Adamu Auwal, Jada Mahmoud Suleiman, Haruna Hauwa Mohammed Sani, Yakubu Bassa Obed, Ibrahim Mohammed Auwal, Balogun Emmanuel Oluwadare, Sakura Takaya, Inaoka Daniel Ken, Kita Kiyoshi, Hirayama Kenji, Culleton Richard, Shuaibu Mohammed Nasir
Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria.
Department of Biochemistry, Modibbo Adama University of Technology Yola, Yola, Nigeria.
Malar J. 2020 Nov 30;19(1):439. doi: 10.1186/s12936-020-03506-z.
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.
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.
The prevalence of the pfmdr1 86Y allele was highest in Kaduna (12.50%, = 10.50, P = 0.02), whilst the 184F allele was highest in Kano (73.10%, = 13.20, P = 0.00), and the pfmdr1 1246Y allele was highest in Yobe (5.26%, = 9.20, P = 0.03). The NFD haplotype had the highest prevalence of 69.81% in Kano ( = 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.
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.
分析耐药相关基因中的单核苷酸多态性(SNP)是监测寄生虫群体中抗疟药物耐药性的常用策略。本研究旨在提供尼日利亚北部疟疾热点地区恶性疟原虫多药耐药1(pfmdr1)基因中N86Y - Y184F - D1246Y单核苷酸多态性流行情况的遗传流行病学数据。
从尼日利亚北部四个州(卡诺州、卡杜纳州、约贝州和阿达马瓦州)的750名有症状患者中收集了Whatman - 3MM滤纸上的恶性疟原虫阳性血样,并通过BigDye(v3.1)终止子循环测序对pfmdr1基因中的三个单核苷酸多态性进行基因分型。利用pfmdr1基因中的单核苷酸多态性构建NYD、NYY、NFY、NFD、YYY、YYD、YFD和YFY单倍型,并使用Pearson卡方检验和Fisher精确(FE)检验对所有数据进行分析。
pfmdr1基因86Y等位基因在卡杜纳州的流行率最高(12.50%,χ² = 10.50,P = 0.02),而184F等位基因在卡诺州最高(73.10%,χ² = 13.20,P = 0.00),pfmdr1基因1246Y等位基因在约贝州最高(5.26%,χ² = 9.20,P = 0.03)。NFD单倍型在卡诺州的流行率最高,为69.81%(χ² = 36.10,P = 0.00),其次是NYD,在阿达马瓦州的流行率为49.00%,然后是YFD,在卡杜纳州的流行率为11.46%。在所研究的任何一个州均未观察到YYY单倍型。
本研究表明,尼日利亚北部存在对青蒿琥酯 - 呋喃丹(AL)中氯氟菲醇成分敏感性降低的恶性疟原虫菌株,且在西北地区占主导地位。