Scientific advances and the end of tuberculosis

Reid, M., Agbassi, Y.J.P., Arinaminpathy, N., Bercasio, A., Bhargava, A., Bhargava, M., Bloom, A., Cattamanchi, A., Chaisson, R., Chin, D. and Churchyard, G., 2023. Scientific advances and the end of tuberculosis: a report from the Lancet Commission on Tuberculosis. The Lancet, 402(10411), pp.1473-1498.

Progress toward ending tuberculosis varies greatly across countries, with some achieving substantial improvements and others making minimal progress. Key challenges include frail health systems, underinvestment, and reliance on one-size-fits-all approaches. Insufficient case finding and diagnosis remain the most significant issues in high-burden countries, where only 38% of all tuberculosis cases were tested with WHO-recommended rapid molecular diagnostics in 2021.

Two-thirds of tuberculosis deaths occurred in just eight countries, with over half of these in India, Indonesia, and Nigeria. Despite these challenges, some sub-Saharan African countries have seen improvements in tuberculosis mortality rates, showing that rapid declines are possible even with existing tools.

Adoption of new technologies, such as the Cepheid Xpert, has been slow due to regulatory, pricing, and infrastructure barriers. Less invasive tests like tongue swabs and urine-based antigen tests show promise but are not yet widely used. Better screening tools are crucial for detecting subclinical tuberculosis, which may drive transmission.

Digital health tools and computer-assisted chest x-ray reading are being explored to enhance case finding. To improve diagnosis, countries must align diagnostic investments with care-seeking behavior and integrate new tools into primary care. Oral swabs and urine LAM tests could expand testing in decentralized settings, while handheld x-rays combined with AI could aid in screening asymptomatic, high-risk populations.

Funders like the Global Fund and USAID are key to scaling up diagnostics in underserved areas. In 2021, private healthcare providers in the seven highest-burden countries diagnosed 1.2 million tuberculosis patients, representing 32% of total notified cases. While diagnostic advancements are critical, achieving the Sustainable Development Goals (SDGs) requires better treatment and prevention tools. Recent advances have reduced treatment duration for drug-susceptible tuberculosis to 4 months and for multidrug-resistant tuberculosis to 6 months, improving adherence, outcomes, and reducing healthcare demands.

In 2022, WHO and the CDC endorsed the 4-month 4HPMZ regimen for drug-susceptible tuberculosis, though it has not been widely adopted. The 2023 TRUNCATE-TB trial supports a 2-month treatment option for multidrug-resistant tuberculosis, but high drug costs, particularly for bedaquiline, remain a barrier.

Economic considerations will likely influence the adoption of new regimens in low-resource settings. Substantial investments in tuberculosis preventive treatment (TPT) are needed to reduce incidence. Shorter TPT regimens, like 3HP and 1HP, show promise, but rifapentine’s lack of registration in many countries hinders their adoption.

The BCG vaccine remains the only licensed tuberculosis vaccine, but introducing new vaccines could significantly reduce treatment costs. Addressing social determinants, such as migration, air pollution, and food insecurity, is crucial as these factors are likely to increase tuberculosis risk.

Since 2009, undernutrition has been recognized as the leading risk factor for tuberculosis. Nutritional support for tuberculosis patients and their households could reduce mortality and incidence. The Copenhagen Consensus estimates that every dollar invested in tuberculosis programs could generate $46 in societal benefits. However, some high-burden countries require support to address unsustainable debt burdens, which could divert resources from tuberculosis and other health programs.

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Furin, J., Cox, H., & Pai, M. (2019). Tuberculosis. Lancet (London, England), 393(10181), 1642–1656.

Global Impact: Tuberculosis (TB) remains the leading infectious cause of death among adults, with over 10 million new cases annually.

Advances in Diagnostics: Rapid molecular testing (e.g., Xpert MTB/RIF) and whole-genome sequencing are improving TB diagnosis and drug resistance detection, though simple point-of-care tests are still lacking.

Treatment of Drug-Susceptible TB: Treatment for drug-susceptible TB remains unchanged, using a standard 6-month regimen of isoniazid, rifampicin, pyrazinamide, and ethambutol.

Drug-Resistant TB Treatment: New drugs (bedaquiline, delamanid) and all-oral regimens have transformed drug-resistant TB care, shortening treatment duration and improving outcomes.

Socioeconomic Factors: Poverty, overcrowding, and poor living conditions are key drivers of TB, perpetuating its high incidence among low-income populations.

Prevention: The BCG vaccine offers protection to children but is less effective for adults. New vaccines and shorter, effective latent TB treatments are under development.

Patient-Centered Care: WHO emphasizes people-centered TB care, including socioeconomic support like cash transfers, to improve outcomes and reduce treatment barriers.

Challenges and Future Needs: Despite technological advances, political commitment and high-quality healthcare access are critical for reducing TB morbidity, mortality, and stigma globally.