NTEP - National Tuberculosis Elimination Programme

Background and Renaming

• Park's Textbook of Preventive and Social Medicine, p. 482

National Strategic Plan (NSP) 2017-2025

Organisational Structure (5-Level Organogram)

1. National Level - Central TB Division (CTD) under MoHFW, headed by DDG-TB. Supported by National TB Institute (NTI, Bengaluru), 6 National Reference Laboratories (NRL) including NIRT Chennai, NITRD Delhi, JALMA Agra, RMRC Bhubaneswar, BMHRC Bhopal.
2. State Level - State TB Officer (STO) at State TB Cell (STC). Supported by State TB Training and Demonstration Centre (STDC) with an Intermediate Reference Laboratory (IRL).
3. District Level - District TB Officer (DTO) coordinates case finding, drug flow, records and NIKSHAY monitoring.
4. Sub-district Level - Manages peripheral health facilities.
5. Peripheral Health Institution (PHI) - The ground-level unit for case identification, treatment initiation, and DOT delivery.

• Park's Textbook of Preventive and Social Medicine, p. 482-484

NTEP-Endorsed TB Diagnostics

1. Smear microscopy for AFB - Ziehl-Neelsen stain or fluorescence stain (LED)
2. Culture - Solid (Lowenstein-Jensen) or Liquid media (MGIT/Bactec)
3. Rapid molecular tests - Line Probe Assay (LPA) or CBNAAT/GeneXpert (real-time PCR for MTB complex)
4. Radiography (CXR) where available
5. Tuberculin skin test (Mantoux)

• Park's Textbook of Preventive and Social Medicine, p. 484

Diagnostic Algorithm (Pulmonary TB)

• All presumptive TB cases undergo sputum smear examination (ZN/LED-FM) - 2 specimens (spot-early morning or spot-spot)
• Smear positive + no DR-TB risk → categorized as microscopically confirmed TB
• Smear negative → CXR; if suggestive, 2nd sample subjected to smear + CBNAAT simultaneously
• CBNAAT also detects rifampicin resistance (RR-TB)

Treatment - Daily Dose Regimen (2019 Guidelines)

Fixed Dose Combinations (FDCs)

Adult Daily Dose Schedule (by weight band)

Drug Dosages (First-line Anti-TB drugs)

• Park's Textbook of Preventive and Social Medicine, p. 221-223

DOTS Strategy

• During intensive phase: patient swallows drugs in presence of a health worker (DOT agent)
• During continuation phase: drugs issued for 1 week in multi-blister combipack; first dose taken in presence of health worker; compliance checked by return of empty packs
• DOT Agents include: MPWs, teachers, ASHA/anganwadi workers, ex-patients, social workers
• DOT Agents receive an incentive of Rs 150 per patient completing treatment

Key New Initiatives

1. NIKSHAY (IT Surveillance System)

• TB patient registration (diagnosis details, DOT provider, HIV status, follow-up, contact tracing, outcomes)
• DR-TB registration
• Culture/DST/LPA/CBNAAT data entry
• Private provider notification
• SMS alerts to patients and programme officers
• Automated reports (case finding, sputum conversion, treatment outcomes)
• 99 DOTS - IT-based adherence tool (digital DOT using missed-call technology)

2. Mandatory TB Notification

3. Ban on TB Serology

4. Direct Benefit Transfer (DBT)

5. Ni-Kshay Mitra Initiative

Drug-Resistant TB (DR-TB) - PMDT Structure

• Nodal DR-TB Centres (N-DR-TBC): Manage M/XDR-TB, pre-treatment evaluation, AIC measures
• District DR-TB Centres (DDR-TBC): Initiate MDR/RR-TB and H mono/poly-DR-TB regimens, manage ADRs
• CBNAAT labs: Diagnose RR-TB at district level
• C&DST labs: Culture and drug susceptibility testing, quality assurance

TB-HIV Coordination

• Intensified TB case finding at all ICTC (Integrated Counselling & Testing Centres) and ART centres
• HIV testing is mandatory for all TB patients
• HIV-positive TB patients receive ART + co-trimoxazole preventive therapy (CPT)
• National framework for joint TB-HIV activities developed in 2007

Pre-treatment Evaluation (Mandatory)

1. Detailed history (including seizures, mental illness, drug/alcohol abuse)
2. Weight and height
3. Complete blood count (CBC)
4. Blood sugar (screen for DM)
5. Liver function tests (LFTs)
6. Blood urea and creatinine (renal function)
7. Urine examination
8. Chest X-ray
9. Pregnancy test (all women of childbearing age)
10. HIV testing

