Antibodies and Clinical Relapse of Murine Typhus Fever Following Early Chemotherapy

Abstract

Treatment with chloramphenicol was initiated early in the course of disease (2-4 days after onset) in 3 cases of murine typhus fever acquired presumably through the respiratory route. Chemotherapy was discontinued 5, 8 and 10 days, respectively, after onset. Clinical relapse occurred promptly in each patient from less than 2 to about 3 days after the last dose of antibiotic. In each instance an array of antirickettsial antibodies was present at the onset of the relapse. The very short interval between withdrawal of drug and onset of relapse makes impractical for murine typhus the same simple interrupted schedule of chemotherapy which was developed earlier for scrub typhus. As an alternative, a regimen is proposed that might compensate for the stage of disease at which treatment is begun. This consists of daily administration of antibiotic until the patient has been afebrile for 48 hours. Then daily therapy is continued until the total time elapsed from onset of disease is equal to about the mean duration of the untreated disease, i.e., until about 12-14 days after onset. The possible mechanisms by which clinical relapse can occur in the face of appreciable antibody levels is discussed. Among others, the possibility is presented of the participation of an immunopathological process in which hypersensitivity and antigen-antibody complexes contribute to tissue damage in the later stages of the disease.