{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T03:22:07Z","timestamp":1781839327689,"version":"3.54.5"},"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The artemisinin derivatives are the preferred antimalaria drugs for treating severe <jats:italic>Plasmodium falciparum<\/jats:italic> malaria. However, their clinical effectiveness compared to each other is unknown. Our objective, therefore, was to evaluate the efficacy and safety of the artemisinin derivatives and quinine for treating severe <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> malaria in children and adults using a network meta-analysis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>Review protocol was registered with PROSPERO, CRD42020218190. We updated the search strategies of three Cochrane systematic reviews which included published and unpublished randomised control trials (RCTs) that have compared specific artemisinin derivatives to quinine in treating severe malaria. Search included CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science and trial registries up to February 2021. We screened studies, extracted data, assessed risk of bias, and quality of evidence in duplicate. Separate network meta-analyses in the frequentist framework, using a random effects model, with quinine as reference, were conducted for adults and children, and rankings were produced using p-scores to assess mortality, parasite clearance, coma recovery, fever clearance, neurological sequela and adverse events.<\/jats:p>\n<jats:p>Searches identified 818 citations, 33 RCTs were eligible. We pooled 7795 children and 3182 adults. The networks involved artesunate, artemether, rectal artemisinin, arteether and quinine. Compared to quinine, artesunate reduced mortality in children (risk ratio (RR), 0.76; 95%CI [0.65 to 0.89], moderate quality), adults (RR, 0.55; 95%CI [0.40 to 0.75], moderate quality) and in cerebral malaria (RR, 0.72; 95%CI [0.55 to 0.94], moderate quality).<\/jats:p>\n<jats:p>Compared to rectal artemisinin and intramuscular arteether, the efficacy and safety of parenteral artesunate, and intramuscular artemether in treating severe malaria are not clear. Rankings showed that none of the artemisinin drugs were consistently superior in all the outcomes assessed. Indirect evidence produced were of very low ratings due to suspected publication bias and imprecision.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Artesunate reduces mortality compared to quinine for both adults and children in Asia and Africa including cerebral malaria. The artemisinin derivatives remain the best treatment for severe malaria but their comparative clinical effectiveness is yet to be fully explored.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0269391","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T17:37:52Z","timestamp":1658338672000},"page":"e0269391","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Comparative efficacy and safety of the artemisinin derivatives compared to quinine for treating severe malaria in children and adults: A systematic update of literature and network meta-analysis"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9859-6628","authenticated-orcid":true,"given":"Nicholas","family":"Nyaaba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana Efua","family":"Andoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Amoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8920-0708","authenticated-orcid":true,"given":"Dominic Selorm Yao","family":"Amuzu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Ansong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Ord\u00f3\u00f1ez-Mena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8416-2159","authenticated-orcid":true,"given":"Jennifer","family":"Hirst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,7,20]]},"reference":[{"key":"pone.0269391.ref001","doi-asserted-by":"crossref","DOI":"10.30875\/60123dd4-en","volume-title":"World Malaria Report 2020:20 years of global progress and challenges [Internet]","author":"World Health Organization","year":"2020"},{"key":"pone.0269391.ref002","unstructured":"Global Health Observatory. 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White","year":"2015","journal-title":"Stata J"},{"key":"pone.0269391.ref035","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"R DerSimonian","year":"1986","journal-title":"Control Clin Trials"},{"key":"pone.0269391.ref036","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1471-2288-13-35","article-title":"A graphical tool for locating inconsistency in network meta-analyses","volume":"13","author":"U Krahn","year":"2013","journal-title":"BMC Medical Research Methodology"},{"issue":"2","key":"pone.0269391.ref037","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/jrsm.1327","article-title":"Assessing the consistency assumptions underlying network meta-regression using aggregate data.","volume":"10","author":"S Donegan","year":"2019","journal-title":"Res Synth Methods [Internet]"},{"key":"pone.0269391.ref038","first-page":"1","article-title":"Ranking 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Abdallah","year":"2014","journal-title":"J Infect Dev Ctries [Internet]"},{"issue":"6","key":"pone.0269391.ref042","first-page":"777","article-title":"Comparison of combinations of parenteral artemisinin derivatives plus oral mefloquine with intravenous quinine plus oral tetracycline for treating cerebral malaria","volume":"70","author":"K Win","year":"1992","journal-title":"Bull World Health Organ [Internet]."