pigs should be used. The material for inoculation usually consists of the nasal dis- charge from the suspected glandered horse, bits of scrapings- MALLEIN 155. from the ulcers, or pieces of other diseased tissue. The method to be followed is precisely the same as with the subcutaneous inoculation of tuberculous material. In these cases there is liable to be a local swelling and abscess. The first symptoms of glanders noticed is usually orchitis. The lymphatic glands in the groin are also enlarged. After the orchitis becomes well advanced, the guinea pig may be chloroformed and examined. Pure cultures of the specific organism can be obtained in most cases from the suppurating foci in the testicle. The spleen is usually enlarged and sprinkled with grayish nodules. Other organs may be involved. The diagnosis by the inoculation of a male guinea pig is known as the Strauss method. Mallein. Mallein is prepared in the same way as tuber- culin. It consists of the glycerinated bouillon in which the glanders bacteria have grown and in which are the products resulting from their multiplication. It has a somewhat fetid odor. In applying the mallein test the horse is injected usually in the neck with the required amount (0.5 to 2 cc. ) of mallein, the quantity depending upon the degree of concentration. If a concentrated mallein is used it should be diluted with a 1 per cent carbolic acid solution to at least 2 cc. The reaction is as follows. In a few hours there forms at the place of injection a hot, inflammatory swelling. It is very painful and in case of glanders quite large. From all sides of the swelling there may radiate wavy lines consisting of swollen lymphatics, hot and painful when touched, extending toward the adjoining glands. When the mallein injection is made aseptically, this swelling never suppurates, but it increases in size during a period of from 24 to 36 hours and persists for several days, when it gradually diminishes and finally disappears at the end of eight or ten days. With the appearance of the local swell- ing the patient becomes dull and dejected, the eyes have an anxious expression, the coat is lusterless, the flanks contracted, the respiration hurried and the appetite is impaired. Frequent shudders are observed to pass through the muscles of the fore legs and sometimes the trunk is subject to violent convulsive movements. The most active and fractious horses become listless and indifferent to their surroundings. These general 156 GLANDERS phenomena constitute what the French call the ' 'organic reac- tion," but they are not always so clearly marked. Differences in their intensity are observed but they are never completely absent. The temperature reaction never fails to show itself. In about eight hours after the injection the temperature of a glan- dered horse gradually rises 1.5 , 2° or 2.5 F. , and even more above the normal. The rise in temperature usually attains its maximum between the tenth and twelfth hour, occasionally not till the fifteenth, and more rarely not until about the •eighteenth hour. An important fact to note is that the reac- tion called forth in glandered horses by the injection of mallein persists for from 24 to 48 hours and in some cases the temper- ature remains above the normal for even a longer time. In practice it is advisable to take the temperature of the suspected animals two or three times before the injection of the mallein, and every two hours, beginning at the eighth and going to the twentieth hour after the injection. It is often sufficient for diagnostic purposes to take the temperature but four times, viz., at 9, 12, 15, and 18 hours after the injection. In healthy horses the injection of mallein, even in a much larger dose, produces no effect on the temperature or the gen- eral condition of the animal. There is produced, however, at the point of injection, a small edematous swelling, somewhat hot and painful to the touch, but the edema instead of increas- ing, diminishes rapidly and disappears in less than 24 hours. The reaction called forth by the injection of mallein in a glandered animal is quite specific. When it occurs one is en- abled to state at once and with certainty that glanders exists, although the lesions may be quite minute or obscure. When the reaction does not take place it is generally considered that the animal tested is not glandered, although the physical examination may suggest it. Notwithstanding the specific action of mallein, its administration can give really useful in- dications according to Nocard "only when, and as far as, we •can remove the causes of error that have been pointed out by ■experience." Eor example it would be imprudent to use mal- lein in case of animals already suffering with an abnormal MALLEI N 157 temperature. The further precautions should be taken that the animals subjected to the test are removed as far as possi- ble from atmospheric variations and the influence of strong sun light, fog, rain and currents of air. If it be true that the majority of horses are not susceptible or nearly so, to these influences, there are still some that are affected by them. So that a rise of 1.5 or 2 degrees in temperature would not neces- sarily indicate a reaction. Again, it must not be forgotten that certain diseases, strangles for instance, frequently produce great daily variations in the temperature, therefore, when there is reason to believe in the presence of a disease of this kind, it is necessary to make sure that the increase of tempera- ture consequent on injection of mallein is persistent, and that the organic reaction is clearly present. The question arises whether animals found by the help of mallein to be glandered ought to be immediately slaughtered Nocard said no. The experience of the last few years goes to prove that among the animals that react there are some which, when removed from the infected center and thereby withdrawn from all chance of new contamination, recover. "We ought therefore, ' ' he continues, ' 'to confine ourselves to the destruc- tion of those which in addition to the reaction, present some clinical indication of the disease, such as ulceration of the nose, indurated glands, suppurative lymphangitis, sarcocele or other pronounced manifestation of the disease. The animals now showing physical signs of affection must simply be removed from among the healthy horses and subjected from time to time, say every two months, to the mallein test. If any of these should eventually show the clinical signs of glanders, it ought to be slaughtered at once. On the other hand, those animals which have stood two successive doses of mallein without reacting ought to be considered definitely cured, re- stored to their places and put to the free disposal of the owners." The views held by Nocard are not universally entertained in this country. It has been shown repeatedly that a good reac- ton, following the injection of mallein, was a sure indication of glanders as revealed by post-mortem. The question, however, 158 GLANDERS •concerning the necessity of immediate slaughter for purposes of protection, when there are no evidences of lesions on physical €xamination, seems to be an open one.' This question which pertains to sanitary police rests, until the results of conclusive investigations are recorded, with those entrusted with the pro- tection of animals and men from this disease. However, the results of certain experiments in the use of mallein as a thera- peutic agent and the fact that certain animals recover when kept in quarantine are very suggestive. Certainly further in- vestigations are needed to determine the safe and equitable dis- position of animals devoid of all symptoms and obvious lesions of glanders, but which give a reaction to the mallein test. 133. Prevention. Isolation of the healthy animals from the infected ones and thorough disinfection of the stable are important. It is also desirable not to bring strange horses in -close contact with home animals, until their freedom from this disease is determined. REFERENCES. 1. Babes. Observations sur la morve. Arch, de Med. Exper. et d'Anat. Pathologic, Vol. Ill (1891), p. 619. 2. BuTXER. Glanders. Bulletin No. 16. Miss. Agr. Expt. Sta- tion, iSpi. 3. Cary. Glanders. Bulletin No. 35. Ala. Agr. Expt. Station of the Agricultural and Mechanical College, Jan. 1892. 4. DE SchweiniTz and Kixborne. The use of mallein for the •diagnosis of glanders in horses and experiments with an albumose ex- tracted from cultures of bacillus mallei. Am. Vet. Review, Vol. XVI (1892), p. 439. 5. Francis. Glanders, tests with mallein. Bulletin No. so. Texas, Agri. Exp. Station, 1894. 6. FroThingham. The diagnosis of glanders by the Strauss method. Jour, of Medical Research, Vol. VI (1901), p. 331. 7. Higgins. Glanders and Mallein. Proceedings Amer. Vet. Med. Asso. 1904, p. 135. 8. I,angER. Untersuchung iiber die differential diagnostische Bedeutung der Rotzagglutination u. s. w. Monatshefte fur prak. Tierheilkunde, Bd. XVI (1905), S. 241. 9. Loeefler and Schutz. On the bacillus of glanders. Deutsch. Med. Wochenschrift, Dec. 1882. Translated, Vol. CXV, New Syden- ham Society. V 10. M'Fadyean. The pulmonary lesions of glanders. Jour of ■Compar. Path, and Then Vol. VIII (1895), p. 50. REFERENCES 1 59 *S ii. M'Fadyean. Glanders. Jour. Compar. Path, and Ther. Vol. XVII (1904), p. 295. 12. Nocard. The value of mallein as a means of diagnosis in doubtful cases of glanders. Jour, of Compar. Path, and Ther. Vol. VIII (1895), p. 227. 13. RabiEaux. Serum diagnosis of glanders, ad. Jour. Compar. Path, and Ther. Vol. XVI (1903) , p. 59. Orig. Jour, de Med. VU. 1902. 14. Reynolds. State control of glanders in Minnesota. Jour, of Compar. Med. and Vet. Archives, Vol. XX (1899). 15. SchuTz. A contribution to the subject of glanders. Jour, of ■Compar. Path, and Ther. Vol. XI ( 189b) , p. 1. 16. SchuTz. Zur Lehre vom Rotre. Archiv. fur zaiss. u. prakt. Tierheilkunde. Bd. XXIV (1898), S. 1. 17. SchuTz and MiESSNER. Sur Serodiagnose der Rotzkrankheit. Archiv. fiir Wiss. u. prakt. Tierhielkunde, Bd. XXXI (1905), S. 353. 18. Smith. On the influence of slight modifications of culture media on the growth of bacteria as illustrated by the glanders bacillus. Journal of Comparative Medicine. (1890), p. 158. 19. Strong. Preliminary report of the appearance in the Philip- pine Islands of a disease clinically resembling glanders. 1902, No. 1, Bureau of Government Laboratories, Manila. 20. Strauss. Sur un moyen diagnostique rapide de la morve. Arch, de Med. Exper. et de Anat. Path. Vol. Ill (1889), p. 460. 21. Williams. Glanders. Bulletin No. 4. Montana Agric. Expt. Station, 1894. 22. Wright. The histological lesion of acute glanders in man and of experimental glanders in the guinea pig. Jour, of Exp. Med. Vol. I (1896), p. 577. 160 INFECTIOUS DISEASES TUBERCULOSIS. Synonyms. Consumption, pearl disease, phthisis, scrofula, tabes, "the great white plague," grapes. § 134. Characterization. Tuberculosis is an infectious disease from which the human species, cattle and swine suffer very extensively and which, under favorable conditions, attacks nearly if not all species of animals including fish. It is a disease of slow development, involving either primarily, or in association with other organs, the lymphatic system. It is characterized by the formation of nodules, or tubercles, in consequence of the activities of Bacterium tuberculosis. It does not destroy life by acute toxemia, but by a chronic and long continued systemic poisoning and by the morbid changes brought about through the localization of these lesions in organs necessary to life. § 135. History. Tuberculosis is one of the oldest dis- eases affecting cattle of which there are identifying records. It seems to have been known to the Jewish people during their Egyptian captivity and the ecclesiastical laws for many cen- turies contained numerous enactments against the consump- tion of flesh from tuberculous animals. In 1370, it was for- bidden in Munich to have on sale the flesh of animals affected with tuberculosis. A number of other cities passed similar ordinances. In 1702, Florinus described the disease and em- phasized the then existing opinion that it was identical with syphilis. This led to the practice of destroying all tubercu- lous animals. In 1783, the Berlin Board of Health rejected the theory of the connection of tuberculosis and syphilis and declared the flesh of affected animals to be fit for food. This led finally to the cancelling of all laws throughout Prussia against the use of flesh for food from animals affected with the disease. Tscheulin, in 1816, recognized in reference to the infection of meat, three degrees of bovine tuberculosis, viz : 1 , in which the tubercles were to be removed ; 2 , in which the diseased parts were to be destroyed and the meat sold at alow price ; and 3, those cases in which the lesions were so exten- sive that the whole carcass must be rejected. HISTORY l6r The study of the lesions themselves gave rise to a num- ber of beliefs concerning their nature. Thus, Virchow, Schiip- pel and others declared that the tubercles in cattle were lym- pho-sarcomata. Leisering considered them simply as sarco- mata. Spinola and Haubner maintained that human and bo- vine tuberculosis were identical. In 1865, Villemin showed that tuberculosis was due to a specific infection. He produced the disease in rabbits by in- oculating them with tuberculous material from human sub- jects. He also produced the disease by feeding experimental animals and by causing them to inhale tuberculous material. Chauveau, in the same year, produced the disease in cows. These results were soon confirmed by Klebs, Cohnheim and Gerlach. These experiments, in which the disease was pro- duced in one species with tuberculous material from another, followed by the discovery by Koch of the specific bacterium of the disease, led to the view that tuberculosis in all species of mammals was identical. This generally accepted belief caused sanitarians to look upon tuberculosis in cattle as a great men- ace to public health. The result was that during the closing decade of the last century, this disease in cattle was treated more vigorously as a menace to the human species than as a destructive disease of animals. In 1896, Dr. Theobald Smith pointed out the fact that for certain animals the tubercle bacteria from cattle were more virulent than those from man and further that there were cer- tain morphological and cultural differences existing between them. In 1898, he published the results of a more extended series of investigations. Since that time a number of investi- gators have arrived at the same conclusion. The fact has come to be well known that certain differences exist between the bacteria of tuberculosis found in the human and in the bovine species. Koch's experiments reported at the tubercu- losis congress in London in July, 1901, give additional evi- dence of a difference in virulence for experimental animals of the bacteria of human and of bovine tuberculosis. To what extent the human species becomes infected from the bovine kind cannot be stated, but the accumulating evidence tends to 162 TUBERCULOSIS the conclusion that bovine tuberculosis is of less significance in its influence upon public health than has heretofore been thought, and of more importance as a rapidly spreading and destructive disease among cattle. It is not proven, however, that the human species is not affected with the bacteria of bovine tuberculosis. The investigations of the last five years have shown that not infrequently human tubercle ma- terial will produce tuberculosis in cattle. The interim report of the Royal Commission appointed in 1901, is important in this connection. Salmon has published an important paper on the relation of human and bovine tuberculosis in reply to Koch's paper of 1901. Concerning its transmission, the con- clusion seems to be warranted, that the virus of tuberculosis spreads very largely among men and cattle from individual to individual of the same species rather than from species to species. It is also demonstrated that cattle may contract, by direct inoculation, tuberculosis from man. § 136. Extent of tuberculosis especially among cattle and swine. The committee on cattle diseases and animal food of the American Public Health Association for 1901 reported the appended statistics concerning the extent and increase of tuberculosis in cattle and swine in various countries. "The slaughter house statistics of Prussia show 14.6 per cent of the cattle and 2.14 per cent of the swine to be tubercu- lous. In Saxony the percentage is 29.13 with cattle and 3. 10 with swine. In the city of Leipzig the figures are 36.4 for cattle and 2.17 for swine. (Siedamgrotzky). Of 20,850 animals in Belgium tested with tuberculin in 1896, 48.88 per cent reacted. Of 25,439 tested in Denmark from 1893 to 1895, 49.3 per cent reacted ; and of 67,263 tested from 1896 to 1898, 32.8 per cent reacted (Bang). An examination of 20,930 cattle in Great Britain, either slaughtered and examined post- mortem or tested with tuberculin, showed 5,441 or 26 per cent affected with tuberculosis. M'Fadyean estimates that 30 per cent of the cows in Great Britain are tuberculous. Figures available in the United States do not cover a sufficient area of GEOGRAPHICAL DISTRIBUTION 1 63 our territory to allow us to make a reliable estimate of the extent of tuberculosis in milch cows. "Our beef cattle as they come to the large packing houses, are as yet comparatively free from tuberculosis. Of 4,841,166 ■cattle slaughtered in the year 1900, under Federal meat inspec- tion, but 5,279 or o. 1 1 per cent were sufficiently affected to cause the condemnation of any part of the carcass. Of 23,336,884 hogs similarly inspected, 5,440 were sufficiently affected to cause a condemnation of some part of the carcass. This is equal to 0.023 P er cent, or slightly more than one-fifth the proportion found in beef cattle. "The slaughter house statistics of all countries show that the percentage of affected hogs increases as the disease becomes more common in cattle, so that we must consider not only the effect of the disease upon beef and milk producing animals but also upon swine. Tuberculosis is more acute with hogs than with cattle, and there is a much greater tendency to gen- eralization, consequently the parts used for human food are more likely to be affected, and if there is a possibility to com- municate the virus through the meat the danger is increased "by this peculiarity of the disease in swine." § 137. Geographical distribution. Tuberculosis is an exceedingly wide spread disease. In earlier times it was quite prevalent among cattle in Central Europe. It seems to have existed in Western Asia and Northern Africa at an early date. From these centers it has spread to nearly every cattle raising country of the world. Its rapid spread during the last fifty years is attributed to the increase in cattle exchange resulting in the introduction of tuberculous animals into healthy herds. It is stated that in many countries, and in large districts with- in others, tuberculosis did not exist until it was introduced •within recent years by the importation of diseased animals. In countries where there has been little or no importation of cattle, and in which the native breeds still exist unchanged, as in many parts of Russia, Austria and Spain, in the north- ern part of Sweden and Norway, and in parts of Africa, tuber- culosis is practically unknown. This is true of the cattle on 164 TUBERCULOSIS the island of Jersey, where for more than a hundred years for- eign cattle have not been introduced. In the United States, the disease is very widely distributed. It is found to a considerable extent in certain localities where the climatic conditions seem to be beneficial for tuberculous people. The explanation for this seems to be that tuberculous animals have been introduced into certain herds in these dis- tricts. There are, however, large areas in which it is practi- cally unknown. The Western steers that are killed in the slaughter houses of Kansas City, Omaha, Sioux City and Chicago are practically free from this disease. Tuberculosis exists, however, in many places where beef cattle are raised, as the result of the introduction of affected breeding stock. In many localities, especially where there is an extensive inter- change of animals, a large percentage of the herds are more or less affected. § 138. Etiology. Tuberculosis is caused by a rod-shaped organism known as Bacterium tuberculosis. It was discovered by Robert Koch in 1882. Schiil- ler and Toussaint had previously studied growths which seem, from the results of their inocula- tion experiments, to have been this organism. The bacterium of tuberculosis is a slender, rod- shaped organism with rounded ends, from 2 to 5/* in length and from 0.3 to 0.5/^ broad. The rods are straight or slightly curved, and occur singly, in pairs FlG - z8 - Bacterum tuberculosis. or in small bundles. Frequently they cross one another. They do not produce spores, but vacuoles are often observed and branching forms have been described. The bacterium of tuberculosis is readily cultivated on artificial media such as blood serum, glycerinated agar and bouillon after it has been adapted to such artificial con- ETIOLOGY 165 ditions.* It is, however, not easy to cultivate it directly from ordinary tuberculous lesions. Although at the time of their discovery, the tubercle bacteria from man and from animals were believed to be identical, they have been found to possess slightly different characters and properties. Smith pointed out in 1898, that morphologically those from cattle were shorter and thicker than those from man, that the growth was slightly different on blood serum, and that they were much more virulent for cattle and rabbits than those from the human species. Since that time his conclusions have been confirmed by a number of investigators. Koch obtained like results. At present, therefore, we must look upon the tubercle bacteria coming from these different species as possessing races or varieties which, perhaps, is the result of their different con- ditions of life. The investigations which have been made with the decidedly different forms of this organism found in tuberculosis of fowls and of fish have led a few experimenters to believe that they are simply varieties of the organism first described by Koch. Further inquiries are necessary to fully satisfy bacteriologists that all of these forms are thus related to the one species. There seems to be no reason for doubt- ing that the bovine and human forms are varieties or races of the same species. The difference in the conditions of life under which they exist in the bodies of men and of cattle are *To accomplish this necessitates a very special and careful proce- dure. Dr. Theobald Smith, of Harvard University (Jour, of Exp. Med., Vol. III., 1898, p. 451) , has the credit of formulating a method by com- bining details in such a manner that the procuring of cultures is, in most cases, possible. Dog serum is used. The method, as he gives it, is as follows : "The dog was bled under chloroform and the blood drawn from a femoral artery, under aseptic conditions, through sterile tubes directly into sterile flasks. The serum was drawn from the clots with sterile pipettes and either distributed at once into tubes or else stored with 0.25 to 0.3 per cent chloroform added. Discontinued sterilization was ren- dered unnecessary. The temperature required to produce a sufficiently firm and yet not too hard and dry serum is for the dog 75° to 76° C. For horse serum it is from \° to 5° lower. The serum was set in a thermo- stat into which a large dish of water was always placed to forestall any abstraction of moisture from the serum. About 3 hours suffice for the 1 66 TUBERCULOSIS quite enough to explain resulting differences in the bacteria. § 139. Symptoms. The symptoms vary according to the course of the disease. There is a chronic form, which is most common, and an acute form or miliary tuberculosis. The symptoms of chronic tuberculosis depend upon the location of the lesions and their extent. When the lesions are situated deeply and are not of great extent, they may not ex- hibit visible evidence of their presence. In such cases, the in- fected animal may present the picture of perfect health and show no disturbance of function. Indeed some animals, in which the lesions are both extensive and widely distributed and which have never presented noticeable signs of the disease, are slaughtered for beef without a suspicion of the presence of tuberculosis until they are examined post-mortem. coagulation. When serum containing chloroform is to be coagulated, I am in the habit of placing the tubes for an hour or longer in a water bath at 55° to 6o° C, or under the receiver of an air pump, to drive off the antiseptic. This procedure dispenses with all sterilization excepting that going on during the coagulation of the serum. It prevents the gradual formation of membranes of salts, which, remaining on the sur- face during coagulation, form a film unsuited for bacteria. Tubes of coagulated serum should be kept in a cold closed space where the oppor- tunities for evaporation are slight. They should always be kept inclined. "The ordinary cotton-plugged test tubes I do not use, because of the rapid drying out permitted by them, as well as the opportunities for infection with fungi. Instead, a tube is used which has a ground glass cap fitted over it. This cap contracts into a narrow tube plugged with