Amodiaquine, sulfadoxine/pyrimethamine, and Combination Therapy for Treatment of Uncomplicated Falciparum Malaria in Kampala, Uganda: A Randomised Trial

Lancet. 2001 Aug 4;358(9279):368-74. doi: 10.1016/S0140-6736(01)05557-X.


Background: Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments include sulfadoxine/pyrimethamine and amodiaquine. Combination of antimalarial agents can increase therapeutic efficacy and delay emergence of drug resistance. We compared the efficacy of sulfadoxine/pyrimethamine, amodiaquine, and an amodiaquine/sulfadoxine/pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance.

Methods: Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala, Uganda, were randomly assigned to receive sulfadoxine/pyrimethamine (25 mg/kg sulfadoxine, and 1.25 mg/kg pyrimethamine) plus placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfadoxine/pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed.

Findings: 90% (400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10%) patients on sulfadoxine/ pyrimethamine, nine of 131 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/pyrimethamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/pyrimethamine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5% vs 13.9%, respectively, risk difference 10.4% [95% CI, 1.6-19.3] p=0.021; parasitological failure in 12.8% vs 26.4%, risk difference 13.6% [1.2-26.0] p=0.041).

Interpretation: Sulfadoxine/pyrimethamine, amodiaquine, and amodiaquine/sulfadoxine/pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/pyrimethamine combination was the most effective, and could be the optimum low-cost alternative to chloroquine in Africa.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Amodiaquine / administration & dosage
  • Amodiaquine / therapeutic use
  • Antimalarials / administration & dosage
  • Antimalarials / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Therapy, Combination
  • Female
  • Humans
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / epidemiology
  • Male
  • Pyrimethamine / administration & dosage
  • Pyrimethamine / therapeutic use
  • Sulfadoxine / administration & dosage
  • Sulfadoxine / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Uganda / epidemiology


  • Antimalarials
  • Amodiaquine
  • Sulfadoxine
  • Pyrimethamine