The Lys-76-Thr mutation in WC/Wand chloroquine resistance in Plasmodium falciparum isolates from Uganda

Recent molecular studies of chloroquine (CQ) resistance of Plasmodium falciparum have demonstrated an association between a mutation in the PƒCRT gene and CQ resistance. We identified wild type and mutant alleles of the PƒCRT 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.

Keywords

Plasmodium falciparumgenetic, analysisgene mutation,PƒCRT,drug resistance,chloroquine,Uganda

Citation

Kyosiimire-Lugemwa, J., Nalunkuma-Kazibwe, A. J., Mujuzi, G., Mulindwa, H., Talisuna, A., & Egwang, T. G. (2002). The Lys-76-Thr mutation in PfCRTand chloroquine resistance in Plasmodium falciparum isolates from Uganda. Transactions of the Royal Society of Tropical Medicine and Hygiene, 96(1), 91-95.https://doi.org/10.1016/S0035-9203(02)90252-X

URI

https://nru.uncst.go.ug/handle/123456789/3617

Collections

Medical and Health Sciences

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