Key points
- TB blood tests (interferon-gamma release assay or IGRA) are methods of determining whether a person is infected with TB bacteria.
- TB blood tests measure the immune response to TB proteins in whole blood.
- Two TB blood tests are commercially available and approved by the U.S. Food and Drug Administration.
Background
About the TB blood test
The TB blood test (interferon gamma release assay [IGRA]) mixes a patient’s blood samples with peptides that simulate antigens derived from TB bacteria and with controls. The TB antigens were chosen because they are found in M. tuberculosis complex, including M. bovis, but they are absent from BCG and from the majority of other mycobacteria.
In most people infected with TB bacteria, specific immunity develops within six to eight weeks. Then, some white blood cells can respond to the simulated TB antigens releasing interferon-gamma (IFN-γ). The tests measure the level of IFN-γ response. Control substances are used for comparison purposes to help verify test results and to determine a person’s background level of IFN-γ.
The U.S. Food and Drug Administration (FDA) has approved these two TB blood tests that are commercially available in the United States:
- QuantiFERON®-TB Gold Plus (QFT-Plus)
- T-SPOT®.TB test (T-Spot)
Comparison of the QFT-Plus and the T-Spot
| Characteristics | QFT-Plus | T-Spot |
|---|---|---|
| Processing time | Within 16 hours (whole blood) | Within 8 to 32 hours (blood cells) |
| M. tuberculosis antigens | ESAT-6 and CFP-10 | ESAT-6 and CFP-10 |
| Measurement | IFN-γ concentration | Number of IFN-γ producing cells (spots) |
| Possible results | Positive, negative, indeterminate | Positive, negative, invalid, borderline |
Advantages and disadvantages of the TB blood test (compared to the TB skin test)
The TB blood tests serve the same purpose as the tuberculin skin test, but they have functional and diagnostic differences.
Advantages
- Requires only one patient visit to do the test
- Does not cause booster phenomenon (unlike the TB skin test)
- Not subject to biases and errors associated with TB skin test placement and reading
- Results can be available within 24 hours
- Unaffected by the bacille Calmette-Guérin (BCG) TB vaccine and most nontuberculosis mycobacteria
Disadvantages
- Blood samples must be processed within 8 to 32 hours after collection
- Errors in collecting or transporting blood specimens or in running and interpreting the test can decrease the accuracy of TB blood tests
- It may take several days for results to be available, depending on the laboratory and clinic
- Tests may be more expensive than TB skin tests
Determining an approach
Reminder
CDC has resources to help health care providers talk to patients about TB testing and treatment.
Health care providers are encouraged to use TB blood tests to test for TB infection. TB blood tests are the preferred method of testing for:
- People who have received the BCG vaccine
- People who might be less likely to return for TB skin test reading and interpretation
Health care providers should take into account the following factors when considering the TB blood test for a patient:
Age
Current CDC guidelines recommend the TB skin test as the method of testing for children younger than 5 years of age, while noting that some experts use TB blood tests in younger children. Health care providers may choose to consult the American Academy of Pediatrics (AAP) guidance1 on the use of TB blood tests in children. The collection of a sufficient blood sample can be a practical barrier to testing very young children with a TB blood test.
Vaccinations
Live virus vaccination
Vaccination with live viruses, including measles, mumps, rubella, oral polio, varicella, and yellow fever may interfere with TB blood test reactions. For persons scheduled to receive a TB blood test, testing should be done:
- Either on the same day as vaccination with live-virus vaccine or
- At least one month after the administration of the live-virus vaccine
Other vaccinations
Vaccination with inactivated viruses does not interfere with TB blood test reactions.
COVID-19 vaccination should not be delayed because of testing for TB infection. TB blood tests are not expected to affect the safety or the effectiveness of COVID-19 vaccines. Testing for TB infection with a TB blood test can be done before, during, or after a COVID-19 vaccination visit.
TB history
TB blood tests (and TB skin tests) should not be performed on people who have written documentation of a previous positive TB test result (TB blood test or TB skin test) or treatment for TB disease. Most people who have a positive TB test result will continue to have a positive test result. Additional TB blood tests will probably not contribute to medical care, regardless of the result.
