Chapter XXVIII: Section XVII: The Communicable Diseases—part I (2)

Lesson’s Motmot (_Momotus lessoni_). The region above and behind the
right clavicle in front of the brachial plexus on the internal surface
of the thorax, exterior to the first and second ribs, and on the
internal surface of the ribs at the junctions of ribs with the alæ of
the sternum, there are many small, irregular, smooth, firm, yellowish
white nodules varying in shape from spherical to sweet potato and in
size from 3 × 3 mm. to 3 × 7 mm. These are found quite homogeneous on
cross section. They do not resemble tubercle or mould infection but
make one think of neuromata. There are also a few present in the left
lateral air sacs, close to but not joining the intestine. The lungs
are apparently normal. Histological section of the masses described as
distributed along the nerves consist of sharply outlined but not well
encapsulated masses made up of irregularly disposed bunches of large
cells with vesicular nuclei in a stroma of loose connective tissue
very inconspicuous in amount. There is also quite a number of small
round cells and a few leucocytes. The large cells first described have
the nucleus eccentric for the most part. Many of them have two nuclei
and a few three and occasionally a giant cell is observed. Blood
vessels have a very delicate wall and are frequently encountered in
the centre of these masses. Atypical mitoses can be found. Here and
there a seal ring placement of the nucleus can be found. A few
eosinophiles are present not definitely placed. Necroses, with large
quantities of nuclear fragments, are scattered irregularly through the
mass. The diagnosis rests between an infectious granuloma, false
neuroma and sarcoma. Tubercle bacilli were found by stain in great
numbers both within and without the cells.

Psittaci. Tuberculosis occurs in this order somewhat more frequently in the varieties whose habitat is the Eastern world, although South American birds also suffer from it in the characteristic manner. There seems to be no difference in the pathology of these two groups. Parrots present very beautifully the separate solid or semisolid nodules of avian tuberculosis, whether they be in the lungs, liver, or spleen. When the lung becomes riddled with masses, coalescence occurs and the whole mass turns into a cast of the hemithorax. Lesions in the liver are mostly isolated, but the spleen often appears like one large pink tuberculous nodule. The liver occupies as usual the first place in organic incidence.

Striges. Owls (and Struthiones—see below) present the interesting exception to the rule of intestinal origin of tuberculosis in birds. Perhaps the platting is incorrect but the birds in the order under discussion had older and much more advanced lesions in the lungs and thoracic serosa than they did in the abdominal organs. That this was true in all three examples is in itself noteworthy. Perhaps they possess less pulmonary and more intestinal resistance. One of these birds showed a small recent cavitation in the posteroinferior angle of one lung.

Accipitres. With one exception the cases of this order occurred among the Falconidæ, that is in hawks, buzzards, and eagles. Their lesions are usually generalized as indicated by the figures for visceral distribution, but that half the number should have the oldest, most prominent lesions in the lungs is curious. Their intestinal tuberculosis seems mostly of the diffuse infiltrative type.

Columbæ. These birds are obviously the most susceptible of all the varieties of which there are sufficient autopsies to make a comparison. Generalized nodular lesions emanating from the intestinal tract comprise their usual form, while most of the hepatic lesions are small miliary and nodular; occasionally one sees caseous masses destroying large sections of the organ. Their intestinal lesions may assume any of the three forms described.

Galli. This is an order of something over the average percentage incidence for the birds but containing families that seem very susceptible to tuberculosis. The small number of Brush Turkeys (_Catheturus lathami_) had 60 per cent. of the disease, while South American Cracidæ had 44 per cent. These two groups raise the incidence for the order. Galli as a group have generalized nodular tuberculosis originating by the intestinal route. This is especially seen in the Phasianidæ, while the very susceptible Cracidæ have much more prominent lesions in the lungs, often of a massive caseous type. It is really astonishing at times how much of the pulmonary tissue is occupied by infiltrate before death has supervened.

Fulicariæ are represented by a special contingent of rails and gallinules. Avian characters are well illustrated in the order. So too the succeeding order, Alectorides, another variety of shore birds, run true to the avian form. It is interesting to note that in the two cases from each of these orders tuberculosis and aspergillosis have been combined. The former has assumed the firm nodular type, while the mycosis has been of the air sac variety. The following case is worth citing as possibly illustrating infection _per cloacam_. There is, however, no trace of this bird having been with a male with the disease.

Demoiselle Crane (_Anthropoides virgo_) ♀ . General tuberculosis
including the oviduct. All organs are thickly beset by caseous
tuberculous nodules except the lungs which have only a few scattered
ones. The oviduct is, for its lower two-thirds, much enlarged, firm,
tough, pale yellow, thickly beset with caseous nodules; upper parts
uninvolved. The kidneys are definitely enlarged, irregular, almost
mulberry-like, brownish yellow, firm and tough. On section the lobules
are irregular, connective tissue increased, urates in pelves.
Tubercles in intestines seem to be wholly peritoneal. This seems like
a tuberculosis of genital origin judging from condensation of
tubercles in the lower abdomen (mass around cloaca). The ovaries are
not involved. Lungs and thoracic air sacs relatively free. The
pericardium shows a whitish thickening of both layers due to the
presence of whitish granules like urates. Histological section of
kidney shows the capsule not greatly altered. Glomeruli largely
negative but a few show hyaline capsular thickening of vacuoles in
tufts or fibrosis in tufts or obliteration of whole structure. Tubules
largely degenerated, distended or distorted. Interstitial tissue
between the tubules definitely but irregularly increased. No real
attempt at regeneration. Few vessels show perivascular fibrous change.
One tubercle seen.

