{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:43:35Z","timestamp":1792115015125,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010889","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Viral hemorrhagic fevers (VHFs) are a group of diseases, which can be endemo-epidemic in some areas of the world. Most of them are characterized by outbreaks, which occur irregularly and are hard to predict. Innovative medical countermeasures are to be evaluated but due to the field specificities of emerging VHF, challenges arise when implementing clinical studies. To assess the state of the art around VHFs, we conducted a systematic review for all reports and clinical studies that included specific results on number of cases, mortality and treatment of VHFs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The search was conducted in January 2020 based on PRISMA guidelines (PROSPERO CRD42020167306). We searched reports on the WHO and CDC websites, and publications in three international databases (MEDLINE, Embase and CENTRAL). Following the study selection process, qualitative and quantitative data were extracted from each included study. A narrative synthesis approach by each VHF was used. Descriptive statistics were conducted including world maps of cases number and case fatality rates (CFR); summary tables by VHF, country, time period and treatment studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 141 WHO\/CDC reports and 126 articles meeting the inclusion criteria. Most of the studies were published after 2010 (n = 97 for WHO\/CDC reports and n = 93 for publications) and reported number of cases and\/or CFRs (n = 141 WHO\/CDC reports and n = 88 publications). Results varied greatly depending on the outbreak or cluster and across countries within each VHF. A total of 90 studies focused on Ebola virus disease (EVD). EVD outbreaks were reported in Africa, where Sierra Leone (14,124 cases; CFR = 28%) and Liberia (10,678 cases; CFR = 45%) reported the highest cases numbers, mainly due to the 2014\u20132016 western Africa outbreak. Crimean-Congo hemorrhagic fever (CCHF) outbreaks were reported from 31 studies in Africa, Asia and Europe, where Turkey reported the highest cases number (6,538 cases; CFR = 5%) and Afghanistan the last outbreak in 2016\/18 (293 cases; CFR = 43%).<\/jats:p>\n                    <jats:p>Regarding the 38 studies reporting results on treatments, most of them were non-randomized studies (mainly retrospective or non-randomized comparative studies), and only 10 studies were randomized controlled trials. For several VHFs, no specific investigational therapeutic option with strong proof of effectiveness on mortality was identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We observed that number of cases and CFR varied greatly across VHFs as well as across countries within each VHF. The number of studies on VHF treatments was very limited with very few randomized trials and no strong proof of effectiveness of treatment against most of the VHFs. Therefore, there is a high need of methodologically strong clinical trials conducted in the context of VHF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0010889","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T13:57:56Z","timestamp":1667224676000},"page":"e0010889","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["The number of cases, mortality and treatments of viral hemorrhagic fevers: A systematic review"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0589-6614","authenticated-orcid":true,"given":"Drifa","family":"Belhadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majda","family":"El Baied","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Mulier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Malvy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"France","family":"Mentr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Laou\u00e9nan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"issue":"12","key":"pntd.0010889.ref001","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.disamonth.2013.10.003","article-title":"Viral hemorrhagic fever viruses.","volume":"59","author":"RB McFee","year":"2013","journal-title":"Dis Mon"},{"key":"pntd.0010889.ref002","unstructured":"CDC. Diseases Caused by High-Consequence Viruses [Internet]. [cited 2022 Jun 1]. Available from: https:\/\/www.cdc.gov\/ncezid\/dhcpp\/vspb\/diseases.html"},{"issue":"2","key":"pntd.0010889.ref003","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.idc.2006.02.001","article-title":"Viral hemorrhagic fevers: current status of endemic disease and strategies for control.","volume":"20","author":"DJ Cleri","year":"2006","journal-title":"Infect Dis Clin"},{"issue":"1","key":"pntd.0010889.