World Tuberculosis Day: How EPIC researchers at U of T are making an impact

Jacqueline Watt (left) and Lauren Ramsay are PhD students at the University of Toronto working to tackle tuberculosis (supplied images)

Tuberculosis (TB) is preventable and curable, yet it remains one of the world’s most deadly infectious threats and a significant global health challenge.

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

On World TB Day, U of T News examines how members of EPIC, the University of Toronto’s Emerging and Pandemic Infections Consortium, are working to tackle the disease – from creating better vaccines to gaining a deeper understanding of TB’s financial toll on patients and families.

Better vaccines

“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 Professor 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 is 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. This is because it generates a relatively weak, short-lived immune response and 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  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,” Watt said.

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.

Financial toll

Researchers are concerned that the financial toll of TB will have a greater impact on the equity-deserving groups that are disproportionally affected by the disease.

“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 in the Institute of Health Policy, Management and Evaluation (IHPME) at the Dalla Lana School of Public Health.

Working with IHPME Professor Beate Sander, a senior scientist at the Toronto General Hospital Research Institute and adjunct scientist at ICES and Public Health Ontario, Ramsay and her colleagues recently launched an online survey for adults with active TB living in urban centres.

The survey asks patients and caregivers about costs that they’ve incurred related to their diagnosis and care such as bus or taxi fare, parking, food and missed work. 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.”

Ramsay will combine the results of the patient survey with estimated health-care costs for a cohort of nearly 8,000 people with TB. The data, which spans 2002 to 2016, will also allow the researchers to look at whether people with TB incur higher health-care costs over their lifetime, even after they’ve been cured of the disease.

“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. “If we want to reduce financial and health-related inequities, TB is a critical area to focus on.”

This story has been edited and condensed; you can see the original here.

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