Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study
By T. Walker, C. Ip, Ruth H Harrell, Jason T. Evans, G. Kapatai, M. Dedicoat, D. Eyre, D. Wilson, P. Hawkey, D. Crook and 7 more. Lancet. Infectious Diseases (Print), 2013
870 citations recorded by the source corpus.
Summary 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<0·0001). Genetic trees and clinical and epidemiological data suggest that super-spreaders were present in two community clusters. Interpretation 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. Funding Medical Research Council, Wellcome Trust, National Institute for Health Research, and the Health Protection Agency.
Subfields: Epidemiology, Infectious Diseases, Surgery
View Paper: https://www.semanticscholar.org/paper/ae7a9c8da37064783e34835fe415b7a26f3ff0d1
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Citations in the corpus
- ClonalFrameML: Efficient Inference of Recombination in Whole Bacterial Genomes (2015, background): “Comparisons of multiple bacterial genomes can be used to investigate within-host diversity and evolution [9,10], to delineate and reconstruct local outbreaks [11 – 13], or to describe the global population structure and epidemiology [14,15].”
- Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis (2015, background): “Whole-genome analysis of these samples (see Methods section) found a median of 16 heterozygous sites per sample, consistent with mixed infections (local transmission or in-host evolution) 44 , although we cannot exclude the possibility of contamination with a closely related strain.”