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      Family Cluster Analysis of Severe Fever with Thrombocytopenia Syndrome Virus Infection in Korea

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          Abstract

          Severe fever with thrombocytopenia syndrome (SFTS) is tick-borne viral disease that was first suspected in China in 2009. The causative virus (SFTSV) was isolated in 2009 and reported in 2011, and SFTSV expanded its geographic distribution in 2012–2013, from China to South Korea and Japan. Most SFTSV infections occur through Haemaphysalis longicornis. However, SFTSV infection can also occur between family members, and nosocomial transmission of SFTSV is also possible through close contact with a patient. In this study, we first analyzed clinical, epidemiological, and laboratory data for SFTS patients and family members of an index patient in Korea. The S segment of SFTSV was amplified from the sera of three patients, and the S segment of SFTSV and IgG specific to SFTSV were detected in the serum from one family member; although this individual had no history of exposure to H. longicornis, she frequently had close contact with the index patient. In Korea, SFTSV infection among family members does not have to be reported, and we suggest that person-to-person transmission of SFTSV among family members is possible in Korea.

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          A family cluster of infections by a newly recognized bunyavirus in eastern China, 2007: further evidence of person-to-person transmission.

          Seven persons in one family living in eastern China developed fever and thrombocytopenia during May 2007, but the initial investigation failed to identify an infectious etiology. In December 2009, a novel bunyavirus (designated severe fever with thrombocytopenia syndrome bunyavirus [SFTSV]) was identified as the cause of illness in patients with similar clinical manifestations in China. We reexamined this family cluster for SFTSV infection. We analyzed epidemiological and clinical data for the index patient and 6 secondary patients. We tested stored blood specimens from the 6 secondary patients using real time reverse transcription polymerase chain reaction (RT-PCR), viral culture, genetic sequencing, micro-neutralization assay (MNA), and indirect immunofluorescence assay (IFA). An 80-year-old woman with fever, leucopenia, and thrombocytopenia died on 27 April 2007. Between 3 and 7 May 2007, another 6 patients from her family were admitted to a local county hospital with fever and other similar symptoms. Serum specimens collected in 2007 from these 6 patients were positive for SFTS viral RNA through RT-PCR and for antibody to SFTSV through MNA and IFA. SFTSV was isolated from 1 preserved serum specimen. The only shared characteristic between secondary patients was personal contact with the index patient; none reported exposure to suspected animals or vectors. Clinical and laboratory evidence confirmed that the patients of fever and thrombocytopenia occurring in a family cluster in eastern China in 2007 were caused by a newly recognized bunyavirus, SFTSV. Epidemiological investigation strongly suggests that infection of secondary patients was transmitted to family members by personal contact.
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            Phylogenetic Analysis of Severe Fever with Thrombocytopenia Syndrome Virus in South Korea and Migratory Bird Routes Between China, South Korea, and Japan.

            Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease. The SFTS virus (SFTSV) has been detected in the Haemaphysalis longicornis, which acts as a transmission host between animals and humans. SFTSV was first confirmed in China in 2009 and has also been circulating in Japan and South Korea. However, it is not known if a genetic connection exists between the viruses in these regions and, if so, how SFTSV is transmitted across China, South Korea, and Japan. We therefore hypothesize that the SFTSV in South Korea share common phylogenetic origins with samples from China and Japan. Further, we postulate that migratory birds, well-known carriers of the tick H. longicornis, are a potential source of SFTSV transmission across countries. Our phylogenetic analysis results show that the SFTSV isolates in South Korea were similar to isolates from Japan and China. We connect this with previous work showing that SFTSV-infected H. longicornis were found in China, South Korea, and Japan. In addition, H. longicornis were found on migratory birds. The migratory bird routes and the distribution of H. longicornis are concurrent with the occurrence of SFTSV. Therefore, we suggest that migratory birds play an important role in dispersing H. longicornis-borne SFTSV.
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              Ecology of the Tick-Borne Phlebovirus Causing Severe Fever with Thrombocytopenia Syndrome in an Endemic Area of China

              Background Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a tick-borne phlebovirus in family Bunyaviridae. Studies have found that humans, domestic and wildlife animals can be infected by SFTSV. However, the viral ecology, circulation, and transmission remain largely unknown. Methodology/Principal Findings Sixty seven human SFTS cases were reported and confirmed by virus isolation or immunofluorescence assay between 2011 and 2014. In 2013–2014 we collected 9,984 ticks from either vegetation or small wild mammals in the endemic area in Jiangsu, China, and detected SFTSV-RNA by real-time RT-PCR in both questing and feeding Haemaphysalis longicornis and H. flava. Viral RNA was identified in larvae of H. longicornis prior to a first blood meal, which has never been confirmed previously in nature. SFTSV-RNA and antibodies were also detected by RT-PCR and ELISA, respectively, in wild mammals including Erinaceus europaeus and Sorex araneus. A live SFTSV was isolated from Erinaceus europaeus captured during the off tick-feeding season and with a high SFTSV antibody titer. Furthermore, SFTSV antibodies were detected in the migratory birds Anser cygnoides and Streptopelia chinensis using ELISA. Conclusions/Significance The detection of SFTSV-RNA in non-engorged larvae indicated that vertical transmission of SFTSV in H. longicornis might occur in nature, which suggests that H. longicornis is a putative reservoir host of SFTSV. Small wild mammals such as Erinaceus europaeus and Sorex araneus could be infected by SFTSV and may serve as natural amplifying hosts. Our data unveiled that wild birds could be infected with SFTSV or carry SFTSV-infected ticks and thus might contribute to the long-distance spread of SFTSV via migratory flyways. These findings provide novel insights for understanding SFTSV ecology, reservoir hosts, and transmission in nature and will help develop new measures in preventing its rapid spread both regionally and globally.
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                Author and article information

                Journal
                Am J Trop Med Hyg
                Am. J. Trop. Med. Hyg
                tpmd
                The American Journal of Tropical Medicine and Hygiene
                The American Society of Tropical Medicine and Hygiene
                0002-9637
                1476-1645
                07 December 2016
                07 December 2016
                : 95
                : 6
                : 1351-1357
                Affiliations
                [1 ]Division of Infectious Diseases, Jeju National University School of Medicine, Jeju, South Korea
                [2 ]Department of Microbiology and Immunology, Jeju National University School of Medicine, Jeju, South Korea
                [3 ]Special Pathogens Laboratory, Department of Virology I, National Institute of Infectious Diseases, Japan
                Author notes
                *Address correspondence to Keun Hwa Lee, Department of Microbiology and Immunology, Jeju National University School of Medicine, 15 Aran 13-gil, Jeju 63241, South Korea. E-mail: yomust7@ 123456jejunu.ac.kr
                †These authors contributed equally to this work.
                Article
                10.4269/ajtmh.16-0527
                5154449
                27928083
                1c750572-1e7e-430e-b625-82d1021e8bfe
                ©The American Society of Tropical Medicine and Hygiene

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 June 2016
                : 14 September 2016
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                Infectious disease & Microbiology
                Infectious disease & Microbiology

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