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🫁 TUBERCULOSIS - PARK'S TEXTBOOK (PSM)

High-Yield Chapter Summary | MBBS University + INICET/NEET PG

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📌 CHAPTER OVERVIEW - QUICK ORIENTATION

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SECTION 1: INTRODUCTION ⭐

Definition: Tuberculosis is a specific infectious disease caused by Mycobacterium tuberculosis. It primarily affects the lungs (pulmonary TB) but can also affect the intestines, meninges, bones/joints, lymph glands, skin, and other tissues.

• Chronic disease with varying clinical manifestations
• Bovine TB: caused by M. bovis - affects cattle; can be communicated to humans
• Pulmonary TB is the most important form in public health

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SECTION 2: PROBLEM STATEMENT 🔥

WORLD EPIDEMIOLOGY

HIGH BURDEN COUNTRIES (HBCs) 🔥

• 8 countries account for two-thirds of global TB burden
• India, Indonesia, China, Philippines, Pakistan, Nigeria, Bangladesh, South Africa
• India leads with highest number of cases globally

INDIA EPIDEMIOLOGY ⭐

⚠ Commonly confused: India's target to eliminate TB is 2025 (not 2030 which is WHO's global target)

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SECTION 3: NATURAL HISTORY OF TUBERCULOSIS 🔥⭐

AGENT FACTORS

The Organism

• M. tuberculosis - facultative intracellular parasite
• Readily ingested by phagocytes; resistant to intracellular killing
• Human strain: responsible for vast majority of cases
• Bovine strain: affects cattle; can infect humans via infected milk
• Indian TB bacillus said to be less virulent than European bacillus

Atypical (Non-tuberculous) Mycobacteria - Classification 🔥

🧠 Mnemonic: "Pretty Shy Naughty Rabbits" = Photochromogens, Scotochromogens, Non-photochromogens, Rapid growers

Source of Infection

1. Human source: Sputum-positive case (untreated/partially treated) - MOST COMMON
   • One case infects 10-15 persons per year
   • Slow-multiplying bacilli = "persisters/dormant bacilli" → seeds of future relapse
2. Bovine source: Infected milk - NOT a major problem in India (milk is boiled)

Communicability

• Infective as long as untreated
• Effective antimicrobial treatment reduces infectivity by 90% within 48 hours 🔥

HOST FACTORS ⭐

ENVIRONMENTAL FACTORS

• Overcrowding - facilitates droplet transmission
• Poor ventilation - prolongs survival of bacilli
• Poor socioeconomic conditions - linked to nutrition and access to care
• Sunlight and fresh air kill bacilli

MODE OF TRANSMISSION ⭐

1. Droplet infection (MAIN ROUTE) - via coughing, sneezing, speaking
   • Droplet nuclei: 1-5 µm diameter - remain suspended in air
   • Contain 1-3 bacilli
2. Droplet nuclei (Wells' droplet nuclei) - dried residue, can remain airborne for hours
3. Ingestion (bovine TB via milk - rare in India)
4. Inoculation (rare - lab workers)
5. Transplacental (congenital TB - very rare)

🔥 High yield: PRIMARY ROUTE = Inhalation of droplet nuclei

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SECTION 4: INDICATORS OF TUBERCULOSIS ⭐🔥

Key Epidemiological Indicators

1. Annual Risk of Tuberculosis Infection (ARTI) / Annual Infection Rate 🔥

Definition: The percentage of the population that gets newly infected with M. tuberculosis every year.

• Estimated from tuberculin surveys (tuberculin conversion rate)
• BEST indicator to evaluate the TB problem and its trend
• Higher rate = Greater TB problem
• Good treatment programme → LOWERS ARTI in the community
• ARTI in India: approximately 1.5% per year (high burden setting)

⚠ ARTI is the single BEST indicator of TB burden - a favourite MCQ!

2. Prevalence of Tuberculosis Infection

• Proportion of the population infected at any given time
• Estimated from tuberculin surveys

3. Annual Incidence of TB Disease (Case Notification Rate)

• Newly detected cases per 100,000 per year

4. Tuberculin Test / Mantoux Test ⭐

🔥 Factors causing FALSE NEGATIVE Mantoux:

• HIV/AIDS, malnutrition, measles, sarcoidosis, lymphoma
• Miliary TB, overwhelming sepsis
• Recent TB infection (<8 weeks - "window period")
• Technical errors (wrong injection technique)

🔥 Factors causing FALSE POSITIVE Mantoux:

• BCG vaccination (cross-reactivity)
• NTM infection
• Booster effect

5. Tuberculin Index

• Percentage of tuberculin-positive persons in a population (usually 14-year-olds)

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SECTION 5: REVISED (2013) WHO DEFINITIONS ⭐🔥

Presumptive Case (Earlier: "TB Suspect")

A patient presenting with symptoms or signs suggestive of TB.

A. CASE DEFINITIONS

• Biological specimen positive by:
  • Smear microscopy, OR
  • Culture, OR
  • WHO-endorsed rapid diagnostic test (WRD, e.g., Xpert MTB/RIF)

• Does NOT fulfil bacteriological criteria
• Diagnosed by clinician based on X-ray, histology, clinical presentation
• Receives full course of TB treatment
• If later found bacteriologically positive → reclassify as bacteriologically confirmed

Classification of TB Cases ⭐

1. Based on Anatomical Site

⚠ Miliary TB = classified as PTB (lung lesions present) Tuberculous pleural effusion WITHOUT lung lesion = EPTB Patient with BOTH PTB + EPTB = classified as PTB

2. Based on Treatment History 🔥

🧠 Mnemonic for treatment history categories: "New Rascals Take Lovers Other Times" = New, Relapse, Treatment failure, Lost to follow-up, Other, Transfer in

3. Based on Drug Resistance 🔥

⚠ New WHO 2021 XDR definition - previously included injectable agents; now includes Bedaquiline/Linezolid. This is a recent update!

4. Based on HIV Status

• HIV-positive TB case
• HIV-negative TB case
• HIV-unknown TB case

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SECTION 6: TREATMENT OUTCOMES ⭐🔥

For Drug-Sensitive TB Patients

For MDR/XDR-TB Patients

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SECTION 7: CONTROL OF TUBERCULOSIS 🔥⭐

THE THREE PILLARS OF TB CONTROL

┌─────────────────────────────────────────────┐
│         TB CONTROL STRATEGY                  │
├─────────────┬───────────────┬───────────────┤
│ CASE FINDING │  TREATMENT    │  PREVENTION   │
│ (Diagnosis)  │(Chemotherapy) │ (BCG/IPT/IEC) │
└─────────────┴───────────────┴───────────────┘

a. NOTIFICATION ⭐

• TB is a notifiable disease in India (since 2012 for all sectors; private sector made mandatory)
• Nikshay portal = national TB notification and management platform 🔥
• All TB cases MUST be notified regardless of sector (public or private)

b. CASE FINDING ⭐

Passive Case Finding

• Patient presents with symptoms → seeks care → diagnosed
• Default approach in most settings

Active Case Finding / Intensified Case Finding (ICF) 🔥

• Going out to find cases proactively in high-risk groups
• Targets:
  • HIV-positive individuals
  • Household contacts of TB patients
  • Slum dwellers, prisoners, migrant workers
  • Diabetics, malnourished individuals
  • Miners, stone-cutters

c. INTENSIFIED TB CASE FINDING (ICF) - Screening Strategies

• Mobile/fixed facility screening
• Door-to-door household screening

• Health care facilities - systematic screening of vulnerable individuals
• Congregate settings: shelters, old age homes, refugee camps, correctional facilities

d. CASE-FINDING TOOLS 🔥⭐

Microbiological Tools

🔥 CBNAAT (Cartridge Based NAAT) = GeneXpert MTB/RIF

• Detects MTB AND Rifampicin resistance simultaneously
• Result in ~2 hours
• Endorsed by WHO as initial diagnostic test
• Used in NTEP as first-line test for presumptive TB

Supportive (Non-Microbiological) Tools

Tuberculin Skin Test (Mantoux)

• (See Section 4 above for details)

TB-IGRA (Interferon Gamma Release Assays) 🔥

• In vitro test detecting IFN-γ release by sensitized T-cells on exposure to TB antigens (ESAT-6, CFP-10)
• Two commercial assays:
  • QuantiFERON-TB Gold In-Tube (QFT-GIT)
  • T-SPOT.TB
• Advantages over TST:
  • NOT affected by BCG vaccination (no false positive)
  • Better specificity
  • Single visit (no need to return for reading)
• Useful for: diagnosing LTBI, healthcare workers, immunocompromised

Chest X-Ray

• Cannot diagnose TB alone; supportive tool
• Useful in: smear-negative PTB, HIV-TB, screening

Adenosine Deaminase (ADA)

• Elevated in TB pleural effusion, TB meningitis, TB pericarditis

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SECTION 8: CHEMOTHERAPY ⭐🔥

PRINCIPLES OF TB TREATMENT

• Every case of active TB requires chemotherapy
• Objective: Cure = eliminate fast AND slowly multiplying bacilli (including "persisters")
• Effects judged by elimination of bacilli from sputum (not by X-ray healing)
• Treatment must be: free of charge, adequate, appropriate, and applied to entire pool of infectors
• Patient compliance is critical - incomplete treatment → relapse + drug resistance

Anti-Tuberculosis Drugs

Classification of Anti-TB Drugs 🔥

FIRST-LINE DRUGS ⭐🔥

🧠 Mnemonic for first-line drugs: RIPES = Rifampicin, Isoniazid, Pyrazinamide, Ethambutol, Streptomycin

🔥 Rifampicin is the cornerstone of modern short-course chemotherapy

⚠ Only RMP is bactericidal against PERSISTERS (dormant bacilli in solid caseous lesions)

Adverse Effects Summary Table ⭐

FIXED DOSE COMBINATIONS (FDCs) ⭐🔥

FDC = Products containing 2 or more active ingredients in fixed doses for a particular indication.

