Status of potential PfATP6 molecular markers for artemisinin resistance in Suriname

Malar J. 2012 Sep 11:11:322. doi: 10.1186/1475-2875-11-322.

Abstract

Background: Polymorphisms within the PfATP6 gene have been indicated as potential molecular markers for artemisinin efficacy. Since 2004, the use of artemisinin combination therapy (ACT) was introduced as first-line treatment of the uncomplicated malaria cases in Suriname. The aim of this research was to determine changes in Suriname in the status of the polymorphic markers in the PfATP6 gene before and after the adoption of the ACT-regimen, particularly of the S769N mutation, which was reported to be associated with in vitro Artemether resistance in the neighboring country French Guiana.

Methods: The PfATP6 gene from Plasmodium falciparum parasites in Suriname was investigated in 28 samples using PCR amplification and restriction enzyme analysis, to assess and determine the prevalence of potentially interesting single nucleotide polymorphisms. The polymorphisms [L263E; A623E; S769N], which may be associated with the artemisinin resistant phenotype were characterized in parasites from three endemic regions before and after the adoption of the ACT-regimen. In addition, the status of these molecular markers was compared in paired P. falciparum isolates from patients with recurring malaria after controlled ACT.

Results: All the investigated samples exhibit the wild-type genotype at all three positions; L263, A623, S769.

Conclusion: All investigated isolates before and after the adoption of the ACT-regimen and independent of endemic region harbored the wild-type genotype for the three investigated polymorphisms. The study revealed that decreased artemisinin susceptibility could occur independent from PfATP6 mutations, challenging the assumption that artemisinin resistance is associated with these mutations in the PfATP6 gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Artemisinins / pharmacology*
  • Calcium-Transporting ATPases / genetics*
  • DNA, Protozoan / genetics
  • Drug Resistance*
  • Female
  • Humans
  • Malaria, Falciparum / parasitology*
  • Male
  • Mutation, Missense
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / isolation & purification
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Suriname

Substances

  • ATP6 protein, Plasmodium falciparum
  • Artemisinins
  • DNA, Protozoan
  • artemisinin
  • Calcium-Transporting ATPases