Anseres. These birds present no especial features so far as percentage or organic incidence are concerned. The individuals are mostly geese and swans, ducks being somewhat more often affected by mycosis than by tuberculosis. However, both these diseases tend to assume the nodular type in Anseres so that the diagnosis should be supported by bacteriological discovery of the respective organisms.

Struthiones. The marked feature of this order is the prominence of the isolated and confluent nodules in the lungs, of apparently greater age, certainly of great size, than similar lesions in the abdominal viscera. Caseation of the avian variety is well illustrated in these birds. The thyroid body was involved in two of the three cases, the ovary in one. The representatives of the Crypturi, two tinamous, came at the same time and lived only a few months. Miliary tuberculosis of the small precaseous variety was the form exhibited by both specimens.

HISTOLOGY OF THE TUBERCULOUS LESIONS.

The initial and characteristic unit of tuberculosis, the miliary tubercle, seems to be constructed upon the same general principles in all cases of the disease and in all members of the zoological groups in our study and in a manner entirely comparable to that well known for man and for the domestic animals. There are, however, certain minute differences which are interesting and may at some time become important. It is customary to speak of the bovine tubercle and of the human variety, but there are also slight variations of the microanatomy of each of these, while one may find on occasion a tubercle of the human type in a cow and _vice versa_. Not all the domestic animals show the bovine form, although in sheep and swine it is approximated very closely. In the horse there is much greater tendency to a central softening and fibrosis is not so common as in the bovine tubercle. I have attempted to study the histological anatomy of each of the zoological orders, but it has not resulted in any profitable discovery. It is, however, possible to contrast the type commonly found in monkeys with that characteristic for man and the ungulates and also to emphasize the construction of the avian tubercle that it may be distinguished from mammalian tuberculosis and from avian mycosis.

FIG. 55. DIFFERENT VARIETIES OF THE MILIARY TUBERCLE.

A.—THE BOVINE FORM SHOWING THE NUMEROUS LANGHANS’ GIANT CELLS, THE
ABUNDANT SMALL EPITHELIOID CELLS. THE MODERATE NUMBER OF SMALL ROUND
CELLS, AND THE ACCOMPANYING CONNECTIVE TISSUE INCREASE. THERE IS
MODERATE CASEATION.
]

FIG. 55. DIFFERENT VARIETIES OF THE MILIARY TUBERCLE.

B.—THE HUMAN TUBERCLE WITH CENTRAL COMPLETE NECROSIS. TYPICAL GIANT
CELLS, ABUNDANT EPITHELIOID CELLS AND THE RELATIVELY NARROW SMALL
ROUND CELL MANTLE.
]

FIG. 55. DIFFERENT VARIETIES OF THE MILIARY TUBERCLE.

C.—THE TUBERCLE FREQUENTLY FOUND IN MONKEY TUBERCULOSIS. WITH RAPIDLY
ADVANCING CENTRAL NECROSIS ENCLOSING MUCH CHROMATIN DEBRIS. THE
ABSENCE OF LANGHANS’ GIANT CELLS. THE PRESENCE OF LARGE, PALELY
STAINING EPITHELIOID CELLS OF LANGHANS’ TYPE AND THE VERY SLIGHT
CIRCUMFERENTIAL REACTION.
]

FIG. 55. DIFFERENT VARIETIES OF THE MILIARY TUBERCLE.

D.—AN AVIAN TUBERCLE WITH CENTRAL SHARPLY MARGINATED NECROSIS
CONTAINING MUCH CHROMATIN DEBRIS. THE IRREGULARLY ARRANGED
POLYNUCLEAR CELLS TYPICAL OF AVIAN TUBERCLES. THE SMALL NUMBER OF
REGULARLY ARRANGED EPITHELIOID CELLS. THE PAUCITY OF SMALL ROUND
CELLS AND THE PRONOUNCED CONNECTIVE TISSUE MANTLE.
]

The tubercle of the Primates is a loosely constructed affair lacking the fibrous mixture of the bovine and the close cellular packing of the human form. Studied from the periphery to the centre, there will be found very little fibrocellular reaction in the immediately surrounding organ, while the mantle of round cells, rather prominent in the human tubercle, is often quite inconspicuous. The principal cellular component of the miliary granuloma is the large pale endo- or epithelioid cell, which is abundant, loosely arranged and without apparent purpose. In the centre is an irregular necrosis usually retaining some chromatic matter, probably the remains of recently destroyed nuclei, but this caseous midpoint does not assume the dense acid staining common for many milia. Giant cells of the Langhan’s or foreign body type are often entirely missing, and when present are scanty. There may be large cells, resembling the aforementioned epithelioid cells, with two or even three large palely staining nuclei, but these latter are arranged irregularly and not like the spokes of a wheel near the cell wall.

This picture suggests a rapidly growing inflammatory mass and indeed this is the type that tuberculosis follows in monkeys. In a few cases gross evidence of fibrosis in the serous surfaces and in the lungs has been observed, but they are too rare to permit one to think that connective tissue activity is an important part of the reaction of this beast to the disease.

The avian tubercle as it rests in the tissue seems like a sharply outlined almost encapsulated body. This is in part due to the homogeneity of its structure and in part to the fibrocellular condensation around the caseous part of the growths. Examined from without inward, there is a round cell mantle, between the elements of which course fine but easily perceptible fibrils; elastic tissue has been seen among them. The small cells continue more deeply than the fibres, to be succeeded in prominence by epithelioid cells of rather dense character, the nuclei especially seeming quite rich in chromatin and round. The rotundity of the nuclei remains not only in the single separate cells forming the middle zone of the cellular cortex, but can be found in the nuclei of the compound or giant cells which comprise the internal layer lying upon the necrotic centre. These giant cells are characteristic for the avian tubercle in assuming a form like syncytia with nuclei arranged in irregular radiating columns. This internal large cell area may completely surround the central necrosis or it may be interrupted by the large single cells. Tubercle bacilli are more common in and between single cells than multinuclear ones. Within the cellular zone lies the necrotic centre, often, indeed usually, full of chromatic debris. This centre is commonly quite amorphous but occasionally one will see what is probably the remains of a coarse coagulum. Between the necrosis and the cells one usually finds a split, a sort of separation of the gangrenous from the living part. Old tubercles with denser fibrous capsule retain this microanatomy in part, but the cellular zone gradually becomes thinner and thinner until all that remains is a narrow cortex of round cells and imperfectly retained multinuclear cells.