glass wool. This plug is not disturbed. The tube is cleaned, filled, and inoculated by removing the cap. With sufficient opportunity for the interchange of air little evaporation takes place, and contamination of the culture is of very rare occurrence. In inoculating these tubes, bits of tissue, which include tuberculous foci, especially the most recent, are torn from the organs and transferred to the serum. Very little crushing, if any, is desirable or necessary. I think many failures are due to the often futile attempts to break up firm tubercules. Nor should the bits of tissue be rubbed into the surface, as is sometimes rec- ommended. After a stay of several weeks in the thermostat, I usually remove the tubes and stir about the bits of tissue. This frequently is the occasion for a prompt appearance of growth within a week, as it seems to put certain still microscopic colonies in or around the tissue into better condition for further development. The thermostat should be fairly constant, as uiged by Koch in his classic monograph, but I SYMPTOMS 167 Since the lesions of tuberculosis vary so much in different cases, it is not possible to give a description of what can be designated the characteristic or even the usual symptoms of this disease. There are, however, certain general manifesta- tions that appear in most of the advanced cases, such as emacia- tion, while the appe- tite continues good. This is always a sus- picious indication and especially if accom- panied by cough, rough coat and tight, harsh skin. Rough or loud respiratory sounds are suspicious, and, in advanced cases, it is often found that the animal groans when pressure is brought to bear upon the chest wall. Many cases bloat habitually. Hard, painless swel- lings (enlarged lymp- hatic glands) beneath the skin in the region of the escutcheon, flank, shoulder or throat are suspicious. Fig. 29. Right lateral aspect of posterior half of steer' s head, {a) Lower jaw, (b) ear passage, (c) horn, (d) styloid process of occipital bone, (e) parotid gland, if) sub- maxillary gland. A. Right parotid lymph gland. B. Right post ma.villary lymph gland. C. Right submaxillary lymph gland. These glands are often the seat of tuber- cular deposits {Smith). look upon moisture as more important. If possible, a thermostat should be used which is opened only occasionally. Into this a large dish of water is placed, which keeps the space saturated. Ventilation should be restricted to a minimum. As a consequence, moulds grow luxuri- antly and even the gummed labels must be replaced by pieces of stiff manila paper fastened to the tube with a rubber band. By keeping the tubes inclined, no undue amount of condensation water can collect in 1 68 TUBERCULOSIS In tuberculosis of the lungs, it may be said that coughing is the most noticeable symptom. It is most common after feeding, drinking, or after rapid moving following a period of repose, but sometimes it occurs without any apparent cause. The cough is usually strong, dry and frequently of a high pitch. Sometimes it is very violent, accompanied by protru- sion of the tongue. Ausculation reveals modified and abnor- mal sounds of different kinds in the lungs ; sibilant, sonorous and mucous rales are most common. A dull sound is often detected on percussion. It is also to be noted that this condi- tion is of slow development and long duration, thus aiding one to distinguish it, in many cases, from bronchitis or pneumonia. Where the mediastinal lymphatic glands are enlarged and press upon the esophagus, it is stated that the animal bloats habitually. Chronic or habitual bloating accompanied by a good appetite and no other evidence of disease of the digestive tract, especially if there is shortness of breath and cough, may be looked upon as strongly indicative of tuberculosis with enlarged mediastinal lymphatic glands. Sometimes large tubercular masses develop on the pleura. In such cases the principal symptom is a friction sound that is heard most distinctly during inspiration. If the masses are large enough they give rise to a dull sound upon percussion. In tuberculosis of the stomach and intestines, digestion is interfered with. This gives rise to poor appetite, frequently to diarrhea and sometimes to alternation of diarrhea and con- stipation. In tuberculosis of the peritoneum or of the lin- ing of the abdominal cavity, the lymphatic glands of the the bottom, and the upper portion of the serum remains moist. The only precaution to be applied to prevent infection with moulds is to thoroughly flame the joint between tube and cap as well as the plugged end, before opening the tube. When test tubes are employed it is well to dip the lower end of the plug into sterile molten paraffin and to cover the tube with a sterilized paper cap. The white bottle caps of the drug- gist are very serviceable." While the tuberculous material is perfectly fresh (uncoiitaminated) and in the early stages of the disease, it is safer to inoculate a guinea pig, and after the lesions begin to develop to chloroform it and make the cultures from the recently affected liver or spleen. SYMPTOMS 169 flank are often enlarged and bard. Sometimes this condition ■can be diagnosed positively by a rectal examination and the ■discovery of the hard, nodular masses. Tuberculosis of the liver does not give rise to obvious symptoms unless the dis- ease is far advanced, in which case jaundice may be observed. In animals in which the post- pharyngeal lym- Rhatic glands are Inlarged from tu- be re ulosis, the breathing is harsh Ind noisy. In this londition there is sometimes difficul- ty in swallowing, Ind particles of chewed up food are occasionally expel- Ks."" W . /- a led from the mouth, M , I 1 ~ ; 0M J either voluntarily, ' ,:.:, '■ ] when it is found that they cannot be k swallowed conven- xSx^r iently ' or by the -mm V' y coughing they oc- casion upon reach- Fig. 30. Dorsal aspect of bovine lungs, (a-a 1 ) ln S the pharynx. right and left caudal lobes, (b-b') r. and I. ven- These enlarged tral lobes, (c-c l ) first and second right cephalic . , lobes, (c 2 ) left cephalic lobe, (e) trachea, (.r x) g lands ma y SOtne- region most frequently involved in the earliest times be detected stages of pulmonary tuberculosis. The lesions , . . at this stage are usually embedded in the lung D y palpation ac- tissue (Smith). complished by plac- ing one hand on each side of the throat above the larynx and then pressing from opposite sides. Tuberculosis of the udder is detected by an enlargement and hardening of the affected part, usually by the absence of pain and the fact that the secretion is not altered until the part 170 TUBERCULOSIS has been diseased for some time. In advanced cases, instead of milk, the udder secretes a yellowish, cloudy and sometimes flocculent liquid. In acute, ,„ rapidly developing cases, there may be pain and edema of the skin. In nearly all cases of udder tuberculosis the supra- mammary lymphatic glands situated above the udder in the middle of the escutch- eon, are enlarged and hard. If there is doubt as to the character of the disease of the udder, the milk, or possibly a piece of excised udder tissue, may be ex- amined bacteriologically. In tuberculosis of the brain, the animal is un- steady and, uncertain in its movements. It lies down much of the time is usually subject to occasional cramps and is apt to carry the head F IG - 3 1 - Trachea and bronchial tubes in an unusual position, of bovine lungs showing attached bron- _ , . ,. , chial glands, (a. a?) Supply right ana Such cases are inclined to left caudal lobes< {b .b^ supply r. and I. advance rapidly and termi- ventral lobes, (c-c 1 ) branches of its right nate in death following supernumerary bronchus, (C) supply coma or convulsions left cephalic lobe, (d) branch to azygons T . . 1 j- r lobe, (e) trachea. A, Left bronchial In tubercular disease of ' K) ' J . , lymph gland. B,Rig lit bronchial lymph the bones and joints, the gland c> Lymph gland base of ^ rfl _, parts are enlarged, there is numeral bronchus. D, gland often be- loss of motion, pain and tween bronchi. The glands A. to £>.,. usually abscess formation are °f ten involved {Smith). followed by the discharge of thick yellow pus. In tubercu- losis of the uterus or ovaries and sometimes in peritoneal tuber- culosis of the cow, the subject is almost continually in heat. SYMPTOMS i7r In tuberculosis of the uterus, there is sometimes a discharge of thick, yellowish material mixed with mucus. In tubercu- losis of the testicles the organs become enlarged and hard. In all advanced cases, the nutrition of the animal is in- terfered with and, sooner or later, the "tuberculous cach- exia" appears. It is, however, in many cases remark- able to note the ex- tent of lesions in animals that are well nourished and present no external signs of disease. Animals killed in prime condition by the butcher are sometimes found to contain extensive and widely distri- b u t e d lesions o f tuberculosis. I n general tubercu- losis, many of the symptoms de- scribed above may occur simultane- ously. The symp- toms of acute mili- ary tuberculosis, "galloping consumption,"- are rapid loss of flesh, depression, poor appetite, cough, weakness, rapid breath- ing, harsh respiratory sounds, some elevation in temperature, increased pulse rate and, sometimes, enlarged lymphatic glands. The course of this form of tuberculosis is always rapid and Fig. 32. Dorsal aspect of bovine lungs showing position of the posterior mediastinal glands ;. (a, b, c, c') caudal, ventral, cephalic lobes, (f) esophagus, (g) muscular pillars of diaphragm, (h) posterior aorta, (i) caudal margin of the lig- ament of the lung. A. Left bronchial gland. Mediastinal glands are shown, most of them resting on the esophagus. The large caudal gland resting on the pillars of the diaphragm is most frequently diseased and often attains an enormous size. The remaining mediastinal glands are arranged in two sets on the right and left margins of the esophagus (Smith) . T7 2 TUBERCULOSIS terminates in death. Acute miliary tuberculosis occurs when large numbers of tubercle bacteria are discharged into the blood or lymph currents. They are then carried to other parts of the body, filtered out in the capillaries of the lungs, liver, spleen, kidneys and elsewhere, causing tubercular lesions in each of these localities. The lesion from which the infectious material ■entered the circulation may have been a comparatively small nodule. This form of the disease is more likely to appear in young animals than in adults, and is more common among swine than in cattle. § 140. Morbid anatomy. The usual direct anatomical •changes following the invasion of tubercle bacteria are the formation of nodules or tubercles. A tubercle has been de- fined as, "a small nonvascular nodule composed of cells vary- ing in form and size with some basement substance between them and with an inherent tendency to undergo central necrosis." In a large number of cases the individual tubercles are distinct and easily recognizable, while in others they are •coalesced, forming a mass of necrotic tissue. The lesions vary, therefore, from well isolated minute or larger nodules to masses or cavities containing a purulent, caseous, or calcified substance. The location of the primary lesion depends upon the chan- nel of infection. If the specific organisms are lodged in the oral cavity or pharynx they may, through an accidental abra- sion of the mucosa, be taken to some of the lymphatic glands about the head ; if they are taken directly through the respira- tory passages into the lungs they either develop nodules in the lung tissue proper, or they are carried through the lymphatic system to the lymph glands draining the lungs where the lesions first appear. If the specific bacteria are first lodged in the intestinal mucosa, primary tubercular ulcers may develop or they may pass into the mesenteric lymphatics or the portal vein. It may happen that the bacteria may be carried by means of the lymph or blood stream and lodged in any part of the body, such as the brain, kidneys, spleen, testes, ovaries, bones, joints, and subcutaneous and intermuscular glands and serous membranes. The evidence at hand, however, seems to MORBID ANATOMY 175 show that in a large majority of cases the primary lesions are located in one of the five following organs : ( i ) in the lungs or the lymphatic glands draining them, (2) in the lymphatic glands about the head, (3) the intestines and mesenteric glands, (4) in the portal glands or liver substance itself, and (5) in the generative organs and udder. It not infrequently happens that the apparent primary lesions occur on the pleura, peritoneum, meninges or synovial membranes while the organs remain free from disease. In such cases the lesions consist of many tubercles varying from one to ten or more millimeters in diameter or of bunches of closely set tubercles which are more or less flattened or irregular in shape, owing to their mutual pressure. Sometimes these tubercles are attached to the serous membrane by a small, tough, fibrous pedicle ; frequently, however, this is absent and the nodules rest bodily upon the membrane. Fig. 33. A drawing of a section of very young tubercles in spleen{Thoma)- The structure of the tubercle consists in the beginning of a few cells surrounding the invading specific organisms. These are soon encased by a zone of epithelioid cells and giant cells 174 TUBERCULOSIS -which is soon surrounded by an outer layer of round or lymphoid cells. The central portion becomes necrosed and as the nodule enlarges the central necrotic portion becomes -correspondingly large. This histological structure of the tubercle is typically illus- trated in the beginning avian tubercle. In cattle there is a strong tendency for the necrotic tissue to become infiltrated with lime salts and encapsulated. In certain species a deposit of fibrous tissue in the outer zone of the tubercle has been observed. In the smaller and more susceptible experimental animals such as the guinea pig and rabbit and frequently in swine, the lesions are of a more diffuse nature infil- trating the interstitial tissue with the tuberculous mass and gradually encroaching upon the parenchyma. Circumscribed tubercles may also be present. In secondary or generalized tuberculosis one or more of the organs such as the omentum, serous membranes, or lym- phatic system may become more or less thickly sprinkled with minute grayish nodules about the size of a millet seed. These tubercles are at first almost the color of mother-of-pearl but later as the central caseous degeneration begins they become grayish. Giant cells are usually numerous. In studying the lesions in a fatal case of tuberculosis one may find with varying modifications one or more of the following conditions : i. The primary lesion may be found in any one of the -organs or membranes. Its comparative age is determined by the character of the anatomical changes. It may be entirely encysted, caseous or calcareous and dead. In addition to the primary focus, there may be a succession of tubercles of various ages distributed in one or more organs. 2. , The lesions may be restricted to one organ, as the liver in which the primary focus has spread by continuity due to its infiltrating nature until the destruction of the tissues of the organ has become so extensive that death results. Such cases do not seem to be common. 3. The primary lesion may be well marked and accom- panied by miliary tubercles sprinkled extensively throughout the organs and tissues of the entire body. Plate II. TUBERCULOUS HEART FROM A COW. MORBID ANATOMY 175 4. The lesions throughout the body may resemble each other very closely, so that difficulty may be experienced in determining the primary focus. In the lungs, two distinct forms of lesions are observed. (1 ) The air cells may be infil- trated with the tuberculous mass spreading directly from the pri- mary focus. This may be puru- lent, caseous or calcareous. The color may be whitish, gray or of a yellowish tinge. (2) The le- sions may consist of miliary tubercles. In later stages these nodules, more or less translucent, may become yellowish, caseated and calcareous in their centers. L,arge tubercular nodules are frequently formed by the mass- ing of several of these minute tubercles. When the lungs are pri- marily attacked the caudal (prin- cipal lobes are most frequently involved. Smith considers the seeming predilection for the larger lobes to be due to mechan- , . . _, . , Fig. 34. Tuberculous focus in ical conditions. The writer has , , ■ , , . lung showing areas of (a) casea- found, however, that in certain Hon, (5) calcification, and (c) herds that have been killed after suppuration. the tuberculin test, the primary and only lung lesions were in the ventral and cephalic lobes. It is important to note that usually the bronchial glands are also involved. When the pleurae are affected the lesions consist of nodules varying in size from that of a millet seed to a large pea, sprinkled more or less thickly on one or both of the visceral or parietal surfaces. These form the ' 'pearl disease' ' (Perlsucht) of the German and the "grape disease" of the English writers. If they become Fig. 35. Photograph of a section from anterior lobe of a tuberculous lung of a cow, showing tubercular infiltrations and calcified areas. MORBID ANATOMY 177 confluent, large masses are found. Tuberculosis of the thoracic glands is very common and usually accompanies lesions in the lungs ; but the lungs may be healthy and the glands involved. (See figures for location Fig. 36. Photograph of pleura showing small tubercular nodules. of glands.) The primary lesions may be and often are found in the lymphatic glands about the head. In the abdominal cavity the organs most frequently in- volved are the peritoneum, mesenteric lymph glands, portal lymph glands and liver. The kidneys, spleen, ovaries and uterus are more rarely the seat of tuberculous tumors. Ulcers in the intestine have not been common in the writer's observa- tion. The ulcers in the cases observed have been isolated with elevated borders and a depressed center. Sections show that the tuberculous infiltration extends outward and to a certain extent undermines the mucosa. Tuberculosis of the testis is sometimes found. The udder often becomes the seat of tubercular deposits in cases of generalized tuberculosis. When the primary infection is restricted to a single focus the disease is said to be localized. When the specific bacteria i 7 8 TUBERCULOSIS are spread from the primary lesion through the agency of the lymph and blood streams, sprinkling other organs with the infecting bacteria each of which becomes the starting point for the development of a new tubercle, the disease has become generalized.* *■! '-jhf* • A ' iH-ii "/.-*r™J?& ■■■■ -'Mm ■ •*• -\ '%>■ ~.f $£ ** "■ Fig. 37. Tubercles on the mesentery of a cow {Harding). It was formerly considered that when the lesions existed in both of the large (abdominal and thoracic) cavities of the body the disease was generalized. It is possible, however, for it to be generalized when the lesions are restricted to the organs of one cavity as the secondary seeding with the bacteria *The Federal meat inspection regulations state that animals affected with "extensive or generalized tuberculosis" are to be condemned. MORBID ANATOMY 179 that have escaped from a primary focus through the circulation may be restricted to the cavity in which the first lesion devel- oped. It seems better, therefore, to accept Ostertag's views Pig. 38. A photograph of the tubercular nodules on the omentum (cover- ing the intestines) from an advanced case of generalized tuberculosis. and classify local and general tuberculosis in accordance with the nature of the lesions rather than their distribution in the body. The fact is worthy of consideration, that very often cattle killed after reacting to tuberculin do not show extensive dis- i8o TUBERCULOSIS tribution of lesions. Frequently animals are killed soon after infection has taken place, in which case the lesions are re- stricted to a single lymphatic gland or other organ. In other cases old lesions of considerable proportion are found as shown in plate II, where the heart muscle is entirely encased in a Fig. 39. A photograph of several tuberculous ulcers in the intestine of a cow. thick calcareous tubercular deposit. In this case, the animal was in good flesh and killed for beef without a suspicion that it was in any way diseased. TUBERCULOSIS IN SWINE. § 141. Channels of infection. It is stated that among swine young animals belonging to the precocious breeds seem to be more liable to tuberculosis than others. In nine cases out of ten the animals are infected by ingestion. The pig easily becomes tuberculous when fed on material rich in SYMPTOMS 181 tubercle bacteria. If pigs are fed on the refuse from dairies and cheese manufactories in districts where there is much tuberculosis in cattle or on tuberculous viscera they readily become infected. Infection through the respiratory tract, while it is certainly possible, seems to be rare. The piggeries where the refuse from butter and cheese factories is fed and those which adjoin abattoirs supply the majority of animals found on post-mortem to be tuberculous. Fig. 40. A photograph of a section of a tuberculous ulcer, showing infiltration under the marginal mucosa. Ostertag has called special attention to this disease as ex- isting among swine in certain parts of northern Denmark and Germany, where there was much tuberculosis in cattle, and where the swine were fed the slime from creamery separa- tors. Experiments show the possibility of infection by means of the sputum of tuberculous people. In the cases which have come to our notice there is very strong evidence that the swine were infected by being fed the milk from tuberculous cows. In one of these cases, the tuber- culin test showed that a large number of the cows from which the milk was obtained were affected. § 142. Symptoms. In most cases tuberculosis of the pig is first recognized at the abattoir. Sometimes, however, it causes local and general troubles, which vary according to the organ or system attacked. The following symptoms have been noted. l82 TUBERCULOSIS IN SWINE Its localization in the abdominal organs causes the arrest of fattening and the progressive wasting of the subject. The mucous membranes become pale, the hide becomes dirty and there is usually either constipation or diarrhea. The animal is in low spirits, the corkscrew of its tail is straightened, the abdomen is pendulous and the eyes are sunken. Palpation of the abdomen is painful and may reveal more or less volumi- nous masses, due to the changes in the mesenteric glands. It is common to find glandular tumors in the submaxillary region or at the thoracic inlet. In this form, the malady may last several months, but death supervenes rapidly if the lesions become generalized by the scattering of the bacteria through the blood stream. Primary pulmonary tuberculosis is very rare but sooner or later lung lesions complicate abdominal tuberculosis. They betray themselves at the outset by a short, dry, abortive cough and by difficult respiration. The cough soon becomes paroxysmal and painful and is often followed by vomiting ; the respiration becomes hurried and gradually pain- ful and more difficult, wasting is very rapid, and death super- venes in a few weeks. The scrofula of swine (glandular tuberculosis) usually shows itself by a puffing up of the face, which a careful exam- ination shows to be lifted up by the subjacent glands, which are enlarged, indurated, still fairly mobile and free from heat or tenderness. The retro-pharyngeal, superior cervical and sublingual glands are usually affected, forming a kind of neck- lace of unequal and knotty tumors, reaching from ear to ear and becoming larger under the neck between the rami of the lower jaw. Similar tumors may be developed at the thoracic inlet, behind the shoulder or in the groin, which, as they increase in size, become harder and more adherent to the neighboring tissues. Sometimes, however, a slight fluctuation is perceptible. The tumor may suppurate and discharge a small quantity of a thick and grumous pus, but the glandular tumor does not disappear and the opening into the abscess re- mains for a long time as a fistula. Plate III. TUBERCULOUS SPLEEN OF HOG. SPLEEN OF HEALTHY HOG. MORBID ANATOMY There may be swellings of the bones, causing a true tuberculous arthritis when the lesions happen to be situated at the level of an epiphysis. Persistent lameness, fistulous wounds suppurating in- definitely, necrosis and caries, are the complications of the lesions of the bone, the development of which is always extremely slow. §143. Morbid anatomy. The manifestations of tuberculosis in swine are exceedingly interest- ing. Nocard found the lesions to consist of miliary granulations which rapidly become caseous, as in cattle, but which more rarely contain calcareous salts. General- ization is common, in which case the viscera are thickly sprinkled with gray granulations which are translucent throughout, or opaque in their centers, and quite analogous to those found in tubercular lesions in other animals. As the disease most often re- sults from ingestion of the virus, the digestive apparatus and the cor- responding lymphatic glands (sub- maxillary, parotid, pharyngeal, su- perior cervical, mesenteric, sub- lumbar, etc.) may be decidedly altered, while the other organs re- main practically intact. Lesions of the