THE ETIOLOGY OF RAT-BITE FEVER
Authors: Francis G. Blake
Journal: The Journal of Experimental Medicine (1916)

The similarity in the cases of rat-bite fever recorded in the literature establishes it as a definite clinical entity. The same symptomatology occurs in cases from Asia, Europe, and America. The greater frequency of the disease in Japan than elsewhere is probably due to the housing conditions and habits of the people resulting in the more frequent occurrence of rat-bites. It does not seem necessary to consider that cases occurring in Europe and America are due to the bites of rats that have been imported from Japan. The clinical picture and course of the disease indicate that it is infectious in origin. Until Schottmüller's case appeared in 1914, the etiology had been undiscovered. He isolated from his case in eight consecutive blood cultures a streptothrix which he has designated Streptothrix muris ratti. His work has been confirmed by the isolation of an identical streptothrix from the blood during life and at autopsy in the case here reported. Further confirmation of the etiological relationship of this organism to the infection in our patient is found in the production of powerful agglutinins for the organism in the blood serum of this case and in the demonstration of the organism in the vegetation on the mitral valve. It is not unreasonable to suppose that Proescher (13) observed the same organism in the sections of the excised wound in his case. Although it is fully realized that Koch's postulates have not been fulfilled in the absence of successful animal experimentation, nevertheless the accumulated evidence here presented leaves little reason to doubt that the specific cause of rat-bite fever is Streptothrix muris ratti. The pathology of rat-bite fever has hitherto been largely a matter of surmise. One autopsy only has been recorded in the literature (Miura (22)), and nothing abnormal was noted other than injection of the pial vessels. The autopsy in the case here reported has proved of considerable interest in the extent and character of the lesions found. A streptothrix septicemia with the localization of the organism in the mitral valve producing an acute ulcerative endocarditis is the most striking feature of the case. The infarcts of the spleen and kidney are a natural sequence of the endocarditis. The subacute lesions of the myocardium, liver, adrenal, and kidneys, glomerular and interstitial, are all of a similar nature, consisting of areas infiltrated with leukocytes, lymphocytes, plasma, and endothelial cells with varying degrees of degeneration of the normal cells of the affected area. In no instance has the presence of the streptothrix in these lesions been demonstrated, and it is not unreasonable to assume that they are toxic in origin. The data here presented may be correlated with the clinical features of rat-bite fever to give us a clear understanding of the course and nature of the disease. The patient is inoculated by the bite of a rat with Streptothrix muris ratti. After a variable incubation period a non-suppurative inflammatory reaction occurs at the site of the wound with extension to the neighboring lymphatics and lymph nodes. Invasion of the blood stream follows, accompanied by the onset of severe toxic symptoms. Clinically the nervous system and frequently the kidneys seem to be especially involved. That the myocardium, liver, and adrenals may also suffer is shown by the autopsy findings in the case reported above. Ulcerative endocarditis is probably a rare occurrence. In the majority of cases after a more or less prolonged course, the disease terminates spontaneously and so may be considered a self-limited infection. This is presumably brought about by the development in the body of a protective mechanism against the streptothrix. That such a process does occur is evidenced by the demonstration of agglutinins in our case. Whether a permanent immunity is acquired after one attack of rat-bite fever is not known. No instances of a second infection are recorded in the literature. Although rat-bite fever varies somewhat in its symptomatology in individual cases, the picture is sufficiently characteristic to make the diagnosis not a difficult matter. The history of a rat-bite, latent incubation period with subsequent non-suppurative inflammatory reaction of the wound, lymphangitis, and enlarged lymph nodes, severe chill at onset, high fever of the relapsing type, intense muscular pain and nervous symptoms, and the characteristic bluish red exanthem, present a symptom-complex not easily overlooked. The disease is frequently complicated by a severe nephritis, and prolonged cases develop a high grade of anemia and cachexia. In the case here reported ulcerative endocarditis occurred. In the large majority of cases the prognosis is favorable for a successful termination. The patients, however, are often incapacitated for a considerable period of time The mortality is about 10 per cent, death usually occurring in the first febrile period apparently from a profound toxemia, or at a later stage due to the development of a severe nephritis. Until recently treatment has been entirely symptomatic and has been of little avail in altering the course of the disease. Miyake has found immediate treatment of the wound by cauterization or with carbolic acid highly efficient as a prophylactic measure. Hata (30) in 1912 introduced salvarsan therapy and reported eight cases so treated, seven of which showed marked and rapid improvement. One case was apparently unaffected. Two of the cases receiving only small doses had a subsequent relapse. Surveyor (31) and Dalal (18) also have reported success with salvarsan injections. It is to be hoped that further experience with this method of treatment will yield equally favorable results.