How do I interpret the results of a Tuberculin (TB) Gold test?

Interpreting TB Gold Test Results

A positive TB Gold (QuantiFERON-TB Gold or QFT-G) test indicates likely Mycobacterium tuberculosis infection and requires appropriate follow-up, while negative results generally rule out infection in immunocompetent individuals but should not be used alone to exclude TB in symptomatic patients. 1

Understanding the TB Gold Test

The QuantiFERON-TB Gold test is an interferon-gamma release assay (IGRA) that:

• Detects interferon-gamma released by sensitized white blood cells when exposed to specific M. tuberculosis antigens (ESAT-6 and CFP-10)
• Offers greater specificity than the tuberculin skin test (TST), particularly in BCG-vaccinated individuals
• Provides results within 24 hours without requiring a follow-up visit
• Cannot differentiate between latent TB infection (LTBI) and active TB disease 1

Interpreting Test Results

Positive Results

When a TB Gold test is positive:

• It indicates likely infection with M. tuberculosis (either latent or active)
• Requires further evaluation to rule out active TB disease
• At minimum, a chest radiograph should be performed to look for abnormalities consistent with TB
• HIV testing is recommended as HIV infection increases the urgency of treating LTBI
• After TB disease is excluded, treatment for LTBI should be considered 1, 2

Negative Results

A negative TB Gold test generally indicates:

• The person is unlikely to have M. tuberculosis infection
• No further evaluation is needed for most healthy adults

However, negative results should be interpreted with caution in:

• Recent contacts of infectious TB cases (repeat test 8-10 weeks after exposure ends)
• Persons with symptoms suggestive of TB disease
• Immunocompromised individuals 1, 2

Indeterminate Results

An indeterminate result:

• Provides no useful information about likelihood of infection
• May be due to high background IFN-γ levels or inadequate response to mitogen
• Follow-up options include repeating the test, performing a TST, or no further testing depending on clinical suspicion
• Inadequate response to mitogen is often associated with immunosuppressive conditions 1

Risk Factors for False-Negative Results

Be aware of factors associated with false-negative results:

• Advanced age (≥65 years) 3
• Immunosuppressive conditions 1, 4
• Malignancy 3
• Lymphocytopenia (total lymphocyte count <1.0 × 10^9/L) 3
• Bilateral disease on chest radiography 3
• High inflammatory markers (elevated CRP) 5
• Low protein and albumin levels 4, 5

Special Considerations

For TB Contacts

• Negative results in recent contacts should be confirmed with repeat testing 8-10 weeks after exposure ends
• For high-risk contacts (children <5 years or severely immunocompromised persons), "window period" prophylaxis may be indicated regardless of initial test results 1

For Immunocompromised Patients

• Maintain high suspicion for TB despite negative results
• Consider empiric TB treatment in high-risk patients with suggestive clinical features 2

For BCG-Vaccinated Individuals

• TB Gold test is more specific than TST in BCG-vaccinated individuals
• Only 30% of BCG-vaccinated adults with positive TST will have positive TB Gold results
• Strong predictors of positive TB Gold after positive TST include: abnormal chest radiograph consistent with healed TB, TST induration ≥16mm, and birth in a high TB incidence country 6

Test Limitations

• Sensitivity for detecting M. tuberculosis infection in untreated culture-confirmed TB is approximately 80% (meaning 20% false negatives) 1, 2
• Blood must be incubated with test antigens within 12 hours of collection 1, 2
• Performance in children under 17 years is not well documented 1

Algorithm for Test Interpretation

1. Positive TB Gold result:

   • Perform chest radiography
   • Evaluate for TB symptoms
   • If abnormal imaging or symptoms present: collect sputum for AFB smear, culture, and NAAT
   • If no evidence of active disease: treat as LTBI

2. Negative TB Gold result:

   • In healthy, asymptomatic individuals: no further evaluation needed
   • In TB contacts: repeat test 8-10 weeks after exposure ends
   • In symptomatic patients: proceed with full TB evaluation regardless of test result
   • In immunocompromised patients: maintain high suspicion for TB

3. Indeterminate TB Gold result:

   • In high-risk individuals: repeat test or perform TST
   • In low-risk individuals: no further testing needed

Remember that TB Gold results should always be interpreted in conjunction with clinical, radiographic, and epidemiological findings, not in isolation.