{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T11:22:27Z","timestamp":1785583347529,"version":"3.56.0"},"reference-count":18,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SIGA Technologies Inc"},{"name":"Foreign, Commonwealth and Development Office and Wellcome","award":["215091\/Z\/18\/Z"],"award-info":[{"award-number":["215091\/Z\/18\/Z"]}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1209135"],"award-info":[{"award-number":["OPP1209135"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\n Background<\/jats:title>\n Monkeypox is a viral zoonotic disease commonly reported in humans in parts of Central and West Africa. This protocol is for an Expanded Access Programme (EAP) to be implemented in the Central African Republic, where Clade I monkeypox virus diseases is primarily responsible for most monkeypox infections. The objective of the programme is to provide patients with confirmed monkeypox with access to tecovirimat, a novel antiviral targeting orthopoxviruses, and collect data on clinical and virological outcomes of patients to inform future research.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The study will be conducted at participating hospitals in the Central African Republic. All patients who provide informed consent to enrol in the programme will receive tecovirimat. Patients will remain in hospital for the duration of treatment. Data on clinical signs and symptoms will be collected every day while the patient is hospitalised. Blood, throat and lesion samples will be collected at baseline and then on days 4, 8, 14 and 28. Patient outcomes will be assessed on Day 14 \u2013end of treatment\u2013and at Day 28. Adverse event and serious adverse event data will be collected from the point of consent until Day 28.<\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n This EAP is the first protocolised treatment programme in Clade I MPXV. The data generated under this protocol aims to describe the use of tecovirimat for Clade I disease in a monkeypox endemic region of Central Africa. It is hoped that this data can inform the definition of outcome measures used in future research and contribute to the academic literature around the use of tecovirimat for the treatment of monkeypox. The EAP also aims to bolster research capacity in the region in order for robust randomised controlled trials to take place for monkeypox and other diseases.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n \n {2a & 2b}<\/jats:bold>\n :\n ISRCTN43307947<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0278957","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T13:43:57Z","timestamp":1715262237000},"page":"e0278957","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Expanded Access Programme for the use of tecovirimat for the treatment of monkeypox infection: A study protocol for an Expanded Access Programme"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4687-8380","authenticated-orcid":true,"given":"Josephine","family":"Bourner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Festus Devincy","family":"Redji Mbrenga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-2212","authenticated-orcid":true,"given":"Christian No\u00ebl","family":"Malaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"Dunning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Rojek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Fandema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Horby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yap","family":"Boum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Nakoun\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Olliaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"issue":"10","key":"pone.0278957.ref001","doi-asserted-by":"crossref","first-page":"306","DOI":"10.15585\/mmwr.mm6710a5","article-title":"Emergence of Monkeypox\u2014West and Central Africa, 1970\u20132017","volume":"67","author":"KN Durski","year":"2018","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"10","key":"pone.0278957.ref002","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1099\/vir.0.81215-0","article-title":"A tale of two clades: monkeypox viruses","volume":"86","author":"AM Likos","year":"2005","journal-title":"Journal of General Virology"},{"key":"pone.0278957.ref003","unstructured":"World Health Organisation. Multi-country monkeypox outbreak: situation update 2022 [11\/10\/2022]."},{"issue":"8","key":"pone.0278957.ref004","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.3201\/eid2508.190112","article-title":"Intrafamily Transmission of Monkeypox Virus, Central African Republic, 2018","volume":"25","author":"C Besombes","year":"2019","journal-title":"Emerg Infect Dis"},{"issue":"1","key":"pone.0278957.ref005","doi-asserted-by":"crossref","first-page":"13085","DOI":"10.1038\/s41598-021-92315-8","article-title":"Genomic history of human monkey pox infections in the Central African Republic between 2001 and 2018","volume":"11","author":"N Berthet","year":"2021","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0278957.ref006","doi-asserted-by":"crossref","first-page":"171089","DOI":"10.1098\/rsos.171089","article-title":"Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time","volume":"5","author":"MS Tiee","year":"2018","journal-title":"R Soc Open Sci"},{"key":"pone.0278957.ref007","unstructured":"World Health Organisation. Monkeypox 2022 [29\/09\/2022]. Available from: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/monkeypox."},{"key":"pone.0278957.ref008","unstructured":"European Medicines Agency. Tecovirimat SIGA 2022 [29\/09\/2022]. Available from: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/tecovirimat-siga."},{"key":"pone.0278957.ref009","unstructured":"FDA approves the first drug with an indication for treatment of smallpox [Internet]. 2018. Available from: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-drug-indication-treatment-smallpox"},{"key":"pone.0278957.ref010","article-title":"Compassionate Use of Tecovirimat for the Treatment of Monkeypox Infection","author":"AN Desai","year":"2022","journal-title":"JAMA"},{"issue":"8","key":"pone.0278957.ref011","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/S1473-3099(22)00228-6","article-title":"Clinical features and management of human monkeypox: a retrospective observational study in the UK","volume":"22","author":"H Adler","year":"2022","journal-title":"Lancet Infect Dis"},{"issue":"14","key":"pone.0278957.ref012","doi-asserted-by":"crossref","first-page":"509","DOI":"10.15585\/mmwr.mm7114a1","article-title":"Monkeypox in a Traveler Returning from Nigeria\u2014Dallas, Texas, July 2021","volume":"71","author":"AK Rao","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"8","key":"pone.0278957.ref013","doi-asserted-by":"crossref","first-page":"ofac377","DOI":"10.1093\/ofid\/ofac377","article-title":"Tecovirimat for the Treatment of Human Monkeypox: An Initial Series From Massachusetts, United States","volume":"9","author":"WR Matias","year":"2022","journal-title":"Open Forum Infect Dis"},{"issue":"9","key":"pone.0278957.ref014","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/S1473-3099(22)00514-X","article-title":"Monkeypox: how will we know if the treatments work?","volume":"22","author":"A Rojek","year":"2022","journal-title":"The Lancet Infectious Diseases"},{"key":"pone.0278957.ref015","article-title":"Monkeypox treatment with tecovirimat in the Central African Republic under an Expanded Access Programme","author":"F Mbrenga","year":"2022","journal-title":"medRxiv"},{"key":"pone.0278957.ref016","unstructured":"European Medicines Agency. Guideline for good clinical practice E6(R2). 2016."},{"key":"pone.0278957.ref017","unstructured":"Semple MG. Clinical characterisation protocol for severe emerging infections ISRCTN2022 [11\/10\/2022]. Available from: https:\/\/www.isrctn.com\/ISRCTN66726260."},{"key":"pone.0278957.ref018","doi-asserted-by":"crossref","unstructured":"Horby P. Antiviral treatment with tecovirimat for patients managed at home with monkeypox ISRCTN2022 [11\/10\/2022]. Available from: https:\/\/www.isrctn.com\/ISRCTN17461766.","DOI":"10.1186\/ISRCTN17461766"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0278957","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T13:44:12Z","timestamp":1715262252000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0278957"}},"subtitle":[],"editor":[{"given":"Sebastien","family":"Kenmoe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,5,9]]},"references-count":18,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0278957","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.11.28.22282846","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,9]]}}}