Novel Technique Finds Undetected Tuberculosis Super-​Spreader in Canada

February 4/2020

by Françoise Makanda, Communications Officer at DLSPH

A U of T-led research team used deep sequencing to find a previously undetected tuberculosis super-spreader in an outbreak in Nunavik, Quebec.

It is the first time the technique is used in tuberculosis transmission in Canada. The researcher’s findings were published today in the eLIFE journal.

“Super-spreading may be playing a key role in transmission in these outbreaks up north,” says the study’s lead, DLSPH Professor Robyn Lee.

“If we can identify specific factors that are associated with super-spreading in Nunavik, when a patient with these characteristics comes into clinic and is diagnosed with tuberculosis, we can ideally triage their contacts, and have them tested more quickly, to help break the chains of transmission.”

According to the Canadian Tuberculosis Reporting System, Nunavik’s rate of infections was 304.0 per 100,000 habitants in 2016 while Canada’s overall rate sat at 4.8 per 100,000 habitants.

DLSPH Professor Robyn Lee

The researchers found one additional super-spreader—an unusually contagious person—who potentially led to 17 additional cases or 35 per cent of the outbreak between 2011 – 2012. With the ‘routine’ sequencing approach, researchers had also previously identified another super-spreader who may have transmitted to 19 additional cases.

“Most of these new cases had attended the same social community gathering houses which were suspected venues of transmission during the outbreak,” Lee adds.

Deep sequencing helped identify variations in patients’ bacterial DNA which found the super-spreader. People living with tuberculosis are not necessarily infected with a single bacterium, says Lee. They may have more than one strain to start with, or the strain may change over time. At times, they can spread different strains to others.

She also says that deep sequencing may provide extra information for public health specialists during outbreaks that happen over short time periods. Recognizing symptoms, early identification and prompt diagnosis are always key to reducing tuberculosis transmission and prevent large numbers of people from becoming infected, she adds.

“Typically, with ‘routine’ whole-genome sequencing, we sequence the genome about 50 to 100 times and we come up with a consensus sequence representing a patient’s bacteria. We compare consensus sequences from different patients to understand transmission. By sequencing the genome from 500 to 1000 times, ten to twenty times more than we would usually sequence, we were able to look for variation in the bacteria within the patient and be confident that this variation is something that’s real and not a potential mistake caused by the sequencing or the way we analyze the data.”

The study was done in collaboration with the Nunavik Regional Board of Health and Social Services, the Harvard T.H. Chan School of Public Health, and McGill University, and was funded by the National Institutes of Health and Canadian Institutes of Health Research.