What is the role of Interferon-Gamma Release Assay (IGRA) in the diagnosis and treatment of tuberculosis (TB)?

Role of Interferon-Gamma Release Assay (IGRA) in TB Diagnosis and Treatment

IGRAs are valuable diagnostic tools for detecting Mycobacterium tuberculosis infection but cannot distinguish between latent TB infection (LTBI) and active TB disease, and should not be used alone for diagnosing active TB. 1

What are IGRAs?

• IGRAs are blood tests that detect interferon-gamma released by T-cells previously sensitized to M. tuberculosis antigens 2
• Two commercially available IGRAs: QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB 1
• Unlike tuberculin skin test (TST), IGRAs are not affected by prior BCG vaccination and require only one patient visit 1, 3

Primary Uses of IGRAs

• Detection of M. tuberculosis infection (latent TB) 1
• Cannot distinguish between latent TB infection and active TB disease 1
• Should not replace standard diagnostic methods for active TB (microbiological and radiographic tests) 1

Advantages of IGRAs over TST

• Higher specificity in BCG-vaccinated individuals 1
• No need for return visit (results available after single blood draw) 1
• No boosting of subsequent test results 1
• No reader bias or placement errors 3
• Higher test completion rates in populations with historically low rates of return for TST reading (e.g., homeless persons, drug users) 1

Limitations of IGRAs

• Cannot differentiate between active TB and latent TB infection 1
• Negative results do not exclude TB infection, especially in immunocompromised individuals 1
• Indeterminate or borderline results may require repeat testing 1
• Limited data on ability to predict progression to active TB 1

Recommended Testing Approaches

The CDC recommends several approaches for using IGRAs:

1. IGRA preferred but TST acceptable:

   • For persons with history of BCG vaccination 1
   • For groups with historically low rates of returning for TST reading 1

2. TST preferred but IGRA acceptable:

   • For children under 5 years of age 1

3. Either TST or IGRA without preference:

   • For TB contacts (with follow-up testing 8-10 weeks after exposure if initial test is negative) 1
   • For occupational screening of healthcare workers 1

4. Both TST and IGRA may be considered when:

   • Initial test is negative but risk for infection, progression, and poor outcomes is high (e.g., HIV-infected persons, children <5 years) 1
   • Clinical suspicion for active TB exists and confirmation of infection is desired 1
   • Initial test is positive and additional evidence of infection would improve compliance 1

Interpretation of IGRA Results

• Positive IGRA in symptomatic patients or those at high risk for TB progression should be considered evidence of M. tuberculosis infection 1
• In healthy persons with low likelihood of TB infection, a single positive IGRA should not be taken as reliable evidence of infection (may be false positive) 1
• For discordant results (positive IGRA/negative TST or vice versa), individualized judgment is required based on test quality, probability of infection, and risk of disease progression 1

Common Pitfalls and Caveats

• Using IGRAs alone to diagnose active TB (not recommended) 1
• Failing to arrange for proper blood collection and timely testing (blood must be collected in proper tubes and tested within required timeframe) 1
• Testing persons at low risk for both infection and progression (increases false positives) 1
• Not considering repeat testing when IGRA results are indeterminate, borderline, or invalid 1
• Ignoring clinical and epidemiological context when interpreting results 1

Special Populations

• Immunocompromised patients: IGRAs may have higher sensitivity than TST; using both tests can increase diagnostic sensitivity 3, 4
• Children: TST is preferred for children <5 years, but IGRA is acceptable; some experts advocate using both to increase sensitivity 1
• BCG-vaccinated individuals: IGRAs are preferred due to higher specificity 1