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Dunyo S, Ord R, Hallett R, et al. Randomised trial of chloroquine/sulphadoxine-pyrimethamine in Gambian children with malaria: impact against multidrug-resistant P. falciparum. PLoS Clin Trials. 2006;1(3):e14doi: 10.1371/journal.pctr.0010014.
Dunyo, S., Ord, R., Hallett, R., Jawara, M., Walraven, G., Mesa, E., Coleman, R., Sowe, M., Alexander, N., Targett, G. A., Pinder, M., & Sutherland, C. J. (2006). Randomised trial of chloroquine/sulphadoxine-pyrimethamine in Gambian children with malaria: impact against multidrug-resistant P. falciparum. PLoS clinical trials, 1(3), e14. https://doi.org/10.1371/journal.pctr.0010014
Dunyo, Samuel, et al. "Randomised trial of chloroquine/sulphadoxine-pyrimethamine in Gambian children with malaria: impact against multidrug-resistant P. falciparum." PLoS clinical trials vol. 1,3 (2006): e14. doi: https://doi.org/10.1371/journal.pctr.0010014
Dunyo S, Ord R, Hallett R, Jawara M, Walraven G, Mesa E, Coleman R, Sowe M, Alexander N, Targett GA, Pinder M, Sutherland CJ. Randomised trial of chloroquine/sulphadoxine-pyrimethamine in Gambian children with malaria: impact against multidrug-resistant P. falciparum. PLoS Clin Trials. 2006 Jul 21;1(3):e14. doi: 10.1371/journal.pctr.0010014. PMID: 16871319; PMCID: PMC1513406.
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PLoS Clin Trials. 2006 Jul 21;1(3):e14. doi: 10.1371/journal.pctr.0010014.

Randomised trial of chloroquine/sulphadoxine-pyrimethamine in Gambian children with malaria: impact against multidrug-resistant P. falciparum.

PLoS clinical trials

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

Affiliations

  1. Farafenni Field Station, Medical Research Council Laboratories, Fajara, The Gambia.

PMID: 16871319 PMCID: PMC1513406 DOI: 10.1371/journal.pctr.0010014

Abstract

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 < 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.

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