The TB Blood Test (IGRA): Clinical Testing Guidance

TB blood tests — interferon-gamma release assays (IGRAs) — show whether a person is infected with TB bacteria by measuring the immune response to TB proteins in whole blood.

How they work

The test mixes a patient's blood with peptides that mimic TB antigens, plus controls. The antigens occur in the M. tuberculosis complex (including M. bovis) but not in BCG or most other mycobacteria. In an infected person, some white blood cells respond to them by releasing interferon-gamma (IFN-γ), which the test measures; the controls help verify results and set each person's background level.

The FDA has approved two commercially available tests:

Compared with the TB skin test

Advantages

• One patient visit.
• No booster effect, unlike the skin test.
• Free of the biases and errors of placing and reading a skin test.
• Results can be ready within 24 hours.
• Not affected by the BCG vaccine or most nontuberculous mycobacteria.

Disadvantages

• Samples must be processed within a set time after collection.
• Errors in collecting, transporting, running or interpreting the test reduce accuracy.
• Results may take several days, depending on the lab and clinic.
• May cost more than the skin test.

When to use it

CDC encourages providers to use TB blood tests. They are preferred for:

• people who have had the BCG vaccine;
• people who may be less likely to return to have a skin test read.

Things to consider:

• Age. Current CDC guidelines recommend the skin test for children under 5, though some experts use blood tests in younger children; drawing enough blood from very young children can be hard.
• Live-virus vaccines (measles, mumps, rubella, oral polio, varicella, yellow fever) may interfere. Test the same day as the vaccine, or at least one month after.
• Inactivated vaccines don't interfere, and COVID-19 vaccination shouldn't be delayed — testing can be done before, during or after the vaccine visit.
• Prior positive test or treatment. Don't retest people with documented earlier positive results or treatment for TB disease; most stay positive, and another test won't help.

Doing the test

1. Confirm a qualified laboratory — some offer only one test, or none.
2. Arrange delivery within the lab's time limit, so the blood cells are still viable.
3. Draw blood following the manufacturer's instructions — they differ between the two tests.
4. Schedule a follow-up visit for results.
5. Provide follow-up evaluation and treatment as needed.

Review the FDA-approved labeling for each test's characteristics, precautions and interpretation.

Reading the results

Labs should report both qualitative results (QFT-Plus: positive, negative or indeterminate; T-Spot: positive, borderline, negative or invalid) and quantitative values for the TB antigen and two controls (nil and mitogen). There's no specific guidance for interpreting the numbers, but they can help in individual cases alongside risk factors.

False positives can come from errors in running or reading the test.

False negatives can happen:

• if infection was recent — it can take 2 to 8 weeks for the immune response to be detectable, so contacts of people with infectious TB who test negative should be retested 8 to 10 weeks after their last exposure;
• in untreated, advanced HIV (AIDS) or severe immunosuppression, such as sepsis;
• from incorrect sample collection, tube handling or test performance.

Next steps

Anyone with a positive result or symptoms of TB disease should be evaluated for TB disease, including a chest X-ray and sputum tests. If latent TB infection is diagnosed, short, convenient treatment is available and is 90% effective at preventing TB disease. A negative blood test does not rule out TB disease, especially in people who are very ill or have HIV.

Report presumed and confirmed TB disease to the health department; latent TB infection is reportable in some states.

Sources

Based on "Clinical Testing Guidance for Tuberculosis: Interferon Gamma Release Assay," Centers for Disease Control and Prevention; a work of the United States government in the public domain.