尼日利亚恶性疟原虫分离株Pfatpase-6基因的分子谱分析

Deborah Adedire, Chiamaka Iwegbulam, Roland Funwei, Temitope Owoeye, Zainab Kashim-Bello, Adeola Orogade, Catherine Falade, Oyekanmi Nash
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摘要

抗疟疾药物耐药性是全球疟疾控制规划面临的最大公共卫生负担之一。当氯喹作为治疗疟疾的首选药物时,恶性疟原虫氯喹耐药转运体和多药耐药突变基因的出现对氯喹的治疗效果产生了破坏性影响。青蒿素已被证明是填补耐药机制留下的化疗方案空白的一种极好的治疗选择。恶性疟原虫的sarco/内质网Ca2+- atp酶同源物(PfATPase-6)被认为是青蒿素的靶点之一。因此,正在其他地方研究Pfatpase-6基因多态性作为青蒿素耐药性的标记。本研究评估了2017年至2018年在尼日利亚奥约州伊巴丹收集的113份恶性疟原虫分离物样本中Pfatpase-6基因中4种恶性疟原虫候选青蒿素耐药生物标志物L263E、E431K、A623E和S769N的当前流行情况。E431K突变发生率为17%。未检出A623E、L263E和S769N。这一结果表明,在尼日利亚,对青蒿素的耐药性要么尚未被选择,要么可能是其他基因突变导致的,如果有的话
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Molecular profile of Pfatpase-6 gene from Plasmodium falciparum isolates in Nigeria
Anti-malarial drug resistance is one of the biggest public health burdens confronting global malaria control programmes. The emergence of P. falciparum chloroquine resistance transporter and multi-drug resistance mutant genes had devastating effects on the therapeutic efficacy of chloroquine when it was the drug of choice for malaria treatment. The artemisinins have proven to be an excellent therapeutic alternative to fill the void in chemotherapeutic options left by resistance mechanisms. The sarco/endoplasmic reticulum Ca2+-ATPase ortholog of P. falciparum (PfATPase-6) has been suggested as one of the targets of the artemisinins. Consequently, Pfatpase-6 gene polymorphisms are being investigated as markers of artemisinin resistance elsewhere. The present study assessed the molecular profile of the current prevalence of four P. falciparum candidate artemisinin resistance biomarkers L263E, E431K, A623E, and S769N in the Pfatpase-6 gene in 113 samples of P. falciparum isolates collected from Ibadan, Oyo State, Nigeria between 2017 and 2018. The frequency of occurrence of E431K mutation was 17% from collected samples. No A623E, L263E and S769N were detected. The result suggests that resistance to artemisinin has either not yet been selected in Nigeria or other genes mutations might be responsible for such, if at all
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