Advancing the diagnosis of scrub typhus with targeted next-generation sequencing

Objective Scrub typhus has nonspecific symptoms, making it easy to miss or underdiagnose. This retrospective study evaluated targeted next-generation sequencing (tNGS) for the early diagnosis of acute Orientia tsutsugamushi infection in terms of feasibility and application value. Methods This retrospective study included 49 patients with suspected scrub typhus as the case group. Among them, 28 patients with eschar or ulcers were assigned to the clinical diagnosis group. The remaining 21 patients without eschar or ulcers formed the clinically suspected group. Additionally, 48 patients with nonscrub typhus bloodstream infections during the same period were included in the negative control group. Clinical data and tNGS results were collected for all the patients. Results No significant differences were found between the clinical diagnosis group and the clinically suspected group in sex, age, time from onset to sampling, season of onset, complications, or clinical prognosis ( p > 0.05). The sensitivity of tNGS for diagnosing scrub typhus was 91.8% (45/49), and the specificity was 100.0% (48/48). No significant differences were observed between the clinically diagnosed group and the clinically suspected group regarding the positivity rate of O. tsutsugamushi detected by tNGS or the therapeutic response to doxycycline ( p > 0.05). Significant changes were observed in the median eosinophil count (EOS), platelet count (PLT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) before and after doxycycline treatment in the case group ( p < 0.001). Conclusion TNGS demonstrated high sensitivity and specificity for the detection of O. tsutsugamushi . It facilitates the early diagnosis of scrub typhus, particularly in suspected cases without eschars. However, prospective studies are needed for validation.