A pooled analysis of the duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine
Bretscher MT., Dahal P., Griffin JT., Stepniewska K., Bassat Q., Baudin E., D'Alessandro U., Djimde AA., Dorsey G., Espie E., Fofana B., Gonzalez R., Juma E., Karema C., Lasry E., Lell B., Lima N., Menendez C., Mombo-Ngoma G., Moreira C., Nikiema F., Ouedraogo JB., Staedke SG., Tinto H., Valea I., Yeka A., Ghani AC., Guerin PJ., Okell LC.
<jats:p>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.</jats:p>