Abstract
Objectives:To compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda.Design:Randomized single-blinded clinical trial.Setting:Apac, Uganda, an area of very high malaria transmission intensity.Participants:Children aged 6 mo to 10 y with uncomplicated falciparum malaria.Intervention:Treatment of malaria with AL or DP, each following standard 3-d dosing regimens.Outcome measures:Risks of recurrent parasitemia at 28 and 42 d, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.Results:Of 421 enrolled participants, 417 (99%) completed follow-up. The unadjusted risk of recurrent falciparum parasitemia was significantly lower for participants treated with DP than for those treated with AL after 28 d (11% versus 29%; risk difference [RD] 18%, 95% confidence interval [CI] 11%–26%) and 42 d (43% versus 53%; RD 9.6%, 95% CI 0%–19%) of follow-up. Similarly, the risk of recurrent parasitemia due to possible recrudescence (adjusted by genotyping) was significantly lower for participants treated with DP than for those treated with AL after 28 d (1.9% versus 8.9%; RD 7.0%, 95% CI 2.5%–12%) and 42 d (6.9% versus 16%; RD 9.5%, 95% CI 2.8%–16%). Patients treated with DP had a lower risk of recurrent parasitemia due to non-falciparum species, development of gametocytemia, and higher mean increase in hemoglobin compared to patients treated with AL. Both drugs were well tolerated; serious adverse events were uncommon and unrelated to study drugs.Conclusion:DP was superior to AL for reducing the risk of recurrent parasitemia and gametocytemia, and provided improved hemoglobin recovery. DP thus appears to be a good alternative to AL as first-line treatment of uncomplicated malaria in Uganda. To maximize the benefit of artemisinin-based combination therapy in Africa, treatment should be integrated with aggressive strategies to reduce malaria transmission intensity.
Highlights
IntroductionIn response to widespread resistance of the parasite to commonly used monotherapies, chloroquine (CQ) and sulfadoxine-pyrimethamine (SP), many countries have recently adopted artemisinin-based combination therapy (ACT) as a first-line regimen for the treatment of uncomplicated malaria [1]
In Africa, treatment of uncomplicated malaria is undergoing dramatic changes
Treatment outcomes were classified according to 2006 World Health Organization (WHO) guidelines as early treatment failure (ETF; danger signs or complicated malaria or failure to adequately respond to therapy days 0–3); late clinical failure (LCF; danger signs or complicated malaria or fever and parasitemia on days 4–42 without previously meeting criteria for ETF or LPF); late parasitological failure (LPF; asymptomatic parasitemia days 7–42 without previously meeting criteria for ETF or LCF); or adequate clinical and parasitological response [16]
Summary
In response to widespread resistance of the parasite to commonly used monotherapies, chloroquine (CQ) and sulfadoxine-pyrimethamine (SP), many countries have recently adopted artemisinin-based combination therapy (ACT) as a first-line regimen for the treatment of uncomplicated malaria [1]. Many African countries have adopted combinations of drugs for first-line malaria treatment that include a compound based on the plant-derived molecule artemisinin. In Uganda, the artemisinin-based compound therapy (ACT) adopted as first-line therapy is artemether-lumefantrine (AL). There are concerns that even though AL and other ACTs successfully treat the initial infection, there is a risk of malaria recurring soon after therapy, in areas where mosquito attack rates are high. The researchers here wanted to compare AL treatment with another ACT, dihydroartemisinin-piperaquine (DP), for treatment of uncomplicated malaria in children who live in an area of Uganda where malaria is transmitted at a very high rate
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