Serological Cross-Reactivity among Orientia tsutsugamushi Serotypes but Not with Rickettsia japonica in Japan

The rickettsial diseases Japanese spotted fever (JSF) and scrub typhus (ST) are caused by Rickettsia japonica and Orientia tsutsugamushi, respectively. The diseases share clinical symptoms, such as fever, rash, and eschar. However, there are no systematical investigations of the serological cross-reactivity between R. japonica and O. tsutsugamushi. Also, the serological cross-reactivity among O. tsutsugamushi serotypes is still unclear. We analyzed 1406 cases tested by indirect immunoperoxidase assay using seven rickettsial antigens—one R. japonica and six O. tsutsugamushi serotypes—between 2003 and 2016 at two reference centers in Japan. Of these, 167 JSF and 190 ST cases were serologically diagnosed. None of the ST cases had a significant increase in IgM titers against R. japonica. Six JSF cases showed IgG titers of ≥40 against O. tsutsugamushi, but no IgG titer showed a significant elevation in the convalescent phase sample. We observed a substantial degree of cross-reactivity between O. tsutsugamushi serotypes. Cross-reactivity was significant among Karp, Hirano/Kuroki, and Kato types and between Gilliam and Irie/Kawasaki types in IgM, while the Shimokoshi type was less cross-reactive than the others. In conclusion, there is no serological cross-reaction between R. japonica and O. tsutsugamushi. The cross-reactivity among O.tsutsugamushi varies depending on serotypes