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      Systematic review of severe fever with thrombocytopenia syndrome:virology, epidemiology, and clinical characteristics

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          Abstract

          Severe fever with thrombocytopenia syndrome (SFTS) was firstly discovered in China in 2010, followed by several reports from many other countries worldwide. SFTS virus (SFTSV) has been identified as the causative agent of the disease and has been recognized as a public health threat. This novel Bunyavirus belongs to the Phlebovirus genus in the family Bunyaviridae. This review also describes the different aspects of virology, pathogenesis, epidemiology, and clinical symptoms on the basis of the published article surveillance data and phylogenetic analyses of viral sequences of large, medium, and small segments retrieved from database using mega 5.05, simplot 3.5.1, network 4.611, and epi information system 3.5.3 software. SFTS presents with fever, thrombocytopenia, leukocytopenia, and considerable changes in several serum biomarkers. The disease has 10 ∼ 15% mortality rate, commonly because of multiorgan dysfunction. SFTSV is mainly reported in the rural areas of Central and North-Eastern China, with seasonal occurrence from May to September, mainly targeting those of ≥50 years of age. A wide range of domesticated animals, including sheep, goats, cattle, pigs, dogs, and chickens have been proven seropositive for SFTSV. Ticks, especially Haemaphysalis longicornis, are suspected to be the potential vector, which have a broad animal host range in the world. More studies are needed to elucidate the vector–animal–human ecological cycle, the pathogenic mechanisms in high level animal models and vaccine development. © 2013 The Authors. Reviews in Medical Virology published by John Wiley & Sons, Ltd.

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          Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination.

          The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.
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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

                Journal
                Rev Med Virol
                Rev. Med. Virol
                rmv
                Reviews in Medical Virology
                BlackWell Publishing Ltd (Oxford, UK )
                1052-9276
                1099-1654
                March 2014
                06 December 2013
                : 24
                : 2
                : 90-102
                Affiliations
                [1 ]Department of Infectious Diseases, Zhejiang Provincial Centre for Disease Control and Prevention Hangzhou, Zhejiang Province, China
                [2 ]National Research Center for Wildlife Born Diseases, Institute of Zoology, Chinese Academy of Sciences Beijing, China
                [3 ]Department of Zoology, Faculty of Science, Kafr El-Sheikh University Kafr El-Sheikh, Egypt
                [4 ]Department of Public Health Surveillance and Advisory, Zhejiang Provincial Centre for Disease Control and Prevention Hangzhou, Zhejiang Province, China
                Author notes
                *Corresponding author: J. Lin, Department of Public Health Surveillance and Advisory, Zhejiang Provincial Centre for Disease Control and Prevention, 630 XinCheng Road, Binjiang District, Hangzhou, Zhejiang Province 310051, China., E-mail: jflin@ 123456cdc.zj.cn
                [†]

                These authors contributed equally to this work.

                Article
                10.1002/rmv.1776
                4237196
                24310908
                76a31d55-f840-4254-a566-38a68d3fc300
                © 2013 The Authors. Reviews in Medical Virology published by John Wiley & Sons, Ltd.

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 30 April 2013
                : 19 October 2013
                : 04 November 2013
                Categories
                Review

                Microbiology & Virology
                Microbiology & Virology

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