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      Epidemiological and Clinical Features of Severe Fever with Thrombocytopenia Syndrome in Japan, 2013–2014

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          Abstract

          Although severe fever with thrombocytopenia syndrome (SFTS) was first reported from Japan in 2013, the precise clinical features and the risk factors for SFTS have not been fully investigated in Japan. Ninety-six cases of severe fever with thrombocytopenia syndrome (SFTS) were notified through the national surveillance system between April 2013 and September 2014 in Japan. All cases were from western Japan, and 82 cases (85%) had an onset between April and August. A retrospective observational study of the notified SFTS cases was conducted to identify the clinical features and laboratory findings during the same period. Of 96 notified cases, 49 (51%) were included in this study. Most case-patients were of advanced age (median age 78 years) and were retired or unemployed, or farmers. These case-patients had a history of outdoor activity within 2 weeks before the onset of illness. The median serum C-reactive protein concentration was slightly elevated at admission. Fungal infections such as invasive aspergilosis were found in 10% of these case-patients. Hemophagocytosis was observed in 15 of the 18 case-patients (83%) whose bone marrow samples were available. Fifteen cases were fatal, giving a case-fatality proportion of 31%. The proportion of neurological abnormalities and serum concentrations of lactate dehydrogenase and aspartate aminotransferase were significantly higher in the fatal cases than in the nonfatal cases during hospitalization. Appearance of neurological abnormality may be useful for predicting the prognosis in SFTS patients.

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          Most cited references20

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          Haemaphysalis longicornis Ticks as Reservoir and Vector of Severe Fever with Thrombocytopenia Syndrome Virus in China

          Transstadial and transovarial virus transmission occur among ticks, and transmission to mice can occur through a tick bite.
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            Clinical progress and risk factors for death in severe fever with thrombocytopenia syndrome patients.

            Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV) with an average fatality rate of 12%. The clinical factors for death in SFTS patients remain unclear. Clinical features and laboratory parameters were dynamically collected for 11 fatal and 48 non-fatal SFTS cases. Univariate logistic regression was used to evaluate the risk factors associated with death. Dynamic tracking of laboratory parameters revealed that during the initial fever stage, the viral load was comparable for the patients who survived as well as the ones that died. Then in the second stage when multi-organ dysfunction occurred, from 7-13 days after disease onset, the viral load decreased in survivors but it remained high in the patients that died. The key risk factors that contributed to patient death were elevated serum aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase fraction, as well as the appearance of CNS (central nervous system) symptoms, hemorrhagic manifestation, disseminated intravascular coagulation, and multi-organ failure. All clinical markers reverted to normal in the convalescent stage for SFTS patients who survived. We identified a period of 7-13 days after the onset of illness as the critical stage in SFTS progression. A sustained serum viral load may indicate that disease conditions will worsen and lead to death.
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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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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                24 October 2016
                2016
                : 11
                : 10
                : e0165207
                Affiliations
                [1 ]Feild Epidemiology Training Program (FETP), National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan
                [2 ]Division of Global Infectious Diseases, Department of Infection and Epidemiology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan
                [3 ]Infectious Disease Surveillance Center, National Institute of Infectious diseases, Shinjuku, Tokyo, Japan
                [4 ]Department of Virology I, National Institute of Infectious diseases, Shinjuku, Tokyo, Japan
                University of Minnesota College of Veterinary Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: TY.

                • Data curation: TY HK.

                • Formal analysis: TY HK.

                • Funding acquisition: MSa KO.

                • Investigation: TY HK.

                • Methodology: TY HK.

                • Project administration: MSa KO.

                • Resources: MSh MSa KO.

                • Software: TY HK.

                • Supervision: KO.

                • Validation: TY TS TM KO.

                • Visualization: HK.

                • Writing – original draft: TY HK KO.

                • Writing – review & editing: TS TM MSa KO.

                ¶ Membership of the SFTS epidemiological research group-Japan is provided in the Acknowledgments.

                Article
                PONE-D-16-20408
                10.1371/journal.pone.0165207
                5077122
                27776187
                4226fb42-d663-4f70-a03b-6525ec6b2d6b
                © 2016 Kato et al

                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
                : 20 May 2016
                : 7 October 2016
                Page count
                Figures: 2, Tables: 4, Pages: 13
                Funding
                Funded by: The Ministry of Health, Labour and Welfare of Japan
                Award ID: H25-Shinko-Shitei-009
                Award Recipient :
                Funded by: the Japan Agency for Medical Research and Development
                Award Recipient :
                This research was supported by grants for Research on Emerging and Re-emerging Infectious Diseases from the Ministry of Health, Labour and Welfare of Japan [H25-Shinko-Shitei-009, http://www.mhlw.go.jp/] and the Research Program on Emerging and Re-emerging Infectious Diseases from the Japan Agency for Medical Research and Development [ http://www.amed.go.jp/]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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