Tuberculosis

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Tuberculosis

๐Ÿฆ  Overview

  • Causative agent: Mycobacterium tuberculosis (acid-fast, aerobic, intracellular rod).

  • Transmission: Airborne droplet nuclei.

  • Reservoir: Humans.

  • Main sites: Lungs (most common), but may spread to any organ (extrapulmonary TB).

⚙️ Pathophysiology

Step Description Key Features
1. Primary infection Bacilli inhaled → phagocytosed by alveolar macrophages Survive by blocking phagolysosome fusion (via sulfatides, cord factor, lipoarabinomannan)
2. Immune response Th1 → IFN-ฮณ → macrophage activation → granuloma (caseating) Limits spread; forms Ghon focus ± LN → Ghon complex → calcifies (Ranke complex)
3. Latent TB Bacilli dormant inside granulomas Asymptomatic, non-contagious
4. Reactivation Weak immunity (HIV, malnutrition, steroids, TNF-ฮฑ inhibitors) Upper lobes (aerobic), cavitations, contagious

๐Ÿ’ก Types of TB

Type Features Contagious Diagnostic Tests Treatment
Latent TB (LTBI) Asymptomatic, normal CXR ❌ PPD/IGRA positive Isoniazid + Rifapentine weekly × 3 mo OR Isoniazid 6–9 mo
Primary TB Usually asymptomatic; may cause mild pneumonia, pleural effusion ✅ (if active) CXR: mid/lower lobe infiltrate, hilar LN, Ghon complex RIPE regimen if active
Reactivation (Postprimary) Fever, weight loss, night sweats, cough ± hemoptysis ✅ CXR: upper lobe cavitary lesions RIPE regimen (6 mo)
Progressive primary TB Seen in immunocompromised; disseminated (miliary) ✅ Miliary pattern on CXR Prolonged therapy

๐Ÿ”ฌ Diagnosis (Active TB)

Test Use Notes
AFB smear (Ziehl-Neelsen or Auramine) Rapid, screening Low sensitivity
Culture (Lรถwenstein-Jensen) Gold standard 2–6 weeks for growth
PCR / NAAT Confirm diagnosis, detect drug resistance Fast & sensitive
CXR / CT Localization, pattern “Cavitation”, “tree-in-bud” pattern
In HIV: Often smear-negative, atypical imaging Use urine LAM assay if CD4 <100

๐Ÿ’Š Treatment (Active TB)

RIPE regimen:

Phase Duration Drugs Notes
Intensive phase 2 months Rifampin, Isoniazid, Pyrazinamide, Ethambutol Start pyridoxine (B6) with INH
Continuation phase 4 months Rifampin + Isoniazid Adjust if resistant strains

๐Ÿ‘‰ Total duration = 6 months (longer for bone, CNS, or disseminated TB).
๐Ÿ‘‰ DOT (Directly Observed Therapy) = standard of care to ensure adherence.

๐Ÿšซ Drug-Resistant TB

Type Definition
Mono-resistant Resistant to one first-line drug
MDR-TB Resistant to INH + Rifampin
Pre-XDR-TB MDR + (fluoroquinolone or injectable)
XDR-TB MDR + (fluoroquinolone + injectable or bedaquiline/linezolid)

Treatment: Tailored regimen (fluoroquinolone + bedaquiline + linezolid ± injectables).

⚠️ Side Effects of First-Line Drugs

Drug Major Adverse Effects Mnemonic
Isoniazid (INH) Hepatitis, peripheral neuropathy, B6 deficiency, lupus INH = Injures Neurons & Hepatocytes
Rifampin (RIF) Orange fluids, hepatotoxicity, ↑ CYP450 R = Red fluids
Pyrazinamide (PZA) Hyperuricemia, hepatitis P = Pain in joints
Ethambutol (EMB) Optic neuritis (red-green blindness) E = Eye toxicity

๐Ÿง  Extrapulmonary TB (Sites & Clues)

Site Key Findings
Lymph nodes Painless cervical lymphadenitis (“scrofula”)
Pleura Effusion
Meninges Chronic meningitis, ↑ protein, ↓ glucose
Spine Pott disease (vertebral collapse)
Genitourinary Sterile pyuria
Adrenal Addison disease
Miliary TB Tiny millet-seed nodules in many organs (hematogenous spread)

๐Ÿงซ Screening for Latent TB

Test Principle Interpretation
PPD (TST) Delayed (Type IV) HSR to tuberculin Positive = prior infection or BCG
IGRA Measures IFN-ฮณ response to TB antigens Unaffected by BCG vaccination

๐Ÿ›ก️ Prevention

  • BCG vaccine: Live attenuated M. bovis, used in endemic areas.

  • Infection control: Airborne isolation (N95, negative pressure room).

  • Treat LTBI to prevent reactivation (↓ risk by ~90%).

๐Ÿ” Quick Summary Mnemonics

“RIPE for TB” = Rifampin, Isoniazid, Pyrazinamide, Ethambutol
Cavitary upper lobe lesion = Reactivation TB
Caseating granuloma = Hallmark lesion
PPD positive but asymptomatic = Latent TB
Cord factor = Virulence → granuloma formation

Latent tuberculosis infection (LTBI)๐Ÿ™Œ

๐Ÿงซ 1. Definition

Latent tuberculosis infection (LTBI) means:

  • The person is infected with Mycobacterium tuberculosis, but

  • No clinical, bacteriologic, or radiographic evidence of active TB disease.

So, the organism is alive but dormant, contained by the immune system.
Patients are asymptomatic and non-infectious, but reactivation can occur later — especially if immunity weakens.

๐Ÿง‍♀️ 2. Epidemiology and Pathophysiology

๐Ÿ“Š Prevalence

  • ~25% of the world’s population is latently infected.

