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印度默瓦特地区恶性疟原虫野外分离株对抗疟药物的体外敏感性及Pfg377基因多态性

In vitro sensitivity to antimalarial drugs and polymorphisms in Pfg377 gene in Plasmodium falciparum field isolates from Mewat, India.

作者信息

Singh Vineeta, Kumar Amit, Gupta Purva

机构信息

a National Institute of Malaria Research [ICMR] , New Delhi , India.

出版信息

Pathog Glob Health. 2017 Jul;111(5):225-233. doi: 10.1080/20477724.2017.1337300. Epub 2017 Jun 12.

DOI:10.1080/20477724.2017.1337300
PMID:28605993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5560199/
Abstract

The malaria infection is the interplay of several complex factors, among which drug resistance and gametocyte biology are the crucial ones. Measurements of the drug sensitivity assays and prevalence of gametocyte genes play a major role in malaria eradication programmes. The purpose of this study was to assess the current drug sensitivity profile in the field isolates and type the Pfg377 gene. In vitro drug sensitivity assay was used to assess the susceptibility of Plasmodium falciparum field isolates collected from Mewat (Haryana), located in Northern region of India to four anti-malarial drugs. The inhibitory concentrations (IC) for the four drugs viz Chloroquine (CQ), Artesunate (AS), Sulphadoxine (SD) and Pyrimethamine (PYR) were in the range of 10.11-113.2, 2.26-4.08, 13.31-43.91 and 0.76-4.91 nM respectively in the evaluated 25 field isolates. The Pfg377 allele typing in the 26 field isolates revealed different types of haplotypes (A, B, C and D) varying by the size and number of repeats and deletions. The Pfg377 allelic types in the cryopreserved and adapted isolates of P. falciparum were compared to determine the parasite lines in them. The allele types or presence of different clones in the same sample could not be correlated significantly with resistance to any of the four drugs tested in the study. Our study revealed different drug sensitivity profiles of field isolates from Mewat region and allele typing of Pfg377 gene revealed different haplotypes of field isolates were circulating in parasite population.

摘要

疟疾感染是多种复杂因素相互作用的结果,其中耐药性和配子体生物学是关键因素。药物敏感性测定和配子体基因流行率的测量在疟疾根除计划中起着重要作用。本研究的目的是评估现场分离株的当前药物敏感性概况并对Pfg377基因进行分型。采用体外药物敏感性试验评估从印度北部哈里亚纳邦梅瓦特采集的恶性疟原虫现场分离株对四种抗疟药物的敏感性。在所评估的25株现场分离株中,四种药物即氯喹(CQ)、青蒿琥酯(AS)、磺胺多辛(SD)和乙胺嘧啶(PYR)的抑制浓度(IC)分别在10.11 - 113.2、2.26 - 4.08、13.31 - 43.91和0.76 - 4.91 nM范围内。对26株现场分离株进行的Pfg377等位基因分型显示出不同类型的单倍型(A、B、C和D),其重复和缺失的大小和数量各不相同。比较恶性疟原虫冷冻保存和适应后的分离株中的Pfg377等位基因类型,以确定其中的寄生虫株系。同一样本中不同克隆的等位基因类型或存在情况与研究中测试的四种药物中的任何一种的耐药性均无显著相关性。我们的研究揭示了梅瓦特地区现场分离株不同的药物敏感性概况,Pfg377基因的等位基因分型显示不同单倍型的现场分离株在寄生虫种群中传播。

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Emergence of sulfadoxine-pyrimethamine resistance in Indian isolates of Plasmodium falciparum in the last two decades.过去二十年中,印度恶性疟原虫分离株对周效磺胺-乙胺嘧啶产生耐药性的情况。
Infect Genet Evol. 2015 Dec;36:190-198. doi: 10.1016/j.meegid.2015.08.027. Epub 2015 Aug 28.
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