WATCH: The only tuberculosis vaccine is a century old. New innovations are around the corner.

Tuberculosis (TB) is an ancient disease that has proven intractable even in recent decades—but that may be about to change. Watch as Puneet Dewan, senior program officer at the Gates Foundation, reveals some of the most exciting innovations in the R&D pipeline that could transform life for people with TB.

Each year, about 1.6 million people die from TB. That’s even more deaths than from HIV and malaria combined. A disproportionate number of those people live in low- and middle-income countries. There’s only one vaccine for TB, and it’s over 100 years old.

Progress against TB has been slow. But now the world is poised to turn the tide in this fight, thanks to new innovations that may dramatically transform how TB is detected, treated, and prevented.

Our foundation supports R&D partners in the public and private sectors that are working to develop next-generation tools for TB. But turning innovations with potential into impact for people affected by this disease will require political commitment and resources.

Puneet Dewan: (In progress) – 3,000 pills over two years with six months of daily injections. I mean, just hell. Okay? And it will only work three quarters of the time, if you took all your meds.

I’m a medical epidemiologist. I’m an internal medicine doctor by training. When I was a medical student, I actually went to go to India. I was in the pediatrics’ ward. And then every day, this kid would be brought in, and he would have a towel over his head. We called that the towel sign at the time. You kind of had to hold something because you knew as soon as they took the towel off, there’d be this giant, swollen head on this little, tiny baby.

And that was actually tuberculous meningitis, and it happened every day, multiple times, day after day. And that was when I realized that, oh, my gosh, that people are actually genuinely suffering from this disease that was nonexistent in my training: tuberculosis. And then to learn that it was eminently treatable was sort of like, this is just wrong, and I actually pivoted my career to focus on public health, specifically to stop brown people from dying of TB.

Part of the reason why TB has been such a persistent problem has been we’ve been trying to get rid of it with really bad tools. We’ve had to rely on a 100-year-old diagnostic test, but it’s not very good. Now there is actually a genuine pipeline. There are several new diagnostics, much lower cost than today’s tests, that would provide the result on the spot to someone wherever they are, even at the lowest point of care.

There’s treatment that’s going to move from six months of a large handful of pills to hopefully two months. There are at least seven drugs in the pipeline in advanced clinical trials, which can be combined into new potent combinations, and that’s fantastic. Some of the vaccine candidates in the pipeline, there are some early signals of possible partial efficacy, which hasn’t happened yet to date with TB vaccines, can actually be deployed in adults and even adults and adolescents so that we can prevent TB from ever happening by boosting people’s immunity. That would be awesome.

And again, like the world had always said that even if you had a vaccine, it wouldn’t matter because you couldn’t vaccinate the world’s population for an infectious disease, right? Again, disproven: COVID. Now we know that if we could come up with a vaccine, there is a mechanism that can actually bring it to people who need it fast. That just kind of redoubles the reasons to find one.

I think that’s the medium term vision in the next sort of three to five years that is genuinely achievable for earlier detection in clinic and even community-based detection, linked to a much simpler treatment.

The most exciting thing is probably point of care molecular testing. That’s really huge. That’s that first step to be able to have it available, instead of being at the 15% to 30% of places where you might visit that, have diagnostic access to TB services. Can it get to the point where it’s as simple as a pregnancy test, where it might be available in the majority of clinical settings? I think that’s probably the thing that’s first, coming first through the pipeline, and we expect to see submissions to WHO for approvals, and validation of data and approvals next year.

The other thing that’s super important right now is the BPaL regimen, so-called for MDR TB treatment. MDR TB treatment for those who have rifampicin resistant TB, regular treatment won’t work, and you need more drugs. Previously, injections, super costly, 3,000 pills over two years, with six months of daily injections. I mean, just hell, okay? And it will only work three-quarters time, if you took all your meds.

Now you’ve got a handful of pills a day for six months. Equivalent, a little harder, but equivalent to standard treatment that could be even decentralized out to regular clinics. It’s like, oh, you’ve got TB. Is it this treatment, the treatment A box or the B box for your treatment? And if it’s MDR, now you get the B box. That’s now being rolled out globally with incredible enthusiasm and demand.

This is sort of the intermediate early dividend of all that drug development research is a much cheaper, easier MDR treatment regimen, and that’s going to really transform the lives of those hundreds of thousands of people who have drug resistant TB today. That’s happening now with enormous scale-up globally and that’s a direct outcome of the research and development investment towards that simple, shorter, safer regimen.

What keeps me going ultimately is seeing those systems change, seeing how a country moves from neglecting a disease to tackling it head on and making it a priority, seeing how much fewer children, for example, are actually getting things like TB meningitis, communities of TB survivors are mobilizing to counsel other communities of TB survivors, and actually taking on the responsibility for seeing that they sustain their treatment. Those are the things that really keep you going.