Tuberculous granulation tissue without definite milia consists entirely of the round cells with small vacuoles and a fine but definite fibrosis. Tuberculomata consist of cells of varying sizes with small round nuclei. Interstitial fibrosis is delicate and barely visible unless especially sought. Giant cells may be encountered but are not so large as in milia. Necrosis occurs but not in an orderly manner in relation to cells as in an isolated tubercle. Tubercle bacilli are very numerous.

FIG. 56.—PHOTOGRAPH OF YOUNGEST AVIAN TUBERCLE AFTER COMPLETE
FORMATION.
]

FIG. 57.—TUBERCULOMA, A SOLID TUMOR-LIKE MASS, CONSISTING OF CLOSELY
PACKED LARGE CELLS FITTED WITH RELATIVELY SMALL ROUND LOOSE NUCLEI.
THESE CELLS ARE CROWDED WITH BACILLI.
]

TYPES OF BACILLARY INFECTION.

According to experimental and statistical research, all the tubercle bacilli of the higher vertebrate classes can be infective for any member of these classes. Thus, for example, human bacilli have been found in many orders of mammalia and in birds. The bovine form has been found in swine. The lesson from this is that while the special predilection of a variety of the tubercle bacillus may be for one kind of animal, it is potentially a virus for other kinds. Hygienic principles have therefore been laid down at the Garden which aim at the protection of all specimens from every variety of tubercle bacillus. For this reason and because the laboratory has not attempted extensive research on bacteriology, few type determinations have been made and those at hand offer nothing new or unusual; they are noted here as a matter of record. Bovine bacilli have been judged by their slow growth and infectivity for rabbits, human bacilli by the reverse of these characters. Avian tubercle bacilli can be cultivated with reasonable ease directly from lesions not bearing a mixed bacterial flora, and grow in a yellow, moist, even, spreading colonization. In our two attempts at infection of guinea-pigs, no success was had, although Rabinowitsch and others had no difficulty in so doing; this strain may vary in virulence as do other tubercle bacilli. No avian culture was obtained from a mammal, but a bovine was found in a parrot and a human in a duck. Bovine bacilli were isolated once from a monkey (see page 496) and in another case of lymphatic type, bacilli of the short heavy blunt shape, supposed to be characteristic of this variety of the germ, could be stained. Monkey tuberculosis in our experience is usually due to the human tubercle bacillus, judging by the staining characters and two successful cultures.

DISCOVERY OF TUBERCULOSIS DURING LIFE.

Fully developed chronic tuberculosis may be recognized with reasonable ease in the human being and some domestic animals. The diagnosis rests largely upon the history and symptoms and partly upon the appearance of the individual and upon signs elicited by physical examination. There is good reason to believe that these latter methods are entirely applicable to certain wild animals, notably those that can be caught and held quiet, but because of their naturally great reserve many specimens offer little reason for suspicion as to their tuberculous condition until near death. Certain ungulates with chronic pulmonary disease get thin and weak but remain on their feet with good appetite and satisfactory discharges for many months. Primates, Carnivora, Rodentia and Aves not uncommonly come to autopsy with very good coats and without great emaciation and yet are heavily infected. It can be stated with fair positiveness that no chain of historical data or gross observations are certainly known to us as indicative of tuberculosis in the wild beast. Coughing is not necessarily characteristic of chronic pulmonary infection, although when continuous it rouses considerable suspicion, especially in the Ungulata. It is to be interpreted with care in all animals that have loose bedding as bits of straw or seeds get into the throat causing irritation; the dust of hay may cause coughing in horses.

However much chronic or fatal tuberculosis may be interesting from the standpoint of pathology or of zoological or visceral incidence, the most important factors in our knowledge of the disease are its early recognition and treatment, either for curative or hygienic purposes. Since we have learned that advanced lesions may exist in an animal without materially affecting its external appearance and behavior, it naturally follows that early cases, possibly of an “open” or infectious character are still less likely to give evidence of their existence. This is well recognized by veterinarians as being true of cattle, but is perhaps less well known, or possibly admitted, by those who handle the very susceptible monkey.

Upon a visit to a foreign garden I was told that experience alone is sufficient to enable an observer to detect tuberculosis, and that the disturbance entailed in physical examination and tuberculin tests is prejudicial to the well-being of all varieties, but especially the delicate ones. I learned later that they had the disease in their exhibition cages all the time but decided to put their method to the test. Shortly after my return from abroad a splendid specimen of Grivet Monkey (_Cercopithecus sabæus_) was condemned by the tuberculin test. He was well studied by the superintendent and two very experienced keepers, all of whom pronounced him one of the finest specimens they had ever seen, and stated that he was behaving quite normally. Despite their protests he was sacrificed, tuberculosis with early cavitation being found in the upper lobe of the left lung. Incidentally vague physical signs were found by auscultation, but as the monkey was unruly and had long pectoral hairs little weight was placed on the observation. However, it is frequently possible to make very thorough physical examination of the lungs of the more tractable specimens, diagnoses of pneumonia and bronchitis being frequently made in this and other parks, so that treatment may be instituted.

