Incidence of malaria and efficacy of combination antimalarial therapies over 4 years in an urban cohort of Ugandan children

Abstract

Background: Combination 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 findings: Children 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/significance: With 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 registration: isrctn.org ISRCTN37517549.

Figure 1. Trial profile.

Figure 2. Incidence of malaria over time.

Incidence of malaria in the full cohort (A), stratified for age (B), and stratified based on distance of residence from a swamp (C) are shown. Smoothed lines were produced in R (version 2.9.0) using Friedman's SuperSmoother and considering 1339 new episodes of malaria over 710,004 person-days of follow up. This analysis did not include the 89 children enrolled in 2007. Monthly rainfall data are from the Uganda Department of Meteorology; measurements were at Makerere University, <2 km from the Mulago III parish, where study subjects resided.

Figure 3. Drug efficacy over time.

The annual 28-day risk of failure of treatment of uncomplicated falciparum malaria with the three study regimens, both unadjusted (considering all recurrences) and adjusted by genotyping (considering only recrudescences) is shown. This analysis did not include episodes of malaria that occurred in 2004. Error bars represent upper limits of the 95% confidence intervals.