Part 6

Stefansky, W. K., ’03. Eine lepraähnliche Erkrankung bei Wanderratten. Cent. f. Bact., Bd. 33, Orig. S. 481. Baum. Jahres., Bd. 19, S. 496.

Endnote 302:

Rabinowitch, L., ’03. Ueber eine Hauterkrankung der Ratten. Cent. f. Bact., Bd. 33, Orig. S. 577. Baum. Jahres., Bd. 19, S. 496.

Endnote 303:

Dean, G., ’03. A Disease of Rats caused by an acid-fast Bacillus. Cent. f. Bact., Orig. Bd. 34, S. 222. Baum. Jahres., Bd. 19, S. 494.

Endnote 304:

Dean, G., ’05. Further Observations on a Leprosy-like Disease of the Rat. Jour. Hyg., vol. 5, p. 99.

Endnote 305:

Tidswell, F., ’06. Note of Leprosy-like Disease of Rats. Lepra, vol. 6, p. 197.

Endnote 306:

English Plague Commission. Jour. Hyg., vol. 7, p. 337. Cited by Wherry.

Endnote 307:

Wherry, W. B., ’08. The Leprosy-like Disease among Rats on the Pacific Coast. Jour. Am. Med. Asso., vol. 50, No. 23. Cent. f. Bact., Ref. Bd. 42, S. 664.

Endnote 308:

Wherry, W. B., ’08. Notes on Rat Leprosy and on the Fate of Human and Rat Lepra Bacilli in Flies. Public Health Reports, U. S. P. H. and M. H. S., vol. 23, p. 1841. Jour. Infec. Dis., vol. 5, p. 507.

Endnote 309:

Mezincescu, D., ’08. Maladie Lépreuse des Rats et ses Relations avec la Lèpre Humaine. Compt. Rend. Soc. Biol., T. 64, p. 514. Cent. f. Bact., Ref. Bd. 42, p. 664.

Endnote 310:

McCoy, G. W., ’08. Rat Leprosy. Public Health Reports, U. S. P. H. and M. H. S., vol. 23, p. 981. Jour. Am. Med. Asso., vol. 51, p. 690.

The writer wishes to express his gratitude to Dr. George Dean for histological material from the natural and experimental disease, and to Doctors Wherry and McCoy for rats inoculated with the disease and normal animals for its propagation.

BACTERIAL DISEASES OF THE RAT, OTHER THAN PLAGUE AND RAT LEPROSY.

By DONALD H. CURRIE,

_Passed Assistant Surgeon, United States Public Health and Marine-Hospital Service_.

So far as is known, the several species of rats that are found about the habitations of man—_Mus norvegicus_, _Mus rattus_, _Mus alexandrinus_, and _Mus musculus_—are naturally subject to but few bacterial diseases as compared to some other animals. Interest in this matter has only recently been aroused, owing to the rôle played by the rat in the spread of bubonic plague. When we consider the immense number of rats that have been examined in connection with antiplague work by trained investigators in recent years, and that to many investigators the thought must have come that the discovery of some rat destroying bacterium would be of the greatest utility, it appears more than probable that few such natural diseases exist.

Plague is the one natural bacterial disease that has demonstrated its power to destroy these rodents in numbers sufficiently large to attract general attention; scientific investigation has only been able to add a few other bacterial diseases, and these are probably for the most part rare ones, causing the death of a very small percentage of the total rat population.

Of the “natural” diseases (i. e., spontaneous, in distinction to diseases that can only be produced artificially, under laboratory conditions) the following are the more important ones:

Rat plague and rat leprosy, which are made the subject of special chapters in this publication, must be mentioned as the most important diseases observed among rat populations.

DANYSZ’S BACILLUS OR BACILLUS TYPHI MURIUM OF LOEFFLER.

These are probably identical organisms, differing only in their degree of virulence, at least their pathogenicity alone distinguishes them in the laboratory. They are both members of the paracolon group. They produce a diffuse cloudiness in broth, ferment glucose but not lactose or saccharose, do not liquefy gelatin nor coagulate milk.

