{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:06:30Z","timestamp":1793113590261,"version":"4.5.0"},"reference-count":42,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,5]]},"abstract":"<jats:p>The efficacies of 3-day regimens of artemether\u2013lumefantrine (AL), artesunate\u2013amodiaquine (AA), and dihydroartemisinin\u2013piperaquine (DHP) were evaluated in 910 children &lt; 5 years old with uncomplicated malaria from six geographical areas of Nigeria. Parasite positivity 1 day and Kaplan\u2013Meier estimated risk of persistent parasitemia 3 days after therapy initiation were both significantly higher, and geometric mean parasite reduction ratio 1 day after treatment initiation (PRRD1) was significantly lower in AL-treated children than in AA- and DHP-treated children. No history of fever, temperature &gt; 38\u00b0C, enrollment parasitemia &gt; 75,000 \u03bcL<jats:sup>\u22121<\/jats:sup>, and PRRD1 &lt; 5,000 independently predicted persistent parasitemia 1 day after treatment initiation. Parasite clearance was significantly faster and risk of reappearance of asexual parasitemia after initial clearance was significantly lower in DHP-treated children. Overall, day 42 polymerase chain reaction\u2013corrected efficacy was 98.3% (95% confidence interval [CI]: 96.1\u2013100) and was similar for all treatments. In a non-compartment model, declines of parasitemias were monoexponential with mean terminal elimination half-life of 1.3 hours and unimodal frequency distribution of half-lives. All treatments were well tolerated. In summary, all three treatments evaluated remain efficacious treatments of uncomplicated malaria in young Nigerian children, but DHP appears more efficacious than AL or AA.<\/jats:p>","DOI":"10.4269\/ajtmh.18-0115","type":"journal-article","created":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T07:01:01Z","timestamp":1529996461000},"page":"649-664","source":"Crossref","is-referenced-by-count":29,"title":["Efficacy of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum Malaria in Under-Five-Year-Old Nigerian Children Ten Years Following Adoption as First-Line Antimalarials"],"prefix":"10.4269","volume":"99","author":[{"given":"Joy C.","family":"Ebenebe","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Nnamdi Azikiwe University, Awka, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godwin","family":"Ntadom","sequence":"additional","affiliation":[{"name":"National Malaria Elimination Programme, The Federal Ministry of Health, Abuja, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Ambe","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Maiduguri, Maiduguri, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robinson","family":"Wammanda","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Ahmadu Bello University, Zaria, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nma","family":"Jiya","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Uthman Dan Fodio University, Sokoto, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finomo","family":"Finomo","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Federal Medical Centre, Yenagoa, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Emechebe","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Imo State University Teaching Hospital, Orlu, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olugbenga","family":"Mokuolu","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, University of Ilorin, Ilorin, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazeem","family":"Akano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chimere","family":"Agomo","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science, University of Lagos, Lagos, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onikepe A.","family":"Folarin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer University, Ede, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Oguche","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Jos, Jos, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Useh","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science, University of Calabar, Calabar, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wellington","family":"Oyibo","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, University of Lagos, Lagos, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Temitope","family":"Aderoyeje","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, University College Hospital, Ibadan, Nigeria;"},{"name":"Institute for Medical Research and Training, University of Ibadan, Ibadan, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Abdulkadir","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, University of Ilorin, Ilorin, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nnenna M.","family":"Ezeigwe","sequence":"additional","affiliation":[{"name":"National Malaria Elimination Programme, The Federal Ministry of