Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks : a retrospective observational study

Timothy M Walker; Camilla Lc Ip; Ruth H Harrell; Jason T Evans; Georgia Kapatai; Martin J Dedicoat; David W Eyre; Daniel J Wilson; Peter M Hawkey; Derrick W Crook; Julian Parkhill; David Harris; A Sarah Walker; Rory Bowden; Philip Monk; E Grace Smith; Tim Ea Peto

doi:10.1016/S1473-3099(12)70277-3

Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks : a retrospective observational study

Timothy M Walker, Camilla Lc Ip, Ruth H Harrell, Jason T Evans, Georgia Kapatai, Martin J Dedicoat, David W Eyre, Daniel J Wilson, Peter M Hawkey, Derrick W Crook, Julian Parkhill, David Harris, A Sarah Walker, Rory Bowden, Philip Monk, E Grace Smith, Tim Ea Peto

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

511 Citations (Scopus)

Abstract

BACKGROUND: Tuberculosis incidence in the UK has risen in the past decade. Disease control depends on epidemiological data, which can be difficult to obtain. Whole-genome sequencing can detect microevolution within Mycobacterium tuberculosis strains. We aimed to estimate the genetic diversity of related M tuberculosis strains in the UK Midlands and to investigate how this measurement might be used to investigate community outbreaks. METHODS: In a retrospective observational study, we used Illumina technology to sequence M tuberculosis genomes from an archive of frozen cultures. We characterised isolates into four groups: cross-sectional, longitudinal, household, and community. We measured pairwise nucleotide differences within hosts and between hosts in household outbreaks and estimated the rate of change in DNA sequences. We used the findings to interpret network diagrams constructed from 11 community clusters derived from mycobacterial interspersed repetitive-unit-variable-number tandem-repeat data. FINDINGS: We sequenced 390 separate isolates from 254 patients, including representatives from all five major lineages of M tuberculosis. The estimated rate of change in DNA sequences was 0·5 single nucleotide polymorphisms (SNPs) per genome per year (95% CI 0·3-0·7) in longitudinal isolates from 30 individuals and 25 families. Divergence is rarely higher than five SNPs in 3 years. 109 (96%) of 114 paired isolates from individuals and households differed by five or fewer SNPs. More than five SNPs separated isolates from none of 69 epidemiologically linked patients, two (15%) of 13 possibly linked patients, and 13 (17%) of 75 epidemiologically unlinked patients (three-way comparison exact p

Original language	English
Pages (from-to)	137-146
Number of pages	10
Journal	The Lancet Infectious Diseases
Volume	13
Issue number	2
Early online date	14 Nov 2012
DOIs	https://doi.org/10.1016/S1473-3099(12)70277-3
Publication status	Published - Feb 2013

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Walker, T. M., Ip, C. L., Harrell, R. H., Evans, J. T., Kapatai, G., Dedicoat, M. J., Eyre, D. W., Wilson, D. J., Hawkey, P. M., Crook, D. W., Parkhill, J., Harris, D., Walker, A. S., Bowden, R., Monk, P., Smith, E. G., & Peto, T. E. (2013). Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks : a retrospective observational study. The Lancet Infectious Diseases, 13(2), 137-146. https://doi.org/10.1016/S1473-3099(12)70277-3

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title = "Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks : a retrospective observational study",

abstract = "BACKGROUND: Tuberculosis incidence in the UK has risen in the past decade. Disease control depends on epidemiological data, which can be difficult to obtain. Whole-genome sequencing can detect microevolution within Mycobacterium tuberculosis strains. We aimed to estimate the genetic diversity of related M tuberculosis strains in the UK Midlands and to investigate how this measurement might be used to investigate community outbreaks. METHODS: In a retrospective observational study, we used Illumina technology to sequence M tuberculosis genomes from an archive of frozen cultures. We characterised isolates into four groups: cross-sectional, longitudinal, household, and community. We measured pairwise nucleotide differences within hosts and between hosts in household outbreaks and estimated the rate of change in DNA sequences. We used the findings to interpret network diagrams constructed from 11 community clusters derived from mycobacterial interspersed repetitive-unit-variable-number tandem-repeat data. FINDINGS: We sequenced 390 separate isolates from 254 patients, including representatives from all five major lineages of M tuberculosis. The estimated rate of change in DNA sequences was 0·5 single nucleotide polymorphisms (SNPs) per genome per year (95% CI 0·3-0·7) in longitudinal isolates from 30 individuals and 25 families. Divergence is rarely higher than five SNPs in 3 years. 109 (96%) of 114 paired isolates from individuals and households differed by five or fewer SNPs. More than five SNPs separated isolates from none of 69 epidemiologically linked patients, two (15%) of 13 possibly linked patients, and 13 (17%) of 75 epidemiologically unlinked patients (three-way comparison exact p",

author = "Walker, {Timothy M} and Ip, {Camilla Lc} and Harrell, {Ruth H} and Evans, {Jason T} and Georgia Kapatai and Dedicoat, {Martin J} and Eyre, {David W} and Wilson, {Daniel J} and Hawkey, {Peter M} and Crook, {Derrick W} and Julian Parkhill and David Harris and Walker, {A Sarah} and Rory Bowden and Philip Monk and Smith, {E Grace} and Peto, {Tim Ea}",

