Todd Neale, Staff Writer, MedPage Today: : February 25, 2011
Sometimes traditional epidemiologic techniques are not enough to get to the bottom of an infectious disease outbreak, as illustrated by a rash of tuberculosis cases in British Columbia from 2006 through 2008.
There were 41 cases identified during the outbreak, and traditional contact tracing failed to uncover a likely source, Patrick Tang, MD, PhD, of the British Columbia Center for Disease Control in Vancouver, and colleagues reported in the Feb. 24 issue of the New England Journal of Medicine.
Initial genotyping of Mycobacterium tuberculosis isolates suggested that a single clone was responsible for the spread of infection.
Only after the addition of social-network analysis and whole-genome sequencing of the bacteria did researchers conclude that the cases were actually caused by two distinct lineages of M. tuberculosis, which likely spread in conjunction with the growth of crack cocaine use at the time.
"As the cost of whole-genome sequencing continues to decrease and next-generation sequencing platforms become integrated into public health practice, combined microbial genomic and epidemiologic approaches like those described here will become an important and tractable first step toward a systems approach to tuberculosis control," Tang and his colleagues wrote.
The outbreak began in a medium-sized community in British Columbia with an adult who was diagnosed with smear-negative pleural tuberculosis in May 2006. A second case with disseminated tuberculosis -- an infant -- was diagnosed in July 2006.
Contact tracing turned up nine additional cases by October 2006, when the British Columbia Center for Disease Control initiated an investigation.
The number of cases peaked in 2007, and by the end of 2008 there were a total of 41 individuals who had been infected. All had the same patterns of mycobacterial interspersed repetitive unit-variable-number tandem repeats, which suggested that the outbreak was caused by a single clone.
Researchers could not identify a single source for the outbreak using traditional contact tracing, so they performed social-network analysis to identify high-risk behaviors and additional people that would not turn up with standard methods.
In this way, the researchers tagged a likely source case, which led to the identification of other infected individuals through previously unreported social interactions and locations, including hotels, a meal center, community centers, and a series of crack houses.
But the information obtained so far still did not fully explain the outbreak.
So the researchers sequenced the complete genomes of 32 M. tuberculosis outbreak isolates and four isolates from the same region but from before the outbreak, which identified two genetically distinct lineages of bacteria that diverged from a common ancestor some time before 2001. That indicates that there were actually two outbreaks occurring at the same time.
"The observation that both lineages had been present in the region for at least five years before the outbreak suggested that a social or environmental factor operating before 2006 triggered the outbreak, rather than a genetic change in the organism," Tang and his colleagues wrote.
With this additional information, the researchers again used social-network analysis, identifying one likely source for the spread of one lineage and two likely sources for the spread of the other. All three patients had smear-positive tuberculosis, had several connections within the social network, and had been symptomatic for several months before treatment.
The researchers called them "superspreaders."
Many of the patients reported transient living conditions, crack cocaine use (61%), and alcohol use (66%).
An analysis of files from the Royal Canadian Mounted Police revealed that the spread of tuberculosis occurred at the same time the use of crack cocaine was increasing in the community, suggesting that drug use may have triggered and sustained the outbreak, according to the researchers.
"A constellation of impaired host immunity, lack of access to healthcare, and crowded, poorly ventilated environments most likely predisposes users to both exposure to and development of tuberculosis," Tang and his colleagues wrote. "Poverty and the highly transitive social networks established by crack users may also contribute to tuberculosis transmission."
The study was supported by grants from Genome British Columbia, Health Canada, the Simon Fraser University Community Trust, the British Columbia Lung Association, the Canadian Cystic Fibrosis Foundation, the Michael Smith Foundation for Health Research, and the Canadian Institutes of Health Research.
Primary source: New England Journal of Medicine: Gardy J, et al "Whole-genome sequencing and social-network analysis of a tuberculosis outbreak" N Engl J Med 2011; 364: 730-739.
http://www.medpagetoday.com/InfectiousDisease/Tuberculosis/25061
Sometimes traditional epidemiologic techniques are not enough to get to the bottom of an infectious disease outbreak, as illustrated by a rash of tuberculosis cases in British Columbia from 2006 through 2008.
