Over the last 100 years, tuberculosis research has saved millions of lives but it has failed to curb the epidemic. While some recent scientific developments are promising, progress is slow, and the tuberculosis health crisis is escalating. Here’s what you need to know.
Tuberculosis (TB) is a curable and preventable infectious disease. And yet, 10.6 million people fell ill with tuberculosis and 1.3 million people died from it in 2022.
The only infectious disease to cause more deaths in recent years was Covid-19, in 2021 and 2022.
The two diseases have other similarities too. Tuberculosis is also spread through the air, it mainly affects the lungs, and common symptoms include coughing, fever and fatigue. However, unlike Covid-19, research into vaccines, treatments and diagnostics for tuberculosis has been neglected for years.
And now, after years of decline, the number of people developing tuberculosis is on the rise.
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In this explainer video, featuring Professor Willem Hanekom and Professor Henry Mwandumba, we dive deeper into the reasons behind the current TB health crisis – and what's needed to bring an end to the deadly disease.
Narrator: Over 100 years ago, scientists developed the first and only vaccine for tuberculosis. We have tests to diagnose it, and drugs that can cure it. But even with all this, why is TB still the deadliest infectious disease?
Over 10 million people fall ill with tuberculosis, or TB for short, every year. About 1 in every 25 cases will be a drug-resistant strain of the disease, making it especially difficult, if not impossible, to treat and cure.
In 2022, 1.3 million people died from TB.
Let's put this in context. TB is the number one deadliest infectious disease. It kills more people than malaria and HIV combined. And although Covid-19 briefly took the top spot for a few years, TB has once again reclaimed its deadly title.
Rewind several years, and TB deaths were actually declining. Progress was slow, but steady. Fast forward to 2020, and you'll spot a sudden change. As the Covid-19 pandemic took hold, TB control programs around the world were disrupted, reversing years of hard-won progress. Deaths and cases started to rise again.
However, the fight against TB was struggling long before Covid-19 hit. To really understand this issue, we need to go further back. Back an entire century.
A hundred years ago, the Bacille Calmette-Guérin vaccine, commonly shortened to BCG, was invented. It played, and still plays, an important role in protecting children from the most deadly forms of TB. But for anyone older, the protection is limited.
That's particularly important to note, because 9 in 10 cases worldwide are in adults and adolescents, not children.
Professor Willem Hanekom: Virtually every new born baby all over the world, or at least in lower- and middle-income countries, are receiving this vaccine very very soon after birth.
Narrator: That's Professor Willem Hanekom, by the way.
Professor Willem Hanekom: Now, adolescents and adults are really the people that spread TB. They have a different kind of TB from childhood TB, and where they've got lots of bugs around and they cough them out and spread the TB in the communities.
Narrator: It's clear the world would benefit from a new TB vaccine.
Luckily, TB is curable. The problem is, millions of people still go untreated. Either because they don't have access to treatments, or they don't know they're infected in the first place.
In some of the worst affected countries, less than half will receive the drugs they need to get well again. And even when there is access to treatment, there's an issue with completion rates — risking further infections.
Here's Professor Henry Mwandumba, to explain some more.
Professor Henry Mwandumba: The minimum duration of treatment that one can have is six months. I mean, if you ask somebody to take TB drugs for six months every single day – it is quite a big ask. But the fact that you're asking the patients to come back to clinic time and time again during the course of treatment – not everybody has the means to get back to clinic to get medications.
Narrator: In 2022, the number of people officially diagnosed with TB reached a record-breaking high of 7.5 million. That's roughly the entire population of Hong Kong or New York City.
Although this is a worryingly high number, it does suggest our global diagnosis systems are recovering after Covid-19-related disruptions.
Despite these likely diagnosis improvements, over 3 million people are missed every year. You might have noticed researchers calling these ‘the missing millions’.
Multiple innovations over the decades have worked to improve diagnosis rates, tackle multidrug-resistant strains, and reduce treatment lengths.
Though, access to these new interventions is still limited in many of the most deeply affected areas, 80% of cases and deaths are in low- to middle-income countries and, right now, the highest numbers of new cases are in South East Asia and Africa.
So, thanks to a deadly combination of patchy diagnosis, unequal access to treatment, and increasingly common drug-resistant strains, TB continues to kill millions year after year.
We need new ideas, fast.
Professor Henry Mwandumba: If you were to talk about multi-drug-resistant TB, then there's specific regions of the world that are hotspots for that. South America, for example. Peru had a big problem. But what we learned from that experience is how we can engage communities in the management of drug-resistant TB. And how we can manage patients with drug-resistant TB at home and not in the hospital setting.
Narrator: Over the last few years, money put into TB services actually decreased: we have just half of what's needed.
