by Samuel Dunyo, Rosalynn Ord, Rachel Hallett, Musa Jawara, Gijs Walraven, Eduardo Mesa, Rosalind Coleman, Maimuna Sowe, Neal Alexander, Geoffrey A. T Targett, Margaret Pinder, Colin J Sutherland
Objectives
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.
Design
We conducted a single-blind, randomised, controlled trial to compare the efficacy of CQ/SP to that of SP or CQ alone.
Setting
The study took place in the town of Farafenni and surrounding villages in the Gambia.
Participants
Participants were children aged 12 mo to 10 y presenting as outpatients with uncomplicated P. falciparum malaria.
Interventions
500 children were randomised to receive CQ, SP, or CQ/SP as supervised treatment and actively followed over 28 d.
Outcome Measures
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 p 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.
Trial Registration
Controlled-Trials.com ISRCTN11805747