Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso

Clin Infect Dis. 2007 Dec 1;45(11):1453-61. doi: 10.1086/522985. Epub 2007 Oct 22.

Abstract

Background: Combination antimalarial therapy is advocated to improve treatment efficacy and limit selection of drug-resistant parasites. We compared the efficacies of 3 combination regimens in Bobo-Dioulasso, Burkina Faso: amodiaquine plus sulfadoxine-pyrimethamine, which was recently shown to be highly efficacious at this site; artemether-lumefantrine, the new national first-line antimalarial regimen; and dihydroartemisinin-piperaquine (DP), a newer regimen.

Methods: We enrolled 559 patients >or=6 months of age with uncomplicated Plasmodium falciparum malaria and randomized them to the 3 regimens. We analyzed the risk of recurrent parasitemia by day 28 and day 42, both unadjusted and adjusted by PCR methods to distinguish recrudescence and new infection.

Results: Complete data were available for 517 (92.5%) of the enrolled subjects. Early treatment failures occurred in 5 patients treated with amodiaquine plus sulfadoxine-pyrimethamine and in 2 patients each treated with the other regimens. The day 28 risk of recurrent parasitemia, unadjusted by genotyping, was significantly higher for patients receiving artemether-lumefantrine than for patients receiving amodiaquine plus sulfadoxine-pyrimethamine (20.1% vs. 6.2%; risk difference, 13.8%; 95% confidence interval, 7.0%-20.7%) or dihydroartemisinin-piperaquine (20.1% vs. 2.2%; risk difference, 17.9%; 95% confidence interval, 11.6%-24.1%). Similar differences were seen for children <5 years of age (54% of the study population) and when outcomes were extended to 42 days. Significant differences were not seen between outcomes for patients receiving amodiaquine plus sulfadoxine-pyrimethamine and outcomes for those receiving dihydroartemisinin-piperaquine. Recrudescences were uncommon (occurring in <5% of patients) in all treatment groups. No serious adverse events were noted.

Conclusions: All regimens were highly efficacious in clearing infection, but considering the risks of recurrent malaria after therapy, the amodiaquine plus sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine regimens were more efficacious than the artemether-lumefantrine regimen (the new national regimen in Burkina Faso) for the treatment of uncomplicated P. falciparum malaria.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amodiaquine / administration & dosage*
  • Amodiaquine / adverse effects
  • Amodiaquine / therapeutic use
  • Animals
  • Antimalarials / administration & dosage
  • Antimalarials / adverse effects
  • Antimalarials / therapeutic use
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / administration & dosage*
  • Artemisinins / adverse effects
  • Artemisinins / therapeutic use
  • Burkina Faso
  • Child
  • Child, Preschool
  • Drug Combinations
  • Drug Therapy, Combination
  • Ethanolamines / administration & dosage*
  • Ethanolamines / adverse effects
  • Ethanolamines / therapeutic use
  • Female
  • Fluorenes / administration & dosage*
  • Fluorenes / adverse effects
  • Fluorenes / therapeutic use
  • Humans
  • Malaria, Falciparum / drug therapy*
  • Male
  • Plasmodium falciparum
  • Pyrimethamine / administration & dosage*
  • Pyrimethamine / adverse effects
  • Pyrimethamine / therapeutic use
  • Quinolines / administration & dosage*
  • Quinolines / adverse effects
  • Quinolines / therapeutic use
  • Sulfadoxine / administration & dosage*
  • Sulfadoxine / adverse effects
  • Sulfadoxine / therapeutic use

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • Quinolines
  • dihydroartemisinic acid
  • Amodiaquine
  • fanasil, pyrimethamine drug combination
  • Sulfadoxine
  • piperaquine
  • Pyrimethamine