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🫁 TUBERCULOSIS (TB) - Complete Exam Notes

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DEFINITION

• Formation of granulomas
• Development of cell-mediated hypersensitivity

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ORGANS AFFECTED BY TB

1. Lungs (most common - Pulmonary TB)
2. Lymph nodes
3. Pleura
4. CNS (brain and meninges)
5. Bones and joints (especially spine)
6. Genitourinary tract (kidneys, bladder, reproductive organs)
7. Gastrointestinal tract and peritoneum
8. Pericardium
9. Skin, Eyes, Liver, Adrenal glands
10. Disseminated/Miliary TB - involves multiple organs at once

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CLINICAL FEATURES

Pulmonary TB - Symptoms:

• Chronic cough, often with haemoptysis (coughing blood)
• Pyrexia (fever of unknown origin)
• Unresolved pneumonia
• Exudative pleural effusion
• Weight loss
• General debility (weakness)
• Spontaneous pneumothorax
• May be asymptomatic - found on chest X-ray

Miliary (Disseminated) TB - Symptoms:

• 2-3 weeks of fever
• Night sweats
• Anorexia (loss of appetite)
• Weight loss, dry cough
• Hepatosplenomegaly may develop
• Headache (may suggest tuberculous meningitis)
• Auscultation: usually normal, but crackles in advanced disease
• Fundoscopy: choroidal tubercles (seen in eye)
• Chest X-ray: 1-2 mm millet seed lesions distributed throughout lung fields
• Anaemia and leucopenia (reflect bone marrow involvement)

Post-Primary Pulmonary TB:

• Occurs from exogenous or endogenous re-infection in a previously sensitized person
• Systemic symptoms: fever, night sweats, malaise, loss of appetite and weight
• Progressive pulmonary symptoms
• Radiological changes:
  • Ill-defined opacification in one or both upper lobes
  • As it progresses: consolidation → collapse → cavitation
  • Extensive disease can displace trachea and mediastinum
  • Caseous lymph nodes may drain into bronchus → tuberculous pneumonia

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INVESTIGATIONS

Why investigate?

• Confirm the diagnosis and exclude other conditions
• Know extent and severity of lesion
• Detect dissemination of lesions
• Detect development of complications
• Evaluate response to treatment

Step 1 - Direct Microscopy of Sputum Smear (MOST IMPORTANT first step):

• Need at least 2 sputum samples (one early morning)
• From spontaneously produced deep cough, or induced sputum
• In selected cases: bronchoscopy and lavage, or lymph node aspiration by EBUS

Stains used:

• LED fluorescent microscopy with Auramine staining - increasingly replacing the traditional
• Ziehl-Neelsen stain (classic acid-fast stain)
• Mercury vapour fluorescent microscopy

Positive smear = Presumptive diagnosis of TB. Definitive diagnosis requires culture. Even negative smear should be cultured (only 10-100 viable organisms needed for culture to be positive)

Culture:

• Slow growth on solid media (Lowenstein-Jensen, Middlebrook) - 4-6 weeks
• Automated/semi-automated liquid media (MGIT) - around 2 weeks
• NAATs (Nucleic Acid Amplification Tests): e.g., Xpert MTB/RIF - detects MTB in less than 2 hours

Drug Sensitivity Testing:

• Gold standard: Culture
• MODS (Microscopically Observed Drug Susceptibility)
• Colorimetric Redox Indicator (CRI)
• Nitrate reductase assay
• Xpert MTB/RIF for rapid identification of rifampicin resistance (important because rifampicin forms the cornerstone of 6-month chemotherapy)
• Line probe assays (LPAs): use PCR to detect resistance to rifampicin, isoniazid, pyrazinamide, ethambutol, and second-line agents

Other tests:

• Adenosine deaminase (ADA): elevated in pleural, pericardial, CSF and ascitic fluid - due to T cell stimulation by mycobacterial antigens
• HIV + TB: lateral flow urinary lipoarabinomannan assay (LF-LAM) in severely ill patients
• Tuberculin skin test (TST/Mantoux): low sensitivity/specificity; useful in primary or deep-seated infection; can be false +ve in BCG vaccinated people
• IGRAs (Interferon Gamma Release Assays): detect IFN-γ released by sensitized T cells in response to MTB-specific antigens (ESAT-6, CFP-10). Two types:
  • T-SPOT.TB test (uses purified T lymphocytes + ELISPOT)
  • QuantiFERON-TB Gold test (uses whole blood + ELISA)
  • More specific and convenient than TST

Specimens needed:

Baseline blood tests:

• Full blood count, CRP, ESR, urea and electrolytes, liver function tests

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DIAGNOSIS (Summary Box 17.51)

Trigger for investigation: Unexplained cough for more than 2-3 weeks (especially in TB-prevalent regions), OR typical chest X-ray/CT changes.

