Association between bacterial homoplastic variants and radiological pathology in tuberculosis.
clinical epidemiology
imaging/CT MRI etc
tuberculosis
Journal
Thorax
ISSN: 1468-3296
Titre abrégé: Thorax
Pays: England
ID NLM: 0417353
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
05
03
2019
revised:
23
03
2020
accepted:
23
03
2020
pubmed:
18
6
2020
medline:
20
8
2020
entrez:
18
6
2020
Statut:
ppublish
Résumé
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 the We performed whole genome sequencing (Illumina HiSeq2000 platform) on 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. This study is the first to compare the
Sections du résumé
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 the
METHODS
We performed whole genome sequencing (Illumina HiSeq2000 platform) on
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 the
Identifiants
pubmed: 32546574
pii: thoraxjnl-2019-213281
doi: 10.1136/thoraxjnl-2019-213281
pmc: PMC7361023
doi:
Substances chimiques
Bacterial Proteins
0
DNA, Bacterial
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
584-591Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: JP and SP are consultants to Next Gen Diagnostics Llc.
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