Tuberculosis (TB) - Adult with Cough & Weight Loss (10 Marks)

a) Diagnosis of Pulmonary Tuberculosis

Clinical Features (Presumptive Diagnosis)

Investigations

1. Sputum Smear Microscopy (ZN stain / Fluorescence)

• Detects acid-fast bacilli (AFB) - so called because M. tuberculosis cannot be decolourised by acid-alcohol after staining (due to mycolic acid-rich cell wall).
• Two sputum samples (spot + morning specimen).
• Cheap, rapid, widely available; lower sensitivity (~60-70%) especially in HIV co-infection.

2. Molecular Tests (CBNAAT/Xpert MTB/RIF)

• GeneXpert MTB/RIF (Cartridge Based Nucleic Acid Amplification Test, CBNAAT): First-line test in India under NTEP; detects M. tuberculosis AND rifampicin resistance simultaneously within 2 hours.
• High sensitivity (~90%) and specificity (~99%).
• Also used upfront in all presumptive TB cases among PLHIV (persons living with HIV).

3. Sputum Culture (Gold Standard)

• Lowenstein-Jensen (LJ) solid medium or liquid MGIT (BACTEC).
• Most sensitive and specific; results take 2-8 weeks.
• Allows drug sensitivity testing (DST).

4. Chest X-Ray

• Findings: upper lobe consolidation, cavitation, fibrosis, hilar lymphadenopathy, miliary shadows.
• Not pathognomonic but highly suggestive.
• In HIV+ patients: less cavitation, more atypical patterns.

5. Tuberculin Skin Test (TST / Mantoux)

• Intradermal PPD (5 TU); read at 48-72 hours.
• Induration ≥10 mm = positive (≥5 mm in immunocompromised/HIV).
• Limitations: false positives with BCG vaccination or NTM infection; false negatives in immunosuppression and advanced TB.
• Not used for diagnosing active TB - used for TB infection.

6. IGRA (Interferon-Gamma Release Assay)

• QuantiFERON-TB Gold Plus / T-SPOT.TB.
• Measures T-cell IFN-γ release to ESAT-6 and CFP-10 antigens.
• More specific than TST; not affected by BCG vaccination.
• Better for TB infection screening; not diagnostic of active disease alone (Harrison's Principles, 22nd ed.).

7. New Antigen-Based Skin Tests (TBST)

• Use ESAT-6/CFP-10 antigens (like IGRAs) but administered like TST.
• WHO-endorsed; comparable accuracy to IGRA, useful in PLHIV and BCG-vaccinated persons.

8. Histopathology

• Biopsy of lymph node, pleura, or other organ: caseating epithelioid granuloma with Langhans' giant cells - hallmark of TB.

9. ADA (Adenosine Deaminase)

• Elevated in pleural fluid, CSF, or pericardial fluid in TB - used as a surrogate marker.

Sources: Harrison's Principles of Internal Medicine 22E; Murray & Nadel's Textbook of Respiratory Medicine; Park's Preventive & Social Medicine

b) Transmission

Key Points:

• Agent: Mycobacterium tuberculosis - rod-shaped, non-spore-forming, thin aerobic, acid-fast bacillus (AFB) measuring 0.5 × 3 µm.
• Mechanism: Infectious persons expel droplet nuclei (1-5 µm) during coughing, sneezing, talking, or singing. These tiny particles remain airborne for hours in enclosed, poorly ventilated spaces.
• Infective dose: Very low - inhalation of as few as 1-10 bacilli can initiate infection.
• Droplet nuclei settle in the alveoli of the lower respiratory tract, where alveolar macrophages phagocytose them - initiating either clearance, latent infection, or active disease.
• Laryngeal TB is the most infectious form.
• Factors increasing transmission: high bacillary load in sputum (smear-positive), cavitatory disease, poor ventilation, prolonged contact, overcrowding.
• M. bovis can be transmitted via unpasteurised milk (gastrointestinal TB).

Sources: Harrison's 22E; Fishman's Pulmonary Diseases; Red Book 2021

c) National Program (NTEP - National Tuberculosis Elimination Programme)

The 5 Pillars of DOTS (Directly Observed Treatment, Short-course):

1. Political commitment - sustained government funding and prioritisation.
2. Passive case detection by sputum smear microscopy (Designated Microscopy Centres - DMCs); now augmented by CBNAAT/GeneXpert as first-line.
3. Standardised short-course chemotherapy under direct observation (see treatment below).
4. Uninterrupted drug supply through a logistics system.
5. Standardised recording and reporting (TB Register, Nikshay portal).

NTEP Key Features (NSP 2017-2025):

TB-HIV Integration (RNTCP/NTEP):

• HIV screening at all DMCs.
• CBNAAT upfront for all presumptive TB in PLHIV.
• Intensified case finding at ART centres.
• Prompt linkage of HIV-TB co-infected patients to ART.

Treatment Regimen Under NTEP:

• Intensive Phase (2 months): HRZE (Isoniazid + Rifampicin + Pyrazinamide + Ethambutol)
• Continuation Phase (4 months): HR (Isoniazid + Rifampicin)
• Total: 6-month daily regimen (2HRZE/4HR)
• Drug-Resistant TB (MDR-TB): treated at designated DR-TB centres with longer regimens (BPaL or other WHO-approved regimens).

d) Prevention

1. BCG Vaccination

• Bacille Calmette-Guérin (BCG) given at birth under India's Universal Immunisation Programme (UIP).
• Provides ~50% protection overall; most effective against severe childhood forms - miliary TB and TB meningitis.
• Does not prevent primary infection or reactivation TB in adults reliably.
• Two novel vaccine trials (M72/AS01E and ID93+GLA-SE) have shown promising efficacy against TB in recent years (Murray & Nadel's Respiratory Medicine).