Health, Abuja, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Happi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer University, Ede, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akintunde","family":"Sowunmi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria;"},{"name":"Department of Clinical Pharmacology, University College Hospital, Ibadan, Nigeria;"},{"name":"Institute for Medical Research and Training, University of Ibadan, Ibadan, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"_","family":"_","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Nnamdi Azikiwe University, Awka, Nigeria;"},{"name":"National Malaria Elimination Programme, The Federal Ministry of Health, Abuja, Nigeria;"},{"name":"Department of Paediatrics, University of Maiduguri, Maiduguri, Nigeria;"},{"name":"Department of Paediatrics, Ahmadu Bello University, Zaria, Nigeria;"},{"name":"Department of Paediatrics, Uthman Dan Fodio University, Sokoto, Nigeria;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"PLoS One","first-page":"e4551","article-title":"Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment","volume":"4","author":"Carrara","year":"2009"},{"key":"b2","series-title":"N Engl J Med","first-page":"455","article-title":"Artemisinin resistance in Plasmodium falciparum","volume":"361","author":"Dondorp","year":"2009"},{"key":"b3","series-title":"Clin Infect Dis","first-page":"e82","article-title":"Artemisinin resistance in Cambodia: a clinical trial designed to address an emerging problem in southeast Asia","volume":"51","author":"Noedl","year":"2010"},{"key":"b4","series-title":"Lancet","first-page":"1960","article-title":"Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study","volume":"379","author":"Phyo","year":"2012"},{"key":"b5","series-title":"Clin Infect Dis","first-page":"784","article-title":"Declining efficacy of artemisinin combination therapy against P. falciparum malaria on the Thai-Myanmar border (2003\u20132013): the role of parasite genetic factors","volume":"63","author":"Phyo","year":"2016"},{"key":"b6","author":"World Health Organization","year":"2015"},{"key":"b7","series-title":"Lancet Infect Dis","first-page":"491","article-title":"The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong Subregion: a molecular epidemiology observational study","volume":"17","author":"Imwong","year":"2017"},{"key":"b8","series-title":"Am J Trop Med Hyg","first-page":"23","article-title":"No evidence of delayed parasite clearance after oral artesunate treatment of uncomplicated falciparum malaria in Mali","volume":"87","author":"Maiga","year":"2012"},{"key":"b9","series-title":"Am J Trop Med Hyg","first-page":"193","article-title":"A major transition in malaria treatment: the adoption and deployment of artemisinin-based combination therapies","volume":"77","author":"Bosman","year":"2007"},{"key":"b10","series-title":"PLoS One","first-page":"e26005","article-title":"Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast","volume":"6","author":"Borrmann","year":"2011"},{"key":"b11","series-title":"N Engl J Med","first-page":"411","article-title":"Spread of artemisinin resistance in Plasmodium falciparum malaria","volume":"371","author":"Ashley","year":"2014"},{"key":"b12","series-title":"Am J Trop Med Hyg","first-page":"1202","article-title":"Polymorphisms in the K13-propeller gene in artemisinin-susceptible Plasmodium falciparum parasites from Bougoula-Hameau and Bandiagara, Mali","volume":"92","author":"Ouattara","year":"2015"},{"key":"b13","series-title":"N Engl J Med","first-page":"991","article-title":"Emergence of indigenous artemisinin-resistant Plasmodium falciparum in Africa","volume":"376","author":"Lu","year":"2017"},{"key":"b14","author":"World Health Organization","year":"2010"},{"key":"b15","author":"World Health Organization","year":"2015"},{"key":"b16","series-title":"PLoS One","first-page":"e6358","article-title":"Safety and efficacy of dihydroartemisinin-piperaquine in falciparum malaria: a prospective multi-centre individual patient data analysis","volume":"4","author":"Zwang","year":"2009"},{"key":"b17","series-title":"Malar J","first-page":"27","article-title":"Randomized non-inferiority and safety trial of dihydroartemisin-piperaquine and artesunate-amodiaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroonian children","volume":"14","author":"Nji","year":"2015"},{"key":"b18","series-title":"Antimicrob Agents Chemother","first-page":"818","article-title":"Efficacy of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010","volume":"57","author":"Leang","year":"2013"},{"key":"b19","series-title":"Am J Trop Med Hyg","first-page":"577","article-title":"Clinical efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria at the China-Myanmar Border","volume":"93","author":"Wang","year":"2015"},{"key":"b20","series-title":"Lancet","first-page":"1378","article-title":"Pyronaridine\u2013artesunate or dihydroartemisinin\u2013piperaquine versus current first-line therapies for repeated