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Infection of Guinea Pigs with Massive Doses of Rickettsiae of Epidemic and Murine Typhus

From the Laboratories of the International Health Division, The Rockefeller Foundation, New York City

Abstract

A severe and often lethal disease, characterized by immediate onset and long duration of fever, significant weight loss, and frequently by the development of paraplegia, has been uniformly produced in guinea pigs inoculated with low dilutions of yolk-sac material infected with epidemic typhus rickettsiae. Bacteriologic cultures, passage experiments and immunologic evidence indicate that this disease was produced by the rickettsia and not by some other extraneous agent.

Evidence has been presented to show that the disease is more severe in large guinea pigs than in small ones, in intracardially inoculated pigs than in those infected by the intraäbdominal route, and possibly, in pigs inoculated during the cooler seasons than in those infected in warm weather. Although the brief incubation period suggests the possibility that the disease is a toxic manifestation similar to that produced in mice by inocula of the same kind, the long duration of illness and the pathologic changes observed suggest that a true infection has occurred. The greater susceptibility of larger guinea pigs, unexpected at first thought, is possibly analogous to the increasing mortality associated with age in human typhus.

Examples from the literature indicate that sources of abundant rickettsiae other than infected yolk sac, i.e., suspensions of lungs from intranasally inoculated animals (1) and of experimentally infected lice (3), may also produce severe disease in guinea pigs. To this list may be added suspensions of liver from intracardially infected cotton rats.

In our experience, both yolk-sac and cotton rat liver suspensions infected with strains of murine typhus rickettsia also produced more severe disease in guinea pigs than that ordinarily produced by more commonly employed inocula. However, lethal outcome was rare, and the onset of fever was usually delayed until the third day after infection. Not too surprising was the failure of intracardially inoculated animals to develop orchitis.

It seems possible that infection of guinea pigs with massive doses of rickettsiae may prove useful in future studies of the chemotherapy of typhus, or as the basis for the development of additional serum-neutralization technics. It has already served the purpose of helping to distinguish the avirulent Strain E of Rickettsia prowazeki from other strains of epidemic typhus rickettsiae (8), and it has proved to be a highly reliable challenge procedure, which lends itself to more certain interpretation than do the classical methods of challenge with less infective material of guinea pig origin.