High initial IgG antibody levels against Orientia tsutsugamushi are associated with an increased risk of severe scrub typhus infection

Background Scrub typhus is a dominant cause of febrile illness in many parts of Asia. Immunity is limited by the great strain diversity of Orientia tsutsugamushi. It is unclear whether previous infection protects from severe infection or enhances the risk. Methods/principal findings We studied IgG antibody levels against O. tsutsugamushi at presentation in 636 scrub typhus patients using enzyme-linked immunosorbent assays (ELISA). The association between ELISA optical density (OD) and risk of severe infection was modelled using Poisson regression. OD was categorised as low (
Author summary In some viral infections, repeat infection is associated with a higher risk of severe disease than the first infection. Clear clinical and epidemiological evidence for this effect only exists for dengue virus infection, but it may also play a role in non-viral infections. Scrub typhus is caused by intracellular bacteria of the Orientia genus, and is among the most common causes of febrile illness in many parts of Asia. Despite being common and potentially fatal, it remains a neglected and under-diagnosed infection. Due to the great strain diversity of Orientia species (especially O. tsutsugamushi) people can experience multiple infections during life. In this study of 636 scrub typhus cases from South India, we found elevated initial IgG antibody levels, possibly from an earlier infection, to be strongly associated with severe disease. The effect was especially pronounced in younger patients and at moderately elevated antibody levels. The findings may be explained by severe infection eliciting an accelerated IgG response or, as in dengue fever, by previous scrub typhus infection enhancing the risk of severe subsequent episodes.