IMPORTANCE OF TRANSMISSION AND KNOWN SUSCEPTIBILITY.

Some light upon possible reasons for the poor condition of an individual animal is of course shed by a knowledge of the disease to which that particular variety is most susceptible, to which may be added the data obtained from previous deaths in the same group or enclosure. Thus, for example, a sickly monkey would be suspected of having tuberculosis or early osteomalacia, whereas no suspicion of these diseases would fall upon the marsupials. The same position would be assumed if a dove and a heron were out of condition.

In so far as enclosures are concerned, the matter is somewhat different. Whenever a case of tuberculosis occurs in a cage, the remaining specimens if any are removed and the place cleaned by soap and water and disinfectant and paint. The naked flame from a blast lamp is used when possible. Out-of-doors enclosures are vacated, spread with lime and allowed to lie fallow for as long a time as practicable. These methods have been in the main successful in clearing a cage of the disease, and all our experience demonstrates the effect of cage hygiene and the selection of non-infective replacements. A few places such as those occupied by doves and guans have not been freed of infection, if one judge by its appearance when new specimens are placed in them, but they may of course be due to the infection from elsewhere. The history of seven years in the new bird house where the hygienic conditions are excellent, seems to indicate that a cage thoroughly cleaned is no longer a source of danger, and that a repetition of tuberculosis in such an enclosure is due to its importation with new exhibits.

The spread of the disease to nearby cages seems to depend upon two factors. If the number of cases has been large and the infection virulent, immediately adjoining cages are involved, but the tendency to spread is directly proportional to the proximity of orders or families that have a high susceptibility for tuberculosis. This second factor seems to be the more important and is illustrated by our experience in one corner of the new bird house. In this area are exhibited certain doves and pheasants, among which are many cases, while the passerine varieties nearby are little affected. So too in the flying cage the disease has occurred in varieties with high general susceptibility. There are at the present writing ten orders on exhibition in this large enclosure and there have been more. An occasional case of the disease occurs, but only in the orders which show it elsewhere. The Herodiones, of which we have had nearly one hundred autopsies and many now are on exhibition, are always well represented in this cage and yet show no tuberculosis. In the ten orders mentioned above three show no cases of the disease.

These observations illustrate the spread of tuberculosis, especially to the most susceptible varieties, and how non-susceptibles under good hygienic conditions fail to become infected even when infected animals are near them. The freedom of activity in the large enclosure is doubtless an important factor.

The history of the past three years with regard to the control of tuberculosis in the small cages shows that twenty-nine were infected, but by the measures employed nineteen have remained free of the disease for one year; three of the remaining ten are known to have received newly arrived and possibly infected specimens.

The accredited method of transmission in birds, the swallowing of material soiled with the feces richly laden with germs, is the principal reason why infected enclosures and their immediate environment are the principal breeding places for tuberculosis. To be sure air currents may blow the virus around, allowing it to light upon food in other cages but this cannot be a great menace if for no other reason than that we have had no epizoötic outbreak of the disease, when there were groups of deaths in doves and guans.

Evidences with which to trace transmissions are much clearer in the birds than in the mammals with the exception of monkeys and some ungulates. Of course cases are perhaps too few in the carnivores and rodents to permit correct deductions but it is very rare that more than one case occurs in the same enclosure containing groups of these varieties. Nor do animals in adjoining cages seem to “catch” the infection. This observation does not suggest that any relaxation of hygiene need be allowed but probably it implies that not many bacilli are excreted by these animals; they cough very rarely. Groups of ungulates (bison and deer) are often known to be infected but just how it has arisen is seldom clear. Transmission from monkey to monkey has been observed so frequently that it cannot be doubted, nor will anyone wonder at it if reflection is given to the close personal contact of these animals during their natural behavior. They huddle, pluck lice from one another, take food from the mouth of another, bite and perform many other actions greatly facilitating the transfer of any virus. Bacilli may also be disseminated by coughing, drooling and with the fecal discharges, for which latter there seems ample opportunity since a notable percentage of cases have intestinal lesions. Monkeys do not seem to raise sputum and expectorate it but they do eject saliva from their lips.

Contraction of the disease from infected cages is believed to have occurred at least once in our experience but the lesson of complete sanitary cleaning of the enclosure learned from that happening, seems to have enabled us to forestall its repetition.

THE TUBERCULIN TEST.

Tuberculosis presents the greatest single problem among the specific infectious diseases which the director of a menagerie must attempt to solve. Even though one may possess a knowledge of its zoological distribution, clinical characters and pathological effects, these are insufficient criteria for its detection at a stage when the animal might be saved by treatment or, what is most important, removed from its companions that they might be protected. To this end there remains but a single procedure for the discovery of the existence of tuberculosis—the use of tuberculin in one of its forms by one of its methods of application. The use of this test in veterinary medicine needs no commentary, having made its place in clinical and hygienic practice for a quarter century or more. Armed with the knowledge of the satisfactory use of the toxins of tubercle bacillus in cows, Dr. Penrose, Dr. C. Y. White, Dr. A. E. Brown and Dr. Leonard Pearson began in 1901 a series of experiments with old tuberculin of Koch which have led to the development of a technique for its use in the detection of infected monkeys. These interesting and instructive animals, being known as highly susceptible since most of the collection died of the disease in those days, and being handled with reasonable ease by experienced men, were investigated as the most important specimens upon which to perfect the method. Other varieties have been studied since and I shall refer to them individually. The greatest amount of work and the most conspicuous success attended the observations upon monkeys and the results of this study are now in daily use in this Garden.

The work, conclusions and results, originated by Doctor Penrose, Doctor White, and Doctor Brown can be described as one of the most completely satisfactory series of observations in scientific medicine. Applying the principle that a tuberculous animal reacts to the injection of tuberculin by a temperature rise, the normal temperature curve of the monkey was studied, that of the tuberculous monkey determined by killing many specimens. This enabled them to state which animal was infected, which was not and to place on exhibition only healthy specimens. Added to this, strict hygienic principles in the housing and handling of the animals have resulted in the elimination of the disease from our exhibition house. Occasionally a case may develop, perhaps from feeding by visitors, but the matter is no longer a problem. I know of no more complete and satisfactory experiment and its practical application than this work, which is condensed in the succeeding paragraphs.[101]

THE TEMPERATURE OF MONKEYS.

The success of the tuberculin test in the lower animals as in man depends chiefly upon the alterations in temperature following the injection of the toxin. It is generally admitted to-day that a healthy animal’s temperature will not be affected by the introduction of this material. There are in addition changes in the pulse and respiration rate and in the physical signs but these are detected with difficulty and are much less definite than thermometric records. The first essential was therefore a thorough familiarity with the normal temperature of the monkey, a requirement which met with considerable difficulty from the beginning since the earliest observations revealed puzzling irregularities. This necessitated the establishment of certain regulations of technique which, after the preliminary tests, have been found satisfactory enough to continue until the present day. All monkeys are received in the quarantine rooms of the laboratory where they are observed by the officials of the Garden and of the laboratory and there they remain in separate cages until passed, as free from tuberculosis, to the exhibition house.

The handling of monkeys for the purpose of taking temperatures is a matter of no small importance since excitement will quite definitely increase the registration. We have been fortunate enough to have in charge of this work since its inception the same man, Keeper McCrosson, who is thoroughly experienced in the care of these beasts and who can catch and hold them with a minimum of disturbance. To him and to the interested laboratory helpers much credit is due. Small specimens like capucins and spider monkeys are caught with the gloved hand or with the protection of a piece of heavy cloth. Larger specimens may be caught in a net while strong monkeys are fitted with a collar and chain by which they are pulled into the corner of the cage and held, while the door is opened to permit a helper to catch the feet and arms. Two experienced men can take the temperature of any monkey that can be handled at all safely. The knowledge of how to do such work reduces the excitement of the animal and renders more accurate the observation of its temperature. During the period of temperature-taking food is given in small quantities and only after the record is made.

Temperatures are taken in all animals by rectum,[102] the thermometer, a separate instrument but always the same for each animal, well greased with plain vaseline, being passed along the anterior rectal wall and allowed to register for twice its indicated speed. During the preliminary work, special instruments of officially standardized accuracy were obtained by Doctor Brown but once the normals were obtained, ordinary good thermometers registering from 94°F. to 108°F. have been employed. If the record vary very much from the expected, such as the figures obtained at the same time on the preceding day, or if the rectum be crowded with feces, the instrument is shaken down and reintroduced. In order to facilitate timing of exposures we use sand glasses of three minute run.

After some experimentation by taking records at various times of day it was found that monkeys as a group do not have a uniform temperature during twenty-four hours but register a higher figure during daylight than during darkness. This is probably due, as I shall discuss, to the period of activity, not to the time of day. Figures obtained at various hours indicated that the highest and lowest temperature would be obtained if records were made at four-hour intervals at three, seven and eleven o’clock AM. and PM. To give the normal temperature of a monkey, the kind and the time of day are necessary adjuncts. Reference to forty- eight hour charts which are used for the illustration of normal records, and for contrast with tuberculin reactions later, will convey to the reader a better idea of the normal daily rhythm of the simian heat regulating system than would verbal description.

CHART A. ORANG UTAN (Simia satyrus). Non-tuberculous at death.
]

NOTE.—In the temperature charts degrees indicated by circles and
connected by dashes are from records made after diagnostic tests by
injecting tuberculin.

The anthropoid apes (Curves A and B) have on the whole a mean temperature nearer the human being than do the lower monkeys, but they too present daily variables far greater than man. The high point of their curve, at three PM., is in the neighborhood of 100°F. the lower point around 97.5°F. From these charts and other records it can be said that while the higher apes have a daily temperature curve with its high point at three PM. and its low point at three AM., there is in them not by any means the regularity of curve to be found in Cercopithecidæ and Cebidæ. Our records of temperatures in the Hylobates (_Gibbons_) are not extensive enough to quote but what we have approach those of the lower monkeys.

CHART B. CHIMPANZEE (Pan niger). Non-tuberculous at death.
]

Graphic curves of the normal temperatures of the various genera of Cercopithecidæ and Cebidæ present striking similarities in the regularity with which the daily rhythm is performed. In the seven genera of which we have accurate records the normal high points fall between 102°–103°F. and the low points between 99°–100°F. while the curve of the four-hourly steps is closely comparable. The curves D to J are composites from charts of animals that have been tested with tuberculin, which thereafter died or were killed and found free from tuberculosis. Not every individual chart that may come to hand necessarily follows the exact course detailed in these illustrative curves but these latter offer a guide as to what is to be expected of the different varieties. They show unequivocally the V-shaped curve of the temperature of the monkey during twenty-four hours.

CHART C. Composite chart of twenty-two non-tuberculous Lemures.
]

The Callitrichidæ or Hapalidæ have failed to show tuberculosis in our Garden and little has been done upon them. As a matter of record there is reproduced the only satisfactory chart at hand (K) taken very early in the researches. It shows a similarity to those of the higher monkeys; because of its very high afternoon record the animal was killed; no tuberculosis was found.

CHART D. Composite chart of eighteen non-tuberculous Cercopithecus.
]

The Lemures, being close to the Primates zoologically and presenting a high incidence of tuberculosis, were included in this study. Observations upon their normal temperature were hampered more than upon that of monkeys and even to-day we cannot feel the same confidence in the records. Irregularity is most marked and they seem easily disturbed by handling. Chart C shows a composite temperature for forty-eight hours of twenty-two proven non-tuberculous Lemures. The tendency for the “night drop” is certainly existent but with much less definiteness than in the Primates.

CONDITIONS WHICH MODIFY THE TEMPERATURE.

CHART E. Composite chart of seventeen non-tuberculous Macacus.
]

Observations by A. E. Brown[103] and by Simpson and Galbraith[104] would seem to indicate that the diurnal variation in monkeys is due to periodicity of activity. Doctor Brown found that the temperature of a night monkey is reversed, that it is higher during the dark than the daylight hours. See chart of Potto (_Perodictus potto_) chart L. The Scotch observers report that if the activity of day monkeys were reversed, daytime being made artificially dark and activity forced during the night, the temperature curves were likewise reversed.

CHART F. Composite chart of eleven non-tuberculous Papio.
]

Perhaps the most important discoveries of these investigators concerned the influence of excitement upon the temperature records. These observers indicate definitely that the greater the physical activity and nervous excitement the higher the thermometric record. We have noted that the substitution of a strange keeper who may not be gentle and tactful with the monkeys can serve to raise the temperature above the records obtained by an experienced man with whose methods the animals are familiar.

A knowledge of these facts dictates at least two important precautions on our part—our specimens must be kept under identic conditions peculiar to their kind, and surroundings must be established offering comfort with a minimum of annoyance in transfer and handling. To this end all specimens upon receipt are put into separate cages suitable to their size and allowed to become accustomed to their surroundings for several days before attempt at temperature-taking is made. Mention has already been made of the experience and interest of the principal keeper; the regularity of records is an attest to his work. Daily three o’clock afternoon temperatures are taken first to accustom the animal to the matter, before test records or tuberculin injections are made.

The existence of pathological states undoubtedly affects normal temperature curves and tuberculin reactions. Gastroenteritis has the effect of increasing the whole level and of making irregular the midday and afternoon records. Respiratory tract disease cannot be said to have a very definite effect; its most frequent influence seems to be to drive the night records lower so that there is a long fall between seven and eleven PM. and a long rise between seven and eleven AM.

THE TEST.

The preliminary rest of the new arrivals having passed daily three o’clock afternoon temperatures are taken until an even level is obtained; this requires usually four days but in very nervous specimens it may be much longer. The afternoon temperature course provides not only a means of teaching the monkey what is coming but supplies us with a high point record for comparison. When a new variety is received, a full normal twenty-four hour record is usually made. This preparatory routine being fulfilled, the animal is injected under the skin of the thigh or flank with freshly diluted mixed bovine and human tuberculin.

THE DOSAGE.

Early trials with this substance revealed the fact that a dosage based upon the weight in comparison to man failed to elicit a definite response whereas if based upon relative weight of cow was too large. The finally determined quantity was arrived at, as was the case in early human and bovine work, by experiment and trial and was as follows: A monkey of five to ten pounds (2.3 to 4.5 kilos) received an initial dose of 1. milligram and for each additional five pounds (2.3 kilos) 0.5 mg.; this is 0.2 to 0.4 mg. per kilo. The amount given to man varies from 2. to 5. mg.; if the body weigh 60 kilos this is 0.03 to 0.08 mg. per kilo. Cows are given usually in this country 400 mg. or, for a cow of 250 kilos, 1.6 mg. per kilo. In the early work, doses comparable to the figure for man failed, whereas at least two animals died very quickly after 1.+ mg. per kilo; 5. mg. was the original high dose. While the death of a monkey after a large dose was of no moment and was perhaps desirable, it would only be the heavily diseased specimens and this would give no criterion upon which to judge the appropriate dose for all. Experience seems to warrant us in continuing with our present figures since all tuberculous monkeys have reacted to it. Subsequent cases for retest are increased from 50 to 100 per cent. depending upon the size of the monkey, the very robust and vigorous ones receiving an increase represented by the higher figure. One monkey injected eight times has risen from 1. to 24. mg. with constantly a negative response over a period of nine years.

Doses for Lemures are relatively higher, averaging 1.5 mg. or about 0.5 mg. per kilo; they are increased in the same manner as above.

THE TEMPERATURE TAKING.

Injections are usually made in the late forenoon, temperature records being started at the usual three PM. hour and continued at four-hour intervals for forty-eight hours, giving thirteen records over two days, a time period presenting two complete cycles of diurnal variation. This was found necessary because certain cases do not react during the first day. Explanation of this was sought in the nature of the lesion but could not be found further than that mild early lesions may give it but it cannot be read as indicative of low activity since one case of laryngeal tuberculosis had this “delayed reaction.” At times it has seemed to occur when the injection fluid formed a blister under the skin, a pocket in the areolar subcutaneous tissue, whence absorption would be slow. Whatever the correct explanation, experience has justified the recording of temperatures for full forty-eight hours.

CHART G. Composite chart of five non-tuberculous Cynopithecus.
]

CHART H. Composite chart of eleven non-tuberculous Ateles.
]

THE REACTION.

