In the US and UK, tuberculosis (TB) is a disease most people only encounter in history class. It is taught alongside the cholera epidemics of the 19th century, the Black Death, and the Spanish flu pandemic. It’s considered a disease of the past.
However, TB is still a major threat in large parts of the world. Someone living in Lesotho, the Central African Republic, or Gabon is at least 3,000 times more likely to die from TB than someone in the US or Denmark. In 2023, 1.25 million people died from the disease, which meant that TB reclaimed its place as the world’s deadliest infectious disease after three years of COVID-19.
How do we currently treat TB?
Most people who develop an active infection can be treated and cured with first-line drugs. In these cases, the infecting strain of Mycobacterium tuberculosis can be killed or controlled with standard antibiotics that have been used for more than 50 years. Treatment typically lasts six to 12 months and costs between $30 and $150 per person.
However, this approach doesn’t work for around 700,000 patients. Drug-resistant TB comes in two forms: multidrug-resistant TB (MDR-TB), which does not respond to the two main first-line drugs, rifampicin and isoniazid, and extensively drug-resistant TB (XDR-TB), which is resistant even to second-line treatments. In 2024, only two in five people with MDR-TB received the recommended treatment, and of those, just 68 percent were successfully cured.
The World Health Organization (WHO) treatment guidelines recommend a six-month oral regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) for MDR-TB. However, this process is far more expensive than standard drugs, costing thousands instead of hundreds of dollars. This is prohibitively expensive for many people and governments in high-burden areas.
Treatment is getting cheaper
To improve access, the Stop TB Partnership’s Global Drug Facility (GDF) announced a 30 percent price reduction for bedaquiline in September, lowering the cost per treatment course to just $63. This brings the full BPaLM regimen below $300 for the first time, now priced at $284 per course.
The price cut is expected to generate over $4.5 million in annual savings for GDF clients and high-burden countries, enabling the purchase of 71,000 additional bedaquiline courses or 16,000 full BPaLM regimens each year. This follows two earlier price reductions in 2025: a 54 percent cut for bedaquiline in February and a 25 percent reduction for pretomanid in April. In total, six WHO-recommended drug-resistant TB regimens now cost under $300.
Health systems are resilient because they have to be — but ultimately it’s the people who most urgently need care who suffer when funding disappears.
- Eve Worrall, Liverpool School of Tropical Medicine
While the recent price cuts will expand access, experts warn that drug prices are only one part of the cost of TB treatment. As Eve Worrall, health economist at the Liverpool School of Tropical Medicine (LSTM), explained to DDN, “any reduction in drug price is welcome and will help countries provide more services. However, drug costs are not the only cost that health systems have to cover to provide adequate TB care.”
Many high-burden countries are already under strain, and recent cuts in international funding are making it harder to maintain TB services. Worrall emphasized that, “Health systems are resilient because they have to be — but ultimately it’s the people who most urgently need care who suffer when funding disappears.”
A vaccine is still the ultimate solution
In the end, prevention is always better than treatment, and an effective vaccine is fundamental to achieving global TB control. As early as 1921, decades before the development of antibiotic treatments, the Bacillus Calmette-Guérin (BCG) vaccine was developed, protecting infants and young children from severe TB.
However, while the BCG vaccine typically reduces the risk of severe tuberculosis by around 70–80 percent in young children, its overall efficacy is highly variable. Controlled trials conducted in different regions have shown protection against pulmonary TB ranging anywhere from zero to 80 percent, with the lowest efficacy observed in areas where the disease is most endemic. This variability is likely influenced by several factors, including differences in circulating TB strains, environmental exposure to other mycobacteria, and variations in host immune response.
Why hasn’t there been a new vaccine in over 100 years?
Mycobacteria are complex organisms, able to evade immune responses and induce immune cellular senescence to create an inflammatory environment that allows the pathogen to persist, causing latent infection.
- Ben Morton, Liverpool School of Tropical Medicine
TB is a hard disease to vaccinate against. This is partly because in most people it infects, the bacteria remain latent — causing no symptoms and leaving them noncontagious.
