When is the TB‑Gold interferon‑gamma release assay indicated, and how should its results be interpreted?

TB-Gold Interferon-Gamma Release Assay (IGRA)

Indications for Testing

The QuantiFERON-TB Gold test may be used in all circumstances where a tuberculin skin test (TST) is recommended, including contact investigations, evaluation of recent immigrants, and serial-testing surveillance programs for infection control such as healthcare worker screening. 1

The FDA-approved indications include:

• Detection of Mycobacterium tuberculosis infection (both latent TB infection and active disease) when used with risk assessment, radiography, and other medical evaluations 1
• As an alternative to TST in all clinical scenarios traditionally requiring tuberculin testing 1
• Particularly valuable in BCG-vaccinated individuals where TST specificity is compromised 1

Test Methodology

The QuantiFERON-TB Gold In-Tube (QFT-GIT) test works as follows:

• Blood (1 ml) is collected into three specialized tubes containing antigens (ESAT-6, CFP-10, and TB7.7 peptides), negative control (heparin alone), and positive control (phytohemaglutinin) 1
• Tubes are incubated for 16-24 hours 1
• Plasma is separated and interferon-gamma concentration measured by ELISA 1
• The TB Response = IFN-γ from antigen-stimulated blood minus IFN-γ from nil control 1

A critical advantage is that blood must be incubated within 12 hours of collection, but the test can be performed immediately after live virus vaccination (including varicella) without any waiting period, unlike TST which requires 4 weeks. 2

Result Interpretation

Positive Result

• Indicates M. tuberculosis infection (either latent or active disease) 1
• Cannot distinguish between latent TB infection and active TB disease 1
• Requires clinical evaluation including chest radiograph and symptom assessment to exclude active disease 1
• For QFT-GIT: Tests with Nil 0.7-8.0 IU/ml and TB Response 25%-50% of Nil are interpreted as positive 1

Negative Result

• Suggests absence of M. tuberculosis infection 1
• Should not be used alone to exclude infection in symptomatic patients or those with high clinical suspicion 1
• Sensitivity approximately 80% in culture-confirmed TB patients, but may be lower in immunocompromised individuals and young children 1, 3

Indeterminate Result

• Occurs when controls fail (inadequate immune response or excessive background) 1
• More common in immunocompromised patients 1
• Requires repeat testing or alternative diagnostic approach 1

Borderline Result (T-SPOT only)

• The T-SPOT test includes a borderline category for 5-7 spots to address test variation near the cutoff 1

Key Advantages Over TST

The test offers superior specificity because ESAT-6 and CFP-10 antigens are absent from BCG vaccine strains and most nontuberculous mycobacteria (except M. kansasii, M. szulgai, and M. marinum). 1

Additional benefits include:

• No boosting effect from repeated testing 1
• Single patient visit required (no return for reading) 1, 4
• Results available within 24 hours 2
• Not affected by prior BCG vaccination 1
• Can be performed immediately after live virus vaccines 2

Important Limitations and Caveats

Sensitivity for latent TB infection may be less than TST, though lack of a confirmatory test makes this difficult to assess definitively. 1

Critical limitations include:

• Cannot differentiate active TB disease from latent infection 1, 5
• Sensitivity not well-established in immunocompromised patients or young children 1, 3
• Cannot predict risk of progression from latent infection to active disease 1
• False-positive results possible with M. kansasii, M. szulgai, and M. marinum infection 1
• Results not interchangeable with TST due to different antigens and interpretation criteria 1

Clinical Application Algorithm

1. Order IGRA when TST is indicated but patient has:

   • Prior BCG vaccination 1
   • Difficulty returning for TST reading 1, 4
   • Recent live virus vaccination 2

2. Interpret positive results by:

   • Obtaining chest radiograph to exclude active disease 1
   • Assessing for TB symptoms (cough, fever, weight loss, night sweats) 1
   • Considering epidemiologic risk factors 1

3. Manage negative results by:

   • Not excluding TB in symptomatic patients 1
   • Considering repeat testing or TST in high-risk immunocompromised patients 1, 3
   • Proceeding with additional diagnostic workup if clinical suspicion remains high 1

4. Handle indeterminate results by:

   • Repeating the test 1
   • Considering TST as alternative 1
   • Evaluating for immunosuppression 1