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Comparative Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Malaria in Ugandan Children

2018; Oxford University Press; Volume: 219; Issue: 7 Linguagem: Inglês

10.1093/infdis/jiy637

1537-6613

Adoke Yeka, Erika Wallender, Ronald Mulebeke, Kibuuka Afizi, Ruth Kigozi, Bosco B. Agaba, Paul Kyambadde, Jimmy Opigo, Simeon Kalyesubula, Joseph Senzoga, Joanna Vinden, Melissa D. Conrad, Philip J. Rosenthal,

Computational Drug Discovery Methods

Abstract Background In Uganda, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PQ) showed excellent treatment efficacy for uncomplicated malaria in prior trials. Because the frequency of resistance to artemisinins and piperaquine is increasing in Southeast Asia and the prevalence of Plasmodium falciparum polymorphisms associated with resistance has changed, we reassessed treatment efficacies at 3 sites in Uganda. Methods For this randomized, single-blinded clinical trial, children aged 6–59 months with uncomplicated falciparum malaria were assigned treatment with AL or DHA-PQ and followed for 42 days. Primary end points were risks of recurrent parasitemia, either unadjusted or adjusted to distinguish recrudescence from new infection. We assessed selection by study regimens of relevant P. falciparum genetic polymorphisms associated with drug resistance. Results Of 599 patients enrolled, 578 completed follow-up. There were no early treatment failures. The risk of recurrent parasitemia was lower with DHA-PQ as compared to AL at all 3 sites at 42 days (26.0% vs 47.0%; P < .001). Recrudescent infections were uncommon in both the DHA-PQ and AL arms (1.1% and 2.2%, respectively; P = .25). Neither regimen selected for pfcrt or pfmdr1 polymorphisms associated with drug resistance. Conclusions AL and DHA-PQ remain effective for the treatment of malaria in Uganda. Neither regimen selected for genetic polymorphisms associated with drug resistance. Clinical Trials Registration ISRCTN15793046.