_B. typhi murium_ (Loeffler) is fatal to mice (_Mus musculus_), but not to rats. M. Danysz isolated a bacillus during an epidemic of field mice which was indistinguishable from the above, except that its virulence was capable of being raised to a point where it would destroy a relatively large percentage of rats inoculated with it by feeding. We see from this that, strictly speaking, it is not a natural disease among rats, still there are cases where its virulence has for a time remained high enough to infect a considerable per cent of rats exposed to those that have sickened of it. Not only is this true in cage experiments, but probably it sometimes occurs in nature after the virus is once thoroughly introduced (an article by M. Danysz; also experience of this service in plague in San Francisco, 1903 to 1905), and may therefore be grouped under the list of “natural” infections. This bacillus is unfortunately of a very unstable nature, in so far as its virulence is concerned; some cultures appearing to be avirulent, while others cause an all but absolute mortality among the rodents eating it.

The duration of the disease is variable and appears to depend somewhat on the size of the dose received, as well as virulence of the culture. We have seen death in thirty-six hours or less following ingestion. On the other hand, it may occur in two weeks. Usually it occurs in from six to twelve days. In a typical case when the animal has lived ten or twelve days it is much emaciated, its tissues are dry, and intestinal hemorrhages are sometimes met with. When the disease is much prolonged a pustular eruption may be present over the skin. The organism can often be isolated from the heart blood by plating, such isolation alone affording means of diagnosis. The only present interest this organism has is as a means of destroying the rat. It was believed to be harmless to man, but more recently cases of human illness have been reported that were believed to have been caused by infection with this bacillus.

PNEUMONIA.

We have recently seen a case of lobar pneumonia in a rat in which a diplococcus was present in pure culture. Possibly connected with this is a condition of abscess of lung, which is not very uncommon. The cavity is filled with a creamy or cheesy matter composed of broken-down cells. Often these cavities break into the pleura. Several morphological types of organisms are found, but from their variation this laboratory has regarded them as secondary or accidental, especially as we have failed to demonstrate that this material was infectious.

STAPHLOCOCCUS ABSCESSES.

These are rather common and may occur subcutaneously or in the superficial muscles of any part of the body.

BACILLUS PSEUDO-TUBERCULOSIS RODENTIUM (PFEIFFER).

This organism that infects rats is of interest from its close resemblance to the plague bacillus. It is difficult to distinguish the two organisms by ordinary cultural or animal tests. The earlier writers claimed that _B. pseudo-tuberculosis rodentium_ could be differentiated by its power of coagulating milk, but more recently this difference has been found to be an inconstant one.

TOYAMA’S BACILLUS.

Toyama has described an organism which he states is pathogenic for _Mus rattus_, field and house mice (_Mus musculus_), but not pathogenic for _Mus norvegicus_.

It causes congestion of lungs, enlargement of lymph nodes, especially in the neck, and enlargement of the spleen. It was isolated from a natural epizootic among _Mus rattus_. It is a nonspore-bearing bacillus, without capsule, stains without showing bipolarity, and grows upon ordinary media.

Among other bacteria that have been described as causing diseases in rats may be mentioned:

_Von Schilling’s bacillus_, allied to Danysz’s organism.

_Bacillus “Eris,”_ a member of the colon group.

_Bacillus muris_, a member of the _B. diphtheria_ group.

Of the bacteria that show virulence for rats under laboratory conditions, but, so far as is known, cause no spontaneous outbreaks, the following are the best-known examples:

_Bacillus bovisepticus_ produces a fatal disease bacillus of swine erysipelas (especially for albino rats), and the bacillus of tetanus.

Of the higher fungi (not strictly bacterial) we have:

_Streptothrix maduræ_ produces local swellings when inoculated artificially.

It has been stated that rats occasionally suffer from a disease similar or identical to the affliction in man known as favus (_Achorion Schönleinii_).

INFECTIONS OF MICE (MUS MUSCULUS).

This species of _Mus_ is very susceptible to a large number of bacterial diseases when inoculated under laboratory conditions. The following are some of the best-known examples:

_B. murisepticus_, _Staphlococcus pyogenes_, _Streptococci_, _Diplococcus pneumoniæ_, _B. pneumoniæ_ (Friedlander), Diplococcus of pleuro-pneumonia of horses, _B. Typhi murium_, _B. anthracis_, B. of malignant edema, _B. tetani_, _B. mallei_, _B. diphtheriæ vitulorum_, _B. bovisepticus_, _B. suisepticus_, the bacillus of Mereshkowsky, and many others. The last-named organism has been utilized to a limited extent for the destruction of mice about dwellings.