small intestine and of the cecum are common and take the form of ulcers of the mucous membrane, of miliary nodules or of tuberculous Tuberculous spleen from a pig. 184 TUBERCULOSIS IN SWINE infiltrations, involving at once the mucous, the muscular, and subserous tissues. The lesions in the liver take the form either of miliary granulations, which are yellow and caseous and scattered in great numbers through the thickness of the organ, or else of rounded nodules which are yellowish white in color, varying in size from that of a pea to a hazel nut and of a tough consistency. On sec- tion they appear sometimes to be firm, homogeneous and fibrous ; sometimes softened in the center, and often infiltrated with calcareous salts. The peritoneum and the pleura are sometimes the seat of an eruption of fine granulations which remain in a s'ate of miliary nodules. Lesions like those in the liver may exist in the lungs, but generally there is found in these organs an innumerable quantity of minute, translucent, gray granulations, caused by the dissemination of tubercle bacteria through the blood stream, in which case the liver, the spleen, the kidneys, the medulla of the bones, and the mammae may be infiltrated with similar growths. It is common to find lesions localized in one or several lymphatic glands. The tonsils and the pharyngeal or sub- maxillary glands are the ones most often affected. They be- come voluminous, hard and knotty, as they have undergone a true fibrous transformation and, consequently, difficult to cut. This is shown by the tissues creaking under the cutting instru- ment. In section they have the appearance of old fibrous tissue ; here and there small yellow foci are seen of a softer consistency, almost caseous ; sometimes veritable purulent collections are found, either encysted or in communication with the exterior. If one submits the caseous or purulent matter to a bacteriological examination, tubercle bacilli are not usually found. The bacterium, however, is present and if this matter is inoculated into the peritoneal cavity or the cellular tissue of guinea pigs it will produce tuberculosis. These chronic glandular lesions, with their very slow pro- gress, have long been looked upon as constituting the scrofula of swine, and to scrofula was also assigned the tuberculous lesions of bones (ribs, vertebrae, articulations, shoulder blades, hip bones) which are common in pigs, both young and old. Plate IV. TUBERCULOUS LUNGS OF HOG. TUBERCULOSIS IN OTHER MAMMALS 1 85 The older authors noted that the ancient scrofula was often accompanied by visceral tuberculosis, but they refused to ad- mit the identity and even the relationship of the two affections. The generalization of the disease, especially in the mus- cular tissue, is reported by several observers. Moule calls at- tention to this peculiarity of the disease. Stockman shows that while the disease is ordinarily generalized, muscular lesions may exist in swine in the absence of generalization. Zschokke has called special attention to the localization of tubercular lesions in the head of swine, especially in the nares and brain. TUBERCULOSIS IN OTHER MAMMALS § 144. Genera affected. It is stated that all species are sometimes attacked. Tuberculosis in the horse is rare, although a total of many cases has been reported. Bang has collected twenty-nine cases. In Saxony .08 per cent of the horses (3,500) that were slaughtered were tuberculous. In this and most countries there are no reliable statistics re- specting the extent of the disease in this species. M'Fadyean has pointed out the fact that in a considerable number of cases of equine tuberculosis, where the horses have been fed milk from tuberculous cows, the morbid anatomy differs but slightly from that in tuberculous cattle. Sheep and other domestic animals are reported to suffer more or less extensively from this disease. All of the so- called tuberculosis in sheep that I have examined proved not to be tuberculosis but the "nodular disease" caused by an animal parasite. Tuberculosis in dogs and cats is quite rare but several cases in each genus have been reported. AVIAN TUBERCULOSIS. § 145. History. In America, tuberculosis in fowls was •described by Pernot in Oregon in 1900. In 1903 Moore and Ward found the disease in California, where in certain flocks it was very destructive. It was recognized by the owners as 1 86 AVIAN TUBERCULOSIS "spotted liver," going light, and rheumatism. In Europe it has been known for a long time. § 146. Symptoms. The symptoms described as quite constant are emaciation, which in advanced cases becomes- extreme, and anemia. The comb, the skin, and the visible mucosa about the head are usually pale. As the course of the disease advances the feath- I ers became ruffled and the fowls I are weak, dumpish and move about very little. The eyes are bright in most cases until the end is near. The appetite is good, and the fowls eat raven- ously until a few days before death. The temperature is in most cases within the normal limits, rarely it is subnormal. The blood is pale. The hemo- globin varies from thirty-five to seventy per cent as tested with Gowers' hetnoglobinometer. The red blood corpuscles vary from 1,010,000 to 2,600,000 per cubic millimeter. There ap- pears to be a slight increase in the number of white corpuscles, especially of the eosinophiles. Tubercular fowls are often lame. Pernot mentions this as Fig. 42. Avian tubercle bac- . , , ■ , . , ,. ,. , one of the important symptoms teria. (/) jrom liver tissue 0/ c j r a fowl, (2) a photograph from in the cases he observed. It is- u preparation from a glycerine due to joint lesions in some agar culture, x about 600. cases. In others it appears to- be due to extensive lesions in the viscera. § 147. The avian tubercle bacteria. These organisms resemble quite closely those of the human and bovine varieties AVIAN TUBERCLE BACTERIA I87 in their size and general morphology as they are found in the tissues of the fowl . A measurement of over two hundred in- dividual organisms in cover glass pre- parations made directly from organs of fowls gave the following : In the liver the length varied from 1.2 to 3.5 yu, in the spleen and in the skin they varied from 1 to 4 /.i in length. A general average gave a length of 2 . 7 fi. They often appear in these preparations in dense masses. Chains made up of a number of short elements are (rarely present. Granules are occasionally observed. In the pre- parations from the skin a considerable number of them contain polar granules and not infrequently three such bodies were noticed in a single individual. Perhaps the most striking feature con- cerning these organisms in the tissues is their enormous numbers. Sibley has called attention to the similarity of avian tubercle bacteria to those of leprosy in that they multiply to such enormous numbers without a pronounced breaking down of the tissues. This variety is more easily obtained in pure culture from the lesions than the human or bovine forms. Moore obtained pure cultures in about 20 per cent of serum tubes inoculated directly from tubercu- lous lesions in fowls. It grows readily on glycerine agar, Dorset's egg medium, , . , . , ... Fig 43. A glycerine agar potato and in glycerine bouillon. cMure of avian tuberde The colonies on glycerine agar vary bacteria. Culture /out from one to three millimeters in diame- weeks old. ter. The central portion is raised and of a slightly yellowish 1 88 AVIAN TUBERCULOSIS tint as observed under a hand lens. This central part is sur- rounded by a flat expansion, about two-thirds the thickness of the center, varying from one-half to one millimeter in width, with ray-like projections radiating from it and extending into the outer and very thin band of growth with a lobulated mar- gin. On the egg medium of Dorset the growth is not more vigorous than that upon glycerine agar. Potato cultures are quite vigorous, wrinkled and of a yellowish-brown color. Fowls inoculated in the abdominal cavity or subcutaneously with from one-half to one cubic centimeter of a glycerine bouillon culture develop either localized or generalized tuber- culosis in from six weeks to three months, but a much longer time is necessary to destroy them. Rabbits and guinea pigs are not readily infected by the inoculation of pure culture. Moore and Ward failed to produce any tuberculous lesions in these species. § 148. Morbid Anatomy. The lesions are widely dis- tributed, and vary much in their location in different indivi- duals. The liver is most frequently involved. The spleen, intestines, mesentery, kidneys, lungs and skin are affected in the order mentioned. The appended table gives the distribution of the lesions in 17 cases observed by the writer. MORBID ANATOMY 189 TABLE SHOWING THE DISTRIBUTION OF LESIONS IN TUBER- CULOUS FOWLS. u •a* S3 K D K K K K K D D K K K K 6.0.B BV= H Organs Involved.* ft. Liver Spleen Intes- tine Mesen- tery Kidney 1 Ovary i Lungs Bones Skin T ^X ? i XXX 3 4 5 106.5 I07 105.2 107.4 I07.2 XXX ; XX XXX XXX XX X 1 X ] XX i t 7 8 XXX X XXX XX XX X X X X 9 XX 108.4 I06.4 107.4 XXX X XXX' X X X 12 13 14 15 16 17 XXX XXX XXX XXX XXX XX XXX ! xxx ! . K D K 106.8 105. XX 1 _ J XX [ XXX XXX *The relative numbers of tubercles are indicated by the number of X's. XXX indicates an extensive invasion, XX a less number of tubercles, and X very few. Figures 44 and 45 show extent of lesions represented by XXX. The tubercles, especially in the liver, in the earlier stages of the disease, are small greyish points varying from 0.25 to 1.0 millimeter in diameter. In advanced cases they are larger. They have a cheesy consistency, and are easily removed from the surrounding tissue. The removed, necrotic nodules have a roughened surface. The color is greyish or whitish in the early stages, but in the later ones it changes to a yellowish tint. Occasionally there are two distinct crops of tubercles, one consisting of nodules 4 to 6 millimeters in diameter and 190 AVIAN TUBERCULOSIS separated by a centimeter or more, and the other of closely set grayish tubercles 0.25 to 0.5 mm in diameter. In some cases the tubercles are few in uumber but larger in size. The liver cells between the tubercles are usually in a state of more or less degeneration, and frequently fat globules are numerous. The blood spaces are more than normally dis- tended with blood. The lesions in the spleen, like those in the liver,- consist of minute or larger tubercles of a grayish or of a yellow- ish tint. The central portions of the larger tubercles are after homogeneous, darker in color and more or less hyaline in appear- ance and consistency. The tubercular growths in the intestine start in the walls of the intestine. They present a glistening appearance, grayish in color and firm to the touch. Frequently they are confluent. When single they vary from 1 to 10 mm in diameter. They are usually sessile on the intestine but on the mesentery they are frequently pedunculated, varying from 2 to 5 mm in length. On section the young tubercles exhibit a gray- ish, glistening surface, but the more advanced nodules contain recognizable necrotic centers. In the larger tubercles on the intestines the necrotic centers frequently open into the lumen. The skin lesions consist of a cellular infiltration usually about the root of the feathers. Frequently the nodules be- come confluent. They may or may not involve the subcuta- neous connective tissue. The microscopic examination of the tubercles of the liver Fig. 44. A photograph of a tuberculous liver from, a fowl. MORBID ANATOMY 191 shows them to consist of a necrotic center surrounded by an irregular zone of epithelioid and giant cells. This is sur- rounded by a band of tissue consisting for the greater part of Fig. 45. A photograph of u tuberculous mesentery of a fowl. There are a few small tubercles on the intestine. liver cells more or less disintegrated, free nuclei and a few infiltrated round cells. This zone is circumscribed by a narrow reactionary band consisting very largely of round cells. This 192 AVIAN TUBERCULOSIS structure is constant in both small and large tubercles, and not strikingly different from the structure of tubercles in certain of the mammals. The larger nodules seem in some instances to be the result of a continuous growth of a single tubercle, and in others to have resulted from the coalescence Fig. 46. A photograph of the head and part of the neck oj a tuberculous fowl. of a number of small ones. The necrotic center and reactionary zone of round cells are beautifully demonstrated by their reaction to nuclear stains. § 149. Differential diagnosis. Tuberculosis in cattle and swine is to be differentiated from actinomycosis, glanders, and various parasitisms resulting in nodules largely in the DIFFERENTIAL DIAGNOSIS 1 93 walls ot the intestine. In cattle the nodules are produced by an Oesophagostoma. In sheep the nodules are caused by O. Columbianum Curtice. In chickens a nodular taeniasis of the intestine is not infrequently mistaken for tuberculosis. Abscesses and necrotic foci due to various agencies must also be distinguished from tubercular lesions. Fig. 47. A photograph of a section of tubercle from a fowl, showing the necrotic center and surrounding zones. Enlarged, In cases of actinomycosis, the ray fungus can usually be detected on a microscopic examination. Bad. mallei can be found either in cultures or by guinea pig inoculations in cases of glanders, and in parasitic diseases the specific animal parasite can be found if diligently sought. A careful study of the recent lesions, especially in the nodules caused by the animal parasites, will show that they are not structurally like the tubercle as described above. From the symptoms and morbid anatomy it is clear that hard and fast lines for diagnosing tuberculosis cannot be laid down. As a rule the lesions are characteristic, although there 194 TUBERCULOSIS are many exceptions. In making a positive diagnosis one must rely upon the discovery microscopically of the specific bacterium, the result of animal inoculation or the effect of tuberculin. The tubercle bacteria can be found by making and properly staining cover-glass preparations from the tuberculous tissues or discharges in a certain number of cases. When these tuber- cular lesions open into the respiratory tract the specific bac- teria can almost always be found in the expectoration. This is especially true in men and Ravenel and others have shown that it is often true in cattle. In old and in the very recent tuberculous lesions, it is not so easy to detect these organisms microscopically. When there is doubt animal inoculation gives quite prompt results. Tuberculosis in fowls is to be differentiated from certain other affections, such as lymphadenoma and sarcoma of the liver, asthenia, nodular taeniasis and excessive infection with the air sac mite {Cytodites nudus). Because of a close simi- larity in the general symptoms, and, in certain cases, of the gross lesions, between tuberculosis and certain other affections, the findings of a somewhat careful examination are necessary to warrant a positive diagnosis. In the living fowl it seems as yet to be impossible to fix upon any diagnostic symptoms. At post-mortem, however, properly stained cover-glass prepa- rations from the tubercles will reveal the presence of tubercle bacteria. This renders the positive diagnosis in the dead fowl a comparatively easy task. The positive diagnosis of tuberculosis rests in : i. Finding the tubercle bacterium on a microscopic examination of the lesions. 2. The production of tuberculosis in experimental ani- mals by inoculating them with the suspected tuberculous material. 3. Obtaining a typical reaction after the injection of tuberculin. § 150. Microscopic examinations. The diagnosis by microscopic examinations is possible when one has the dis- charge from a lesion, such as the sputum when the lungs are DIFFERENTIAL DIAGNOSIS 1 95 involved. In case of tubercular abscesses, the examinations should be made from the scrapings of the walls of the abscess rather than from the purulent contents. It is often possible to find tubercle bacteria in sections of the diseased organs. A method for staining tubercle bacteria. Stain the cover-glass with fresh carbol fuchsin. Place a few drops of the stain on the film side of the cover-glass preparation and hold it over a flame with forceps until steam is given off. Allow the hot stain to act for from 3 to 5 minutes, or the preparation may be floated on the carbol fuchsin in a watch glass without heat. In this case it is allowed to act for from 10 to 15 minutes. The preparation is then rinsed in water and decolorized by treating it with a \of solution of nitric or sulphuric acid for from \ to 1 minute. It is again rinsed in water, when it is ready for examination. It can be dried and mounted permanently in balsam. The tubercle bacteria should be stained a deep reddish color. All other bacteria or animal tissue in the preparation should be nearly or quite decolorized. If desired, a counter-stain, such as alkaline methylene blue, may be used after decolorizing ; that is, the preparation should be again stained for about 1 minute in alkaline methylene blue, rinsed in water, and examined as before. In these preparations the tubercle bacteria are red and the other organisms and cells are blue. A counter-stain is of little value in preparations made for simple diagnostic purposes. When a counterstain is desired Gabbett's decolorizing and counter-staining solution is very convenient. GABBETT'S SOLUTION Methylene blue (powder) .... 2 grams 10% sulphuric acid 100 cc. After staining with the carbol fuchsin treat the preparations with this mixture until the film has a faintly bluish tint. This solution decolorizes and counter-stains at the same time. § 151. Animal inoculation for purposes of diagnosis. Guinea pigs are preferable, although rabbits may be used. With tuberculous tissue either of the two methods described below may be employed. 1. A small piece (about the size of a pea or bean) of the tissue may be inserted under the skin by first making an incision with a sharp scalpel through the skin and superficial fascia, and then with a pair of fine forceps insert the bit of tissue well under the skin and close the opening with one or more sutures. ' 2. The tissue may be crushed in a mortar and thoroughly / 196 TUBERCULOSIS mixed with a few cubic centimeters of sterile water or bouillon and then injected with a hypodermic syringe. The needle should be of large calibre. If it is suspected milk, it may be injected into the abdominal cavity. If the material is tuber- culous and contains living tubercle bacteria, the death of the animal follows in from three weeks to four months. Usually the lymphatic glands in the groin and axilla are enlarged and often caseous. If a guinea pig is used, the liver, spleen, lungs and kidneys are liable to be affected, in the order named ; if a rabbit, the lungs are often the first of the viscera to be attacked. 3. In avian tuberculosis it is necessary to use chickens instead of guinea pigs. They may be inoculated subcutane- ously or into the abdominal cavity. Several weeks may be necessary for the disease to develop sufficiently to distinguish the lesions or to enable one to find the bacteria microscopically. §152. Tuberculin test. The tuberculin test is the best, and in a large majority of tuberculous cases among animals and in man, the only means of positively detecting the disease in the living individual. Tuberculin. Tuberculin is the concentrated liquid, usually glycerinated bouillon, on which tubercle bacteria have grown until the products resulting from their multiplication have become imparted to the medium in sufficient quantity to inhibit their further development. It is not definitely determined just what these products are or just how they are elaborated. Briefly stated, the preparation of tuberculin consists in the following procedures : 1. The preparation of the culture medium (glycerinated bouillon), distributing it in suitable flasks and inoculating it with the growth from a pure culture of tubercle bacteria. 2. The flasks are placed in an incubator at a temperature of about 37" C. where they remain until the growth ceases. The length of time necessary to accomplish this depends upon the age and condition of the culture from which the inoculations were made. From four to ten weeks are usually required. 3. After the maximum growth is attained, the cultures are sterilized by heat, either by boiling in a closed water bath or heating to a higher temperature in an autoclave. TUBERCULIN TEST 1 97 4. After sterilization, the cultures are filtered to remove all of the dead bacteria, and then the filtrate is evaporated over a water bath to the desired degree. 5. The concentrated liquid is passed through a Pasteur or Berkefelter filter, standardized, bottled and labeled for distribution. It should be perfectly clear although its color may vary. If it is cloudy it should be rejected. It will be seen from the method of preparation that tuber- culin cannot possibly contain living tubercle bacteria. It is heated on two occasions to a temperature and for a length of time far in excess of that required to destroy them, besides being passed through a filter capable of removing all bacteria. The original tuberculin or lymph of Koch was concen- trated to one-tenth of the volume of the saturated culture. This gave a thick, syrupy liquid owing to the presence of the glycerine. The diagnostic dose which came to be recom- mended for cattle of medium weight was 0.25 c.c. On account of its consistency as well as the minuteness of the dose, it was found to be practicable to dilute this quantity with seven parts of a diluent. A weak solution of carbolic acid was ordinarily used. The difficulties and the danger of contamination involved in making the dilutions in the field led to the method of diluting the tuberculin in the laboratory before sending it out. This has been the practice of the Bureau of Animal Industry for a number of years. Equally as good results are obtained by concentrating the saturated culture to the point where 2 c. c. contains an equivalent of the 0.25 c.c. of the highly concen- trated lymph. This process avoids the necessity of dilutions and, with the addition of a few drops of carbolic acid, the weaker solution keeps perfectly. Tuberculin in the dose necessary to bring out its diagnostic effect is harmless for healthy animals. Thousands of observa- tions that have been reported assure us of this fact. Tuber- culin is in daily use in every state in the Union, in Canada and in every country of Europe, yet so far as can be learned not a single case of injury following its use has been reported. In the tuberculous animal it produces a rise of temperature which, within certain limits, follows a definite course usually termin- 198 TUBERCULOSIS ating in from 18 to 24 hours after the injection. Occasionally the temperature remains above the normal for a longer time. The temperature usually begins to rise in about eight hours giving a steady but quite rapid elevation for from 1 to 3 hours, A continuous high elevation for from 2 to 4 hours, possibly longer, and a gradual decline. This is practically constant, be the raise moderate or extreme. In addition to the elevation in temperature there is sometimes a marked nervous chill. Why we get this reaction* is not positively determined. Applying the tuberculin test. In brief, the method for applying the tuberculin test in cattle is as follows : 1. The normal temperature of the animal to be tested must be determined. It is recommended that it be taken hourly or every two hours for the day preceding the test. In *Trudeau {Johns Hopkins Hospital Bulletin, July, 1899) gives the fol- lowing summary of the mechanism of the tuberculin reaction. "The most generally accepted theory at present in regard to it is, briefly, the small dose of tuberculin injected is a partly specific irritant both to tuberculous foci and to the susceptible organism in general. It produces intense hyperemia of all tuberculous tissue in the (body local reaction), and as the result of this hyperemia much toxin stored up in the tubercles themselves is thrown into the general circulation and produces fever and character- istic symptoms which go to make up what is termed 'a general reaction.' That these poisons stirred up in the tubercles are in part at least derived from the dead or weakened bacilli has been shown by the experiments of Babes and Proca, who found that if two sets of rabbits be injected with equal quantities of living and dead bacilli, the latter react to the tuberculin test at a much earlier period than those inoculated with living germs. This hypothesis that the general reaction is brought about by toxins already stored up in the tuberculous lesions and exploded as it were by the hyperemia produced about these lesions as the result of the test of injection of tuberculin, is borne out by the fact that a greater amount of albumose can be recovered from the evaporated urine col- lected during the reaction than was contained in the test injection also by clinical observations which indicate that patients suffering from localized surgical tuberculous processes of limited extent, and where the vascular supply to the part is limited, require a larger test injection to produce the reaction than those who have extensive or scattered visceral lesions in highly vascular organs like the lungs. " The reader is referred to this paper for a careful consideration of the vexed questions relating to tuberculosis. TUBERCULIN TEST t 99 practice veterinarians usually take the temperature but once or twice before injecting the tuberculin. 