title: The Lys-76-Thr mutation in PfCRT and chloroquine resistance in Plasmodium falciparum isolates from Uganda.
abstract: Recent molecular studies of chloroquine (CQ) resistance of Plasmodium falciparum have demonstrated an association between a mutation in the PfCRT gene and CQ resistance. We identified wild type and mutant alleles of the PfCRT codon 76 in baseline pre-CQ treatment P. falciparum isolates collected during 1999 and investigated their relationship to CQ efficacy in 3 different sites with different levels of CQ parasite resistance in Uganda. Of 32 isolates from Mulago Hospital, all were mutant (100%), while of 45 isolates from Tororo, 5 (11%) were mixed wild type and mutant and 40 (89%) were mutants only. Of 41 isolates from Apac, 13 (32%) were mixed wild type and mutant whereas 28 (68%) were mutants only. The finding of 100% prevalence of the Thr-76 mutant allele in all isolates at the 3 sites was remarkable. We found no association between the presence of Thr-76 mutation and treatment outcome at all the sites. However, the prevalence of the wild-type Lys-76 allele was higher in Apac, an area with lower CQ parasite resistance, compared to Tororo and Mulago which have relatively higher CQ parasite resistance. The Thr-76 allele as a marker of CQ resistance is probably useful in regions where the allele frequency has not yet plateaued.
authors.affiliation: Department of Medical Parasitology, Med Biotech Laboratories, P.O. Box 9364, Kampala, Uganda.
authors.forename: J
authors.initials: J
authors.lastname: Kyosiimire-Lugemwa
authors.forename: A J
authors.initials: AJ
authors.lastname: Nalunkuma-Kazibwe
authors.forename: G
authors.initials: G
authors.lastname: Mujuzi
authors.forename: H
authors.initials: H
authors.lastname: Mulindwa
authors.forename: A
authors.initials: A
authors.lastname: Talisuna
authors.forename: T G
authors.initials: TG
authors.lastname: Egwang
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002738:Chloroquine / Q000627:therapeutic use*; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009154:Mutation / Q000235:genetics*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D015800:Protozoan Proteins; D014454:Uganda
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine