Context

• More than a century after the introduction of the BCG vaccine, tuberculosis (TB) remains one of the world's deadliest infectious diseases.
• Despite significant medical advances, TB continues to impose a heavy burden, particularly in low- and middle-income countries (LMICs) such as India.
• Recent findings from the PreVenTB trial provide evidence that moderately effective vaccines can play a meaningful role in this effort.

Understanding the Complexity of Tuberculosis

• Multiple Disease Pathways
  • TB is caused by Mycobacterium tuberculosis, but its progression varies widely among individuals.
  • Following exposure, some people develop latent infection and remain symptom-free for years. Others may develop subclinical disease before progressing to active TB.
• Pulmonary and Extrapulmonary Tuberculosis
  • Active TB manifests in two major forms:
    • Pulmonary TB (PTB), which affects the lungs and drives disease transmission.
    • Extrapulmonary TB (EPTB), which affects organs outside the lungs and is often difficult to diagnose.
  • The existence of multiple disease pathways makes it unrealistic to expect a single vaccine to prevent every form of TB.
  • Effective disease control therefore requires multiple interventions working together.

Significance of the PreVenTB Trial and Key Findings

• Real-World Evidence
  • The PreVenTB trial, conducted across 18 sites in India, involved more than 12,700 participants who were household contacts of TB patients.
  • The study evaluated two vaccine candidates: VPM1002 and Immuvac.
• Key Findings
  • The trial reported:
    • Around 50% efficacy of VPM1002 against EPTB.
    • More than 60% efficacy among certain groups of children and adolescents.
    • Evidence of protection against progression from infection to disease.
  • These findings are significant because they demonstrate effectiveness under real-world conditions and address forms of TB that have often received less attention in vaccine research.

Addressing the Hidden Burden of Extrapulmonary TB

• Why EPTB Matters?
  • Extrapulmonary TB is frequently underdiagnosed and associated with substantial morbidity and mortality.
  • Its diagnosis is often delayed due to the absence of typical respiratory symptoms.
• Public Health Benefits
  • Reducing EPTB cases can lower healthcare costs, decrease patient suffering, and improve quality of life.
  • The strong efficacy signals observed among children and adolescents also support the possibility of a future booster-dose strategy for TB prevention.

The Role of Nutrition in TB Prevention

• Impact of Nutritional Status
  • The trial demonstrated lower vaccine effectiveness among individuals with low Body Mass Index (BMI).
  • This finding highlights the close relationship between nutrition and immune function.
• Integrating Nutrition with TB Control
  • Addressing undernutrition should be considered an essential component of TB control strategies.
  • Vaccination programs are likely to achieve better outcomes when combined with nutritional support initiatives.

Policy Implications and Operational Advantages

• Benefits of VPM1002
  • It is a single-dose vaccine. It is based on a modified BCG platform.
  • It can be produced through large-scale manufacturing.
  • It is suitable for cost-effective deployment in resource-constrained settings.
• Lessons from Previous Public Health Decisions
  • India has previously adopted innovative health technologies before international endorsement was fully established.
  • Examples include:
    • TrueNat for TB diagnosis.
    • Covaxin during the COVID-19 pandemic.
    • Indigenous rotavirus vaccines.
  • These experiences demonstrate the value of acting on strong evidence rather than waiting indefinitely for perfect solutions.

Steps Required in Achieving TB Elimination

• Strengthening Diagnostic Systems
  • Improved diagnostics can identify infections at earlier stages, including latent and subclinical cases, enabling timely intervention and reducing transmission.
• Expanding Preventive Therapy
  • Preventive treatment can stop latent infections from progressing into active disease, thereby reducing the overall burden of TB.
• The Importance of Vaccination
  • Vaccination remains a critical component of TB control, especially in regions where access to healthcare services is uneven.
  • Even vaccines with moderate effectiveness can contribute significantly when deployed strategically.
• Towards a Smarter TB Strategy
  • TB elimination requires an integrated approach that combines:
    • Diagnostics
    • Preventive therapy
    • Targeted vaccination
    • Case management
    • Nutritional supplementation
    • Sustained public health investment
  • No single intervention can eliminate TB on its own. A combination of complementary strategies is essential for long-term success.

Conclusion

• The complexity of the disease demands a multi-layered strategy that addresses prevention, diagnosis, treatment, and broader social determinants of health.
• The PreVenTB trial provides encouraging evidence that vaccines such as VPM1002 and Immuvac can reduce both PTB and EPTB, particularly among high-risk populations.
• Rather than waiting indefinitely for an ideal vaccine, policymakers should prioritise evidence-based interventions capable of delivering immediate public health benefits.
• A pragmatic and integrated approach offers the most realistic pathway toward controlling one of humanity's oldest and most persistent diseases.