: Routine assessment of the efficacy of artemisinin-based combination therapies (ACTs) is critical for the early detection of antimalarial resistance. We evaluated the efficacy of ACTs recommended for treatment of uncomplicated malaria in five sites in Democratic Republic of the Congo (DRC): artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Children aged 6–59 months with confirmed Plasmodium falciparum malaria were treated with one of the three ACTs and monitored. The primary endpoints were uncorrected and polymerase chain reaction (PCR)-corrected 28-day (AL and ASAQ) or 42-day (DP) cumulative efficacy. Molecular markers of resistance were investigated. Across the sites, uncorrected efficacy estimates ranged from 63% to 88% for AL, 73% to 100% for ASAQ, and 56% to 91% for DP. PCR-corrected efficacy estimates ranged from 86% to 98% for AL, 91% to 100% for ASAQ, and 84% to 100% for DP. No pfk13 mutations previously found to be associated with ACT resistance were observed. Statistically significant associations were found between certain pfmdr1 and pfcrt genotypes and treatment outcome. There is evidence of efficacy below the 90% cutoff recommended by WHO to consider a change in first-line treatment recommendations of two ACTs in one site not far from a monitoring site in Angola that has shown similar reduced efficacy for AL. Confirmation of these findings in future therapeutic efficacy monitoring in DRC is warranted.

CONTEXT AND OBJECTIVESThe fight against malaria is threatened by the emergence and expansion ofPlasmodium falciparumresistance to antimalarial drugs, to the point of questioning treatment patterns drawn by control programs. The objective of this work was to do a critical appraisal of the national guidelines for the treatment of malaria in the Democratic Republic of the Congo.METHODSTo estimate the selective pressure that leads to the emergence ofP. falciparumresistance to antimalarials, a cross-sectional survey was conducted on antimalarials in circulation in pharmacies in Kinshasa. Anex vivoevaluation of theP. falciparumresistance to antimalarial drugs and the analysis of molecular markers of Sulfadoxine-pyrimethamine resistance were conducted in the provinces of Kinshasa and Kongo Central during 2014 and 2015.RESULTS.The following antimalarial drugs were found in 404 pharmacies: Artemisinin-based combination therapies 88.1%, quinine 80.9%, Sulfadoxine-Pyrimethamine 56.4%, oral artemisinin-based monotherapies 23.0% and traditional medicine 30.2%. Artemether-lumefantrine combinations were the most frequently dispensed drugs (93% of pharmacies). The decrease in the susceptibility ofP. falciparumisolates to antimalarials was as follows: chloroquine 65.7%, quinine 52.6%, monodesethylamodiaquine 25%, mefloquine ~ 45%, dihydroartemisinin 1.3%, piperaquine 1.6%, and doxycycline 4.3%. No isolates were found to be lumefantrine-resistant. The prevalence of mutations was high inpfdhfr(N51I: 98.5%, C59R: 88.2%, and S108N: 99.4%) andpfdhps(A437G: 97.8%). ThepfdhpsA581G,pfdhpsK540E,pfdhfrI164L, andpfdhpsA613S mutations were 14%, 17.5%, 0.1%, and 0.6%, respectively.CONCLUSIONThese findings show a highex vivoresistance ofP. falciparumto quinine, the antimalarial that plays an important role in the fight against malaria in the DRC. The present work highlights the complexity of the inappropriate antimalarials distribution. This shows the lack of regulation in the distribution system, potentially affecting the dynamics of resistance.