{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:49:50Z","timestamp":1792669790866,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010289","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000}}],"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000276","name":"Department of Health and Social Care","doi-asserted-by":"crossref","award":["EPIDZK3812"],"award-info":[{"award-number":["EPIDZK3812"]}],"id":[{"id":"10.13039\/501100000276","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Ribavirin is currently the standard of care for treating Lassa fever. However, the human clinical trial data supporting its use suffer from several serious flaws that render the results and conclusions unreliable. We performed a systematic review of available pre-clinical data and human pharmacokinetic data on ribavirin in Lassa. In in-vitro studies, the EC50 of ribavirin ranged from 0.6 \u03bcg\/ml to 21.72 \u03bcg\/ml and the EC90 ranged from 1.5 \u03bcg\/ml to 29 \u03bcg\/ml. The mean EC50 was 7 \u03bcg\/ml and the mean EC90 was 15 \u03bcg\/ml. Human PK data in patients with Lassa fever was sparse and did not allow for estimation of concentration profiles or pharmacokinetic parameters. Pharmacokinetic modelling based on healthy human data suggests that the concentration profiles of current ribavirin regimes only exceed the mean EC50 for less than 20% of the time and the mean EC90 for less than 10% of the time, raising the possibility that the current ribavirin regimens in clinical use are unlikely to reliably achieve serum concentrations required to inhibit Lassa virus replication. The results of this review highlight serious issues with the evidence, which, by today standards, would be unlikely to support the transition of ribavirin from pre-clinical studies to human clinical trials. Additional pre-clinical studies are needed before embarking on expensive and challenging clinical trials of ribavirin in Lassa fever.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010289","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T17:38:18Z","timestamp":1648661898000},"page":"e0010289","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":75,"title":["Ribavirin for treating Lassa fever: A systematic review of pre-clinical studies and implications for human dosing"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3139-3321","authenticated-orcid":true,"given":"Alex P.","family":"Salam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Duvignaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Jaspard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Malvy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Tarning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero L.","family":"Olliaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W.","family":"Horby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"pntd.0010289.ref001","first-page":"11","article-title":"Baseline mapping of Lassa fever virology, epidemiology and vaccine research and development.","volume":"3","author":"HJ Hallam","year":"2018","journal-title":"Vaccines"},{"key":"pntd.0010289.ref002","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.antiviral.2018.09.009","article-title":"The WHO R&D Blueprint: 2018 review of emerging infectious diseases requiring urgent research and development efforts","volume":"159","author":"MS Mehand","year":"2018","journal-title":"Antiviral research"},{"key":"pntd.0010289.ref003","author":"World Health Organisation","year":"2018","journal-title":"2018 Annual review of diseases prioritized under the Research and Development Blueprint."},{"key":"pntd.0010289.ref004","author":"Nigeria Center for Disease Control","year":"2018","journal-title":"National Guidelines for Lassa Fever Case Management"},{"key":"pntd.0010289.ref005","author":"World Health Organisation","year":"2014","journal-title":"Clinical Management of Patients with Viral Haemorrhagic Fever"},{"issue":"1","key":"pntd.0010289.ref006","first-page":"20","article-title":"Lassa fever. 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