Abstract
BackgroundPolymorphisms 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.MethodsThe 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.ResultsAll the investigated samples exhibit the wild-type genotype at all three positions; L263, A623, S769.ConclusionAll 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.
Highlights
Polymorphisms within the Plasmodium falciparum Ca2+ -ATPase coding gene (PfATP6) gene have been indicated as potential molecular markers for artemisinin efficacy
Various independent experimental approaches corroborate the emerging of artemisinin resistance: reports of cure rates below 75% after artemether-lumefantrine treatment in Cambodia [5]; the production of artemisinin-resistant strains in vivo in the rodent malaria model Plasmodium yoelii [6]; the selection of genetically stable and transmissible parasites resistant to artemisinin and artesunate in P. chabaudi chabaudi [7] and the observation of in vitro resistance to Artemether in isolates from French Guiana [8] and in travelers returning from sub-Saharan Africa [9]
Sufficient Deoxyribonucleic Acid (DNA) was recovered for all 28 samples and single nucleotide polymorphic assays were successfully performed for all three amino acid positions 263, 623 and 769
Summary
Polymorphisms within the PfATP6 gene have been indicated as potential molecular markers for artemisinin efficacy. Various independent experimental approaches corroborate the emerging of artemisinin resistance: reports of cure rates below 75% after artemether-lumefantrine treatment in Cambodia [5]; the production of artemisinin-resistant strains in vivo in the rodent malaria model Plasmodium yoelii [6]; the selection of genetically stable and transmissible parasites resistant to artemisinin and artesunate in P. chabaudi chabaudi [7] and the observation of in vitro resistance to Artemether in isolates from French Guiana [8] and in travelers returning from sub-Saharan Africa [9] These observations demonstrate that malaria parasites are genetically and biologically capable of sustaining stable resistance to artemisinins, and that this resistance can be selected through drug pressure
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