title: Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial.
abstract: BACKGROUND
  Increasing drug resistance limits the choice of efficacious chemotherapy against Plasmodium falciparum malaria in Africa. Amodiaquine still retains efficacy against P falciparum in many African countries. We assessed the safety, treatment efficacy, and effect on gametocyte carriage of adding artesunate to amodiaquine in three randomised trials in Kenya, Sénégal, and Gabon.
  
  
  METHODS
  We enrolled 941 children (400 in Kenya, 321 in Sénégal, and 220 in Gabon) who were 10 years or older and who had uncomplicated P falciparum malaria. Patients were randomly assigned amodiaquine (10 mg/kg per day for 3 days) plus artesunate (4 mg/kg per day for 3 days) or amodiaquine (as above) and placebo (for 3 days). The primary endpoints were parasitological cure rates at days 14 and 28. Analysis was by intention to treat and by an evaluability method.
  
  
  RESULTS
  Both regimens were well tolerated. Six patients in the amodiaquine-artesunate group and five in the amodiaquine group developed early, drug-induced vomiting, necessitating alternative treatment. By intention-to-treat analysis, the day-14 cure rates for amodiaquine-artesunate versus amodiaquine were: 175/192 (91%) versus 140/188 (74%) in Kenya (D=16.7% [95% CI 9.3-24.1], p<0.0001), 148/160 (93%) versus 147/157 (94%) in Sénégal (-1.1% [-6.7 to 4.5], p=0.7), and 92/94 (98%) versus 86/96 (90%) in Gabon (8.3% [1.5-15.1], p=0.02). The corresponding rates for day 28 were: 123/180 (68%) versus 75/183 (41%) in Kenya (27.3% [17.5-37.2], p<0.0001), 130/159 (82%) versus 123/156 (79%) in Sénégal (2.9% [-5.9 to 11.7], p=0.5), and 80/94 (85%) versus 70/98 (71%) in Gabon (13.7% [2.2-25.2], p=0.02). Similar rates were obtained by evaluability analysis.
  
  
  CONCLUSIONS
  The combination of artesunate and amodiaquine improved treatment efficacy in Gabon and Kenya, and was equivalent in Sénégal. Amodiaquine-artesunate is a potential combination for use in Africa. Further investigations to assess the potential effect on the evolution of drug resistance, disease transmission, and safety of amodiaquine-artesunate are warranted.
authors.affiliation: Navrongo Health Research Centre, Navrongo, Ghana.
authors.forename: M
authors.initials: M
authors.lastname: Adjuik
authors.forename: P
authors.initials: P
authors.lastname: Agnamey
authors.forename: A
authors.initials: A
authors.lastname: Babiker
authors.forename: S
authors.initials: S
authors.lastname: Borrmann
authors.forename: P
authors.initials: P
authors.lastname: Brasseur
authors.forename: M
authors.initials: M
authors.lastname: Cisse
authors.forename: F
authors.initials: F
authors.lastname: Cobelens
authors.forename: S
authors.initials: S
authors.lastname: Diallo
authors.forename: J F
authors.initials: JF
authors.lastname: Faucher
authors.forename: P
authors.initials: P
authors.lastname: Garner
authors.forename: S
authors.initials: S
authors.lastname: Gikunda
authors.forename: P G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: S
authors.initials: S
authors.lastname: Krishna
authors.forename: B
authors.initials: B
authors.lastname: Lell
authors.forename: M
authors.initials: M
authors.lastname: Loolpapit
authors.forename: P B
authors.initials: PB
authors.lastname: Matsiegui
authors.forename: M A
authors.initials: MA
authors.lastname: Missinou
authors.forename: J
authors.initials: J
authors.lastname: Mwanza
authors.forename: F
authors.initials: F
authors.lastname: Ntoumi
authors.forename: P
authors.initials: P
authors.lastname: Olliaro
authors.forename: P
authors.initials: P
authors.lastname: Osimbo
authors.forename: P
authors.initials: P
authors.lastname: Rezbach
authors.forename: E
authors.initials: E
authors.lastname: Some
authors.forename: W R J
authors.initials: WR
authors.lastname: Taylor
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*; D037621:Artemisinins; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005681:Gabon; D006801:Humans; D007223:Infant; D007630:Kenya; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects*; D012675:Senegal; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000655:Amodiaquine; D000077332:Artesunate