Scientists supported by Genome BC have set a new standard for studying outbreaks of infectious disease by combining advanced genomics with a detailed map of the social relationships between cases to investigate a recent outbreak of tuberculosis in a BC community.
The study tracked 41 individuals who developed tuberculosis: patient interviews revealed a tightly-knit community where most patients knew one another, while DNA fingerprinting of the bacterial samples from each individual showed them to be identical to each other. These two factors together made reconstructing the outbreak family tree impossible.
In order to get a more detailed picture of how TB spread through the community, researchers from the BC Centre for Disease Control (BCCDC), Canada's Michael Smith Genome Sciences Centre and Simon Fraser University turned to whole genome sequencing to discern subtle genetic differences between different bacterial strains. These slight differences allowed them to identify individual transmission events, in which one patient can be identified as the most likely source of the subsequent patient's infection. By looking at all of the transmission events revealed by the data, the researchers were able to identify not only where the outbreak organism had originated, but also how it had moved throughout the community.
"Genome sequencing used to be prohibitively expensive, so it was simply impossible to sequence the bacteria from all the patients involved in an outbreak and we had to go with the next best thing, DNA fingerprinting," says Dr. Jennifer Gardy at the BCCDC. "Now, however, sequencing tens, hundreds, or thousands of bacterial isolates is very doable in a reasonable timeframe and at a manageable cost. We can figure out how these bacteria are related to each other by comparing their genome sequences, and when we overlay that information onto a map of the social relationships between cases we can actually reconstruct the path by which an infectious agent worked its way through a population."
Understanding how an organism enters and spreads through a population is key to public health efforts to manage an outbreak and prevent future cases. This particular study revealed that rather than chains of transmission, in which one person infects another who then infects another and so on, this outbreak was the result of bursts of transmission, where some individuals infected several contacts and others infected none. Knowledge of patterns like this can be used to identify which individuals in a community or in an outbreak should be proactively screened for disease and treated promptly if they test positive thereby mitigating the incidence of these bursts of infection.
"Our findings are already starting to influence how we investigate other TB outbreaks and how we're screening people who might be at risk for developing TB," says Gardy. "We've been able to take our study's findings and put them into practice right away."
"Being able to fund this timely and critical research is what makes Genome BC unique and in this instance, assisting outside of our traditional programs had a significant public impact. Genomics technology was crucial to the success of this study and reflects the value it can lend to public health in a larger context," says Dr. Alan Winter, President and CEO of Genome BC.
The BC researchers' findings have caught the eye of the wider medical community -- their findings will be published in the February 24th issue of the New England Journal of Medicine.
- Jennifer L. Gardy et al. Whole-Genome Sequencing and Social-Network Analysis of a Tuberculosis Outbreak. NEJM, February 24, 2011 DOI: 10.1056/NEJMoa1003176
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