title: Whole-genome sequencing and social-network analysis of a tuberculosis outbreak.
abstract: 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.).
authors.affiliation: British Columbia Centre for Disease Control, Vancouver, BC, Canada.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gardy
authors.forename: James C
authors.initials: JC
authors.lastname: Johnston
authors.forename: Shannan J
authors.initials: SJ
authors.lastname: Ho Sui
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Cook
authors.forename: Lena
authors.initials: L
authors.lastname: Shah
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Brodkin
authors.forename: Shirley
authors.initials: S
authors.lastname: Rempel
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Robert
authors.initials: R
authors.lastname: Holt
authors.forename: Richard
authors.initials: R
authors.lastname: Varhol
authors.forename: Inanc
authors.initials: I
authors.lastname: Birol
authors.forename: Marcus
authors.initials: M
authors.lastname: Lem
authors.forename: Meenu K
authors.initials: MK
authors.lastname: Sharma
authors.forename: Kevin
authors.initials: K
authors.lastname: Elwood
authors.forename: Steven J M
authors.initials: SJ
authors.lastname: Jones
authors.forename: Fiona S L
authors.initials: FS
authors.lastname: Brinkman
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brunham
authors.forename: Patrick
authors.initials: P
authors.lastname: Tang
mesh_terms: D000328:Adult; D001955:British Columbia / Q000453:epidemiology; D019970:Cocaine-Related Disorders / Q000150:complications; D016358:Contact Tracing; D004196:Disease Outbreaks; D005260:Female; D016680:Genome, Bacterial; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012944:Social Support; D011795:Surveys and Questionnaires; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D055815:Young Adult