Comparison of sulfadoxine-pyrimethamine, unsupervised artemether-lumefantrine, and unsupervised artesunate-amodiaquine fixed-dose formulation for uncomplicated plasmodium falciparum malaria in Benin: a randomized effectiveness noninferiority trial

J Infect Dis. 2009 Jul 1;200(1):57-65. doi: 10.1086/599378.


Background: We compared sulfadoxine-pyrimethamine (SP) with unsupervised artemether-lumefantrine (AL) and unsupervised amodiaquine-artesunate (ASAQ) fixed-dose formulation for the treatment of uncomplicated malaria in children in Benin.

Methods: This open-label, noninferiority comparative trial included children aged 6-60 months. The follow-up period was 6 weeks, and the primary objective was a comparison of polymerase chain reaction (PCR)-adjusted effectiveness rates at day 28.

Results: The study included 240 children (48 received SP, and 96 each received AL and ASAQ). The intention-to-treat analysis showed effectiveness rates on day 28 of 20.8%, 78.1%, and 70.5% for SP, AL, and ASAQ, respectively. After adjustment for PCR results, these rates were 27.1%, 83.3%, and 87.4%, respectively. The per-protocol analysis (217 patients) showed effectiveness rates on day 28 of 21.7%, 88.0%, and 76.1% for SP, AL, and ASAQ, respectively. After adjustment for PCR results, these rates were 28.3%, 94.0%, and 93.2%, respectively. SP was less effective than the other drugs in the PCR-adjusted analysis, whereas AL and ASAQ were equally effective. The rate of new infection was higher among children treated with ASAQ than among those treated with AL.

Conclusions: This was the first trial, to our knowledge, to compare unsupervised AL with unsupervised ASAQ fixed-dose formulation; both treatments provided high PCR-adjusted day 28 effectiveness rates. Efficacy rates for SP were surprisingly low. Clinical trials registration. NCT00460369.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Amodiaquine / therapeutic use*
  • Animals
  • Antimalarials / therapeutic use*
  • Artemisinins / therapeutic use*
  • Artesunate
  • Benin
  • Child, Preschool
  • Drug Combinations
  • Drug Therapy, Combination
  • Ethanolamines / therapeutic use*
  • Female
  • Fluorenes / therapeutic use*
  • Humans
  • Infant
  • Lumefantrine
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / prevention & control
  • Malaria, Falciparum / transmission
  • Male
  • Polymerase Chain Reaction
  • Pyrimethamine / therapeutic use*
  • Sulfadoxine / therapeutic use*


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

Associated data