NTEP FDC Regimens (2019 onwards - Daily Regimen):

• Intensive Phase (IP): 4-FDC = H + R + Z + E (HRZE)
• Continuation Phase (CP): 3-FDC = H + R + E (HRE)

• Dispersible 3-FDC = H + R + Z (HRZ) [for IP]
• Dispersible 2-FDC = H + R [for CP]

Standard Treatment Regimen (Drug-Sensitive TB) 🔥⭐

🔥 NTEP moved from Thrice-weekly (DOTS) to DAILY regimen in 2019 - this is a major recent update!

⚠ Weight-band based dosing is used in NTEP for FDC administration

Pre-Treatment Evaluation ⭐

1. Detailed history (mental illness, seizures, drug/alcohol)
2. Weight & height
3. CBC
4. Blood sugar (screen for DM)
5. LFT
6. Blood urea & creatinine (renal function)
7. Urine R/M
8. Chest X-ray
9. Pregnancy test (women of childbearing age)
10. HIV testing (mandatory in ALL TB cases)

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SECTION 9: DRUG-RESISTANT TUBERCULOSIS (DR-TB) 🔥⭐

Types of Drug Resistance

Primary (Pre-treatment) Resistance

• Resistance in patient who has NEVER received the drug
• Can occur due to:
  • Infection with already resistant strain
  • Spontaneous mutation during rapid multiplication
  • Transfer of episomes (non-chromosomal heritable genes)

Secondary (Acquired) Resistance

• Bacteria were sensitive at start of treatment but became resistant DURING treatment
• Caused by inadequate treatment

Causes of Drug-Resistant TB (Programmatic) 🔥

• Genetic mutation in TB bacilli

• Non-compliance with treatment
• Irregular drug intake
• Premature cessation of treatment

• Inadequate drug supply
• Poor quality drugs
• Wrong treatment regimen
• Insufficient duration of treatment
• No supervision

🧠 Mnemonic for DR-TB causes: "3 Ps" = Patient (non-compliance), Programme (inadequate), Pill (poor quality/supply)

MDR-TB Treatment 🔥⭐

Drug Classification for MDR-TB (WHO)

MDR-TB Regimens in NTEP 🔥

Key Newer Drugs 🔥

DR-TB Centres

• DDR-TBC: District Drug-Resistant TB Centre
• NDR-TBC: Nodal Drug-Resistant TB Centre (referral for complex cases)
• NDR-TBC manages: additional drug resistance, drug intolerance, failing regimen, treatment interruption >1 month

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SECTION 10: BCG VACCINATION ⭐🔥

Key Facts

🔥 BCG is MOST effective against severe forms (miliary TB, TB meningitis) in children - up to 80%

⚠ BCG does NOT prevent adult pulmonary TB reliably (inconsistent data across countries) - this is a commonly confused concept!

BCG Testing (Mantoux Post-BCG)

• Tuberculin test becomes positive after BCG vaccination
• Cannot distinguish BCG-induced positivity from true infection
• IGRA is preferred in BCG-vaccinated individuals

BCG Scar

• Appears at 2-6 weeks post-vaccination
• Scar indicates successful vaccination (but absence does NOT mean failure)

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SECTION 11: PREVENTIVE THERAPY / LATENT TB INFECTION (LTBI) 🔥

Isoniazid Preventive Therapy (IPT) ⭐🔥

Latent TB Infection (LTBI): Infection with M. tuberculosis without active disease; positive tuberculin test/IGRA but no symptoms/signs.

Vulnerable Groups Recommended for LTBI Testing and Treatment:

1. PLHIV
2. Household contacts of bacteriologically confirmed PTB (especially children <5 yrs)
3. Patients starting anti-TNF treatment, dialysis, organ transplant
4. Silicosis patients

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SECTION 12: NATIONAL TUBERCULOSIS ELIMINATION PROGRAMME (NTEP) ⭐🔥

(Formerly RNTCP - Revised National Tuberculosis Control Programme)

Historical Timeline 🔥⭐

🔥 RNTCP renamed NTEP in 2017 - Very common MCQ!

DOTS (Directly Observed Treatment, Short-course)

🧠 Mnemonic for DOTS components: "PC-DS-ME" = Political Commitment, Case Detection, Drug supply (regular), Short-course chemotherapy under supervision, Monitoring & Evaluation

Nikshay Portal 🔥

• Online notification platform for TB
• All TB patients registered on Nikshay
• Mandatory for public and private sector

Nikshay Poshan Yojana (NPY) 🔥

• Direct Benefit Transfer scheme
• ₹500/month for nutritional support to every notified TB patient
• Till treatment completion

NIKSHAY MITRA (2022) 🔥

• Community support initiative
• Individuals, organizations, corporate adopt TB patients
• Provide nutritional, vocational, and psychosocial support

Programme Structure (NTEP Levels)

🔥 TU (Tuberculosis Unit) covers ~500,000 population - key MCQ fact!

Microscopy Centre

• 1 per 100,000 population (in high prevalence areas: 1 per 50,000)
• Provides free sputum microscopy

NTEP Laboratory Network (LNS) - Levels 🔥

Directly Observed Treatment (DOT) Provider Options

• Healthcare worker
• Community volunteer (ASHA)
• Family member (not preferred but allowed)

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SECTION 13: CHILDHOOD TUBERCULOSIS ⭐

Key Features

• Children <15 yrs = 12% of global TB burden
• Children <5 yrs are MOST VULNERABLE (poor immunity)
• Primary source = infected adult in household
• Paucibacillary disease (smear often negative)
• Extra-pulmonary forms more common in children
• Primary complex = Ghon's focus + regional lymphadenopathy

Diagnosis in Children

• Difficult - smear often negative
• CBNAAT (Xpert) recommended
• Gastric lavage (early morning) if child cannot expectorate
• Mantoux test (may be false negative in severely malnourished)
• Chest X-ray

Treatment in Children (NTEP)

• Dispersible FDC tablets (child-friendly)
• IP: 2HRZ (2 months - 3 FDC: H+R+Z)
• CP: 4HR (4 months - 2 FDC: H+R)
• Weight-band based dosing

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SECTION 14: TB AND COMORBIDITIES 🔥⭐

TB AND HIV ⭐🔥

TB AND DIABETES (TB-DM) 🔥

TB AND TOBACCO 🔥

1. Relevance of quitting
2. Risk of continuing
3. Reward of quitting
4. Roadblock to quitting
5. Repeat at each visit

TB AND COVID-19 🔥

• COVID-19 pandemic → reversed progress towards global TB targets
• India: TB notifications fell >50% (March to April 2020 during lockdown)
• COVID-19 impacts on TB services:
  • Fewer facilities providing TB care
  • Reduced case detection
  • Treatment interruptions
  • Worsening outcomes
  • Increased poverty → undernutrition → worsened TB burden
• Physical distancing → may reduce TB transmission but offset by longer infectiousness

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SECTION 15: SURVEILLANCE ⭐

Surveillance in TB = 2 aspects:

1. Surveillance of TB situation (measuring ARTI, case rates)
2. Surveillance of control measures (BCG coverage, treatment outcomes)

• Nikshay serves as the national TB surveillance platform
• Active vs. passive surveillance
• Quarterly reports from TU to DTC to State to National level

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SECTION 16: REHABILITATION ⭐

• Less important with success of domiciliary chemotherapy
• Groups needing rehabilitation:
  • Chronically ill, still excreting TB bacilli
  • Those who had lung resection
• Most patients can continue normal work and life during treatment (outpatient basis)

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SECTION 17: END TB STRATEGY (WHO) 🔥⭐

Targets (by 2030)

Milestones (by 2020)

• 20% reduction in TB incidence rate
• 35% reduction in TB deaths

India's NSP (National Strategic Plan 2017-2025)

• DETECT - Diagnose all TB patients
• TREAT - Ensure all diagnosed TB patients complete treatment
• PREVENT - Prevent TB by BCG, IPT, infection control
• BUILD - Build and sustain an enabling ecosystem

🔥 India's target: TB elimination by 2025 (defined as <1 case per million population/year)

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🟠 PAEDIATRIC TB (Block 6 content) ⭐

• Covered under childhood TB section above
• Extra features:
  • TB in pregnancy: more challenging management
  • Preferred drugs: INH, RMP, EMB safe in pregnancy; PZA - used cautiously; Streptomycin - CONTRAINDICATED (ototoxicity to foetus)
  • Congenital TB: rare but possible

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📋 ONE-PAGE RAPID REVISION SHEET

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TUBERCULOSIS - RAPID REVISION

AGENT: M. tuberculosis | FACULTATIVE INTRACELLULAR PARASITE
SOURCE: Human (sputum+ve) | Bovine (milk)
TRANSMISSION: DROPLET NUCLEI (1-5 µm) - PRIMARY ROUTE
INFECTIVITY: 10-15 persons/yr/case | Reduced 90% in 48hrs with treatment

EPIDEMIOLOGY:
• Global cases (2019): 10 million | Deaths: 1.2M (+208K HIV)
• India: 26% global burden | Target: ELIMINATE by 2025
• 1/3 world infected; 5-10% develop disease

INDICATORS:
• BEST INDICATOR: ARTI (Annual Risk of TB Infection)
• Mantoux: 1TU PPD RT23 | ID | Read 48-72h | +ve ≥10mm

DEFINITIONS (2013 WHO):
• Presumptive case (was: TB suspect)
• Bacteriologically confirmed vs Clinically diagnosed
• New / Relapse / Tx failure / LTFU / Others
• MDR-TB: INH + RMP resistant | XDR: MDR + FQ + Bdq/Lzd
• Treatment success = Cured + Treatment completed

FIRST-LINE DRUGS (RIPES):
• R = Rifampicin | H = INH | Z = PZA | E = EMB | S = Streptomycin
• ONLY RMP kills PERSISTERS | INH strongest for fast-multiplying

FDC REGIMEN (NTEP 2019 - DAILY):
• New PTB: 2HRZE + 4HRE = 6 months
• TBM/Spinal: 2HRZE + 10HRE = 12 months
• Daily (not thrice-weekly) since 2019

MDR-TB:
• Causes: Non-compliance, inadequate Rx, poor drug supply
• Group A: FQ + Bedaquiline + Linezolid (always include)
• Shorter regimen: 9-11 months | Longer: 18-20 months
• Bedaquiline: new drug - ATP synthase inhibitor

BCG:
• Live attenuated M. bovis | Birth | ID | Left arm
• ~80% effective against miliary/meningeal TB in children
• Variable efficacy against adult PTB

NTEP (renamed from RNTCP in 2017):
• DOTS 5 components: Political commitment, SSM, FDC under DOT, Drug supply, Monitoring
• TU covers 500,000 population
• Microscopy: 1 per 100,000 population
• Nikshay: notification portal
• NPY: ₹500/month nutritional support
• DAILY regimen since 2019 (replaced thrice-weekly)

COMORBIDITIES:
• HIV: 50-100x risk | ART within 2 wks (CD4<50) | CPT given
• DM: 2-3x risk | Screen all TB for DM
• Tobacco: 3x prevalence | 38% TB deaths linked
• COVID-19: >50% fall in notifications (Apr 2020)

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⭐ TOP 25 MOST IMPORTANT POINTS

1. M. tuberculosis = facultative intracellular parasite
2. Primary route of transmission = Inhalation of droplet nuclei (1-5 µm)
3. One infectious PTB case infects 10-15 persons/year
4. Treatment reduces infectivity by 90% within 48 hours
5. 1/3 world population infected; only 5-10% develop disease
6. India has 26% of global TB burden; TARGET: eliminate by 2025
7. ARTI = BEST indicator of TB problem in community
8. Mantoux test: 1 TU PPD RT23, intradermal, read at 48-72 hours; ≥10mm = positive
9. IGRA (QuantiFERON/T-SPOT): NOT affected by BCG vaccination; better specificity
10. 2013 WHO: TB suspect renamed "Presumptive TB case"
11. MDR-TB = Resistance to at least INH + Rifampicin
12. XDR-TB (new 2021) = MDR/RR-TB + resistance to FQ + Bedaquiline or Linezolid
13. CBNAAT (Xpert MTB/RIF): TB detection + RIF resistance in 2 hours; WHO-endorsed first test
14. Rifampicin = ONLY drug active against dormant/persister bacilli
15. Pyrazinamide = active in acidic environment (inside macrophages)
16. Ethambutol = causes optic neuritis (colour vision, reversible)
17. Streptomycin = CONTRAINDICATED in pregnancy (foetal ototoxicity)
18. NTEP daily FDC regimen (2019): 2HRZE + 4HRE = 6 months for new PTB
19. TBM / Spinal TB: 12 months treatment (2HRZE + 10HRE)
20. RNTCP renamed to NTEP in 2017; India target TB elimination by 2025
21. TU (Tuberculosis Unit) covers 500,000 population
22. DOTS 5 components (remember for MCQ): Political commitment, sputum microscopy, standardized Rx under DOT, regular drug supply, monitoring
23. BCG: ~80% effective against miliary/TBM in children; variable against adult PTB
24. HIV increases TB risk 50-100 times; ART within 2 weeks if CD4 <50
25. Nikshay Poshan Yojana: ₹500/month nutritional support to all notified TB patients

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🔥 TOP 20 MCQ FACTS

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📝 TOP 10 UNIVERSITY SAQ/LAQ QUESTIONS

1. SAQ: Define ARTI. Why is it considered the best indicator of TB burden? (5 marks)
2. LAQ: Describe the Revised 2013 WHO definitions of TB cases and treatment outcomes. (10 marks)
3. SAQ: Discuss the role of DOTS in TB control. Write the 5 components of DOTS. (5 marks)
4. LAQ: Describe the NTEP (formerly RNTCP) - its structure, objectives, and treatment regimen. (15 marks)
5. SAQ: What is MDR-TB? Write the causes and management of drug-resistant TB. (5 marks)
6. SAQ: Describe the Mantoux test - technique, reading, interpretation, and significance. (5 marks)
7. LAQ: Describe the epidemiology of tuberculosis in India and the world. Include global burden, India's burden, and indicators. (10 marks)
8. SAQ: Write a note on BCG vaccination - type, schedule, efficacy, and limitations. (5 marks)
9. SAQ: Describe TB-HIV co-infection - epidemiology, management, and IPT. (5 marks)
10. LAQ: Describe the natural history of tuberculosis including agent, host, and environmental factors. (10 marks)

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🩺 TOP 10 VIVA QUESTIONS (with answers)

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⚠ COMMON MISTAKES STUDENTS MAKE

1. Confusing India's TB elimination target (2025) with WHO's (2030)
2. Saying TB is transmitted by droplets (incorrect - mainly by DROPLET NUCLEI - the dried, smaller residue)
3. Forgetting that Miliary TB is classified as PTB (not EPTB)
4. Wrong Mantoux reading time - must be 48-72 hours, NOT 24 or 72+ hours
5. Saying "TB suspect" - outdated term; correct term is "Presumptive TB case" (2013 change)
6. XDR-TB definition - using old definition (injectable agents) instead of new 2021 WHO definition (Bedaquiline/Linezolid)
7. BCG efficacy confusion - BCG is highly effective (80%) against miliary/meningeal TB in children, NOT against adult PTB
8. Forgetting RNTCP → NTEP rename (2017)
9. Saying DOTS is still thrice-weekly - India shifted to DAILY regimen in 2019
10. Forgetting that ARTI, not prevalence or incidence, is the BEST indicator of TB burden
11. Saying INH kills persisters - Only RIFAMPICIN kills persisters/dormant bacilli
12. Missing HIV testing is MANDATORY for ALL TB patients in NTEP

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✅ LAST-MINUTE REVISION CHECKLIST

• Definition of TB (M. tuberculosis, facultative intracellular)
• Droplet nuclei as the primary mode of transmission
• 10-15 persons/yr infected by one case; 90% infectivity reduction in 48 hrs
• Global TB stats 2019 (10 million, 1.2M deaths, India = 26%)
• India's elimination target = 2025
• ARTI = BEST indicator; measured by tuberculin surveys
• Mantoux: 1 TU PPD RT23, ID, 48-72 hrs, ≥10 mm = positive
• IGRA advantages over Mantoux
• 2013 WHO definitions: Presumptive, Bacteriologically confirmed, Clinically diagnosed
• 4 classification criteria (site, history, drug resistance, HIV)
• MDR-TB = INH + RIF; XDR-TB (2021) = MDR + FQ + Bdq/Lzd
• Treatment outcomes: Cured, Treatment completed, Failed, Died, LTFU, Not evaluated
• DOTS 5 components
• Standard NTEP regimen: 2HRZE + 4HRE (6 months, DAILY)
• TBM: 12 months treatment
• First-line drugs: RIPES (bactericidal vs bacteriostatic)
• RMP = only drug against persisters
• EMB = optic neuritis; PZA = acidic environment; SM = avoid in pregnancy
• BCG: live attenuated M. bovis; birth; left arm; 80% efficacy (miliary/TBM)
• NTEP structure: National/State/District/TU(500K)/Microscopy centre (100K)
• RNTCP → NTEP (2017); Daily regimen since 2019
• Nikshay = notification portal; NPY = ₹500/month
• HIV: 50-100x TB risk; ART within 2 wks if CD4 <50; CPT mandatory
• DM: 2-3x TB risk; screen all TB patients for DM
• Tobacco: 38% TB deaths linked; 3x prevalence in smokers
• COVID-19: >50% fall in TB notifications (April 2020)
• Bedaquiline: ATP synthase inhibitor; new class; QT prolongation

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🫁 TUBERCULOSIS - PARK'S TEXTBOOK (PSM)

Part 2 - Detailed Programme, Drugs, Newer Initiatives & Complete Revision

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SECTION 18: SECOND-LINE ANTI-TB DRUGS ⭐🔥

Complete Drug Classification for DR-TB

ANTI-TB DRUGS
├── FIRST-LINE (HRZES)
│   ├── Bactericidal: H, R, Z, S
│   └── Bacteriostatic: E
└── SECOND-LINE
    ├── Injectable aminoglycosides: Kanamycin (Km), Amikacin (Am), Capreomycin (Cm)
    ├── Fluoroquinolones: Levofloxacin (Lfx), Moxifloxacin (Mfx)
    ├── Oral bacteriostatic: Cycloserine (Cs), Ethionamide/Prothionamide (Eto/Pto), PAS
    └── Newer agents: Bedaquiline (Bdq), Delamanid (Dlm), Linezolid (Lzd), Clofazimine (Cfz)

Key Second-Line Drug Details ⭐🔥

Fluoroquinolones (FQ)

• Levofloxacin (Lfx) and Moxifloxacin (Mfx) - most important in MDR-TB regimens
• Bactericidal
• Group A drugs (always include in MDR-TB regimen)
• Avoid in children (cartilage damage concerns) unless no alternative

Aminoglycosides (Second-Line Injectables)

• Kanamycin (Km): Bactericidal; active against streptomycin-resistant, INH-resistant, cycloserine-resistant strains
• Amikacin (Am): Same spectrum as kanamycin; used if Km resistant
• Capreomycin (Cm): Cyclic polypeptide; similar to aminoglycosides in action
• All cause: ototoxicity, nephrotoxicity, vestibular damage

Cycloserine (Cs) 🔥

• Mainly bacteriostatic
• Active against bacilli resistant to INH or streptomycin, and against atypical mycobacteria
• Mechanism: Inhibits bacterial cell wall synthesis (D-alanine analog)
• Side effects: neuropsychiatric (psychosis, depression, seizures)
• Pyridoxine (Vit B6) given to prevent neurological side effects

Thioacetazone ⚠

• Bacteriostatic
• NEVER use in HIV patients - causes severe, potentially fatal skin reactions (Stevens-Johnson syndrome)
• Rapidly diffuses into body tissues; crosses placenta; secreted in milk
• Side effects: GI disturbances, haemolytic anaemia, blurring of vision, urticaria

Macrolides

• Azithromycin and Clarithromycin - have activity against TB bacilli
• Used for atypical mycobacterial infections and relapse cases

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Bedaquiline (BDQ) - MUST KNOW 🔥⭐

Eligibility for Bedaquiline:

1. MDR/RR-TB with resistance to FQ or SLI
2. XDR-TB
3. Mixed pattern resistant TB
4. Treatment failure of MDR-TB with FQ/SLI resistance

Contraindications for Bedaquiline (and Delamanid): 🔥

• Pregnancy and lactation
• Uncontrolled cardiac arrhythmia requiring medication
• QTcF ≥500 ms at baseline
• History of additional QT risk factors (heart failure, hypokalaemia, family history of long QT)

⚠ Key teaching point: Both Bedaquiline AND Delamanid cause QTcF prolongation - ECG monitoring is MANDATORY

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Delamanid (DLM) 🔥

⚠ Delamanid vs Bedaquiline: Both are newer drugs for DR-TB; both cause QT prolongation; Bdq is for ≥18 yrs (Dlm for ≥6 yrs); different mechanisms

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Drug Dosages - First-Line Anti-TB Drugs (NTEP) ⭐

🔥 Streptomycin is used only in certain situations in NTEP: TB meningitis or as replacement if ADR to another first-line drug.

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FDC Weight-Band Dosing for Adults ⭐

🔥 If patient's weight increases by >5 kg and crosses to next weight band → increase to next higher weight band FDC

Paediatric FDC Treatment (NTEP) ⭐

• 6 weight bands used for paediatric dosing
• Family member can provide DOT for paediatric patients
• Adolescents (10-19 yrs): treated as adults

Steroid Use in TB ⭐

• Adjunctive therapy indicated in:
  • TB pericarditis (reduces constrictive pericarditis risk)
  • TB meningitis (reduces mortality and complications)
• High dose steroids tapered over 6–8 weeks

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SECTION 19: MDR-TB STANDARD REGIMENS - DETAILED ⭐🔥

Complete MDR-TB Regimen Table

🧠 Mnemonic for Shorter MDR regimen drugs: "Make Kites Every Cool Zebra Hop" = Mfx, Km, Eto, Cfz, Z, Hh (high dose), E

WHO Group A, B, C Classification for MDR Regimen Construction 🔥

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DR-TB Follow-Up Monitoring Key Points ⭐

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SECTION 20: NTEP PROGRAMME STRUCTURE - DETAILED ⭐🔥

Organization Structure (Top to Bottom)

NATIONAL LEVEL
Ministry of Health and Family Welfare (MoHFW)
    │
Central TB Division (CTD)
    │── AS & DG (RNTCP & NACO)
    │── DDG-TB (Deputy Director General TB)
    │── Joint Secretary (Admin/Financial control)
    │── National TB Institute (NTI), Bengaluru
    │── 6 National Reference Laboratories (NRLs)
    │
STATE LEVEL
State TB Cell (STC)
    │── State TB Officer (STO) - full-time, trained at national level
    │── STDC (State TB Training & Demonstration Centre)
    │   ├── Training Unit
    │   ├── Supervision & Monitoring Unit
    │   └── IRL (Intermediate Reference Laboratory)
    │── State Drug Store (SDS): 1 per 5 crore population
    │
DISTRICT LEVEL
District TB Centre (DTC)
    │── District TB Officer (DTO) - full-time
    │── DR-TB Centre (DRTB-C): District & Nodal levels
    │
SUB-DISTRICT LEVEL
Tuberculosis Unit (TU) - covers ~500,000 population
    │── Medical Officer TB Control (MOTC)
    │── Treatment Organizer (TO)
    │── Senior Treatment Supervisor (STS)
    │── Senior TB Lab Supervisor (STLS)
    │
PERIPHERAL LEVEL
Designated Microscopy Centre (DMC)
    │── 1 per 100,000 population
PHC / CHC / Sub-district Hospital
    │── DOT centre

National Reference Laboratories (NRLs) 🔥⭐

🔥 NTI Bengaluru = Head NRL for NTEP - frequently asked in MCQs

STDC (State TB Training and Demonstration Centre)

• 3 units: Training unit, Supervision & Monitoring unit, IRL
• Operational Research is also a component of STDC

Tuberculosis Unit (TU) - Sub-district Level ⭐🔥

Designated Microscopy Centre (DMC) ⭐

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SECTION 21: PATIENT-WISE BOX SYSTEM ⭐

• Patient-wise boxes contain the FULL COURSE of treatment
• Drugs packaged in blister packs
• IP: each blister pack = one day's medication
• CP: each blister pack = one week's supply
• Box colours by category:
  • Red: Category I patients
  • Blue: Category II patients

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SECTION 22: TB CARE IN THE PRIVATE SECTOR ⭐🔥

~70% of patients in India seek care first in the private sector (NSSO data)

Issues in Private Sector TB Care:

• Delays in diagnosis
• Over-dependence on X-ray for diagnosis
• Use of multiple non-standard regimens
• Inappropriate treatment durations
• No mechanism to ensure full course completion
• No recording of treatment outcomes
• No referral/transfer system

Public vs Private Sector - Comparison Table ⭐

Private Sector Engagement (NTEP) 🔥

• Mandatory notification of all TB cases in private sector (since 2012)
• Nikshay platform for private sector notification
• Public-Private Mix (PPM) strategy
• PP-DOTS: Providing free NTEP drugs to private patients
• NGO/corporate partnerships

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SECTION 23: PROGRAMMATIC MANAGEMENT OF DRUG-RESISTANT TB (PMDT) ⭐🔥

PMDT Structure (DR-TB Centres)

DDR-TBC vs NDR-TBC 🔥

Pre-treatment Evaluation at DR-TBC ⭐

• Detailed history
• Baseline biochemical investigations
• ECG (mandatory - QTcF monitoring for Bdq/Dlm)
• Correct electrolyte imbalance before treatment start
• Counselling (patient + family members)
• HIV testing
• Initial home visit by DTO

Pharmacovigilance 🔥

WHO definition: "Science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem."

• Fundamental activity to inform patient safety in healthcare
• Public health surveillance activity
• Priority: establish pharmacovigilance at DR-TBC level
• aDSM (active drug safety monitoring) - part of DR-TB programme

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SECTION 24: DRUG RESISTANCE SURVEILLANCE (DRS) ⭐

• DRS under NTEP conducted to determine prevalence of drug resistance
• Target: New sputum smear-positive PTB AND previously treated sputum smear-positive PTB patients
• Primary MDR-TB in India: ~2.8% (new cases) 🔥
• Drug resistance in re-treatment cases is much higher
• Prevalence of drug resistance = indicator of effectiveness of TB control activities

🔥 Drug resistance in re-treatment cases is significantly higher than new cases - always emphasize this!

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SECTION 25: NEWER INITIATIVES IN NTEP ⭐🔥

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SECTION 26: VULNERABLE GROUPS FOR TB SCREENING 🔥⭐

A vulnerable group = any group in which prevalence/incidence of TB is significantly higher than the general population

Recommended Vulnerable Groups for Intensified Case Finding:

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SECTION 27: TB AND PREGNANCY ⭐🔥

⚠ MOST important fact: Streptomycin = ONLY anti-TB drug absolutely contraindicated in pregnancy (ototoxicity to foetus)

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SECTION 28: NATIONAL STRATEGIC PLAN (NSP) 2017–2025 ⭐🔥

Vision

"TB-Free India with zero deaths, disease and poverty due to TB"

4 Strategic Pillars - DTPB 🔥⭐

🧠 Mnemonic: "DTPB" = "Don't Treat Patients Badly"

NSP Targets (by 2025): 🔥

Key Strategies of NSP:

1. Private sector engagement
2. Active case finding
3. Drug-resistant TB case management
4. Addressing social determinants (especially nutrition)
5. Robust surveillance system
6. Community engagement and multi-sectoral approach

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SECTION 29: END TB STRATEGY (WHO 2015-2035) ⭐🔥

Milestones and Targets

3 Pillars of End TB Strategy:

1. Integrated patient-centred TB care and prevention
2. Bold policies and supportive systems
3. Intensified research and innovation

3 Principles:

1. Government stewardship and accountability
2. Strong coalition with civil society
3. Protection and promotion of human rights, ethics and equity

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SECTION 30: INDICATIONS FOR HOSPITALIZATION IN TB ⭐

Most TB patients are managed as OUTPATIENTS (domiciliary treatment)

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SECTION 31: DIAGNOSIS ALGORITHM IN NTEP 🔥⭐

Adult PTB Diagnosis Algorithm (NTEP)

Presumptive TB patient (cough ≥2 weeks + other symptoms)
        │
   CBNAAT (Xpert MTB/RIF) [First test]
   ┌─────────────────────────────┐
   │                             │
MTB detected                MTB NOT detected
   │                             │
RIF resistant?           Clinical suspicion still high?
   │                             │
  YES: DR-TB pathway       Chest X-ray + clinical assessment
   │                             │
  NO: Start 2HRZE+4HRE    CXR suggestive? → Treat as PTB
   (Daily regimen)        CXR not suggestive? → Consider alternatives

Paediatric TB Diagnosis Algorithm (NTEP) 🔥

Presumptive paediatric TB
        │
CBNAAT (preferred) OR smear microscopy
        │
MTB detected → Microbiologically confirmed TB → Treat
        │
MTB NOT detected
        │
Chest X-ray + Mantoux (2 TU PPD RT23)
        │
    ┌───────────────────────────┐
    │                           │
CXR highly suggestive      CXR non-specific
(miliary/lymphadenopathy/  (consolidation, etc.)
 cavitary)                     │
    │                      TST positive (≥10mm)?
Treat regardless of TST        │
                           Yes → Treat
                           No → Consider alternative Dx
                               Antibiotics (NOT quinolones/linezolid)
                               Persist → Refer to expert

⚠ Key: Do NOT use quinolones, linezolid, or amoxicillin-clavulanic acid as antibiotics in suspected paediatric TB - these have anti-TB activity and can mask diagnosis or lead to inappropriate reliance on empirical treatment!

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SECTION 32: TB PREVENTIVE THERAPY - DETAILED ⭐🔥

Isoniazid Preventive Therapy (IPT) / LTBI Treatment

Who Should Receive IPT (NTEP eligibility): 🔥

🔥 Active TB must ALWAYS be ruled out BEFORE starting IPT - if active TB is present, IPT alone will cause drug resistance!

TB Preventive Therapy for Children - NTEP Doses:

• INH: 10 mg/kg/day (max 300 mg)
• Duration: 6 months
• Given at DMC/PHC level

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SECTION 33: HIV-TB CO-INFECTION - DETAILED MANAGEMENT ⭐🔥

Epidemiology

• HIV-positive TB patients: 8.2% of global TB burden (2019)
• TB leading cause of death in PLHIV
• HIV increases risk of TB by 50-100 times
• HIV-TB co-infection deaths: 208,000 (2019)

Management Principles:

Treat TB First, Then Start ART

Co-trimoxazole Preventive Therapy (CPT) 🔥

• Given to ALL HIV-positive TB patients
• Reduces overall mortality by preventing Pneumocystis pneumonia, toxoplasmosis, bacterial infections
• Given throughout TB treatment and continued beyond

IPT for PLHIV

• After completing TB treatment → give IPT (6-9 months)
• IPT reduces TB incidence in PLHIV by 33-62%

Drug Interactions - RMP and ART 🔥⚠

• Rifampicin is a potent CYP450 enzyme inducer
• Reduces plasma levels of most protease inhibitors (PIs) by 75-90%
• Preferred ART in TB-HIV: Efavirenz-based regimen (EFV not significantly affected by RMP)
• Avoid: Nevirapine (NVP) is affected by RMP; PIs (lopinavir, ritonavir) - levels too low with RMP

⚠ Key interaction: Rifampicin + Protease Inhibitors = treatment failure due to drastically reduced PI levels → use Efavirenz-based ART in TB-HIV

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SECTION 34: TB AND DIABETES MELLITUS - DETAILED 🔥

Bidirectional Relationship

• DM → TB: 2-3x increased risk of TB; impaired immunity (neutrophil function, macrophage killing)
• TB → DM: TB causes hyperglycaemia; worsens glycaemic control

Impact of DM on TB Outcomes:

• More smear-positive cases
• More cavitary disease
• More treatment failure
• More drug resistance
• More relapse
• Higher mortality

India Context:

• India has one of the highest DM burdens worldwide
• ~25-30% TB patients in India have coexisting DM
• "Double burden" problem

Screening Protocol:

• Every TB patient must be screened for DM (FBS or RBS or HbA1c)
• Every DM patient with respiratory symptoms → screen for TB

Drug Interactions - TB drugs + DM drugs: ⚠

• RMP is a CYP450 inducer → reduces blood glucose-lowering effect of sulphonylureas and may affect metformin
• Monitor blood sugar closely during TB treatment
• INH can cause hypoglycaemia in some cases

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SECTION 35: TB AND TOBACCO - KEY FACTS 🔥

How Tobacco Worsens TB:

1. Toxic chemicals cause bronchial surface damage
2. Weakens immune response against TB bacteria
3. Increases risk of TB infection AND active TB
4. Affects clinical manifestations
5. Increases relapse risk
6. Impairs sputum conversion
7. Increases drug resistance
8. Increases TB mortality

Recording and Counselling in NTEP:

• Tobacco use status recorded in TB Treatment Card at registration
• 5 R's for tobacco cessation counselling:
  1. Relevance of quitting
  2. Risk of continuing
  3. Reward of quitting
  4. Roadblock to quitting
  5. Repeat at each visit

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SECTION 36: TB AND COVID-19 - KEY POINTS 🔥

COVID-19 Impacts on TB Services:

• Fewer health facilities providing out-patient TB care
• Fewer facilities providing MDR-TB care
• Lockdowns → TB patients unable to reach treatment facilities
• Worsening treatment outcomes due to interruptions
• Loss of income → increased poverty → undernutrition → worse TB outcomes
• Potential reversal of progress towards End TB targets

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SECTION 37: INFECTION CONTROL IN TB ⭐

Administrative Controls (most important) 🔥

1. Triage of patients - separate TB suspects
2. Fast-tracking of presumptive TB for diagnosis
3. Cough etiquette education
4. Respiratory hygiene
5. Separation of infectious TB patients

Environmental Controls

1. Natural ventilation - open windows (most cost-effective)
2. Mechanical ventilation with negative pressure rooms
3. Ultraviolet germicidal irradiation (UVGI) - kills airborne bacilli
4. HEPA filters in air handlers

Personal Protective Equipment (PPE)

• N95 respirators for healthcare workers in high-risk settings
• Note: surgical masks protect others from the patient; N95 protects the wearer from airborne particles

🔥 Administrative controls are the MOST IMPORTANT and MOST COST-EFFECTIVE - always prioritized first

