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      Combination effects of ribavirin and interferons on severe fever with thrombocytopenia syndrome virus infection

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          Abstract

          Background

          Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by SFTS virus and characterized by a high case fatality rate. Currently, there is no effective therapy for the disease. While the administration of ribavirin does not improve the case fatality rate or viral load in patient blood, it can inhibit viral infection in vitro.

          Methods

          Vero cells were pre-treated with interferons (IFNs) α, β, and γ alone and in combination with ribavirin drugs and inoculated with SFTS virus. Three days later, supernatants were harvested and subjected to virus titration. An unpaired t-test was used for statistical analysis of the drugs’ effects.

          Results

          While the effects of IFNγ at high concentrations were slightly weaker than those of the other IFNs, all IFNs showed dose-dependent inhibitory effects. The combined usage of IFNs with ribavirin at 90 % effective concentrations showed large inhibitory effects, with over a 3 log 10 reduction in viral titers.

          Conclusions

          The combined usage of one of type-I/II IFNs with ribavirin drastically reduced SFTS virus infection and therefore may be useful in the treatment of SFTS.

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          Clinical progress and risk factors for death in severe fever with thrombocytopenia syndrome patients.

          Zhong-Tao Gai, Ying. Zhang, Mi-Fang Liang … (2012)
          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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            Systematic review of severe fever with thrombocytopenia syndrome:virology, epidemiology, and clinical characteristics

            Shelan Liu, Chengliang Chai, Chengmin Wang … (2013)
            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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              Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in china who had severe fever with thrombocytopenia syndrome.

              Wei. Liu, Qing-Bin Lu, Ning Cui … (2013)
              The wide distribution and high case-fatality ratio of severe fever with thrombocytopenia syndrome (SFTS) have made it a significant public health problem. This study was designed to identify the predictors of fatal outcomes and to evaluate the effectiveness of antiviral therapy in treating SFTS virus (SFTSV)-infected patients. A cross-sectional study was performed in a general hospital located in Xinyang city, whereas the largest number of patients with SFTS in China were treated during 2011-2012. The primary outcome for the treatment effect analysis was death. Other outcomes included sequential platelet levels and viral loads observed throughout the hospitalization and the interval between the initiation of ribavirin therapy and the return of the platelet count to a normal level. A total of 311 SFTSV-infected patients were included in the study. The most frequent clinical presentations were fever, weakness, myalgia, and gastrointestinal symptoms. Each patient had thrombocytopenia, leukopenia, or both. The case-fatality ratio (CFR) was 17.4% (95% confidence interval [CI], 13.1%-21.6%). Older age (odds ratio [OR], 1.061; 95% CI, 1.023-1.099; P = .001), decreased level of consciousness (OR, 5.397; 95% CI, 2.660-10.948; P 1200 U/L; OR, 2.620; 95% CI, 1.073-6.399; P = .035) and creatine kinase (>800 U/L; OR, 2.328; 95% CI, 1.129-4.800; P = .022) were significantly associated with fatal outcome. The CFRs were similar between patients who received ribavirin and those who did not. Ribavirin treatment showed no significant effect on either platelet counts or viral loads during hospitalization of patients with fatal or nonfatal cases. These findings can improve knowledge about the characteristics of patients with fatal outcomes and the use of antiviral drug for SFTS.
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                Author and article information

                Contributors
                Masayuki Shimojima: +81-42-848-7020 , shimoji-@nih.go.jp
                Shuetsu Fukushi: fukushi@nih.go.jp
                Hideki Tani: htani@nih.go.jp
                Satoshi Taniguchi: re-tani@nih.go.jp
                Aiko Fukuma: Fukuma@nih.go.jp
                Masayuki Saijo: msaijo@nih.go.jp
                Journal
                Journal ID (nlm-ta): Virol J
                Journal ID (iso-abbrev): Virol. J
                Title: Virology Journal
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1743-422X
                Publication date (Electronic): 2 November 2015
                Publication date PMC-release: 2 November 2015
                Publication date Collection: 2015
                Volume: 12
                Electronic Location Identifier: 181
                Affiliations
                Department of Virology I, Chief, Special Pathogens Laboratory, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011 Japan
                Article
                Publisher ID: 412
                DOI: 10.1186/s12985-015-0412-3
                PMC ID: 4630909
                PubMed ID: 26527529
                SO-VID: bc4cacbb-b6b0-4367-a336-722573ece53f
                Copyright © © Shimojima et al. 2015
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 9 June 2015
                Date accepted : 28 October 2015
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2015

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: combination effect,interferon,ribavirin,sfts,sfts virus
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: combination effect, interferon, ribavirin, sfts, sfts virus

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