Efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) for the treatment of uncomplicated Plasmodium falciparum malaria among children 6-59 months in three sentinel sites of Sierra Leone, 2021-2022.

Antimalarial drug resistance leads to increased treatment failures, prolonged illness, and increased mortality. The World Health Organization (WHO) recommends malaria-endemic countries regularly (ideally biennially) assess the efficacy of commonly used antimalarials. An evaluation of Sierra Leone's first and second-line antimalarials assessed artemether-lumefantrine (AL) in three sentinel sites-Bo, Bombali, and Kenema-and artesunate-amodiaquine (ASAQ) in two sites-Bo and Bombali. Children 6 months to 5 years old with uncomplicated malaria were enrolled in the 28 day in vivo efficacy study using the WHO-recommended protocols. Genotyping at three markers (msp1, msp2 and the PolyA microsatellite) and match counting using the WHO 3/3 algorithm were used to distinguish recrudescence from new infection, PCR-uncorrected and corrected efficacy results were calculated, and molecular markers of antimalarial resistance were analyzed. Of 1777 children screened, 496 reached a study endpoint. Kaplan-Meier uncorrected efficacy for AL was 89.5% (95% CI 84-95%) in Bo, 96.1% (95% CI 92-100%) in Bombali, and 93.2% (95% CI 89-98%) in Kenema; for ASAQ, estimates were 92.0% (95% CI 86-98%) in Bo and 94.5% (95% CI 90-99%) in Bombali. PCR-corrected Kaplan-Meier efficacy was 100% in all AL arms, 100% for ASAQ in Bo, and 99.1% (95% CI 97-100%) for ASAQ in Bombali.New infections accounted for 72.7% (16/22) and 63.6% (7/11) of recurrent parasitemia in the AL and ASAQ arms, respectively. No validated or candidate Pfk13 mutations were detected, and while some Pfmdr1 and Pfcrt polymorphisms were observed, no clear pattern of association with treatment failure was evident. Therefore, our study provides evidence that AL and ASAQ remain efficacious for treatment of P. falciparum infection in Sierra Leone.