When it comes to an infectious disease outbreak, it’s never enough to simply diagnose and treat patients who get sick. To stop the spread, the BC Centre for Disease Control must also locate the source of the disease and identify everyone who may have been exposed.
This type of detective work is used to control tuberculosis (TB), a highly-contagious bacterial infection that primarily attacks the lungs. While many people don’t consider TB to be a disease of modern times, it remains a significant health issue in certain Canadian populations. Poor nutrition, substandard or transient housing, illicit drug use and genetic factors can all make individuals more vulnerable to TB infection. The bacterium can lay dormant in a person for many years before it becomes active, meaning that many people may be infected without any signs of illness.
Traditional methods for investigating an outbreak are two-fold. The first approach is epidemiological, where diagnosed individuals provide a list of people they come into contact with on a regular basis. At the same time, simple genotyping – which looks at DNA sequences on specific locations of the bacterial genome – determines whether all TB patients in an outbreak carry the same disease strain, which would point to a single source of infection.
Recently however, the BCCDC was confronted with a medical mystery. Traditional tracing methods were yielding no clear infection source in a TB outbreak that began in 2006. In less than three years, a total of 41 cases were diagnosed in a single community.
Easier to follow up
“We believe we’re really on to something important. These new methods make it much easier to identify transmission events and target the right people for follow-up.”
Dr. Jennifer Gardy
What was needed was a deeper level of understanding, according to Dr. Jennifer Gardy, head of BCCDC’s Genome Research Laboratory. First, epidemiologists implemented a more detailed contact tracing method called social network analysis to identify key people, places and behaviours that might contribute to the spread of TB. Second, Gardy and her research colleagues decided to analyze the entire bacterial genome of each TB patient.
“Surprisingly, we discovered that even though they all had the same genotype, there was actually a significant degree of genetic diversity lurking below the surface,” she explains.
This led the team to identify two separate strains of TB circulating in the community, each originating from different individuals who became ill with active disease around the same time. Combining this information with the social network analysis allowed the BCCDC to identify three TB “superspreaders,” who were the direct source of the majority of infections. “Finding these spreaders is key to stopping an outbreak,” says Gardy.
The results of this work demonstrate the power of a combined approach to investigating disease outbreaks. “We believe we’re really on to something important,” says Gardy. “These new methods make it much easier to identify transmission events and target the right people for follow-up.”
Fraction of the cost
Five years ago researchers would have had trouble sequencing two or three bacterial genomes – let alone the 36 sequenced for this research project – with DNA segments processed a few hundred at a time.
Today’s high-throughput technology processes millions of DNA segments at a time, for just a fraction of the cost of the old method. This high-volume/low-cost processing capability opens the door for many new avenues of research.
Jennifer Gardy leads BCCDC’s Genome Research Laboratory and is an adjunct professor in the department of microbiology and immunology at UBC.
Genome British Columbia
Simon Fraser University's Community Trust
Health Canada's First Nations and Inuit Health group