ORGANIC DISEASES OF THE RAT, INCLUDING TUMORS.

By GEORGE W. MCCOY,

_Passed Assistant Surgeon, United States Public Health and Marine-Hospital Service_.

The lesions described here are those that have been found in the routine examination of rats for plague infection in the federal laboratory at San Francisco during the past year, in which time approximately 120,000 rats have been examined.

As the subject had no special bearing upon the plague investigations, but little time was spent in examining and recording the nature of organic lesions that were observed. Notes, however, were made of many of the conditions which were encountered, and these notes have been used as the basis of this paper.

It is well known that various lower animals are subject to some of the so-called organic diseases from which man suffers, and not a little experimental work has been done in endeavoring to establish in animals certain of the lesions commonly found in human pathology.

_Usefulness of wild rats for laboratory purposes._

We would call special attention to the fact that wild rats suffer spontaneously from cirrhosis of the liver, fatty degeneration of the liver, nephritis, and calculi of the urinary tract, and would, therefore, probably furnish excellent subjects for the experimental investigation of these diseases.

The objection may be made that the very fact that these animals do suffer from these diseases spontaneously makes them unsuitable for experimental purposes, as one could not be certain that any lesions found were not spontaneously developed rather than that they were due to the conditions imposed in an experiment. In reply to this objection we would say that the most of these organic lesions occur so rarely in rats in nature that one could almost ignore them.

The ease with which wild rats are obtained and the readiness with which they adapt themselves to the conditions of life in captivity are factors which should make them more extensively used for laboratory purposes than is the case at present. We have described (New York Medical Journal, Feb. 6, 1909) the methods that have been found useful in keeping and handling these rodents. Without going into details here we may say that if rats of approximately the same size are kept together in a cage there will be practically no mortality from fighting. Of course, there should be no overcrowding. Rats should be fed meat or cheese and plenty of green food such as carrots or cabbage. In our experience in San Francisco it has been found practicable to keep for a year one series of ten inoculated wild rats without any loss. Judging from my experience I have no hesitancy in saying that the natural mortality in the laboratory is higher among both guinea pigs and white rats than it is among wild rats.

It is almost certain that some of the lesions described below are due to animal parasites, or to bacteria, but no such causative agent has been identified.

CIRCULATORY APPARATUS.

We have seen no lesion of the circulatory system with the exception of a few cases of pericardial effusion. The most extreme example was one in which the pericardial sac was dilated to such an extent that it filled almost the entire cavity of the thorax. The fluid in the sac was blood stained and there were a number of recent adhesions between the visceral and the parietal surfaces of the pericardium.

PULMONARY APPARATUS.

Pleural effusion, as is stated in another place, is an important sign of plague infection. A clear, watery effusion has been found in a few cases in rats that were not plague infected.

One example has come under observation of a large _Mus norvegicus_ that had both pleural cavities almost entirely filled with a milky fluid. The lungs were compressed and congested. Microscopical examination for animal parasites and for bacteria was negative.

A condition of consolidation of the lungs which closely resembles the stage of gray hepatization in lobar pneumonia in man is seen occasionally. The area may involve half of a lung. Upon microscopical examination one finds the air spaces and the small bronchi filled with leucocytes. There was no cavity formation in any of the cases that have come under observation.

Two relatively common purulent conditions of the lungs are encountered. In the first of these, large and more or less distinctly loculated sacs are found, which are filled with yellow semifluid caseous matter; in the second, the lesion is of much the same nature, but the material in the sac has the consistency of tough, ropy mucus. Aside from the main focus of this sort, numerous smaller areas of the same nature are seen scattered through the otherwise normal parts of the lungs. The extent of some of these purulent processes is remarkable. We have seen cases in which the chest cavity was almost filled by the lesions described.

DIGESTIVE TRACT.

CIRRHOSIS OF THE LIVER.

It was a matter of surprise to find well-marked cases of hepatic cirrhosis in rats, as this disease in man has been pretty generally regarded as very largely due to intemperance in the use of alcoholic beverages. Such an etiology hardly accounts for the condition in the rat. The lesion is by no means rare; well-marked cases are encountered probably as often as once in a thousand rats. We have never seen it in a young rat, probably because the condition develops slowly and the rat reaches adult life before the process is complete. The organ is usually somewhat yellowish, very firm, often, but not always, somewhat shrunken in size. The surface of the whole organ is covered with small, rounded elevations; a typical “hobnail-liver” in miniature.

Microscopically we find various degrees of increase of connective tissue. In a well-marked case the capsule is much thickened, and heavy bands of connective tissue run through the organ in every direction. This increase of connective tissue is most marked in the vicinity of the portal vein and its companion vessels. The microscope will show that in some fields over half of the structure is made up of fibrous tissue. The liver cells that remain appear to be normal. The presence of animal parasites in the liver is frequently associated with a considerable hypertrophy of the connective tissue of the organ. In a majority of cases of hepatic cirrhosis, however, no parasites are to be found. One case has come under observation in which the surface of the liver was covered with a number of flattened, wart-like elevations. Upon section nothing was to be found to account for this except an enormous overgrowth of connective tissue.

FATTY DEGENERATION OF THE LIVER.

A considerable number of cases of well-marked fatty degeneration of the liver have been seen. At times the fatty change is so extensive that the organ floats when placed in water. Microscopically the liver cells are found to be extensively infiltrated with fat granules.

HERNIÆ.

A few ventral herniæ have been observed. In the majority of the cases the sac contained intestine only and this was easily reduced. On two occasions other viscera have been found in the sac; the spleen on one occasion and in another case along with several loops of intestine which were easily reduced there was found the upper extremity of the right division of the uterus which carried a cyst about 1 centimeter in diameter. The cyst was partly adherent to the sac of the hernia. The other division of the uterus was dilated and full of pus. The hernial sac is rarely situated in the median line. One inguinal hernia has been seen.

GENITO-URINARY TRACT.

NEPHRITIS.

Nephritis is a rather common condition in rats. Among the large (old) ones it will be found probably once in every fifteen or twenty examined. It has been found to be especially frequent in rats that are suffering from the leprosy-like disease, as probably two-thirds of those having that interesting infection will show marked evidence of nephritis. The kidney is usually brownish or grayish, mottled, friable and often shows cysts upon the surface and in the substance of the organ. Some of these cysts may be as large as a pea, or indeed even much larger. The capsule strips very readily.

Microscopically the lesions are found to be due partly to epithelial and partly to interstitial change. There is a marked increase of connective tissue rather irregularly distributed throughout the organ. The epithelial cells show various degrees of degeneration; the nuclei are stained very lightly, or not at all; granular change of the protoplasm is well marked. Some tubules are encountered in which the epithelial cells are entirely wanting.

Cyst formation is a conspicuous feature in many of the cases. These cysts vary considerably in size, are often filled with granular débris, and are more or less completely lined with epithelial cells which are sometimes flattened. At times the epithelial lining is entirely wanting. The glomeruli, on the whole, appear to be better preserved than are the tubules. Occasionally areas are found in which there is a very marked round cell infiltration between the epithelial structure. One of the most marked cases of nephritis we have observed was in a large female _Mus alexandrinus_, in which both kidneys were almost entirely replaced by cystic formation, the largest cyst being perhaps 3 centimeters in diameter by 4 centimeters in length, and full of a clear, watery fluid. So extensive was the cystic formation that only a few remnants of kidney tissue remained. Microscopical examination showed a marked increase in the capsular and interstitial connective tissue, a shrinking of the glomeruli, which were surrounded by well-marked fibrous capsules, and extensive cyst formations. The lining of some of these cysts was made up of epithelial cells. Others were quite bare. This rat had, in addition, a large, rough calculus in the urinary bladder.

ABSCESS OF THE KIDNEY.

