Why Tuberculosis Still Spreads Despite Effective Preventive Treatment

Tuberculosis prevention has reached a paradox. Effective preventive regimens exist, diagnostic tools are improving and global targets are clear, yet millions of people at risk still fall through the cracks before protection begins. The key problem is no longer simply whether prevention works, but whether health systems can identify those at risk, start them on therapy, support them through completion and address the social conditions that keep transmission alive.

A new article Expanding the Frontiers of Tuberculosis Prevention: Moving from Targeted Preventive Therapy to Integrated Public Health Strategies, published in Tropical Medicine and Infectious Disease, advances this argument. Authored by Kannamkottapilly Chandrasekharan Prajitha, Anam Anil Alwani and Pruthu Thekkur of the Centre for Operational Research at the International Union Against Tuberculosis and Lung Disease, the viewpoint is based on studies from India, South Africa, Kazakhstan, Zimbabwe and Uganda to show why TB prevention must move beyond isolated clinical interventions and become an integrated public-health strategy.

The Prevention Gap Begins Before Treatment

For decades, TB programmes concentrated on finding people with active disease and treating them effectively. That approach saved lives, but it did not sufficiently interrupt transmission or reduce the enormous reservoir of people living with tuberculosis infection. The paper notes that roughly one-quarter of the global population may harbour TB infection, although only a fraction will progress to active disease. The challenge is identifying who is at greatest risk and reaching them before illness develops.

The stakes are particularly high in South-East Asia, the Western Pacific and Africa, which together account for 85% of global TB cases. The World Health Organization's End TB Strategy calls for a 90% reduction in incidence and a 95% reduction in mortality by 2035. Those goals cannot be met through treatment of active disease alone.

The evidence reviewed in the viewpoint shows that risk is distributed unevenly. Healthcare workers in high-burden settings face repeated occupational exposure; one prospective cohort in tertiary hospitals in India found TB infection prevalence of nearly 38%. Household contacts of people with pulmonary TB and people living with HIV also remain priority groups because of their elevated risk of infection or progression.

However, current diagnostic tools have limits. Tuberculin skin tests and interferon-gamma release assays can detect infection, but they cannot reliably predict which individuals will develop active TB. New antigen-based skin tests may improve specificity and operational convenience, but affordability, cold-chain requirements, repeat visits and integration into national guidelines will determine whether they are useful at scale.

Expanding testing without improving risk prediction may generate larger lists of infected people without giving programmes a clear basis for prioritising scarce treatment resources. Biomarkers and better tools for identifying subclinical TB could improve targeting in the future, but the paper is clear that immediate progress depends on making existing prevention systems function more consistently.

Effective Regimens Are Being Defeated by Weak Delivery

Tuberculosis preventive treatment is one of the strongest tools available to stop infection from progressing to disease. Shorter regimens, including one- and three-month options, can improve acceptability and completion compared with longer courses. But the evidence assembled in the paper shows that treatment effectiveness is being undermined by failures that occur before the first dose is taken.

Studies from Zimbabwe and Uganda reveal losses throughout the prevention cascade: contact identification, screening, exclusion of active disease, eligibility assessment and treatment initiation. Medicine stock-outs, documentation gaps, limited provider knowledge and weak follow-up repeatedly disrupt care. In several settings, completion was high among people who actually started treatment, suggesting that the largest breakdown may occur in connecting eligible individuals to therapy in the first place.

This finding changes how programmes should measure success. Reporting treatment completion alone can create a misleading picture if large numbers of people disappear earlier in the pathway. National TB systems need indicators for every stage of the cascade, from contact tracing to adherence and management of adverse events.

The viewpoint also underlines the value of integrating services. People living with HIV are among those at highest risk of progression to active TB, yet separate programmes, repeated visits and fragmented records can discourage uptake. Integrating preventive treatment into HIV and primary-care services could reduce duplication, simplify patient journeys and improve continuity.

