New vaccine shows how Canada can tackle TB

Tuberculosis (TB) has long reigned as the world’s deadliest infectious disease, prompting UN member states in 2018 to commit 0.1% of their overall research spending on this scourge. Canada has consistently missed this target (set at USD $25.3 million), and by 2020, with the global Covid-19 pandemic getting under way, the country was still falling short by 20 per cent.

“We see huge gaps between what UN member states have committed, and what they are actually spending on TB research,” says Lena Faust, a PhD candidate in epidemiology at the McGill International Tuberculosis Centre and a member of Stop TB Canada, a network of TB researchers and advocates working to end TB at home and abroad. “For example, in 2019, Canada only spent 76 per cent of its commitment, placing it behind countries such as New Zealand, the UK and the United States.”

She adds that Canadian funding for research into TB drugs and vaccines is particularly lacking – a striking contrast to the investments in COVID-19 vaccines.

“The TB vaccine we use today, the Bacillus Calmette-Guérin (BCG), is more than 100 years old and it doesn’t even work that well,” notes Faust. “BCG can prevent severe forms of TB in children, but it doesn’t prevent the most common form of TB, which is pulmonary TB in adults. Meanwhile, dozens of different COVID-19 vaccines have been approved in just over a year. That’s the kind of investment we need for TB innovation.”

In 2020, while the world’s attention was focused on rising case numbers of COVID-19, more than 10 million people developed active TB and 1.5 million people died of it. While Canada has one of the lowest rates of TB globally, Indigenous Peoples and foreign-born Canadians are disproportionately infected. In fact, rates in Inuit communities are more than 300 times higher than for those who are Canadian-born and non-Indigenous.

However, there is some good news on the horizon. A team of Canadian researchers at McMaster University is developing an inhalable TB vaccine that would act as a booster to strengthen immune protection right at the site of infection — the lungs. If successful, it would be among the first new effective TB vaccines in the world.

And on March 24 this year, World TB Day, Canada’s Minister of International Development, Harjit Sajjan, announced $11 million in new investments into TB REACH, an initiative to provide grants to global partners for testing innovations that increase the number of people diagnosed and treated for TB. It also aims to improve treatment success rates in communities with limited access to care.

“Canada has shown real leadership in the global response to TB, including as a founding partner of TB REACH,” says Faust. “We have a responsibility, both domestically and globally, to work on eliminating TB. It’s like COVID-19 – you can’t end it here in Canada until you end it everywhere.

“But to maintain Canada’s credibility, we also need to invest in TB research domestically,” Faust adds. “We have to follow through with our own goals, such as eliminating TB in Inuit Nunangat (the homeland of the Inuit in Canada) by 2030. I’m not sure we’re going to make that target. All of this is complicated by the fact that we haven’t been measuring our progress on TB elimination in a timely manner.”

Dr. Gonzalo Alvarez is a leader in TB research for Inuit communities. He’s chair of the Taima program of research (“Taima” means “stop” in Inuktitut) and a scientist at the Ottawa Hospital Research Institute (OHRI). Since 2007, he has also been providing pulmonary care for residents of Nunavut and in his Ottawa Hospital respirology and tuberculosis clinics.

“Up north, there’s a lot of TB transmission related to social determinants of health, such as crowded housing and challenges with access to health care,” he says. “A key element to control the spread of TB is treating latent TB infection (also known as “sleeping TB”) before it turns to active TB disease.”

Five years ago, Dr. Alvarez and his team decided to see if they could get a new, safer treatment for latent TB called 3HP rolled out in Nunavut. The old treatment was an antibiotic called isoniazid, which can cause liver damage. It also requires nine months of daily medication, totaling 270 doses.

3HP treatment requires just eight doses — one a week for eight weeks — and is significantly less toxic. While 3HP had been approved by the FDA in the United States in 2015, it was not approved by Health Canada and no one was using it in Canada yet.

“There are often massive gaps between having a new, effective treatment and using it where it really matters, which for TB are the Inuit communities,” explains Dr. Alvarez. “There are serious barriers to getting 3HP into these remote areas, including extreme weather, cultural challenges, high rates of staff burnout and the geography. ”

However, with funding from the Public Health Agency of Canada (PHAC) and working closely with Inuit partners, Dr. Alvarez and his team were able to conduct a successful implementation study of 3HP in Iqualuit, the capital of Nunavut.

They had good uptake of the treatment by patients. It was found to be cost-effective and 3HP was approved by Nunavut as the first line of care for latent TB — the first Canadian jurisdiction to do so.

“We’re so proud of this because it’s often the places that need a treatment most that are the last ones to receive them,” says Dr. Alvarez. “Approving 3HP as the standard of care for treating latent TB is a big step forward in breaking the cycle of transmission. The Government of Nunavut is doing a full-court press on TB. Natan Obed, president of Inuit Tapiriit Kanatami [representing the 65,000 Inuit living in Canada], has also done tremendous work. He’s managed to get the federal government to think more seriously about TB.”

More recently, Dr. Alvarez studied patients in Ottawa treated for latent TB before and after 3HP became available. They showed that 90 per cent of patients who took 3HP completed the therapy, a significant improvement over the traditional treatment.

In March 2022, this research, combined with his work in Nunavut, resulted in a new, transformational recommendation that 3HP be used as a first-line treatment for latent TB across Canada.

Still, Dr. Alvarez recognizes that much more needs to be done. He believes the single most important thing Canada needs to do now is to fund TB vaccine development, followed by improving treatment of latent TB.

“We’re still using the old BCG vaccine and it’s not solving the problem,” he explains. “In terms of prevention, we’d like to shorten the course of antibiotics even further. Imagine what we could do with a seven-day regimen. That would be a planetary game-changer.”

While Canada’s 2022 budget made no direct reference to combatting TB, Stop TB Canada says that much of the budget’s priorities are relevant to ending TB, such as improving housing in the North and the detection of public health emergencies. But they warn that a resurgence of TB in Canada is becoming a growing and real risk.

Dr. Alvarez remains cautiously optimistic.

“Because of the COVID-19 pandemic, the world has taken a step back from its fight against TB,” he concludes. "Canada needs to be doing everything it can to fight this disease. While the money earmarked by Canada for TB is a start, we’ll require much more financial support to achieve the ultimate goal — which is eliminating TB altogether.”

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