A pooled analysis of the duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine

Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) are the most commonly-used treatments against Plasmodium falciparum malaria in Africa. The lumefantrine and amodiaquine partner drugs may provide differing durations of post-treatment prophylaxis, an important additional benefit to patients. Analyzing 4214 individuals from clinical trials in 12 sites, we estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ after allowing for transmission intensity. However, the duration varied substantially between sites: where wild type pfmdr1 86 and pfcrt 76 parasite genotypes predominated, AS-AQ provided ∼2-fold longer protection than AL. Conversely, AL provided up to 1.5-fold longer protection than AS-AQ where mutants were common. We estimate that choosing AL or AS-AQ as first-line treatment according to local drug sensitivity could alter population-level clinical incidence of malaria by up to 14% in under-five year olds where malaria transmission is high.