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Journal of Tropical Pediatrics Advance Access originally published online on December 10, 2006
Journal of Tropical Pediatrics 2007 53(1):27-31; doi:10.1093/tropej/fml076
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© The Author [2006]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Mutations in Plasmodium falciparum Chloroquine Resistance Transporter and Multidrug Resistance Genes, and Treatment Outcomes in Ghanaian Children with Uncomplicated Malaria

Nancy O. Duaha, Michael D. Wilsona, Anita Ghansaha, Ben Abuakua, Dominic Edohb, Neils B. Quashiea,c and Kwadwo A. Korama

aNoguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG581, Legon, Ghana
bZoology Department, and cCentre for Tropical Clinical Pharmacology and Therapeutics, University of Ghana Medical School, Accra, Ghana

Correspondence: N.O. Duah, Noguchi Memorial Institute for Medical Research, P. O. Box LG581, Legon-Accra. Tel.: +233 (0)21 501178; Fax: +233 (0)21 502182; E-mail < Nancy.Duah{at}lshtm.ac.uk>.


  Abstract

The association between the clinical outcome of chloroquine treatment and mutations in the putative Plasmodium falciparum chloroquine resistance transporter (Pfcrt) gene at codon 76 and multidrug resistance gene 1 (Pf mdr1) at codon 86 were investigated among 406 children with uncomplicated malaria presenting at five sentinel health centres in Ghana. Presence of mutations in isolates taken at pre-treatment and on day of recurrence of parasites was detected using PCR followed by RFLP techniques. The prevalence of Pfcrt T76 mutants was 80% at Hohoe, 46% at Navrongo, 98% at Tarkwa, 61% at Sunyani and 46% at Yendi. The prevalence of the mutant Pfmdr1 at Hohoe, Navrongo, Tarkwa, Sunyani and Yendi were 78, 58, 95, 53 and 42%, respectively. Significant association between the Pfcrt mutation and treatment outcome was observed at Hohoe and Sunyani (p < 0.05), but not at Navrongo, Tarkwa or Yendi (p > 0.05). Similarly, a statistical significant association between Pfmdr1 86 and treatment failures was observed at Hohoe and Sunyani (p < 0.05) but not at the other three sites. A positive correlation was found between mutant Pfcrt prevalence only and treatment failures with a Spearman's {rho}-value of 0.872 and a p-value = 0.027. All parasite isolates from samples taken at recrudescence from patients with chloroquine treatment failures were found to have both Pfcrt and Pfmdr mutations.

Key Words: chloroquine • resistance • genetic markers • Pfcrt • Pfmdr • mutations


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