Chapter III: Part 3

Indian Plague Commission (Journal of Hygiene, 1907, Vol. VII, No. 6,
p. 761).

Endnote 19:

Indian Plague Commission (Journal of Hygiene, 1906, Vol. VI, No. 4).

RAT RECORD CARD.

[Legend: O = Ordinary; W = White belly; R = Red; Go. = Gopher rat; S =
Small; M = Medium; L = Large; M. R. = Mus rattus; M. N. = Mus
norvegicus.]

───┬────────┬───────────────┬─────┬────────┬────────────┬─────┬───────── No.│ Date. │District No. 6.│Sex. │ Size. │ M. N. │M. R.│Pregnant. ───┼────────┼───────────────┼──┬──┼──┬──┬──┼──┬──┬──┬───┼──┬──┼───────── „ │ „ │ „ │M.│F.│S.│M.│L.│O.│W.│R.│Go.│O.│W.│ „ ───┼────────┼───────────────┼──┼──┼──┼──┼──┼──┼──┼──┼───┼──┼──┼───────── 19 │Dec. 10,│ 401 Fillmore │1 │ │ │1 │ │ │ │1 │ │ │ │ │ 1908 │ street │ │ │ │ │ │ │ │ │ │ │ │ 20 │ do │ do │ │1 │ │ │1 │1 │ │ │ │ │ │ [S]7 ───┴────────┴───────────────┴──┴──┴──┴──┴──┴──┴──┴──┴───┴──┴──┴─────────

Footnote S:

Number of fœtuses.

PLAGUE RAT CARD.

PLAGUE RAT NO. 50.

Date: June 20, 1908. Species: _M. norvegicus_. From District No. 6, sewer, Haight and Steiner Streets. Condition: Badly injured by trap; thorax crushed. Subcutaneous injection: General, marked. Lymphatic glands, bubo or other lesions: Right inguinal bubo, caseous. Liver: Typical whitish granules. Spleen: Large, dark, firm. Pleural effusion: Unable to say. Purulent or caseous foci: Diagnosis from gross lesions: Plague. Diagnosis from smears: Plague (spleen and bubo). Cultures: _B. pestis_ recovered from liver culture. Inoculation, guinea pig No. 50 A, +6.25.08. Vaccination, guinea pig No. 50 B, +6.26.08. Date suspicious: Date positive: June 20, 1908. Date negative:

A HOEN & CO BALTIMORE.

NECROPSY APPEARANCE OF PLAGUE-INFECTED RAT
]

A HOEN & CO BALTIMORE

NECROPSY APPEARANCE OF NORMAL RAT
]

RAT LEPROSY.

By WALTER R. BRINCKERHOFF, S. B., M. D.,

_Assistant Director Leprosy Investigation Station, United States Public
Health and
Marine-Hospital Service, Honolulu, Hawaii_.

INTRODUCTION.

The leprosy-like disease of the rat is of great interest to leprologists because of its close similarity to the disease leprosy in man. Its practical importance to those engaged in the study of the human disease is increased by the fact that it can be artificially propagated under laboratory conditions from animal to animal and, still more important, can be transferred from the species in which it occurs naturally (_Mus norvegicus_) to a more tractable laboratory animal (_Mus albus_). The brief description of the affection which follows is intended to assist in its recognition and to stimulate the interest of investigators in the disease, which presents problems replete with interest to the study of pathology or bacteriology and of great promise to those engaged in the investigation of human leprosy. It is earnestly hoped that the investigation of this disease will be undertaken in general medical research laboratories, as it is extremely probable that certain of the most difficult problems presented by leprosy in man can be studied in this disease of the rat, and if solved there the information gained can be directly applied to the solution of the analogous problems in the human disease.

REVIEW OF LITERATURE.

The first publication on rat leprosy was made by Stefansky (1903), who observed the disease in Odessa during an antiplague campaign against rats.

Rabinowitch (1903) found the disease among rats in Berlin and confirmed the work of Stefansky.

Dean (1903) discovered the disease independently in London, and in a later publication (1905) reports success in transferring the disease by artificial inoculation.

Tidswell (1906) reports a case of the disease in a rat caught in Sydney, New South Wales, Australia.

The English Plague Commission observed the disease in India in 1907 (Wherry).

Wherry (1908) and McCoy (1908) report upon the finding of the disease in rats caught in San Francisco, Cal.

Mezincescu (1908) has studied the disease and attempted to determine its relationship to known human lepra by complement fixation tests.

DESCRIPTION OF DISEASE.

_Geographical occurrence._—It would be premature at present to make didactic statements as to the geographical distribution of the disease, for its discovery has usually depended upon antiplague measures, which are not world-wide in their scope. In spite of this it seems profitable to briefly review the known occurrence of the disease in relation to that of human leprosy. When such a comparison is made we note that the disease is present among the rats of Berlin, a city which is practically free from human lepra. On the other hand in Honolulu, which is an endemic focus of human leprosy, in the examination of 16,000 rats, during an antiplague campaign, no case of rat leprosy was encountered. In addition to the scrutiny of the rats examined for plague in Honolulu, an attempt was made to obtain leper rats by offering a reward for a rat, dead or alive, infected with the disease. This offer was given wide publicity in the Territory, but brought no results.

_Occurrence of the disease._—The proportion of rats infected with the disease in different localities varies greatly, as will be seen in the following table:

TABLE 1.—_Proportion of leper rats to the total rats examined._

───────────────────────────┬───────────────────────────┬─────────────── Place. │ Observer. │ Proportion. ───────────────────────────┼───────────────────────────┼─────────────── │ │ _Per cent._ Odessa │Stefansky [301] │ 4–5.000 Sydney │Tidswell [305] │ .001 San Francisco │Wherry [308] │ .210 Do │McCoy [310] │ .160 Honolulu │Currie[T] │ .000 ───────────────────────────┴───────────────────────────┴───────────────

Footnote T:

Personal communication.

Rats in the late stage of the disease are easily recognized by the presence of a patchy alopecia associated with cutaneous and subcutaneous nodules, which may or may not be the site of open ulcers. The diagnosis can be readily confirmed by a microscopic examination of a smear from an ulcer or a nodule, which will show the specific bacillus of the disease in enormous numbers.

Stefansky[301] describes two clinical types of the disease, the one localized particularly in the lymph nodes, the other in the skin and muscles. The glandular type was the more common. Dean[304] thinks that no line of demarcation can be drawn between these clinical types.

Dean[304] and Wherry[307] both mention that attention was attracted to the diseased animals by the fact that they were seen abroad during daylight in an obviously sick condition.

The skin, in a well-developed case of the disease, presents a patchy alopecia coincident with thickening and nodule formation, which is situated in the subcutaneous tissue. The cut surface of the nodules or thickenings is light yellow in color, is clean, dry, and cheese-like. In the region of the nodules the skin is atrophic, and ulcers often form on the prominent parts of the affected area. The subcutaneous fat tissue is diminished in amount. Histologically the process is seen to be practically confined to the subcutaneous tissue and to consist essentially in the presence of cells rich in protoplasm, with vesicular nuclei, whose cell body is more or less completely filled with slender acid-fast bacilli. The subcutaneous fat is replaced by such a tissue. All investigators who have studied the disease agree in emphasizing the similarity of the histology of the lesion to that in leprosy in man.

When the musculature is involved the muscle fibers atrophy and the fibers are infiltrated with the specific bacilli. The affected muscle is friable, and macroscopically grayish white in color.

The peripheral lymph nodes are commonly involved, though McCoy[310] reports a case in which only the pelvic and mesenteric nodes were diseased, and in the Tidswell case[305] the peripheral nodes were not enlarged. The typically affected nodes are enlarged, sometimes measuring as much as 3 centimeters in the greatest extent, firm, and, on section, opaque pale yellow-white in color. In the experimental disease the writer has frequently found the characteristic bacilli of the disease in peripheral lymph nodes which were very slightly enlarged and presented no macroscopic lesion. Dean[304] has observed invasion of the submaxillary or salivary glands by extension from infected cervical lymph nodes. Wherry[308] notes that in his cases he did not find the submaxillary or cervical glands involved, which fact he contrasts with two early cases in which the skin and adjacent axillary or inguinal nodes were involved.

