‘The infectious disease that nobody ever thinks about’

Sarah Fortune_Big 3
The Big 3: Three questions, three answers

March 23, 2022 – Before COVID, tuberculosis was the leading infectious disease killer in the world. To mark World TB Day, March 24, Sarah Fortune, John LaPorte Given Professor of Immunology and Infectious Diseases and a TB expert, discusses the state of the disease worldwide, obstacles to fighting it, and the latest research.

Q: What is the current state of TB globally?

A: We had been making slow but incremental progress over the past 20 years. We were nowhere close to being able to meet the World Health Organization’s TB elimination goals, but TB incidence was slowly creeping down. And then COVID totally upended everything. People aren’t getting treated, people can’t get drugs, and all that progress has just been erased.

TB is the great infectious disease that nobody ever thinks about. If you asked 100 people on the street in Boston about TB, most people would say that it had been eliminated in the 1960s or so. There’s a huge disconnect between the burden of global TB disease and the perceived importance of addressing the burden. That’s true even in areas where TB is endemic. One of the reasons is that TB disproportionately affects the most resource-limited people and, as with many things, there’s a tendency to not prioritize their problems.

Between one quarter and one third of the world’s population is latently infected with TB, meaning that their infection is hidden or dormant. Each year, roughly 10 million get sick, and 1 million die—and many of them are children. The largest global burden is in India, but there are hotspots for multidrug-resistant TB in Ukraine, Moldova, and Belarus. So it’s not just COVID that’s upending TB treatment, but also the war between Russia and Ukraine.

About half a million people fall ill with multidrug-resistant TB every year. It’s expensive and complicated to treat and has potentially life-threatening side effects. And the rate of drug-resistant TB has increased in recent years, even when overall TB numbers were dropping.

Q: What are the biggest challenges to fighting TB?

A: One issue is that the drug regimen for TB is complicated. For just garden-variety TB, the treatment is six months of drugs that you take every day. For the first two months you take four drugs, and the last four months you take two drugs. So you can just imagine the complexity of that. Even just getting people those medicines is hard, and it has been made even harder with the disrupted supply chains associated with COVID.

We also haven’t had really good diagnostics to identify which particular strain of TB people had, so that it could be determined which drug regimens were best. In the past we’ve given people poorly matched therapy, which can make a quasi-resistant strain of TB even more drug-resistant.

If we had a better vaccine, that could be a game changer. There is a vaccine called BCG (Bacillus Calmette-Guérin) that’s often given to babies on the first day of their lives in many parts of the world where TB is common. It protects babies against TB meningitis, but it doesn’t protect adults against respiratory TB. We don’t know yet exactly how to develop a better vaccine for TB, so that’s a big scientific challenge.

There are also major political challenges. Because of COVID, we now understand what is possible if the world is committed to addressing an infectious disease. And I think we also now understand what the world has not been willing to do for TB patients.

Q: How is TB research faring?

A: It’s both “glass half full” and “glass half empty.” The TB field is actually cutting-edge for thinking about applying new immunologic, bacteriologic, and implementation approaches in terms of trying to address core needs in the field. Still, the investment in TB is roughly 1/100th of the investment in HIV and one iota of the current investment in COVID. I think we’re doing great with what we’ve got, but if we want to solve the problem, the world needs to do more.

In my lab, we’re trying to figure out how to make treatments more effective. One discovery I’m very excited about is that we’ve identified a new form of antibiotic resistance in TB, and genetic markers for that resistance. With this new ability to identify drug-resistant TB variants, we should be able to tailor treatment for patients to improve outcomes.

I am excited for the future. Although the COVID moment has been terrible for the world, it has also reminded us what is possible with collective action. And I hope that we retain even just a sliver of that sense of shared commitment and the potential for scientific advancement that really does impact people’s lives, and that we increase the ambition with which we approach TB other big global health problems.

Karen Feldscher