Plasmodium falciparum multidrug resistance gene-1 polymorphisms in Northern Nigeria: implications for the continued use
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Malaria Journal Open Access
RESEARCH
Plasmodium falciparum multidrug resistance gene‑1 polymorphisms in Northern Nigeria: implications for the continued use of artemether‑lumefantrine in the region Auwal Adamu1, Mahmoud Suleiman Jada2, Hauwa Mohammed Sani Haruna3, Bassa Obed Yakubu1, Mohammed Auwal Ibrahim1, Emmanuel Oluwadare Balogun1, Takaya Sakura4, Daniel Ken Inaoka4, Kiyoshi Kita4, Kenji Hirayama5, Richard Culleton6 and Mohammed Nasir Shuaibu1*
Abstract Background: 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. 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 analysed using Pearson Chi square and Fisher’s exact (FE) tests. Results: The 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. Conclusion: The 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. Keywords: Anti-malarial drug resistance, P. falciparum, Single nucleotide polymorphisms, pfmdr1, Haplotypes Background Anti-malarial drug resistance is a major impediment to malaria chemotherapy in sub-Saharan Africa [1] largely because Plasmodium falciparum rapidly develops
*Correspondence: [email protected] 1 Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria Full list of author information is available at the end of the article
resistance to drugs [2]. Resistance to anti-malarial drugs occurs through drug-selection of spontaneous mutations in P. falciparum that confer tolerance to the drug [3]. The selection and spread of drug resistant P. falciparum is facilitated by the rapid genome replication rate and by a relatively high mutation rate per generation of the parasite [4, 5]. The speed of selection of mutants within parasite populations depends upon the pharmacokinetics of the drug itself and its degree of usage within a given host
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