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

PLoS One. 2010 Jul 30;5(7):e11759. doi: 10.1371/journal.pone.0011759.


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: ISRCTN37517549.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amodiaquine / therapeutic use
  • Antimalarials / therapeutic use*
  • Artemether
  • Artemisinins / therapeutic use
  • Artesunate
  • Child
  • Child, Preschool
  • Drug Combinations
  • Drug Therapy, Combination
  • Ethanolamines / therapeutic use
  • Female
  • Fluorenes / therapeutic use
  • Humans
  • Incidence
  • Infant
  • Lumefantrine
  • Malaria / drug therapy*
  • Malaria / epidemiology*
  • Male
  • Pyrimethamine / therapeutic use
  • Sulfadoxine / therapeutic use
  • Treatment Outcome
  • Uganda / epidemiology


  • Antimalarials
  • Artemisinins
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • Amodiaquine
  • fanasil, pyrimethamine drug combination
  • Artesunate
  • Sulfadoxine
  • Artemether
  • Lumefantrine
  • Pyrimethamine

Associated data

  • ISRCTN/ISRCTN37517549