The experience gained with these monkeys supported definitely the general opinion that tuberculin injected into healthy animals will not disturb the temperature but will produce decided changes in that of tuberculous animals. The reaction in the tuberculous animals may assume several characters, of which usually two are combined in a chart. The commonest and most convincing is a definite rise in the first twelve hours, amounting to one degree or more; rarely it may be three degrees (W). This is followed either by a maintenance of a high level or an attempt to perform the night drop. It may be said that in general there is an abortive attempt in nearly all tuberculin reactions to simulate the V of the normal cycle; this can be seen in charts M, N, O and P. Another rise may be attempted during a similar period of the second twenty-four hours or the whole course may at that time approximate the normal. A modification of this type of reaction is the performance of the whole daily rhythm on a high level, set, as it were, by the initial three PM. record. This form is confusing at times and has been responsible for at least one of our mistakes. Combined with this high level of curve is a tendency for the second twenty-four hours to be higher than the first day (See Variegated Cebus Q and Sooty Mangabey R and Chacma Baboon W). The second type of reaction, illustrated by chart S, fails to resemble the normal daily cycle of the monkey temperature but has sudden rises and falls as its characteristic feature. We have learned to look with suspicion on all charts with sudden marked changes of record even if they follow in the main a rhythmic course. The sudden fall exhibited by a very sick monkey illustrated by Grivet Monkey (T) and Campbell’s Monkey (U) is a bad sign. It has been met more often in advanced caseous pulmonary tuberculosis than in any other tuberculous lesion. On two occasions it has been seen in the absence of tuberculosis so that retest is indicated if the specimen be valuable; such animals however rarely survive the disturbance incident to the test as they are usually suffering with some serious disease. Illustrative charts of several positive reactions serve to elucidate their character better than description. If comparison and contrast of the normal and post- injectional temperature be made, the conclusions are definite.

CHART I. Composite chart of eight non-tuberculous Cercocebus.
]

CHART J. Composite chart of twenty non-tuberculous Cebus.
]

It cannot be said that any type of reaction indicates a particular form of disease although the last type, the falling of the temperature beyond the thermometric registration point, usually means advanced lesions especially of the caseous pneumonic form. A very small lesion may give a definite reaction as in Cebus (V).

CHART K. GEOFFROY’S MARMOSET (Leontocebus geoffroyi). Non-tuberculous.
]

The examples given are those of a definite character but there are many charts that vary from the normal upon which a decision is extremely difficult to make. Such animals are held in quarantine to be retested after the lapse of three months. Early in the work a suspected specimen was reinjected after two weeks, failed to give a reaction but died in about two months of tuberculosis. The nullification of the test by previous injections of tuberculin is well known. Three months’ interval permits a disappearance of the non-sensitivity and allows any latent tuberculosis, possibly stimulated by the toxin, to develop. Repetition upon the same monkey has occurred as high as ten times without apparent harm.

CHART L. POTTO (Perodicticus potto). Healthy.
]

There are sometimes in human beings local reactions at the point of injections. These have been entirely lacking from our monkey specimens. Nor have we ever seen secondary tuberculous lesions appear at the point of the needle-stick. Aseptic syringes and generally cleanly technique have also protected against local abscesses. When an animal is injected he may scratch or pick at the spot for a minute or two but thereafter seems to ignore it entirely.

CHART M. MONGOOSE LEMUR (Lemur mongoz). Tuberculous.
]

CHART N. BLACK HANDED SPIDER MONKEY (Ateles geoffroyi). Tuberculous.
]

RESULTS.

The value of the test can best be estimated by a recital of the mortality of monkeys, from tuberculosis, since its inception. Before the test was started practically every monkey in the collection for sufficient length of time to be exposed died from the disease. The average duration of exhibition life of all specimens up to 1903 did not exceed eleven months. The time has risen almost uninterruptedly until now it is thirty-five months. There are, at time of writing, sixty-eight specimens in the cages which have been on view from one to one hundred and eighty-five months with an average of fifty-four months. These figures speak for themselves as evidence of the reduction of infection. The average mortality from enteritis and degenerative bone disease has remained about the same through all these years. Percentage figures such as are recorded in our yearly report are misleading because all monkeys written into the property record of the Garden are listed and since some of these specimens remain in quarantine, they do not properly belong to the exhibition collection. Up to 1906 when the test technique was perfected nearly all deaths were due to tuberculosis, the figure for 1906 (including experimental animals) being 78 per cent. However from February 1906 to October 1907 and from then until May 1910 no case of tuberculosis occurred in the exhibition cages and both deaths at these given times seem like infection from visitors. During the next three years thirteen monkeys died of the disease in the exhibition and many more in quarantine. By 1913 the outbreak was stamped out. Its explanation is not so very far to seek. In the fall of 1910 we obtained some suspected monkeys which were kept in one of the quarantine rooms. After repeated testing two were passed. From them five cases are known to have originated and it was not until in 1912 when the whole exhibition house was cleaned of specimens, thoroughly disinfected and fumigated and until every specimen was retested, that the infection passed. In 1914 no cases occurred, while in 1915 a case either slipped through undetected or was a visitor infection; 1916 two cases, 1917 one case, 1918 one case (see orangutan charts), 1919 and 1920 none and 1921 one case, 1922 no cases. Since 1912 the whole monkey collection has been tested every two years, a method which enabled us to catch a small group in 1916 and has protected the collection since then. Three of the six monkeys specified above were never placed free in the general cages of the exhibition house, they being segregated in smaller cages. One, the orang, was with its mate in an isolated cage. The other two were in larger cages and their history suggests visitor infections.

CHART O. RHESUS MACAQUE (Macacus rhesus). Tuberculous.
]

CHART P. ORANG UTAN (Simia satyrus). Tuberculous.
]

We have never underestimated the possibility that an occasional very early case might evade detection by this test but we believe the history just outlined warrants us in depending upon it for the protection of the exhibition. By the tuberculin test we have detected the existence of the disease in twenty-three per cent. of specimens. Every condemned specimen, forty-one, showing tuberculosis, gave a positive test. Fifteen monkeys condemned on their temperature charts failed to show the disease. Eight per cent. of the tests resulted in suspicious charts, and the animals finally died of the disease in quarantine. Fifty-six tuberculous monkeys died on exhibition, of which thirty-one were original there and twenty-five their contacts. Twelve of the thirty-one were in the early stages of the work, thirteen due to our misadventure of 1910 and the remainder, six, scattered over nine years.

