Efficacy and Safety of Artemether-Lumefantrine Against Uncomplicated Falciparum Malaria Infection in Tanzania, 2022: A Single-Arm Clinical Trial.

Background: Artemether-lumefantrine (AL) is the first-line antimalarial drug for the treatment of uncomplicated malaria in Tanzania. The World Health Organization (WHO) recommends regular efficacy monitoring of antimalarial drugs to inform case management policy decisions. This study assessed the safety and efficacy of AL for treating uncomplicated Plasmodium falciparum malaria in Tanzania in 2022.

Methods: Children aged 6 months to 10 years with uncomplicated P falciparum malaria were recruited from 4 sentinel sites and treated with the standard 6-dose, 3-day regimen for AL. Clinical and parasitological responses were monitored for 28 days using the WHO standard protocol. Genotyping based on msp1, msp2, and glurp was used to distinguish recrudescence from reinfection. Sanger sequencing was used to detect K13 mutations.

Results: Three hundred fifty-two participants, 88 per site, were enrolled. Four withdrew and 55 experienced parasite recurrence. The polymerase chain reaction (PCR)-corrected Kaplan-Meier efficacies were 89.9% in Pwani, 95.0% in Kigoma, 94.4% in Tanga, and 98.9% in Morogoro. No K13 mutations were found.

Conclusions: Artemether-lumefantrine remains highly efficacious in 3 regions of Tanzania, but the PCR-corrected efficacy in Pwani fell below the WHO-defined 90% threshold at which policy change is recommended. Implementing strategies to diversify artemisinin-based combination therapies to ensure effective case management in Tanzania is critical.