Tuberculosis: major progress, but far from a solved problem
TB remains the world’s leading infectious killer, and while shorter all-oral regimens (~6 months vs ~18-24 months for legacy regimens) have materially improved the treatment burden for drug-resistant disease, major unmet need remains in access, resistance surveillance and regimen optimization.
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an airborne bacterial infection that most commonly manifests as a respiratory infection, although it can also become disseminated and involve multiple organ systems. Despite being both preventable and curable, TB remains one of the world’s most serious infectious diseases. The World Health Organization (WHO) estimates that 10.7 million people developed TB in 2024 and 1.23 million died, including 150,000 people living with HIV. TB is the leading cause of death from a single infectious agent worldwide, a position it has arguably continuously held since the exacerbating urbanization and industrialization efforts of the 19th century. To note, there have been short periods of exception, such as the Spanish Flu (1918-1920) and COVID (2020-2022) pandemics.
The burden of disease remains concentrated in lower- and middle-income settings, especially across South-East Asia, the Western Pacific and Africa. According to the 2025 WHO Global Tuberculosis Report, these three regions accounted for 34%, 27% and 25% of global incident TB cases in 2024, respectively. TB also continues to exact a disproportionate toll in people living with HIV: WHO states that TB remains the leading cause of death in this population, accounting for an estimated 30% of AIDS-related deaths worldwide in 2019. That persistent overlap between TB and HIV underscores how it remains defining comorbidity in immunocompromised populations, even in the era of supportive antiretroviral therapy.
Drug-resistant TB has compounded this public health challenge by making treatment longer, more toxic and more operationally difficult. Historically, rifampicin-resistant and multidrug-resistant TB (RR/MDR-TB) was treated with complex regimens built around older second-line agents, often including injectable antibiotics and extending for 18-24 months. The WHO notes that the longest remaining MDR/RR-TB regimens still run 18-20 months and may include amikacin (aminoglycoside antibiotic) as a last-resort option. In addition to the high treatment burden, healthcare system utilization, and distribution-limiting cold chain requirements, these treatments are associated with poor safety and tolerability, including increase frequency of hearing loss, neuropathy and other irreversible adverse effects associated with historical second-line regimens.
Within the last two years, the treatment paradigm has shifted decisively toward shorter, all-oral regimens. WHO’s 2024 rapid communication first signaled a new 6-month regimen based on bedaquiline, delamanid and linezolid, combined with levofloxacin and/or clofazimine (or BDLLfxC). That change was formally consolidated on 15 April 2025, when WHO recommended BDLLfxC as a novel all-oral 6-month option for MDR/RR-TB, including patients with additional fluoroquinolone resistance. WHO’s implementation guidance notes that this regimen may be particularly useful where pretomanid, a relatively novel (FDA-approved in August 2019) and highly efficacious anti-mycobacterial agent, is unavailable or contraindicated, and that it can be used across broad patient groups. This includes children, adolescents, people living with HIV, and pregnant or breastfeeding women in defined clinical settings.
Recent advances have therefore meaningfully reduced patient burden, but the current landscape still leaves substantial room for improvement. Otsuka’s quabodepistat development program is explicitly targeting shorter, less toxic and better tolerated regimens for drug-resistant TB, illustrating that the innovation agenda has already moved toward further simplification. Meanwhile, recent commentary in high-impact journals such as The New England Journal of Medicine and The Lancet has warned that resistance to bedaquiline, linezolid and other core agents could threaten the durability of current regimens. The next phase of TB innovation will therefore need to focus not only on further reducing the treatment duration, but also on rapid detection of drug-susceptibility, better regimen selection per case, and resistance surveillance robust enough to protect the effectiveness of the new standard of care.
Accessibility remains a key issue: While the WHO describes MDR-TB as both a public health crisis and a health security threat, only about two in five people with drug-resistant TB accessed treatment in 2024. This was further exacerbated by the cold-chain requirements for some injectable components of legacy regimens, highly variable healthcare infrastructure in affected geographies, and the cost of newer, more efficacious medicines. In 2023, Johnson & Johnson announced that it would not enforce bedaquiline patents in 134 low- and middle-income countries, explicitly aiming to support high-quality generic supply. At the same time, TB Alliance reported in April 2025 that pretomanid pricing through the Global Drug Facility had fallen 25%, significantly lowering the cost of a full bedaquiline, pretomanid and linezolid with or without moxifloxacin (BPaL/M) treatment course. Despite these steps, there remains significant room for improvement in facilitating patient access, particularly set against the backdrop of reduced global health financing putting many already-vulnerable initiatives at risk: External health aid was projected to drop ~30-40% in 2025 vs 2023, prompting the WHO to issue new mitigating guidance.
Selected sources
- WHO TB fact sheet
- WHO Global Tuberculosis Report 2025: disease burden and incidence
- WHO TB and HIV page
- WHO rapid communication on drug-resistant TB treatment updates
- WHO announcement on revised DR-TB treatment guidance (15 April 2025)
- WHO TB Knowledge Sharing Platform guidance on BDLLfxC
- WHO overview of DR-TB treatment pathways and regimen durations
- Johnson & Johnson press release on bedaquiline patent non-enforcement in LMICs
- TB Alliance press release on pretomanid price reduction and BPaL/M access
- Otsuka press release on quabodepistat development in TB
- The Lancet commentary on injectable burden in drug-resistant TB
- NEJM commentary on modern DR-TB regimen durability and resistance risk
