Salim AbdullaIshag AdamGeorge O. AdjeiMartin A. AdjuikBereket AlemayehuRichard AllanEmmanuel ArinaitweElizabeth A. AshleyMamadou S. BaHubert BarennesKaren I. BarnesQuique BassatElisabeth BaudinNicole Berens-RihaAnders BjörkmanFrançois BompartMaryline BonnetSteffen BorrmannTeun BousemaPhilippe BrasseurHasifa BukirwaFrancesco ChecchiPrabin DahalUmberto D'AlessandroMeghna DesaiAlassane DickoAbdoulaye A. DjimdéGrant DorseyOgobara K. DoumboChris J. DrakeleyStephan DuparcTeferi EshetuEmmanuelle EspiéJean François EtardAbul M. FaizCatherine O. FaladeCaterina I. FanelloJean François FaucherBabacar FayeOumar FayeScott FillerJennifer A. FleggBakary FofanaCarole FoggNahla B. GadallaOumar GayeBlaise GentonPeter W. GethingJosé P. GilRaquel GonzálezFrancesco GrandessoBryan GreenhouseBrian GreenwoodAnastasia GrivoyannisPhilippe J. GuerinJean Paul GuthmannKamal HamedSally HamourSimon I. HayEva Maria HodelGeorgina S. HumphreysJimee HwangMaman L. IbrahimDaddi JimaJoel J. JonesVincent JullienElizabeth JumaPatrick S. KachurPiet A. KagerErasmus KamugishaMoses R. KamyaCorine KaremaIfakara Health InstituteUniversity of Khartoum Faculty of MedicineUniversity of GhanaINDEPTH NetworkInternational Center for AIDS Care and Treatment ProgramsMENTOR InitiativeInfectious Diseases Research CollaborationEpicentreUniversite Cheikh Anta DiopCentre MURAZFrench Foreign AffairsWorldWide Antimalarial Resistance NetworkUniversity of Cape TownCentro de Investigação em Saúde de ManhiçaInstituto de Salud Global de BarcelonaLudwig-Maximilians-Universitat MunchenKarolinska University HospitalSanofi S.A.Kenya Medical Research InstituteUniversitat TubingenGerman Centre for Infection ResearchLondon School of Hygiene &amp; Tropical MedicineRadboud University Nijmegen Medical CentreInstitut de Recherche pour le Developpement DakarUganda Malaria Surveillance ProjectWorldWide Antimalarial Resistance Network (WWARN)Nuffield Department of Clinical MedicinePrins Leopold Instituut voor Tropische GeneeskundeMedical Research Council UnitCenters for Disease Control and PreventionUniversity of Bamako Faculty of Medicine, Pharmacy and Odonto-StomatologyUniversity of California, San FranciscoMedicines for Malaria VentureJimma UniversityIRD Centre de MontpellierMahidol UniversityUniversity of IbadanIRD Institut de Recherche pour le DeveloppementUniversite Paris DescartesBesançon University Medical CenterThe Global Fund to Fight AIDS, Tuberculosis and MalariaMonash UniversityPortsmouth Hospitals NHS TrustTropical Medicine Research Institute SudanNational Institute of Allergy and Infectious DiseasesSwiss Tropical and Public Health Institute (Swiss TPH)Centre Hospitalier Universitaire VaudoisUniversity of OxfordKarolinska InstitutetFaculdade de Ciencias, Universidade de LisboaBinghamton University State University of New YorkUniversity of Washington, SeattleInstitut de Veille SanitaireNovartis Pharmaceuticals CorporationUCLWellcome Trust Centre for Human GeneticsNational Institutes of Health, BethesdaLiverpool School of Tropical MedicineCentre de Recherche Médicale et SanitaireFederal Ministry of Health - EthiopiaMinistry of Health and Social WelfareAcademic Medical Centre, University of AmsterdamCatholic University of Health and Allied SciencesMakerere UniversityMinistry of HealthDrugs for Neglected Diseases InitiativeProjecto de Saúde de BandimKolding SygehusCentre de Recherches Médicales de LambarénéUniversity of LondonMédecins Sans FrontièresEuropean &amp; Developing Countries Clinical Trials PartnershipFederal Ministry of Health SudanUppsala UniversitetUniversity of Abomey-CalaviUniversity of CocodyInstitut Pasteur du CambodgeRoyal Tropical Institute - KITUniversity of CalabarInstitute of Tropical Diseases Research and PreventionMbarara University of Science and TechnologyTropical Diseases Research CentreMuhimbili University of Health and Allied SciencesInstitut de Recherche en Sciences de la SantéUniversite Marien Ngouabi2018-11-232018-11-232015-09-07BMC Medicine. Vol.13, No.1 (2015)174170152-s2.0-84941618712https://repository.li.mahidol.ac.th/handle/123456789/36334© 2015 WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group. Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results: In total, 29, 493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13, 664), artesunate-amodiaquine (n = 11, 337) and dihydroartemisinin-piperaquine (n = 4, 492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). Conclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.Mahidol UniversityMedicineArticleSCOPUS10.1186/s12916-015-0445-x