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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Whole-genome sequencing and social-network analysis of a tuberculosis outbreak
New England Journal of Medicine, Volume 364, No. 8, Year 2011
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Description
Background: An outbreak of tuberculosis occurred over a 3-year period in a medium-size community in British Columbia, Canada. The results of mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) genotyping suggested the outbreak was clonal. Traditional contact tracing did not identify a source. We used whole-genome sequencing and social-network analysis in an effort to describe the outbreak dynamics at a higher resolution. Methods: We sequenced the complete genomes of 32 Mycobacterium tuberculosis outbreak isolates and 4 historical isolates (from the same region but sampled before the outbreak) with matching genotypes, using short-read sequencing. Epidemiologic and genomic data were overlaid on a social network constructed by means of interviews with patients to determine the origins and transmission dynamics of the outbreak. Results: Whole-genome data revealed two genetically distinct lineages of M. tuberculosis with identical MIRU-VNTR genotypes, suggesting two concomitant outbreaks. Integration of social-network and phylogenetic analyses revealed several transmission events, including those involving "superspreaders." Both lineages descended from a common ancestor and had been detected in the community before the outbreak, suggesting a social, rather than genetic, trigger. Further epidemiologic investigation revealed that the onset of the outbreak coincided with a recorded increase in crack cocaine use in the community. Conclusions: Through integration of large-scale bacterial whole-genome sequencing and social-network analysis, we show that a socioenvironmental factor - most likely increased crack cocaine use - triggered the simultaneous expansion of two extant lineages of M. tuberculosis that was sustained by key members of a high-risk social network. Genotyping and contact tracing alone did not capture the true dynamics of the outbreak. (Funded by Genome British Columbia and others.) Copyright © 2011 Massachusetts Medical Society.
Authors & Co-Authors
Gardy, Jennifer L.
Canada, Vancouver
Bc Centre for Disease Control
Canada, Vancouver
The University of British Columbia
Johnston, James Cameron
Canada, Vancouver
Bc Centre for Disease Control
Ho Sui, Shannan J.
Canada, Vancouver
Bc Centre for Disease Control
Canada, Burnaby
Simon Fraser University
Cook, Victoria E.
Canada, Vancouver
The University of British Columbia
Shah, Lena
Canada, Vancouver
Bc Centre for Disease Control
Canada, Ottawa
Public Health Agency of Canada
Varhol, Richard J.
Canada, Vancouver
Canada‘s Michael Smith Genome Sciences Centre
Birol, Inanç
Canada, Vancouver
Canada‘s Michael Smith Genome Sciences Centre
Sharma, Meenu Kaushal
Canada, Winnipeg
National Microbiology Laboratory
Elwood, Kevin R.
Canada, Vancouver
Bc Centre for Disease Control
Canada, Vancouver
The University of British Columbia
Jones, Steven J.M.
Canada, Vancouver
Canada‘s Michael Smith Genome Sciences Centre
Canada, Surrey
Fraser Health, Canada
Brinkman, Fiona SL L.
Canada, Burnaby
Simon Fraser University
Brunham, Robert C.
Canada, Vancouver
Bc Centre for Disease Control
Canada, Vancouver
The University of British Columbia
Tang, Patrick K.C.
Canada, Vancouver
Bc Centre for Disease Control
Canada, Vancouver
The University of British Columbia
Statistics
Citations: 706
Authors: 13
Affiliations: 8
Identifiers
Doi:
10.1056/NEJMoa1003176
ISSN:
00284793
Research Areas
Genetics And Genomics
Study Design
Case-Control Study