Clinical and histological features of inoculation site skin lesions in cynomolgus monkeys experimentally infected with Orientia tsutsugamushi

Abstract

Cynomolgus monkeys, as animal models of scrub typhus, are typically infected with Orientia tsutsugamushi by intradermal inoculation. However, the clinical and histological features at the O. tsutsugamushi inoculation sites, akin to "eschars" at chigger inoculation sites in humans, have not been fully characterized. We intradermally inoculated one medial thigh of six cynomolgus monkeys with semi-purified O. tsutsugamushi (Karp). Within 7 days, two animals developed scrub typhus-like eschars and four had dusky plaques, accompanied by inguinal lymphadenopathy. Biopsies of eschars and an enlarged regional lymph node resembled human disease and stained positively for O. tsutsugamushi by Giemsa, anti-Karp fluorescent antibody, or streptavidin alkaline phosphatase. O. tsutsugamushi-specific IgM and IgG antibody levels measured in both of two monkeys rose steadily after infection. This pilot study shows that cynomolgus intradermally inoculated with O. tsutsugamushi replicate the localized cutaneous pathogenesis of human scrub typhus infections, strengthening the value of this animal model.