Understanding the Persistent Challenge of Drug-Resistant Tuberculosis in India

India bears a significant portion of the global tuberculosis burden, accounting for nearly one-fourth of multidrug-resistant and rifampicin-resistant TB cases worldwide. According to recent estimates, approximately 147,000 MDR-TB cases occur annually in the country, underscoring the urgency for effective interventions. The National TB Elimination Programme (NTEP), under the Ministry of Health and Family Welfare, has made strides in reducing TB incidence by 21% from 237 to 187 per lakh population between 2015 and 2024. However, drug-resistant forms like MDR-TB—defined as tuberculosis resistant to at least isoniazid and rifampicin—and RR-TB, resistant specifically to rifampicin, complicate treatment and strain healthcare resources.

Traditional treatments for these conditions often span 9 to 20 months, involving injectable drugs that cause severe side effects, poor patient adherence, and high dropout rates. This prolonged therapy not only increases morbidity and mortality but also escalates costs for both patients and the health system. In response, global health bodies like the World Health Organization (WHO) have endorsed shorter all-oral regimens, paving the way for studies like the recent ICMR-NIRT evaluation.

Evolution from Injectable to All-Oral Regimens in TB Management

The shift toward all-oral regimens marks a paradigm change in TB therapy. Earlier protocols relied on second-line drugs administered via injections, leading to toxicity, hospitalization needs, and treatment interruptions. India's NTEP introduced bedaquiline-containing shorter regimens in recent years, but a mixed standard of care (SoC) persists: 42% shorter (9-11 months) and 58% longer (18-20 months) options. These include drugs like levofloxacin, clofazimine, and cycloserine, with bedaquiline for initial phases.

Newer regimens such as BPaL—comprising bedaquiline (a diarylquinoline that inhibits ATP synthase in mycobacteria), pretomanid (a nitroimidazole prodrug effective against dormant bacteria), and linezolid (an oxazolidinone protein synthesis inhibitor)—and BPaLM (BPaL plus moxifloxacin, a fluoroquinolone)—offer 6-month durations without injectables. Originating from trials like Nix-TB and ZeNix, these have shown promising interim results with cure rates exceeding 80%.

ICMR-NIRT Study: Rigorous Economic Evaluation Methodology

Published on December 31, 2025, in the Indian Journal of Medical Research, the study by researchers from ICMR-National Institute for Research in Tuberculosis (NIRT) in Chennai—including lead author Malaisamy Muniyandi—employs a sophisticated Markov decision-analytic model. This model simulates lifetime outcomes for a cohort of 48,563 MDR/RR-TB patients over 14 years under India's NTEP. Health states tracked include cure, recurrence, loss to follow-up, failure, and death, with transitions informed by clinical trials (e.g., TB-PRACTECAL) and meta-analyses.

Costs, from a health system perspective, encompass drugs, nutritional support (INR 500/month), treatment supporter incentives (INR 5,000), and diagnostics like CBNAAT (INR 1,036). A 3% discount rate applies to future costs and quality-adjusted life years (QALYs). Sensitivity analyses—one-way (OWSA), probabilistic (PSA with 1,000 iterations), and scenario variations—validate robustness, while budget impact assesses one-year financial shifts.Explore research opportunities in TB economics at NIRT-like institutes.

Key Cost-Effectiveness Findings: BPaL Emerges as a Winner

The base-case analysis reveals striking results. Total discounted costs for 48,563 patients: BPaL at INR 2,515 million, BPaLM at INR 2,644 million, versus mixed SoC at INR 2,630 million. BPaL saves INR 115 million overall, equating to INR 379 less per patient per additional QALY gained (negative ICER, indicating dominance). BPaLM, slightly costlier, costs INR 37 more per QALY but yields superior outcomes.

Direct medical costs per course: shorter SoC INR 24,784, longer INR 43,013, BPaL INR 37,279, BPaLM INR 39,738. Shorter durations and higher cure rates (84% BPaL, 87% BPaLM vs. 71%/65%) drive savings.Read the full ICMR-NIRT study.

Superior Health Outcomes: QALY Gains and Cure Rates

BPaL gains 0.30 million QALYs, BPaLM 0.38 million over SoC, reflecting better utility scores (0.87 cure vs. lower for ongoing states). PSA confirms BPaL's 91% probability of dominance across thresholds. These gains stem from reduced recurrence (due to higher efficacy) and shorter disruptions to productivity.

• Higher cure rates minimize long-term disability and death.
• Shorter therapy boosts adherence, cutting loss-to-follow-up.
• Lower toxicity (no injectables) reduces adverse event management costs.

Budget Impact: Scalable Savings for NTEP Implementation

One-year budget impact: BPaL saves INR 106 million; BPaLM adds INR 13 million. Scenario analyses show greater savings as longer SoC proportions rise. Threshold analysis indicates BPaLM turns cost-saving with a mere 1% drug price drop via bulk procurement. This aligns with NTEP's resource optimization for TB elimination by 2025 (extended goals).PIB on study implicationsClinical research jobs advancing TB solutions.

Challenges and Considerations for Programmatic Rollout

Despite promise, hurdles include confirming eligibility via drug susceptibility testing (DST), linezolid-induced neuropathy monitoring, pretomanid supply chains, and provider training. Real-world effectiveness may vary from trial data, necessitating pharmacovigilance. Patient costs (societal perspective excluded) and diagnostics remain unmodeled.

• Diagnostic delays in DST for fluoroquinolone resistance.
• Adverse events: myelosuppression, optic neuritis.
• Equity: ensuring access in rural/high-burden areas.

India's August 2024 BPaLM rollout announcement signals progress, but scaling requires investment.

Expert Views and Global Context

Experts hail the study as pivotal evidence for adoption, echoing WHO endorsements. Treatment success for MDR-TB hovers at 46% in India, far below global targets; BPaL could elevate this. Globally, countries like South Africa report cost savings with BPaL for XDR-TB. In India, NTEP integration could halve treatment periods, aiding 63,939 notified MDR cases (2023).Build your academic CV for TB research roles.

Future Outlook: Accelerating India's TB Elimination

This ICMR-NIRT research bolsters NTEP's trajectory toward elimination, potentially saving billions long-term. Future trials will refine real-world data, while AI-driven diagnostics and generics enhance affordability. Stakeholders urge swift policy shifts for universal BPaL access.TB research positions in India.

By prioritizing evidence-based regimens, India can curb DR-TB transmission, safeguard economies, and inspire global efforts.

Photo by Tegar Oakley on Unsplash

Career Opportunities in TB Research and Public Health

The study highlights ICMR-NIRT's role in translational research, opening doors for epidemiologists, economists, and clinicians. With rising funding for TB, professionals can contribute to trials, modeling, and policy. Platforms like AcademicJobs connect talent to higher-ed jobs, professor positions, and university roles driving health innovations. Explore Rate My Professor for insights or career advice to advance in this vital field.