Prevalence of pfmdr1 alleles associated with artemether-lumefantrine tolerance/resistance in Maputo before and after the implementation of artemisinin-based combination therapy

Abstract

BackgroundMozambique implemented artemisinin-based combinations therapy (ACT) using artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in 2009. AL remains highly efficacious, but widespread use may soon facilitate emergence of artemisinin tolerance/resistance. The prevalence of pfmdr1 different alleles in Maputo and Mozambique is not known, either after or before the introduction of ACT. Pfmdr1 molecular markers related to Plasmodium falciparum susceptibility were analysed before and after transition to ACT.MethodsA first group of samples was collected between June 2003 and June 2005 and a second group in the period between March 2010 and March 2012. Three alleles were analysed by PCR-RFLP: N86Y, Y184F and D1246Y, in the pfmdr1 gene.ResultsAlleles N86, 184F and D1246 increased from 19.5, 19.6 and 74.4% in 2003–2005 to 73.2, 22.7 and 96.7% in 2010–2012, respectively. After implementation of ACT (2010–2012), pfmdr1 haplotypes, either two- and three-codon basis, were generally less diverse than before the implementation of ACT (2003–2005). The prevalence of haplotypes N86-184Y, N86-D1246 and 184Y-D1246 increased from 12,2, 27.3 and 71.7% in 2003–2005 to 59.4, 84.3 and 78.6% in 2010–2012. The three-codon basis haplotypes NFD and NYD also increased significantly during the same period.ConclusionThe alleles N86 and 184 F and the triple haplotype N86-184 F-D1246 showed a significantly increased prevalence after introduction of ACT.

Pfmdr1 gene polymorphism of Plasmodium falciparum isolates from asymptomatic individuals of Dienga, southeastern Gabon

“…Our results did not confirm the study of Lekana-Douki et al, which reports a rise in the prevalence of genotype N86 in Franceville after the use of AS-AQ [24] and a study conducted in Mozambique [38].…”

Plasmodium Falciparum Multidrug Resistance Gene-1 N86Y-Y184F-D1246Y Polymorphisms in Northern Nigeria: Implications for the Continued Use of Artemether-Lumefantrine in the Region

“…The pfmdr1 haplotypes used in this study were based on eight previously reported haplotypes associated with artemether lumefantrine-tolerance; pfmdr1 N86Y, Y184F and D1246Y single nucleotide polymorphisms in different P. falciparum populations from Africa [22,27].…”

Whole-Genome Sequencing to Evaluate the Resistance Landscape Following Antimalarial Treatment Failure With Fosmidomycin-Clindamycin

“…ACTs, introduced in Mozambique in 2004 [37], may have selected for parasites able to withstand drug treatment, such as FSM-CLN. Alleles of PfK13 (Kelch13, PF3D7_1343700) have been implicated in artemisinin resistance.…”