Genomic Sequencing as an Epidemiological Tool to Combat Tuberculosis

June 15, 2016

Initially labeled by the ancient Greeks as phthisis, which translated into meaning consumption, tuberculosis was recognized in antiquity as to seemingly consume the afflicted, as their weight dropped drastically during disease progression. Today, tuberculosis (TB) still affects almost one-third of the world’s population and remains a leading cause of death with a mortality rate of roughly 1.5 million people. Tracking disease outbreaks are critical to controlling the spread of the deadly infection and protecting the public health.

Now, a team of researchers from the University of British Columbia (UBC), along with colleagues at the Imperial College in London, believe they have developed the ability to determine when a TB outbreak is over.

This novel research demonstrates that genomic analysis can be used to establish when a TB outbreak has ended—extremely valuable knowledge that can assist public health investigators understand an outbreak's dynamics and guide a real-time public health response. Genomic analysis involves sequencing and analyzing the complete genetic instructions of the pathogens causing a disease, and using that data to infer who might have infected whom. By looking for mutations that are shared between the pathogens taken from different people, researchers can see whose pathogens are most closely related to each other, suggesting potential transmission. 

"Declaring the end of a TB outbreak is a difficult thing to do," explained senior study author Jennifer Gardy, Ph.D., assistant professor in UBC's School of Population and Public Health and a senior scientist at the British Columbia Centre for Disease Control. "Because the bacterium that causes TB can lie dormant in someone's lung for months or even years before it causes disease, we had no way of knowing whether a TB case we have just diagnosed was a recent infection—suggesting the outbreak is still going on—or whether the person was infected years ago."

The investigators employed mathematical and statistical techniques to evaluate a TB outbreak that began in May 2008 and was able to determine when each outbreak case was infected. This provided public health officials with a way to determine when disease transmission had stopped, and the outbreak had ended. They were able to declare the outbreak over in January 2015, after the data had indicated no disease transmission had occurred since mid-2012.

The research team applied next-gen sequencing techniques to obtain the genomes from 48 TB cases, isolated between May 2008 and April of 2011, as part of a

real-time public health outbreak investigation.

The authors wrote that the data obtained from these cases demonstrated that “although active tuberculosis (TB) cases were diagnosed through 2013, no transmission events took place beyond mid-2012. Subsequent cases were the result of progression from latent TB infection to active disease and not recent transmission. This evolutionary genomic approach was used to declare the outbreak over in January 2015.”

The findings from this study were published recently in Microbial Genetics through an article entitled “Declaring a tuberculosis outbreak over with genomic epidemiology.”

"By using a series of techniques from the world of mathematics and statistics, we can come up with an estimated time at which each infection occurred," Dr. Gardy noted. "This information is incredibly useful to the public health officials managing an outbreak. Responding to an outbreak requires a lot of effort and resources, and we need to know when we can step down our response."

Dr. Gardy added that "genomics has been used to monitor infectious disease outbreaks before, but this is the first time it's ever been possible to declare a complicated outbreak of TB over. It really opens up new doors in the world of TB control."