| Summary: | Chloroquine combined with primaquine has been the recommended antimalarial treatment for Plasmodium vivax malaria infections for sixty years but the efficacy of this treatment regimen is threatened by chloroquine resistance. In this study we describe the prevalence of mutations in the P. vivax gene, Pvmdr1 among samples collected in seven endemic countries. The mutations are thought to be associated with chloroquine resistance and here we looked for evidence of drug selection by characterising polymorphism in DNA repeat regions (microsatellite (MS) loci) flanking the Pvmdr1 gene. Mutations in the Pvmdr1 gene were mainly identified at codons T958M, Y976F and F1076L. Just 2.4% of samples were wildtype at all three codons, while 63% were single mutants (MYF). Clear geographic differences in the prevalence of these Pvmdr mutation combinations were observed. At the flanking MS loci, we found high levels of diversity, and significant differentiation between geographic sites. This pattern of variation could indicate directional selection through local drug pressure. In summary, our observations suggest that Pvmdr1 mutations and thus, chloroquine resistance has emerged independently on multiple occasions even within the same population.
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