  • Risk of reactivation is ~5–10% lifetime, but ~10% per year in high-risk groups (HIV, immunosuppressed).

⚙️ Mechanism

  1. M. tuberculosis is inhaled → reaches alveoli → phagocytosed by macrophages.

  2. Granuloma formation (caseating) limits spread → bacilli remain dormant.

  3. If immune control weakens → granuloma breaks down → reactivation TB.

⚠️ 3. Who Should Be Screened for LTBI

Screening is not for everyone — it’s targeted to:

๐Ÿง Groups at high risk of infection:

  • Close contacts of smear-positive TB patients

  • Immigrants from high-incidence regions

  • Healthcare workers, prison staff, homeless shelters

  • Children/adolescents exposed to adults with TB

๐Ÿ’ฅ Groups at high risk of reactivation:

  • HIV infection

  • Immunosuppressive therapy (corticosteroids, anti-TNF, methotrexate)

  • Chronic diseases (diabetes, CKD, silicosis, malnutrition)

  • Post-transplant, hematologic malignancy

  • Elderly

๐Ÿงช 4. Screening Tests

Two main immunologic tests:

1️⃣ Tuberculin Skin Test (TST or PPD)

  • Intradermal injection of purified protein derivative.

  • Read after 48–72 hours.

  • Measure induration, not redness.

Interpretation thresholds:

Induration Positive in
≥5 mm HIV+, immunosuppressed, close contact, old healed TB lesion
≥10 mm Recent immigrants, IV drug users, CKD, diabetes, high-risk workers
≥15 mm Healthy individuals with no risk factors

False positives: Prior BCG vaccine, infection with nontuberculous mycobacteria.
False negatives: Immunosuppression, recent TB infection (<8 weeks), very old TB, viral infections, sarcoidosis.

2️⃣ Interferon-Gamma Release Assay (IGRA)

  • Measures IFN-ฮณ released by T cells after exposure to TB-specific antigens (e.g., ESAT-6, CFP-10).

  • Examples: QuantiFERON-TB Gold, T-SPOT.TB

✅ Advantages:

  • Single visit (no return for reading)

  • Unaffected by BCG vaccination

  • Higher specificity

๐Ÿšซ Limitations:

  • Costly

  • May be indeterminate in very immunosuppressed patients

๐Ÿ”Ž 5. After a Positive Test

A positive TST or IGRA only indicates infection, not disease.
So next step:

  1. Rule out active TB:

    • History: cough >2 weeks, fever, weight loss, night sweats

    • Exam: lymphadenopathy, crackles, cachexia

    • Chest X-ray: look for infiltrates, cavitations, nodules

    • If abnormal → sputum AFB smear/culture/PCR

  2. If CXR and symptoms are negative, diagnosis = LTBI.

๐Ÿ’Š 6. Treatment of Latent TB

Goal → eradicate dormant bacilli and prevent reactivation.

๐Ÿฉน Recommended regimens (CDC/WHO endorsed):

Regimen Duration Frequency Comments
3HP (isoniazid + rifapentine) 3 months Weekly Preferred short regimen; not for pregnancy or children <2
3HR (isoniazid + rifampin) 3 months Daily Safe in pregnancy
4R (rifampin alone) 4 months Daily For INH resistance or intolerance
6H / 9H (isoniazid alone) 6–9 months Daily Classic regimen; longer but effective

Add pyridoxine (vitamin B6) 25–50 mg/day with isoniazid to prevent peripheral neuropathy.

⚕️ 7. Monitoring During Therapy

Baseline:

  • LFTs (ALT/AST)

  • CBC (for rifampin)

During therapy:

  • Stop drug if transaminases >3× ULN with symptoms or >5× ULN without symptoms.

  • Watch for:

    • Hepatitis (fatigue, nausea, jaundice)

    • Peripheral neuropathy (give pyridoxine)

    • Rifampin: orange secretions, drug interactions (OCPs, warfarin)

๐Ÿคฐ 8. Special Situations

Pregnancy:

  • Delay treatment until postpartum unless high risk (HIV+, recent contact).

  • Safe regimens: 3HR, 4R, or 6–9H + pyridoxine

  • Avoid rifapentine (3HP) due to limited data.

HIV:

  • Treat LTBI after excluding active TB.

  • Any regimen can be used, but drug interactions with antiretrovirals must be checked.

Children:

  • Treat similarly but prefer INH monotherapy (6–9 months) if <2 years old.

๐Ÿงฌ 9. Pathogenesis of Reactivation (Active TB)

  • Granuloma disruption due to:

    • Immunosuppression (HIV, steroids)

    • Malnutrition

    • Diabetes

    • Aging

  • Reactivation typically occurs in upper lobes (high O₂ tension).

๐Ÿ’‰ 10. Prevention — BCG Vaccine

  • Bacillus Calmette–Guรฉrin (attenuated M. bovis strain)

  • Given in infancy in high-burden countries.

  • Protects mainly against:

    • Miliary TB

    • TB meningitis in children

  • Causes false-positive PPD, but does not affect IGRA.

๐Ÿ“‹ 11. Key Comparison

Feature Latent TB Active TB
Symptoms None Cough, fever, weight loss
Contagious ❌ No ✅ Yes
CXR Normal Abnormal (infiltrates, cavities)
AFB smear Negative Positive
Treatment goal Prevent reactivation Cure infection
Public health risk Low High

๐Ÿง  12. Key Takeaways for Exams

  • Positive TST or IGRA → always rule out active TB before treatment.

  • INH + B6 is mainstay if rifamycins not suitable.

  • 3HP is the shortest, most effective modern regimen.

  • Reactivation risk highest in HIV, steroids, diabetes, CKD, elderly.

  • BCG protects infants, but not adults from pulmonary TB.


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