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

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.

Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda.

“…In Tororo, this regimen was widely used in different drug trials for malaria treatment [47,48] and chemoprevention [24,[49][50][51][52]. Previous studies indicated that dihydroartemisinin-piperaquine treatment selected the N86Y allele in pfmdr1 in Uganda [48,[52][53][54], albeit one study questioned this association [55]. Approximately one third of parasites possessed the N86Y in 2010-2013 in Tororo [9], which was much higher than that found in our study area (2%).…”

Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda

“…In Tororo, this regimen was widely used in different drug trials for malaria treatment [47,48] and chemoprevention [24,[49][50][51][52]. Previous studies indicated that dihydroartemisinin-piperaquine treatment selected the N86Y allele in pfmdr1 in Uganda [48,[52][53][54], albeit one study questioned this association [55]. Approximately one-third of parasites possessed the N86Y in 2010-2013 in Tororo [9], which was much higher than that found in the studied area (2%).…”

High therapeutic efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated falciparum malaria in Somalia

“…AL, the most commonly recommended ACT medicine in malaria-endemic countries, remains highly efficacious in Africa, despite its use as first-line treatment of uncomplicated falciparum malaria for more than a decade [25–41]. DHA/PPQ has recently been adopted as second-line treatment in several malaria-endemic countries in the African and Eastern Mediterranean regions, and the available data show high efficacy [25, 27, 30, 34–37, 39, 41, 42]. This high efficacy may be explained by the recent introduction of DHA/PPQ as second-line treatment, suggesting weak drug pressure through its limited use.…”