There were 41 cases identified during the outbreak, and traditional contact tracing failed to uncover a likely source, Patrick Tang, MD, PhD, of the British Columbia Center for Disease Control in Vancouver, and colleagues reported in the Feb. 24 issue of the New England Journal of Medicine.
Initial genotyping of Mycobacterium tuberculosis isolates suggested that a single clone was responsible for the spread of infection.
Only after the addition of social-network analysis and whole-genome sequencing of the bacteria did researchers conclude that the cases were actually caused by two distinct lineages of M. tuberculosis, which likely spread in conjunction with the growth of crack cocaine use at the time.
"As the cost of whole-genome sequencing continues to decrease and next-generation sequencing platforms become integrated into public health practice, combined microbial genomic and epidemiologic approaches like those described here will become an important and tractable first step toward a systems approach to tuberculosis control," Tang and his colleagues wrote.
The outbreak began in a medium-sized community in British Columbia with an adult who was diagnosed with smear-negative pleural tuberculosis in May 2006. A second case with disseminated tuberculosis -- an infant -- was diagnosed in July 2006.
Contact tracing turned up nine additional cases by October 2006, when the British Columbia Center for Disease Control initiated an investigation.
The number of cases peaked in 2007, and by the end of 2008 there were a total of 41 individuals who had been infected. All had the same patterns of mycobacterial interspersed repetitive unit-variable-number tandem repeats, which suggested that the outbreak was caused by a single clone.
Researchers could not identify a single source for the outbreak using traditional contact tracing, so they performed social-network analysis to identify high-risk behaviors and additional people that would not turn up with standard methods.
In this way, the researchers tagged a likely source case, which led to the identification of other infected individuals through previously unreported social interactions and locations, including hotels, a meal center, community centers, and a series of crack houses.
But the information obtained so far still did not fully explain the outbreak.
So the researchers sequenced the complete genomes of 32 M. tuberculosis outbreak isolates and four isolates from the same region but from before the outbreak, which identified two genetically distinct lineages of bacteria that diverged from a common ancestor some time before 2001. That indicates that there were actually two outbreaks occurring at the same time.
"The observation that both lineages had been present in the region for at least five years before the outbreak suggested that a social or environmental factor operating before 2006 triggered the outbreak, rather than a genetic change in the organism," Tang and his colleagues wrote.
With this additional information, the researchers again used social-network analysis, identifying one likely source for the spread of one lineage and two likely sources for the spread of the other. All three patients had smear-positive tuberculosis, had several connections within the social network, and had been symptomatic for several months before treatment.
The researchers called them "superspreaders."
Many of the patients reported transient living conditions, crack cocaine use (61%), and alcohol use (66%).
An analysis of files from the Royal Canadian Mounted Police revealed that the spread of tuberculosis occurred at the same time the use of crack cocaine was increasing in the community, suggesting that drug use may have triggered and sustained the outbreak, according to the researchers.
"A constellation of impaired host immunity, lack of access to healthcare, and crowded, poorly ventilated environments most likely predisposes users to both exposure to and development of tuberculosis," Tang and his colleagues wrote. "Poverty and the highly transitive social networks established by crack users may also contribute to tuberculosis transmission."
The study was supported by grants from Genome British Columbia, Health Canada, the Simon Fraser University Community Trust, the British Columbia Lung Association, the Canadian Cystic Fibrosis Foundation, the Michael Smith Foundation for Health Research, and the Canadian Institutes of Health Research.
Primary source: New England Journal of Medicine: Gardy J, et al "Whole-genome sequencing and social-network analysis of a tuberculosis outbreak" N Engl J Med 2011; 364: 730-739.
http://www.medpagetoday.com/InfectiousDisease/Tuberculosis/25061
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