pfmdr1 Amplification and Fixation of pfcrt Chloroquine Resistance Alleles in Plasmodium falciparum in Venezuela

Molecular tools are valuable for determining evolutionary history and the prevalence of drug-resistant malaria parasites. These tools have helped to predict decreased sensitivity to antimalarials and fixation of multidrug resistance genotypes in some regions. In order to assess how historical drug policies impactedPlasmodium falciparum in Venezuela, we examined molecular changes in genes associated with drug resistance. We examinedpfmdr1 andpfcrt in samples from Sifontes, Venezuela, and integrated our findings with earlier work describingdhfr anddhps in these samples. We characterizedpfmdr1 genotypes and copy number variation,pfcrt genotypes, and proximal microsatellites in 93 samples originating from surveillance from 2003 to 2004. Multicopypfmdr1 was found in 12% of the samples. Twopfmdr1 alleles, Y184F /N1042D /D1246Y (37%) and Y184F /S1034C /N1042D /D1246Y (63%), were found. These alleles share ancestry, and no evidence of strong selective pressure on mutations was found.pfcrt chloroquine resistance alleles are fixed with two alleles:S tct VMNT (91%) andS agt VMNT (9%). These alleles are associated with strong selection. There was also an association betweenpfcrt ,pfmdr1 ,dhfr , anddhps genotypes/haplotypes. Duplication ofpfmdr1 suggests a potential shift in mefloquine sensitivity in this region, which warrants further study. A bottleneck occurred inP. falciparum in Sifontes, Venezuela, and multidrug resistance genotypes are present. This population could be targeted for malaria elimination programs to prevent the possible spread of multidrug-resistant parasites.