CHART Q. VARIEGATED CEBUS (Cebus variegatus). Tuberculous.
]

CHART R. SOOTY MANGABEY (Cercocebus fuliginosus). Tuberculous.
]

Another interesting experience concerns the exhibition of a group of Rhesus Macaques in an open “band stand” cage. The idea arose in an attempt to find a separate exhibition space for some good specimens that gave unsatisfactory charts, with the purpose of applying at the same time the “open air” treatment if tuberculosis existed. The experiment has been entirely successful since in the eleven years during which this enclosure has been used there has been but a single case of tuberculosis among twenty-six monkeys. Curiously enough this exception gave a good chart and we suspect it was a visitor infection; no secondary case arose from it. The animals housed in this cage keep in excellent condition, their coats responding to our severe winter by increasing in thickness and glossiness. Frozen toes, fingers and tails are sometimes seen but these monkeys seem just as happy as the others. Breeding is active and the young are lusty and husky. Practically the only deaths are due to accident, or to abuse of old and less vigorous members of the colony. We are unable to give comparative exhibition periods and death rates for monkeys in the large house and this open cage because some specimens have been changed from one to the other but it is certain that the appearance of the “band stand” monkeys is better than those in the house and there are four of eleven animals in the former which have been there eleven years and only four among the seventy in the exhibition house for that length of time.

CHART S. VERVET MONKEY (Cercopithecus lalandii). Tuberculous.
]

CHART T. GRIVET MONKEY (Cercopithecus sabæus). Tuberculous.
]

The results of the foregoing work seem to demonstrate that the tuberculin test permits the separation of tuberculous and non- tuberculous monkeys and that its employment serves the purpose of maintaining a healthy exhibition by excluding infected specimens. These experiences form further corroboration of the facts that tuberculosis begets tuberculosis, that a healthy individual is not a source of infection. It follows that an obviously tuberculous animal should not, need not, be a source of danger; the hidden or unrecognized case is the menace. There is little or no problem when an unequivocally good or bad temperature record is obtained; it is when there are slight variations from the standard for the group that decision as to the disposition of the specimen must be made. Nearly always such specimens are retested until the records are definite. If they be constantly irregular the animal is either sacrificed or exhibited in a separate cage far from other monkeys. It is by the sacrificing of infected specimens or the segregation of suspected ones that our collection is kept clear of disease.

CHART U. CAMPBELL’S MONKEY (Cercopithecus campbelli). Non-tuberculous.
(See page 533).
]

Hygiene of a general character must be maintained also. Our quarantine rooms are disinfected by formaldehyde and mechanical cleansing after every case detected as tuberculosis, and painted every two years. Monkeys associated with infected ones, are retested and then given a bath of carbolized water before being put on exhibition. The exhibition house is mechanically and chemically disinfected at the injection time each two years. All keepers are examined for tuberculosis upon beginning their employment and those handling monkeys, periodically thereafter. When a case of tuberculosis dies, all animals in the same and adjoining cages are removed for retest and the enclosure scrubbed and disinfected.

CHART V. WEEPER CEBUS (Cebus capucinus). Tuberculous.
]

There is a source of tuberculosis upon the importance of which we can only speculate—the visitor. There were two isolated cases in animals which had passed the test with unexceptionable charts, three and four months on exhibition; curiously enough no other cases occurred in their cages. These we have laid to visitor infection since no previous exposure can be traced for the specimens and no secondary cases occurred.

I can conclude this discussion of the tuberculin test and of the control of tuberculosis by its use, by mentioning the possibilities for the solution of the problem in man. While the eradication of the disease cannot be accomplished as easily as if a potential source could be eliminated by sacrifice, it will come in direct relation to the earliness of detection of infection and isolation of the sources of danger. Not so much the cough-racked consumptive but the unrecognized early lesion whose bearer hawks and spits in public places or at home, unaware of his malign power!

CHART W. CHACMA BABOON (Papio porcarius). Tuberculous.
]

THE SKIN AND EYE TESTS WITH TUBERCULIN.

The first of these can be dismissed briefly, for in a few cases it was absolutely of no value. A known tuberculous monkey was injected _into_ the skin of the chest with 0.5 mg. of old tuberculin. The small bleb disappeared in a few hours and was followed by no reaction whatsoever. Other attempts likewise failed, some of them I believe due to the technical difficulty of injecting into the skin. This tissue is very thin, delicate and loose at the less hairy places where a reaction might be read—arm, chest, abdomen. The hairless parts of the rump might be used, but are so often scratched and soiled with dirt that readings might be misleading. The Von Pirquet test was done on the first mentioned specimen and was likewise negative. His tuberculin test was afterward positive.

CHART X. BLACK APE (Cynopithecus niger). Tuberculous.
]

The ophthalmic reaction is highly spoken of in the New York Zoological Park and has been used elsewhere. It was tried by me at the time Doctor Blair first discussed it, but with variable results. One set of two monkeys was treated with Calmette’s purified tuberculin into the conjunctival sac and given a subcutaneous dose of old tuberculin. Another set received 1 per cent. old tuberculin into the conjunctivæ and the usual subcutaneous dose. Although all these monkeys gave a temperature reaction only one gave a conjunctival reaction. Fearing that the two tests simultaneously might be an unfair trial, another poor specimen was given an eye test which resulted negatively; a later subcutaneous test and autopsy revealed the disease. Because of these experiences and the fear that any reacting conjunctivæ might become secondarily infected from the uncertain personal hygiene of the beast, we decided to omit this method and rely upon the temperature test.

PATHOLOGICAL EFFECTS OF THE INJECTION OF TUBERCULIN.