Abstract
BackgroundCombination therapies are now recommended to treat uncomplicated malaria. We used a longitudinal design to assess the incidence of malaria and compare the efficacies of 3 combination regimens in Kampala, Uganda.Methodology/Principal FindingsChildren aged 1–10 years were enrolled from randomly selected households in 2004–05 and 2007, and were followed at least monthly through 2008. Insecticide-treated bednets (ITNs) were provided in 2006. Children were randomized upon their first episode, and then treated for all episodes of uncomplicated malaria with amodiaquine/sulfadoxine-pyrimethamine (AQ/SP), artesunate/amodiaquine (AS/AQ), or artemether/lumefantrine (AL). Risks of parasitological failure were determined for each episode of uncomplicated malaria and clinical parameters were followed. A total of 690 children experienced 1464 episodes of malaria. 96% of these episodes were uncomplicated malaria and treated with study drugs; 94% were due to Plasmodium falciparum. The rank order of treatment efficacy was AL > AS/AQ > AQ/SP. Failure rates increased over time for AQ/SP, but not the artemisinin-based regimens. Over the 4-year course of the study the prevalence of asymptomatic parasitemia decreased from 11.8% to 1.4%, the incidence of malaria decreased from 1.55 to 0.32 per person year, and the prevalence of anemia (hemoglobin <10 gm/dL) decreased from 5.9% to 1.0%. No episodes of severe malaria (based on WHO criteria) and no deaths were seen.Conclusions/SignificanceWith ready access to combination therapies and distribution of ITNs, responses were excellent for artemisinin-containing regimens, severe malaria was not seen, and the incidence of malaria and prevalence of parasitemia and anemia decreased steadily over time.Trial Registrationisrctn.org ISRCTN37517549
Highlights
Malaria is one of the most important infectious diseases in the world
We studied the comparative efficacy of 3 antimalarial combination therapies in an urban cohort of children in Kampala, a city with a level of malaria transmission that is relatively low for sub-Saharan Africa
We present a final evaluation of the relative efficacies of the 3 combination antimalarial therapies, changes in the prevalence of malarial parasitemia and incidence of malaria over time, and other clinical features in this urban cohort of Ugandan children
Summary
Malaria is one of the most important infectious diseases in the world. The problem is greatest in sub-Saharan Africa, where infection with Plasmodium falciparum, the most virulent human malaria parasite, is responsible for hundreds of millions of illnesses and about one million deaths each year [1]. Recent advances have led to some optimism regarding the control of malaria, and there have been documented decreases in malarial incidence in a number of parts of Africa [2,3,4,5,6]. The problem remains great, with little improvement in much of Africa, and improved malaria control interventions are needed. With increasing resistance to older therapies, current WHO recommendations call for the treatment of uncomplicated malaria in Africa with artemisinin-based combination therapy (ACT). The non-ACT combination regimen amodiaquine/sulfadoxine-pyrimethamine has shown good antimalarial efficacy in many [13,14,15,16], but not all [7,12] trials in Africa, and is recommended by the WHO as an alternative therapy for malaria when ACTs are unavailable. Combination therapies are recommended to treat uncomplicated malaria. We used a longitudinal design to assess the incidence of malaria and compare the efficacies of 3 combination regimens in Kampala, Uganda
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