Microscopically the lymph nodes show large numbers of cells in the sinuses similar to those in the skin lesions. Multinuclear giant cells are frequently observed which may measure as much as 70 to 80 microns[304]. The protoplasm of the cells is loaded with the specific bacilli of the disease. The lymph follicles, trabeculæ, and capsule of the glands are also invaded by the bacilli.

The internal organs are relatively slightly affected in the natural disease. Small foci have been found in the liver by Dean[304] and in the liver and spleen by McCoy[310]. Wherry[307] reports finding the bacilli in smears from both the liver and spleen. The writer has found microscopic lesions containing the characteristic bacilli in the liver in a case of the experimental disease.

Lesions have been observed in the bone marrow by Dean[304], and the same author states that the nerves are invaded by the bacilli of the disease. McCoy[310] found the bacilli in the urinary bladder in one case.

With a disease showing such a striking similarity to human leprosy, attention has naturally been directed to the bacteriological examination of the nasal mucus. Dean[304] and Wherry[307] have both found the characteristic bacilli in the nasal mucus, while McCoy[310] has failed to do so. The writer’s experience has been confined to the experimental disease, and in his animals the nasal examinations have been negative.

ETIOLOGY.

The accepted etiological factor in the disease is an acid-fast bacillus 3 to 5 microns in length and 0.5 micron wide. The bacilli resemble very closely the lepra bacillus of man, but seem to have somewhat greater power to hold carbol-fuchsin stain against mineral acids. The bacilli often have rounded ends and may be curved. The beaded appearance so often seen in lepra bacilli is common. The bacilli show the same tendency to form bundles that is such a marked characteristic of _Bacillus lepræ_. To one familiar with the microscopic appearance of smears from the discharges and lesions of human leprosy the picture presented by similar preparations from the disease of the rat is most striking.

The organism does not grow on the usual culture media—Stefansky [301], Rabinowitch[302], Dean[304], Tidswell[305]—or on certain special media—Dean[304].

The organism is not pathogenic for the guinea pigs—Dean[304], Tidswell[305]—rabbit, mouse, monkey—Dean[304]. The disease can be transmitted to black and white rats—Dean[304], Wherry.

SUMMARY.

In the leprosy-like disease of rats we have an affection which closely resembles, both in its etiological factor and in its pathology, the disease leprosy in man. The fact that the disease is readily propagated in a laboratory animal permits of its investigation in any laboratory. It is earnestly hoped that the study of this disease will be taken up by bacteriologists and pathologists, as in this way valuable information may be gained which will be applicable to the problems presented by leprosy in man.

BIBLIOGRAPHY.

Endnote 301:

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.

Tyzzer[106] found in a mouse a primary adenocarcinoma of the lung and an adenoma of the kidney. Loeb[107] found that upon the transplantation of a pure gland-like tumor (carcinoma) which originated in the submaxillary gland of a Japanese mouse both carcinoma and spindle cell sarcoma were developed, and this observation, that transplanted tumors may give rise to a different histological growth from that which was transplanted, has been made by others. Tyzzer[108] reports 20 spontaneous tumors in mice. Of these tumors 12 were papillary cyst-adenomas of the lung and were mostly very minute, some of them microscopic; 2 were cyst-adenomas of the kidney; 2 lymphosarcoma, 1 of the groin and 1 of the mediastinum, and 4 were adenocarcinoma. These 20 spontaneous tumors occurred in 16 mice, 4 of them having tumors of 2 different types. Ehrlich and Apolant[109] record the occurrence in a white mouse of a mixed tumor (carcinoma sarcomatodes). Saul[110] mentions spontaneous papillary adenocarcinoma and teleangiectatic carcinoma both in the mammary glands of mice.