2. The tuberculin is injected subcutaneously in the side of the neck. Care must be taken that the syringe is sterile and the site of injection should be disinfected. The size of the dose depends upon the preparation of tuberculin, that is the degree of concentration. 3. Beginning 6 or 8 hours after the injection, the tem- perature should be taken hourly, or at least every two hours, for fully three-fourths of a day. 4. During the time of testing, the cattle should be kept quiet and free from all exposure, and fed normally. 5. In case of reaction, there should be a rise of at least 1.5° F. above the maximum individual normal temperature as determined on the preceding day. The elevation should come on gradually, remaining practically at its fastigium for a few hours and gradually subside. Erratic elevations of short dura- tion are to be excluded. In cases of doubt the animals should be retested. 6. Animals advanced in pregnancy and those known to be suffering from any disease or in oestrum should be excluded. All methods of treatment, including exposure to cold, or kind of food and drink which would tend to modify the temperature should be avoided. Animals in which the disease is far advanced sometimes fail to react. 7. The dose should vary to correspond with the weight of the animal. The dose for an adult cow of average weight is 0.25 c.c. of the concentrated Koch tuberculin. In cases of a second test within a few days, the quantity of tuberculin injected should be larger than for the first test. Ward has pointed out the fact that fowls do not give a diagnostic reaction to tuberculin made from either the avian or mammalian varieties of the tubercle bacteria. In cattle there is a marked variation in the normal daily temperature. A fluctuation of two or even three degrees within 24 hours is frequently found. Cold water when drunk in considerable quantities lowers the temperature from two ta four degrees. A temporary excitement usually causes an eleva- 200 TUBERCULOSIS tion of from i to 1.5° F. There are also marked variations in the temperature of the same animal on consecutive days. The temperature at 12 noon and 12 midnight are often the same. In some cases the maximum elevation for the day occurs near midnight and on the following day the minimum temperature appears at that time. It is not uncommon for the maximum temperature to occur twice in the same day and occasionally several times within the twenty-four hours. There are marked individual variations in the effect of ordinary conditions upon the temperature, such as food, excitement or temperature of the air. A hot spell causes a rise of two and in some cases four degrees. The average temperature of the animals in three herds tested by Howe and Ryder were 102. 5 , 102.6°, and ioi° F. respectively. In a well kept Government herd that was tested with tuberculin, the temperature of part of the animals was taken hourly for 24 and part of them for 16 hours preceding the injection. An examination of the records* shows the average daily variation of 20 animals in which the temperature was taken for 24 hours to be 2.31° F. The maximum individual variation in a single day was 4.3 F. , the minimum 0.5 F. In 25 other animals where the temperature was taken for 16 hours, the average variation was 1.79 F. In these the maximum variation was 3.2" F., the minimum o. 6° F. Ten healthy animals (did not react to tuberculin) in the same herd gave an average variation of 2.08 F. In these the maximum daily variation was 4.1 F. , the minimum i° F. The lowest temperature was usually, but not invariably, in the morning and the highest in the afternoon or evening. I have appended the records of the temperature of two of these animals. ♦Bulletin No. 7, Bureau of Animal Industry, U. S. Department of Agriculture, Washington, D. C. The tests were made by Drs. F. L,. Kilborne and E. C. Schroeder, under the direction of Dr. Theobald Smith. NORMAL TEMPERATURE 20I THE INITIAL TEMPERATURE OF TWO COWS, WITH RATE OF PULSE AND NUMBER OF RESPIRATIONS PER MINUTE. Cow, No. I Cow, No. 2 Hour Tempera- ture Pulse Resp. 18 Tempera- ture 98.6 Pulse. Resp. 9 A. M. 99.8 48 48 15 10 " 99-5 66 18 98.6 60 15 II " 99.0 60 15 99.0 60 15 12 100.8 54 15 99-4 54 15 I P. M. 101.4 54 15 1 00.0 54 18 2 101.6 48 15 100.2 54 18 3 " 102.0 60 24 100.4 72 24 4 " 103.0 66 24 102.7 72 24 5 " 103.3 66 24 102.8 72 27 6 " 103. 1 57 18 103.0 60 27 7 " 102.2 60 20 102.4 60 24 8 " 103.0 56 16 102.0 60 24 9 " 103. 1 52 24 102.2 50 24 10 " 102.5 60 20 102.0 50 18 ii " 102.5 60 20 102.0 60 20 12 midnight 102.4 56 16 101.6 54 20 I A. M. 101.8 60 20 101.4 58 24 2 " 102.0 64 18 102.2 58 18 3 " 102.0 60 18 101.6 38 18 4 " 102.2 54 24 101.5 60 24 5 " 101.6 56 24 102.0 60 18 6 " 101.8 60 18 102.2 60 20 8 " 102.5 56 16 103.2 60 18 In view of these normal temperature variations, which often exceed the tuberculin reaction, it is obvious that before applying the test the normal temperature of the animals should be approximately determined and that when they are being subjected to the test they should be cautiously protected, otherwise the comparatively slight elevation necessary to detect the disease may be disguised. As the reaction seems to be the result of an affinity exist- ing between the tuberculin and the living tuberculous lesion, it is natural to suppose that when the two are brought together in the same animal it would invariably take place. Experience has shown that it almost always does. It is important to understand, as far as possible, the reason for the exceptions 202 TUBERCULOSIS and the extent to which they occur. The reported failures of the tuberculin tests fall into two distinct classes. i. There is a reaction and no disease is found. In explaining this alleged error, the records of the cases which have come to my attention have been so deficient in data con- cerning the normal temperature variation of the animals, and the incompleteness of the post-mortem examinations, that it seems possible for the error to rest with the observer quite as much as with the tuberculin. Unfortunately we are as yet unable to determine by the reaction the extent of the disease, so that a beginning lesion no larger than a walnut may cause a pronounced rise of temperature and such a tubercle may be difficult to find, especially if located in the marrow of some bone or in the nervous system. *t-.oo s:io &ZO j:jo JT.-4-O S.SO <5,/0 7.00 &*oo 9.JO /r /OS ioz (DftAfi /r r*> ZELY Or Wa TCn A T 39' '/= :&/ too 99 Fig. 48. Chart showing the effect of drinking cold water upon the temperature of a cow. 2. There is no reaction and the disease exists. It is- generally admitted that advanced cases often fail to react, but here the test itself is of little importance, as the disease can be detected by the clinician on physical examination. When, however, tuberculin is carefully prepared and scientifically administered, these exceptions are exceedingly rare. The practical value of tuberculin lies in its efficiency in the arts of comparative and sanitary medicine. It is in the practical application that difficulties are encountered. The PREVENTION 203. many details and precautions enumerated as absolutely essential to the best results are often considered too tedious and time consuming, and consequently the practice has come toa generally into vogue of neglecting or ignoring many of the precautions. In order that the test may be practicable, some practitioners resort to a shorter method of procedure even at the risk of an occasional error. § 153. Preventibn. Tuberculosis, like other infectious diseases, can be very largely prevented. To accomplish this it is necessary to keep tuberculous animals from entering the healthy herds. If they are admitted and later the fact is dis- covered, it is necessary to remove them and to thoroughly dis- flovfrs Arreff Injection Fig. 49. Irregular temperatures following tuberculin that are not caused by tuberculosis (Curtice). infect the stable. In eliminating the disease from a herd by means of the tuberculin test, it is necessary to retest the non- reacting animals after six months or a year has passed in order to find any case that might have been infected, but in which the disease had not begun to develop, at the time of the first test. § 154. The control of tuberculosis in cattle. Several methods have been proposed to eliminate tuberculosis from cattle. The one introduced by Prof. Bang of Cophenhagen, Denmark, and generally known as the Bang method has proven to be most successful. It consists in the slaughter of 204 TUBERCULOSIS the advanced cases and the isolation of the reacting animals which are kept for breeding purposes. The calves are sepa- rated from their dams immediately after birth and fed upon the milk of healthy cows or the sterilized milk of the reacting ones. This method has enabled many owners of infected animals to replenish their herds in from four to six years. In countries where it has been generally applied the percentage of tuberculous cattle has been wonderfully reduced. The vaccination of cattle against tuberculosis has been proposed as a prophylactic measure. The method has been extensively tried by Pearson in America and von Behring n Germany. Its effectiveness can not be predicted at this time. A.M. 900 /'-oo P.M. /.oo ■3.00 roc f*00 // oo AM. / oo &,oo jroo VOO toe /os / — - \ / 5 /O-f- / \fr / \ ,5 \ \ \ .s /or. „\ sand cases of sickness among horses. At \ t ^» Wiirtemberg, Hering reports it once in 3000 ^ \ ' •--p cases of disease among the horses in the cavalry. It has also been noted that in some Fig. 56.' Bacillus veterinary hospitals it does not occur for long tetani. periods, while at other times several cases may appear in rapid succession. It is, however, a wide spread disease. § 181. Etiology. Tetanus is caused by a slender bacil- lus 2 to 5 ^ in length. It forms spores which are at the end of the organism giving it somewhat the appearance of a pin. ETIOLOGY 239 On account of this it has been designated the "pin bacillus." It is anaerobic. This organism was first observed by Nicolaier in 1885, although Carle and Rattone showed in 1884, that this disease could be transmitted from man to animals by inocula- tion with the pus from the local lesion. In 1889, Kitasato iso- lated the bacillus and studied it in pure culture. This bacillus stains readily with the aniline dyes, especially with carbol- fuchsin. It takes the Gram stain. It grows well in nutrient gelatin, agar or bouillon and on blood serum at the temperature of the body and in an atmosphere of hydrogen or in the absence of air as in deep agar cultures. The addition of a little grape sugar facilitates its growth. It has the distinction of producing the most powerful (poisonous ) toxin of auy known bacteria, 0.23 of a milligram being estimated as a fatal dose for a man of 175 pounds weight. The fact that this bacillus is an anaerobe renders its culti- vation of little practical value in diagnosing the disease. Al- though it is not distributed in the body, it can usually be found in cover-glass preparations, made from the local lesion and stained with carbol fuchsin. Bacillus tetani is found in the soil. It has been found in hay dust, in the mortar of old masonry, in the dust in rooms, barracks and hospitals and in the arrow poison of certain savages in the New Hebrides. They obtain it by smearing their arrow heads with mud from crab holes in the swamps. It is reported that certain savages in Africa destroy their enemies by putting bits of broken glass mixed with certain soils in their shoes. The cause of death is tetanus. Mold rich in horse manure seems to be the most favorable abode for it. It has been stated that it exists in all soils. There are good reasons for believing that this is an over estimate of the wide- ness of its distribution. It certainly is more numerous in some localities than in others. The tetanus bacillus is very resistant, especially in its spore form, to destructive agents such as drying and the or- dinary disinfectants. Kitasato found that a 5 per cent solution of carbolic acid applied for ten hours failed to kill the spores. Tizzoni and Cattani found that mineral and organic acids pro- 240 TETANUS duced no effect upon the dried spores. Behring found that iodine trichloride possesses a strong antiseptic effect upon them. They are not affected by the gastric fluids. It has been noted by Kitt that the dried spores in pus have retained their viru- lence for sixteen months. They are destroyed when subjected to a temperatare of 100° C. in water or steam for ten minutes. The bacilli in the vegetative state are readily destroyed by the usual strong disinfectants, such as 5 per cent carbolic acid. A number of bacilli closely resembling B. tetani have been described. This renders a careful study of the suspected organism necessary, as it is difficult in some cases to determine B. tetani microscopically. The guinea pig inoculation affords a ready means of differentiation whenever fresh material is available. The period of incubation. — The shortest period which seems to be reported is a few hours and the longest is six weeks. In horses the period of incubation is usually from four to twenty days. After inoculation with pure cultures it is from four to five days and in sheep from two to four days. In guinea pigs inoculated with infected soil the incubation period is usually not over forty-eight hours and often less than that. § 182. Mode of infection. As the bacillus of tetanus is widely distributed in the soil and consequently on articles contaminated with it, the most common modes of infection are punctures, scratches, and pricks made by splinters, nails or infected instruments (traumatic tetanus). It may follow slight abrasions of the skin where infected earth comes in con- tact with the lacerated epidermis. Infection through wounds in the intestinal mucosa do not seem to have been clearly dem- onstrated. The most usual method seems to be by pricks and nail punctures, in which case the virus can be carried well into the living tissues and there is little or no bleeding to wash it out. Infection often occurs in young foals and lambs through the freshly broken umbilical cord (tetanus neon- atorum). Park has found that mice, guinea pigs, rabbits, rats, horses, goats and a few other animals inoculated with pure culture have a period of incubation of from one to three days. SYMPTOMS 241 In man it varies from one to twenty days. There are, how- ever, a few exceptionally long periods reported. It has been noted by Richter and others that the shorter the period of in- cubation the more severe the disease, the mortality being over 90 per cent in the first and about .50 per cent when the sym- toms were slow in appearing. § 183. Symptoms. The first symptoms are often ob- scure and may be overlooked for several days or they may be ushered in suddenly with violent and extensive tonic spasms. The tetanic spasms usually begin in the muscles of the head and neck, extending from these to the muscles of the throat, trunk and extremities. It often happens that the spasms first appear in the hind quarters and extend forward. There is stiffness of the parts affected. If in the head, the muscles of mastication are first attacked with spasms, while if the hind quarters are first attacked, there are usually spasms of the muscles of the tail. The muscles at the site of inoculation are frequently the first to show spasms and, if the disease is of a mild type, they may be the only ones to exhibit symptoms. Friedberger and Frbhner have grouped the muscles which are attacked with the more obvious effects upon the appearance of the animal. They are as follows : 1. The muscles of mastication. The contraction of these muscles is called trismus or "lockjaw." According to the degree of contraction, the jaws remain in more or less close contact, rendering prehension or mastication difficult or im- possible. 2. The other muscles of the head. These are spasmodi- cally contracted in different degrees. Spasms of the muscles of the ears cause the ears to be ' 'pricked' ' and their tips to be drawn together ; of the recti muscles of the eyes, cause the eyes to be retracted in the orbit with protrusion of the nictitat- ing membrane ; of the nose, produce dilatation of the nostrils ; of the dilator of the upper lip, give an abnormal shape to the opening of the mouth. The muscles of the tongue, of degluti- tion and of the larynx are also usually attacked by spasms. 3. The extensor muscles of the neck. Contraction of these muscles causes a stiff, outstretched carriage of the head and 242 TETANUS ' 'ewe neck. ' ' The muscles of the neck become hard and tense to the touch. 4. The extensor muscles of the back. Spasms of these muscles are manifested by an extremely hard condition of the muscles of the back, loins and croup. Several conditions may arise : orthotonous in which the neck is stretched out and the back and croup are carried horizontally or, opisthotonous in which the head is raised or drawn back and the vertebral column slightly depressed. This is the most common occur- rence. There may be a lateral curvature of the cervical vertebrae which is uncommon and also a convex curvature of the vertebrae which is very rarely observed. The tail, espe- cially in horses, is often raised and occasionally said to be straight with the back. 5. The muscles of the limbs. The spasms in these muscles make the limbs stiff and cause the animal to assume an attitude in which the fore legs are extended forward and laterally and the hind ones backward and laterally. They are bent at the joints only with difficulty. The contraction of the muscles of the abdomen gives the animal a tucked up appear- ance and the spasms of the muscles of respiration render breathing difficult. Besides the spasms the animal shows an increased reflex irritability and heightened sensibility. These manifest them- selves in excitement, timidity and intensified muscular con- tractions if irritated. Sweating is common, especially in severe cases. In mild cases it may be absent. There is usually little or no change in the internal temperature. In fatal cases the temperature is usually constantly high toward the last. The high temperature (104° to 106 F.) usually continues for some time after death. Bayer has observed in a horse, 24 hours before death, a temperature of 102 F. ; one and a half hours before death, 105 F.; at the moment of death, in" F. ; and fifty minutes after death, 113 F. There is frequently no increase in the number of pulse beats until severe exacerba- tions set in. The frequency of the pulse is much greater in animals which continue recumbent than in those which keep upon their feet. The pulse is often hard and small and the MORBID ANATOMY 243 walls of the arteries are spasmodically tense. In many cases, however, it is full, soft and easily compressible. There is, as a rule, an increase in the number of respirations, which may become very high if the respiratory muscles are attacked. The number varies according to the excited condition of the animal. The respirations may increase four fold without a corresponding increase in the pulse beat. The breathing may reach from 80 to 100 per minute. In character the respirations are shallow on account of the fixed condition of the ribs and the spasms of the muscles which compress the abdomen. There may be cyanosis and catarrh of the nasal mucosa, ■coughing and in fatal cases symptoms of hyperemia and -edema of the lungs and often pneumonia (usually aspiration in nature) . There is constipation due to lack of peristalsis and the rigid condition of the muscles which compress the abdomen. Micturition becomes less frequent and more difficult. Complete retention of urine is said to occur in some cases. The urine has a high specific gravity and occasionally con- tains albumen. Some animals can eat readily while others eat, if at all, with great difficulty. They like to play with drink set before them and often try to satisfy their thirst, which seems to increase as the disease advances. In fatal cases the animals seem to be perfectly conscious to the last. They seem to be possessed of a feeling of terror. §184. Morbid anatomy. The gross examination of the tissues at post-mortem of animals dead from tetanus is usually negative. It has been pointed out by Goldscheider and Flatau that in experimental animals there are certain characteristic changes in the motor cells of the anterior horns of the spinal cord which in the order of their development depend upon the concentration of the toxin or virulence of the bacteria injected and upon the duration of the disease. The changes are pri- marily an enlargement of the nuclei, which at the same time become more indistinct ; then follows an enlargement and dis- integration of Nissl's cell-granules with an enlargement of all of the nerve cells. These investigators also found that where antitoxin had been used it had a distinct retarding influence upon these changes. They found like lesions in the 244 TETANUS spinal cord of a human subject dead of tetanus. Very similar results have been obtained by Matthes, Westphal, Goebel and others. The lesions point to the anterior horns of the spinal cord as the primary seat of origin of the tetanic contractions. The changes pointed out above are said by Moschowitz to be characteristic of tetanus and constantly found. The motor ganglia cells of the anterior horns of the spinal cord seem at present, therefore, to be the most likely source of the spasms, due apparently to a specific affinity between those cells and the tetanus toxin. It is possible to explain also the local spasms on this hypothesis as the toxin elaborated by the nerves terminating in the affected region. The experiments of Tizzoni and Cattani suggest the possibility of such a theory. There is, however, need for further investigation on this subject. A considerable number of lesions may be found elsewhere in the body, none of which can be considered as characteristic of the disease, but which are secondary to the tonic contractions. The blood owing to lack of oxidation maybe dark colored, tarry, of a greasy appearance and tardy in coagulating. There may be numerous ecchymoses and sanious exudates in the sub- serous and mucous membranes. The lungs may be variously affected according to the extent of the trouble with the respiratory muscles. Thus, congestion, edema, hemorrhages, pneumonia, emphysema and hypostatic congestions have been described. In the heart there are usually epi- and endocardial hemorrhages. The muscles may contain hemorrhages. The fibers of the muscles may show cloudy swelling, a loss of the transverse striae and changes in the nuclei. The liver may be swollen and abnormally yellow in color. The hepatic cells often show fatty degeneration. The spleen is often swollen, it may be engorged with blood or soft and flabby. The kidneys may or may not show degenerative changes. The bladder is usually distended with urine and its mucous membrane is often sprinkled with ecchymoses. The digestive tract may show areas of congestion and ecchymoses. The dtiration of the disease varies in different species and in different individuals of the same species. In the horse it may last for two or three days only or it may continue for several DIFFERENTIAL DIAGNOSIS 245 weeks. In cattle the course is usually less rapid, but it rarely runs longer than two weeks. In sheep it usually terminates fatally within a week and often in two or three days. §185. Differential diagnosis. Tetanus, while possess- ing quite characteristic symptoms, may be mistaken for a number of other affections or specific diseases. Among those which should receive special attention are cerebro-spinal men- ingitis and rabies (for the symptoms and lesions see those dis- eases), rheumatism, eclampsia, catalepsy, convulsions in the newly born and pyemic polyarthritis in lambs and foals. The symptoms of tetanus which are perhaps the most diagnostic are (1) the continuous tonic spasms of different groups of muscles, (2) the apparent clearness of mind (if we may attribute such a quality to animals), and (3) the absence of fever in the beginning of the symptoms. The general atti- tude of the animal is also of much value. If the infected wound can be found, it is often possible to obtain cover-glass preparations in which the tetanus bacilli can be found. Nega- tive results are in this case not to be considered as final, for it is practically impossible to make these examinations suffi- ciently thorough to be sure of the absence of these bacilli, if they are not found. If they are found the diagnosis may be considered as positive. In poisoning with strychnine, there are symptoms which at first may be more confusing. This form of poisoning usually occurs in dogs where tetanus is rare, and again in strychnine poisoning the suddenness of the attack, the rapidity of the course and the increased reflex irritability are valuable diagnostic features. In differentiating tetanus from other affections, as those in the newly born, the bacteriological exam- ination of preparations made from the end of the umbilicus may be of much assistance. § 186. Prevention. Owing to the wide distribution of tetanus bacilli, precautions can consist only of the careful and thorough disinfection of all wounds. With animals at pas- ture, it is impossible often to know of the wounds until it is too late to apply this measure. In stables where the disease becomes prevalent, the floors and siding should be thoroughly 246 TETANUS disinfected and special watchfulness exercised to find at the earliest moment any injury by which infection could occur. The practitioner should learn as soon as possible the tetanus infected lands and stables in his community and, knowing these, give wise instruction to his clients to take such precau- tions as are possible. In case operations are to be performed on animals in such stables an immunizing dose of tetanus antitoxin may be administered. This practice is followed in many places in Europe. If the present knowledge of this disease is properly availed of, there should be only occasional cases which as yet there seems to be no way to avoid. § 187. Tetanus antitoxin. It was first pointed out by Behring and Kitasato that animals could be made immune to tetanus by using cultivations of the tetanus bacilli which had been attenuated with iodine trichloride. The blood serum of such immunized animals has the power to immunize healthy animals against the disease and to render the toxin in animals affected with tetanus inert. The antitoxin is prepared now, however, by injecting horses with the filtrate of bouillon cultures, either alone or with a quantity of antitoxin. After the first dose the animal becomes tolerant to a certain degree so that by repeated and constantly increasing doses complete resistance to the toxin is acquired. When this point is reached the serum usually possesses a strong antitoxic power. As a practical remedy for the disease in animals the recorded results from the use of this antitoxin are somewhat contradic- tory. In human practice the results are similar. Moschcowitz has collected 290 cases in man where it has been used sub- cutaneously, with 173 recoveries and 117 deaths or a mortality of 40.33 per cent. In a total of 48 cases where the antitoxin was injected intracerebrally 23 recovered and 25 died, a mortality of 52.08 per cent. Some interesting experiments suggested by Krokiewitz directed toward the finding of a specific treatment consist in the injection of an emulsion of brain" substance. Primarily this method of treatment is based upon the hypothesis, set up by Goldscheider and Flatau, who, as a result of their research came to the conclusion that "The morphological changes in REFERENCES 247 the nerve cells are the expression of a chemical process, i.e., of the chemical combination of the toxins with the nerve cells. Every nerve cell possesses atom groups which have a certain affinity for the atom groups of the tetanus toxin and are able to combine with them." Wassermann and Takaki substantiated this hypothesis experimentally. These observers injected into experimentally tetanized animals an emulsion of spinal cord, obtained from a freshly killed animal, to test, if possible, whether the nerve cells of the dead animal also have this affinity for the tetanus toxin, like the nerve cells of the living animal. By this experiment, they have come to the conclusion that every part of the nervous system, particularly the brain of the examined animals including man, has a definite and positive tetanus antitoxic power ; and that the injection of normal brain substance into experimentally tetanized animals has the power to save life. Further work in this direction is necessary to fully demonstrate the efficiency of this procedure. REFERENCES. 1. Behring and KitasaTO. Ueber das Zustandekommen der Diphtherie — Immunitat und der Tetanus — Immunitat bei Thieren. Deutsche Med. Wochenschrift, Bd. XVI (1890), S. 113. 2. KitasaTO. Uber der Tetanusbacillus. Zeit. f Hygiene, Bd. VII (1889), S. 225. 3. KitasaTO. Experimentelle Untersuchungen iiber das Tetanus- gift. Zeit.f. Hygiene, Bd. X (1891), S. 267. 4. MoschcowiTz. Tetanus, a study of the nature, excitant, lesions symptomatology, and treatment of the disease, with a critical summary of the results of serum therapy. Studies from the Department of Path- ology of the College of Physicians and Surgeons, Columbia University, Vol. VII (1899-1900). (M. gives pathology and antitoxin treatment, summary of cases and full bibliography.) 5. McFari,and. Tetanus and vaccination. The fournal of Medi- cal Research, Vol. VII (1902), p. 474. 248 INFECTIOUS DISEASES BLACK LEG. Synonyms. Black quarter, symptomatic anthrax, quarter ill, quarter evil, gangrenous emphysema, charbon symptomatique (Fr.), Rauschbrand (Gr. ) § 188. Characterization. Black quarter is an acute infectious disease of cattle characterized by the development of an emphysematous swelling of the subcutaneous tissues and muscles. The lesions are usually located upon and ordinarily extend over the greater part of a hind quarter or of a shoulder. The disease does not spread from animal to animal by simple contact but the infection takes place apparently from a com- mon source, the soil. The virus seems to exist in the soil in certain localities only. Like tetanus, it is a disease following a wound infection. Symptomatic anthrax is a disease of cattle, sheep and goats, although the two latter species are rarely attacked. Guinea pigs are very susceptible to inoculation. It is reported that horses, asses and white rats develop local lesions when inocu- lated subcutaneously with the virus. Other animals seem to be immune. In cattle, it rarely occurs in the very young, under six months, and in adults after the fourth year. § 189. History. It is supposed that black quarter has existed for hundreds of years, although it was not until late in the last century that it was positively differentiated and recog- nized as a distinct and specific disease. The descriptions given in many of the earlier epizootics designated as anthrax correspond more exactly with the present knowledge of black quarter than they do of anthrax. In 1782, Chabert classified the various anthracoid dis- eases, recognized at that time into three groups, (1) anthrax fever or where the disease manifested itself without external swelling, (2) true anthrax, where the lesions consisted at first of small, hard and very painful swellings followed or accompanied by fever and other general symptoms, and (3) symptomatic anthrax, where the swelling was preceded by a rise of temperature, loss of appetite and symptoms of general depression. This classification obtained for nearly a century. Boutrolle, in 1797, refers to a disease which he called mal de HISTORY 249 cuisse (quarter evil) because it affected the animal in the thigh. Viborg described the disease in Denmark, where it has long been known to the laymen and designated by them as raslesyge ("rattle disease"). Its clinical features were very accurately described by Walraff in 1856. In 1879, Arloing, Cornevin and Thomas proved the causal relations of a certain microorganism to this disease and thus established its specific nature. A year later (1880) they described the specific microorganism and demonstrated that the disease could be produced by inocu- lating susceptible animals with it. Since that time both the organism and the disease itself have been studied by many investigators. In this country, it has been under investiga- tion during the last few years by the Bureau of Animal Industry. § 190. Geographical distribution. Black quarter ex- ists to some extent in nearly every country in the world. It is reported as occurring in the most northern latitudes in which cattle are kept, as well as in the temperate and tropical zones. In Europe, it occurs on the pastures on the Alps, where for five months in the year the ground is covered with snow and ice and in America it is quite common in certain northern districts. It has been reported from Asia and from Northern and Southern Africa. In the United States, it prevails to a greater extent than is generally supposed. The states and territories which, according to the reports of the Bureau of Animal Industry, suffer most from it are Texas, Oklahoma, Kansas, Nebraska, Colorado, North and South Dakota and Indian Territory ; but a number of the other Western States are badly infected. Manj' of the states east of the Mississippi river have infected localities, but in a few of the eastern and southern states it seems not to exist. During the last few years infected locali- ties have been found in New York where there has been an annual loss from this disease, but where prior to recent inves- tigations the cause of death has been attributed to poisoning. § 191. Etiology. Black leg is caused by Bacillus chait- veaui. This organism varies from 3 to 6yu in length and from 0.5 to i.yu in width. The ends are rounded and it produces 250 BLACK LEG spores. It stains readily with ordinary aniline dyes and also after the gram method. In cultures long involution forms are often observed. It is anaerobic. In suitable culture media under anaerobic conditions or in animal tissues (other than blood) it multiplies rapidly with the evolu- $> tion of gas. The presence of spores ren- ^ <^ @s=> ders it very resistant to natural destructive <** $<& agencies and to the common disinfectants. C <&, * The bacillus of black leg or its spores are @ » ^ supposed to gain entrance to the tissues of 1 ® ^^ animals through abrasions of the skin or, „ _ ., ... .. , , .. Fig. 57. Baal- possibly, the mucous membranes of the • 3I ., .... lus of blackleg . mouth or intestine. J & The period of incubation is not known in cattle but it is supposed to be very short. Guinea pigs inoculated with a culture of the organism die in from one to three days. § 192. Symptoms. The first symtoms may be either general or local in character. Arloing, Cornevin and Thomas believe that general symptoms always precede the local mani- festations. Norgaard reports finding cattle with marked local lesions but few animals suffering from general symptoms, al- though the latter may have preceded the former and have subsided. A general symptom is elevation of temperature, reach- ing in some cases 107° F. It usually falls to the normal or even subnormal before death. There is loss of appetite, loss of rumination and pronounced depression. Respiration be- comes accelerated, reaching 140 per minute or even higher. The animal moves with difficulty and lies down frequently. At first the visible mucous membranes are congested and within twelve to fifteen hours they have a dirty leaden or purplish color. The local symptoms may appear on different parts of the body except below the knee or hock joints and on the tail. They are less frequently found about the head. They usually appear on the thighs, neck, shoulders and lower region of the chest. The swelling is at first small and painful. It spreads rapidly and may. in a few hours attain to a large size, when it MORBID ANATOMY 25 1 becomes characterized by a crackling and gurgling sound when the hand is passed over it. On percussion it gives a clear, tympanic sound due to the collection of gas in the affected tissues. At the center of the larger swellings the skin becomes dry and parchment-like, cool to the touch and painless upon pressure. If lanced, a dark reddish, frothy fluid flows from the wound. It emits a disagreeable odor. In some cases there is but one swelling but usually there are two or more which may become confluent. The lymph glands adjacent to the swellings are much enlarged. There is usually trembling of the muscles, which, as death approaches, may develop into violent convulsions. Hun has pointed out the interesting fact that in a very large percentage of cases the swellings appear on the right side. There seems to be no explanation given for this local- ization. In this country, records are wanting of observations on this point. Arloing has called attention to a mild form of this disease in which the symptoms are slight debility, loss of appetite and slight local swelling. § 193. Morbid anatomy. After death the carcasses of animals which have died of this disease soon become distended with gas. This is due in part to the fermentation in the digestive tract and in part to the formation of gas in the sub- cutaneous tissues due to the presence of the specific bacillus. The subcutaneous distension is especially marked in the region of the swellings but it extends for a considerable distance from these foci in the direction of least resistance. The tympanitic condition often causes the two legs on the upper side of the carcass to extend out straight without touching the ground. A dark, blood-colored frothy discharge flows from the nostrils and anus. Decomposition takes place very rapidly except in the affected muscles, which retain a sweetish-sour odor for a considerable time after other parts of the carcass have become putrid. The skin covering the swelling is often affected with dry gangrene. The subcutaneous connective tissue is yellow, gelatinous, infiltrated with blood and bubbles of gas which 252 BLACK LEG escape if the tumor is incised. The muscles underneath the tumors are of a dirty brown or of a blackish color. At other places they are dark red or dark yellow and, when exposd for some time to the air, they may have a golden lustre. They are brittle, putrid and very rich in fluids. They crackle on palpa- tion. When incisions are made into them, blood of a frothy, greasy, tarry appearance and of a sickish, fetid odor issues from them when they are squeezed. The fibres of the muscles show extremely varied degenerative changes. The gases that are present in the muscles are inflammable and burn with a bluish flame on being ignited. They are said to have but little odor, on which account itis assumed that they consist of carburetted hydrogen. They are also said to contain carbonic acid but no oxygen. An exact chemical analysis of these gases seems not to have been made. The lymph glands near the tumors are enlarged and full of blood. They contain hemorrhages and are infiltrated with a serous fluid. The afferent lymph vessels are sometimes distended with gases, giving them the appearance of strings of beads. Changes similar to those of the external muscles appear in the muscles of the tongue and pharynx when the disease, as may happen in rare cases, is localized on the oral and pharyngeal mucous membranes. A large amount of blood-red exudate is frequently found in the abdominal cavity. In other cases only a small quantity of a serous fluid is present. In still others no changes at all appear. The abdominal changes seem to be determined by the swelling of the muscles, that is, whether it has or has not spread to the peritoneum. Yellow gelatinous and hemorrhagic infiltrations are often met with on the omentum, mesentery and in the neighborhood of the kidneys. The mucous mem- brane of the stomach and small intestine is frequently swollen, congested and infiltrated with hemorrhages, in which case the contents of the intestine are bloody. The liver is hyperemic, but the spleen is usually normal. In the thoracic cavity, the pleurae in the neighborhood of the swollen parts of the skin and mediastinum are sometimes hemorrhagic. The pleurae may also show large ecchymoses, MORBID ANATOMY 253 in which case the thoracic cavity contains a sero-sanious exu- date. Hemorrhages are sometimes present in the lungs, peri- cardium, myocardium and under the endocardium. The muscular tissue of the heart is very soft, but the other muscles show only slight changes. The mucous membrane of the bronchi are sometimes hyperemic and sprinkled with hemor- rhages. The blood is of a normal color and coagulates readily. The fluids of the muscles have, according to Feser, an acid reaction, and the flesh becomes rapidly putrid. The bacilli of black-leg are found only in small numbers if at all in the blood during life, but abundantly a few hours after death. They are numerous in the local lesions. The duration of the disease is from one to three days. Occasionally it is longer. The prognosis is grave. § 194. Differential diagnosis. Black quarter is to be differentiated from anthrax, the "corn-stalk" disease, septi- cemia hemorrhagica and various forms of poisoning. Usually the localized subcutaneous lesions are sufficient to differentiate black quarter from these other affections. It often happens, however, that post-mortem changes have so modified the car- cass before it can be examined that the diagnosis is question- able. In this and all doubtful cases or where only small por- tions of tissue are sent for examination, it is necessary to resort to a more definite method or methods, such as the microscopic examination, cultures and animal inoculation. 1. Microscopic examination. Cover-glass preparations made from the fresh tissues will ordinarily exhibit the specific bacteria. They are easily distinguished in case of anthrax, black quarter and often with septicemia hemorrhagica, while in the "corn-stalk" disease and cases of poisoning character- istic bacteria are not found. It is important to eliminate putri- factive bacteria, when the animals have been dead for some hours. 2. Cultures. Ordinary culture media inoculated with the tissues from a case of anthrax will give growths of the anthrax bacterium, and from cases of septicemia hemorrha- gica that of Bad. bovisepticum, but with the other two dis- 254 BLACK LEG eases they will remain clear if uncontaminated. The black quarter bacillus will grow on these media only when placed in anaerobic conditions. In case of the "corn stalk" disease the media will continue to be clear. 3. Animal inoculation. Guinea pigs inoculated in the deeper subcutaneous tissues with pure cultures of black leg bacteria or with bits of tissue from the affected area of another animal dead from the disease, death ensues in from one to two days. It is preceded by a rise of temperature, loss of appetite and general indisposition. The site of inoculation is swollen and painful and drops of bloody serum may some- times be seen exuding from it. At autopsy the subcutaneous cellular tissues and underlying muscles present a condition of emphysema and extreme edema. The edematous fluid is often blood stained and the muscles are of a blackish or blackish brown color. The lymphatic glands are markedly hyperemic. The internal viscera present but little alteration visible to the naked eye. In the blood stained serous fluid about the point of inoculation short bacilli are present in large numbers. These often present slight swellings at the middle or near the end. They are not seen as threads but lie singly in the tis- sues. If the autopsy is made immediately after death, these organisms may not be detected in the internal organs, but if not made until after a few hours, they will be found there also. In early autopsies only the vegetative forms of the bacilli may be found, but later (in from twenty to twenty-four hours) spore-bearing rods may be detected. With the "corn- stalk" disease the inoculated animals will remain well. §195. Prevention. In checking the spread of the disease it is very important wherever it is possible to remove the well animals from the infected field and to restrict the sick ones to a small one. The swellings should not be opened and the discharge scattered over the field. The dead animals should be burned if possible, otherwise buried deeply and covered well with lime as soon as possible after death. Birds and other animals should not be allowed to feed upon the car- casses and the skin should not be removed. Every precaution 4:o restrict the spread of the bacteria of this disease should be PREVENTION _ 255. taken. It is very desirable to thoroughly disinfect the ground where the animal lay at the time of death. The spores are very resistant both to disiniectants and the natural destructive agencies such as sunlight and drying. It is not wise to use land upon which animals have contracted the disease for graz- ing purposes for susceptible species. § 196. Preventive inoculation. Several methods of fortifying exposed animals against the infection of sympto- matic anthrax virus have been proposed. In 1880, .^.rloing, Cornevin and Thomas demonstrated at Chaumont that animals injected with the filtrate of cultures of this virus into the jugu- lar vein were protected against inoculation with the strong virus. It was found, however, that this method was difficult, as the vein had to be exposed and the greatest care was neces- sary to prevent infection of extra vascular tissue in introduc- ing and withdrawing the syringe. Later these investigators attenuated the virus by heating it to a temperature of 100 to 104 C. and injecting it into the subcutis of the shoulder. This gave a partial immunity which was reinforced after eight or ten days by a second inoculation of a virus that had been heated from 90 to 94 C. for six hours. They injected the virus where the subcutis is quite dense, such as at the end of the tail where only local swellings would occur. This process is known as "the French method," Arloing's or the "Lyons method." In 1888, Kitt of the Veterinary College in Munich, after a careful investigation of the subject proposed a single injec- tion method using a virus attenuated by heating at a tempera- ture of from 85 to 90 C. for six hours. A single injection of this vaccine would usually confer immunity. He further modified Arloing's method by making the injections in the shoulder region where the skin is looser and the operation easier. Later, Kitt made further important investigations concerning preventive vaccines for this disease. In the fall of 1896, investigations preparatory to the preparation of a black quarter vaccine were begun in the Bureau of Animal Industry at Washington by Dr. Nbrgaard under the direction of Dr. Salmon. The various European 256 BLACK LEG methods were tried. The one finally adopted consists of a single vaccine, the Arloing principal with Kitt's modification. The material used for the vaccine is obtained from a fresh blackleg tumor, by pounding the muscle tissue in a mortar with the addition of a little water and squeezing the pulp through linen cloth. The juice is spread in layers on plates and dried quickly at a temperature of about 35° C. This temperature does not in the least affect the bacteria, and the dry virus obtained in this way retains a high degree of virulence for two years or longer. When vaccine is to be prepared, the dried material is pul- verized and mixed in a motar with two parts water until it forms a semifluid homogeneous mass. This is spread in a thin layer on a suitable glass dish and placed in an oven, the temperature of which may be regulated with exactness. The reason for mixing the dried muscle with water is to insure a quicker and more uniform attenuation. The temperature^ the oven is previously brought up to 95 ° to 99 ° C. , and the virus is allowed to remain in it for six hours. When removed it appears as a brownish scale, which is easily detached from the dish. This scale is pulverized and put up in packages con- taining 10 doses each. Before it is used, it is mixed with 10 c.c. of water, filtered and the filtrate injected in doses of one cubic centimeter. REFERENCES. 1. Fisher. Blackleg in Kansas, and protective inoculation. Kan. State Agric. Exper. Station, 1901. 2. Lewis. Symptomatic anthrax. Bulletin No. 27. Oklahoma State Agric. Exper. Station, 1897. 3. Mayo. Blackleg. Bulletin No. 69. Kan. State Agric. Expt. Station, 1897, p. 108. 4. Norgaard. Blackleg in the United States and the distribution of vaccine by the Bureau of Animal Industry. Annual Report of the Bureau of Animal Industry, U. S. Dept. Agric. 1898. 5. Norgaard. Blackleg. Its nature, cause and prevention. Cir- cular No. 23. U. S. Bureau of Animal Industry, 1898. 6. PETERS. Blackleg. Its nature, cause and prevention. Bulletin No. 65. Neb. State Agric. Exper. Station, 1900. 7. Paouin. Black-leg. Bulletin No. 12. Mo. Agric. Expr. Station, 1890. 8. Salmon. Black quarter. Annual Report Bureau of Animal Indushy, U. S. Dept. of Agric. 1893-4. INFECTIOUS DISEASES 257 FOOT-ROT IN SHEEP. § 197. Characterization. Foot-rot in sheep is an infec- tious disease characterized by a specific inflammation of the tissues just above the horny part of the cleft of the foot, which extends downward, undermining the horny portion. It ap- pears in epizootic and enzootic forms. Sheep are most often attacked, although other species are reported to be susceptible. § 198. History. Foot-rot has been recognized for more than a hundred years. It has been described from various parts of Europe by Chabert, Pictet and Gohier. It seems to have first appeared in this country late in the eighteenth cen- tury. It has recently been investigated by Mohler and Wash- burn. They found a specific organism, and thus differentiated it from the streptococcic infection. § 199. Etiology. The cause of this form of foot-rot is, according to Mohler and Washburn, an anaerobic organism, Bacillus necrophorus. This organism is isolated with difficulty from these lesions because of the association with it of other bacteria. The most sat- isfactory method is by inoculating white mice or rabbits subcutane- ously with the diseased tissue and from their organs it can be obtained in pure culture. The time required to kill these animals is usually from four to twelve days. The period of iucu ba- tion in small animals is Pig. 58. Bacillus necrophorus (after but a few days. In the Mohler). naturally contracted dis- ease in sheep it is uncertain. In cases produced by inocula- tion of the specific bacillus from three to ten or more days elapse before symptoms appear. 25» FOOT-ROT IN SHEEP § 200. Symptoms. L,ameness is the first symptom noted. If examined prior to this, Mohler reports a moist area of the skin just above the horny part of the cleft of the foot. The inflammatory condition extends rapidly to tissue beneath the horny part. There is often a discharge of a thin, purulent fluid. Mohler states that the discharge emits a pungent, disa- greeable odor which is characteristic of this infection. There is emaciation which may be due quite as much to the inability of the lame sheep to procure food as from the specific action of the bacillus. The duration of the disease varies from a few weeks to several months. The cases are said usually not to terminate fatally. § 201. Morbid Anatomy. The tissue changes are those of a purulent exudative inflammation. As the process under- mines the horny portion of the hoof it may slough, and granulating tis- sue, commonly called "fungoid growths," develop. The invasion of the organism and the extending of the necrosis may continue until the tendons, ligaments and even the bones may be attacked. There is going on at this time reparation processes which usually terminate in a peculiar growth composed of horny elements, dense epithelial cells, and granulation tissue (Mohler). § 202. Differential diagnosis. Foot-rot in sheep is to be differentiated from inflammation of the feet caused by strep- tococcic infection, purulent inflammation of the interdigital space, the stoppage of the duct of the interungulate or biflex gland, and contagious foot and mouth disease. Pig. 59. Necrotic area in the liver of a rabbit;(C)liver cell, (B) inflammatory zone, (A) necrotic center (Mohler). REFERENCES. 1. Ernst. Ueber nekrose9 und den nekrosebacillus (streptochrix necrophora). Monatsheft f prakt. Tierheilk. Bd. XIV (1902), S. 193. 2. Mohi,er and Washburn. Foot-rot of sheep, its nature, causes, and treatment. Bulletin No. 63. U. S. Bureau of Animal Industry, 1904. INFECTIOUS DISEASES 259 MISCELLANEOUS INFECTIONS WITH BACILLI. § 203. Enzootic in cattle caused by a bacillus of the enteritidis group. In 1902, Mohlerand Buckley* described an outbreak caused by B. enteritidis among cattle in a stable of 21 animals of which 8 contracted the disease and died. Three others exhibited the early symptoms. The symptoms were first refusal of food, suspension of urination and diminution in lactation. There was excessive salivation in some cases. The temperature varied from 102. 7 to 104. 1 ° F. The visible mucosae were congested. There was a mild expression in the eyes and the animals were very excitable. The gait was irregular. Convulsions set in prior to death. The duration of the disease varied from two days to several weeks. The morbid anatomy varied. In the acute cases the anatomical changes were very slight. The most noticeable and characteristic lesion observed consisted of petechial hem- orrhages under the endocardium. These were present in every case. There were occasional blood extravasations in the intestinal mucosa. There was marked injection of the blood vessels of the meninges and blood tinted fluid in the cavity. The chronic cases presented a wider range of lesions in the organs. Cultures of the bacillus were obtained from the different organs. The bacilli were found in small numbers in cover- glass preparations made from the organs. The organism was fatal to experimental animals and to calves. It was more virulent than the bacillus of hog cholera obtained from hogs dead of that disease. *Mohi,ER and BUCKLEY. Report on an enzootic among cattle caused by a bacillus of the enteritidis group. (Illustrated and bibli- ography. ) Annual Report of the Bureau of Animal Industry, 1902. i jovivi-ii.mt i-WL'.? hi r i;v i jui>o Since Gaertner first discovered this organism in 1888 in the meat of a diseased cow, it has been isolated by others from both animals and man. It has been found to produce toxic properties that are pathogenic for animals, and several people have been reported to have become ill from eating broth made from meat containing this organism. During the last few years several bacilli differing slightly from Gaertner's bacillus have been isolated from cases of meat poisoning. Bacilli of this group, or at least of closely related groups, have frequently been found to stand in a causal relation to the lesions with which they were associated. The more important of these are Bacillus typhi murium obtained by Ivoeffler in 1890 from an enzootic among mice, the bacillus isolated by Mereshkowsky in 1895 from the ground squirrel, and Bacillus psittacosis isolated by Nocard in 1893 from the organs of parrots. In addition to these, other bacilli have been found appar- ently as the etiological factor in isolated cases among animals. CHAPTER VII. DISEASES CAUSED BY BACTERIA FAMILY SPIRILLACE-ffi. § 204. General Consideration of Spirillaceae. This family of bacteria has very few species among the pathogenic microorganisms. The spirillum of Asiatic cholera, and of re- current fever in man, together with a few recorded epizootics among fowls and birds caused by one or more of its genera, seem to circumscribe the etiological activity of this family. § 205. Diseases of animals caused by spirillaceae. The diseases of fowls reported to be caused by these organisms "fc "'%&. have not been found in this ■. '**(*»/% country. It is not unlikely that some one or more of the many as yet mysterious dis- eases of poultry may be caused by members of this family. It is interesting to note that spirilla are not un- common in the bacterial con- tents of the intestines. It is believed that many of these are anaerobes which would explain the difficulty encoun- Fig. 60. Spirochaete anserina tered in trying to isolate them from the blood of a goose, {After j n pure cu i ture Cantacuzine). Sakharoff ' studied, in 1 89 1 , a peculiar disease of geese and showed it to be caused by a spirillum. It was designated spirochaete anserina. Cantacu- zene has studied the mode of destruction of the spirilla. He found that they are destroyed by and within the macrophages of the spleen. ■dO-i DISEASES tAUSKD BY HFIKIL1,ACEAB The morbid anatomy in the affections caused by the spirilla appear to be largely engorgement of the spleen and swelling of the liver with fatty degeneration of the parenchy- matous tissue. The heart muscle is sometimes affected. Areas of necrosis have been described in the solid viscera. It is stated that the blood of the diseased fowl is not in- fectious 48 hours after it has been removed from the fowl but that if injected into a healthy fowl it will confer immunity against a virulent infection. Marchoux and Salimbeni found that if the fresh blood of the diseased fowl was heated for 5 minutes at a temperature of 55 C. it would confer immunity but if it was heated for 10 minutes this property was lost. Theiler found spirilla in the blood of the cattle in the Transvaal. He has also found spirilla in the blood of horses and sheep. REFERENCES. 1. CANTACUzijNE. Recherches sur la spirillose des oies. Annals de V Inst. Pasteur, Vol .XIII (1899), p. 529. 2. GabriTSCHEWsky. Beitrage zur Pathologic und Serotherapie der spirochaten — Infektionen. Cent. f. Backterol. Bd. XXIII ( 1898) y S. 365, und 778. 3. Sakharoff. Spirochaeta anserina et la septicemic des oies. Annals de I' Inst. Pasteur, Vol. V (1891), p. 564. CHAPTER VIII. DISEASES CAUSED BY FUNGI. ACTINOMYCOSIS. Synonyms . Lumpy jaw, wooden tongue, big head. §206. Characterization. Actinomycosis belongs to the class of affections known as the infectious granulomata. It is a chronic disease determined by the presence of a specific cause — the ray fungus — which by irritation stimulates the formation of new growths consisting of round cells, epithelioid cells, giant cells and fibrous tissue. The neoplasms appear as tumors having either a tendency to develop into large and hard masses or to suppurate. It has been suggested that the suppuration was due to a secondary infection by pyogenic bacteria. Cattle (genus Bos. ) are most often attacked. Horses, dogs, pigs, sheep and elephants are slightly susceptible and a few cases have been reported in each. Men are susceptible but this disease is rarely found in the human subject. Other species seem to be immune. § 207. History. The early history of this disease is quite obscure. Prior to the discovery of its specific cause, it was much confused with other diseases resembling it more or less closely in certain gross appearances. It was designated by a variety of names, the more common of which are swelled head, lumpy jaw, big head, fibroma, sarcoma, and osteosarcoma. It is popularly known in the United States as "lumpy jaw" and in Europe as "wooden tongue." The popular names were probably suggested by the character of the lesions which differ to a marked degree. It was recognized as a specific disease by Rivolta in 1868, by Perroncito in 1875 and by Bollinger in 1877. The ray fungus was undoubtedly observed prior to this by Iyebert and Robin, both of whom failed to recognize it as a vegetable parasite. The fungus was carefully described by Dr. Harz, a botan- ist, who gave it the name actinomyces or ray fungus. Bol- linger was the first to carefully study the disease in cattle and to demonstrate the power of the ray fungus to produce dis- ease. With this discovery of Bollinger in 1877, actinomycosis became recognized as a definite, specific disease which could in most cases at least be differentiated from the other affec- tions with which it had hitherto been confused. In 1845 von I_,angenbeck of Kiel observed and made drawings of peculiar bodies in a case of vertebral caries in man which it is now be- lieved were rosettes of the ray fungus. In 1878, Israel demon- strated the disease in man. Since that time it has been care- fully studied and described by a number of investigators. § 208. Geographical distribution. Actinomycosis is quite widely distributed throughout North and South America and Europe. It is much more prevalent in certain countries and districts than in others. The observation has been made that animals pastured upon low lands and in river valleys are more liable to contract it than those feeding upon high and dry ground. It has also been noted that cattle fed upon rough or coarse forage are more ^prone to the disease on account of abrasions of the buccal mucosa than those kept upon less harsh food. It is very difficult to procure reliable statistics concerning the extent to which it occurs. The observations which have been made at the union stock yards, Chicago, show one case of actinomycosis in from 1600 to 1700 cattle. The statistics from the abattoirs in Berlin show one case to 4150 cattle and one in 8000 pigs. These figures do not, however, indicate the extent of the disease among the farm animals as they are collected from those animals presented for slaughter only. At the clinic of the New York State Veterinary College there is presented for treatment a very few cases each year. In the Mississippi Valley and in the South-west it seems to be more prevalent than it is east of the Alleghany Mountains. ETIOLOGY 265 § 209. Etiology. Actinomycosis is produced by a fungus, Cladothrix actinomyces, commonly known as the "ray fungus." * The disease is the result of its multiplying in the tissues and not from the elaboration of a toxin. Undoubtedly the bacteria often associated with the fungus in suppurating lesions are of some significance. Wright states that he believes they play an important part in the extension of the disease. tt^%'tVl ^f jHpti?TS*[fi i.fjklYis , ^'t^^-irv^f^'iKiW^ fi '■■* ^^^^^^^^w^^wAM %%l iOt^w. ^ Fig. 61. A rosette of the ray fungus together with different forms of the single club ends. X 2500. ( After Crookshank) . The fungus appears in minute, yellowish granules in the lesions. When examined microscopically, these granules are found to be made up of rosettes varying in size from 10 to 200yU in diameter, the average size ranging from 30 to 40//. This fungus can be cultivated on artificial media. It stains somewhat feebly with the aniline dyes. The rosettes are composed of a number of club-shaped *The cladothrix is placed among the higher bacteria. There are many varieties of the actinomyces. Until they are better understood it seems to be best to group them with the fungi. Al_±±JNUM¥UU51S structures (rays), radiating from the central mass which is composed of the mycelial part of the fungus. The club- shaped bodies vary in size but usually they are from i to io/* long. The rays are connected with the central portion by fine thread-like structures which are not readily demonstrated. In tearing or crushing the rosette, the clubs break off at or near their junction with the mycelial threads. Some investi- gators have mentioned a polymorphous form of actinomyces in which coccoid and rod-shaped structures are found.. These are doubtless the end of the clubs which first appear in focus- ing on a rosette. The mycelial threads are wider in some portions than in others. In the narrowest places the walls seem to touch each other. Whether this irregularity is natural or the result of twisting the mycelial thread is not determined. The myce- lium is much more difficult to stain than the clubs. In some cases it seems to branch. The filaments can rarely be seen in the rosettes as they occur in the suppurating lesions. The natural habitat of this fungus is said to be on certain plants. According to Brazzola, they vegetate on the grasses, chiefly on Hordeum murinum. He discovered quantities of the fungi between the vegetable fibres of barley which were imbedded in the gums of animals. Johne, Piana, Bostroem and others have found it on the awns of corn which were imbedded in the tonsils of pigs and in the tongues of cattle. Mayo, after making a careful study of this disease, states that the actinomyces are probably a degenerative form of some fungus which grows naturally upon food stuffs or grain. Bostroem entertains the view that they develop exclusively on grain, particularly on the awns of barley. The period of incubation is not known. §210. Infection. While actinomycosis is an infectious disease it does not seem to be transmitted directly from one animal to another. Numerous investigators have tried to pro- duce the disease by inoculating cattle, calves, sheep, goats, pigs, dogs, cats, rabbits and guinea pigs wiili actinomycotic lesions. The results have almost invariably been negative when pus was used, but the disease has developed after inocu- INFECTION 267 lating cattle with pieces of tissue containing the fungus in its vegetating state. It is believed that the infection occurs in susceptible species by the introduction of the fungus on food stuffs. The supposition is that the parasite gains entrance to the living tissues through slight wounds of the mucous membrane of the mouth or throat and perhaps the alveoli of diseased teeth or during the shedding of the milk teeth. It multiplies and ex- tends from the points of entrance. After the infected awns once gain lodgment, especially between the teeth, they are tf_ ' " .-i & [Mm WBpmm ^^^&^&?*.^BU 'Mm ■^■•^HH^w- fa Fig. 62 Head of a steer with actinomycosis of the lower jaw. {Photographed by Hopkins) . removed only with difficulty. The favorite points for the act- inomyces to enter the tongue is on the upper surface midway between the dorsum and the tip. The lungs may be the seat of primary infection due to the inhalation of the fungus. The disease has been rarely observed primarily in the udder but frequently in the subcutaneous ^tissue about the head. In man the source of infection is more obscure. Many cases have been reported where the individuals did not come in contact with diseased animals and were not occupied in agricul- tural pursuits or in handling grain but were glaziers, tailors and various shop tenders. There are a few cases reported, however, where the circumstantial evidence points to direct infection from diseased animals. The present knowledge of this fungus indicates that it must attain to a certain stage or period in its development before it will live and multiply in living animal tissues. It has been observed that, as a rule, cattle become infected when they are kept upon dry food. § 211. Symptoms. Actinomycosis is manifested by a firm swelling or tumor usually situated in the region of the head or throat. It is first recognized as a slight swelling of the affected part resembling somewhat the result of a bruise. It is stated by those who have had much experience with the disease that many cases of actinomycosis seem to be caused by blows or injuries received while struggling in stanchions. The enlargement gradually increases in size. It is ordinarily sharply defined from the surrounding tissues. Upon manipulation the tumor feels hard and dense. In the region of the throat it may be fluctuating. After a ■variable length of time, the tumor-like mass may soften in one or more places, rupture and discharge a rather thick, yellowish and more or less sticky, purulent substance. The discharge may continue or, as often happens, the opening heals temporarily only to rupture again. The discharge often takes place into the cavity of the mouth or throat. Sometimes the neoplastic tissue increases in amount until it gradually forces its way through the opening, resembling somewhat a cauliflower in appearance. The actinomycotic growth fre- quently increases rapidly in size after it has discharged. In later stages the teeth may become ulcerated and loose. When the tongue is affected the animal finds it difficult to eat. The organ is swollen and in advanced cases hangs from the mouth. There is in these cases profuse salivation. When the pharynx is affected there is difficulty in swallowing and when the larynx is attacked there is difficulty in breathing. In this country the tumor is most frequently seen on the ex- MORBID ANATOMY 269 ternal surface of the jaw. It is stated by Salmon that it usually begins in the connective tissue beneath the skin but soon extends to the bone, which it penetrates. Actinomycosis of the cervical vertebrae may cause spinal paralysis. When the lungs are attacked the animal may present the appearance of one suffering from a chronic pulmonary disease such as tuberculosis. Actinomycosis is not a rapidly fatal disease. Animals rarely if ever die from its immediate effects. The length of time during which they survive depends very largely upon the location of the tumor and the rapidity of its development. If the tumor is situated where it does not interfere serious- ly with prehension, masti- cation or swallowing of food or where it does not occlude or press upon the respira- tory passages the animal usually survives for several years. When death occurs it is usually due to inani- tion, the animal being un- able to take sufficient food, although the drain upon the system by the long con- tinued discharge of pus must be severe. Mayo re- ports several cases where the disease was watched for five or six years and where it would possibly have continued several years more had not the animals been destroyed. Most animals which become affected with actinomycosis are either destroyed, treated, or slaughtered for beef in the early stages of the disease. §212. Morbid anatomy. The new actinomycotic growths have in or near their centers rosettes of the ray fungus sur- rounded usually by giant cells. These in turn are surrounded by tissue consisting principally of epithelioid and spindle shaped, connective tissue cells, among which giant cells may Fig. 63. A drawing of a very young actinomycotic growth. A. actino- myces ; B, giant cell ; C, surrounding reactionary zone. 270 ACTINOMYCOSIS appear. As these cells increase in number they press against the surrounding tissues, thus producing the hard and dense tumor-lilce growths. This is especially true when they are located in the connective tissue. In certain other positions, such as the liver, the inflammatory cells are surrounded by a fibrous tissue frame-work which gives to the lesion a honey comb appearance. On section a disagreeable "nutty" odor is given off which Mayo considers to be quite characteristic of the disease. The outside of the tumor is usually composed of a dense layer of fibrous connective tissue. Extending from the periphery toward the center, the tissue becomes less dense and is composed largely of epithelioid cells. In the softer tissue there are often cavities of greater or less size filled with a viscid purulent substance in which the small, yellowish granules of the ray fungus can be found. If this pus is spread Fig. 64. A drawing of an actinomycotic jaw. in a thin layer on a smooth surface granules composed of the "ray fungus" can often be seen with the unaided eye. These pus cavities are usually connected with each other by small sinuses but sometimes they are separated by bands of fibrous tissue. If the disease is in the bone, usually in the head, as it is MORBID ANATOMY 271 when the specific organism gains entrance and begins to grow in the interior of the jaw, the bone tissue about the organism becomes in places disintegrated and absorbed and pockets are formed containing the fungus. While the interior of the bone is being broken down and absorbed by the action of the acti- nomycotic growth within, its diameter is being increased by the deposition of new tissue until it may become several times its normal size. Fig. 65. Photograph of a section through an actinomycotic jaw ; (a) tooth, {6) bone, (c) actinomycotic tissue. The lesions spread in most cases by gradual invasion of the tissues surrounding the infected point. At the seat of in- fection, minute, inflammatory points appear, which extend at their periphery and unite to form larger areas of diseased tissue. These masses tend to extend in one direction and to heal in another, leaving behind bands of cicatricial tissue. The process usually differs widely from that of a simple inflam- mation. In its progress the disease shows no preference for structures but invades one tissue after another so that all may be involved alike. The lymphatics show no constant tendency to become 272 ACTINOMYCOSIS involved. Metastasis occurs in a very small proportion of the cases. When it does, as reported by Ponfick, large areas may be simultaneously affected. He reports a case in the human subject in which the left jugular vein was perforated by a mass of the fungi resulting in the formation of actinomycotic infarcts in the lungs, spleen, brain, and heart. In cattle, actinomycosis usually appears in one or more of the following locations. 1. In the maxillary bones. Here it generally results in large tumor-like growths. Actinomycosis of the jaw usually Fig. 66. Actinomycosis of the upper jaw. {Photograph by Hopkins) . commences with flat granulations of the gums and mucous membranes in the neighborhood of the teeth and spreads finally to the medullary tissues of the bone arid to the perios- teum, soon giving rise to the osseous tumor. From the maxil- lary bone the disease may advance either to the subcutaneous connective tissue and the skin or to the oral cavity in the direction of the molar teeth, which become displaced. 2. In the tongue. When the lesions appear in this organ it takes the form of an indurating glossitis. The tongue be- MORBID ANATOMY 275 comes thickly sprinkled with round or oval, hard, fibrous nodules which finally become purulent or chalky at the center. Around these there is a considerable increase of connective tissue which leads to the atrophy of the muscle fibers. Upon section the tongue is found to be hard and often gritty. The indurated tongue is often eroded from friction and various deformities of this organ are reported. 3. In the pharynx. Here the disease usually takes the form of soft polypoid or fungoid nodules or lumps with a smooth surface and short peduncle. These nodules vary in size often reaching that of a goose's egg. These polypoid growths may cause great difficulty in swallowing and likewise interfere with respiration. Tumors of this kind may form in Fig. 67.' Actinomycosis of the tongue, "-wooden tongue" {Photo- graphed by Hopkins). the esophagus or trachea. Rarely actinomycotic growths occur at other places in the alimentary tract. There are some cases in which the lesions are not restricted to the digestive tract. 4. In the skin and subcutaneous tissue. The lesions of the skin and subcutis are found chiefly on the head and neck. They usually consist of firm nodules from the size of a hazel nut to that of a man's fist or even larger. Sometimes these nodules are pedunculated and at others they are attached to ^74 ACTINOMYCOSIS the skin by a broad base. Instead of the hard tumor there may occur soft granular fungoid proliferations covered with a brown crust or with a purulent secretion. At other times minute nodules appear in these proliferations and the skin becomes thickened and indurated. However, the skin lesions may become very large. In this organ, the disease may be •either primary or secondary. 5. In the lymph glands . Actinomycosis often appears in the lymph glands of the head, larynx and pharynx. The parotid and submaxillary glands are sometimes involved as secondary infections. It is reported that the sub-parotid glands are most frequently affected. 6. In the lungs. The lesions in the lungs vary. They may consist of firm, somewhat yellowish nodules which event- ually become calcareous in their center and vary in size from mere specks to that of a pea. This form is spoken of as miliary actinomycosis. In the second form the actinomycotic foci soften and become filled with a gray muco-purulent fluid. The lesion may spread to the pleurae and even reach to the surface of the body by penetrating through the thoracic wall. The bronchial glands and the mucosa of the air passages may also become affected. 