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MANAGEMENT

Principle:

1. Intensive phase - rapidly reduces bacterial population
2. Continuation phase - destroys remaining bacteria

Standard Treatment (WHO Recommendations - Box 17.52):

If isoniazid resistance is high: continuation phase uses HRE (4 months)

• Fixed dose tablets combining 2-3 drugs are preferred
• Treatment should be started immediately in any patient who is smear +ve, or smear -ve but with typical chest X-ray changes and no response to standard antibiotics

Special Situations:

• Meningeal TB: 12 months
• Spinal TB with cord involvement: ethambutol may be replaced by streptomycin
• Pyridoxine should be given to pregnant women and malnourished patients (to reduce risk of peripheral neuropathy from isoniazid)

Setting of Treatment:

• Most patients can be treated at home
• Hospital admission needed if: uncertain diagnosis, medication intolerance, poor adherence, adverse social conditions, risk of MDR-TB

Non-infectious after:

• 2 weeks of appropriate therapy (if no drug resistance)

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ADVERSE DRUG REACTIONS (Box 17.53)

• Rifampicin turns urine, tears, and secretions orange/red - warn patients
• Women on oral contraceptives must use alternative contraception (rifampicin reduces efficacy)
• Ethambutol and streptomycin: use with caution in renal impairment
• Adverse reactions occur in about 10% of patients (more common with HIV co-infection)
• Hepatotoxicity: significant in only 2-5%, but baseline LFTs and regular monitoring needed
• If hepatotoxicity occurs: stop treatment, let LFTs recover, then reintroduce drugs one by one. Switch to less hepatotoxic regimen (streptomycin, ethambutol, fluoroquinolones)

Glucocorticoids (Steroids):

• Pericardial disease
• Meningeal TB
• Endobronchial disease (in children)
• TB of ureter
• Pleural effusions
• Extensive pulmonary disease

Surgery:

• Massive haemoptysis
• Loculated empyema
• Constrictive pericarditis
• Lymph node suppuration
• Spinal disease with cord compression

Monitoring Response:

• Sputum smear at 2 months and 5 months
• Failure = positive smear OR multidrug resistant strain

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CONTROL AND PREVENTION

1. Detection of Latent TB:

• Most people exposed to MTB harbour bacteria in a dormant state - non-infectious but at risk
• Lifetime risk of TB in latent infection: 5-15% (majority within first 5 years)
• Detected by: TST (can be false +ve with BCG) or IGRAs (more specific)
• Asymptomatic contact who tests +ve with normal chest X-ray → chemoprophylaxis:
  • Adults up to 65 years
  • HIV-infected close contacts of smear-positive patients
  • Regimen: Rifampicin + Isoniazid for 3 months OR Isoniazid alone for 6 months
• Close contacts should receive BCG vaccination or chemotherapy
  • 10-20% of close contacts of smear +ve pulmonary TB patients have TB infection
  • 2-5% of contacts of smear -ve, culture +ve cases have evidence of infection

2. Directly Observed Therapy (DOT):

• Major factors in prolonged illness: poor adherence, risk of relapse, emergence of drug resistance
• DOT = supervised administration of therapy 3 times a week to improve adherence

3. TB and HIV/AIDS:

• Mortality is high; TB is a leading cause of death in HIV patients
• All TB patients should be tested for HIV

4. Drug-Resistant TB:

• Drug-resistant TB: resistance to any first-line agent
• MDR-TB (Multidrug Resistant): resistance to at least rifampicin + isoniazid ± other drugs
• XDR-TB (Extensively Drug Resistant): resistance to rifampicin + isoniazid + any quinolone + at least one injectable second-line agent
• More common in: prior history of TB, inadequate treatment, HIV infection
• Requires prolonged treatment with less effective, more toxic and more expensive drugs

5. BCG Vaccine:

• Live attenuated vaccine derived from M. bovis
• Given by intradermal injection
• Highly immunogenic
• Effective in preventing disseminated disease and tuberculous meningitis in children
• Efficacy in adults is inconsistent
• Should NOT be given to: immunocompromised patients, pregnant women

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QUICK EXAM MNEMONICS

• Isoniazid → Neuropathy (peripheral)
• Rifampicin → Red urine + Reduced OCP efficacy
• Pyrazinamide → Gout (hyperuricaemia)
• Ethambutol → Eye damage (retrobulbar neuritis)
• Streptomycin → Sound loss (8th nerve damage)

• MDR = Resistant to R + H
• XDR = Resistant to R + H + Quinolone + 1 injectable

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🧠 TB Made Super Easy - Memory Edition

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1. WHAT IS TB? (The Simple Story)

🧠 Memory trick: "TB = Tiny Bacteria that builds Jail Cells (granulomas)"

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2. CLINICAL FEATURES - The "COWPS" Story 🐄

🧠 Mnemonic: "COWPS" - A sick cow with tuberculosis!

