Efficacy of artesunate + sulphadoxine/pyrimethamine and artemether + lumefantrine and dhfr and dhps mutations in Somalia: evidence for updating the malaria treatment policy

Abstract

Objective: To determine the therapeutic efficacy of artesunate + sulphadoxine/pyrimethamine (AS + SP) and artemether + lumefantrine (AL), and to investigate the presence of molecular mutations associated with resistance, to inform national malaria treatment policy.

Methods: One-arm prospective studies were conducted in three study sites in Somalia in 2013 and 2015 to evaluate the efficacy of AS + SP and AL among patients with uncomplicated falciparum malaria. Outcomes included clinical and parasitological response over 28 days, and the presence of dihydrofolate reductase (dfhr) and dihydropteroate synthase (dhps) and mutations.

Results: Among patients treated with AS + SP, the PCR-corrected treatment failure rate was 12.3%. The majority of patients (89%) carried either the quintuple mutations (51I/108N + 437G/540E/581G or 51I/59R/108N + 437G/540E) or the quadruple mutation (51I/108N + 437G/540E). All patients who failed treatment with AS + SP carried the quintuple mutation (51I/108N + 437G/540E/581G). In the studies of AL, the PCR-corrected treatment failure rate was <6%. All patients in both treatment groups cleared their parasitaemia by day 3.

Conclusions: The findings demonstrate a failing first-line treatment (AS + SP), with a failure rate above the threshold (10%) for policy change, and a high prevalence of quintuple mutations. In contrast, AL was highly efficacious. Based on these findings and the results from a previous AS + SP study, AL was selected to replace AS + SP as the first-line treatment for uncomplicated malaria in Somalia in 2016. Dihydroartemisinin + piperaquine (DHA + PPQ) has been recommended as the second-line treatment. Routine monitoring of recommended ACTs should continue to inform treatment policy.

Keywords: Plasmodium falciparum; Artesunato + sulfadoxina/pirimetamina; Artésunate + sulfadoxine/pyriméthamine; Somalia; Somalie; artemeter + lumefantrina; artemether + lumefantrine; artesunate + sulphadoxine/pyrimethamine; artéméther + luméfantrine; dihidroartemisinina + piperaquina; dihydroartemisinin + piperaquine; dihydroartémisinine + pipéraquine; efficacité; efficacy; eficacia.