Humoral and cellular responses in scrub typhus patients reflecting primary infection and reinfection with Rickettsia tsutsugamushi

The IgM and IgG responses of 103 patients from the Pescadores Islands of Taiwan with typical signs and symptoms of scrub typhus, from whom Rickettsia tsutsugamushi had been isolated, were studied by the indirect microimmunofluorescent antibody test. Some aspects of the non-antigen specific cellular response were also investigated in a subset of these patients. Two distinct types of anti-rickettsial antibody responses were encountered. In 78 patients (Type 1 responders) the initial response, generally appearing by 8 days after onset of illness and rapidly increasing in titer, was IgM. IgG did not appear until 12 days and increased in titer more slowly. In 25 patients (Type 2 responders) the initial response, detectable by 6 days, was IgG, while the IgM response, detectable in only 16 of these patients, was variable in development and persistence. The IgA response, tested only in six patients of each group, was transient and occurred almost exclusively in the Type 1 responders. In later convalescence (>40 days after onset) IgG was the predominant anti-rickettsial antibody class in both groups and lasted approximately 1 year. The specificity of serological reactions towards the Gilliam, Karp, and Kato serotypes was more clearly shown in the IgM response of both groups of patients. During the course of the study, 14 patients from both groups exhibited serological evidence of subsequent reinfection, not accompanied by clinical disease. The cellular response was characterized by depressed levels of activated T cells (A-T cells) during acute illness (0-7 days post onset) and the early phase of convalescence (8-15 days after onset) in the Type 1 responders, and by elevated A-T cell levels in both groups during the later stages of recovery. Type 1 and Type 2 responders also differed in age and in the clinical manifestations of disease. Type 1 responders were younger, exhibited a higher incidence of rash and conjunctivitis, and a somewhat greater incidence of transient fever and relapse, following tetracycline or doxycycline therapy. Type 2 responders exhibited a higher incidence of generalized lymphoadenopathy. These results suggest that the Type 1 response reflects primary infection, while Type 2 indicates reinfection. The Type 2 response was comparable to that of the 14 cases of reinfection documented only by their antibody response. It is concluded that reinfection with R. tsutsugamushi is a relatively common occurrence in highly endemic areas, and that cell-mediated immunity, as evidenced by marked A-T cell responses in both patient groups, may play an important role in recovery from scrub typhus.