^{Jacqueline Watt (left) and Lauren Ramsay are PhD students at the University of Toronto working to tackle tuberculosis.}

March 24, 2023

By Betty Zou

Tuberculosis (TB) remains one of the world’s most deadly infectious threats and a significant global health challenge. The World Health Organization estimates that in 2021, 10.6 million people became sick with the disease and 1.6 million people died of TB, which is both preventable and curable.

These numbers represent the first increase in TB incidence and death in over a decade as the COVID-19 pandemic, coupled with regional conflicts and instability, disrupted vital vaccination and screening programs and reversed years of progress in the global fight to end TB.

While 95% of TB cases occur in low- and middle-income countries, the disease still poses a significant public health concern in Canada, where it disproportionately affects Indigenous communities and people born outside of Canada. According to Health Canada, the rate of TB among Inuit peoples is roughly 15 times higher than the rate among the general population.

Members of the University of Toronto’s Emerging and Pandemic Infections Consortium are working to tackle TB from multiple angles, from creating better vaccines to gaining a deeper understanding of TB’s financial toll on patients and families.

“The BCG vaccine has been used worldwide since the early 1970s and while we’ve known that there are limitations with the vaccine, no one has been able to come out with something better,” said Jacqueline Watt, a PhD student in Jun Liu’s lab in the department of molecular genetics in U of T’s Temerty Faculty of Medicine.

The vaccine is typically given to babies and effective in protecting against rare forms of TB where the infection spreads to multiple sites in the body. However, childhood vaccination offers limited protection in adults against pulmonary TB, the most common type of disease that affects the lungs.

One reason for the BCG vaccine’s suboptimal effectiveness is that it generates a relatively weak, short-lived immune response. The other is that the vaccine is based on a bacteria species that is related, but not identical, to the bacteria that causes TB, Mycobacterium tuberculosis.

Watt and her colleagues are addressing both of these challenges by developing a new vaccine candidate using M. tuberculosis. To turn the disease-causing bacteria into a disease-protective one, the researchers deleted a single gene from the bacteria’s DNA, effectively removing its ability to cause illness.

Their early results are promising. In animal models of TB, their vaccine candidate offered greater and longer-lasting protection than the BCG vaccine and stimulated a much more robust immune response.

“The next thing I want to do is look into why it could be more protective to see if we can learn more about what parts of the immune response are important for protection versus disease progression,” said Watt.

In addition to developing better vaccines against TB, researchers in the Liu lab are also uncovering new insights into how M. tuberculosis uses molecules called small RNAs to regulate gene expression. They have identified a protein they’re calling SRB that serves as a chaperone to help small RNAs attach to their targets. While similar proteins have been found in other bacteria, this is the first time that such a protein has been described in TB-causing bacteria.

In a recent experiment, the researchers found that the SRB protein binds roughly 800 different small RNAs. Many of them have roles in key processes like bacterial metabolism and stress response and could be good targets for new drugs to treat TB, which are badly needed to combat the rise in drug-resistant strains of M. tuberculosis.

When it comes to rolling out a new treatment or vaccination program, healthcare funders often use economic models to determine the cost effectiveness of a new intervention. These models typically include data about costs incurred by the healthcare system but in the case of TB, they lack information about the financial burden incurred by the patient and their families.

“In Canada, we know quite a bit about the cost effectiveness of various TB interventions like screening programs and diagnostic tests, but we don’t know a lot about direct patient costs and costs to their caregivers,” said Lauren Ramsay, a PhD student working with Beate Sander in the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health.

To fill that gap, Ramsay and her colleagues recently launched an online survey for adults with active TB living in urban centres. The survey, which is the first of its kind in Canada, asks patients and caregivers about costs that they’ve incurred related to their TB diagnosis and care such as bus or taxi fare, parking, food and missed work. The researchers aim to recruit 50 patients at three TB clinics in Toronto and one in Ottawa. Because TB predominantly affects Indigenous peoples and people born outside of Canada, they are offering translation services to ensure that language is not a barrier in completing the survey.

“From the patient and caregiver perspective, we expect that the costs will be quite significant because there is a mandatory isolation period that most people with TB have to complete. Depending on the type of TB and how responsive it is to treatment, this could be as long as several months in rare cases,” said Ramsay. “During that time, you’re unable to go to work and you’re relying on your network to support you financially.”

Much like how COVID-19 lockdowns amplified existing inequities, the researchers are concerned that the financial toll of TB will have a greater impact on the equity-seeking groups that are disproportionally affected by the disease.

To obtain a more comprehensive view about the economic burden of TB in Ontario, Ramsay will be combining the results of the patient survey with estimated healthcare costs for a cohort of nearly 8,000 people with TB. The data from ICES, which spans 2002 to 2016, will also allow the researchers to look at whether people with TB incur higher healthcare costs over their lifetime, even after they’ve been cured of the disease.

Ramsay expects that this work will help inform future economic evaluations about the rollout of new TB interventions in Ontario and could be applicable to other parts of the country. More than that, she wants to see more supports for people with TB.

“I hope that this work can shine a light on where costs are highest for specific groups of people and spur discussions about services that can be provided to reduce the financial inequities that result from and are worsened by TB,” she said.

“It’s important we recognize that TB is still a challenge facing people in Canada and in Ontario and that it largely impacts equity-seeking groups. If we want to reduce financial and health-related inequities, TB is a critical area to focus on.”