Polymorphisms of the artemisinin resistant marker (K13) in Plasmodium falciparum parasite populations of Grande Comore Island 10 years after artemisinin combination therapy.
Polymorphisms of the artemisinin resistant marker (K13) in Plasmodium falciparum parasite populations of Grande Comore Island 10 years after artemisinin combination therapy.
复制标题
青蒿素联合治疗10年后大科摩罗岛恶性疟原虫群体中青蒿素抗性标记物（K13）的多态性
DOI：
10.1186/s13071-015-1253-z
复制
发表时间：
2015-12-15
影响因子：
3.2
通讯作者：
Song J
中科院分区：
文献类型：
--
作者：
Huang B;Deng C;Yang T;Xue L;Wang Q;Huang S;Su XZ;Liu Y;Zheng S;Guan Y;Xu Q;Zhou J;Yuan J;Bacar A;Abdallah KS;Attoumane R;Mliva AM;Zhong Y;Lu F;Song J
恶性疟原虫疟疾是科摩罗的一个重大公共卫生问题，青蒿素联合疗法仍然是治疗急性无并发症恶性疟原虫的首选。与K13-propeller基因突变相关的青蒿素耐药恶性疟原虫在东南亚的出现和传播，对ACT疗效构成潜在威胁。恶性疟原虫K13-螺旋桨基因突变的检测可能提供有关疟原虫对青蒿素敏感性变化的第一手信息。本研究的目的是确定从科摩罗联盟的大科摩罗岛收集的恶性疟原虫分离株中突变K13-螺旋桨基因的流行率，该分离株自2004年以来一直使用ACT。在2006年3月和2007年10月（n = 118）以及2013年3月和2014年12月（n = 89）期间，从该岛共收集了207株恶性疟原虫临床分离株。采用巢式PCR和DNA测序分析所有分离株的K13螺旋桨基因单核苷酸多态性（SNP）和单倍型。2006-2007年仅有3个样本在K13-螺旋桨基因中携带SNP，一个具有同义（G538 G）取代，另一个具有两个非同义（S477 Y和D584 E）取代，导致两个突变单倍型（2.2%，2/95）。在2013 - 2014年的分离株中发现了3个同义突变（R471 R，Y500 Y和G538 G）（5.9%，5/85）和7个非同义替换（21.2%，18/85），其中9个突变单倍型（18.8%，16/85）。然而，没有多态性与青蒿素耐药性在东南亚检测到任何寄生虫。这项研究表明，在8年（2006-2014年）的时间里，岛上恶性疟原虫种群的K13螺旋桨基因多样性增加。然而，在亚洲，没有一个已知与青蒿素耐药性相关的多态性在所检查的寄生虫种群中被检测到。我们的数据表明，大科摩罗的恶性疟原虫种群仍然对青蒿素有效敏感。我们的研究结果为恶性疟原虫种群提供了关于与青蒿素耐药性相关的基因突变的见解，并将有助于科摩罗制定和更新抗疟指南。
Plasmodium falciparum malaria is a significant public health problem in Comoros, and artemisinin combination therapy (ACT) remains the first choice for treating acute uncomplicated P. falciparum. The emergence and spread of artemisinin-resistant P. falciparum in Southeast Asia, associated with mutations in K13-propeller gene, poses a potential threat to ACT efficacy. Detection of mutations in the P. falciparum K13-propeller gene may provide the first-hand information on changes in parasite susceptibility to artemisinin. The objective of this study is to determinate the prevalence of mutant K13-propeller gene among the P. falciparum isolates collected from Grande Comore Island, Union of Comoros, where ACT has been in use since 2004. A total of 207 P. falciparum clinical isolates were collected from the island during March 2006 and October 2007 (n = 118) and March 2013 and December 2014 (n = 89). All isolates were analysed for single nucleotide polymorphisms (SNPs) and haplotypes in the K13-propeller gene using nested PCR and DNA sequencing. Only three 2006–2007 samples carried SNPs in the K13-propeller gene, one having a synonymous (G538G) and the other having two non-synonymous (S477Y and D584E) substitutions leading to two mutated haplotypes (2.2 %, 2/95). Three synonymous mutations (R471R, Y500Y, and G538G) (5.9 %, 5/85) and 7 non-synonymous substitutions (21.2 %, 18/85) with nine mutated haplotypes (18.8 %, 16/85) were found in isolates from 2013 to 2014. However, none of the polymorphisms associated with artemisinin-resistance in Southeast Asia was detected from any of the parasites examined. This study showed increased K13-propeller gene diversity among P. falciparum populations on the Island over the course of 8 years (2006–2014). Nevertheless, none of the polymorphisms known to be associated with artemisinin resistance in Asia was detected in the parasite populations examined. Our data suggest that P. falciparum populations in Grande Comore are still effectively susceptible to artemisinin. Our results provide insights into P. falciparum populations regarding mutations in the gene associated with artemisinin resistance and will be useful for developing and updating anti-malarial guidance in Comoros.