title: Assessment of the efficacy of antimalarial drugs recommended by the National Malaria Control Programme in Madagascar: up-dated baseline data from randomized and multi-site clinical trials.
abstract: BACKGROUND
  In order to improve the monitoring of the antimalarial drug resistance in Madagascar, a new national network based on eight sentinel sites was set up. In 2006/2007, a multi-site randomized clinical trial was designed to assess the therapeutic efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP), amodiaquine (AQ) and artesunate plus amodiaquine combination (ASAQ), the antimalarial therapies recommended by the National Malaria Control Programme (NMCP).
  
  
  METHODS
  Children between six months and 15 years of age, with uncomplicated falciparum malaria, were enrolled. Primary endpoints were the day-14 and day-28 risks of parasitological failure, either unadjusted or adjusted by genotyping. Risks of clinical and parasitological treatment failure after adjustment by genotyping were estimated using Kaplan-Meier survival analysis. Secondary outcomes included fever clearance, parasite clearance, change in haemoglobin levels between Day 0 and the last day of follow-up, and the incidence of adverse events.
  
  
  RESULTS
  A total of 1,347 of 1,434 patients (93.9%) completed treatment and follow-up to day 28. All treatment regimens, except for the chloroquine (CQ) treatment group, resulted in clinical cure rates above 97.6% by day-14 and 96.7% by day-28 (adjusted by genotyping). Parasite and fever clearance was more rapid with artesunate plus amodiaquine, but the extent of haematological recovery on day-28 did not differ significantly between the four groups. No severe side-effects were observed during the follow-up period.
  
  
  CONCLUSIONS
  These findings (i) constitute an up-dated baseline data on the efficacy of antimalarial drugs recommended by the NMCP, (ii) show that antimalarial drug resistance remains low in Madagascar, except for CQ, compared to the bordering countries in the Indian Ocean region such as the Comoros Archipelago and (iii) support the current policy of ASAQ as the first-line treatment in uncomplicated falciparum malaria.
authors.affiliation: Malaria Unit Research, Institut Pasteur de Madagascar, Antananarivo, Madagascar. dmenard@pasteur.mg
authors.forename: Didier
authors.initials: D
authors.lastname: Ménard
authors.forename: Arsène
authors.initials: A
authors.lastname: Ratsimbasoa
authors.forename: Milijaona
authors.initials: M
authors.lastname: Randrianarivelojosia
authors.forename: Léon-Paul
authors.initials: LP
authors.lastname: Rabarijaona
authors.forename: Lucie
authors.initials: L
authors.lastname: Raharimalala
authors.forename: Olivier
authors.initials: O
authors.lastname: Domarle
authors.forename: Laurence
authors.initials: L
authors.lastname: Randrianasolo
authors.forename: Arthur
authors.initials: A
authors.lastname: Randriamanantena
authors.forename: Martial
authors.initials: M
authors.lastname: Jahevitra
authors.forename: Valérie
authors.initials: V
authors.lastname: Andriantsoanirina
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Rason
authors.forename: Rogelin
authors.initials: R
authors.lastname: Raherinjafy
authors.forename: Emma
authors.initials: E
authors.lastname: Rakotomalala
authors.forename: Luciano
authors.initials: L
authors.lastname: Tuseo
authors.forename: Andrianirina
authors.initials: A
authors.lastname: Raveloson
mesh_terms: D000293:Adolescent; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007223:Infant; D008270:Madagascar; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D009313:National Health Programs; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials