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Latent Tuberculosis Infection (LTBI)

BASICS

  • Definition: LTBI is an asymptomatic, non-contagious condition following exposure to Mycobacterium tuberculosis. It carries a 5–10% lifetime risk of progression to active TB, especially in immunocompromised individuals.
  • Public Health Importance: Over 80% of active TB cases in the U.S. arise from untreated LTBI. Prevention and treatment of LTBI is a cornerstone of TB elimination efforts.

EPIDEMIOLOGY

  • Global LTBI prevalence: ~2 billion
  • Active TB cases (2020): ~10 million globally; ~1.1 million children
  • U.S. LTBI prevalence: Estimated 13 million
  • U.S. Active TB cases (2022): 8,300

High-Risk Groups (U.S.)

Risk Factors Notes
Immigrants from high-TB burden regions Especially Africa, Asia, Eastern Europe
HIV or other immunosuppression Highest risk of progression
Homelessness, incarceration, drug use Social determinants of health
Congregate living Nursing homes, prisons, shelters
Healthcare and lab workers Especially those working with mycobacteria
Children with recent exposure High progression risk

ETIOLOGY

  • Causative organisms:
  • Mycobacterium tuberculosis
  • Mycobacterium bovis
  • Mycobacterium africanum

PATHOPHYSIOLOGY

  • Infection leads to containment by host immune response → granuloma formation
  • Bacilli remain dormant; may reactivate when immune system is weakened
  • Greatest risk of activation is within 2 years of initial infection

CLINICAL PRESENTATION

LTBI

  • Asymptomatic
  • No physical exam findings
  • No radiologic evidence of active disease

Rule out Active TB

  • Symptoms to inquire:
  • Chronic cough (>2–3 weeks)
  • Fever
  • Night sweats
  • Weight loss
  • Hemoptysis

DIAGNOSIS

Screening Tests

Test Description Notes
Tuberculin Skin Test (TST) PPD 5 U intradermally; read 48–72 hrs later Interpretation depends on risk factors
Interferon-Gamma Release Assays (IGRA) QuantiFERON or T-SPOT.TB Preferred for BCG-vaccinated individuals

TST Interpretation (mm of induration)

Risk Group Positive if ≥
HIV+, recent TB contact, immunosuppressed 5 mm
Children <4 years, high-risk medical conditions 10 mm
Healthy individuals without risk factors 15 mm

Radiographic & Lab Workup

  • Chest X-ray: Rule out active TB
  • AFB smear & culture: Only if concern for active disease
  • Labs:
  • CBC, liver enzymes (if treatment planned)
  • HIV screening
  • Hepatitis panel if INH/RIF considered

TREATMENT

Goals

  • Prevent progression to active TB
  • Reduce community transmission
  • Part of U.S. TB elimination strategy

Treatment Principles

  • Rule out active TB before treating LTBI
  • Use Directly Observed Therapy (DOT) if adherence is uncertain
  • Treat during pregnancy if recent infection or HIV+; otherwise defer to postpartum

First-Line Regimens

Regimen Duration Notes
RIF daily 4 months 10 mg/kg (max 600 mg)
INH + RIF daily 3 months INH 15 mg/kg (max 900 mg)
INH + Rifapentine weekly (3HP) 3 months DOT required, weight-based dosing
INH alone 6–9 months Alternative if other regimens not suitable

Key Considerations

  • Monitor for hepatotoxicity, esp. with INH
  • Use pyridoxine (vitamin B6) 25–50 mg/day with INH to prevent neuropathy
  • Rifamycins have significant drug interactions (esp. OCPs, warfarin)

SPECIAL POPULATIONS

Pediatric

  • Follow public health protocols
  • Test newborns if maternal TB suspected
  • Separate mother and infant if mother contagious (case-by-case basis)

Geriatric

  • Require two-step TST before entering long-term care
  • Monitor INH side effects closely

FOLLOW-UP & MONITORING

  • Monthly follow-up during treatment:
  • Adherence monitoring
  • Symptoms of hepatotoxicity
  • Repeat liver enzymes if:
  • Patient becomes symptomatic
  • HIV+, liver disease, pregnancy/postpartum
  • No need to repeat CXR unless symptoms arise or treatment is reconsidered

PREVENTION

  • Screen high-risk individuals (immigrants, contacts of TB cases, immunocompromised)
  • Screen all household contacts if one member has LTBI
  • Vaccination status (BCG): use IGRA over TST if available

PROGNOSIS

  • Excellent with full adherence to treatment
  • Nonadherence → persistent LTBI, not resistance
  • Retreatment not required if therapy incomplete

COMPLICATIONS

  • Progression to active TB
  • Hepatotoxicity (esp. with INH)
  • Peripheral neuropathy (preventable with B6)
  • Drug-drug interactions (rifamycins)

CODES

  • ICD-10: R76.11 — Nonspecific reaction to tuberculin skin test

CLINICAL PEARLS

  • LTBI is asymptomatic but carries a significant risk for reactivation.
  • IGRA preferred over TST in BCG-vaccinated individuals.
  • Short-course rifamycin-based regimens are now favored due to better adherence and fewer side effects.
  • All positive LTBI tests warrant evaluation and treatment unless contraindicated.
  • LTBI treatment does not cause resistance if interrupted, but relapse risk remains.