Latent TB Infection (LTBI): Diagnosis, Progression Risk, and Treatment

Latent TB infection (LTBI) means Mycobacterium tuberculosis is present in the body but controlled by the immune system—no symptoms, not contagious. Approximately 25% of the world's population has LTBI.

Pathogenesis

• Inhaled bacilli → alveolar macrophages → granuloma formation → caseous necrosis → calcification
• Bacilli persist in a dormant state (non-replicating, metabolically altered) within granulomas
• Immune containment: CD4+ T cells, IFN-γ, TNF-α are critical

Progression to Active TB (Reactivation)

Lifetime risk ~5–10% if untreated; highest in the first 2 years post-infection. Risk multipliers include:

• HIV (CD4 <200): 10%/year
• TNF-α inhibitors, immunosuppressants: 2–10x risk
• Diabetes, CKD, silicosis, gastrectomy, low BMI: 2–4x risk
• Age: Young children (<5) and elderly >60
• Recent infection: Contacts of active cases

Diagnosis

• TST (Mantoux): Intradermal PPD; induration ≥5–15 mm (risk-stratified)
• IGRA (QuantiFERON-TB Gold, T-SPOT.TB): Blood test measuring IFN-γ response; no BCG cross-reactivity, single visit
• Both indicate infection, not active disease. Chest X-ray required to rule out active TB.

Treatment Regimens (CDC/WHO)

• 3HP: Weekly isoniazid 900 mg + rifapentine 900 mg × 12 weeks (preferred, high completion)
• 4R: Daily rifampin 600 mg × 4 months (alternative, less hepatotoxicity)
• 3HR: Daily isoniazid 300 mg + rifampin 600 mg × 3 months
• 6–9H: Daily isoniazid 300 mg × 6–9 months (traditional, lower completion)

Baseline LFTs; monitor monthly if risk factors. HIV: check drug interactions (rifamycins decrease ART levels).

Public Health Impact

Treating LTBI in high-risk groups is essential for TB elimination. Cascade: test → treat → complete → prevent active cases → reduce transmission.