Association of cg2 and pfmdr1 genotype with chloroquine resistance in field samples of Plasmodium falciparum from Nigeria.
This study examines polymorphisms in 2 genes (pfmdr1 and cg2), which have been associated with resistance to chloroquine in Plasmodium falciparum, to determine their value as predictors of resistance status. Among field samples from children in Zaria, northern Nigeria, the Tyr-86 polymorphism in pfmdr1 and Ala-281 and the Dd2 kappa repeat of cg2, were significantly associated. In 8 samples classified resistant by the micro-in vitro test, or, where this failed, by in vivo trial, 7 showed the cg2 Dd2 type kappa repeat, and 6 of these had both the Ala-281 allele and the pfmdr1 Tyr-86 allele. In 26 chloroquine-sensitive samples, none had this combination of 3 polymorphisms (P = 0.00002). This indicates 75% sensitivity and 100% specificity in detection of resistance and shows a positive predictive value for resistant infections of 100%. The negative predictive value, because of sensitivity less than 100%, would depend on the prevalence of resistance. Where prevalence of resistance is approx. 21% as in Zaria, the negative predictive value would be 94%, while in Gabon, with a prevalence of ca 73% it would be 60%. The use of (cg2: Ala-281, Dd2 kappa. pfmdr1: Tyr-86) genotype detection as a predictive epidemiological tool to examine the distribution of chloroquine-resistance in parts of Africa is therefore possible. The sensitivity of detection of resistant strains still requires improvement.
Adagu
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Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK. I.Adagu@lshtm.ac.uk
Warhurst
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D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D017125:Genes, Protozoan; D005838:Genotype; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000469:parasitology*; D009549:Nigeria; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins / Q000235:genetics*
D018528:ATP-Binding Cassette Transporters; C109422:CG2 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine