From the Guidelines
Interferon-Gamma Release Assays (IGRAs) are recommended as confirmatory tests for false positive tuberculin skin tests (TST) in individuals who have received BCG vaccination or have been exposed to non-tuberculous mycobacteria, particularly when TST results are positive but clinical suspicion for tuberculosis is low. The guidelines for using IGRAs as confirmatory tests are based on the higher specificity of IGRAs compared to TST, especially in BCG-vaccinated populations where TST false positives can reach 30-50% 1.
Key Points to Consider
- IGRAs should be used when TST results are positive but clinical suspicion for tuberculosis is low, especially in BCG-vaccinated individuals where false positives are common.
- The standard approach is to perform an IGRA test (such as QuantiFERON-TB Gold or T-SPOT.TB) within 3 months of a positive TST result.
- IGRAs have higher specificity than TST because they measure T-cell response to antigens specific to Mycobacterium tuberculosis that are not present in BCG or most non-tuberculous mycobacteria.
- If the IGRA is negative following a positive TST in a low-risk individual with BCG vaccination history, the TST result is typically considered a false positive, and preventive therapy may be unnecessary.
- However, in high-risk individuals (immunocompromised patients, recent TB contacts), a positive TST should be taken seriously regardless of IGRA results, and clinical judgment should guide management decisions 1.
Situations Where IGRAs May Be Considered
- When the initial test (TST or IGRA) is negative in high-risk individuals, such as those with HIV infection or children aged <5 years.
- When clinical suspicion exists for active tuberculosis, and confirmation of M. tuberculosis infection is desired.
- When additional evidence of infection is required to encourage compliance, such as in foreign-born health-care workers who believe their positive TST result is attributable to BCG.
- In healthy persons who have a low risk for both infection and progression, requiring a positive result from the second test as evidence of infection increases the likelihood that the test result reflects infection. It is essential to consider the individual's risk factors, medical history, and clinical presentation when interpreting IGRA and TST results, as the guidelines emphasize the importance of clinical judgment in managing patients with suspected tuberculosis infection 1.
From the Research
Guidelines for Using Interferon-Gamma Release Assay (IGRA) as a Confirmatory Test
- The IGRA is used as a confirmatory test for false positive Tuberculin Skin Test (TST) results, especially in individuals who have received bacille Calmette-Guérin (BCG) vaccination 2.
- The use of IGRA is recommended in cases where the TST result is positive, but the patient has a low risk of tuberculosis (TB) infection, or when the TST result is uncertain 3.
- IGRA is preferred over TST in patients receiving methotrexate therapy, as methotrexate use can lead to false-positive TST results 4.
- In high school students with TST-positive results who have had contact with another student who had TB, the use of confirmatory IGRA can help focus the targeting of latent TB infection (LTBI) treatment to fewer contacts 5.
Indications for Using IGRA as a Confirmatory Test
- BCG-vaccinated individuals with a positive TST result 2
- Patients receiving methotrexate therapy with a positive TST result 4
- Contacts of TB patients with a positive TST result, especially in high BCG-vaccinated populations 5
- Individuals with a positive TST result, but a low risk of TB infection 3