PT  - JOURNAL ARTICLE
AU  - Louis Grandjean
AU  - Joha Monteserin
AU  - Robert Gilman
AU  - Julia Pauschardt
AU  - Sakib Rokadiya
AU  - Cesar Bonilla
AU  - Viviana Ritacco
AU  - Julia Rios Vidal
AU  - Julian Parkhill
AU  - Sharon Peacock
AU  - David AJ Moore
AU  - Francois Balloux
TI  - Association between bacterial homoplastic variants and radiological pathology in tuberculosis
AID  - 10.1136/thoraxjnl-2019-213281
DP  - 2020 Jul 01
TA  - Thorax
PG  - 584--591
VI  - 75
IP  - 7
4099  - http://thorax.bmj.com/content/75/7/584.short
4100  - http://thorax.bmj.com/content/75/7/584.full
SO  - Thorax2020 Jul 01; 75
AB  - 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 Mycobacterium tuberculosis genome.Methods We performed whole genome sequencing (Illumina HiSeq2000 platform) on M. tuberculosis isolates 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 the M. tuberculosis genome 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.