Supply chains deserve equal attention. A short-course regimen is not truly available if procurement failures make it intermittent. Governments and development partners frequently focus on purchasing medicines, but programme performance also depends on forecasting demand, maintaining stocks, training providers and ensuring that facilities can document and monitor treatment.

The immediate lesson is practical rather than technological: countries can make major gains by strengthening systems that already exist. Better medicines and diagnostics matter, but their public-health value is limited when routine delivery remains unreliable.

Poverty, Stigma and Distance Are Part of the Transmission Chain

The paper insists that TB prevention cannot be reduced to a prescription. Poverty, undernutrition, overcrowding, diabetes, smoking, migration and poor access to healthcare shape who becomes infected, who progresses to disease and who reaches treatment in time. A mixed-methods study from South Africa found that people often followed complex routes before entering formal TB care, including seeking help from pharmacies and traditional healers. Transport costs, work obligations, stigma and financial pressure delayed diagnosis and treatment. These are not peripheral barriers; they are mechanisms through which transmission continues.

The evidence supports a broader definition of prevention. Social protection, nutritional support, safer housing and income security may reduce both vulnerability and the costs of accessing care. Employers can also play a role by allowing workers to attend appointments without losing wages and by improving infection control in workplaces.

For high-burden countries, this creates a governance challenge. Health ministries cannot address housing, employment, food insecurity or transport alone. Progress requires coordination across social welfare, labour, education, urban development and local government. Civil society and community organisations are equally important because they can identify barriers that routine programme data overlook and help reduce stigma.

This multisectoral approach aligns TB prevention with the Sustainable Development Goals, particularly SDG 3 on health, SDG 1 on poverty, SDG 2 on hunger, SDG 8 on decent work and SDG 10 on inequality. It also reflects a larger shift in global health away from narrowly vertical disease programmes towards stronger primary healthcare and social protection.

The risk, however, is that multisectoral language becomes a substitute for accountability. The viewpoint argues for coordinated action, but governments will need clear responsibilities, financing arrangements and measurable outcomes if collaboration is to move beyond policy statements.

The Next Breakthrough Is Implementation at Scale

Emerging technologies may reshape TB prevention over the longer term. Biomarkers could improve risk stratification, new vaccines could reduce infection or disease progression, and digital tools could support education, adherence and follow-up. But the paper warns that innovation must be judged by feasibility, affordability, equity and relevance to routine programmes.

A digital adherence system that assumes constant connectivity may exclude poor or remote patients. A highly accurate test may have limited value if it requires expensive equipment, repeated visits or specialised staff. A new vaccine may still fail to reach those at greatest risk if supply chains and primary-care systems remain weak.

For policymakers, the priority should therefore be sequencing. In the short term, countries should reduce losses across the prevention cascade, secure medicine supplies, train health workers, integrate services and improve monitoring. In the medium term, economic evaluations should include the full costs of contact investigation, eligibility assessment, counselling, follow-up and programme management—not only the price of medicines. In the longer term, new diagnostics, biomarkers, vaccines and digital tools can be introduced where they demonstrably improve equity and population-level impact.

The viewpoint is not a systematic review and does not quantify the comparative effectiveness of every intervention. It draws on studies from a special issue, meaning its evidence base is selective rather than exhaustive. Even so, its strategic conclusion is difficult to dismiss: TB prevention is failing less because of a lack of scientific options than because fragmented systems do not consistently deliver them.

It has major implications for donors and multilateral institutions. Funding models should move beyond short project cycles and commodity procurement towards sustained investment in workforce capacity, supply chains, surveillance, community delivery and social protection. Implementation research must also become more central, especially in resource-constrained settings where interventions proven under controlled conditions may struggle in routine practice.

The global TB response already knows many of the people who should be prioritised and many of the treatments that can protect them. The unresolved question is whether countries can build systems capable of reaching them before infection becomes disease. Until that gap closes, the promise of prevention will remain stronger on paper than in practice.