Adjunctive Therapy

• Steroids are indicated as adjunctive therapy in:
  • TB pericarditis
  • TB meningitis
  • Initial high dose, tapered over 6-8 weeks

Recent Updates (2025-2026)

• National Guidelines for Management of DR-TB (March 2025) released
• National Guidance on Differentiated TB Care (March 2025) published
• TB Mukt Bharat Abhiyan Campaign 2026 - awareness and active case finding drive
• Ni-Kshay Mitra Initiative updated with new guidance 2026

Multidrug-Resistant Tuberculosis (MDR-TB)

Definition and Classification

Global Epidemiology

• Estimated 400,000 cases of RR/MDR-TB occurred in 2023, representing 3.2% of new and 16% of previously treated cases (Harrison's 22E, 2025)
• Only 189,000 MDR/RR-TB cases were enrolled on treatment in 2023 - largely due to lack of culture and DST capacity worldwide
• >50% of all MDR/RR-TB cases occur in 5 countries:
  • India: 27% (highest global burden)
  • Russian Federation: 7.4%
  • Indonesia: 7.4%
  • China: 7.3%
  • Philippines: 7.2%
• Countries of the former Soviet Union have the highest proportions among new TB cases (up to one-third)
• Harrison's Principles of Internal Medicine 22E, p. 1425

Pathogenesis of Drug Resistance

1. Primary resistance - patient infected from the start by a resistant strain
2. Acquired resistance - develops in the infecting strain during inadequate treatment (most common cause)

• Monotherapy or functionally inadequate regimens (fewer than 2 active drugs)
• Poor-quality drugs or substandard preparations
• Non-adherence to treatment
• Drug malabsorption

• Harrison's Principles of Internal Medicine 22E, p. 1441

Diagnosis of DR-TB under NTEP

• All TB patients tested for rifampicin (R) and isoniazid (H) resistance
• All RR-TB patients tested for fluoroquinolone (FQ) and second-line injectable (SLI) resistance

NTEP-Endorsed Diagnostics for DR-TB

1. CBNAAT/GeneXpert - detects MTB and rifampicin resistance; first-line rapid molecular test
2. Line Probe Assay (LPA) - First-line LPA (FL-LPA) for H and R; Second-line LPA (SL-LPA) for FQ and SLI resistance
3. Liquid culture + DST (MGIT/Bactec) - definitive culture and drug susceptibility
4. Whole Genome Sequencing - emerging for comprehensive resistance profiling

Drug Grouping for Longer MDR-TB Regimens (WHO/NTEP Classification)

• Park's Textbook of Preventive and Social Medicine, p. 224; Harrison's 22E, p. 1442

Standard DR-TB Regimens under NTEP

1. H Mono/Poly DR-TB (R-susceptible, H-resistant)

• Duration: 6 months (all oral, single phase)

2. Shorter MDR-TB Regimen (9-11 months)

3. All-Oral Longer MDR-TB Regimen (18-20 months)

• Bedaquiline given for first 6 months of an 18-20 month regimen
• Remainder: Lfx + Lzd + Cfz + Cs continued
• Park's Textbook of Preventive and Social Medicine, p. 225

Latest WHO 2024 Recommendations (Updated in Harrison's 22E)

Option 1: BPaLM - 6-Month All-Oral Regimen (PREFERRED for most patients)

• Treatment success ~90% in trials (Nix-TB, ZeNix, TB-PRACTECAL)
• For: MDR/RR-TB or pre-XDR-TB, age ≥14 years, all forms except disseminated/CNS/osteoarticular TB
• Not for: pregnant/breastfeeding women (pretomanid safety unclear), prior >1 month exposure to Bdq/Pa/Lzd
• If FQ resistance: drop moxifloxacin → use BPaL (3 drugs, 6 months)

Option 2: BDL + Lfx + Cfz - 6-Month Regimen

• Alternative when pretomanid not available

Option 3: 9-Month All-Oral Bedaquiline-Containing Regimens

• Bdq + Lfx(or Mfx) + Eto + Cfz + Z + H(high-dose) + E
• Bdq + Dlm + Lzd + Lfx + Cfz (various endTB trial arms)
• For patients without extensive disease and minimal prior SLD exposure

Option 4: Individualized Longer Regimen (≥18 months)

• Composed using WHO priority grouping (Groups A, B, C)
• Duration: 15-17 months after culture conversion; intensive phase 6-7 months
• For complex cases, children, pregnant women (ethionamide replaced with Lzd 600 mg)
• Harrison's Principles of Internal Medicine 22E, p. 1442-1443

Key Drugs in MDR-TB - Mechanisms and Notes

Bedaquiline (Bdq)

• Class: Diarylquinoline (first novel mechanism drug approved since 1971 - FDA 2012)
• MOA: Inhibits mycobacterial ATP synthase - bactericidal against both replicating and non-replicating bacilli
• Dose: 400 mg OD x 2 weeks, then 200 mg three times/week x 22 weeks, taken with food
• Half-life: ~5.5 months (very long - slow release from peripheral tissues)
• ADEs: Nausea, arthralgia, headache; hepatotoxicity; QT prolongation (FDA black-box warning)
• Cross-resistance: With clofazimine (via MmpL5 efflux pump upregulation)
• NTEP eligibility: Age >6 years for MDR/RR-TB; ≥18 years for standard use (6-17 years - DCGI approval needed)

Pretomanid (Pa)

• Class: Nitroimidazoloazine (nitroimidazole; related to delamanid)
• MOA: Dual mechanism - inhibits mycolic acid synthesis (aerobic/replicating); releases nitric oxide (anaerobic/non-replicating)
• Dose: 200 mg OD x 6 months (oral)
• Half-life: ~16 hours
• ADEs: Neuropathy, headache, acne, anemia, GI symptoms, hepatotoxicity, QT prolongation, rash, hyperamylasemia
• FDA-approved 2019 for XDR-TB/pre-XDR-TB/treatment-nonresponsive MDR-TB

Linezolid (Lzd)

• Class: Oxazolidinone
• MOA: Inhibits bacterial protein synthesis (50S ribosome)
• Dose: 600 mg/day preferred (1200 mg/day used in older trials - more toxic)
• ADEs: Bone marrow suppression, peripheral neuropathy (irreversible), optic neuropathy; serotonin syndrome risk with serotonergic agents; add pyridoxine supplementation

Delamanid (Dlm)

• Class: Nitroimidazole
• Use: Children 3-17 years (Bdq alternative); Group C drug in longer regimens
• NTEP: Age 6-17 years preferred; 3-6 years with DCGI approval

Clofazimine (Cfz)

• Class: Riminophenazine (antileprous drug)
• Active in MDR-TB; Group B drug
• ADEs: Skin/corneal discoloration; QT prolongation
• Katzung's Basic and Clinical Pharmacology 16E, p. 1319-1321; Harrison's 22E

Safety Monitoring During MDR-TB Treatment

• Harrison's Principles of Internal Medicine 22E, p. 1443

Special Situations

MDR-TB + HIV

• Initiate ART within 2 weeks of TB treatment if CD4 ≤50/μL
• Initiate ART by 8-12 weeks if CD4 ≥50/μL
• Exception: TB meningitis - delay ART initiation
• Rifampicin has significant interactions with PIs and NNRTIs - may substitute rifabutin
• BPaLM regimen may be used regardless of HIV status

MDR-TB in Pregnancy

• BPaLM: Avoid (pretomanid safety not established)
• 9-month regimen: Replace ethionamide with linezolid 600 mg daily
• Kanamycin/amikacin: Avoid (ototoxicity to fetus)
• Bedaquiline: May be used when benefits outweigh risks

MDR-TB in Children

• Age <14 years: Longer regimens preferred
• Bedaquiline: ≥6 years (DCGI approval 6-17 yrs in India); standard ≥18 yrs
• Delamanid: Approved from 3 years
• Weight-based dosing for all drugs

Treatment Outcomes (WHO Definitions)

NTEP PMDT Structure (Treatment Infrastructure)

• Park's Textbook of Preventive and Social Medicine, p. 485-487; India's National Guidelines for Management of DR-TB (March 2025)

Key Points Summary

• MDR-TB = resistance to at least H + R; India carries 27% of the global MDR-TB burden
• Fully oral regimens are now standard - injectables (kanamycin, capreomycin) no longer recommended
• BPaLM (6 months) is the preferred regimen for MDR/RR-TB and pre-XDR-TB (WHO 2022/2024)
• Drug grouping: Group A (all 3: FQ + Bdq + Lzd) → Group B (Cfz, Cs) → Group C for longer regimens
• QT monitoring mandatory for all patients on Bdq, Dlm, Cfz, or fluoroquinolones
• Ban on injectables (kanamycin/capreomycin) in standard regimens due to worse outcomes
• Treatment duration: 6 months (BPaLM), 9-11 months (shorter oral), or 18-20 months (longer regimen)
• India's NTEP DR-TB guidelines were updated in March 2025