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

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 tuber...

Full description

Saved in:
Bibliographic Details
Published in:The Lancet infectious diseases Vol. 13; no. 2; pp. 137 - 146
Main Authors: Walker, Timothy M, Ip, Camilla LC, Harrell, Ruth H, Evans, Jason T, Kapatai, Georgia, Dedicoat, Martin J, Eyre, David W, Wilson, Daniel J, Hawkey, Peter M, Crook, Derrick W, Parkhill, Julian, Harris, David, Walker, A Sarah, Bowden, Rory, Monk, Philip, Smith, E Grace, Peto, Tim EA
Format: Journal Article
Language:English
Published: London Elsevier Ltd 01.02.2013
Lancet Publishing Group
Elsevier Limited
Elsevier Science ;, The Lancet Pub. Group
Subjects:
Bacterial diseases
Biological and medical sciences
Cluster Analysis
Community-Acquired Infections - epidemiology
Community-Acquired Infections - microbiology
Confidence Intervals
Cross-Sectional Studies
Deoxyribonucleic acid
Disease control
Disease Outbreaks - classification
DNA
Genetic diversity
Genetic Linkage
Genome, Bacterial - genetics
Households
Human bacterial diseases
Humans
Infectious Disease
Infectious diseases
Longitudinal Studies
Medical research
Medical sciences
Mutation Rate
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Observational studies
Outbreaks
Polymorphism, Single Nucleotide
Retrospective Studies
Sequence Analysis, DNA
Tandem Repeat Sequences
Tuberculosis
Tuberculosis and atypical mycobacterial infections
Tuberculosis, Pulmonary - epidemiology
Tuberculosis, Pulmonary - microbiology
Tuberculosis, Pulmonary - transmission
United Kingdom - epidemiology
United Kingdom
Europe
British Isles
Epidemic
Nucleotide sequence
Mycobacterial infection
Epidemiology
Infection
Tuberculosis
Mycobacterium tuberculosis
Mycobacteriales
Bacteriosis
Mycobacteriaceae
Bacteria
Actinomycetes
Genome
Sequencing
ISSN:1473-3099, 1474-4457, 1474-4457
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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<0·0001). Genetic trees and clinical and epidemiological data suggest that super-spreaders were present in two community clusters. Whole-genome sequencing can delineate outbreaks of tuberculosis and allows inference about direction of transmission between cases. The technique could identify super-spreaders and predict the existence of undiagnosed cases, potentially leading to early treatment of infectious patients and their contacts. Medical Research Council, Wellcome Trust, National Institute for Health Research, and the Health Protection Agency.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ObjectType-Article-2
ObjectType-Feature-1
These authors also contributed equally
These authors contributed equally
ISSN:1473-3099
1474-4457
1474-4457
DOI:10.1016/S1473-3099(12)70277-3