期刊
THORAX
卷 75, 期 7, 页码 584-591出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/thoraxjnl-2019-213281
关键词
tuberculosis; imaging; CT MRI etc; clinical epidemiology
资金
- Wellcome Trust [201470/Z/16/Z, WT098600, HICF--T5-342]
- EU FP7--PEOPLE-2013--IRSES --Marie Curie Action DEANN International Research Staff Exchange Scheme [19061]
- BBSRC GCRF scheme
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- Department of Health [WT098600, HICF--T5-342]
- Wellcome Trust [201470/Z/16/Z] Funding Source: Wellcome Trust
Background Understanding how pathogen genetic factors contribute to pathology in TB could enable tailored treatments to the most pathogenic and infectious strains. New strategies are needed to control drug-resistant TB, which requires longer and costlier treatment. We hypothesised that the severity of radiological pathology on the chest radiograph in TB disease was associated with variants arising independently, multiple times (homoplasies) in theMycobacterium tuberculosisgenome. Methods We performed whole genome sequencing (Illumina HiSeq2000 platform) onM. tuberculosisisolates from 103 patients with drug-resistant TB in Lima between 2010 and 2013. Variables including age, sex, HIV status, previous TB disease and the percentage of lung involvement on the pretreatment chest radiograph were collected from health posts of the national TB programme. Genomic variants were identified using standard pipelines. Results Two mutations were significantly associated with more widespread radiological pathology in a multivariable regression model controlling for confounding variables (Rv2828c.141, RR 1.3, 95% CI 1.21 to 1.39, p<0.01; rpoC.1040 95% CI 1.77 to 2.16, RR 1.9, p<0.01). The rpoB.450 mutation was associated with less extensive radiological pathology (RR 0.81, 95% CI 0.69 to 0.94, p=0.03), suggestive of a bacterial fitness cost for this mutation in vivo. Patients with a previous episode of TB disease and those between 10 and 30 years of age also had significantly increased radiological pathology. Conclusions This study is the first to compare theM. tuberculosisgenome to radiological pathology on the chest radiograph. We identified two variants significantly positively associated with more widespread radiological pathology and one with reduced pathology. Prospective studies are warranted to determine whether mutations associated with increased pathology also predict the spread of drug-resistant TB.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据