In vivo and in vitro analysis of chloroquine resistance in Plasmodium falciparum isolates from Senegal
- PMID: 15986248
- PMCID: PMC2579896
- DOI: 10.1007/s00436-005-1406-7
In vivo and in vitro analysis of chloroquine resistance in Plasmodium falciparum isolates from Senegal
Abstract
To determine the predictive value of chloroquine (CQ) resistance markers in Senegal, Plasmodium falciparum DNA polymorphisms in pfmdr1and pfcrt were examined in relation to clinical outcome. Despite CQ treatment, 17% of patients had parasitemia after 28 days. Examination of molecular markers of CQ resistance revealed that 64% of all isolates had the T76 resistant allele at the pfcrt locus, while 30% carried the Y86 resistant allele at the pfmdr1 locus. The pfcrt T76 allele was present not only in all in vivo resistant isolates, 89% of in vitro resistant isolates, but also in 35% of in vitro sensitive isolates. The pfmdr1 N86Y polymorphism did not correlate with in vitro or in vivo CQ resistance. Our data suggest that the pfcrt T76 allele alone is required but not a sufficient predictor for in vivo CQ resistance.
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References
-
- Basco LK, Ringwald P. Analysis of the key pfcrt point mutation and in vitro and in vivo response to chloroquine in Yaounde, Cameroon. J Infect Dis. 2001;183:1828–1831. - PubMed
-
- Carlton JM, Fidock DA, Djimde A, Plowe CV, Wellems TE. Conservation of a novel vacuolar transporter in Plasmodium species and its central role in chloroquine resistance of P. falciparum. Curr Opin Microbiol. 2001;4:415–420. - PubMed
-
- Chen N, Russell B, Staley J, Kotecka B, Nasveld P, Cheng Q. Sequence polymorphisms in pfcrt are strongly associated with chloroquine resistance in Plasmodium falciparum. J Infect Dis. 2001;183:1543–1545. - PubMed
-
- Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, Coulibaly D. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med. 2001a;344:257–263. - PubMed
-
- Dorsey G, Kamya MR, Singh A, Rosenthal PJ. Polymorphisms in the Plasmodium falciparumpfcrt and pfmdr-1 genes and clinical response to chloroquine in Kampala, Uganda. J Infect Dis. 2001;183:1417–1420. - PubMed
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