SNPs on ABC Transporters and in vivo Malaria Parasite Non Clearance after Chloroquine Treatment in Malian Children

Abstract

Background: pfcrt K76T mutation was demonstrated to play a central role in the P. falciparum resistance to chloroquine. Aim: To find any association between mutant alleles of pfcrt K76T, pfmdr1 N86Y, pfG30 and pfG47 and the in vivo parasite non clearance after chloroquine treatment in Mali. Methodology: We carried out a chloroquine efficacy study in 196 children suffering from uncomplicated malaria in a rural village of Kollé, Mali, using WHO protocol. Subjects were treated with standard dose of chloroquine and followed for 14 days. Parasite DNA was extracted from finger prick blood blotted onto filter paper and genotypes were analyzed by different PCR methods. Results: The mutant alleles pfcrt 76T and pfmdr1 86Y were associated with parasite non clearance withp=0.00001 and 0.03 respectively. However, the association of SNPs on pfG30 and pfG47 genes with parasite non clearance was not statistically significant, p =0.43 and 0.57 respectively. The logistic regression analysis showed that the mutant allele pfmdr186Y contributed positively to the pfcrt 76T parasites non clearance (p=0.02). Conclusion: These findings have shown that pfcrt76T and pfmdr1 86Y alleles are associated with the in vivoparasite non clearance, but not SNPs on the new putative transporters genes.