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1741-7015-10-31","article-title":"Viral hemorrhagic fevers: advancing the level of treatment.","volume":"10","author":"G Ippolito","year":"2012","journal-title":"BMC Med"},{"issue":"10174","key":"pntd.0010889.ref005","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/S0140-6736(18)33132-5","article-title":"Ebola virus disease","volume":"393","author":"D Malvy","year":"2019","journal-title":"The Lancet"},{"issue":"4","key":"pntd.0010889.ref006","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.idc.2019.08.003","article-title":"Viral hemorrhagic fevers other than Ebola and Lassa.","volume":"33","author":"M Iannetta","year":"2019","journal-title":"Infect Dis Clin"},{"issue":"1","key":"pntd.0010889.ref007","first-page":"1","article-title":"Anti-Ebola therapy for patients with Ebola virus disease: a systematic review.","volume":"19","author":"JS Lee","year":"2019","journal-title":"BMC Infect Dis"},{"key":"pntd.0010889.ref008","author":"CDC","journal-title":"Diseases Caused by High-Consequence Viruses"},{"issue":"1","key":"pntd.0010889.ref009","first-page":"1","article-title":"The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.","volume":"2","author":"J Peterson","year":"2011","journal-title":"Ott Ott Hosp Res Inst"},{"key":"pntd.0010889.ref010","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/9781119536604.ch8","article-title":"Assessing risk of bias in a randomized trial.","author":"JP Higgins","year":"2019","journal-title":"Cochrane Handb Syst Rev Interv."},{"issue":"8154","key":"pntd.0010889.ref011","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/S0140-6736(79)92335-3","article-title":"Efficacy of immune plasma in treatment of Argentine haemorrhagic fever and association between treatment and a late neurological syndrome","volume":"2","author":"JI Maiztegui","year":"1979","journal-title":"Lancet Lond Engl"},{"issue":"3","key":"pntd.0010889.ref012","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jinf.2009.01.014","article-title":"Efficacy of oral ribavirin treatment in Crimean-Congo haemorrhagic fever: a quasi-experimental study from Turkey.","volume":"58","author":"N Elaldi","year":"2009","journal-title":"J Infect."},{"issue":"9","key":"pntd.0010889.ref013","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1093\/cid\/cit527","article-title":"Severity scoring index for Crimean-Congo hemorrhagic fever and the impact of ribavirin and corticosteroids on fatality","volume":"57","author":"B Dokuzoguz","year":"2013","journal-title":"Clin Infect Dis Off Publ Infect Dis Soc Am"},{"issue":"4","key":"pntd.0010889.ref014","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jinf.2008.07.007","article-title":"A preliminary study to evaluate the effect of intravenous ribavirin treatment on survival rates in Crimean-Congo hemorrhagic fever.","volume":"57","author":"MA Cevik","year":"2008","journal-title":"J Infect."},{"key":"pntd.0010889.ref015","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofw172.531","article-title":"Ribavirin in treatment of crimean-congo hemorrhagic fever (CCHF): An international multicenter retrospective analysis.","volume":"3","author":"G. 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Tulek","year":"2012","journal-title":"Clin Microbiol Infect"},{"issue":"1","key":"pntd.0010889.ref018","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jcv.2009.11.007","article-title":"The efficacy of ribavirin in the treatment of Crimean-Congo hemorrhagic fever in Eastern Black Sea region in Turkey.","volume":"47","author":"I Koksal","year":"2010","journal-title":"J Clin Virol Off Publ Pan Am Soc Clin Virol."},{"issue":"12","key":"pntd.0010889.ref019","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1086\/375058","article-title":"The efficacy of oral ribavirin in the treatment of crimean-congo hemorrhagic fever in Iran","volume":"36","author":"M Mardani","year":"2003","journal-title":"Clin Infect Dis Off Publ Infect Dis Soc Am"},{"issue":"6","key":"pntd.0010889.ref020","first-page":"497","article-title":"Comparative study between Ribavirin and Ribavirin plus Intravenous Immunoglobulin against Crimean Congo hemorrhagic fever.","volume":"18","author":"H Salehi","year":"2013","journal-title":"J Res Med Sci Off J Isfahan Univ Med Sci."},{"key":"pntd.0010889.ref021","first-page":"ciz344","article-title":"Impact of Intravenous Fluid Therapy on Survival Among Patients with Ebola Virus Disease: An International Multisite Retrospective Cohort Study","author":"A.R. 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