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来自尼日利亚西南部疟原虫基因分子分析的青蒿素耐药现状。

Status of Artemisinin Resistance in Malaria Parasite from Molecular Analyses of the Gene in Southwestern Nigeria.

机构信息

Parasitology and Mycology Laboratory, Université Cheikh Anta Diop, Dakar, Senegal.

Division of Vector Borne Diseases, ICMR-National Institute of Research in Tribal Health, Jabalpur, India.

出版信息

Biomed Res Int. 2018 Oct 3;2018:2305062. doi: 10.1155/2018/2305062. eCollection 2018.

DOI:10.1155/2018/2305062
PMID:30402465
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6192135/
Abstract

Evolution and spread of malaria parasite capable of evading antimalarials are the prime concern to malaria control. The currently effective drug, artemisinin (ART), is under threat due to detection of ART-resistant parasites in the Southeast Asian countries. It has been shown that amino acid (AA) mutations at the () gene provide resistance to ART. Nigeria, a part of the Sub-Saharan Africa, is highly endemic to malaria, contributing quite significantly to malaria, and resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) combination drugs has already been reported. Since artemisinin combined therapy (ACT) is the first-line drug for treatment of uncomplicated malaria in Nigeria and five amino acid mutations have been validated in the gene alongside with candidate mutations for ART resistance, we performed molecular surveillance for mutations (following PCR and DNA sequence analyses) in this gene from two southwestern states of Nigeria. Statistical analyses of DNA sequences were also performed following different evolutionary models. None of the different validated and candidate AA mutations of gene conferring resistance to ART could be detected in sampled in the two southwestern states of Nigeria. In addition, DNA sequencing and sequence analyses indicated neither evolutionary selection pressure on the gene nor association of mutations in gene with mutations of other three genes conferring resistance to CQ and SP. Therefore, based on the monomorphism at the gene and nonassociation of mutations of this gene with mutations in three other drug-resistant genes in malaria parasite , it can be proposed that malaria public health is not under immediate threat in southwestern Nigeria concerning ART resistance.

摘要

疟原虫逃避抗疟药物的进化和传播是疟疾控制的首要关注点。目前有效的药物青蒿素(ART)由于在东南亚国家发现了对 ART 有抗药性的寄生虫而受到威胁。已经表明,()基因的氨基酸(AA)突变提供了对 ART 的抗性。尼日利亚是撒哈拉以南非洲的一部分,疟疾高度流行,对疟疾的贡献相当大,而且已经报道了对氯喹(CQ)和磺胺多辛-乙胺嘧啶(SP)联合药物的耐药性。由于青蒿素联合疗法(ACT)是尼日利亚治疗无并发症疟疾的一线药物,并且在()基因中已经验证了五种与 ART 耐药性相关的 AA 突变以及候选突变,我们对尼日利亚西南部的两个州进行了该基因的分子监测(采用 PCR 和 DNA 序列分析)。还根据不同的进化模型对 DNA 序列进行了统计分析。在尼日利亚西南部的两个州采集的样本中,均未检测到()基因中导致 ART 耐药的不同验证和候选 AA 突变。此外,DNA 测序和序列分析表明,()基因既没有进化选择压力,也没有该基因的突变与 CQ 和 SP 耐药的其他三个基因的突变相关联。因此,根据()基因的单态性以及该基因的突变与疟原虫中其他三个耐药基因的突变无关,我们可以提出,在尼日利亚西南部,ART 耐药性不会立即对疟疾公共卫生构成威胁。

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