Abstract. This study was performed to determine the nationwide antigenic diversity of Orientia tsutsugamushi in South Korea. Sequence analysis was performed around variable domains I and II of a 56-kDa protein-encoding gene. We used eschar to overcome the disadvantages of conventional serotyping. The serological passive hemagglutination assay (PHA) was assessed based on the genotyping results. We analyzed 153 isolates from scrub typhus patients in major endemic areas and found that Boryong was the major strain (68.6%). New strains were also identified: Taguchi (19.6%), Kanda/Kawasaki (9.2%), and UAP7 (1.3%). PHA yielded significantly fewer positive results among Kawasaki strains ( P < 0.001), which are not included in the PHA antigen panel. In South Korea, Boryong was still the predominant strain, but the sequence analysis identified new changes in minor strains (30.1%). This antigenic drift had a negative effect on the PHA results. Periodic surveillance of the contemporary strains using sequence analysis is needed.

We prospectively evaluated severity predictors in terms of host, microorganism, and treatment factors in 153 eschar-positive scrub typhus patients. Severity was assessed with the Acute Physiology and Chronic Health Evaluation (APACHE) II score (< 10 versus ≥ 10) and predefined criteria of severe complications. Genotypes of Orientia tsutsugamushi were determined. Independent risk factors for severity (APACHE II score ≥ 10) were old age, diabetes mellitus, serum osteopontin > 100 ng/mL, and a group of underlying diseases (congestive heart failure, cerebrovascular disease, chronic liver disease, bronchial asthma, and chronic obstructive lung diseases). Anemia (≤ 10 g/dL) and C-reactive protein > 10 mg/dL were indicators of current severity. Neither the delay in antibiotics administration nor strain types (Boryong, Taguchi, or Kanda/Kawasaki) contributed to the severity. The risk factors for severe complications were similar. Serum osteopontin > 100 ng/mL had a negative predictive value of 96% for severe complications. This marker can be used to rule out severe disease status.