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Therapeutic Efficacy of Artemisinin-Based Combination Therapies in Democratic Republic of the Congo and Investigation of Molecular Markers of Antimalarial Resistance

Moriarty, Leah F., Nkoli, Papy Mandoko, Likwela, Joris Losimba, Mulopo, Patrick Mitashi, Sompwe, Eric Mukomena, Rika, Junior Matangila, Mavoko, Hypolite Muhindo, Svigel, Samaly S., Jones, Sam, Ntamabyaliro, Nsengi Y., Kaputu, Albert Kutekemeni, Lucchi, Naomi, Subramaniam, Gireesh, Niang, Mame, Sadou, Aboubacar, Ngoyi, Dieudonné Mumba, Muyembe Tamfum, Jean Jacques, Schmedes, Sarah E., Plucinski, Mateusz M., Chowell-Puente, Gerardo, Halsey, Eric S. and Kahunu, Gauthier Mesia (2021) 'Therapeutic Efficacy of Artemisinin-Based Combination Therapies in Democratic Republic of the Congo and Investigation of Molecular Markers of Antimalarial Resistance'. American Journal of Tropical Medicine and Hygiene, Vol 105, Issue 4, pp. 1067-1075.

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Abstract

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.

Item Type: Article
Subjects: WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WB Practice of Medicine > Therapeutics > WB 330 Drug therapy
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.4269/ajtmh.21-0214
Depositing User: Stacy Murtagh
Date Deposited: 21 Sep 2021 09:29
Last Modified: 10 Dec 2021 11:51
URI: https://archive.lstmed.ac.uk/id/eprint/18980

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