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沙特阿拉伯采用基于青蒿素的联合疗法 11 年后,恶性疟原虫 pfmdr1 基因的多态性分析。

Polymorphism analysis of pfmdr1 gene in Plasmodium falciparum isolates 11 years post-adoption of artemisinin-based combination therapy in Saudi Arabia.

机构信息

Medical Research Centre, Jazan University, Jazan, Kingdom of Saudi Arabia.

Vector-Borne Diseases Research Group, Jazan University, Jazan, Kingdom of Saudi Arabia.

出版信息

Sci Rep. 2022 Jan 11;12(1):517. doi: 10.1038/s41598-021-04450-x.

Abstract

A total of 227 Plasmodium falciparum isolates from Jazan region, southwestern Saudi Arabia were amplified for the P. falciparum multi-drug resistance 1 (pfmdr1) gene to detect point mutations 11 years after the introduction of artemisinin-based combination therapy (ACT) in Saudi Arabia. The pfmdr1 86Y mutation was found in 11.5% (26/227) of the isolates while the N86 wild allele was detected in 88.5%. Moreover, 184F point mutations dominated (86.3%) the instances of pfmdr1 polymorphism while no mutation was observed at codons 1034, 1042 and 1246. Three pfmdr1 haplotypes were identified, NFSND (74.9%), NYSND (13.7%) and YFSND (11.4%). Associations of the prevalence of 86Y mutation and YFSND haplotype with participants' nationality, residency and parasitaemia level were found to be significant (P < 0.05). The findings revealed significant decline in the prevalence of the pfmdr1 86Y mutation in P. falciparum isolates from Jazan region over a decade after the implementation of ACT treatment. Moreover, the high prevalence of the NFSND haplotype might be indicative of the potential emergence of CQ-sensitive but artemether-lumefantrine-resistant P. falciparum strains since the adoption of ACT. Therefore, continuous monitoring of the molecular markers of antimalarial drug resistance in Jazan region is highly recommended.

摘要

在沙特阿拉伯引入基于青蒿素的联合疗法(ACT) 11 年后,对来自沙特阿拉伯西南部吉赞地区的 227 株恶性疟原虫分离株进行了恶性疟原虫多药耐药 1(pfmdr1)基因扩增,以检测点突变。在 227 株分离株中发现 pfmdr1 86Y 突变 11.5%(26/227),而野生等位基因 N86 则检测到 88.5%。此外,184F 点突变主导(86.3%) pfmdr1 多态性,而在密码子 1034、1042 和 1246 未观察到突变。鉴定了三种 pfmdr1 单倍型,NFSND(74.9%)、NYSND(13.7%)和 YFSND(11.4%)。发现 86Y 突变和 YFSND 单倍型的流行率与参与者的国籍、居住和寄生虫血症水平之间存在显著关联(P<0.05)。研究结果表明,在实施 ACT 治疗 10 多年后,吉赞地区恶性疟原虫分离株中 pfmdr1 86Y 突变的流行率显著下降。此外,由于采用了 ACT,NFSND 单倍型的高流行率可能表明 CQ 敏感但青蒿琥酯-咯萘啶耐药的恶性疟原虫株的出现。因此,强烈建议在吉赞地区持续监测抗疟药物耐药的分子标志物。

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