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研究揭示结核患者咳嗽气溶胶培养物阳性的决定因素
2020-06-30 21:25

南非开普敦大学Keertan Dheda课题组的最新工作,发现了耐药性和药敏性肺结核患者咳嗽气溶胶培养物阳性的细菌和宿主决定因素。相关论文于2020年6月29日在线发表在《自然—医学》上。

研究人员表示,耐药结核病(TB)的迅速流行威胁着全球健康。尽管机理尚不清楚,但人们普遍认为耐药菌株的感染性不如药物敏感菌株。
 
因此,研究人员假设与耐药结核病患者相比,耐药结核病患者中可呼吸的、由咳嗽气溶胶产生的可培养结核分枝杆菌比例更低,并且包括分枝杆菌基因组变异在内的多种因素将预测可培养咳嗽气溶胶的产生。研究人员检测了452例结核病患者(227例耐药)气溶胶(≤10μm)中的菌落形成单位,比较了临床特征,并对痰中的结核分枝杆菌进行了分枝杆菌全基因组测序、休眠表型和药敏分析。
 
在考虑治疗时间后,研究人员发现几乎一半的耐药结核病患者咳嗽气溶胶培养物阳性。出人意料的是,分枝杆菌的基因组变异、谱系和休眠状态均未预测咳嗽气溶胶培养物阳性。然而,分枝杆菌痰中的细菌负荷和临床特征(包括较低的症状评分和更强的咳嗽)具有很强的预测性,从而支持了有针对性的传播干预措施。有效的治疗在很大程度上消除了咳嗽气溶胶培养物的阳性率,但是,这并不总是那么迅速。
 
这些数据质疑了当前的范例,为公共卫生策略提供了信息,并表明需要将与结核病传播相关的研究工作重新转向宿主与病原体之间的相互作用。
 
附:英文原文

Title: Bacterial and host determinants of cough aerosol culture positivity in patients with drug-resistant versus drug-susceptible tuberculosis

Author: Grant Theron, Jason Limberis, Rouxjeane Venter, Liezel Smith, Elize Pietersen, Aliasgar Esmail, Greg Calligaro, Julian te Riele, Marianna de Kock, Paul van Helden, Tawanda Gumbo, Taane G. Clark, Kevin Fennelly, Robin Warren, Keertan Dheda

Issue&Volume: 2020-06-29

Abstract: A burgeoning epidemic of drug-resistant tuberculosis (TB) threatens to derail global control efforts. Although the mechanisms remain poorly clarified, drug-resistant strains are widely believed to be less infectious than drug-susceptible strains. Consequently, we hypothesized that lower proportions of patients with drug-resistant TB would have culturable Mycobacterium tuberculosis from respirable, cough-generated aerosols compared to patients with drug-susceptible TB, and that multiple factors, including mycobacterial genomic variation, would predict culturable cough aerosol production. We enumerated the colony forming units in aerosols (≤10μm) from 452 patients with TB (227 with drug resistance), compared clinical characteristics, and performed mycobacterial whole-genome sequencing, dormancy phenotyping and drug-susceptibility analyses on M. tuberculosis from sputum. After considering treatment duration, we found that almost half of the patients with drug-resistant TB were cough aerosol culture-positive. Surprisingly, neither mycobacterial genomic variants, lineage, nor dormancy status predicted cough aerosol culture positivity. However, mycobacterial sputum bacillary load and clinical characteristics, including a lower symptom score and stronger cough, were strongly predictive, thereby supporting targeted transmission-limiting interventions. Effective treatment largely abrogated cough aerosol culture positivity; however, this was not always rapid. These data question current paradigms, inform public health strategies and suggest the need to redirect TB transmission-associated research efforts toward host–pathogen interactions.

DOI: 10.1038/s41591-020-0940-2

Source: https://www.nature.com/articles/s41591-020-0940-2

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章:《自然—医学》:Online/在线发表

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