7. In other organs. Actinomycosis has been reported rarely as attacking the udder, spermatic cord, brain, spleen, liver, muscle, diaphragm, peritoneum, inguinal glands, vagina, uterus and cervical vertebrae. Assmann has recently summarized the literature on the dissemination of the lesions and has concluded that generalized actinomycosis is not rare in occurrence. He gives a detailed description of eleven cases in cattle and hogs. It is stated by Salmon that in England the disease appears most often in the tongue, in Denmark the soft parts of the head are affected most frequently while in some parts of Ger- many it is most frequently found in the pharynx. In the United States it usually appears in the lower jaw. In man as in cattle, the appearance of the lesions vary according to the part infected. In some cases the lesions closely resemble those of chronic inflammation but in others, such as the liver SYMPTOMS 275 or skin they are often characteristic. In the lungs the lesions have frequently been mistaken for tubercle. Usually the dis- ease affects the head and if the maxillary bones are attacked the teeth are usually lost. Actinomycosis in swine. Actinomycosis appears in this species in the lower jaw, larynx, lungs, wounds caused by castration, in the mammary gland, muscles and bones. The character of the lesions does not differ to any marked extent in swine from those in cattle or man. In case of bone infection purulent cavities and sinuses are formed in which the yellow granules of the fungus occur. It is reported that occasionally pigs suffer from generalized actinomycosis. Duncker has found in the muscles of the pig a variety of the ray fungus which has been called Actinomyces muscolorum suis, to dis- tinguish it if possible from the bovine species. Its relation to the actinomyces bovis has not been clearly determined. It is reported to have been found frequently. Actinomycosis in horses and sheep. In the horse, acti- nomycosis of the bones, tongue, trachea, spermatic cord and submaxillary glands has been observed. The disease is reported to have been mistaken for glanders. The affection known as schirrhous cord seems to be due in rare cases to an infection by the ray fungus. One such case has occurred in the clinic of this institution. A very few cases of this disease have been reported in sheep, the lesions being restricted to the lungs or muscles. § 213. Differential diagnosis. In cattle actinomycosis is to be differentiated (1) from tuberculosis, especially of the lungs, glands of the throat, head and the udder, (2) various forms of glossitis, polypoid growths in the pharynx, fibroma, sarcoma and osteosarcoma of the jaw, parotitis and cellulitis. The writer has seen a few cases of bacterial infection of the maxillary glands giving rise to the formation of large quan- tities of caseous matter which caused swelling and firmness suggestive of actinomycotic tumors. In one instance a speci- men reported to be actinomycosis was examined and found to contain a piece of bone about three inches long which had become wedged between the teeth and cheek and surrounded 276 ACTINOMYCOSIS by inflammatory tissues. Frbhner calls attention to conta- gious diseases as possibly being mistaken for this disease. The affection recently described by Lignieres as actino- bacillosis is to be distinguished from actinomycosis of the skin. It is thought, however, by many workers that, actinobacill- osis is a variety of actinomycosis. In making a positive diagnosis of actinomycosis it is necessary to make a microscopic examination of some of the diseased tissue or of the discharged pus in which the ray fungus may be found if the disease is actinomycosis. It is impossible to obtain this positive proof from the living animal when the disease is situated in the internal organs. With these it is necessary to depend largely upon the history and general condition of the animal. In preparing the discharged pus for a microscopic examination it is usually sufficient to crush one or more of the yellowish granules between a slide and cover-glass. It is of advantage to wash it with a dilute solution of caustic soda to clear away the pus cells. The rosettes are easily recognized with a low magnification. In man, actinomycosis is to be differentiated from certain forms of tuberculosis and the Madura foot disease which was described by Carter, in i860, as a "fungous disease." This is a chronic, locally spreading inflammation of the foot, rarely of the hand, causiug the destruction of the part involved and giving rise to a great overgrowth of connective tissue. My- cetoma almost invariably attacks the hand or foot and accord- ing to Carter there are no secondary deposits in the viscera. In actinomycosis the extremities are rarely attacked and the viscera are often the seat of the disease ; further the mycetoma is a disease of hot climates while actinomycosis is a disease of the temperate latitudes. The fungus of the two affections seem to be closely related but as yet their identity has not been established. § 214. Specific treatment. The investigations of Thomassen, Nocard, and Norgaard and the experience of a large number of veterinarians have proved very conclusively the specific, curative effect of iodide of potassium. According to Salmon the iodide of potassium is given in doses of from 1.5 SANITARY CONSIDERATION 277 to 2.5 drams dissolved in water and administered in a drench, once a day. The dose should vary somewhat with the size of the animal and with the effects that are produced. If the dose is sufficiently large there appear signs of iodism in the course of a week or ten days. The skin becomes scurvy, and the eyes moistened. There is nasal catarrh and loss of appetite. When these symptoms appear the medicine may be suspended for a few days and afterwards resumed in the same dose. The cure requires from three to six week's treatment. Some ani- mals do not improve with the administration of iodide of potas- sium and these are generally the ones which show no signs of iodism. If there is no sign of improvement after the animals have been treated four or five weeks and the medicine has been given in as large doses as appears desirable, it is an indication that the particular animal is not susceptible to the curative effects of the drug and the treatment should be abandoned. It is not, however, advisable to administer iodide of potas- sium to milch cows, as it will considerably reduce the milk secretion or stop it altogether. Furthermore, a great part of the drug is excreted through the milk making it unfit for use. It should not be given to animals in advanced pregnancy, as there is danger of producing abortion. § 215. Sanitary consideration. The literature upon this subject is largely to the effect that actinomycosis is rarely if ever either contagious or infectious in the sense that it can be transmitted from one animal to another or from one of the lower animals to man. There seems to be no indisputable case on record of such a transmission, although a few cases are very suggestive. It is the opinion of most pathologists that when the disease is restricted to small tumors and these are localized, that the affected parts should be destroyed but the remainder of the carcass may be used for human consumption. In Bulletin No. 2, of the Board of Live Stock Commis- sioners of Illinois, published in 189 1 , is the report of the some- what famous trial in the Peoria county circuit court of the case of J. B. Greenhut et al. vs. John M. Pearson et al. to recover damages for the rejection and destruction of certain actinomy- 278 ACTINOMYCOSIS cotic cattle, in which is given the testimony of a large number of distinguished veterinarians and sanitarians concerning the wholesomeness of the meat of cattle affected with this disease. Although at that time there was a strong popular sentiment against the use of such animals, the jury after a forty hours' consideration reported their inability to agree and were dis- charged by the court. The most conspicuous feature of this evidence was the inability of the witnesses to produce satis- factory evidence of the communicability of the disease from animal to man. This evidence did much to show that the danger from this disease in eating meat of affected animals was after all a matter of opinion, fear or sentiment rather than a demonstrated fact. Mayo, in his bulletin upon the subject, states that there is no danger of persons contracting this disease from eating the flesh of affected animals provided the visibly diseased portions are removed. REFERENCES. 1. Bostrobm. Untersuchungen iiber das Aktinomykose des Men- schen. Beitrag. zur path. Anat. u. zur. allgr. Pathologic, Bd. IX (1891), S.i. 2. Israel. Neue Beobachtungen auf den Gebeite des Mykosen des Menscben. Virchow's Archives, Bd. LXXVI (1878), S. 11. 3. Mayo. Actinomycosis bo vis or "lumpy-jaw." Bulletin No. jS, Kansas State Agric. Exp. Station, 1892. 4. Nocard. Notes sur l'actinomycose des animaux. Recueil de Med. Vttir. Vol. LXIX (1892), p. 167. 5. Salmon. Treatment of lumpy-jaw or actinomycosis in cattle. Bulletin No. 2, U. S. Bureau of Animal Industry, 1893. 6. Salmon. Actinomycosis or lumpy-jaw. Annual Report t Bureau of Animal Industry, 1893-4, p. 88. 7. Wolff and Israel. Ueber Reincultur des Actinomyces und seine Uebertragbarkeit auf Thiere. Virch. Arch. Bd. XXVI (l89i),S. II. 8. Wright. The biology of the microorganism of actinomycosis. The Jour, of Med. Research, Vol. XIII (1905), p. 349. INFECTIOUS DISEASES 279 ACTINOBACILLOSIS. § 216. Characterization. Actinobacillosis is described as an infectious disease of cattle, characterized by its clinical resemblance to actinomycosis. It is caused by an organism which "resembles, in a marked degree, the bacterium of Fowl Cholera." It arranges itself in the tissues in "rosette" or ray- like forms. It is thought by some workers to be a variety of actinomycosis. It is described as an independent and distinct disease. § 217. History. Iyignieres and Spitz described, in 1902, a disease in cattle resembling actinomycosis but which was caused by a bacterium. Until 1900-01 this affection was not differentiated from actinomycosis. Nocard, in 1902, identified the disease in France. In 1904, Higgins described four cases in Canada. These appear to be the only records we have of this affection. § 218. Geographical distribution. It is reported by Lignieres and Spitz to be epizootic in Argentine Republic. It has been described in France, and in Canada. § 219. Etiology. This disease is caused, according to its investigators, by a bacterium which arranges itself in the tissues in a rosette or ray-like appearance. It is aerobic, facultative anaerobic, non-motile and of a variable size, rang, ing between 1.0 and 1.8 /a in length and from 0.4 to 0.6 in breadth. According to Higgins, it has a distinct polar arrange- ment of the protoplasm as observed in the hanging drop preparation. It stains with the ordinary aniline dyes.* It does not take the Gram stain. *Higgins recommends the Romanowsky stain as modified by Dut- ton and Todd for sections or preparations from pus. The formula for the stain and method for its use are as follows : Stain: Eosin, aquous solution 1 part Borrell's Blue 1 " Water 8 parts Mix just before using and filter. Suspend the preparations ( sections fixed to the slide ) upside down over the stain to saturate them from below, to avoid precipitate. Stain in this solution for thirty minutes. Wash thoroughly in w^:er, then in a 10% solution of tannic acid, which will brighten the color, and again wash in water. Dehydrate in alcohol, clear and mount in xylol balsam. The 9tain as above prepared spoils quickly. * 280 ACTINOBACILLOSIS In the fresh tissues or in sections it appears in granules the same as the actinomycosis. The actinobacillose is virulent for guinea pigs and rabbits. When inoculated into the abdominal cavity with pure cultures guinea pigs die in from nineteen to thirty-one days (Higgins) of generalized actinobacillosis. These are reported to be characteristic and different from those of any of the other observed infective agents. According to Higgins, "Small peariy-wbite nodules appear just beneath the peritoneal and pleural membranes, varying from i.o to 5.0 mm. in diameter. Fig. 68. A photograph of a section of a tumor stained by Gram's method but not fully decolorized. X about 1,000. (After Higgins). The liver presents lesions throughout its substance, the sur- face being mottled. The spleen shows, usually, a varying number of nodules. The great mesenteric fold of the omentum has in every instance been the seat of extensive lesions. The kidneys present nodules beneath their serous covering, but none have been observed in the substance of the organ. The stomach and intestines usually present nodules on their serous surfaces, varying from 1.0 to 0.5 mm. in diameter." There are other lesions such as ulcers in the stomach, nodules MORBID ANATOMY 28 1 in the heart and pericardium. Subcutaneous inoculations are usually followed by similar lesions. Rabbits are said to react the same as guinea pigs. Nocard found an intravenous injection fatal to dogs in 24 hours. In horses a local abscess resulted which healed rapidly. The method of infection has not been fully explained, but it is supposed that the organisms are taken with food as in ■cases of actinomycosis. The organism agglutinates in serum of animals affected with actinobacillosis, It is destroyed in 10 miuutes at 62°C. It grows best at incubator temperature (37°C.) It is not rapidly destroyed by freezing. § 220. Symptoms. They do not appear, in cattle, to be differentiated from those of actinomycosis. § 221. Morbid anatomy. The lesions are very similar to those of actinomycosis. The location of the affected parts varies. Lignieres describes it attacking the skin, lymphatic glands, tongue, pharynx, mammary glands, the viscera and bones. The tissue changes appear to be an infiltration of puru- lent material, and the new formation of connective tissue. The skin is often affected. In the single specimen which the writer has had an opportunity to study, the ray-like arrange- ment of the organism and the tissue immediately surround- ing it, could not be easily distinguished from a section of actinomycosis. § 222. Differential diagnosis. Actinobacillosis is to be differentiated from actinomycosis, tuberculosis, perhaps certain parasitic diseases of the skin, and localized bacterial infections. The diagnosis is made from the various locations of the lesions. The more important of these is the apparent selec- tion of the skin. The examination of the fresh pus does not reveal the yellow granules as observed in actinomycosis but when squeezed between two cover-glasses they are said to be distinct. The actinobacillosis does take the gram stain, it is in- fectious for guinea pigs and rabbits, and it is readily cultiva- ted on artificial media. It appears to be transmitted more often to cattle by cohabitation than actinomycosis. 282 ACTINOBACILLOSIS The differentiation from any parasitic trouble is made by- the finding of the animal parasite. The nature of the lesions and the finding of tubercle bacteria in the discharge by micro- scopic examination, or by producing tuberculosis in guinea pigs by inoculations, would differentiate it from tuberculosis. § 223. Prevention. As the natural habitat of actinoba- cillose is not known, the source of infection is undetermined and consequently effective preventive measure not are known. The fact that it seems to spread from infected to healthy cattle necessitates the isolation "of the infected. It is more desirable when possible to separate the well from the infected animals. REFERENCES. 1. Higgins. Actinobacillosis. Bulletin No. 1, Biological Lab- oratory Department of Agriculture. Dominion of Canada, 1904. also Proceedings Amer. Vet. Med. Asso. 1904. 2. LigniSrES and Spitz. Actinobacillose. Contribution a VHude affections connuer soos le nom d'aclinomycose. Buenos Aires, 1902. 3. L,ignie:res and Spitz. Actinobacillose. Recueil de MMicine Vetirinaire, 1903. 4. Nocard. Actinobacillose der Zunge , fhar. des Vet. Med. Berlin, Bd. I/VI (1903), p. 695, (abstract). INFECTIOUS DISEASES 283. LEECHES. Synonyms. Summer sore, leeching, barsati, barsdti, bar- sattee, barsatti, bausette, bursati, bursatie, burusattee, bursatti y bursautee, bursautie, bursauttie, bursottee and burusauttee. These names have been derived from the Indian word burns or bursal, meaning rain or rain sore, it having been supposed that the malady was associated with the rainy season. §224. Characterization. "Leeches" or "Leeching" is an infectious disease quite prevalent among the horse kind in Florida with lesions localized on the skin or the mucosa of the head. It is thought by many that this affection is identical with the disease known as bursattee* in India. § 225. History. Neal of Florida described this disease as affecting horses and cattle. He believes it to be peculiar to that section, where he states it is common and very fatal to- horses and mules. There are hundreds of ponds in the central portion of the state around the margins of which there is usually a belt of grassy prairie, water grass and water lilies. Into these grassy places the horses, mules and cows often go during the summer and feed all day in the water. He adds, "after a varying .exposure to the influence, or whatever it may be called, of the 'pond,' a slight lump or elevation of the skin, may be found on some part of the body that has been sub- merged. To the touch it will feel as if a grain of shot were lodged beneath the skin. In eight or ten days the skin sloughs off centrally over this hard spot, leaving a bloody, bruised-like surface. This rapidly grows in size till in a few weeks there is a raw surface from 4 inches to a foot square. This oozes blood and serum, but no pus. An examination will usually show a mass of yellow, gritty growth, coral like in shape, embedded in a mass of bruised, bloody tissue, dark in color and the edges roughened, elevated above the skin, and the skin decaying at the outside of the ulcer. The leech *It seems to be true that an entirely different affection is known by the same name in the northern portion of the United States. The term "Leeches" is also applied to the condition following the invasion of the liver fluke {Fasciola hepatica). 284 LEECHES invades almost any tissue, but seems most common on the legs, abdomen and sides. Occasionally it is found in the head. The invaded tissues decay slowly and apparently without pain. I have seen hoofs cut off, the abdomen opened, the eyes eaten out and the teeth destroyed." In this country the disease has not attracted very much attention, nor has it been considered of much economic import- ance. An explanation for this may be offered on account of its seemingly non-contagious character and because it has been thought to be confined to comparatively limited areas, and be- cause the animals, although infected, may yet be utilized for some purposes. On account of the chronic course of the disease the affected animals are often killed from a sentiment of mercy before the disease can terminate fatally. Although this affection presents many points of similarity to the one found in India, the question of their complete iden- tity ought to be held in abeyance until a more thorough inves- tigation can be made. In a recent publication, Dawson, of the Florida Experi- ment Station, states "that 'leeches' or bursattee is a common disease in Florida, which manifests itself in the formation of tumor- growths which have some of the characters of actinomy- cotic tumors. Its structure is fibrous, and contains many sinuses, which discharge a bloody, "honey-like" fluid. It is a fatal, infectious disease, which has its origin in the skin and finally penetrates all the tissues. Here and there in the tumor tissue yellow bodies with root like projections may be found. These bodies are called 'leeches' by the natives. They consist of the mycelia of the fungus which causes the disease. The only remedy is the complete removal of the tumor and adjacent tissue at once. The application of caustics and disinfectants makes matters infinitely worse, as they stimulate the tissues to renewed growth-activity. In Florida the disease affects only the genus equinus." In 1896, some of the diseased tissue from cases of this affection in Florida, were sent to the Bureau of Animal Indus- try for investigation. They were studied by Fish, who made HISTORY 285 an extended report on the results of his findings. He also gave a very complete review of the literature. Hodgson, in 1853, referred to the sores as cancerous ulcers and Hart in 1872, was strongly inclined to pronounce it cancer, although he could not confirm this vieWjStructurally by microscopic examination of the tissue. It seems to be generally accepted that the disease is peculiar to the Tropics, but cases have been reported in Kansas and Minnesota in the United States, not only during the summer months, but when the thermometer registered below zero. We might also ex- pect that the disease would exist in Mexico and Central and South American countries, where the conditions of tempera- ture and moisture are favorable. Reports show that a high temperature is essential for the development of the disease, although exceptional cases are noted as occurring during the cold season. Moisture does not seem to be necessary, since many cases develop when the season is dry. It is, however, an important factor. Statistics show that cases are more numerous and that the disease assumes a more aggravated form during the wet season. In India, native as well as foreign bred horses are sus- ceptible, but according to some writers, none of the other equine species are affected. In the United States mules and cattle are said to develop it, but not as readily as the horse. Outbreaks among cattle are comparatively rare. Thin-skinned animals are more sus- ceptible than thick-skinned ones. Some discrepancy of opinion exists as to the kind of horses most likely to take the disease (assuming that bursattee and leeches are similar). Neal states that only horses of good blood leech, and the Cuban and Texan ponies are as a rule exempt. Anderson states that it is the coarsely bred and hard-worked horses that are the most susceptible. The well-bred ones, having the advantage of good hygienic surroundings, rarely contract it. § 226. Geographical distribution. Bursattee has been reported from Burmah and Hindoostan. It is thought that the prevalence of the disease is associated with the principal river systems of India. In the hilly, rocky and consequently 286 LEECHES -drier districts there is a very noticeable diminution or absence of it. Outside of India there seems to have been no cases of this malady reported except in the United States, unless upon fur- ther investigation certain mycotic diseases which have been ■described in Europe should prove to be identical with it. I^yford (1866) reported it in Minnesota, Anderson (1889) in Kansas> and Alabama, and Neal (1887) and Bitting (1894) in Florida. The latter writer states, that it is "now known all over the United States except in that region lying east of Alleghany mountains and north of the Potomac river." A few cases have been presented for treatment in the clinic of the New York State Veterinary College. § 227. Etiology. A summary of the literature shows that among the old theories "Leeches" was believed to be a blood disease in many ways not unlike syphilis, scrofula and farcy. The "fly theory" of the causation and dissemination of bursattee was entertained by the natives of India as early as 1820. Jackson, in 1842, seems to have been the first to believe that there was any connection between the disease and a fungus. Jackson suggested, in 1842, that the disease might be re- lated to a fungus or to a vegetable parasite. Collins, in 1874, ■expressed a similar belief. F. Smith, in 1879 and 1884, seems to have been the first to have worked along this line. He was able to find fungi in every fresh specimen of the sores that he examined. Steel, in 1881, also found fungal elements in these sores. T.Smith, Fig. 69. A piece from the in 1893, examined some alcoholic Up of an affected horse, show- material and gave expression to * w f ^eral diseased foci the belief that the disease was ^ caused by a fungus. Fish, in 1896, found a fungus embedded in the diseased tissue. He did not name it neither did he obtain it in pure culture, but his illustrations are very clear in showing the existence of a fungus. Fish gives m detail the Plate V. _.:-, A , '. .>•*<, :.- :•' ■'?•:■; / '':*'''-■ ';• . - ' ■ wiV>: .: Fungus. MORBID ANATOMY 287 methods he employed. It is to his work that we are indebted for the more careful description of the morbid changes. § 228. Morbid anatomy. As a rule the lesions are near the surface. Where the diseased portion has become well developed there is usually a more or less complete detachment of the central inflammatory growth from the surrounding tissue. This nodular or "kunkur" growth may vary in its density according to the stage of its development. During the early stages it is soft and easily cut ; later it becomes firmer and ultimately assumes a hard or "gritty" character. In cutting sections it is generally the exception to cut through the nodule or kunkur evenly and to have it retain its proper relation with the other parts. Even if successful in cutting, the nodule drops out after some of the other proces- ses. In the specimens examined the lesions were confined entirely to the skin and subcutaneous tissue ; no traces of muscular or glandular structure were observed. Around the cen- tral portion of the inflammatory growth there is a zone of leuco- cytes of the mononuclear and polynuclear varieties, the latter predominating. They are em- bedded in an abundant stroma of connective tissue which is in a Fig 70. From the same lip, but greater or less stage of degenera- skon'ittg a larger infected area tion. The central portion of the (Fish). zone is in some cases very closely packed with the leucocytes, while toward the periphery they are more loosely arranged and cause a marked irregularity of the margin from their uneven drifting into the tissue beyond. There is generally one and perhaps more points where this in- filtration occurs quite extensively. In some of the prepara- tions the wandering cells have been traced as far as the surface of the epidermis. Occasionally there may be found a narrow area at the per- phery of the nodule, as seen in cross section, which is lighter in color and less dense in texture than the central mass, evidently an extension of the growth. 