• Fever for 2-3 weeks
• Night sweats + anorexia
• Hepatosplenomegaly (liver and spleen swell)
• Headache (TB got into the brain!)
• Chest X-ray: millet seeds (tiny 1-2mm spots everywhere) - that's WHY it's called miliary (millet = tiny grain)

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3. INVESTIGATIONS - The "SDC-NI" Ladder 🪜

STEP 1 (Bottom) → Sputum Smear (ZN stain / Auramine) - quickest
STEP 2          → Culture (gold standard, takes 2-6 weeks)
STEP 3          → NAAT / Xpert MTB/RIF (fastest, < 2 hours!)
STEP 4 (Top)    → Drug Sensitivity Testing

🧠 Memory trick: "Spit on the Culture, then NAAT it" (Smear → Culture → NAAT)

• Smear +ve = you can presume TB, but you need culture to confirm
• Xpert MTB/RIF = detects TB AND rifampicin resistance in under 2 hours
• Ziehl-Neelsen (ZN) stain = the classic acid-fast stain for TB

• Mantoux / Tuberculin skin test = old method, not very reliable (BCG causes false +ve)
• IGRA (QuantiFERON / T-SPOT) = modern, more accurate blood test. Measures IFN-gamma released when your T cells see TB antigens

🧠 Memory trick: "IGRA = Immune Guards Recognise Antigen"

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4. THE DRUGS - The "RIPE" Framework 🍎

🧠 Mnemonic: "RIPE fruit cures TB" - Rifampicin, Isoniazid, Pyrazinamide, Ethambutol

START OF RACE (2 months) = All 4 drugs: R + I + P + E  (intensive)
FINISH LINE (4 months)   = Only 2 drugs: R + I         (continuation)
TOTAL RACE = 6 months

🧠 Story: "You need all 4 players at the START of the race, but by the end only 2 are left running"

• Meningeal TB = 12 months (brain needs longer)
• Streptomycin replaces Ethambutol in spinal TB

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5. SIDE EFFECTS - The "RIPES" Table with Stories 🏥

🧠 Use the phrase: "Rifampicin Ruins Liver, Isoniazid Injures Nerves, Pyrazinamide Pinches Joints, Ethambutol Erases Eyesight, Streptomycin Steals Sound"

⚠️ 3 drugs cause Hepatitis: Rifampicin, Isoniazid, Pyrazinamide (remember: RIP your liver 💀)

🧠 Rifampicin special warning: Reduces the pill (OCP) efficacy - tell female patients!

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6. STEROIDS - When to Add Them? "PUMP ME"

🧠 Mnemonic: "PUMP ME with steroids"

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7. MDR vs XDR - The "More Dangerous, eXtremely Dangerous" Rule

🧠 Think of it as levels of a video game boss:

• MDR = Level 1 Boss (resists R + I)
• XDR = Final Boss (resists R + I + quinolone + injectable)

• Prior history of TB
• Inadequate/incomplete treatment
• HIV infection

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8. PREVENTION - "BCG + DOT + IGRA"

🧠 All TB patients must be tested for HIV (they are deadly partners)

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9. THE MASTER CHEAT SHEET 📋

TB = MTB bacteria → granulomas → CMI hypersensitivity

SYMPTOMS (COWPS): Cough, unresOlved pneumOnia, Weight loss, Pyrexia, Spontaneous pneumothorax

INVESTIGATIONS: Smear → Culture → NAAT (Xpert < 2 hrs)

TREATMENT:
  2 months: RIPE (Rifampicin + Isoniazid + Pyrazinamide + Ethambutol)
  4 months: RI
  TOTAL: 6 months

SIDE EFFECTS:
  R = Red urine, Rifampicin ruptures liver
  I = Isoniazid Injures nerves (give B6!)
  P = Pyrazinamide = Painful gout
  E = Ethambutol = Eyes
  S = Streptomycin = Sound (deaf)
  RIP liver = Rifampicin + Isoniazid + Pyrazinamide all cause hepatitis

MDR = Resists R + I
XDR = MDR + Quinolone + Injectable

BCG = Live vaccine, works in children
DOT = 3x/week supervised
Test ALL TB for HIV

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🔁 Quick Recall Test (cover the answers and try!)

1. What bacteria causes TB? → M. tuberculosis
2. What is miliary TB? → Disseminated TB, millet seed X-ray pattern
3. First step in investigation? → Sputum smear (ZN stain)
4. Definitive diagnosis? → Culture
5. Fastest test? → Xpert MTB/RIF (< 2 hours)
6. Treatment duration? → 6 months (2 RIPE + 4 RI)
7. Which drug turns urine red? → Rifampicin
8. Which drug damages eyes? → Ethambutol
9. Which drug causes deafness? → Streptomycin
10. 3 drugs causing hepatitis? → RIP - Rifampicin, Isoniazid, Pyrazinamide
11. MDR-TB = resistant to? → Rifampicin + Isoniazid
12. When to use steroids? → PUMP ME (Pericardial, Ureter, Meningeal, Pleural, Massive pulmonary, Endobronchial)

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