青蒿素耐药性与监测:叙述性综述

A. A. Iwuafor, G. I. Ogban, U.E. Emanghe, P.C. Erengwa, A.B. Offiong, G. E. Nsor, P. A. Owai
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摘要

青蒿素耐药性是撒哈拉以南非洲国家疟疾治疗失败的主要原因之一,在这些国家,以青蒿素为基础的联合疗法是治疗无并发症疟疾的一线疗法。发现单核苷酸多态性(snp)的发生与抗疟药耐药性有关。对于青蒿素,snp发生在13号染色体上的Kelch 13-propeller基因位点。青蒿素耐药性监测战略包括持续监测Kelch 13-propeller生物标志物,以检测可能预示该地区出现耐药性的突变的出现。在这篇叙述性综述论文中,我们审查了现有文献,以弥合知识差距,并强调撒哈拉以南非洲常规监测青蒿素耐药性的重要性。我们在PubMed数据库和Google Scholar中检索了同行评议的关于青蒿素耐药性的文章、报告和摘要,使用以下关键词;“青蒿素耐药性”、“抗疟药物耐药性”、“基于青蒿素的联合疗法”、“Kelch 13-螺旋桨”、“K13-螺旋桨基因”和“K13分子标记”。本文综述了青蒿素衍生物、以青蒿素为基础的联合治疗、青蒿素的分子作用、青蒿素耐药的定义、青蒿素耐药的遗传基础和Kelch 13的发现,以及开展青蒿素耐药监测的重要性。分子监测可以为卫生保健决策者提供疟疾治疗即将面临的威胁的预测。当药物联合治疗时更是如此,例如,分子监测可以提示一种药物正在失效,尽管事实上联合治疗仍然明显有效。
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Artemisinin drug resistance and monitoring: a narrative review
Artemisinin drug resistance is one of the major reasons for malaria treatment failures in the sub-Saharan African countries where artemisinin-based  combination therapy (ACT) is the first-line treatment for uncomplicated malaria. The occurrence of single nucleotide polymorphisms (SNPs) is found to  correlate with antimalarial drug resistance. With artemisinin, the SNPs occurs at the Kelch 13-propeller gene locus on chromosome 13. The artemisinin  drug resistance surveillance strategy involves continuous monitoring of Kelch 13-propeller biomarker to detect emergence of mutations which could  herald drug resistance in the region. In this narrative review paper, we examined existing literature to bridge the knowledge gap and accentuate the  importance of routine surveillance for artemisinin resistance in sub-Saharan Africa. We conducted our search on PubMed database and Google Scholar to  identify peer-reviewed articles, reports, and abstracts on artemisinin drug resistance using the following keywords; ‘artemisinin drug resistance’,  ‘antimalarial drug resistance’, ‘artemisinin-based combination therapy’, ‘Kelch 13-propeller’, ‘K13- propeller gene’, and ‘K13 molecular marker’. The review  provided pertinent information on artemisinin derivatives, artemisinin-based combination therapy, molecular action of artemisinin, definition of  artemisinin resistance, genetic basis of artemisinin drug resistance and discovery of Kelch 13, and the importance of artemisinin resistance surveillance.  Molecular surveillance can provide healthcare policy makers a forecast of impending threats to malaria treatment. This is more so when drugs are in  combination therapy, for instance, molecular surveillance can give a hint that one drug is failing despite the fact that in combination, it is still apparently  clinically effective. 
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