title: A randomised trial to assess the efficacy and safety of chlorproguanil/dapsone + artesunate for the treatment of uncomplicated Plasmodium falciparum malaria.
abstract: We tested the efficacy and safety of chlorproguanil/dapsone co-administered with artesunate (CD+A) for the treatment of uncomplicated Plasmodium falciparum malaria in children compared with amodiaquine+sulfadoxine/pyrimethamine (AQ+SP) at two different sites in Rwanda. The trial was open label and 800 patients were randomly assigned to AQ+SP (n=400) or CD+A (n=400). Patients were hospitalised for 3 days and then followed-up weekly until Day 28 after treatment. Clinical and parasitological outcomes were recorded. Results showed that neither treatment was adequately efficacious. At one site, the adequate clinical and parasitological response (ACPR), PCR-adjusted, was 73.3% in the CD+A arm and 87.8% in the AQ+SP arm (P<0.001), and at the second site the ACPR, PCR-adjusted, was 70.5% in the CD+A arm and 38.1% in the AQ+SP arm (P<0.001). The combination CD+A is considered an alternative to, or replacement for, SP in Africa because CD has been shown to be effective in patients for whom SP treatment has failed and, with its short half-life, it is expected to exert less selection pressure for resistant parasites than SP. However, the results of this trial indicate that in an area of high SP resistance, CD+A may not be the best choice.
authors.affiliation: London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. caterina.fanello@lshtm.ac.uk
authors.forename: C I
authors.initials: CI
authors.lastname: Fanello
authors.forename: C
authors.initials: C
authors.lastname: Karema
authors.forename: D
authors.initials: D
authors.lastname: Ngamije
authors.forename: A
authors.initials: A
authors.lastname: Uwimana
authors.forename: V
authors.initials: V
authors.lastname: Ndahindwa
authors.forename: C
authors.initials: C
authors.lastname: Van Overmeir
authors.forename: W
authors.initials: W
authors.lastname: Van Doren
authors.forename: J
authors.initials: J
authors.lastname: Curtis
authors.forename: U
authors.initials: U
authors.lastname: D'Alessandro
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects; D000077332:Artesunate; D002675:Child, Preschool; D003622:Dapsone / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D002727:Proguanil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D012423:Rural Health; D012432:Rwanda / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; C007030:chlorproguanil; D003622:Dapsone; D002727:Proguanil