And whilst research investment has been increasing slowly, it’s still well below the USD 5 billion goal set by the United Nations.
The result? More of what's happening right now: Higher levels of TB, increasing drug resistance, inadequate solutions.
It's also worth mentioning that around the first year of the Covid-19 pandemic, the world funnelled at least USD 104 billion into developing Covid-19 vaccines and therapeutics. That huge number is 162 times more than governments spent on TB research in 2020, despite both being the top two most deadly infectious diseases.
Now, some positive updates. The Covid-19 pandemic actually reinforced a need for collaboration and a focus to end TB.
Back in January 2023, the WHO accounced plans to use lessons from the Covid-19 response to set up a new council for TB vaccines.
At the 2023 UN General Assembly, world leaders approved new targets to help end the TB epidemic.
Naomi Wanjiru: So many commitments have been done today to ensure that TB is on top of the agenda and that, one day, we shall end TB.
Narrator: And, after a hundred long years, there’s finally been breakthroughs in new vaccine development.
While this progress is reassuring, there's big challenges ahead.
The pace of innovation just hasn't been fast enough. We still need to find ways to secure funding and close the gap, invest in more research, as well as keep pushing for affordable, accessible, equitable solutions.
Only then, will we move closer to a future without TB.
There is only one licensed vaccine for tuberculosis: the Bacille Calmette-Guérin (BCG) vaccine.
It was invented over 100 years ago, and while it has saved millions of lives since, it has limitations. The BCG vaccine provides protection against the most severe forms of tuberculosis in children but offers variable and limited protection for adolescents and adults.
And although tuberculosis can be cured with a combination of antibiotics, until recently, the standard course of drugs took six to nine months to complete, and treatment for drug-resistant tuberculosis took up to two years with much lower chances of cure.
New treatment options have become available in the last ten years to help reduce treatment lengths, remove toxic drugs from regimens and tackle the growing tide of multi-drug-resistant tuberculosis. However, access to these drugs in many of the most deeply affected countries is still challenging.
Diagnosis rates are also low. Of the 10.6 million people estimated to have developed active tuberculosis in 2022, around 3 million were undiagnosed or unreported.
Meanwhile, drug-resistant tuberculosis poses a persistent and deadly threat to global health security. In 2022 alone, over 400,000 cases occurred worldwide, with diagnosis and treatment of drug-resistant tuberculosis falling well short of global targets.
So, despite being declared a global public health emergency 30 years ago, the world still faces high disease prevalence, increasing drug resistance and inadequate resources to limit further spread.
The pace of tuberculosis innovation has not matched this need – with insufficient political interest and financial investment contributing to the slow progress of research and development.
Developing new tools to tackle this epidemic would save millions of lives. But first, we need to transform research and development for tuberculosis.
Although funding for research into new tuberculosis vaccines, treatments and diagnostic tools has been slowly increasing, it still falls well below the estimated US$5 billion needed every year to reach global targets to end TB by 2030.
Private sector financing has been persistently low because tuberculosis primarily impacts low- and middle-income countries – accounting for over 80% of all cases. Tuberculosis products are not expected to secure sufficient return on investment, and as a result, industry sources only make up about 10% of the overall investment.
Vaccine development has particularly suffered. While governments spent around $90 billion on research for the Covid-19 vaccine in the first year of the pandemic, the total spent on developing a new tuberculosis vaccine is a fraction of that – just $1.1 billion in the last 11 years [PDF].
Even as newer products have been approved, these have not been equitably available as high prices have limited access to some of the communities that need them most.
After almost 50 years of limited innovation, the last decade has shown the life-saving potential if we can reinvigorate the field and ensure equitable access to new products.
For example, safer, quicker and more effective oral treatments have replaced painful injectable drugs with toxic side effects, and other new, promising drug candidates are in development.
There have also been breakthroughs in the development of new tuberculosis vaccines. Like the M72 vaccine candidate, which showed around 50% efficacy results in the phase 2b study and entered phase 3 trials in March 2024. If approved, this could prevent up to 30 million cases by 2050.
Wellcome is investing in tuberculosis research and development, focussing on the countries that are most impacted by the disease.
We want to make sure that new vaccines to tackle all forms of tuberculosis are developed in a way that ensures the products are accessible and affordable to the people who need them most, and with the urgency that the devastating health crisis in these communities demands.
The world needs a new vaccine to fight tuberculosis (TB). A new multimillion-pound global study funded by Wellcome and the Bill & Melinda Gates Foundation could provide a solution.
Our infectious disease programme focuses on intervening earlier with better products and tools. Our work in tuberculosis will do just that by transforming the research and development ecosystem to prioritise public health and ensure accessibility and availability for all.
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