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澳大利亚新南威尔士州(2010 年至 2016 年)输入性恶性疟原虫疟疾的耐药性筛查和趋势分析。

Resistance screening and trend analysis of imported falciparum malaria in NSW, Australia (2010 to 2016).

机构信息

Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Westmead Clinical School, Faculty of Medicine and Health, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, New South Wales, Australia.

School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia.

出版信息

PLoS One. 2018 May 29;13(5):e0197369. doi: 10.1371/journal.pone.0197369. eCollection 2018.

Abstract

BACKGROUND

The World Health Organization currently recommends artemisinin (along with a partner drug) as the global frontline treatment for Plasmodium falciparum malaria. Artemisinin resistant P. falciparum are now found throughout the greater Mekong subregion of South East Asia. Several polymorphisms in the parasite's kelch gene have been demonstrated to confer artemisinin resistance. While genotypes within the greater Mekong subregion are thoroughly examined in the literature, P. falciparum populations within several areas that do not (yet) have endemic resistance are underrepresented.

RESULTS

This investigation characterised the Pfkelch13 propeller domains from 153 blood samples of 140 imported cases of P. falciparum malaria in New South Wales from 2010 to 2016. A low level of propeller domain diversity was observed, including the C580Y coding mutation most strongly associated with artemisinin resistance in South East Asia. The resistance genotype was found in a sample originating in Papua New Guinea, where this mutation, or artemisinin treatment failure, have not been previously reported. Sequencing a panel of geographically informative polymorphisms within the organellar genomes identified the C580Y parasite as having Oceanic origins. Patient data analysis revealed that New South Wales, Australia, P. falciparum malaria cases often originated from regions with limited drug resistance screening.

CONCLUSIONS

The C580Y finding from outside of the greater Mekong subregion supports the consensus to upscale molecular surveillance of artemisinin resistance outside of South East Asia. The genetic screening results identify a risk of importing resistant falciparum malaria to Australia, supporting an ongoing surveillance protocol to pre-empt treatment failure and contribute to global data gathering.

摘要

背景

世界卫生组织目前推荐青蒿素(与一种联合药物)作为治疗恶性疟原虫疟疾的全球一线治疗药物。目前在东南亚大湄公河次区域的大部分地区都发现了对青蒿素具有抗药性的恶性疟原虫。寄生虫kelch 基因中的几个多态性已被证明可导致对青蒿素的耐药性。虽然该地区的基因型在文献中得到了充分的研究,但在几个尚未出现地方性耐药的地区,恶性疟原虫种群的代表性不足。

结果

本研究对 2010 年至 2016 年新南威尔士州 140 例输入性恶性疟原虫疟疾 153 份血样中的 Pfkelch13 螺旋桨结构域进行了特征分析。观察到螺旋桨结构域的多样性水平较低,包括与东南亚青蒿素耐药性最密切相关的 C580Y 编码突变。在一个源自巴布亚新几内亚的样本中发现了耐药基因型,此前在该地区尚未报告过这种突变或青蒿素治疗失败。对细胞器基因组中一组具有地理信息的多态性进行测序,确定了 C580Y 寄生虫起源于海洋。对患者数据的分析表明,澳大利亚新南威尔士州的恶性疟原虫病例通常来自耐药性筛查有限的地区。

结论

在大湄公河次区域以外发现的 C580Y 结果支持了在东南亚以外地区加大对青蒿素耐药性进行分子监测的共识。遗传筛选结果表明,澳大利亚有输入耐药性恶性疟原虫的风险,支持持续的监测方案,以预防治疗失败,并为全球数据收集做出贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa04/5973583/3c9eea5055be/pone.0197369.g001.jpg

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