What are Interferon Gamma Release Assays (IGRAs)?
Interferon gamma release assays (IGRAs) are blood tests used to detect the presence of
Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). They measure the release of interferon-gamma (IFN-γ), a cytokine, from T-cells in response to specific TB antigens. Unlike the traditional tuberculin skin test (TST), IGRAs do not require the patient to return for a reading, offering a more convenient option for TB screening.
How do IGRAs work?
When a person is infected with TB, their immune system sensitizes T-cells to recognize and respond to TB antigens. In an IGRA, a sample of the patient’s blood is mixed with these specific antigens. If the person has been exposed to TB, their T-cells will release IFN-γ. The amount of IFN-γ released is then measured, providing an indication of whether the individual has been infected with TB.
What are the advantages of IGRAs over the TST?
1.
Specificity: IGRAs have higher specificity and are less likely to produce false-positive results in individuals vaccinated with the
Bacille Calmette-Guérin (BCG) vaccine or those exposed to non-tuberculous mycobacteria.
2.
Single Patient Visit: Unlike the TST, which requires a follow-up visit 48-72 hours later to read the test, IGRAs require only one patient visit to draw blood.
3.
Objective Measurement: IGRAs provide quantitative results, reducing the subjectivity involved in reading and interpreting the TST.
What are the limitations of IGRAs?
While IGRAs present distinct advantages, they also have certain limitations:
1. Cost: IGRAs are generally more expensive than the TST, which may limit their accessibility in resource-constrained settings.
2. Sensitivity: While IGRAs are specific, their sensitivity can vary, and they may not be as effective in detecting TB in very young children or immunocompromised individuals.
3. Indeterminate Results: Occasionally, results from IGRAs can be indeterminate, requiring further testing or repetition of the assay.
Who should be tested using IGRAs?
IGRAs are particularly useful in specific populations:
- Individuals with a history of BCG vaccination: Since IGRAs are not influenced by the BCG vaccine, they are ideal for those who have been vaccinated, preventing false-positive results common with the TST.
- Healthcare workers and high-risk groups: Those frequently exposed to TB can benefit from the convenience and specificity of IGRAs.
- Foreign-born individuals from high-prevalence countries: Given their increased risk for latent TB infection, IGRAs can provide accurate screening in these populations.
How are IGRA results interpreted?
The interpretation of IGRA results involves understanding three possible outcomes:
1. Positive Result: Indicates TB exposure and the presence of latent TB infection, necessitating further evaluation to rule out active TB disease.
2. Negative Result: Suggests no TB infection, but may require repeat testing if there is a high suspicion of exposure or symptoms are present.
3. Indeterminate Result: May occur due to technical issues or patient factors such as immunosuppression. Such results require further follow-up or alternative testing methods.
Are IGRAs used for diagnosing active TB disease?
IGRAs are primarily used to detect latent TB infection and are not intended as a standalone diagnostic tool for active TB disease. For active TB, a combination of clinical evaluation, microbiological culture, and imaging studies, such as chest X-rays, are essential. IGRAs can, however, be part of a comprehensive diagnostic approach when evaluating suspected TB cases.
What future developments are expected in IGRAs?
Research is ongoing to enhance the performance and accessibility of IGRAs. Developments may include:
- Improved Sensitivity: Efforts to increase sensitivity, particularly in special populations, such as young children and the immunocompromised.
- Point-of-Care Testing: Innovations could lead to IGRAs being available as rapid, point-of-care tests, increasing accessibility worldwide.
- Expanded Antigen Panels: Incorporating additional antigens to improve detection rates and accuracy.
Conclusion
Interferon gamma release assays are a valuable tool in the detection of latent TB infection, offering advantages in specificity and convenience over traditional methods. While they have limitations, ongoing research and technological advancements aim to address these challenges and improve their utility in global TB control efforts.
