What is the purpose of Interferon-Gamma Release Assay (IGRA)?

From the Guidelines

Interferon-Gamma Release Assays (IGRAs) are the preferred method for detecting latent tuberculosis infection, especially in individuals with a history of BCG vaccination, due to their higher specificity and convenience compared to tuberculin skin tests (TSTs) 1.

Key Points

• IGRAs are blood tests that measure the immune response to TB bacteria by detecting the release of interferon-gamma from T-cells.
• The two main FDA-approved IGRAs are QuantiFERON-TB Gold Plus and T-SPOT.TB.
• IGRAs are recommended for diagnosing latent TB infection in individuals at high risk, such as healthcare workers, immigrants from TB-endemic countries, immunocompromised patients, and those with a history of BCG vaccination.
• IGRAs have improved specificity and convenience compared to TSTs, but may be more expensive.
• Additional testing, such as chest X-ray and sputum culture, is needed to distinguish between latent TB infection and active TB disease.

Recommendations

• IGRAs should be used as aids in diagnosing M. tuberculosis infection, particularly in individuals with a high risk of infection or progression to active tuberculosis 1.
• IGRAs should be performed and interpreted according to established protocols using FDA-approved test formats, and in compliance with Clinical Laboratory Improvement Amendment (CLIA) standards 1.
• A chest X-ray should be included in TB-screening procedures, especially as a negative IGRA or TST cannot exclude active TB or rule out latent TB 1.

Considerations

• False negatives can occur in immunocompromised patients, very young children, or those with recent TB exposure.
• IGRAs may not be suitable for individuals with a low risk of infection and progression to active tuberculosis, as the majority of positive results may be false positives 1.
• The choice of IGRA test (Quantiferon or EliSPOT) does not affect the diagnosis, as concordance between different IGRAs is good 1.

From the Research

IGRA Overview

• IGRA (Interferon-Gamma Release Assay) is a test used to detect latent tuberculosis infection (LTBI) 2, 3, 4, 5, 6
• It measures the immune response to Mycobacterium tuberculosis, the bacteria that causes tuberculosis 2, 3, 4, 5, 6

Comparison with Tuberculin Skin Test (TST)

• IGRA is preferred over TST in certain populations, such as those who have received the bacille Calmette-Guérin (BCG) vaccine 3, 5, 6
• IGRA has a higher specificity than TST, but its sensitivity is also higher 5
• TST can produce false-positive results due to cross-reaction with BCG vaccination, while IGRA is less affected by this 6

Predictive Value

• IGRA has a better predictive ability than TST for the progression of latent infection to active tuberculosis disease 4
• The positive predictive value of IGRA is higher than that of TST, but still relatively low 4
• The negative predictive value of IGRA is high, indicating that a negative result can rule out LTBI with high confidence 4

Clinical Applications

• IGRA can be used to identify individuals with LTBI who are at high risk of progressing to active tuberculosis disease 2, 4
• Preventive treatment can be targeted at individuals who test positive with IGRA, reducing the risk of progression to active disease 4
• Dual testing with IGRA and TST may improve detection of LTBI, but further confirmation is needed 4