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从赤道几内亚比奥科岛分离出的恶性疟原虫K13螺旋桨蛋白和PfATPase6基因中与青蒿素耐药性相关的多态性有限。

Limited artemisinin resistance-associated polymorphisms in Plasmodium falciparum K13-propeller and PfATPase6 gene isolated from Bioko Island, Equatorial Guinea.

作者信息

Li Jian, Chen Jiangtao, Xie Dongde, Eyi Urbano Monsuy, Matesa Rocio Apicante, Ondo Obono Maximo Miko, Ehapo Carlos Sala, Yang Liye, Yang Huitian, Lin Min

机构信息

Institute of Basic Medical Sciences, College of Basic Medicine, Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, People's Republic of China.

Laboratory Medical Center, Huizhou Municipal Central Hospital, Huizhou 516001, People's Republic of China; The Chinese Medical Aid Team to the Republic of Equatorial Guinea, Guangzhou 510000, People's Republic of China.

出版信息

Int J Parasitol Drugs Drug Resist. 2016 Jan 12;6(1):54-59. doi: 10.1016/j.ijpddr.2015.11.002. eCollection 2016 Apr.

Abstract

OBJECTIVE

With emergence and geographically expanding of antimalarial resistance worldwide, molecular markers are essential tool for surveillance of resistant Plasmodium parasites. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain are shown to be associated with artemisinin (ART) resistance in vivo and in vitro. This study aims to investigate the ART resistance-associated polymorphisms of K13-propeller and PfATPase6 genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea (EG).

METHODS

A total of 172 samples were collected from falciparum malaria patients on Bioko Island between 2013 and 2014. The polymorphisms of K13-propeller and PfATPase6 genes were analyzed by Nest-PCR and sequencing.

RESULTS

Sequences of K13-propeller and PfATPase6 were obtained from 90.74% (98/108) and 91.45% (139/152) samples, respectively. The 2.04% (2/98) cases had non-synonymous K13-propeller A578S mutation but no found the mutations associated with ART resistance in Southeast Asia. For PfATPase6, the mutations were found at positions N569K and A630S with the mutation prevalence of 7.91% (11/139) and 1.44% (2/139), respectively. In addition, a sample with the mixed type at position I723V was discovered (0.72%, 1/139).

CONCLUSIONS

This study initially offers an insight of K13-propeller and PfATPase6 polymorphisms on Bioko Island, EG. It suggests no widespread ART resistance or tolerance in the region, and might be helpful for developing and updating guidance for the use of ART-based combination therapies (ACTs).

摘要

目的

随着全球范围内抗疟药物耐药性的出现和地理范围的扩大,分子标记物是监测耐药疟原虫的重要工具。最近,恶性疟原虫(Plasmodium falciparum)的PF3D7_1343700 Kelch螺旋桨(K13螺旋桨)结构域中的单核苷酸多态性(SNP)已被证明与体内外青蒿素(ART)耐药性相关。本研究旨在调查赤道几内亚(EG)比奥科岛恶性疟原虫分离株中K13螺旋桨和PfATPase6基因与青蒿素耐药性相关的多态性。

方法

2013年至2014年间,从比奥科岛的恶性疟疾病人中总共收集了172份样本。通过巢式PCR和测序分析K13螺旋桨和PfATPase6基因的多态性。

结果

分别从90.74%(98/108)和91.45%(139/152)的样本中获得了K13螺旋桨和PfATPase6的序列。2.04%(2/98)的病例具有非同义K13螺旋桨A578S突变,但未发现与东南亚青蒿素耐药性相关的突变。对于PfATPase6,在N569K和A630S位置发现了突变,突变发生率分别为7.91%(11/139)和1.44%(2/139)。此外,发现了1个在I723V位置为混合型的样本(0.72%,1/139)。

结论

本研究初步揭示了赤道几内亚比奥科岛K13螺旋桨和PfATPase6的多态性。这表明该地区不存在广泛的青蒿素耐药性或耐受性,可能有助于制定和更新基于青蒿素的联合疗法(ACTs)的使用指南。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ec5/4805774/21db8da0d906/fx1.jpg

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