Whole-genome sequencing and social-network analysis of a tuberculosis outbreak

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...

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Main Authors: Gardy, J., Johnston, J., Ho Sui, S., Cook, V., Shah, L., Brodkin, E., Rempel, S., Moore, R., Zhao, Y., Holt, R., Varhol, Richard, Birol, I., Lem, M., Sharma, M., Elwood, K., Jones, S., Brinkman, F., Brunham, R., Tang, P.
Format: Journal Article
Published: 2011
Online Access:http://hdl.handle.net/20.500.11937/39071
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author Gardy, J.
Johnston, J.
Ho Sui, S.
Cook, V.
Shah, L.
Brodkin, E.
Rempel, S.
Moore, R.
Zhao, Y.
Holt, R.
Varhol, Richard
Birol, I.
Lem, M.
Sharma, M.
Elwood, K.
Jones, S.
Brinkman, F.
Brunham, R.
Tang, P.
author_facet Gardy, J.
Johnston, J.
Ho Sui, S.
Cook, V.
Shah, L.
Brodkin, E.
Rempel, S.
Moore, R.
Zhao, Y.
Holt, R.
Varhol, Richard
Birol, I.
Lem, M.
Sharma, M.
Elwood, K.
Jones, S.
Brinkman, F.
Brunham, R.
Tang, P.
author_sort Gardy, J.
building Curtin Institutional Repository
collection Online Access
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.
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spelling curtin-20.500.11937-390712017-09-13T14:20:16Z Whole-genome sequencing and social-network analysis of a tuberculosis outbreak Gardy, J. Johnston, J. Ho Sui, S. Cook, V. Shah, L. Brodkin, E. Rempel, S. Moore, R. Zhao, Y. Holt, R. Varhol, Richard Birol, I. Lem, M. Sharma, M. Elwood, K. Jones, S. Brinkman, F. Brunham, R. Tang, P. 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. 2011 Journal Article http://hdl.handle.net/20.500.11937/39071 10.1056/NEJMoa1003176 restricted
spellingShingle Gardy, J.
Johnston, J.
Ho Sui, S.
Cook, V.
Shah, L.
Brodkin, E.
Rempel, S.
Moore, R.
Zhao, Y.
Holt, R.
Varhol, Richard
Birol, I.
Lem, M.
Sharma, M.
Elwood, K.
Jones, S.
Brinkman, F.
Brunham, R.
Tang, P.
Whole-genome sequencing and social-network analysis of a tuberculosis outbreak
title Whole-genome sequencing and social-network analysis of a tuberculosis outbreak
title_full Whole-genome sequencing and social-network analysis of a tuberculosis outbreak
title_fullStr Whole-genome sequencing and social-network analysis of a tuberculosis outbreak
title_full_unstemmed Whole-genome sequencing and social-network analysis of a tuberculosis outbreak
title_short Whole-genome sequencing and social-network analysis of a tuberculosis outbreak
title_sort whole-genome sequencing and social-network analysis of a tuberculosis outbreak
url http://hdl.handle.net/20.500.11937/39071