쯔쯔가무시병의 혈청학적 분자생물학적 역학 조사 및 중증 열성 혈소판 감소증 바이러스 동시 감염 조사 연구

Abstract

1. Introduction: Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi. Huaiyangshan banyangvirus (formerly Severe fever with thrombocytopenia syndrome virus (SFTSV)) is a tick-borne virus that can cause hemorrhagic fever. Severe fever with thrombocytopenia syndrome (SFTS) is emerging in Eastern Asia, including China, South Korea, and Japan, which are endemic region of scrub typhus. As the two infections overlap epidemiologically and clinically, knowledge on the local prevalence of the vector-borne infections is critical in target-oriented investigation and treatment.2. Methods: To investigate the genotypic diversity of O. tsutsugamushi and potential coinfection with SFTSV in South Korea and Myanmar, 2,328 sera collected from patients with acute febrile illness in South Korea from 2000 to 2003 and 152 sera obtained from suspected patients with scrub typhus in Myanmar during 2018 were examined. I performed serological and molecular diagnosis of scrub typhus and SFTS. Phylogenetic analysis of both pathogens were also performed by sequencing of the amplified genes from O. tsutsugamushi and SFTSV.3. Results: Among 2,328 samples from Korean patients, serological analysis detecting specific IgG against SFTSV NP antigen identified 37 positive samples (1.6%). Molecular detection of SFTSV NP gene and O. tsutsugamushi tsa56 gene by PCR using the 37 specimens revealed 9 positive for SFTSV and 14 positive for O. tsutsugamushi, respectively. Sequencing of 14 Orientia-specific PCR products showed the presence of 3 genotypes, including Boryong (1/37, 2.7%), Karp (8/37, 21.6%) and Gilliam (4/37, 10.8%) genotypes. In addition, 4 specimens were positive for both SFTSV NP gene and O. tsutsugamushi tsa56 gene, indicating coinfections. Among 152 Myanmar samples, 9 samples (5.9%) were positive for O. tsutsugamushi tsa56 gene and sequencing of the PCR products revealed the presence of 5 genotypes, Karp A (4/9, 44,4%), Karp B (1/9, 11.1%), Kato B (2/9, 22.2%), Gilliam (1/9, 11.1%) and JG_C (1/9, 11.1%). 5 samples were positive for SFTSV NP gene-specific PCR (5/152, 3.28%). These 5 SFTSV NP gene positive samples were all negative for O. tsutsugamushi tsa56 gene, but 3 of them carried high titers (≥1:2,560) of IgG or IgM or both antibodies specific to O. tsutsugamushi, as measured by indirect immunofluorescence assay. 4. Conclusion: In this study, serological and molecular surveillance of sera collected from suspected scrub typhus patients in South Korea and Myanmar revealed serological prevalence and genotypic heterogeneity of O. tsutsutsugamushi. Moreover, potential coinfection of O. tsutsugamushi and SFTSV was identified by serological and molecular surveillance. These results suggest that SFTSV infections might have been spread more widely in Eastern Asia. Therefore, continuous surveillance of SFTS patients needs to be conducted in the local area. In addition, more reliable differential diagnosis techniques and prevention and control measures are required for better clinical practices and outcomes in the endemic regions of multiple tick-borne and mite-borne pathogens.