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SECTION 38: IMPORTANT MCQ DATES AND NUMBERS ⭐🔥

Critical Numerical Values

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SECTION 39: IMPORTANT YEARS IN TB (CHRONOLOGY) ⭐🔥

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SECTION 40: ACTS, COMMITTEES AND POLICIES ⭐

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SECTION 41: COMMONLY ASKED VIVA AND EXAM TOPICS 🔥⭐

"Previous Year Favourite" Topics

1. ARTI - definition, measurement, significance (every exam)
2. DOTS - components, advantages (every exam)
3. RNTCP vs NTEP - what changed, when, targets
4. MDR-TB vs XDR-TB - definitions, causes, management
5. Mantoux test - full technique, interpretation, causes of false positive/negative
6. BCG vaccination - details, efficacy, limitations
7. Standard treatment regimen - doses, duration, categories
8. TB-HIV co-infection - epidemiology, management, drug interactions
9. Drug-resistant TB - primary vs secondary, causes, newer drugs
10. Bedaquiline - mechanism, indications, contraindications

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🗂 COMPREHENSIVE TABLES FOR LAST-MINUTE REVISION

═══════════════════════════════════════════════

TABLE A: First-Line Drug Mechanisms and Side Effects ⭐🔥

TABLE B: Anti-TB Drug Contraindications ⭐

TABLE C: NTEP Regimens Summary ⭐🔥

TABLE D: Nikshay Ecosystem ⭐🔥

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📋 COMPLETE RAPID REVISION SHEET (PART 2 ADDITIONS)

═══════════════════════════════════════════════

ADDITIONAL HIGH-YIELD FACTS - PART 2

SECOND-LINE DRUGS:
• Group A (always): FQ + Bedaquiline + Linezolid
• Bdq: ATP synthase inhibitor; QT prolongation; t½ 5.5 months after stopping
• Dlm: Nitroimidazole; ≥6 yrs; QT prolongation
• Cycloserine: bacteriostatic; neuropsychiatric SE; inhibits cell wall (D-alanine)
• Thioacetazone: NEVER in HIV (fatal skin reactions)

NTEP STRUCTURE:
• NTI Bengaluru = Head NRL
• STDC = 3 units (Training, S&M, IRL)
• State Drug Store: 1 per 5 crore population
• DDR-TBC: initiates standard MDR regimen
• NDR-TBC: complex/additional resistance cases

PATIENT-WISE BOX:
• Full course in box; Red=Cat I, Blue=Cat II
• IP blister: 1 day; CP blister: 1 week

PRIVATE SECTOR:
• 70% patients in India seek private care first
• Issues: irrational Rx, no outcome recording, over-reliance on X-ray
• Mandatory notification since 2012

NSP 2017-2025 - DTPB:
• Detect, Treat, Prevent, Build
• Target: 80% incidence reduction; 90% mortality reduction; 0% catastrophic
• Elimination: <1 case per million/year by 2025

TB-PREGNANCY:
• Safe: H, R, E (PZA - usually included)
• CI: Streptomycin (foetal ototoxicity)
• CI: Bedaquiline, Delamanid

TB-HIV:
• ART within 2 weeks if CD4<50; 8 weeks if CD4>50
• Use Efavirenz-based ART (RMP enzyme induction)
• CPT for ALL HIV-TB patients
• Rifampicin + PI = dangerous interaction (PI levels drop 75-90%)

INFECTION CONTROL:
• Administrative > Environmental > PPE (priority order)
• Administrative = MOST important, MOST cost-effective
• N95 respirator for HCW; not surgical mask

LATENT TB (LTBI/IPT):
• INH 5mg/kg/day (children 10 mg/kg) x 6 months
• MUST rule out active TB first
• Eligible: PLHIV, contacts <5 yrs, silicosis, immunosuppressed
• Rule out active TB first - critical!

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🔥 PART 2: TOP 20 MCQ FACTS (ADDITIONAL)

⚠ Note: Mantoux for paediatric TB uses 2 TU PPD RT23 (not 1 TU as in adults) - frequently confused!

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📝 TOP 10 UNIVERSITY SAQ/LAQ (PART 2 ADDITIONS)

1. LAQ: Write a detailed note on the structure and organization of NTEP. Include all levels from national to peripheral. (15 marks)
2. SAQ: What is MDR-TB? Describe the causes, classification, and management of drug-resistant TB in NTEP. (10 marks)
3. SAQ: Write a note on newer anti-TB drugs - Bedaquiline and Delamanid. Include mechanism, indications, and contraindications. (5 marks)
4. LAQ: Describe the National Strategic Plan 2017-2025 for TB elimination. Include vision, pillars (DTPB), objectives, and targets. (10 marks)
5. SAQ: Write a note on TB in pregnancy - safe drugs, contraindicated drugs, and management principles. (5 marks)
6. SAQ: Describe the programmatic management of drug-resistant TB (PMDT) in India. Include DR-TB centres and regimens. (5 marks)
7. SAQ: What are the vulnerable groups for TB? Describe the screening strategies for intensified case finding. (5 marks)
8. SAQ: Discuss the role of private sector in TB control. Describe the advantages and disadvantages of public and private sector care. (5 marks)
9. SAQ: Describe the infection control measures in TB. (5 marks)
10. SAQ: Describe Isoniazid Preventive Therapy (IPT) - indications, dose, duration, and eligibility criteria. (5 marks)

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🩺 TOP 10 VIVA QUESTIONS (PART 2)

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⚠ COMMON MISTAKES - PART 2

1. Confusing Mantoux dose in children: Paediatric algorithm uses 2 TU PPD RT23 (not 1 TU used in adults/standard)
2. Forgetting ECG is mandatory before starting Bedaquiline (QTcF monitoring)
3. Giving Quinolones/Linezolid as empirical antibiotics in presumptive paediatric TB - These have anti-TB activity and should NOT be given as they can mask the diagnosis
4. Confusing DDR-TBC with NDR-TBC functions - District initiates standard regimen; Nodal manages complex/additional resistance
5. Forgetting State Drug Store coverage: 1 SDS per 5 crore population (not per state)
6. Confusing NSP 2017-2025 targets: India's own target is 80% incidence reduction (not WHO 2030's 90%)
7. Missing that IPT dose in children = 10 mg/kg (adults = 5 mg/kg)
8. Forgetting to rule out active TB before IPT - most critical step; active TB + INH monotherapy = drug resistance
9. Thinking Bedaquiline is safe in pregnancy - it is absolutely CONTRAINDICATED
10. Mixing up NTI location: NTI = Bengaluru (not Delhi); NIRT = Chennai; NITRD = Delhi
11. Forgetting that Thioacetazone is contraindicated in HIV - a classic MCQ trap
12. Confusing 1-day (IP) vs 1-week (CP) blister pack in patient-wise box

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✅ LAST-MINUTE REVISION CHECKLIST - PART 2 ADDITIONS

• Second-line drug groups: A (FQ + Bdq + Lzd), B (Cfz + Cs), C (rest)
• Bedaquiline: ATP synthase inhibitor; QT prolongation; t½ 5.5 months; CI: pregnancy, QTcF ≥500
• Delamanid: nitroimidazole; ≥6 yrs; QT prolongation
• Cycloserine: bacteriostatic; inhibits cell wall; neuropsychiatric SE; give pyridoxine
• Thioacetazone: NEVER in HIV (fatal skin reactions)
• NTEP structure: CTD → State (STO/STDC/SDS) → District (DTO/DTC) → TU → DMC
• 6 NRLs: NTI Bengaluru (head), NIRT Chennai, NITRD Delhi, JALMA Agra, Bhubaneshwar, Bhopal
• STDC 3 units: Training + S&M + IRL
• State Drug Store: 1 per 5 crore
• Patient-wise box: Red=Cat I, Blue=Cat II; IP=daily blister, CP=weekly blister
• Private sector: 70% patients seek care there; mandatory notification since 2012
• NSP 2017-2025 = DTPB; targets: 80%/90%/0%; <1 case/million = elimination
• TB pregnancy: H, R, E safe; PZA (use with caution); Streptomycin = ABSOLUTELY CI
• TB-HIV: ART within 2 wks (CD4<50); Efavirenz preferred; CPT for all; avoid PIs with RMP
• TB-DM: 2-3x risk; screen all TB for DM; RMP reduces sulphonylurea effect
• IPT: 5 mg/kg/day (adults) / 10 mg/kg/day (children); 6 months; rule out active TB first
• Infection control: Administrative > Environmental > PPE
• Nikshay Mitra: 2022; community adoption for TB patients
• CBNAAT expansion: 1180 machines covering all districts
• Universal DST introduced; 55% TB cases offered uDST (2019, 3rd quarter)
• COVID-19 TB impact: >50% fall in notifications April 2020
• Paediatric Mantoux: 2 TU PPD RT23 (not 1 TU)
• DR-TB follow-up: ECG at 2 weeks, then monthly (first 6 months for longer regimen)

