title: Molecular surveillance of drug-resistant Plasmodium vivax using pvdhfr, pvdhps and pvmdr1 markers in Nouakchott, Mauritania.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratoire de Biotechnologies,  Faculté des Sciences et Techniques, Université de Nouakchott,  Mauritania.
authors.forename: Khadijetou
authors.initials: K
authors.lastname: Mint Lekweiry
authors.forename: Ali
authors.initials: A
authors.lastname: Ould Mohamed Salem Boukhary
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Gaillard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wurtz
authors.forename: Hervé
authors.initials: H
authors.lastname: Bogreau
authors.forename: Jamal Eddine
authors.initials: JE
authors.lastname: Hafid
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Trape
authors.forename: Housem
authors.initials: H
authors.lastname: Bouchiba
authors.forename: Mohamed Salem
authors.initials: MS
authors.lastname: Ould Ahmedou Salem
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
authors.forename: Leonardo K
authors.initials: LK
authors.lastname: Basco
authors.forename: Sébastien
authors.initials: S
authors.lastname: Briolant
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D018628:Gene Dosage; D006801:Humans; D016780:Malaria, Vivax / Q000453:epidemiology / Q000469:parasitology*; D008435:Mauritania / Q000453:epidemiology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010453:Peptide Synthases / Q000235:genetics*; D010966:Plasmodium vivax / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: D016054:DNA, Protozoan; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010453:Peptide Synthases; D015800:Protozoan Proteins; D013762:Tetrahydrofolate Dehydrogenase; C541684:Mdr1 protein, Plasmodium vivax; C020041:dihydrofolate synthetase