Saul showed that by planting the common liver worm of the rat (_Cysticercus fasciolaris_) subcutaneously in a mouse he was able to develop a tumor which partook of the nature of a malignant (carcinomatous) growth. It will be seen by an examination of the data presented below relating to spontaneous tumors in wild rats that a considerable number of them have been associated with the presence of the parasite Saul used in his experiments. He also states[111] that Borrel found worms or their remnants in malignant tumors of mice.

When metastases occur in mouse tumors the most usual seat of the secondary growths is in the lungs, thus Tyzzer[112] observed metastases in 4 cases out of 73 mice inoculated with the Jensen tumor. He demonstrated that the metastases took place by the blood vessels, not by the lymphatic channels, although the tumors were of a carcinomatous nature.

Simon[113], who reviews the subject of mouse tumors with special reference to the subject of immunity, remarks that mouse carcinomata, although found most frequently in old females, when transplanted grows equally well in males, and better in young than in old animals. It has been found by some observers that a rat or a mouse unsuccessfully inoculated with a strain is thereafter immune, to even the most virulent strain.

Haaland[114] and other writers have found a marked variation in the susceptibility of different races of mice to mouse carcinoma.

Ehrlich[115] and his co-workers Apolant and Haaland have recorded many experiments in transplantation of tumors of mice. They have demonstrated that moderate heating of a mouse tumor lengthens the incubation period, diminishes the number of successful transplantations, and brings about certain changes in the histology of the tumors reproduced.

Gay[116] found a difference in the susceptibility of white rats from different sources. In his work with carcinoma in rats he found metastases regularly in the lungs and rarely in the lymph nodes. He was able to raise the virulence of the tumor by transplantation of the lung metastases. This increase of virulence was shown by increase in the rapidity in growth, increase in metastases, and the increase of the epithelial elements over the stroma.

Brooks[117] in considering the subject of tumors in animals concludes that true neoplasms are very rare in wild animals living under natural conditions. It should be stated, however, that Brooks refers especially to higher mammals such as are found in zoological collections.

TUMORS OF WILD RATS.

A new growth is found approximately once in every thousand rats examined in San Francisco. Ninety-two tumors have been examined microscopically. Time has been available for the study of but one or at the most two sections from each tumor and while in some cases the diagnosis was easily made in others there was room for considerable difference of opinion as to the nature of the growth. It is obvious that it is hardly fair to expect to make a final diagnosis in every case from one or two sections taken from one part of the growth, and it is possible that further study will throw more light upon the histological nature of some of them.

_Location._—The largest number of the tumors have been found in the subcutaneous tissue of either the thorax or of the abdomen, and as the majority of these have been found in female rats we have assumed that they were probably of mammary origin. The growths were occasionally located directly under the nipple, but in such cases the nipple was not retracted, and it was exceptional to find any ulceration. The tumors were very rarely adherent to the surrounding tissue. After the subcutaneous tissue tumors were found most frequently in the liver. Histologically, the most of these growths were sarcomas and the majority of them had a parasite, the _Cysticercus fasciolaris_, in some part of the tumor. This parasite, as is well known, is the larval stage of a tapeworm found in the cat. These tumors of the liver were frequently associated with an enormous number of secondary growths varying in size from a millet seed to 1 centimeter in diameter scattered through the omentum, mesentery, and other abdominal structures.

Several growths have been found in the kidney, mostly of an epithelial nature, one being a particularly well-marked example of a cystic papilloma. A few have been found in connection with other parts of the genito-urinary tract. A large bloody tumor, which upon microscopical examination was found to be an angiosarcoma, replaced a testicle. A large growth, apparently an endothelioma, was found near the end of one horn of the bicornuate uterus.

METASTASES.

Metastases have been found in a number of cases of sarcoma and a smaller number of cases of the epithelial growths. Most frequently the secondary tumors were in the liver, the mesentery or the kidney.

_Size._—In proportion to the size of the rat the tumors were quite large, scarcely any under 1 centimeter in diameter having been observed, and they varied from this to a growth several centimeters in diameter.

HISTOLOGICAL STRUCTURE.

The following tumors may be regarded as of the connective tissue type:

LIPOMATA.

One typical lipoma has been found. It was located in the subcutaneous tissue of the thorax and was similar in gross and microscopical appearance to the tumors of the same nature in man.

FIBROMATA.

A considerable number of subcutaneous tumors have been typical hard fibromas, others were fibromas in which there were a few cell nests that led to the suspicion that perhaps a malignant change was taking place in the tumor, or that a malignant growth was being converted into one of a benign nature.

SARCOMATA.

Typical spindle cell sarcomas have been encountered a number of times. A few round cell sarcomas were found in which there were usually a number of giant cells, but hardly enough to justify one in designating the growths as giant cell sarcomas. Several other growths have been seen which gave the impression of being sarcomas but left one in some doubt as to whether the tissue might not be of the nature of a granuloma.

Many tumors of the epithelial type were encountered which may be classed together.

ADENOMATA AND CARCINOMATA.

Several very typical adenomas and cystic adenomas have been found. A few tumors were observed that presented the appearance of carcinomas. A large number of growths were observed that apparently stood between the adenoma and the carcinoma and there was room for legitimate difference of opinion about any one of these, and in fact, different pathologists who have examined sections of these tumors have expressed different opinions as to the nature of the growths.

REFERENCES.

Endnote 101:

Hanau (Fortsch. der Med., vol. 7, 1889, May 1, p. 321).

Endnote 102:

Herzog (Journal Med. Research, 1902, vol. 8, old series, p. 74).

Endnote 103:

Loeb (Journal Med. Research, 1901, vol. 6, p. 28; also vol. 3, p. 44,
and vol. 17, p. 299).

Endnote 104:

Flexner and Jobling (Journal Am. Med. Assn., 1907, vol. 48, p. 420).

Endnote 105:

Gaylord and Clowes (Journal Am. Med. Assn., 1907, vol. 48, p. 15).

Endnote 106:

Tyzzer (Journal Am. Med. Assn., 1906, vol. 47, p. 1237).

Endnote 107:

Loeb (Univ. of Pa. Med. Bull., 1907, vol. 19, No. 5).

Endnote 108:

Tyzzer (Journal Med. Research, vol. 17, No. 2, p. 155).

Endnote 109:

Ehrlich and Apolant (Berl. klin. Woch., 1907, vol. 44, pp. 399 and
1401).

Endnote 110:

Saul (Centralblatt für Bact., etc., Aug. 27, 1907, vol. 47).

Endnote 111:

Saul (Centralblatt für Bact., etc., 1909, vol. 49, p. 4).

Endnote 112:

Tyzzer (Journal Med. Research, vol. 17, No. 2, p. 137).

Endnote 113:

Simon (International Clinic, vol. 2, 18th series).

Endnote 114:

Haaland (Berlin, klin. Woch., 1907, vol. 44, p. 73).

Endnote 115:

Ehrlich, Apolant and Haaland (1906, Berlin, klin. Woch., vol. 43, No.
2).

Endnote 116:

Gay (1909, Journal Med. Research, Vol. XX, No. 2).

Endnote 117:

Brooks (1907, Am. Jour. of Med. Sciences, Vol. CXXXIII).

THE ECTOPARASITES OF THE RAT.

By NATHAN BANKS,

_Assistant Entomologist, Bureau of Entomology_.

The ectoparasites of the rat fall naturally into three groups, the fleas, the lice, and the mites. These three groups are widely separated from each other, the mites belonging to the class Arachnida, having four pairs of legs, no segmentation to the body, no antennæ, and no compound eyes. The fleas and lice belong to the class Insecta. The lice are near the order Hemiptera, sucking insects without a complete metamorphosis, while the fleas are related to the Diptera and pass through a complete metamorphosis. All of these three groups, however, agree in one character—they are wingless. The mites and lice have flattened or depressed bodies, while the fleas have compressed bodies. All three groups have many other species which infest various other animals. Few, if any, of these parasites confine themselves to the rat, and all can walk or jump in the adult condition, so that they can easily transfer their attentions from one rat to another or to some other host. The majority of them are known to occur on mice, and several of the fleas and mites will readily attack man.

