Evidence map›Paper›PMID 23158499›Full record

ArticleThe Lancet. Infectious diseases2013

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

Timothy M Walker, Camilla L C Ip, Ruth H Harrell, Jason T Evans, Georgia Kapatai, Martin J Dedicoat, David W Eyre, Daniel J Wilson, Peter M Hawkey, Derrick W Crook and 7 more

Open access · hybridAbstract read
In one paragraph

Article in The Lancet. Infectious diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 576 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
576citing papers in PubMed, 3 pooled it
32.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

576 citing papers in PubMed, 3 syntheses or guidelines pooled it, 968 citations in OpenAlex.

  1. Pooled it
  2. ClinicalFrontiers in microbiology · 2025
    Pooled it
  3. Pooled it
  4. Article
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  6. Whole-genome sequencing reveals a novelApplied and environmental microbiology · 2026
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  17. Understanding recurrence inJournal of clinical microbiology · 2026
    Review
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  19. Long-term refined genomic analysis of tuberculosis clusters to distinguish between ongoing transmission, reactivations or diagnostic delays, Almería, Spain, 2003 to 2024.Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2026
    Article
  20. Article

516 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 1 country.

Timothy M WalkerNuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. timothy.walker@ndm.ox.ac.uk
Camilla L C 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 E A Peto
Heart of England NHS Foundation Trust · GBJohn Radcliffe Hospital · GBUniversity of Oxford · GBWellcome Sanger Institute · GBHeartlands Hospital · GB

Funding

Biotechnology and Biological Sciences Research CouncilDepartment of Health DRF-2010-03-40Department of Health G0800778Medical Research Council G0800778Medical Research Council MR/J011398/1Wellcome TrustWellcome Trust 087646/Z/08/ZWellcome Trust 098051
6 · The paper itself

Abstract

backgroundTuberculosis 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.

methodsIn 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.

findingsWe 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.

interpretationWhole-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.

fundingMedical Research Council, Wellcome Trust, National Institute for Health Research, and the Health Protection Agency.

Indexed as

Disease OutbreaksCluster AnalysisCommunity-Acquired InfectionsConfidence IntervalsCross-Sectional StudiesGenetic LinkageGenome, BacterialHumansLongitudinal StudiesMutation RateMycobacterium tuberculosisPolymorphism, Single NucleotideRetrospective StudiesSequence Analysis, DNATandem Repeat SequencesTuberculosis, Pulmonary

Identifiers

PMID23158499
PMCPMC3556524
OpenAlexW2168358002

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.