From the Guidelines
Interferon-Gamma Release Assays (IGRAs) are recommended as confirmatory tests for false-positive tuberculin skin tests (TST) in individuals with low to moderate risk for tuberculosis (TB) infection or disease, as stated in the 2010 guidelines 1.
Guidelines for Using IGRA as a Confirmatory Test
The guidelines suggest that IGRA can be used to confirm false-positive TST results, especially in individuals with a low likelihood of TB infection or disease. This is because IGRA has improved specificity compared to TST, particularly in individuals who have received BCG vaccination or have been exposed to non-tuberculous mycobacteria 2.
High-Risk Individuals
For high-risk individuals, a positive TST should generally be considered valid regardless of a negative IGRA result, as the consequences of missing a true TB infection outweigh the risks of unnecessary treatment. High-risk groups include:
- People with HIV infection
- Recent close contacts of TB cases
- Individuals with radiographic findings suggestive of prior TB
- Organ transplant recipients
- Those on immunosuppressive medications (especially TNF-alpha inhibitors)
- Children under 5 years of age who have been exposed to TB
- Persons with fibrotic changes on chest radiography consistent with prior TB Having just one of these risk factors is sufficient to classify someone as high-risk; patients do not need to meet all criteria 2.
Criteria for High-Risk Classification
The criteria for high-risk classification are based on the individual's specific risk factors, the degree of exposure to TB, and the likelihood of progression to active disease. A comprehensive clinical assessment should be performed to determine the individual's risk level and guide treatment decisions 1.
Limitations of TST and IGRA
Both TST and IGRA have limitations, and the decision to treat should be based on a comprehensive clinical assessment rather than relying solely on test results. The guidelines emphasize the importance of considering epidemiologic and medical history, as well as other clinical information, when making decisions about medical or public health management 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 (Mantoux) test results, especially in individuals with prior BCG vaccination 3, 4.
- A two-step procedure for LTBI screening is recommended, which includes an initial Tuberculin skin test (TST) followed by an IGRA for individuals with a positive TST result 3, 4.
Criteria for High-Risk Individuals
- High-risk individuals who may be considered to have a positive Tuberculin test result despite a negative IGRA result include: + Those with increasing age 3. + Males 3. + Individuals from countries with a high prevalence of tuberculosis (TB) 3. + Those with a shorter time since arrival in the United States 3. + Individuals with increasing TST size 3. + Healthcare workers (HCWs) with frequent and direct contact with active TB patients 5. + HCWs working in TB-related departments for a longer duration 5.
IGRA Performance in Different Populations
- IGRAs have excellent specificity and are more specific than the TST in individuals vaccinated with BCG 6.
- The sensitivity of IGRAs is similar to the TST in persons categorized into clinical gradients of exposure 6.
- IGRAs are more sensitive than the TST in immune-compromised individuals, such as those with HIV infection 7.
- There is insufficient evidence on IGRA performance in children, immune-compromised persons, and the elderly 6.