The Current Landscape and Future Directions of TB

At the 2025 ESCMID Global Congress in Vienna, OUCRU Director Guy Thwaites presented a compelling overview of the TB landscape and the need for transformational change in research, diagnostics, and treatment to meet the World Health Organization's (WHO) End TB goals.

Despite years of effort and innovation, TB remains the world’s leading infectious disease killer, having retaken this position from COVID-19. According to the WHO's 2024 report, 10.8 million people were infected in 2023, with 1.25 million deaths. Dishearteningly, TB-related mortality has shown little reduction in recent years, highlighting the limits of existing control measures and the urgent need for better tools and strategies.

The WHO’s 2015 End TB Strategy aimed for a 90% reduction in TB deaths and a 10% yearly drop in incidence by 2035. However, current trends show only a 1.5% annual decline in incidence. This stark shortfall is attributed largely to outdated tools. For instance, diagnostic and vaccine technologies—like the BCG vaccine and the Mantoux skin test—have remained unchanged for decades and are less effective against modern TB challenges, particularly drug-resistant strains.

Poverty also plays a pivotal role in the spread and persistence of TB. Low-income countries continue to bear the heaviest burden, often due to poor healthcare infrastructure, underfunded TB programs, and broader socio-economic inequalities. Although TB is known to be a disease of poverty, global research funding has remained nearly stagnant since 2015, despite the scale of the crisis.

Amidst this difficult backdrop, promising developments offer renewed hope. One of the most anticipated breakthroughs is GSK’s M72/AS01E vaccine, which showed strong efficacy in a Phase II trial and is now being tested in a large Phase III trial involving over 20,000 participants. If successful, this vaccine could provide a much-needed boost to TB prevention, especially in high-risk regions.

Diagnostic innovations have also advanced significantly. Molecular tests like Xpert MTB/RIF and its improved version, Xpert Ultra, offer rapid and more accurate TB detection. However, they remain underutilized globally, with only around 50% of diagnoses relying on WHO-recommended methods. Meanwhile, immunological tests like QuantiFERON and T-SPOT offer enhanced specificity, but even these fail to capture the complexity of TB infection, which may range from latent to subclinical stages rather than a simple binary model.

Research is also uncovering deeper layers of TB pathology. A study using PET/CT imaging showed high rates of subclinical TB that often progressed to active disease, supporting the need for a new diagnostic framework that reflects TB’s complex biology. In parallel, genetic sequencing technologies are enhancing our ability to detect drug resistance and tailor treatments, though cost remains a major barrier for many countries.

Treatment options are evolving rapidly. New regimens, such as the all-oral BPaL (bedaquiline, pretomanid, and linezolid) combination, have dramatically improved outcomes for drug-resistant TB. Shorter regimens for drug-sensitive TB, including 4-month and even 8-week treatments, are also being tested with promising results. These advances could transform patient experiences, reduce costs, and improve adherence—if drug resistance doesn't outpace progress.

The rise of resistance to newer drugs like bedaquiline is an urgent concern. Increasing cases of resistance threaten to undermine gains in treating multidrug- and extensively drug-resistant TB. In response, the UNITE4TB initiative is accelerating research into new drugs and therapeutic targets. With a growing pipeline of candidates and new drug classes in development, the TB treatment landscape is on the brink of significant change.

Looking forward, Thwaites advocated for a new model of TB research that centers local leadership, cuts bureaucracy, and fosters innovation within high-burden countries. Instead of top-down, externally led trials, future research must empower national TB programs and build sustainable, context-specific capacity. While challenges remain, the momentum around vaccines, diagnostics, and treatments offers genuine hope. According to Thwaites, the sun is not setting but rising on TB research—and with coordinated global effort, ending TB is still an achievable goal. 

Source: Wright K. Tackling Tuberculosis: The Current Landscape and Future Directions. EMJ Microbiol Infect Dis. 2025;6[1]:26-30.