title: Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso.
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.
authors.affiliation: Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
authors.forename: Issaka
authors.initials: I
authors.lastname: Zongo
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.forename: Noel
authors.initials: N
authors.lastname: Rouamba
authors.forename: Christian
authors.initials: C
authors.lastname: Dokomajilar
authors.forename: Yves
authors.initials: Y
authors.lastname: Séré
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Jean Bosco
authors.initials: JB
authors.lastname: Ouédraogo
mesh_terms: D000655:Amodiaquine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002050:Burkina Faso; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010963:Plasmodium falciparum; D011739:Pyrimethamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011804:Quinolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013413:Sulfadoxine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010879:Piperazines
chemical_list: D000655:Amodiaquine; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011739:Pyrimethamine; D011804:Quinolines; D013413:Sulfadoxine; C520462:dihydroartemisinic acid; C001205:fanasil, pyrimethamine drug combination; C034759:piperaquine; D010879:Piperazines