Mutations in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance genes, and treatment outcomes in Ghanaian children with uncomplicated malaria.
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.
Duah
Nancy O
NO
Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG581, Legon, Ghana. Nancy.Duah@lshtm.ac.uk
Wilson
Michael D
MD
Ghansah
Anita
A
Abuaku
Ben
B
Edoh
Dominic
D
Quashie
Neils B
NB
Koram
Kwadwo A
KA
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
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D003062:Codon; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine