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Tuberculosis (TB) - Complete Exam Guide

PART 1: THE PATHOGEN AND EPIDEMIOLOGY

• Estimated incidence: 2.82 million new cases (199/1,00,000 population) in 2022
• Estimated mortality: 3,31,000 deaths (23/1,00,000) in 2022
• ~2% of TB patients are HIV co-infected
• MDR-TB: 2.5% in new cases, 13% in previously treated cases

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PART 2: TYPES OF TB

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PART 3: DIAGNOSIS

• Ziehl-Neelsen (ZN) staining - primary tool under NTEP
• Designated Microscopy Centres (DMCs): 1 per 1,00,000 population (1 per 50,000 in tribal/hilly areas)
• 2 sputum samples (spot-morning-spot)

• Solid media: LJ (Lowenstein-Jensen), takes 6-8 weeks
• Liquid media: BACTEC, MGIT - faster

• GeneXpert MTB/RIF (CBNAAT): Simultaneous MTB detection + rifampicin resistance in ~2 hours. Expanded to 1,180 centres covering all districts under NTEP
• Line Probe Assay (LPA): Detects MTB complex + isoniazid + rifampicin resistance

• Intradermal injection of 2 TU PPD (5 TU in some countries), read at 48-72 hrs
• Induration ≥10 mm = positive (≥5 mm in HIV/immunocompromised)

• QuantiFERON-TB Gold, T-SPOT.TB
• Not affected by BCG vaccination; better specificity than TST

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PART 4: TREATMENT REGIMENS

First-Line Drugs (Mnemonic: RIPE or HRZE)

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Standard Regimen for Drug-Susceptible TB (Harrison's 22E, 2025)

• 9 months total if: cavitary disease + positive 2-month culture, OR pyrazinamide not completed, OR delayed sputum conversion
• Meningeal TB: 9-12 months (continuation phase extended to 10 months)
• Bone/Joint TB: 9 months recommended by some guidelines
• Culture-negative TB: 2HRZE + 2HR (4 months total)

• Found non-inferior to standard 6-month HRZE; WHO conditional recommendation

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NTEP Treatment Categories (Classical RNTCP - for exam reference)

Note: Under updated NTEP guidelines, daily fixed-dose combinations (FDCs) are used for all categories. Boxes are colour-coded: Red for Category I, Blue for Category II. Each blister pack for the intensive phase contains 1 day's medication; for the continuation phase, 1 week's supply.

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Treatment of Latent TB Infection (LTBI)

1. Isoniazid + Rifapentine weekly x 3 months (3HP) - regimen of choice; DOT for once-weekly
2. Rifampin daily x 4 months - preferred for HIV-negative
3. Isoniazid + Rifampin daily x 3 months
4. Isoniazid daily or twice weekly x 6-9 months (6 months acceptable)

• HIV-positive individuals (priority in high-burden countries)
• Children under 5 who are household contacts of PTB
• Recent close contacts of infectious TB
• Silicosis, diabetes, chronic renal failure
• Prisoners, homeless, illicit drug users
• Immigrants from high-burden countries (in low-burden settings)

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Drug-Resistant TB (DR-TB) Treatment

• Group A (always include): Levofloxacin/Moxifloxacin, Bedaquiline, Linezolid
• Group B (add if needed): Clofazimine, Cycloserine/Terizidone
• Group C (use when A+B insufficient): Ethambutol, Delamanid, Pyrazinamide, Imipenem-cilastatin, Amikacin, Ethionamide, PAS

• FDA-approved for XDR-TB and treatment-intolerant MDR-TB (Nix-TB study)
• Pretomanid: 200 mg daily; a nitroimidazole that inhibits mycolic acid biosynthesis

• Shorter regimen: 9-12 months (launched 2018, expanded nationwide)
• Longer regimen: 18-24 months (for complicated MDR-TB)
• Bedaquiline expanded from 2018; >46,000 DR-TB patients on shorter regimen

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PART 5: PSM - NATIONAL TB ELIMINATION PROGRAMME (NTEP)

Historical Milestones

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NTEP Goals (SDG Targets, baseline 2015)

• 80% reduction in TB incidence
• 90% reduction in TB mortality
• Zero TB patients/households facing catastrophic costs

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DOTS Strategy - 5 Components

1. Political will and administrative commitment
2. Diagnosis by quality-assured sputum smear microscopy
3. Adequate supply of quality-assured short-course chemotherapy drugs
4. Directly Observed Treatment (DOT)
5. Systematic monitoring and accountability

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STOP TB Strategy Components (2006, WHO)

1. Pursuing quality DOTS - expansion and enhancement
2. Addressing TB/HIV and MDR-TB
3. Contributing to health system strengthening
4. Engaging all care providers
5. Empowering patients and communities
6. Enabling and promoting research (diagnosis, treatment, vaccine)

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NTEP Organizational Structure (5 Levels)

• Medical Officer - TB Control (MO-TC)
• Senior Treatment Supervisor (STS)
• Senior TB Laboratory Supervisor (STLS) - 1 per 5 lakh population

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National Reference Laboratories (NRLs)

1. NTI, Bengaluru
2. NIRT, Chennai
3. NITRD, New Delhi
4. JALMA, Agra
5. • 2 others (6 NRLs total)

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4 Strategic Pillars of NTEP/NSP 2017-25