FLEAS—SIPHONAPTERA.

These wingless, compressed insects are known to all, but few have taken the trouble to look at them with much care. The adult female flea deposits her eggs among the hairs or fur of the host animal, but, unlike the eggs of many parasites, these are not fastened to the hairs and fall freely to the ground. These eggs are oval, whitish, and smooth, and about one-half millimeter long. The larvæ escape from the eggs in two to five days. They are enabled to break the eggshell by a slender process on the top of the head which disappears after the first molt. This larva is a slender, legless, cylindrical creature, whitish or yellowish in color, with a head and 13 segments. There are a few scattered hairs or bristles on the body and at the tip is a pair of corneous processes. On the upper part of the head is a pair of short, slender appendages, the antennæ or feelers. At the front of the head is a pair of biting jaws or mandibles. These larvæ feed on almost any kind of refuse; some have been reared on the sweepings from rooms. There is always some organic matter in this refuse, and this is doubtless their nourishment. The larvæ in houses usually crawl into cracks or under carpets and feed on the dust that occurs in such places. Those that infest wild animals probably feed on the refuse in the nests or retreats of these animals. They remain in the larval stage from a week to ten days, sometimes two weeks, molting the skin three times in this interval. Then they spin flat, white, silken cocoons, in which they transform to the pupal stage. Sometimes the cocoon is covered with particles of dust. In from five to eight days the adult flea emerges from the cocoon. The period of their transformation is affected by the temperature and moisture. In warm, damp weather a generation may develop in ten days or two weeks, but usually about eighteen days to three weeks elapse from the egg to adult. Although some moisture seems necessary to their development, an excess is apt to destroy the larvæ.

FIG. 6.—Flea, showing the various parts.
]

The leaping ability of adult fleas is familiar to all. No part of the leg is particularly enlarged, so that the jump is made by the entire leg as in the leaf-hopper insects, and not by the hind part of the leg as in grasshoppers and flea-beetles. The size of fleas is not as variable as in many insects. Most are about 2 to 3 millimeters long, while the range is about 1.5 to 6 millimeters. The adult flea has a hard, strongly chitinized body. The head is small, and on each side bears a short jointed antenna, which may repose in a groove or depression. Most species have a small, simple eye, but several forms are normally without eyes. The sides of the head below the antennæ are called the genæ. At the lower front end of the head is the mouth and mouth parts. The latter consist of a pair of triangular maxillæ with jointed maxillary palpi and a beak or proboscis made up of one median and four lateral pieces. The outer pair of lateral pieces is the labrum with the imperfectly jointed labial palpi. They serve as a sheath for the other organs, which are more slender. The inner pair of pieces are considered to be the mandibles and the median piece a labrum or hypopharynx. Others call this piece the unpaired piercing organ, the lingua, or the syringostome. There are other interpretations of the homologies of the mouth parts, but the above is the most generally adopted one. The labrum and the mandibles are roughened and constitute the piercing organs which the flea inserts into the host to tap a blood vessel. On the lower part of the head there is frequently a series or comb of stout spines. Similar spines sometimes occur on the posterior border of the pronotum. These series of spines are called “ctenidia,” and they are of great value in classification. Behind the head are three segments, or zoonites, each bearing a pair of legs. These together form the thorax. The upper surface is called the notum (pronotum, mesonotum, etc.). The sides are the pleura—sometimes “epimera” is used; and the ventral part is the sternum. Each of the thoracic segments has a spiracle, or a breathing pore, on each side. The first segment of the thorax, called the “prothorax,” is shorter than the others, and, as above stated, frequently has a row of ctenidia, or spines, on its posterior border. The next segment is the mesothorax, and the third the metathorax. The metathorax usually has some stout bristles in rows on its pleura, which are enlarged and called “epiphyses,” formerly called “squama aliforme.” The basal one or two segments are sometimes partly covered by the epiphyses or the metathorax. These segments consist of a dorsal plate, or tergite, and a ventral plate, or sternite. Behind the thorax is the abdomen of 9 apparent segments. Seven of these segments have a spiracle or breathing pore on the sides. The last segment, or pygidium, bears the genital organs; in the male certain processes called “claspers” at each side of the genital opening. The anal aperture is at the end of the ninth segment between the dorsal and ventral plates. The claspers have a main curved part, and a slender backward projection called the “manubrium,” and at the apex an articulated clawlike process called “the movable finger.” At the tip of the abdomen of the female there is a short median piece called the “style.” The legs consist of five parts: The coxa, a large basal piece; the trochanter, a minute piece at the end of the coxa; the femur, which is usually slightly swollen in the middle; the tibia, which usually has stout bristles or spines on its posterior side; and the tarsus, which consists of five parts or joints. The basal joint is often the longest, and the comparative lengths of these joints is expressed by a formula, as 60–45–32–18–30. The last, or fifth, joint has been called the “metatarsus,” but this name is better applied to the basal joint. At the tip of the last tarsal joint is a pair of stout claws. The coxæ of legs II and III show a longitudinal suture.