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Walker, TM, Ip, CL, Harrell, RH, Evans, JT, Kapatai, G, Dedicoat, MJ, Eyre, DW, Wilson, DJ, Hawkey, PM, Crook, DW, Parkhill, J, Harris, D, Walker, AS, Bowden, R, Monk, P, Smith, EG & Peto, TE 2013, 'Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks : a retrospective observational study', The Lancet Infectious Diseases, vol. 13, no. 2, pp. 137-146. https://doi.org/10.1016/S1473-3099(12)70277-3

TY - JOUR

T1 - Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks : a retrospective observational study

AU - Walker, Timothy M

AU - Ip, Camilla Lc

AU - Harrell, Ruth H

AU - Evans, Jason T

AU - Kapatai, Georgia

AU - Dedicoat, Martin J

AU - Eyre, David W

AU - Wilson, Daniel J

AU - Hawkey, Peter M

AU - Crook, Derrick W

AU - Parkhill, Julian

AU - Harris, David

AU - Walker, A Sarah

AU - Bowden, Rory

AU - Monk, Philip

AU - Smith, E Grace

AU - Peto, Tim Ea

PY - 2013/2

Y1 - 2013/2

N2 - BACKGROUND: Tuberculosis incidence in the UK has risen in the past decade. Disease control depends on epidemiological data, which can be difficult to obtain. Whole-genome sequencing can detect microevolution within Mycobacterium tuberculosis strains. We aimed to estimate the genetic diversity of related M tuberculosis strains in the UK Midlands and to investigate how this measurement might be used to investigate community outbreaks. METHODS: In a retrospective observational study, we used Illumina technology to sequence M tuberculosis genomes from an archive of frozen cultures. We characterised isolates into four groups: cross-sectional, longitudinal, household, and community. We measured pairwise nucleotide differences within hosts and between hosts in household outbreaks and estimated the rate of change in DNA sequences. We used the findings to interpret network diagrams constructed from 11 community clusters derived from mycobacterial interspersed repetitive-unit-variable-number tandem-repeat data. FINDINGS: We sequenced 390 separate isolates from 254 patients, including representatives from all five major lineages of M tuberculosis. The estimated rate of change in DNA sequences was 0·5 single nucleotide polymorphisms (SNPs) per genome per year (95% CI 0·3-0·7) in longitudinal isolates from 30 individuals and 25 families. Divergence is rarely higher than five SNPs in 3 years. 109 (96%) of 114 paired isolates from individuals and households differed by five or fewer SNPs. More than five SNPs separated isolates from none of 69 epidemiologically linked patients, two (15%) of 13 possibly linked patients, and 13 (17%) of 75 epidemiologically unlinked patients (three-way comparison exact p

AB - BACKGROUND: Tuberculosis incidence in the UK has risen in the past decade. Disease control depends on epidemiological data, which can be difficult to obtain. Whole-genome sequencing can detect microevolution within Mycobacterium tuberculosis strains. We aimed to estimate the genetic diversity of related M tuberculosis strains in the UK Midlands and to investigate how this measurement might be used to investigate community outbreaks. METHODS: In a retrospective observational study, we used Illumina technology to sequence M tuberculosis genomes from an archive of frozen cultures. We characterised isolates into four groups: cross-sectional, longitudinal, household, and community. We measured pairwise nucleotide differences within hosts and between hosts in household outbreaks and estimated the rate of change in DNA sequences. We used the findings to interpret network diagrams constructed from 11 community clusters derived from mycobacterial interspersed repetitive-unit-variable-number tandem-repeat data. FINDINGS: We sequenced 390 separate isolates from 254 patients, including representatives from all five major lineages of M tuberculosis. The estimated rate of change in DNA sequences was 0·5 single nucleotide polymorphisms (SNPs) per genome per year (95% CI 0·3-0·7) in longitudinal isolates from 30 individuals and 25 families. Divergence is rarely higher than five SNPs in 3 years. 109 (96%) of 114 paired isolates from individuals and households differed by five or fewer SNPs. More than five SNPs separated isolates from none of 69 epidemiologically linked patients, two (15%) of 13 possibly linked patients, and 13 (17%) of 75 epidemiologically unlinked patients (three-way comparison exact p

U2 - 10.1016/S1473-3099(12)70277-3

DO - 10.1016/S1473-3099(12)70277-3

M3 - Article

C2 - 23158499

SN - 1474-4457

VL - 13

SP - 137

EP - 146

JO - The Lancet Infectious Diseases

JF - The Lancet Infectious Diseases

IS - 2

ER -

Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks : a retrospective observational study

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