Tuberculosis today: Unraveling a paradox in modern healthcare

• Despite unprecedented scientific advancements in prevention, treatment, and diagnostics, tuberculosis remains the world's deadliest infectious disease 

• Geopolitical instability and population displacement have dramatically altered airborne transmission dynamics, bringing a resurgence of multidrug-resistant TB across Europe 

• Eliminating TB requires a swift shift towards non-sputum-based diagnostic approaches

When it comes to tuberculosis today, the world is witnessing a profound scientific contradiction in infectious disease management. In research laboratories, the battle against Mycobacterium tuberculosis has never been more sophisticated. In the real world, tuberculosis remains the world's deadliest infectious disease, claiming 1.23 million lives in 2024 alone, surpassing the combined casualties of malaria and HIV.^1,2

At this year’s International Roche Infectious Diseases Virtual Science Talks (IRIDS) 2026, held to commemorate World Tuberculosis Day, Professor and Doctor Christoph Lange, Medical Director of the Research Center Borstel, Leibniz Lung Center in Borstel, Germany, delivered a sweeping overview of where the global fight against tuberculosis stands and what actions can be taken to overcome this devastating disease.

In the clinical therapeutics pipeline, there are 20 new drug candidates moving through development phases and 18 vaccine candidates under active evaluation.^1,2 Complex platform trials, such as the EU-funded Paradigm 4TB initiative, are evaluating 12 different drug regimens simultaneously to establish new standards of care.¹ According to Prof. Lange, it is not known “whether in any other field of infectious diseases or medicine a platform trial having 12 arms in parallel has ever been evaluated. Probably this is now unique for tuberculosis.”

Concurrently, there is a very good track record in reducing the duration of preventive treatment for individuals who test positive on IGRA or a skin test, and who are at risk for future development of tuberculosis (TB).³ For instance, while the official recommendation in 1965 still required 12 to 18 months of isoniazid monotherapy, by 2020 the standard had successfully evolved to just a single month of combined isoniazid and rifapentine.³

Yet despite the push for new medicines, vaccines, and diagnostics, the reality is that global health systems are not making enough progress in implementing available technologies to prevent or treat this disease.² The vaccine currently used in most settings is more than 100 years old and, although 88% of newborns receive it, its efficacy is drastically limited.⁴ It only protects children up to the age of 5 years, and adult revaccination does not prevent the development of TB.^5,6

While there are candidates in the vaccine pipeline, a major breakthrough remains out of reach, with the most promising option demonstrating just 50% protection.^7,8 “This vaccine may be a game changer, although it is not leading to the elimination of tuberculosis, because 50% is not enough,” affirms Prof. Lange.

In fact, Prof. Lange explains that "We are actually at the peak of the TB epidemic in absolute numbers." According to the World Health Organization (WHO), approximately 25% of the world's population may carry a latent TB infection—effectively 10.7 million new active cases each year.² In addition, large numbers of individuals who suffer from TB are asymptomatic, and around a quarter of those who have the detection of Mycobacterium tuberculosis by PCR or culture from sputum are considered contagious.⁹ “This new finding over a large proportion of asymptomatic TB individuals has consequences for TB control in high-burden settings,” says Prof. Lange. Longitudinal data from the WHO confirms the sharp upward trajectory, with global incidence rising from 10.1 million in 2022 to over 10.7 million by 2024.^2,10

Unfortunately, children account for 11% of global active cases of TB—a population in which microbiological confirmation remains particularly difficult.²  Moreover, 5.8 % of those affected have an active HIV co-infection, a comorbidity that has improved over the past decade thanks entirely to the scale-up of HIV antiretroviral therapy rather than improved TB control.¹⁰

It should also be noted that a single nation, India, bears 25% of the total global disease burden.² Thus, as Prof. Lange points out, "any solution for tuberculosis that does not have India in its aim will not work on a global level." For Prof. Lange, any broad eradication framework must prioritize localized intervention in high-burden countries to achieve meaningful international results.²

Systemic resource imbalances leave healthcare networks highly vulnerable to sudden social, geopolitical, and environmental changes that can alter the aerosol transmission dynamics of TB.²

Geopolitical instability is driving a resurgence of TB in regions that had previously achieved low-incidence status.² Between 2010 and 2020, Ukraine successfully reduced its TB burden through targeted public health infrastructure.² However, beginning in 2022 as a result of the war, there has been an acceleration of airborne transmission due to displaced civilian populations crowding into poorly ventilated underground shelters and metro stations.² Within two short years, the incidence of TB in Ukraine has spiked back up from 71 to 112 cases per 100,000, reversing a decade of public health victories.^2,11

This regional destabilization also directly impacts cross-border health security. Displaced populations have reshaped the European epidemiological map, with Ukrainian individuals now accounting for 50 percent of all multidrug-resistant (MDR-TB) notifications across the European Union.¹² This influx complicates regional care pathways, particularly as migration remains a primary clinical vector for TB. Within the EU, 30% of all reported cases occur in individuals born outside the union.¹³ The risk for migrant cohorts to present with TB-HIV co-infection, and MDR-TB is significantly higher, and elevates the statistical risk for unfavorable treatment outcomes.¹⁴

According to Prof. Lange, in order to disrupt TB transmission chains, clinical workflows must pivot toward decentralized testing.² The traditional diagnostic paradigm relies heavily on sputum collection, and this methodology creates a significant bottleneck.² Sputum collection is frequently unfeasible in pediatric cohorts and in patients with advanced HIV co-infection.² In the case of HIV-positive patients, HIV-induced immunosuppression often presents as paucibacillary lung disease or extrapulmonary TB, and conventional sputum smears frequently return false negatives. This leaves a significant portion of active cases completely undetected by standard surveillance mechanisms.² Such a diagnostic gap directly compromises HIV healthcare investments, as the large majority of active TB patients remain completely asymptomatic, displaying neither fever nor cough during active transmission phases.⁹

Decentralized molecular diagnostics go a long way in removing these barriers.² Rapid, non-invasive tongue and buccal swabs capture mycobacterial DNA via PCR without requiring sputum production.¹⁵ For pediatric care, stool-based PCR testing offers a critical alternative, achieving a 70 percent sensitivity rate in small children.¹⁶ Prof. Lange further explained that "all the small children who are not able to produce any sputum—they all have stool. It is amazing that from this very dense ecological environment, the TB DNA can be extracted, amplified, and drug susceptibility even predicted.” Shifting to battery-operable, near point of care (nPOC) molecular platforms allows health systems to move highly sensitive diagnostic assets out of centralized laboratories and directly into peripheral clinics, refugee stations, and mobile health units.²

The world is currently managing TB with an uncoordinated strategy. Historical epidemiological data confirms that nations like Denmark brought their TB incidence down from 600 to 50 per 100,000 before modern antimicrobial therapy existed, by focusing entirely on the optimization of socio-structural conditions, targeted nutrition, and diagnostic mobilization.^17,18 Prof. Lange affirms that “we have the highest number of vaccines for TB prevention in the pipeline. We have a large number of diagnostic tests close to the clinic. We have 20 new TB medicines in clinical evaluation. Implementation is the problem.” That implementation, in Prof. Lange’s opinion, begins with using the right tools to successfully manage this deadly epidemic. In that sense, molecular diagnostics are the linchpin of this effort, bridging the gap between cutting-edge science and the frontline medical reality on the ground.¹³