2. Treatment of Latent TB Infection (LTBI) / TB Preventive Therapy (TPT)

• Isoniazid Preventive Therapy (IPT): 6H (6 months Isoniazid) or 3HP (3 months weekly Isoniazid + Rifapentine).
• Indicated for: household contacts of smear-positive cases, PLHIV, immunocompromised individuals.
• Prevents progression from infection to active TB.
• Under NTEP: all PLHIV on ART and household child contacts <5 years are given TPT.

3. Infection Control Measures

• Prompt respiratory isolation of suspected/confirmed TB patients.
• Triage and fast-tracking of presumptive TB patients.
• Patients wear surgical masks during transport within facilities.
• Symptom-based screening at entry points to health facilities.

• Adequate natural or mechanical ventilation (minimum 12 air changes/hour in isolation rooms).
• Negative-pressure isolation rooms.
• Upper-room germicidal ultraviolet irradiation (UVGI) for air disinfection.

• N95 respirators (not ordinary surgical masks) for health care workers in high-risk settings.

4. Public Health Measures

• Contact tracing: All household and close contacts of smear-positive index cases to be screened (symptom screen + chest X-ray + TST/IGRA).
• Active case finding (ACF): Community-wide screening using Xpert has shown 44% reduction in TB prevalence in screened vs. control communities (Murray & Nadel's).
• Nutritional support: Undernutrition is a major risk factor; Nikshay Poshan Yojana addresses this.
• Reducing overcrowding, improving ventilation in prisons, slums, and congregate settings.
• Ensuring pasteurisation of milk (prevents M. bovis transmission).
• End TB Strategy (WHO): Target 90% reduction in TB deaths and 80% reduction in incidence by 2030.

Sources: Harrison's Principles of Internal Medicine 22E; Murray & Nadel's Textbook of Respiratory Medicine; Park's Textbook of Preventive & Social Medicine; India NTEP/PIB 2025; Detect-Treat-Prevent-Build NSP strategy

c) National Program — NTEP (National Tuberculosis Elimination Programme)

Full Form

Goal

Target

Beneficiaries

• All TB patients in India — regardless of age, sex, or economic status.
• Priority groups: PLHIV (persons living with HIV/AIDS), malnourished individuals, diabetics, immunocompromised persons, prisoners, migrants, tribal populations, slum dwellers.
• Household contacts of smear-positive TB cases (for contact tracing and TB Preventive Therapy).
• Children under 5 years in contact with TB cases.

Funds

• Primarily funded by the Government of India (Central Government) through the National Health Mission (NHM).
• Additional support from Global Fund to Fight AIDS, TB and Malaria (GFATM).
• USAID and World Bank have also contributed historically.
• Nikshay Poshan Yojana (NPY): Direct Benefit Transfer of ₹500 per month to every notified TB patient for nutritional support, transferred directly to their bank account via DBT.
• Pradhan Mantri TB Mukt Bharat Abhiyaan (2022): Encourages "Ni-kshay Mitras" (donors/corporates/individuals) to adopt and support TB patients financially and nutritionally.

Strategies (DETECT - TREAT - PREVENT - BUILD)

1. DETECT (Early & Universal Detection)

• Universal Drug Susceptibility Testing (UDST): All diagnosed TB patients tested for drug resistance at the start.
• CBNAAT / GeneXpert MTB/RIF as first-line diagnostic at all levels (detects TB + Rifampicin resistance simultaneously within 2 hours).
• Active Case Finding (ACF): Community-level door-to-door screening in high-burden areas.
• Intensified Case Finding (ICF) at ART centres, ICTC, prisons, slums.
• Nikshay Portal: Digital web-based case notification and tracking system for every TB patient.

2. TREAT (Prompt & Effective Treatment)

• Daily regimen (replaces old thrice-weekly intermittent DOTS):
  • Intensive phase (2 months): HRZE (Isoniazid + Rifampicin + Pyrazinamide + Ethambutol)
  • Continuation phase (4 months): HR (Isoniazid + Rifampicin)
• Directly Observed Treatment (DOT): Frontline health worker or treatment supporter observes drug intake.
• MDR-TB / DR-TB: Treated at designated DR-TB centres; newer regimens include BPaL (Bedaquiline + Pretomanid + Linezolid).
• Patient support: Nikshay Poshan Yojana (₹500/month), free drugs and diagnostics.
• Private sector engagement (PPM - Public-Private Mix): All private practitioners mandated to notify TB cases on Nikshay.

3. PREVENT (Preventing New Infections)

• TB Preventive Therapy (TPT): Isoniazid Preventive Therapy (6H) or 3HP regimen for:
  • All PLHIV on ART
  • Household contacts of smear-positive cases
  • Child contacts under 5 years
• BCG vaccination at birth (Universal Immunisation Programme).
• Infection control in health facilities: ventilation, N95 masks for HCWs, isolation of infectious patients.
• TB-HIV collaboration: HIV testing of all TB patients; co-trimoxazole prophylaxis; prompt ART initiation.

4. BUILD (Strengthening Systems)

• Strengthening laboratory networks (DMCs, CBNAAT labs, culture & DST labs - IRL/NRL).
• Human resource development: Training of medical officers, health workers, lab technicians.
• Accountability systems: Nikshay, quarterly reporting, death audits.
• Research & Innovation: New vaccines (M72/AS01E), shorter regimens, point-of-care diagnostics.
• Inter-sectoral coordination: Convergence with NHM, NACO (HIV), NCD programmes, Ayushman Bharat.

Sources: Park's Textbook of Preventive & Social Medicine; India NTEP - PIB 2025; NSP Detect-Treat-Prevent-Build strategy