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🏆 INTEGRATION TABLE: DIFFERENCES TO REMEMBER ⭐🔥

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RESPIRATORY INFECTIONS — PARK'S PSM

Complete Chapter Summary | MBBS / INICET / NEET PG

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SECTION 1: ACUTE RESPIRATORY INFECTIONS (ARI)

Definition & Classification

• ARI = inflammation of respiratory tract from nose to alveoli; wide range of symptoms
• Classified by anatomical site:

Epidemiology / Problem Statement

• Most common human ailment
• Leading cause of morbidity and mortality in children under 5 and elderly
• Pneumococcal infections: ~0.294 million deaths/year in children <5 yrs (2015)
• Most common bacterial cause of pneumonia: Streptococcus pneumoniae
  • Responsible for 78% of lobar pneumonia, 13% of bronchopneumonia
• Second most common bacterial cause: Haemophilus influenzae type b (Hib)
• Most common viral cause of pneumonia: Respiratory Syncytial Virus (RSV)
• In HIV-infected children: Pneumocystis jirovecii (formerly carinii)
• In less developed countries: Measles and Whooping cough = important causes of severe ARI

Causative Agents

WHO Classification of ARI in Children (2 months to 5 years)

Fast Breathing Cut-offs (WHO) ⭐

Mnemonic: "6-5-4" for <2m, 2-12m, 1-5yr

ARI in Young Infants (< 2 months)

ARI Management Principles

• First dose oral Co-amoxiclav / Amoxicillin for pneumonia (outpatient)
• Cotrimoxazole was earlier first-line; replaced due to resistance
• Hospitalize if: severe pneumonia, unable to feed, cyanosis, age <2 months with danger signs
• Antibiotic of choice: Amoxicillin (for pneumonia in children)
• IMNCI (Integrated Management of Neonatal and Childhood Illnesses) - WHO/UNICEF strategy integrating ARI management

Control of ARI

Specific Protection

• PCV (Pneumococcal Conjugate Vaccine): Protects against S. pneumoniae; introduced in National Immunization Programme
• Hib vaccine: Protects against H. influenzae type b pneumonia/meningitis; in UIP schedule
• Influenza vaccine: Annual vaccination for high-risk groups
• Measles vaccine: Prevents measles-associated pneumonia

Non-Specific Control

• Breastfeeding (exclusive for 6 months) — protective against ARI
• Zinc supplementation — reduces pneumonia severity and duration
• Vitamin A supplementation — reduces measles-related ARI mortality
• Reduce indoor air pollution (cooking smoke, tobacco smoke)
• Handwashing
• Avoiding overcrowding

GAPPD Targets (Global Action Plan for Pneumonia and Diarrhoea)

• 90% coverage of vaccines (PCV, Hib, measles, pertussis)
• 90% access to pneumonia and diarrhoea case management (80% in every district)
• ≥50% exclusive breastfeeding for first 6 months
• Virtual elimination of paediatric HIV

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SECTION 2: INFLUENZA ⭐

Introduction

• Acute respiratory tract infection caused by influenza virus
• Types: A, B, C, D — only A and B cause epidemics and pandemics
• Characterized by sudden onset of chills, malaise, fever, myalgia, cough

Influenza Virus Subtypes

Antigenic Variation — KEY CONCEPTS ⭐

Mnemonic: Drift = gradual (epidemic); Shift = sudden (pandemic)

Epidemiology

Historical Pandemics

Agent Factors

• Influenza A — infects humans, birds, pigs, horses, seals
• Reservoir: Aquatic birds (natural reservoir for influenza A)
• Pigs act as "mixing vessels" (reassortment of human + avian strains)

Source and Transmission

• Source: Infected humans (respiratory secretions); infected birds (for avian)
• Transmission: Droplets, droplet nuclei, contact with contaminated surfaces
• Incubation period: 1–3 days (range: 1–4 days)
• Communicability: 1 day before to 3–5 days after onset of illness (children up to 7 days)

Clinical Features

• Abrupt onset; constitutional symptoms > respiratory symptoms
• Fever (38–40°C), severe headache, malaise, myalgia, anorexia
• Dry cough, sore throat, nasal congestion
• Complications: Viral pneumonia, secondary bacterial pneumonia, myocarditis, encephalitis, Reye's syndrome (children on aspirin)

High-Risk Groups for Severe Influenza

• Elderly (≥65 years)
• Children <5 years (especially <2 yrs)
• Pregnant women
• Immunocompromised
• Chronic diseases: DM, cardiac, pulmonary, renal, liver
• Morbidly obese
• Healthcare workers

Diagnosis

• Clinical (during epidemic)
• Lab: Rapid influenza diagnostic tests (RIDTs); RT-PCR (gold standard)
• Viral culture (reference labs)

Treatment

• Oseltamivir (Tamiflu): Neuraminidase inhibitor; oral; drug of choice; most effective if started within 48 hours of symptom onset
• Zanamivir: Inhaled neuraminidase inhibitor
• Amantadine/Rimantadine: M2 channel blockers; only active against Influenza A; high resistance rates — no longer recommended
• Supportive care: antipyretics, fluids; avoid aspirin in children (Reye's syndrome)

Prevention and Control

• Influenza vaccine = primary prevention tool (annual)
• Types of influenza vaccines:
  1. Inactivated Influenza Vaccines (IIV) — trivalent (TIV) or quadrivalent (QIV); IM injection
  2. Live Attenuated Influenza Vaccine (LAIV) — intranasal; FluMist; for 2–49 years
• WHO recommends vaccine composition annually based on surveillance
• Vaccine efficacy: ~60% in healthy adults; lower in elderly
• Herd immunity target: 75% population vaccination

Influenza Surveillance

• WHO Global Influenza Surveillance and Response System (GISRS)
• ~150 National Influenza Centres worldwide
• India: National Institute of Virology (NIV), Pune = key surveillance centre

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SECTION 3: AVIAN INFLUENZA (BIRD FLU) — H5N1 ⭐

"Once H5N1 adapts to humans, it will no longer be a bird virus — it will be a human influenza virus"

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SECTION 4: PANDEMIC INFLUENZA A (H1N1) 2009 — SWINE FLU ⭐

India's H1N1 Surveillance Structure:

• Flu surveillance hospitals (ILI and SARI sentinel surveillance)
• ILI = Influenza-Like Illness; SARI = Severe Acute Respiratory Infection

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SECTION 5: SEVERE ACUTE RESPIRATORY SYNDROME (SARS) ⭐

Introduction

• Communicable viral disease caused by SARS-CoV (a novel coronavirus)
• First recognized: China (Guangdong province), November 2002
• Global outbreak: 2003; ended July 2003
• ~8,098 probable cases; ~774 deaths worldwide; case fatality ~9.6%
• WHO declared global alert: March 12, 2003

Agent Factors

• SARS-CoV = novel coronavirus; single-stranded RNA virus
• Differs genetically from previously known coronaviruses
• Reservoir: Horseshoe bats (probable primary reservoir); civet cats (amplifying host)
• Sensitive to UV, ether, ethanol, chlorine-containing disinfectants

Transmission

• Droplets (primary); contact; possible airborne in hospital settings
• Incubation period: 2–7 days (max 10 days; WHO used 10 days for quarantine)
• Infectious during symptomatic phase; peak transmission ~day 10 of illness

Clinical Features

• Prodromal phase (days 1–4): High fever (>38°C), malaise, chills, headache, myalgia, rigor
• Respiratory phase (days 3–7): Dry cough, dyspnoea, hypoxaemia; progresses to ARDS in 10–20%
• No upper respiratory symptoms (rhinorrhoea absent) — distinctive

WHO Clinical Case Definition of SARS

• Fever >38°C AND
• Cough or difficulty breathing AND
• Close contact with suspected/probable SARS case OR history of travel to/residence in SARS-affected area within 10 days

• Suspected case with chest X-ray findings consistent with pneumonia or ARDS, OR
• Positive SARS-CoV test, OR
• Unexplained respiratory illness causing death with autopsy positive for ARDS of unknown cause

Diagnosis

• RT-PCR for SARS-CoV (respiratory samples, stool)
• ELISA for antibodies (after 3 weeks)
• CXR: bilateral infiltrates; ground glass opacities

Case Fatality Rate: ~9.6% overall; higher in elderly (>65 yrs: ~50%)

Control and Prevention

• Isolation of suspected/probable cases (negative pressure room)
• Droplet + contact precautions for all; airborne precautions for aerosol-generating procedures
• Quarantine for 10 days (incubation period)
• No approved vaccine at time of outbreak
• Contact tracing; travel restrictions during outbreak

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SECTION 6: CORONAVIRUS DISEASE-19 (COVID-19) ⭐

Introduction

• Caused by SARS-CoV-2 (novel betacoronavirus)
• First recognized: Wuhan, China, December 2019
• WHO declared Public Health Emergency of International Concern (PHEIC): January 30, 2020
• WHO declared Pandemic: March 11, 2020

Agent Characteristics

Variants of Concern (VOC)