Ben Morton, a clinical infectious disease researcher and translational scientist at LSTM, told DDN, “Mycobacteria are complex organisms, able to evade immune responses and induce immune cellular senescence to create an inflammatory environment that allows the pathogen to persist, causing latent infection.”
The population of people carrying around latent TB infections is truly massive. A recent study compiling blood test estimates found that about 24 percent of people on Earth have TB, with rates ranging from 12–14 percent in Europe and the Americas to over a third in Africa and Southeast Asia. Of those with latent infections, around five to 15 percent will eventually develop active, contagious TB.
Morton noted that the complexity of the immune response, combined with sub-optimal animal models and the lack of a reliable correlate of protection — a measurable immune response that predicts whether a vaccine will work — makes it challenging to select promising pre-clinical vaccine candidates. He also emphasized that conducting field studies is complicated, particularly due to difficulties in diagnosing and clearing TB in study participants.
These challenges make TB vaccine development especially difficult. In theory, a successful vaccine would both prevent people from becoming infected and stop existing latent infections from turning into active disease. But researchers still don’t know exactly what kind of immune response provides protection against TB. Without this benchmark, scientists have to rely on large, costly, and time-consuming clinical trials to find out whether a vaccine truly works.
To overcome these challenges, Morton and his team at LSTM are developing a TB human challenge model, in which healthy volunteers are deliberately exposed to a safe form of TB bacteria. Using the live BCG vaccine as the challenge agent, volunteers receive an intradermal injection, and skin biopsies taken two weeks later allow researchers to track bacterial growth and immune responses. The team is also testing less invasive monitoring methods and developing a fluorescent BCG strain for real-time tracking.
By requiring fewer participants than conventional clinical trials and reducing the time needed to test a candidate, this approach improves the economic feasibility of vaccine development. Developed with the LSTM Accelerator Research Centre, University of Oxford, and the Malawi Liverpool Wellcome Trust, the model will be adapted for high-burden settings like Malawi, offering a faster, more reliable path to identify the most promising vaccines and treatments for difficult-to-vaccinate diseases like TB.
A new vaccine on the horizon
Reaching the WHO’s End TB Strategy goals of a 95 percent reduction in TB deaths and a 90 percent reduction in new infections worldwide by 2035 requires a new, broadly effective vaccine. This vaccine would need to protect adolescents and adults, the groups at highest risk of TB, while also safeguarding young children. Vaccines also offer the best long-term hope of controlling the rapid rise of MDR-TB.
One of the most promising candidates is M72/AS01E, now in a landmark Phase 3 clinical trial sponsored by the Gates Medical Research Institute and funded by the Bill & Melinda Gates Foundation and the Wellcome Trust. The trial includes sites across four African countries and Indonesia. Originally developed by GSK in collaboration with Aeras Technologies and the International AIDS Vaccine Initiative, M72 could become the first new TB vaccine in more than a century, and the first ever to protect adults and adolescents.
The M72 trial has enrolled 20,000 participants and is still in its early stages, but its prior results are encouraging. In a 2019 study, M72 demonstrated nearly 50 percent efficacy over three years in preventing TB-infected adults from developing active, contagious disease. “We haven’t had results like that since basically BCG,” said Lee Fairlie, Director of Maternal and Child Health at Wits Reproductive Health and HIV Institute and one of the lead investigators, in a press release.
A separate Phase 2 study published this August also found that M72 had an acceptable safety profile and generated strong immune responses in people living with human immunodeficiency virus (HIV). This is important as people living with HIV are among the most vulnerable to TB, and vaccines often show reduced efficacy in this group. Demonstrating both safety and strong immune responses suggests that M72 could protect even those at highest risk.
If M72 performs similarly in its Phase 3 trial and wins regulatory approval, it could transform global TB control. WHO estimates suggest that widespread vaccination could prevent 76 million new TB cases over the next 25 years, potentially ending TB’s reign as the world’s deadliest infectious disease.
