title: Randomised trial of chloroquine/sulphadoxine-pyrimethamine in Gambian children with malaria: impact against multidrug-resistant P. falciparum.
abstract: OBJECTIVE
  In the Gambia, the combination of chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) has replaced CQ monotherapy for treatment of malaria caused by Plasmodium falciparum. We measured the efficacy of the combination CQ/SP, and the prevalence of parasites carrying alleles associated with resistance to CQ or SP.
  
  
  METHODS
  We conducted a single-blind, randomised, controlled trial to compare the efficacy of CQ/SP to that of SP or CQ alone.
  
  
  METHODS
  The study took place in the town of Farafenni and surrounding villages in the Gambia.
  
  
  METHODS
  Participants were children aged 12 mo to 10 y presenting as outpatients with uncomplicated P. falciparum malaria.
  
  
  METHODS
  500 children were randomised to receive CQ, SP, or CQ/SP as supervised treatment and actively followed over 28 d.
  
  
  METHODS
  Primary outcome was parasitaemia at any time during follow-up. Secondary outcomes were PCR-confirmed recrudescent infections among treatment failures, and clinical failure requiring rescue medication by day 28. Pretreatment parasite isolates from 161 patients were tested for the presence of resistance-associated genetic markers.
  
  
  RESULTS
  The prevalence of parasitological failure by day 28 for the CQ group was 60.3%, compared to 17.6% for SP (odds ratio [OR], 0.106; 95% confidence interval [CI], 0.057-0.194; p < 0.001) and 13.9% for CQ/SP (OR versus CQ, 0.140; 95% CI, 0.078-0.250; p < 0.001). There was no difference between the SP and CQ/SP groups (OR, 1.324; 95% CI, 0.705-2.50). The projected prevalence of PCR-corrected treatment failure was 30.2, 6.06, and 3.94% in the CQ, SP, and CQ/SP groups, respectively. The pfdhfr-triple mutant and pfdhps-437G mutation were common, with prevalences of 67.4 and 51.2%, respectively. Pretreatment carriage of pfdhps-437G and of multidrug-resistant parasite genotypes was associated with treatment failure in the SP group, but not in the CQ or CQ/SP groups.
  
  
  CONCLUSIONS
  The combination of CQ/SP was an efficacious treatment for uncomplicated malaria in Gambian children in this study, but the frequent occurrence of multidrug-resistant parasites suggests that this observed efficacy is not sustainable.
authors.affiliation: Farafenni Field Station, Medical Research Council Laboratories, Fajara, The Gambia.
authors.forename: Samuel
authors.initials: S
authors.lastname: Dunyo
authors.forename: Rosalynn
authors.initials: R
authors.lastname: Ord
authors.forename: Rachel
authors.initials: R
authors.lastname: Hallett
authors.forename: Musa
authors.initials: M
authors.lastname: Jawara
authors.forename: Gijs
authors.initials: G
authors.lastname: Walraven
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mesa
authors.forename: Rosalind
authors.initials: R
authors.lastname: Coleman
authors.forename: Maimuna
authors.initials: M
authors.lastname: Sowe
authors.forename: Neal
authors.initials: N
authors.lastname: Alexander
authors.forename: Geoffrey A T
authors.initials: GA
authors.lastname: Targett
authors.forename: Margaret
authors.initials: M
authors.lastname: Pinder
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Sutherland