Complex Cytokine Responses in Imported Scrub Typhus Cases, Germany, 2010-2018

Scrub typhus is a life-threatening zoonotic disease, which is caused by Orientia tsutsugamushi, an obligatory intracellular Gram-negative bacterium. It is transmitted by Leptotrombidium mites in endemic regions of Southeast Asia. So far, data on imported scrub typhus cases to non-endemic areas and immunological descriptions are rare. Eleven scrub typhus cases that had been diagnosed by the German National Reference Center for Tropical Pathogens between 2010 and 2018 were retrospectively reviewed for clinical symptoms, laboratory changes, and travel destinations. Patient sera were included if follow-up samples showed simultaneous seroconversion for IgM and IgG antibody responses by immunofluorescence assays or concurrence with the first serum sample. The median of seroconversion was week 2 after symptom onset. Cytokine levels were measured over time, demonstrating simultaneously upregulated major Th1, Th2, and Th17 cytokines in the acute phase of infection followed by normalization during convalescence. This study underlines the complex mixed cytokine response elicited by scrub typhus and highlights clinical and diagnostic aspects of imported infections with O. tsutsugamushi.