288 LEECHES In the specimens examined the parts where the lesions abounded were not characterized by a rich vascular supply. The few vessels that were encountered were not of a normal char- acter ; their walls were thickened, and the endothelium, in- stead of presenting the usual flattened appearance, was irregu- larly cylindrical. Although the condition was not observed, it is not impossible that the hyphae of the fungus may develop to such an extent as to compress or actually penetrate the walls of the vessels, causing inflammatory changes sufficient to per- mit, in the course of time, a disorganization or absorption of a portion of the vessel itself, and that ultimately it may become incorporated in the nodule. The nodules are generally irregularly cone shaped and are of variable size. In section they reveal a very dense struc- ture, the framework of which forms a close reticulum. Within the meshes are what appear to be leucocytes in various stages of disintegration, j AyL*.^ and free nuclei. Among these, at places, I ^P^f there can be seen small bodies of nearly the '-*^ ■■ same size as the nuclei and taking the stains Fig. 71. An iso- in the same way, but differing in form. At Med nodule show- one, portion of its circumference the substance twg the charac - . . , , , tenstic rough- of the body is seen to draw itself toward a ened ^ coral _ like point and in favorable preparations that point appearance of the has been followed some little distance as a mass {Fish). delicate filament. In most cases the filament remains un- stained, or, as observed in a Gram-eosin preparation, the club end may stain blue and the filament red. Exceptionally one may find a clear area or vacuole in one of the clubs. From the fact that the filament is not usually traceable to its central connection a more or less flagellate appearance is given to the fungus, which represents a condition not believed to exist. Not infrequently small spherical bodies are found not far from the clubs which take the stain readily and whose size is sufficiently small to admit of the possibility of their being spores. The free ends of many of the clubs point toward the periphery of the nodule, but this is not a constant feature. The framework of the nodule stains very slightly or not MORBID ANATOMY 289 at all and shows among the enmeshed corpuscles as a very irregular, distorted and somewhat glistening network. It is this portion of the nodule that gives the hard, gritty feeling, and is probably due to a greater or less deposition of lime salts along the reticulum. It appears that the framework of the nodule is composed of a mycelial net, which in the course of development has become more or less calcified. As a result of the treat- ment of the nodules with a 10 per cent cold solution of caustic potash, a very profuse and intricately branched fun- gus became apparent. The branching is of an irregular order. In places there is seen in the filament a central axis, which takes the stain, and around this appears a trans- parent or hyaline sheath of varying size. In certain of the teased preparations (Biondi-Ehrlich Fig. 72. The fungus. Toluidin stain) the wall of the filament, blue preparation {Fish). instead of being smooth and homogeneous, appears roughened, as if covered with very minute but numerous spinous processes. In the sections of the tissue in which the fungus appeared the substance of the filament was not uniform. In places it was drawn together in an irregular manner, with intervening clear spaces of greater or less area. In some places the filaments show distinct septa, but the latter are not common, Some of the club-like endings, especially those that are elongated, show a septum at the union with the filament proper. Scattered among and coiled around the ordinary filaments there have been observed much more slender ones apparently devoid of any external sheath. There have also been observed numerous small circular bodies of inconstant size. They have been seen lying freely 290 LEECHES in the meshes of the mycelium and also closely applied to the filaments. These bodies are not spherical, but thin and flat- Fig. 73. A section through a nodule showing its dense texture, with a portion of its peripheral zone made up of hyphtz with leucocytes in- terspersed. Methylene blue and eosin stain. No. 4 ocular, 8mm. objec- tive. Camera lucida drawing (Fish). tened, and some of them present a curved appearance, convex on the outer side and concave on the inner side. They sug- gest the possibility of having been closely applied to the fila. MORBID ANATOMY 2QI meats and have something of a scale-like arrangement. With possibly one exception, no trace of blood ^vessels has been found in the nodules. In the circumnodular tissue pathologic conditions exist, consisting of certain areas of tissue necrosis. There is an infiltration of the connective tissue with a great number of wandering cells. In some places there are well-defined nests in the stroma of the connective tissue, simulating, perhaps, a cancerous appearance. The character of the cells, which present a curiously vacuolated condition, would, however, tend to eliminate this view. The vacuoles vary in number and size, the average number being i to 12 in a cell. In some preparations numerous leucocytes, of the mono- nuclear and polynuclear varieties, had drifted away from the nodule. They were for the most part elongated, and in all the nucleus or nuclei appeared to be in a healthy condition. The cells contained numerous small bodies, which took a deep orange color with the Biondi-Ehrlich stain. In places adja- cent to these leucocytes there were frequently noticed a number of these small bodies apparently lying free in the tissue. No definite cell wall was distinguished in the leucocytes. The vacuolated cells are present in greater numbers than the heavily laden leucocytes. In the former nuclei were present and presented various phases of change. In some there is a single nucleus, which may be circular, crescentic, or in the form of a dumb-bell ; in others there may be two or more nuclei which in advanced cases appear only as remnants. In extreme cases no nuclei at all are visible. The wall of the wandering cell differs from that of the leucocytes proper in possessing an appreciable thickness. This thickened boundary apparently gives considerable rigidity to the cells, as nearly all of them are approximately circular in form. Their average diameter is about 8 microns. In one specimen there appeared to be large giant cells, measuring from 12 to 18 microns and apparently possessing quite a distinct cell wall. Within each giant cell there is some appearance of vacuolated cells, each with a single nucleus and fairly well-defined cell boundary. As 292 LEECHES many as eight or ten of these nuclei have been counted in a single giant cell. There is the possibility that these apparent giant cells are simply some of the vacuolated cells fused together, but the nuclei are well defined and take the stain very intensely, which is not commonly the case in the ordinary vacuolated cells. The connective-tissue cells surrounding the nodule show marked signs of degeneration, their cytoplasm in most cases being extremely vacuolated. Among these connective- tissue cells, which for the most part are quite branching and elon- gated, is another class of cells which are in general of an oval or elliptical form. The noteworthy appearance of these cells is the presence of numerous dots in the cytoplasm which take the methylene blue and toluidin blue stains very deeply. The appearance is, indeed, very much as if the cells were filled with micrococci. These are the granule cells of Waldeyer, or still further differentiated as the plasma cells, in contradis- tinction to the "mastzellen" or "food cells," which indicate an exalted degree of nutrition. The nucleus of the plasma cell takes the stain very slightly, or not at all, and is almost entirely obscured by the numerous "granules" in the cyto- plasm. These cells are well differentiated by the toluidin blue stain, as they take a deep purple color, while the sur- rounding cells are blue. Bitting has figured the jaw bone of a horse quite exten- sively affected with this disease. He believes that the lesions about the mouth result from the animal biting the affected areas on the body. Neyrick reports finding the inflammatory growths in the lungs of an affected subject, and Burke has reported them in the liver. There are no other lesions described in the internal organs although Neal writes that any tissue may be invaded. § 229. Treatment. On the ground that the fungus sup- posed to be the cause of this disease may be closely related to the ray fungus of actinomycosis, the use of iodide of potas- sium has been recommended. It is reported to be fairly suc- cessful. The efficiency of this drug as a specific needs further confirmation. REFERENCES 293 DESCRIPTION OF PLATE V. Fig. 1. Showing a young fungus embedded in the tissue {lip). Fig. 2. Showing scale-like bodies embracing the filaments. Fig. 3. Showing young branches of the fungus, and in one place the transparent sheath. Hematoxylin preparation. Fig. 4. Mycelium with scale-like bodies lying among the fila- ments. Hematoxylin. Fig. 5. Vacuolated filaments. Hematoxylin. Fig. 6. Branches showing a well-developed, transparent sheath. In places the axis of the branch is disconnected and occasionally there is a faint sign of a septum. Hematoxylin. No. 4 ocular, 2 mm. objective. Camera lucida {After Fish). REFERENCES. 1. Bitting. Leeches or leeching. Bullelin No. 25, Florida Agri- cultural Experiment Station, 1894. 2. Fish. A histological investigation of two cases of an equine mycosis, with a historical account of a supposed similar disease called bursattee occurring in India. Aunual Report, Bureau of Animal In- dustry, U. S. Dept. of Agriculture, 1895-6. p. 229. (This report con- tains full bibliography to literature on Bursattee. ) 3. NEAL. Leeching of horses and cattle. Annual Report, Bureau of Animal Industry, U. S. Dept. of Agriculture, 1887-8. p. 489. 294 INFECTIOUS DISEASES PNEUMONOMYCOSIS. § 230. Species of fungi. The literature contains a num- ber of reports of cases of mycosis in the lower animals as well as in man due to infection with different moulds. The genus Aspergillus seems to infect and to produce lesions in animals more frequently than the members of other genera. In fact, Aspergillusfumigatus seems to be the only important pathogenic species. The lesions encountered as a result of its invasion are largely restricted to the respiratory tract. Pneumonomycosis has been reported in a number of cases. Cadeac, Schneide- miihl, Friedberger and Frohner, Ostertag and Kitt have all called attention to mycotic pneumonia. Renon considers the lesions resulting from aspergillus infection as a pseudo-tuber- culosis which he would designate as ' ' Aspergillar tuberculo- sis." Aspergillar pneumonia is, however, quite rare. § 231. Description and method of cultivation of the mould. The aspergillus fungus is readily cultivated artifi- cially. It grows on most of the ordinary culture media used in bacteriology if the reaction is acid ; it develops poorly in alkaline media. The well-known Raulin's fluid is reported to be the best medium for its cultivation, especially where the aspergillus must be isolated from mixed growths, as in the ex- amination of sputum. Sabourand's* solution of maltose also gives good results. For ordinary use potato, with or without glycerin, gives excellent results. A paste made by rubbing up crumbs of stale bread in water is also a good medium. Growth is said to be more rapid, however, in Raulin's fluid than in any other medium, the mycelium appearing in from five to twelve hours and spores forming in from twelve to fifteen hours. The growth is first a velvety white, soon becoming a delicate bluish * The formula recommended by Ravenel is as follows: Maltose, 3.70 grams. Peptone, 0.75 grams. Distilled water, 100.00 c.c. To this may be added gelatin or agar to solidify it, the latter being preferable, a9 the aspergillus grows best, and forms fruit best at 37° to 39° C. ASPERGILLUS FUMIGATUS 295 green, which grows darker. On Raulin's fluid it changes after some days to a dark brown. Cultures on potato retain the green color for a long time, while those on bread paste become brown. The fungus retains its vitality in cultures for many months unimpaired. Its development has been reported when inoculated from cultures three or four years old. Spores do not form in a temperature below 20 C. and like the mycelium they require fresh access to oxygen for their best development. They measure 2.5 to 3/* in diameter. In nature the spores are widely distributed but seem to be especially abundant in grain and vegetable matter. They have considerable power of re- sistance to heat and to chemical agents. They -are killed by a temperature of 60° C. in five and one-half hours. In moist heat and in a solution of bichloride of mercury 1 to 1,000 they are destroyed in fifteen minutes. Aspergillus fumigatus is differentiated from other species by its color in cultures, the high temperature at which it grows, the size of its spores and by its patho- genesis. Aspergillus glaucus is the one most likely to be confounded with it. It may be differentiated from A. fumigatus by its ability to grow at low temperature, its deli- cate green color, the large diameter of its spores — 9 to 15/i — and its lack of pathogenic power. The mode of infection is through the respiratory tract. Only a small number of the spores in- spired are able to reach the alveoli, the greater number of them being arrested in the tracheal and bronchial secretions. Hildebrant has shown that, having reached the alveoli, they penetrate the epithelial lining without difficulty. Both animals and man seem to possess immunity to intestinal infection. Renon has produced it only a few times experimentally. The aspergillus does not form a toxin. Its pathogenic Fig. 74. Aspergillus fumi. galus in fruit. 296 PNEUMONOMCOSIS power is due entirely to lesions produced by the masses of mycelium which cause a necrosis of the cells and a leucocytic reaction which diminishes the functions of the organs, the final result being an enfeebled condition of the animal and a lessened resistance to hurtful influences. When fruit hyphae can form, the myriads of spores given off by them may be carried to other parts of the organ. In this way the foci rapidly multiply and practically the entire organ becomes invaded. The opinion held by some authors that in the mould mycoses there is "no fructification or actual multiplication" of the infecting agent and that the "number of the diseased foci corresponds exactly with the number of spores introduced, ' ' is erroneous both for the disease naturally contracted as well as for the experimental form. In the produced lesions, fruit formation is exceptional ; but it has been observed by Renon to take place only where there is full communication with the air. It has been observed only in the lung. It is extremely rare for aspergillosis to pass from one animal to another. The infection can only take place with the spores. Pneumonomycosis in cattle. Recently Pearson and Ravenel have described a very interesting case of pneumonomycosis in a cow due to A. fumigatus. As this seems to be the only care- fully described case in this species of animals listed in this country their description of the symptoms and lesions is very largely incorporated here. The case was in a Jersey cow six years old. She had been in poor condition for six months prior to bringing her to the Veterinary Hospital where "she was tested with tuberculin with no reaction. At this time she did not eat, was weak and depressed, respiration labored and from 40 to 90 per minute. Pulse rapid. Percussion of the chest walls gave a sound that if anything was clearer and louder than the normal percussion sound. Upon auscultation it was found that the vesicular and bronchial murmurs were consider- ably increased in intensity and accompanied here and there by sibilant rales. She coughed violently at times. Six days after she came to the hospital the breathing became more rapid and difficult and the pulse very much accelerated. The animal did not eat, grew weak rapidly and died four days later, or ten days after admission to the hospital. Composite drawing of section of Lung through nodule of aspergillus, origin. F. fibrin in alveoli. S. fruit hyphae and spores of fungus. (Ravenel.) MORBID ANATOMY 297 § 232. Morbid anatomy. The anatomical changes given here are restricted to the case of Pearson and Ravenel. The animal was much emaciated. The mucous membrane of the small intestine was catarrhal and showed a small amount of erosion. All the organs were normal except the lungs. The most striking feature on external examination was the extreme amount of emphysema. The lobules were separated from each other by 3 to 5 mm. and even at some distance from the borders one could see through the crevices by transmitted light. On the surface, the sub-pleural connective tissue was distended by large blebs. Upon palpation the lung crackled and numerous hard nodules could be felt. On section numer- ous dark red nodules appeared in the surrounding normal tissue. In each lung there were from fifty to sixty of these nodules, from 5 to 12 mm. in diameter. Most of them were dark red and closely resembled partially organized blood clots. However, on crushing a portion in glycerin between two slides and examining it under the microscope, they were found to be made up almost entirely of a felted network of mycelial threads. Between these large nodules there were numberless smaller areas of much the same color, 1 to 2 mm. in diameter, not per- ceptible to the touch as nodules but which were of the same character and were no doubt foci of recent origin. These were seen especially well in portions of the lung which were pre- served by Pick's method, the slight bleeching of the tissue bringing them into relief. On opening some of the inter- lobular emphysematous spaces, small, whitish, mouldy look- ing patches were noticed which bordered the cavity. Scrap- ings of these patches were made up entirely of perfect fruit hyphae, with myriads of spores. The diagnosis of a mould mycosis was in this way made at once and confirmed by cul- tures and examination of sections. Cultures were made on glycerinated potato, bouillion and plain agar, by opening a nodule with sterile instruments and tearing out a small portion of the center, which was transferred to the culture tubes and placed in an incubator at 39 C. Abundant growth was ob- tained on the potato by the end of thirty-six hours, white at first but soon changing to a yellowish and later to a dark green 298 PNEUMONOMYCOSIS color. The growth in the bouillon and agar was slow. Plates and flasks of bread paste were made, and these with potato were employed for all subsequent cultures. The formation of the fruit hyphae was studied. The spores measured from 2.5 to 3.5/i in diameter. By these means the culture was identified as the aspergillus fumigatus. The experiments on other animals were limited to the inoculation of one rabbit, into the aural vein of which one-half cubic centimeter of a suspension of the spores was injected. The animal died in forty-four hours and from the liver and kidneys cultures were recovered. All of the organs were examined in sections, but the mycelium was detected in two only. Microscopic examination. The nodules were hardened and embedded some in collodion and some in paraffin. Various staining methods were tried, hematoxylin and eosin, carbol- thionine, Gramandlithium carmine with Weigert's fibrin stain. Good results were obtained with all, but the carmine and Weigert gave the most beautiful picture and by this method the fungus was most perfectly demonstrated, the spores and mycelium taking on a deep purple color. The histology was studied largely in sections stained with hematoxylin and eosin. The bronchial epithelium was normal in places, but, for the most part, the columnar cells had been replaced by a sort of membrane, which appear to be made up almost entirely of a felt-work of mycelial threads. From this membrane hyphas grew out into the lumen of the bronchus, and here, owing no doubt to the supply of air, fruit hyphse arose, with perfect sterigmata and spores. There was no cellular nor other exudate and very little debris. The under surface of this membrane was of looser texture and contained some cellular in- filtration made up of round cells, leucocytes, proliferated con- nective tissue cells and red blood corpuscles. The adjacent structures were closely filled with a cellular infiltration with a quantity of mycelium of the same description, this extended to the neighboring alveoli, which under low power appeared to have preserved their outline but with greater amplification are seen to have lost all their normal structure, showing clumps of homogeneous, irregular masses which stained faintly with eosin and were probably of connective tissue origin. MICROSCOPIC STRUCTURE 299 In these areas the mycelium followed the alveolar wall as a trellis, the tissue seeming to afford no obstacle to its advance. Within the alveoli was a finely granular debris, with some coarser particles, probably the remains of cells. In sections stained with carbol-thionine large numbers of mast cells were seen in the alveolar walls. Bordering these degenerated areas were alveoli which had retained their normal structure and were filled with a network of fibrin holding in its meshes a few cells. In other parts of the sections were areas resembling those just described, but in which all anatomical land marks had been destroyed, so that it was impossible to tell whether or not the spaces seen were bronchi. Some sections show a widespread interstitial and alveolar hemorrhage, the blood showing a considerable increase in the number of leucocytes. The capillaries were congested and areas of edema with thickening of the alveolar walls were not un- common. There were peribronchitis and arteritis, while in some sec- tions arterial thrombosis was seen, the thrombus being pene- trated by mycelium, though no fruit was found. Areas were also found in which the alveoli were filled with a cellular exudate producing consolidation and thickening of the alveolar walls. Emphysema, both interstitial and vesicular, was marked and often extreme. Around the borders of the interstitial cavities is a distinct zone made up of red blood cells, leucocytes and homogeneous material, which was yellowish in fresh as well as in stained sections. These areas contain very little mycelium. All sections show a small amount of anthracosis. The appearance of sections varied in different nodules as they were taken further and further away from the center. In general the fungus was thickest at the center, so thick in many instances that the lung tissue was hidden entirely and grew less as we went outward. The tissue changes noted took place in a zone beyond the greatest growth of the fungus. In other nodules the fungus is evenly distributed throughout, following the alveolar walls. In these the tissue changes were slight. At times the fungus grew in dense, brush like clusters, closely resembling actinomycosis under low amplification. 300 PNEUMONOMYCOSIS This form was considered to show a marked reaction and resist- ance on the part of the animal and a lowered vitality in the fungus. When found it indicated that the aspergillosis was a primary and not a secondary or terminal affection. No giant cells were found in any section. Fruit formation was not observed in the substance of the tissues at any time. It was observed most frequently in bronchi, which were for the most part denuded of their epi- thelium, and next in emphysematous cavities, where it could be detected in clusters by the naked eye. Fruit was found in sections, in spaces the nature of which it was impossible to determine accurately. Wherever the formation of fruit was seen, there were innumerable free spores as well as those still attached to the sterigmata, but in no case were spores detected in the substance of the tissues. In many sec- tions, especially those from near the center of the no- dules, the mass of mycelium was so dense that the struc- ture of the tissues was obscured. Be- sides the dense growths resembling actinom y c o s i s al- W-¥ & rea dv described, ft§ ,' ' .'^*PfpP sV other brush like clus- i ^h* > J ters not unlike them & f . , Fig. 75. Necrosis in the kidney of a rabbit Were tre