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在一次长期的家庭疫情暴发期间,从单耐药向广泛耐药前演变。

evolution from monoresistance to pre-extensive drug resistance during a prolonged household outbreak.

作者信息

Greif G, Coithino C, Bentancor M N, Robello C

机构信息

Laboratorio de Interacciones Hospedero-Patógeno/Unidad de Biología Molecular, Institut Pasteur de Montevideo, Montevideo, Uruguay.

Comisión Honoraria de Lucha Anti-Tuberculosis y Enfermedades Prevalentes. Departamento de Laboratorio, Montevideo, Uruguay.

出版信息

J Clin Tuberc Other Mycobact Dis. 2024 Oct 14;37:100482. doi: 10.1016/j.jctube.2024.100482. eCollection 2024 Dec.

DOI:10.1016/j.jctube.2024.100482
PMID:39497756
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11532306/
Abstract

Whole genome sequencing (WGS) is sensitive tool for the analysis of tuberculosis transmission and drug-resistance. We used WGS to analyze the evolution from isoniazid monoresistance to MDR/preXDR during a prolonged household outbreak. The outbreak started with a isoniazid resistant strain (katG S315T mutation) and evolve in two cases to pre-XDR phenotype (with mutations in katG, rpoB, embB, pncA and gyrA genes). Based on WGS data and epidemiological interview we proposed a possible chain of transmission an evolution of the strains. Similar intra-patient and inter-patient acquisition of variability was observed, making difficult to distinguish reinfection or reactivation. Analysis of WGS data together with epidemiological clinical history are discussed in order to distinguish between prolonged infections or transition from latency to reactivation. Classical interview and clinical history taking should be consider to fully understanding WGS data. With a still low incidence of TB cases, Uruguay could use universal WGS of all isolates to reduce time of diagnosis, detect outbreaks and perform public actions to reduce TB incidence.

摘要

全基因组测序(WGS)是分析结核病传播和耐药性的灵敏工具。我们使用WGS分析了在一次长期家庭疫情期间从异烟肼单耐药到耐多药/广泛耐药前的演变情况。此次疫情始于一株异烟肼耐药菌株(katG S315T突变),并在两例病例中演变为广泛耐药前表型(katG、rpoB、embB、pncA和gyrA基因发生突变)。基于WGS数据和流行病学访谈,我们提出了菌株可能的传播链和演变情况。观察到患者内和患者间类似的变异性获得情况,难以区分再感染或再激活。讨论了结合WGS数据与流行病学临床病史分析,以区分长期感染或从潜伏到再激活的转变。应考虑采用经典访谈和临床病史采集来全面理解WGS数据。鉴于乌拉圭结核病病例发病率仍然较低,该国可对所有分离株进行普遍WGS,以缩短诊断时间、检测疫情并采取公共行动降低结核病发病率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a4/11532306/75b66211f14c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a4/11532306/75b66211f14c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a4/11532306/75b66211f14c/gr1.jpg

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本文引用的文献

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Clin Microbiol Infect. 2019 Nov;25(11):1377-1382. doi: 10.1016/j.cmi.2019.03.022. Epub 2019 Apr 11.
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Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden.瑞典南部使用全基因组测序对结核分枝杆菌分离株的传播动力学研究。
Sci Rep. 2019 Mar 20;9(1):4931. doi: 10.1038/s41598-019-39971-z.
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Acquires Limited Genetic Diversity in Prolonged Infections, Reactivations and Transmissions Involving Multiple Hosts.
在涉及多个宿主的长期感染、再激活和传播过程中获得有限的遗传多样性。
Front Microbiol. 2018 Jan 19;8:2661. doi: 10.3389/fmicb.2017.02661. eCollection 2017.
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Mycobacterium tuberculosis and whole-genome sequencing: how close are we to unleashing its full potential?结核分枝杆菌与全基因组测序:我们离充分发挥其潜力还有多远?
Clin Microbiol Infect. 2018 Jun;24(6):604-609. doi: 10.1016/j.cmi.2017.10.030. Epub 2017 Nov 3.
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XDR-TB transmission in London: Case management and contact tracing investigation assisted by early whole genome sequencing.XDR-TB 在伦敦的传播:通过早期全基因组测序辅助的病例管理和接触者追踪调查。
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TGS-TB: Total Genotyping Solution for Mycobacterium tuberculosis Using Short-Read Whole-Genome Sequencing.TGS-TB:利用短读长全基因组测序技术的结核分枝杆菌全基因分型解决方案
PLoS One. 2015 Nov 13;10(11):e0142951. doi: 10.1371/journal.pone.0142951. eCollection 2015.
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Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study.全基因组测序用于预测结核分枝杆菌药物敏感性和耐药性:一项回顾性队列研究。
Lancet Infect Dis. 2015 Oct;15(10):1193-1202. doi: 10.1016/S1473-3099(15)00062-6. Epub 2015 Jun 23.
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