},{"key":"pone.0269391.ref043","first-page":"32","article-title":"Comparative efficacy of quinine and artesunate in the treatment of severe malaria: a randomized controlled trial","volume":"7","author":"N Haroon","year":"2005","journal-title":"JK Sci."},{"key":"pone.0269391.ref044","article-title":"Randomized comparative study of artesunate intravenously and quinine in loading dose IV on severe and complicated malaria","author":"T Anh","year":"1989","journal-title":"Vietnam"},{"issue":"4","key":"pone.0269391.ref045","first-page":"768","article-title":"Preliminary report: A comparative clinical trial of arthemeter and quinine in severe falciparum malaria","volume":"23","author":"J Karbwang","year":"1992","journal-title":"Southeast Asian J Trop Med Public Health"},{"issue":"5","key":"pone.0269391.ref046","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/0035-9203(93)90092-5","article-title":"An open randomized comparative study of intramuscular artemether and intravenous quinine in cerebral malaria in children","volume":"87","author":"O Walker","year":"1993","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"pone.0269391.ref047","author":"T Anh","journal-title":"Comparative study of intravenous artesunate followed by oral mefloquine versus intra"},{"issue":"6","key":"pone.0269391.ref048","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/0035-9203(95)90437-9","article-title":"Comparison of artemether and quinine in the treatment of severe falciparum malaria in south-east Thailand","volume":"89","author":"J Karbwang","year":"1995","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"2","key":"pone.0269391.ref049","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1056\/NEJM199607113350202","article-title":"A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria","volume":"335","author":"TT Hien","year":"1996","journal-title":"N Engl J Med"},{"key":"pone.0269391.ref050","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1056\/NEJM199607113350201","article-title":"A trial of artemether or quinine in children with cerebral malaria","volume":"335","author":"MB Van Hensbroek","year":"1996","journal-title":"N Engl J Med"},{"issue":"3","key":"pone.0269391.ref051","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/S0035-9203(96)90260-6","article-title":"An open randomized trial of artemether versus quinine in the treatment of cerebral malaria in African children","volume":"90","author":"S Murphy","year":"1996","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"2","key":"pone.0269391.ref052","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/00034983.1998.11813272","article-title":"Randomized comparison of intramuscular artemether and intravenous quinine in adult, Melanesian patients with severe or complicated, plasmodium falciparum malaria in Papua New Guinea","volume":"92","author":"RA Seaton","year":"1998","journal-title":"Ann Trop Med Parasitol"},{"issue":"1","key":"pone.0269391.ref053","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1046\/j.1365-3156.1998.00166.x","article-title":"Intramuscular artemether vs intravenous quinine: An open, randomized trial in Malawian children with cerebral malaria","volume":"3","author":"TE Taylor","year":"1998","journal-title":"Trop Med Int Heal"},{"key":"pone.0269391.ref054","first-page":"450","article-title":"Clinical response and parasite clearance in childhood cerebral malaria: A comparison between intramuscular artemether and intravenous quinine","volume":"75","author":"A Ojuawo","year":"1998","journal-title":"East Afr Med J"},{"issue":"3","key":"pone.0269391.ref055","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0001-706X(99)00031-5","article-title":"Comparative efficacy of intramuscular artemether and intravenous quinine in Nigerian children with cerebral malaria","volume":"73","author":"PE Olumese","year":"1999","journal-title":"Acta Trop"},{"issue":"4","key":"pone.0269391.ref056","doi-asserted-by":"crossref","first-page":"524","DOI":"10.4269\/ajtmh.2000.62.524","article-title":"A randomized controlled trial of artemotil (\u03b2-arteether) in Zambian children with cerebral malaria","volume":"62","author":"PE Thuma","year":"2000","journal-title":"Am J Trop Med Hyg"},{"issue":"5","key":"pone.0269391.ref057","doi-asserted-by":"crossref","first-page":"229","DOI":"10.4269\/ajtmh.2001.64.229","article-title":"Clinical trial of \u03b2-arteether versus quinine for 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Childrenwith Severe Falciparum Malaria with Quinine and Artemether","volume":"2","author":"O Osonuga","year":"2011","journal-title":"World J Med Sci"},{"issue":"4","key":"pone.0269391.ref068","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3889\/MJMS.1857-5773.2009.0077","article-title":"Parasitaemia changes in the course of treatment of severe malaria patients with artemether and quinine (A preliminary study).","volume":"2","author":"O Osonuga","year":"2009","journal-title":"Maced J Med Sci"},{"issue":"2","key":"pone.0269391.ref069","first-page":"42","article-title":"Temperature changes in the course of treatment of severe malaria patients with artemether and quinine","volume":"6","author":"O Osonuga","year":"2011","journal-title":"Asian J Med Sci"},{"issue":"2","key":"pone.0269391.ref070","first-page":"107","article-title":"Comparison of the effectiveness of artemether and quinine for treatment of severe malaria in children, Bangui, Central African 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