What tests are positive with latent Tuberculosis (TB) infection?

Diagnostic Tests for Latent Tuberculosis Infection

Latent tuberculosis infection (LTBI) is diagnosed through positive tuberculin skin test (TST) and/or interferon-gamma release assay (IGRA) results in the absence of active TB disease. 1

Primary Diagnostic Tests

• Tuberculin Skin Test (TST):

  • Positive result defined as induration ≥5 mm in high-risk individuals 2, 1
  • Measures delayed-type hypersensitivity response to purified protein derivative (PPD)
  • May be falsely positive in BCG-vaccinated individuals 2
  • May be falsely negative in patients on immunosuppressive therapy:
    • Corticosteroids for >1 month
    • Thiopurines or methotrexate for >3 months
    • During active inflammatory bowel disease even without immunosuppression 2

• Interferon-Gamma Release Assays (IGRAs):

  • Two main types: QuantiFERON-TB Gold and T-SPOT.TB 1, 3
  • Measure T-cell release of interferon-gamma in response to M. tuberculosis-specific antigens
  • More specific than TST in BCG-vaccinated individuals 2, 1
  • Preferred in BCG-immunized individuals 2
  • May complement TST for increased sensitivity 2, 4

Diagnostic Algorithm

1. Initial screening should include:

   • Patient history (TB exposure, risk factors)
   • Chest X-ray
   • TST and/or IGRA 2, 1

2. Positive LTBI diagnosis is made when:

   • Positive TST (≥5 mm induration) and/or positive IGRA
   • No radiological evidence of active TB
   • No clinical symptoms of active TB 2

3. Additional considerations:

   • Abnormal chest radiograph suggestive of old TB (calcification >5 mm, pleural thickening, linear opacities) should be considered indicative of LTBI even if other criteria are absent 2
   • Booster TST may be appropriate for patients on immunomodulators with negative initial TST 2

Special Populations

• HIV-infected patients:

  • Should be tested at initiation of care 2
  • Repeat testing recommended if initial result is negative but CD4 count increases to >200 cells/μL after starting antiretroviral therapy 2, 1
  • Close contacts of infectious TB should be treated for LTBI regardless of TST/IGRA results 2, 1

• Patients starting anti-TNF therapy:

  • Screening mandatory before initiating therapy 2, 1
  • Combination of TST and IGRA may be optimal approach 5
  • IGRA preferred in BCG-vaccinated individuals 2
  • Complete treatment of LTBI required before starting anti-TNF therapy 1

Limitations of Current Tests

• Neither TST nor IGRA can:

  • Differentiate between LTBI and active TB 3, 6
  • Distinguish reactivation from reinfection
  • Predict progression to active disease 3
  • Evaluate effectiveness of LTBI treatment 6

• Both tests have reduced sensitivity in immunocompromised patients 3

Important Pitfalls to Avoid

• Failing to rule out active TB before diagnosing LTBI 1
• Misinterpreting false-negative TST results in immunosuppressed patients 2
• Overlooking the need for booster TST in patients on immunomodulators 2
• Relying solely on TST in BCG-vaccinated individuals 2, 1
• Confusing LTBI with active TB, which requires different management 1

The combination of TST and IGRA testing provides higher sensitivity for LTBI diagnosis than either test alone, particularly in immunocompromised populations 4. When both tests are used, the diagnosis of LTBI can increase by approximately 10-11% compared to using TST alone 4.