What are the differences between the PPD (Purified Protein Derivative) test, TB Gold (Interferon-Gamma Release Assay), and TB spot test for diagnosing tuberculosis infection?

Comparison of TB Diagnostic Tests: PPD vs. TB Gold vs. TB SPOT

The Interferon-Gamma Release Assays (IGRAs), including TB Gold and T-SPOT.TB, are superior to the traditional PPD skin test for diagnosing tuberculosis infection due to their higher specificity, particularly in BCG-vaccinated individuals and immunocompromised patients. 1

Overview of Testing Methods

PPD (Purified Protein Derivative) Test

• Mechanism: Traditional tuberculin skin test that measures delayed-type hypersensitivity reaction to tuberculin antigens 1
• Administration: Intracutaneous (Mantoux) method with 0.1 mL of PPD (5 TU) injected beneath the skin surface 1
• Reading: Requires measurement of induration (not erythema) at 48-72 hours by trained personnel 1
• Interpretation: Based on risk factors:
  • ≥5 mm: HIV-infected persons, recent TB contacts, immunosuppressed patients
  • ≥10 mm: High-risk populations (immigrants, healthcare workers)
  • ≥15 mm: Persons with no risk factors 2

TB Gold (QuantiFERON-TB Gold)

• Mechanism: IGRA that measures interferon-gamma release in response to specific M. tuberculosis antigens (ESAT-6 and CFP-10) 1
• Administration: Blood-based test requiring viable white blood cells 1
• Processing: Separate aliquots of fresh whole blood are incubated with controls and peptide mixtures 1
• Advantages: Not affected by BCG vaccination; requires only one patient visit 1

T-SPOT.TB (TB SPOT)

• Mechanism: ELISA-based IGRA that also measures interferon-gamma response to TB-specific antigens 1
• Administration: Blood-based test requiring peripheral blood mononuclear cells 1
• Processing: More labor-intensive but potentially more sensitive in immunocompromised patients 1

Key Differences

Specificity

• PPD: Lower specificity (false positives with BCG vaccination and nontuberculous mycobacteria) 1
• IGRAs (TB Gold and T-SPOT.TB): Higher specificity due to use of M. tuberculosis-specific antigens (ESAT-6 and CFP-10) 1

Sensitivity

• PPD: Reduced sensitivity in immunocompromised patients (up to 25% false negatives) 2
• IGRAs: Better performance in HIV-infected and other immunosuppressed patients 1, 3

Practical Considerations

• PPD:

  • Requires patient return for reading at 48-72 hours 1
  • Subject to reader variability and bias 1
  • Affected by prior BCG vaccination 1
  • Lowest cost option 1

• IGRAs (TB Gold and T-SPOT.TB):

  • Single patient visit required 1
  • Not affected by BCG vaccination 1
  • Requires specialized laboratory processing 1
  • Higher cost 1
  • TB SPOT may have slightly higher sensitivity in immunocompromised patients than TB Gold 1

Clinical Algorithm for Test Selection

1. For BCG-vaccinated individuals:

   • Prefer IGRAs (TB Gold or T-SPOT.TB) due to higher specificity 1

2. For immunocompromised patients (HIV, transplant, on biologics):

   • Prefer IGRAs, with T-SPOT.TB potentially offering highest sensitivity 1, 2
   • If using PPD, use ≥5 mm threshold for positivity 2

3. For serial testing (healthcare workers):

   • Consider the potential for conversions and reversions with IGRAs 4
   • CDC guidelines suggest IGRAs may be used in all circumstances where TST is recommended 1

4. For resource-limited settings:

   • PPD remains practical due to lower cost and minimal equipment needs 1
   • Consider two-step testing in settings where boosting may occur 5

Important Pitfalls and Caveats

• Neither PPD nor IGRAs can distinguish between active TB and latent TB infection 1
• False-negative results can occur with all tests in severely immunocompromised patients 2
• PPD requires proper administration technique and standardized reading to be reliable 1
• IGRAs require proper specimen handling to maintain viable white blood cells 1
• For patients on corticosteroids, testing should ideally be performed before initiating therapy due to potential false-negative results 2
• Do not rely solely on negative test results to exclude TB in symptomatic patients 2

Remember that these tests identify infection with M. tuberculosis but cannot determine whether a person has active disease. Positive results should be followed by appropriate clinical evaluation, including chest radiography and bacteriological studies when active TB is suspected.