Abstract
BackgroundThe analysis of single nucleotide polymorphism (SNPs) in drug-resistance associated genes is a commonly used strategy for the surveillance of anti-malarial drug resistance in populations of parasites. The present study was designed and performed to provide genetic epidemiological data of the prevalence of N86Y-Y184F-D1246Y SNPs in Plasmodium falciparum multidrug resistance 1 (pfmdr1) in the malaria hotspot of Northern Nigeria.MethodsPlasmodium falciparum-positive blood samples on Whatman-3MM filter papers were collected from 750 symptomatic patients from four states (Kano, Kaduna, Yobe and Adamawa) in Northern Nigeria, and genotyped via BigDye (v3.1) terminator cycle sequencing for the presence of three SNPs in pfmdr1. SNPs in pfmdr1 were used to construct NYD, NYY, NFY, NFD, YYY, YYD, YFD and YFY haplotypes, and all data were analysed using Pearson Chi square and Fisher’s exact (FE) tests.ResultsThe prevalence of the pfmdr1 86Y allele was highest in Kaduna (12.50%, 2 = 10.50, P = 0.02), whilst the 184F allele was highest in Kano (73.10%, 2 = 13.20, P = 0.00), and the pfmdr1 1246Y allele was highest in Yobe (5.26%, 2 = 9.20, P = 0.03). The NFD haplotype had the highest prevalence of 69.81% in Kano (2 = 36.10, P = 0.00), followed by NYD with a prevalence of 49.00% in Adamawa, then YFD with prevalence of 11.46% in Kaduna. The YYY haplotype was not observed in any of the studied states.ConclusionThe present study suggests that strains of P. falciparum with reduced sensitivity to the lumefantrine component of AL exist in Northern Nigeria and predominate in the North-West region.
Highlights
The analysis of single nucleotide polymorphism (SNPs) in drug-resistance associated genes is a commonly used strategy for the surveillance of anti-malarial drug resistance in populations of parasites
Prevalence of Single nucleotide polymorphisms (SNPs) in pfmdr1 codons 86, 186 and 1246 Of the 750 P. falciparum positive samples collected from the four states in Northern Nigeria, 500 were successfully genotyped for the pfmdr1 N86Y, Y184F and D1246Y alleles, possibly due to a very low parasite density in the remaining samples
The prevalence of the mutant pfmdr1 86Y allele was observed to be significantly (P = 0.02) different across the states, with highest prevalence of 12.50% obtained in Kaduna state, followed by Kano with 4.68% and 2.00% in Adamawa state (Fig. 2a)
Summary
The analysis of single nucleotide polymorphism (SNPs) in drug-resistance associated genes is a commonly used strategy for the surveillance of anti-malarial drug resistance in populations of parasites. The present study was designed and performed to provide genetic epidemiological data of the prevalence of N86Y-Y184F-D1246Y SNPs in Plasmodium falciparum multidrug resistance 1 (pfmdr1) in the malaria hotspot of Northern Nigeria. Anti-malarial drug resistance is a major impediment to malaria chemotherapy in sub-Saharan Africa [1] largely because Plasmodium falciparum rapidly develops. Single nucleotide polymorphisms (SNPs) in the P. falciparum multidrug resistance gene (pfmdr1) have been shown to modulate the susceptibility of the parasite to the long acting partner drug in Artemisinin-based combination therapy (ACT) [6], but are not associated with resistance to artemisinin. Some genetic studies involving pfmdr have suggested opposing selective pressures following separate use of the drugs, in which parasites harbouring N86, 184F, D1246 pfmdr genotypes predominate in African countries that recommend AL as first line antimalarial drug, whilst those carrying 86Y, Y184 and 1246Y pfmdr genotypes predominate in African countries that use AS-AQ as frontline anti-malarial therapy [7]
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