Molecular Epidemiology of Plasmodium falciparum kelch13 Mutations in Senegal Determined by Using Targeted Amplicon Deep Sequencing
Molecular Epidemiology of Plasmodium falciparum kelch13 Mutations in Senegal Determined by Using Targeted Amplicon Deep Sequencing
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DOI：
10.1128/aac.02116-16
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发表时间：
2017-03-01
影响因子：
4.9
通讯作者：
Ndiaye, Daouda
中科院分区：
文献类型：
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作者：
Talundzic, Eldin;Ndiaye, Yaye D.;Ndiaye, Daouda
东南亚出现的恶性疟原虫对青蒿素的耐药性威胁着全世界的疟疾控制和消除活动。恶性疟原虫13号染色体kelch基因的多重多态性（Pfk13）与青蒿素耐药性有关。监测在日益增加的药物压力下可能出现的人群中的潜在耐药位点是一项重要的公共卫生活动。在此背景下，来自塞内加尔的一项观察性监测研究中的恶性疟原虫感染使用靶向扩增子深度测序（TADS）对Pfk13多态性进行基因分型。这些结果与之前报道的来自世界各地的Pfk13多态性进行了比较。本研究共鉴定了22个Pfk13螺旋桨结构域多态性，其中12个以前未报道过。有趣的是，在本研究中发现的10个多态性中，在这些密码子位置上都有不同的氨基酸替代。大多数多态性以低频率存在，并且局限于单个分离株，这表明它们可能是自然进化的寄生虫种群的一部分的短暂多态性。这项研究的结果强调需要确定人群中存在的潜在耐药位点，这些位点可能在不断增加的药物压力下出现。
The emergence of Plasmodium falciparum resistance to artemisinin in Southeast Asia threatens malaria control and elimination activities worldwide. Multiple polymorphisms in the P. falciparum kelch gene found in chromosome 13 (Pfk13) have been associated with artemisinin resistance. Surveillance of potential drug resistance loci within a population that may emerge under increasing drug pressure is an important public health activity. In this context, P. falciparum infections from an observational surveillance study in Senegal were genotyped using targeted amplicon deep sequencing (TADS) for Pfk13 polymorphisms. The results were compared to previously reported Pfk13 polymorphisms from around the world. A total of 22 Pfk13 propeller domain polymorphisms were identified in this study, of which 12 have previously not been reported. Interestingly, of the 10 polymorphisms identified in the present study that were also previously reported, all had a different amino acid substitution at these codon positions. Most of the polymorphisms were present at low frequencies and were confined to single isolates, suggesting they are likely transient polymorphisms that are part of naturally evolving parasite populations. The results of this study underscore the need to identify potential drug resistance loci existing within a population, which may emerge under increasing drug pressure.