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


Guerra-Assunção, J; Crampin, A; Houben, R; Mzembe, T; Mallard, K; Coll, F; Khan, P; Banda, L; Chiwaya, A; Pereira, R; McNerney, R; Fine, P; Parkhill, J; Clark, T; Glynn, J; (2015) Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area. Elife, 4. ISSN 2050-084X DOI: 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: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: MEIRU
TB Centre
PubMed ID: 25732036
Web of Science ID: 351863500001
URI: http://researchonline.lshtm.ac.uk/id/eprint/2124250

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