Plasmodium falciparum Multidrug Resistance Gene-1 N86Y-Y184F-D1246Y Polymorphisms in Northern Nigeria: Implications for the continued use of artemether-lumefantrine in the region

Abstract

Background: The analysis of single nucleotide polymorphism (SNPs) in drug-resistance associated genes is a commonly used strategy for the surveillance of antimalarial 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.Methods: Plasmodium 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 analyzed using Pearson Chi-square and Fisher's exact (FE) tests.Results: The prevalence of the pfmdr1 86Y allele was highest in Kaduna (12.50%, 𝜒² = 10.50, P = 0.02), whilst the 184F allele was highest in Kano (73.10%, 𝜒² = 13.20, P = 0.00), and the pfmdr1 1246Y allele was highest in Yobe (5.26%, 𝜒² = 9.20, P = 0.03). The NFD haplotype had the highest prevalence of 69.81% in Kano (𝜒² = 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.Conclusion: The present study shows that P. falciparum strains with potential reduced susceptibility to the lumefantrine component of AL exist in Northern Nigeria and predominate in the North-West region.