title: Mutations in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance genes, and treatment outcomes in Ghanaian children with uncomplicated malaria.
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.
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG581, Legon, Ghana. Nancy.Duah@lshtm.ac.uk
authors.forename: Nancy O
authors.initials: NO
authors.lastname: Duah
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wilson
authors.forename: Anita
authors.initials: A
authors.lastname: Ghansah
authors.forename: Ben
authors.initials: B
authors.lastname: Abuaku
authors.forename: Dominic
authors.initials: D
authors.lastname: Edoh
authors.forename: Neils B
authors.initials: NB
authors.lastname: Quashie
authors.forename: Kwadwo A
authors.initials: KA
authors.lastname: Koram
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D016009:Chi-Square Distribution; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology*; D003062:Codon; D018432:Drug Resistance, Multiple; D005260:Female; D017125:Genes, Protozoan / Q000235:genetics; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D009154:Mutation; D010963:Plasmodium falciparum / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D003062:Codon; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine