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M. tuberculosis microvariation is common and is associated with transmission: analysis of three years prospective universal sequencing in England

Wyllie, David H; Do, Trien; Myers, Richard; Nikolayevsky, Vlad; Crook, Derrick; Peto, Tim; Alexander, Eliza; ... Smith, E Grace; + view all (2022) M. tuberculosis microvariation is common and is associated with transmission: analysis of three years prospective universal sequencing in England. Journal of Infection , 85 (1) pp. 31-39. 10.1016/j.jinf.2022.05.011. Green open access

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Abstract

Background: The prevalence, association with disease status, and public health impact of infection with mixtures of M. tuberculosis strains is unclear, in part due to limitations of existing methods for detecting mixed infections. Methods: We developed an algorithm to identify mixtures of M. tuberculosis strains using next generation sequencing data, assessing performance using simulated sequences. We identified mixed M. tuberculosis strains when there was at least one mixed nucleotide position, and where both the mixture's components were present in similar isolates from other individuals, compatible with transmission of the component strains. We determined risk factors for mixed infection among isolations of M. tuberculosis in England using logistic regression. We used survival analyses to assess the association between mixed infection and putative transmission. Findings: 6,560 isolations of TB were successfully sequenced in England 2016-2018. Of 3,691 (56%) specimens for which similar sequences had been isolated from at least two other individuals, 341 (9.2%) were mixed. Mixed infection was more common in lineages other than Lineage 4. Among the 1,823 individuals with pulmonary infection with Lineage 4 M. tuberculosis, mixed infection was associated with significantly increased risk of subsequent isolation of closely related organisms from a different individual (HR 1.43, 95% CI 1.05,1.94), indicative of transmission. Interpretation: Mixtures of transmissible strains occur in at least 5% of tuberculosis infections in England; when present in pulmonary disease, such mixtures are associated with an increased risk of tuberculosis transmission. Funding: Public Health England; NIHR Health Protection Research Units; European Union.

Type: Article
Title: M. tuberculosis microvariation is common and is associated with transmission: analysis of three years prospective universal sequencing in England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jinf.2022.05.011
Publisher version: https://doi.org/10.1016/j.jinf.2022.05.011
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: M. tuberculosis Transmission Mixed infection Introduction
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10149008
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