treatment of uncomplicated malaria: a randomised, multicentre, open-label, longitudinal, controlled, phase 3b\/4 trial","volume":"391","author":"Sagara","year":"2018"},{"key":"b21","series-title":"Am J Trop Med Hyg","first-page":"925","article-title":"Efficacy of artemisinin-based combination treatments of uncomplicated falciparum malaria in under-five year-old Nigerian children","volume":"91","author":"Oguche","year":"2014"},{"key":"b22","series-title":"Trans R Soc Trop Med Hyg","first-page":"1","article-title":"Severe falciparum malaria","volume":"94","author":"World Health Organization","year":"2000"},{"key":"b23","series-title":"Trop Med Int Health","first-page":"7","article-title":"Severe malaria","volume":"19","author":"World Health Organization","year":"2014"},{"key":"b24","author":"World Health Organization","year":"2003"},{"key":"b25","series-title":"Am J Trop Med Hyg","first-page":"20","article-title":"Molecular analysis of Pasmodium falciparum recrudescent malaria infection in children treated with chloroquine in Nigeria","volume":"70","author":"Happi","year":"2004"},{"key":"b26","author":"World Health Organization","year":"2009"},{"key":"b27","series-title":"BMC Infect Dis","first-page":"110","article-title":"Early rising asexual parasitaemia in Nigerian children following a first dose of artemisinin-based combination treatments of falciparum malaria","volume":"17","author":"Sowunmi","year":"2017"},{"key":"b28","series-title":"Am J Trop Med Hyg","first-page":"936","article-title":"Therapeutic efficacies of artemisinin-based combination therapies in Nigerian children with uncomplicated falciparum malaria during five years of adoption as first-line treatments","volume":"84","author":"Gbotosho","year":"2011"},{"key":"b29","author":"Anon","year":"2016"},{"key":"b30","author":"Anon","year":"2013"},{"key":"b31","author":"World Health Organization","year":"2017"},{"key":"b32","series-title":"J Infect Dis","first-page":"570","article-title":"In vivo parasitological measures of artemisinin susceptibility","volume":"201","author":"Stepniewska","year":"2010"},{"key":"b33","author":"Federal Ministry of Health","year":"2005"},{"key":"b34","series-title":"Am J Trop Med Hyg","first-page":"181","article-title":"Artemisinin-based combination treatment of falciparum malaria","volume":"77","author":"Nosten","year":"2007"},{"key":"b35","series-title":"PLoS One","first-page":"e57689","article-title":"Reduced susceptibility of Plasmodium falciparum to artesunate in southern Myanmar","volume":"8","author":"Kyaw","year":"2013"},{"key":"b36","series-title":"Cochrane Database Syst Rev","first-page":"CD000016","article-title":"Amodiaquine for treating malaria","volume":"2","author":"Olliaro","year":"2003"},{"key":"b37","series-title":"Antimicrob Agents Chemother","first-page":"1052","article-title":"Population pharmacokinetics of piperaquine after two different treatment regimens with dihydroartemisinin-piperaquine in patients with Plasmodium falciparum malaria in Thailand","volume":"52","author":"Tarning","year":"2008"},{"key":"b38","series-title":"CPT Pharmacometrics Syst Pharmacol","first-page":"e132","article-title":"Population pharmacokinetics and antimalarial pharmacodynamics of piperaquine in patients with Plasmodium vivax malaria in Thailand","volume":"3","author":"Tarning","year":"2014"},{"key":"b39","series-title":"PLoS Med","first-page":"e1002212","article-title":"Population pharmacokinetic properties of piperaquine in falciparum malaria: an individual participant data meta-analysis","volume":"14","author":"Hoglund","year":"2017"},{"key":"b40","series-title":"Malar J","first-page":"335","article-title":"Early variations in Plasmodium falciparum dynamics in Nigerian children after treatment with two artemisinin-based combinations: implications on delayed parasite clearance","volume":"9","author":"Michael","year":"2010"},{"key":"b41","series-title":"Mal Chemother Ctrl Elim","first-page":"235498","article-title":"Early changes in Plasmodium falciparum asexual and sexual populations in children with acute infections following treatment with artemisinin-based combination drugs","volume":"1","author":"Sowunmi","year":"2012"},{"key":"b42","series-title":"Expert Opin Pharmacother","first-page":"1303","article-title":"Can new treatment development combat resistance in malaria?","volume":"17","author":"White","year":"2016"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/99\/3\/article-p649.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/99\/3\/article-p649.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/99\/3\/article-p649.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T19:48:35Z","timestamp":1722455315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/99\/3\/article-p649.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,5]]},"references-count":42,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.18-0115","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,5]]}}}