A female _Mus norvegicus_ had on one side of the neck a large cavity full of caseous matter. In each kidney there were five or six circumscribed collections of pus, the largest of which was about the size of a pea. Microscopical sections through these abscesses showed that they were walled off from the kidney structure proper by beginning connective tissue formation. The abscess cavity was filled with polynuclear leucocytes, some of them very markedly disintegrated. The epithelial structure of the kidney proper showed some parenchymatous degeneration.

ATROPHY OF A KIDNEY.

On one occasion we have seen a kidney represented by a very small flattened mass of tissue, the nature of which was not quite clear until microscopical examination showed a few fairly well-defined glomeruli and a few cell groupings suggestive of tubules. Whether the condition was congenital or acquired is not known. The other kidney appeared to be normal in every respect. There was no evidence of compensatory hypertrophy.

VESICAL CALCULI.

The bladder of rats very frequently contains very irregularly shaped, rough, somewhat branching concretions. These concretions are rather soft and tough and are dirty white in color.

In addition to these concretions we have seen several cases of well-marked vesical calculi. In one case 21 smooth round stones which completely filled the bladder were found. The total weight of the stones was 3.8 grams. In another case 6 calculi were found, the total weight of which was 7.8; the largest one weighing 5 grams. In a third case 8 smooth, round stones weighing 1.7 grams were found, the largest of which weighed 0.6 gram. The last two cases were female rats; the sex of the first was not recorded.

In each of these cases the bladder showed to the naked eye very marked evidence of inflammation. The mucous membrane was reddened, villous, and covered with tenacious mucus. In one case in which microscopical examination was made the mucous membrane was found to be covered with pus cells, the surface layers of which were undergoing degeneration.

Diseases of the genital tract in the human race analogous to those mentioned below are so generally regarded as due for the most part to infections from impure sexual relations that it was a distinct surprise to find such lesions in rodents.

In the male abscesses are occasionally met with in connection with the seminal vesicles. We have seen them varying in size from a pea to a sac whose contents would have measured 3 or 4 cubic centimeters. In the female purulent collections in the horns of the bifid uterus are encountered, but they are rare. We have seen cases that were anatomically exactly like the purulent lesions so commonly found in the fallopian tubes of women. In one case one horn of the uterus was closed at both ends and distended by a thin, watery pus into a large sausage-shaped mass about the size of an index finger. The opposite horn of the uterus contained six fœtuses. A very curious case was one in which four fœtuses, each one a little less than an inch in length, were found lying in the midst of a large, yellowish, puttylike mass that distended one horn of the uterus into a balloon-shaped mass about 3 centimeters in diameter. The fœtuses were partly dried, and had evidently been dead for a long time.

TUMORS.

Tumors among rats and mice are not infrequent when these animals are kept in captivity, and the tumors of mice especially have been made the subject of very extensive experiments for the purpose of determining the mode of transmission, the question of immunity, and other subjects that might throw light upon malignant growths in the human family. White or tame rats have been much less used than mice. However, it is interesting to note that the earliest observations on the successful transplantation of a malignant growth from one animal to another was that of Hanau[101], who reported a carcinoma of the external genitals of a white rat and he succeeded in transplanting this tumor into other white rats.

I shall not make any attempt to review the enormous literature on tumors in tame rats and mice, but shall merely mention some of the more important points that have been learned in an experimental way in regard to this subject. The histological nature of the tumors found in white rats was of particular interest, as we wished to compare them with the tumors that have come under observation among the wild rats in San Francisco.

In addition to Hanau’s case of carcinoma cited above the following tumors of white rats are mentioned. Herzog[102] observed a cystic sarcoma of the neck of a white rat. Loeb[103] mentions three tumors of white rats; an adenoma in the mammary gland, an adenocarcinoma of the pancreas, and a carcinoma of the thyroid. Flexner and Jobling[104] report a mixed cell sarcoma of the seminal vesicles of a white rat. This tumor upon transplantation showed a marked tendency to produce metastases. Gaylord and Clowes[105] report cases of fibrocarcinoma of white rats arising apparently from infected cages, and they present evidence that in certain breeding establishments carcinoma is endemic among the white mice. Spontaneous tumors are much more frequently met with in mice than in rats, and a number of epidemics of malignant growths have been observed among mice in captivity.