Artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Liberia: in vivo efficacy and frequency of molecular markers

• Published in: Malaria Journal
• Main Authors: Victor S. Koko, Marian Warsame, Benjamin Vonhm, Moses K. Jeuronlon, Didier Menard, Laurence Ma, Fahn Taweh, Lekilay Tehmeh, Paye Nyansaiye, Oliver J. Pratt, Sei Parwon, Patrick Kamara, Magnus Asinya, Aaron Kollie, Pascal Ringwald
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2022
• Subjects: Artesunate–amodiaquine; Artemether–lumefantrine; Plasmodium falciparum; Efficacy; Molecular markers of antimalarial drug resistance; Liberia; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-022-04140-7; https://doaj.org/article/405018a636c24806a5ef73c716f54617

Abstract Background Artesunate–amodiaquine (ASAQ) and Artemether–lumefantrine (AL) are the recommended treatment for uncomplicated Plasmodium falciparum malaria in Liberia. Intermittent preventive treatment with sulfadoxine/pyrimethamine is also recommended for pregnant women. The therapeutic efficacy of Artesunate–amodiaquine and Artemether–lumefantrine, and the frequency of molecular markers associated with anti-malarial drug resistance were investigated. Methods The therapeutic efficacy of ASAQ and AL was evaluated using the standard World Health Organization protocol (WHO. Methods for Surveillance of Antimalarial Drug Efficacy. Geneva: World Health Organization; 2009. https://www.who.int/malaria/publications/atoz/9789241597531/en/ ). Eligible children were recruited and monitored clinically and parasitologically for 28 days. Polymorphisms in the Pfkelch 13, chloroquine resistance transporter (Pfcrt), multidrug resistance 1 (Pfmdr-1), dihydrofolate reductase (Pfdhfr), and dihydropteroate synthase (Pfdhps) genes and copy number variations in the plasmepsin-2 (Pfpm2) gene were assessed in pretreatment samples. Results Of the 359 children enrolled, 180 were treated with ASAQ (89 in Saclepea and 91 in Bensonville) and 179 with AL (90 in Sinje and 89 in Kakata). Of the recruited children, 332 (92.5%) reached study endpoints. PCR-corrected per-protocol analysis showed ACPR of 90.2% (95% CI: 78.6–96.7%) in Bensonville and 92.7% (95% CI: 83.4.8–96.5%) in Saclepea for ASAQ, while ACPR of 100% was observed in Kakata and Sinje for AL. In both treatment groups, only two patients had parasites on day 3. No artemisinin resistance associated Pfkelch13 mutations or multiple copies of Pfpm2 were found. Most samples tested had the Pfcrt 76 T mutation (80/91, 87.9%), while the Pfmdr-1 86Y (40/91, 44%) and 184F (47/91, 51.6%) mutations were less frequent. The Pfdhfr triple mutant (51I/59R/108 N) was the predominant allele (49.2%). For the Pfdhps gene, it was the 540E mutant (16.0%), and the 436A mutant (14.3%). The quintuple ...