1. Detect - Early, complete case detection
2. Treat - Prompt, quality-assured treatment
3. Prevent - Preventive therapy, infection control
4. Build - Enabling environment, health system strengthening

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NTEP Objectives (RNTCP original)

1. Achieve ≥85% cure rate of infectious (smear-positive) TB cases through DOTS
2. Detect ≥70% of estimated cases through quality sputum microscopy

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Key NTEP Initiatives

• Case-based, web-based IT surveillance system (NI + KSHAY = eradication of TB)
• Functions: patient registration, diagnosis details, HIV status, follow-up, contact tracing, outcomes, DR-TB management, private facility notification
• SMS alerts to patients and programme officers
• 99-DOTS: IT-enabled adherence tool initially for HIV-TB patients

• Mandatory for ALL healthcare providers (public + private) to notify every TB case to District Health Officer/Municipal Health Officer monthly

• Import, manufacture, sale, distribution and use of serological tests for TB diagnosis banned by GoI
• Reason: Poor specificity, highly variable antibody response

• Direct benefit transfer: ₹500/month to TB patients for nutritional support throughout treatment
• Linked with NIKSHAY + Aadhaar

• GeneXpert/CBNAAT at all districts
• ~55% of notified TB cases offered UDST (2019 data)

• Expanded from 2018
• BPaLM for XDR-TB

• Systematic screening in high-risk populations: tribal, slums, prisons, orphanages, transit camps, old age homes

• Public-private partnership model
• Ensures notification and systematic treatment of private sector TB patients
• ₹500 incentive for notification + ₹500 for reporting treatment outcome (to private providers)

• Community engagement initiative
• "Ni-kshay Mitras" (donors/supporters adopted TB patients)

• Shift from thrice-weekly to daily dosing with Fixed Dose Combinations
• 6 weight bands for paediatric FDC

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Patient-Wise Box System

• Drugs supplied in colour-coded patient-wise boxes for full course
• Red box: Category I patients
• Blue box: Category II patients
• Intensive phase: blister pack = 1 day's medication
• Continuation phase: blister pack = 1 week's medication

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Drug Resistance Surveillance (DRS) under NTEP 2014-16

• MDR-TB prevalence: 2.84% in new cases, 11.60% in retreatment cases
• DR-TB Centres: 147 Nodal DR-TB Centres (NDR-TBC) - 1 per ~10 million population
• District DR-TB Centres (DDR-TBC): 1 per district - for uncomplicated RR-TB

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TB/HIV Co-management

• Integrated TB/HIV services: collaborative TB/HIV activities
• All TB patients screened for HIV
• All HIV-TB co-infected patients started on ART (regardless of CD4 count)
• TB treatment is started first; ART added after 2-8 weeks

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PART 6: GLOBAL TB PROGRAMS AND STRATEGIES

End TB Strategy (WHO, 2014-2035)

• Vision: Zero TB deaths, disease, and suffering
• Targets (from 2015 baseline):
  • By 2020: 20% reduction in incidence, 35% reduction in deaths
  • By 2025: 50% reduction in incidence, 75% reduction in deaths
  • By 2030 (SDG): 80% reduction in incidence, 90% reduction in deaths
  • By 2035: 90% reduction in incidence, 95% reduction in deaths

STOP TB Partnership (2001)

• Coordinates global TB efforts
• Developed Global Plan to Stop TB

WHO Global TB Report 2023 Key Figures

• Global incidence: 10.6 million (2022)
• India: 2.8 million cases (~27% of global burden)
• India's progress: 16% decline in incidence, 18% decline in deaths (2015-2022)

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PART 7: SPECIAL SITUATIONS (HIGH-YIELD)

TB in Pregnancy

• INH + Rifampicin + Ethambutol for 9 months (avoid Pyrazinamide in 1st trimester per older guidelines; WHO now recommends standard HRZE)
• Streptomycin is CONTRAINDICATED (ototoxicity to fetus)
• INH requires pyridoxine (B6) supplementation
• 3HP (Isoniazid + Rifapentine) is NOT recommended in pregnancy

TB Meningitis

• Duration: 9-12 months (continuation phase 10 months per Harrison's)
• Steroids: Dexamethasone/Prednisolone adjunct reduces mortality
• Ethambutol has poor CNS penetration - some guidelines substitute with Streptomycin/Ethionamide

Hepatotoxicity from Anti-TB Drugs

• All four first-line drugs can cause hepatitis (H, R, Z)
• Monitoring: LFTs baseline + if symptomatic
• If ALT >3x ULN with symptoms or >5x ULN without symptoms - stop all hepatotoxic drugs
• Reintroduce one at a time: R first, then H, then Z

BCG Vaccine

• Given at birth (or within first year) under UIP
• Protects against miliary TB and TB meningitis in children (70-80% efficacy)
• Does not protect against adult pulmonary TB

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QUICK REVISION MNEMONICS

• H (isoniazid): Hepatitis, Hyper-reflexia (neuropathy)
• R (rifampicin): Red-orange secretions, Rashes, Rifts enzyme interactions
• Z (pyrazinamide): Z-ero uric acid (hyperuricemia), Z-ap liver
• E (ethambutol): Eye (optic neuritis)

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