Martin A. AdjuikRichard AllanAnupkumar R. AnvikarElizabeth A. AshleyMamadou S. BaHubert BarennesKaren I. BarnesQuique BassatElisabeth BaudinAnders BjörkmanFrançois BompartMaryline BonnetSteffen BorrmannPhilippe BrasseurHasifa BukirwaFrancesco ChecchiMichel CotPrabin DahalUmberto D'AlessandroPhilippe DeloronMeghna DesaiGraciela DiapAbdoulaye A. DjimdeGrant DorseyOgobara K. DoumboEmmanuelle EspiéJean Francois EtardCaterina I. FanelloJean François FaucherBabacar FayeJennifer A. FleggOumar GayePeter W. GethingRaquel GonzálezFrancesco GrandessoPhilippe J. GuerinJean Paul GuthmannSally HamourArmedy Ronny HasugianSimon I. HayGeorgina S. HumphreysVincent JullienElizabeth JumaMoses R. KamyaCorine KaremaJean R. KiechelPeter G. KremsnerSanjeev KrishnaValérie LameyreLaminou M. IbrahimSue J. LeeBertrand LellAndreas MartenssonAchille MassougbodjiHervé MenanDidier MénardClara MenéndezMartin MeremikwuClarissa MoreiraCarolyn NabasumbaMichael NamboziJean Louis NdiayeFrederic NikiemaChristian NsanzabanaFrancine NtoumiBernhards R. OgutuPiero OlliaroLyda OsorioJean Bosco OuédraogoLouis K. PenaliMbaye PeneINDEPTH NetworkMENTOR InitiativeNational Institute of Malaria Research IndiaEpicentreUniversite Cheikh Anta DiopCentre MURAZFrench Foreign AffairsWorldWide Antimalarial Resistance NetworkUniversity of Cape TownCentro de Investigação em Saúde de ManhiçaInstituto de Salud Global de BarcelonaKarolinska InstitutetSanofi S.A.Universitat TubingenGerman Centre for Infection ResearchInstitut de Recherche pour le Developpement DakarUganda Malaria Surveillance ProjectIRD Institut de Recherche pour le DeveloppementUniversite Paris DescartesWorldWide Antimalarial Resistance Network (WWARN)Nuffield Department of Clinical MedicinePrins Leopold Instituut voor Tropische GeneeskundeMedical Research Council UnitCenters for Disease Control and PreventionDrugs for Neglected Diseases InitiativeUniversity of Bamako Faculty of Medicine, Pharmacy and Odonto-StomatologyUniversity of California, San FranciscoInstitut Pasteur de DakarIRD Centre de MontpellierMahidol UniversityBesançon University Medical CenterMonash UniversityUniversity of OxfordUCLBadan Penelitian Dan Pengembangan Kesehatan, Kementerian Kesehatan Republik IndonesiaKenya Medical Research InstituteMakerere UniversityMinistry of HealthCentre de Recherches Médicales de LambarénéUniversity of LondonCentre de Recherche Médicale et SanitaireUppsala UniversitetUniversity of Abomey-CalaviUniversity of CocodyInstitut Pasteur du CambodgeUniversity of CalabarMbarara University of Science and TechnologyTropical Diseases Research CentreInstitut de Recherche en Sciences de la SantéUniversite Marien NgouabiUnited States ArmyOrganisation Mondiale de la SanteCentro Internacional de Entrenamiento e Investigaciones MedicasWorldWide Antimalarial Resistance Network (WWARN)-West Africa Regional CentreInstitut Pasteur de MadagascarMenzies School of Health ResearchLondon School of Hygiene &amp; Tropical MedicineUNICEFCentre Hospitalier et Universitaire de YaoundeDrugs for Neglected Diseases initiativeUniversity of Washington, SeattleUniversite de la Mediterranee Aix-Marseille IICentre National de Recherche et de Formation sur le Paludisme (CNRFP)World Wide Antimalarial Resistance Network (WWARN)-Asia Regional CentreUniversity of Maryland School of MedicineMédecins sans Frontières/HollandMedical Action MyanmarInfectious Diseases Research CollaborationMédecins Sans FrontièresEast Africa Regional OfficeHopitaux universitaires de GeneveSwiss Tropical and Public Health Institute (Swiss TPH)Universitat Basel2018-11-232018-11-232015-03-31BMC Medicine. Vol.13, No.1 (2015)174170152-s2.0-84928776445https://repository.li.mahidol.ac.th/handle/20.500.14594/36484© The WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group; licensee BioMed Central. Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. Conclusions: There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.Mahidol UniversityMedicineArticleSCOPUS10.1186/s12916-015-0301-z