Efficacy and Safety of Artesunate + Amodiaquine and Artemether + Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Madagascar, 2020

Abstract

The efficacy of artesunate + amodiaquine (ASAQ) and artemether + lumefantrine (AL) for treating malaria was investigated in Madagascar in 2020. A randomized parallel-group study was conducted at four health centers (Antsenavolo, Vohitromby, and Matanga in the southeastern region and Ankazomborona in the northwestern region). The therapeutic efficacy and safety of ASAQ and AL were assessed using the WHO protocol, with a 28-day follow-up period. Children aged 6 months to 14 years with uncomplicated Plasmodium falciparum (P. falciparum) malaria were randomly assigned to receive either ASAQ or AL. Genotyping assays for the pfK13 gene were conducted on P. falciparum isolates obtained from dry blood samples collected on Day 0. Of 765 enrolled patients, 709 (92.7%) reached the study endpoint. Among the per-protocol population, crude adequate clinical and parasitological response (ACPR) rates were 99%, 99%, 100%, and 100% for Antsenavolo, Vohitromby, Matanga, and Ankazomborona, respectively, in the ASAQ group and 98%, 91%, 90%, and 100% for the same locations, respectively, in the AL group. Polymerase chain reaction-corrected ACPR rates were 100% for the ASAQ group at all study sites, whereas for the AL group, they were 98.8% in Antsenavolo, 97.6% in Vohitromby, 100% in Matanga, and 100% in Ankazomborona. Day 3 slide positivity rates were 0%, 1%, 1%, and 0% for Antsenavolo, Vohitromby, Matanga, and Ankazomborona, respectively. During follow-up, mild and moderate adverse events, including gastrointestinal issues (abdominal pain and vomiting) and headache, were reported in 10.2% (72/709) of patients. Of 727 samples successfully analyzed for pfK13, no mutation associated with artemisinin resistance was observed. The study results reveal that ASAQ and AL remain safe and efficacious for treating uncomplicated P. falciparum malaria in Madagascar.