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      Risk Factors for Bunyavirus-Associated Severe Fever with Thrombocytopenia Syndrome: A Community-Based Case-Control Study

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          Abstract

          Background

          Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus. Previous studies about risk factors for SFTSV infection have yielded inconsistent results, and behavior factors have not been fully clarified.

          Methods

          A community-based, 1:4 matched case-control study was carried out to investigate the risk factors for SFTS in China. Cases of SFTS were defined as laboratory-confirmed cases that tested positive for real-time PCR (RT-PCR) for severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) or positive for IgM antibodies against SFTSV. Controls of four neighborhood subjects were selected by matching for sex, age, and occupation. Standardized questionnaires were used to collect detailed information about their demographics and risk factors for SFTSV infection.

          Results

          A total of 334 subjects participated in the study including 69 cases and 265 controls. The median age of the cases was 59.5 years, 55.1% were male, and 87.0% were farmers. No differences in demographics were observed between cases and controls. In the final multivariate analysis, tick bites two weeks prior to disease onset (OR = 8.04, 95%CI 3.34–19.37) and the presence of weeds and shrubs around the house (OR = 3.46, 95%CI 0.96–12.46) were found to be risk factors for SFTSV infection; taking preventative measures during outdoor activities (OR = 0.12, 95%CI 0.01–1.01) provided greater protection from SFTSV infection.

          Conclusions

          Our results further confirm that SFTSV is transmitted by tick bites and prove that preventative measures that reduce exposure to ticks can prevent SFTSV infection. More efforts should be directed toward health education and behavior change for high-risk populations, especially outdoor workers, in SFTS endemic areas.

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          Most cited references19

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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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            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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              A National Assessment of the Epidemiology of Severe Fever with Thrombocytopenia Syndrome, China

              First discovered in rural areas of middle-eastern China in 2009, severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis affecting hundreds of cases reported in China each year. Using the national surveillance data from 2010 to 2013, we conducted this retrospective epidemiological study and risk assessment of SFTS in China. We found that the incidence of SFTS and its epidemic areas are continuing to grow, but the case fatality rate (CFR) has steadily decreased. SFTS most commonly affected elderly farmers who acquired infection between May and July in middle-eastern China. However, other epidemiological characteristics such as incidence, sex ratio, CFR, and seasonality differ substantially across the affected provinces, which seem to be consistent with local agricultural activities and the seasonal abundance of ticks. Spatial scan statistics detected three hot spots of SFTS that accounted for 69.1% of SFTS cases in China. There was a strong association of SFTS incidence with temporal changes in the climate within the clusters. Multivariate modeling identified climate conditions, elevation, forest coverage, cattle density, and the presence of Haemaphysalis longicornis ticks as independent risk factors in the distribution of SFTS, based on which a predicted risk map of the disease was derived.
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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
                15 November 2016
                2016
                : 11
                : 11
                : e0166611
                Affiliations
                [1 ]Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China
                [2 ]Medical School, Nanjing University, Nanjing, Jiangsu Province, China
                [3 ]Department of Acute Infectious Disease Control and Prevention, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China
                [4 ]Department of Disease Control and Prevention, Gulou District Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China
                [5 ]Department of Acute Infectious Disease Control and Prevention, Chuzhou Municipal Center for Disease Control and Prevention, Chuzhou, Anhui Province, China
                [6 ]Department of Acute Infectious Disease Control and Prevention, Lishui District Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China
                [7 ]Department of Acute Infectious Disease Control and Prevention, Xuyi County Center for Disease Control and Prevention, Huai’an, Jiangsu Province, China
                [8 ]Department of Acute Infectious Disease Control and Prevention, Yixing County Center for Disease Control and Prevention, Wuxi, Jiangsu Province, China
                University of Texas Medical Branch, UNITED STATES
                Author notes

                Competing Interests: All of the authors declare no conflict of interest here.

                • Conceptualization: CB.

                • Data curation: JH XW.

                • Formal analysis: JH XW WZ.

                • Funding acquisition: CB.

                • Investigation: LH HH WC LL AS XL SY JZ WT.

                • Methodology: JH ZL.

                • Project administration: FT FZ.

                • Resources: LH HH WC LL AS XL SY JZ WT.

                • Software: JH.

                • Supervision: FT FZ.

                • Validation: FT FZ.

                • Visualization: JH ZL CB.

                • Writing – original draft: JH.

                • Writing – review & editing: ZL CB.

                Article
                PONE-D-16-23445
                10.1371/journal.pone.0166611
                5112944
                27846273
                eb52f7c4-7b90-4260-9e1e-b2f1a93fee9a
                © 2016 Hu 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
                : 11 June 2016
                : 1 November 2016
                Page count
                Figures: 0, Tables: 3, Pages: 10
                Funding
                Funded by: the Science & Technology Demonstration Project for Emerging Infectious Diseases Control and Prevention
                Award ID: BE2015714
                Funded by: funder-id http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81373055
                Award Recipient :
                Funded by: the 10th Summit of Six Top Talents of Jiangsu Province
                Award ID: WS-2013-061
                Award Recipient :
                This study was financially supported by the Science & Technology Demonstration Project for Emerging Infectious Diseases Control and Prevention(No. BE2015714), and partly supported by Natural Science Foundation of China (No.81373055), and the 10th Summit of Six Top Talents of Jiangsu Province (WS-2013-061). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Epidemiology
                Disease Vectors
                Ticks
                Biology and Life Sciences
                Organisms
                Animals
                Invertebrates
                Arthropoda
                Arachnida
                Ixodes
                Ticks
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Medicine and Health Sciences
                Health Care
                Health Risk Analysis
                Biology and Life Sciences
                Organisms
                Plants
                Weeds
                Biology and Life Sciences
                Organisms
                Plants
                Shrubs
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Fevers
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Fevers
                Medicine and Health Sciences
                Hematology
                Thrombocytopenia
                People and Places
                Demography
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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                Uncategorized

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