Testing guidelines
Health care providers should be properly trained on how to conduct a TB blood test. Health care providers should read the instructions from the manufacturer and follow the steps below:
- Confirm arrangements for testing in a qualified laboratory. Some laboratories may only offer one type of TB blood test, or none at all.
- Arrange for delivery of the blood sample to the laboratory within the time the laboratory specifies to ensure testing of samples containing viable blood cells.
- Draw a blood sample from the patient according the test manufacturer's instructions. Note that the instructions for blood collection and initial processing are different for the two TB blood tests.
- Schedule a follow-up appointment for the patient to receive test results.
- Provide follow-up evaluation and treatment as needed based on test results.
How to interpret test results
Interpretation of TB blood test results depends on the test being used:
QFT-Plus results are based on the amount of IFN-γ that is released in response to the antigens and to the control substances after the blood has been incubated these substances.
T-Spot results are based on comparing the number of IFN-γ producing cells (spots) produced after the blood has been incubated with these substances.
Laboratories should provide both the qualitative and quantitative results:
- For qualitative results
- QFT-Plus results are reported as positive, negative, or indeterminate.
- T-Spot results are reported as positive, borderline, negative, or invalid.
- QFT-Plus results are reported as positive, negative, or indeterminate.
- Quantitative results are reported as numerical values that include responses to the TB antigen and two controls, nil and mitogen.
- Specific guidance is not available for interpreting quantitative IGRA results.
- These results may be helpful for understanding qualitative results in individual cases, in combination with risk factors.
- Specific guidance is not available for interpreting quantitative IGRA results.
Interpretation of TB blood test results
A positive test result usually means TB infection. More tests, such as a chest radiograph, are needed to rule out TB disease.
A negative test result means TB infection is unlikely, but cannot be excluded, especially if the patient:
- Has signs and symptoms consistent with TB disease or
- Has a high risk for developing TB disease once infected with TB bacteria (e.g., the patient is immunocompromised)
A borderline, indeterminate (QFT-Plus only), or invalid (T-spot only) test result means the test did not provide useful information about the likelihood of TB infection. Repeating a TB blood test or performing a TB skin test may be useful.
Test accuracy
False-positive results
Errors in running and interpreting the test can decrease the accuracy of TB blood tests and lead to false-positive results. Health care providers should perform the test according to the manufacturer’s instructions.
False-negative results
Some people have a negative TB blood test result even though they are infected with TB bacteria.
False-negative TB blood test results may occur if the TB infection occurred within 8 weeks of testing because it can take 2 to 8 weeks after being infected with TB bacteria for the body's immune system to mount a response detectable by the test. Negative TB blood test results for contacts of persons with infectious TB disease should be confirmed with a repeat test 8 to 10 weeks after their last exposure to TB.
Patients with untreated, advanced HIV infection (or AIDS) or advanced immunosuppression, such as sepsis, can also have false-negative results.
Other factors that can cause a false-negative TB blood test result:
- Incorrect blood sample collection,
- Incorrect handling of the blood collection tubes, or
- Incorrect performance of the assay.
What to do with test results
A person with a positive TB blood test result or symptoms of TB disease should be evaluated for TB disease. This includes performing:
- A chest radiograph and
- Appropriate bacteriologic examinations of sputum specimens
If latent TB infection is diagnosed, short and convenient treatment regimens are available. Treatment for latent TB infection is 90% effective for preventing the development of TB disease. Your state or local TB program can provide additional information on treating latent TB infection.
It is important to note that a negative TB blood test results does not exclude the diagnosis of TB disease, especially for patients with severe TB illness or infection with HIV.
Reminder
Presumed and confirmed cases of TB disease should be reported to the health department. Latent TB infection is a reportable condition in some states.
Contact your state TB program for the reporting requirements in your state.
- 2024. "Tuberculosis", Red Book: 2024–2027 Report of the Committee on Infectious Diseases, Committee on Infectious Diseases, American Academy of Pediatrics, David W. Kimberlin, MD, FAAP, Ritu Banerjee, MD, PhD, FAAP, Elizabeth D. Barnett, MD, FAAP, Ruth Lynfield, MD, FAAP, Mark H. Sawyer, MD, FAAP. Available from: https://publications.aap.org/redbook/book/755/chapter/14083107/Tuberculosis