title: Sulphadoxine/pyrimethamine versus amodiaquine for treating uncomplicated childhood malaria in Gabon: a randomized trial to guide national policy.
abstract: BACKGROUND
  In Gabon, following the adoption of amodiaquine/artesunate combination (AQ/AS) as first-line treatment of malaria and of sulphadoxine/pyrimethamine (SP) for preventive intermittent treatment of pregnant women, a clinical trial of SP versus AQ was conducted in a sub-urban area. This is the first study carried out in Gabon following the WHO guidelines.
  
  
  METHODS
  A random comparison of the efficacy of AQ (10 mg/kg/day x 3 d) and a single dose of SP (25 mg/kg of sulphadoxine/1.25 mg/kg of pyrimethamine) was performed in children under five years of age, with uncomplicated falciparum malaria, using the 28-day WHO therapeutic efficacy test. In addition, molecular genotyping was performed to distinguish recrudescence from reinfection and to determine the frequency of the dhps K540E mutation, as a molecular marker to predict SP-treatment failure.
  
  
  RESULTS
  The day-28 PCR-adjusted treatment failures for SP and AQ were 11.6% (8/69; 95% IC: 5.5-22.1) and 28.2% (20/71; 95% CI: 17.7-38.7), respectively This indicated that SP was significantly superior to AQ (P = 0.019) in the treatment of uncomplicated childhood malaria and for preventing recurrent infections. Both treatments were safe and well-tolerated, with no serious adverse reactions recorded. The dhps K540E mutation was not found among the 76 parasite isolates tested.
  
  
  CONCLUSIONS
  The level of AQ-resistance observed in the present study may compromise efficacy and duration of use of the AQ/AS combination, the new first-line malaria treatment. Gabonese policy-makers need to plan country-wide and close surveillance of AQ/AS efficacy to determine whether, and for how long, these new recommendations for the treatment of uncomplicated malaria remain valid.
authors.affiliation: National Malaria Control Programme - Division for Disease Control, Ministry of Health, Brazzaville, Congo. basilensimba@aol.com
authors.forename: Basile
authors.initials: B
authors.lastname: Nsimba
authors.forename: Vincent
authors.initials: V
authors.lastname: Guiyedi
authors.forename: Modeste
authors.initials: M
authors.lastname: Mabika-Mamfoumbi
authors.forename: Jean Romain
authors.initials: JR
authors.lastname: Mourou-Mbina
authors.forename: Edgard
authors.initials: E
authors.lastname: Ngoungou
authors.forename: Marielle
authors.initials: M
authors.lastname: Bouyou-Akotet
authors.forename: Romaric
authors.initials: R
authors.lastname: Loembet
authors.forename: Rémy
authors.initials: R
authors.lastname: Durand
authors.forename: Jacques
authors.initials: J
authors.lastname: Le Bras
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Kombila
mesh_terms: D000655:Amodiaquine / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D000077332:Artesunate; D002675:Child, Preschool; D004094:Dihydropteroate Synthase / Q000235:genetics; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005681:Gabon; D006291:Health Policy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D009154:Mutation; D010963:Plasmodium falciparum / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011739:Pyrimethamine / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000655:Amodiaquine; D000077332:Artesunate; D013413:Sulfadoxine; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine