Molecular surveillance of drug-resistant Plasmodium vivax using pvdhfr, pvdhps and pvmdr1 markers in Nouakchott, Mauritania

Abstract

Plasmodium falciparum and Plasmodium vivax occur in Mauritania. Drug-resistant P. falciparum has been reported, but the drug-resistance status of P. vivax is unknown. The aims of the present study were to determine the prevalence of mutant pvdhfr, pvdhps and pvmdr1 genes and of pvmdr1 gene amplification in P. vivax isolates in Nouakchott, the capital city of Mauritania, and to establish a baseline for molecular surveillance of drug-resistant P. vivax in the country. Between 2007 and 2009, 439 febrile patients were screened for malaria in Nouakchott. The sequences of pvdhfr, pvdhps and pvmdr1 markers in 110 P. vivax isolates were determined by direct sequencing of PCR products. The pvmdr1 gene copy number was determined by real-time PCR. The majority of the isolates with a successful PCR amplification (76/86, 88%) were characterized to be of the wild-type pvdhfr genotype, while the remaining 10 isolates carried the S58R and S117N double mutations. All isolates had the wild-type pvdhps genotype SAKAV. For pvmdr1, 75 of 103 (73%) had the wild-type Y976, and 28 (27%) carried the mutant F976. Most (98%) carried the mutant L1076 codon. Of 105 isolates, 102 (97%) had one copy and 3 (3%) had two copies of the pvmdr1 gene. The prevalence of mutations associated with antifolate resistance is low in Mauritania. Further studies are required to determine the roles of pvmdr1 mutations and gene amplification in conferring drug resistance. These data will serve as a baseline for further monitoring of drug-resistant malaria.