Epidemiology

• Affected >200 countries/territories
• As of Feb 2021 (Park's data): ~11.08 crore cases; 24.5 lakh deaths; 77.4% recovery
• USA: highest cases; followed by Brazil, Russia, UK, France
• India: 2nd highest in Asia-Pacific

Transmission

• Droplets (primary — particles >5 µm)
• Airborne (in enclosed spaces with poor ventilation; particles <5 µm)
• Contact (contaminated surfaces — fomites; though less important)
• Feco-oral (virus shed in stool; significance unclear)
• Incubation period: 2–14 days (median ~5–6 days)
• R₀ (basic reproduction number): ~2–3 (original strain); higher for Delta/Omicron

Clinical Spectrum ⭐

Risk Factors for Severe Disease

• Age >60 years
• Cardiovascular disease, DM, hypertension, chronic lung disease
• Cancer, immunocompromised
• Obesity
• Males (higher severity than females)

Diagnosis of COVID-19 ⭐

Virological Tests (detect active infection)

Antibody Tests (detect past infection / seroprevalence)

Chest Imaging

Laboratory Findings in COVID-19

• Lymphopenia (negative prognostic factor; most characteristic)
• Normal or decreased total WBC
• Elevated LDH, liver enzymes, CRP, creatinine kinase
• Normal procalcitonin (unless bacterial co-infection)
• Elevated NLR (neutrophil-to-lymphocyte ratio) — poor prognosis marker
• Elevated D-dimer, ferritin, IL-6 in severe cases

COVID-19 Clinical Case Definitions (India — ICMR/MoHFW)

Management of COVID-19 ⭐

Severity-Based Classification and Action

Drug Treatment (as per Park's edition)

SpO₂ <94% — admit; <90% — ICU/critical care trigger

Warning Signs Requiring Immediate Medical Attention

• High-grade fever persisting
• Breathlessness or SpO₂ <95%
• Chest pain
• New confusion / altered sensorium
• Focal weakness

Home Care for COVID-19 (Mild Cases)

• Home isolation in a well-ventilated room (separate from family)
• Triple-layer surgical mask for patient
• Caregiver: triple-layer mask; N95 if high risk
• SpO₂ monitoring
• Paracetamol for fever
• Adequate hydration
• No sharing of utensils/towels
• Isolation ends: 10 days from symptom onset + 3 days fever-free

Post-COVID Follow-up Protocol

• Continue COVID-appropriate behaviour (mask, hand hygiene, distancing)
• Breathing exercises, mild-moderate exercise, yoga/pranayama
• Balanced diet; adequate rest; no smoking/alcohol
• Monitor: temperature, BP, SpO₂, blood sugar (in DM)
• Watch for warning signs: fever, SpO₂ <95%, breathlessness, chest pain

• First follow-up: within 7 days of discharge
• Subsequent: nearest qualified practitioner
• Severe cases: stringent follow-up

Public Health Surveillance for COVID-19

1. Detect and investigate all COVID-19 cases
2. Monitor transmission trends
3. Guide public health interventions
4. Identify risk factors and vulnerable populations
5. Monitor healthcare system capacity

• Sentinel surveillance: ILI and SARI sentinel sites
• Syndromic surveillance: Monitoring fever clinics, emergency departments
• Sero-surveys: Population-level antibody prevalence surveys (ICMR conducted multiple)
• Genomic surveillance: Variant tracking (INSACOG network in India)

COVID-19 Vaccines ⭐

India's COVID-19 Vaccination Programme

• Launched: January 16, 2021
• Priority: Healthcare workers → Frontline workers → 60+ yrs → 45+ yrs → 18+ yrs → 12–18 yrs (later)
• Vaccines used: Covaxin and Covishield initially
• CoWIN platform = digital vaccination management system

Dead Body Management (COVID-19)

• Bodies do NOT need to be placed in sealed bags (unless body fluids present)
• Standard precautions (PPE) for handling
• No restriction on religious/cultural practices
• Cremation or burial both allowed

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SECTION 7: MERS-CoV (Middle East Respiratory Syndrome) ⭐

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SECTION 8: COMPARISON TABLE — SARS vs MERS vs COVID-19 ⭐

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SECTION 9: INFLUENZA VACCINES — DETAILED ⭐

Types of Influenza Vaccines

1. Inactivated Influenza Vaccines (IIV)

• Route: Intramuscular (IM) — deltoid
• Annual composition updated by WHO
• Recommended in: elderly (≥65 yrs), HCW, pregnant women, chronic disease patients, children 6 months–5 years

2. Live Attenuated Influenza Vaccine (LAIV)

• Brand: FluMist (intranasal spray)
• Route: Intranasal
• Age: 2–49 years (not for immunocompromised, pregnant, <2 yrs, >49 yrs)
• Cold-adapted strains replicate in cooler nasal mucosa (not lower RT)
• Induces mucosal IgA + systemic immunity
• Contraindicated: immunocompromised, pregnant, children on aspirin, egg allergy (relative)

Influenza Vaccine Efficacy

• Healthy adults: ~60–70%
• Elderly: 40–60% (lower due to immunosenescence)
• Protection begins: ~2 weeks after vaccination

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SECTION 10: KEY POINTS ON NATIONAL PROGRAMMES FOR ARI

National ARI Control Programme (India)

• Launched: 1990 (later integrated into IMNCI)
• Objectives: Reduce pneumonia mortality in children under 5
• Strategy: Standard case management at PHC level; identify cases by fast breathing + chest indrawing
• Drug of choice at community level: Co-trimoxazole (initially); now Amoxicillin

Integrated Management of Neonatal and Childhood Illnesses (IMNCI) ⭐

• WHO/UNICEF strategy adopted in India
• Integrates management of ARI, diarrhoea, malaria, measles, malnutrition, neonatal conditions
• Uses colour-coded chart booklet (Pink Book)
• Promotes breastfeeding, immunization, nutrition counselling
• Community IMNCI = F-IMNCI (Facility-based IMNCI)

Vaccines in National Immunization Programme for ARI Prevention ⭐

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SECTION 11: SUMMARY COMPARISON — ALL RESPIRATORY INFECTIONS ⭐

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SECTION 12: HIGH-YIELD MCQ FACTS ⭐

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SECTION 13: COMMON MISTAKES / FREQUENTLY CONFUSED

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SECTION 14: MNEMONICS ⭐

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RAPID REVISION — ONE-PAGE CHEAT SHEET

ARI FAST FACTS
══════════════
Most common bacterial pneumonia: S. pneumoniae (78% lobar pneumonia)
Most common viral pneumonia: RSV
Fast breathing: 60/50/40 (< 2m / 2-12m / 1-5yr) — "6-5-4"
Drug: Amoxicillin (outpatient); Refer if Very Severe/Severe
PCV + Hib vaccine in UIP = prevention

INFLUENZA FAST FACTS
════════════════════
Types A, B, C, D — only A & B cause epidemics; only A causes pandemics
Drift = gradual = epidemic (annual); Shift = sudden = pandemic (every 10-40 yrs)
IP: 1-3 days; Infectious: day before to 3-5 days after
Annual burden: 3-5 million severe; 290,000-650,000 deaths
Attack rate: adults 5-10%; children 20-30%; peak in 3-4 weeks
Pandemics: 1918 (H1N1 Spanish), 1957 (H2N2 Asian), 1968 (H3N2 Hong Kong), 2009 (H1N1 Swine)
Drug: Oseltamivir within 48 hrs; Zanamivir inhaled; Amantadine obsolete
Vaccine: IIV (IM) or LAIV (intranasal, 2-49 yrs only)
Aspirin CI in children (Reye's syndrome)

AVIAN FLU (H5N1)
════════════════
IP: 2-5 days | CFR: ~60% | Bird-to-human
Diagnosis: RT-PCR | Treatment: Oseltamivir
Vaccine: 2 doses, 28 days apart (18-64 yrs)

SWINE FLU 2009
══════════════
H1N1 swine-origin; Mexico origin; Pandemic June 2009
Affects young adults (unlike seasonal flu); lower RT infection
Treatment: Oseltamivir

SARS
════
SARS-CoV; China Nov 2002; 8,098 cases; CFR 9.6%
IP: 2-7 days (max 10; quarantine = 10 days)
No rhinorrhoea; droplet; ARDS in 10-20%
No approved vaccine; supportive treatment

MERS
════
MERS-CoV; Saudi Arabia 2012; R0 <1
Reservoir: Dromedary camels; CFR ~35%
IP: 2-14 days; No sustained person-to-person

COVID-19
════════
SARS-CoV-2; Wuhan Dec 2019; PHEIC Jan 30, 2020; Pandemic March 11, 2020
ssRNA; 60-140 nm; betacoronavirus
IP: 2-14 days; Inactivated by: UV, ether, ethanol, chlorine; NOT by chlorhexidine
Lymphopenia = hallmark; HRCT = bilateral peripheral GGO (lower lobes)
Dexamethasone: only in severe (SpO2 <94%) — reduces mortality
Covaxin (inactivated) + Covishield (viral vector); launched Jan 16, 2021

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