EXPERIMENTAL RAT-BITE FEVER
Authors: Kikutaro Ishiwara, Toyoitsiro Ohtawara, Kotaro Tamura
Journal: The Journal of Experimental Medicine (1917)

1. We have confirmed Ogata's results in experimental rat-bite fever caused by the bite of rats. 2. In our experiments with guinea pigs, swelling and congestion of the bitten parts, swelling of the subcutaneous lymph nodes, fever, and loss of weight were the typical symptoms. The progress of the fever was not so regular as in human cases, but we find records in the literature of patients who showed irregular fever types or were afebrile. The chief points that we noted in the anatomical view of the guinea pigs were swelling and congestion of the lymph gland system and acute changes in the adrenals and kidneys. 3. If an emulsion made from the lymph glands, cerebral substance, or the adrenals, or the heart's blood of a guinea pig of the original generation is inoculated subcutaneously or intraperitoneally into a fresh guinea pig, the animal invariably dies with the usual symptoms of fever and swelling of the lymph glands. The anatomical changes in this case were the same as those of the original guinea pig, except that the course was shorter and more regular. The same result was observed in further generations. No change was observed in pathogenicity, and in the guinea pigs of the original and further generations a species of spirochete as the causative agent was always observed. The incubation period in the original generation was from 1 to 2 weeks, and in further generations about 1 week. 4. When a mouse or white rat was inoculated, spirochetes always appeared in the peripheral blood, but no other symptoms developed. When peripheral blood drawn from a mouse thus treated was inoculated into a fresh mouse or a fresh white rat and peripheral blood drawn from the mouse and rat was inoculated into a fresh guinea pig, they all became infected and the guinea pigs always died. Thus we found that rats and mice are media but not victims of the disease, while guinea pigs are both media and victims of it. 5. In the rhesus monkey on which we made our experiment we witnessed a process similar to that of human rat-bite fever, and our spirochotes were observed in other animals into which blood drawn from the monkey was inoculated. 6. In the original animals spirochetes were seen chiefly toward the end of the process and the conditions as to the period previous to it are not yet clearly known. In further generations of all the animals we used, spirochetes were found in the peripheral blood 4 or 5 days after inoculation, and gradually multiplied until the greates number was reached about the 10th day after inoculation. They then began to decrease; yet spirochetes could be observed over 2 months later. 7. We have found spirochetes chiefly in the adrenals of the animals by Levaditi's method, but have not yet ascertained their distribution in other organs. 8. Our spirochete is short, round, and highly motile; it stains readily, and has few spirals. We have not yet observed an undulating membrane, but have seen what we believe to be flagellum at each end. 9. The identification of our spirochete with other species must be left for further study. The spirochete which Futaki, Takaki, Taniguchi, and Osumi found in two patients with rat-bite fever, seems to differ from ours in form. 10. Spirochetes disappear from the blood of the animals as a result of the injection of salvarsan, thus indicating that the spirochete is arsentropic.