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间日疟原虫氯喹抗性分离株中Pvmdr1突变的遗传模式的全球评估

Global assessment of genetic paradigms of Pvmdr1 mutations in chloroquine-resistant Plasmodium vivax isolates.

作者信息

Spotin Adel, Mahami-Oskouei Mahmoud, Ahmadpour Ehsan, Parsaei Mahdi, Rostami Ali, Emami Shima, Gholipour Saba, Farmani Mostafa

机构信息

Department of Parasitology and Mycology, Faculty of Medicine Tabriz University of Medical Sciences, Tabriz, Iran.

Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Trans R Soc Trop Med Hyg. 2020 May 7;114(5):339-345. doi: 10.1093/trstmh/traa002.

DOI:10.1093/trstmh/traa002
PMID:32100835
Abstract

BACKGROUND

Chloroquine (CQ) is generally prescribed as the front-line antimalarial drug of choice to treat Plasmodium vivax infections; however, some clinical CQ-resistant P. vivax isolates have been indigenously reported around the world during the last decade.

METHODS

In this study, P. vivax isolates (n=52) were obtained from autochthonous samples in southeast Iran during 2015-2017. The genomic DNA of samples was extracted, amplified (nested PCR) and sequenced by targeting the multidrug-resistance 1 gene. To verify the global genetic diversity of CQ-resistant P. vivax strains, the sequences of Pvmdr1 originating from Asia and the Americas were retrieved.

RESULTS

A total of 46 haplotypes were grouped into three distinct geographical haplogroups. The haplotype diversity and occurrence rates of Pvmdr1 976F/1076L mutations indicate that the efficacy of CQ is being compromised in Mexico, China, Nicaragua, Thailand, Brazil (2016), Ethiopia, Mauritania (2012) and southwest India in the near future. The cladistic phylogenetic tree showed that Pvmdr1 sequences isolated from the southeast Asian clade has a partial sister relationship with the American clade.

CONCLUSIONS

The current findings will serve as a basis to develop appropriate malaria control strategies and public health policies in symptomatic imported malaria cases or plausible CQ-resistant P. vivax strains.

摘要

背景

氯喹(CQ)通常被指定为治疗间日疟原虫感染的一线抗疟首选药物;然而,在过去十年中,世界各地均有本土报告出现一些对氯喹耐药的间日疟原虫分离株。

方法

在本研究中,2015年至2017年期间从伊朗东南部的本地样本中获取了间日疟原虫分离株(n = 52)。提取样本的基因组DNA,通过靶向多药耐药1基因进行扩增(巢式PCR)和测序。为了验证对氯喹耐药的间日疟原虫菌株的全球遗传多样性,检索了来自亚洲和美洲的Pvmdr1序列。

结果

总共46个单倍型被分为三个不同的地理单倍群。Pvmdr1 976F/1076L突变的单倍型多样性和发生率表明,在不久的将来,氯喹在墨西哥、中国、尼加拉瓜、泰国、巴西(2016年)、埃塞俄比亚、毛里塔尼亚(2012年)和印度西南部的疗效正在受到影响。分支系统发育树显示,从东南亚分支分离的Pvmdr1序列与美洲分支有部分姐妹关系。

结论

目前的研究结果将为制定针对有症状的输入性疟疾病例或可能对氯喹耐药的间日疟原虫菌株的适当疟疾控制策略和公共卫生政策提供依据。

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