RAT LEPROSY.
Reading edition
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.
50The 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
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.
51Stefansky[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.
52The 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.
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