Fleas as a rule prefer certain hosts, but are not as particular in this regard as are many parasites. Those species which are best known are found to attack several hosts, including man. This catholicity of taste is what makes them dangerous parasites, the possible transmitters not only of plague, but also of consumption, leprosy, etc. The fleas are treated by various writers under other names, such as _Aphaniptera_, and _Suctoria_. About 300 species are described, and perhaps as many more will be gathered by collectors. Formerly all fleas were kept in the genus _Pulex_; now they are arranged in many genera, and these genera grouped into families. No less than eight such families are recognized by some authorities on this group. The species that occur on rats belong to three families, which may be separated as follows:

1. Thoracic segments much shortened and constricted;
labial palpi apparently not jointed; third joint
of antennæ without subjoints; no ctenidia;
abdomen of female becomes more or less swollen _Sarcopsyllidæ_

Thoracic segments not shortened nor constricted;
labial palpi with joints; third joint of antennæ
with several more or less distinct subjoints;
ctenidia often present; abdomen of female never
distinctly swollen 2

2. Posterior tibial spines in pairs _Pulicidæ_

Posterior tibial spines mostly single and more
numerous _Ctenopsyllidæ_

CTENOPSYLLIDÆ.

To this family belongs the _Ctenopsylla musculi_ Dugès.

This was formerly placed in the genus _Typhlopsylla_. The head is rather acute in front and has four ctenidia each side; the eyes are very small; the pronotal comb has 22 spines; each dorsal segment of the body has two rows of hairs; the basal row of smaller hairs. The proportions of joints in the hind tarsus are: 45–25–17–8–14. Length 1.8 to 2.5 millimeters. This species is abundant on rats and mice in Europe and other countries; recently it has been taken in California and Florida on rats and mice.

PULICIDÆ.

This family includes the greater number of fleas. They have been arranged in many genera, six of which have been taken from rats. These are separable as follows:

1. Head without ctenidia; eyes distinct 2

Head and pronotum with ctenidia; last tarsal joint
with four pairs of lateral spines 5

2. Pronotum with ctenidia; female with one
antepygidial bristle on each side _Hoplopsyllus_.

Pronotum without ctenidia 3

3. Last tarsal joint with four pairs of lateral
spines; female with one antepygidial bristle each
side 4

Last tarsal joint with five pairs of lateral
spines; female with two to five antepygidial
bristles each side _Ceratophyllus_.

4. Mesosternite very narrow, without internal rod-like
incrassation from the insertion of coxa upward _Pulex_.

Mesosternite with a rod-like internal incrassation
from the insertion of coxa upward _Xenopsylla_.

5. Eyes rudimentary; female with two to five
antepygidial bristles each side _Neopsylla_.

Eyes distinct; female with but one antepygidial
bristle each side _Ctenocephalus_.

_Hoplopsyllus_, one species, described as a _Pulex_.

_Hoplopsyllus anomalus_ Baker.