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Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area

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Guerra-Assunção, J. A., Crampin, A. C., Houben, R. M. G. J., Mzembe, T., Mallard, K., Coll, F., Khan, P., Banda, L., Chiwaya, A., Pereira, Rui P. A., McNerney, R., Fine, P. E. M., Parkhill, J., Clark, T. G. and Glynn, J. R. (2015) Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area. eLife, 4 . e05166. doi:10.7554/eLife.05166 ISSN 2050-084X.

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Official URL: http://dx.doi.org/10.7554/eLife.05166

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Abstract

To improve understanding of the factors influencing tuberculosis transmission and the role of pathogen variation, we sequenced all available specimens from patients diagnosed over 15 years in a whole district in Malawi. Mycobacterium tuberculosis lineages were assigned and transmission networks constructed, allowing ≤10 single nucleotide polymorphisms (SNPs) difference. We defined disease as due to recent infection if the network-determined source was within 5 years, and assessed transmissibility from forward transmissions resulting in disease. High-quality sequences were available for 1687 disease episodes (72% of all culture-positive episodes): 66% of patients linked to at least one other patient. The between-patient mutation rate was 0.26 SNPs/year (95% CI 0.21–0.31). We showed striking differences by lineage in the proportion of disease due to recent transmission and in transmissibility (highest for lineage-2 and lowest for lineage-1) that were not confounded by immigration, HIV status or drug resistance. Transmissions resulting in disease decreased markedly over time.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Journal or Publication Title: eLife
Publisher: eLife Sciences Publications Ltd.
ISSN: 2050-084X
Official Date: 3 March 2015
Dates:
DateEvent
3 March 2015Published
Volume: 4
Article Number: e05166
DOI: 10.7554/eLife.05166
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)

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