Quantiferon Gold
Two kinds of immunological methods are used for detecting Mycobacterium tuberculosis infection: tuberculin skin tests (TSTs) and interferon-?release assay (IGRA) blood tests. These tests are the only means for detecting latent M.tuberculosis infection, and they also contribute to diagnosing tuberculosis (TB) disease. When findings such as chest radiography and mycobacterial cultures are sufficient for confirming or excluding theTB diagnosis, the results from a TST or anIGRA blood test might be unnecessary. Nevertheless, most TB cases in the United States are diagnosed with a set of findings including results from one of these tests. When TB disease is strongly suspected, specific treatment should be started regardless of results from TST or an IGRA blood test.
Blood assays for tuberculosis, commonly referred to as interferon gamma release assays (IGRAs), are based on the principle of interferon-gamma being critical to regulation of the cell-mediated immune response to Mycobacterium tuberculosis (MTB) infection. Currently available FDA-approved IGRA assays for MTB include Quantiferon and T-spot TB. Both assays measure the interferon-gamma response to MTB proteins, including early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10). Because these assays quantitate a biologic response, testing of a fresh blood specimen having adequate viable white blood cells is crucial to obtaining accurate results.
Oxford Immunotec sells the T-SPOT.TB test, which received pre-market approval from the FDA in July 2008. A tube of blood is drawn and centrifuged. Mononuclear cells are added to a microtiter plate that contains solid phase antibodies to ?-interferon. Peptide antigens identical to ESAT-6, a protein virulence factor of M. tuberculosis, are introduced. T-cells which have been sensitized to M. tuberculosis secrete ?-interferon, which binds to the solid phase antibodies. Substrate is added and the amount of gamma interferon is quantified.
QuantiFERON-TB Gold (QFT-Gold), uses a cocktail of peptides including ESAT-6, CFP-10, and TB7.7(p4)) to stimulate pre-sensitized T-cells to release ?-interferon, which is then measured via ELISA. QuantiFERON-TB Gold Plus (QFT-Plus) only uses ESAT-6 and CFP-10 as stimulatory peptides.
The CDC has published guidelines for use of blood assays for the diagnosis of latent and active TB (MMWR 2010;59,No. RR-5).
- In general, an IGRA may be used in all situations for which TST is indicated. An IGRA is the test of choice in two instances; for people who have received BCG, either as a vaccine or as chemotherapy and under circumstances where the tested person is unlikely to return to have the TST read.
- Either TST or IGRA may be used to test contacts of people with active TB infection, and in screening for occupational exposures.
- Routine testing with both TST and an IGRA is not generally recommended. Exceptions include suspected active TB in immune compromised patients, or indeterminate results from either test.
- TST testing is preferred for children aged <5 years.
Neither IGRA nor TST can distinguish active from latent tuberculosis. CDC recommends that persons with a positive TST or IGRA be evaluated for the likelihood of TB infection. A diagnosis of latent TB requires that active TB be excluded by history & physical examination, chest X-ray, and cultures when indicated. Although both sensitivity and specificity of the IGRA tests is high, negative results are not sufficient to exclude infection in suspect cases. Positive results may occur due to infection with other mycobacterial organisms, including M. kansasii, M. szulgai, and M. marinum, due to their production of ESAT-6 and CFP-10.
Effective March 4, 2013 Saint Luke’s Microbiology began performing Quantiferon testing in-house, replacing the T-spot TB that was sent to a reference laboratory. A special collection kit with specific handling requirements is required for these specimens, due to the presence of antigens and controls within the collection tubes. Specimens must be received by the laboratory as soon as possible after collection to decrease the likelihood of indeterminate results. Specimens received greater than 16 hours after collection cannot be processed. Results are reported as positive, indeterminate, or negative.
- CDC.UpdatedguidelinesforusinginterferongammareleaseassaystodetectMycobacterium tuberculosisinfection—UnitedStates,2010.MMWR2010;59(RR-5). http://www.cdc.gov/mmwr/PDF/rr/rr5905.pdf.
- AmericanThracicSociety.Diagnosticstandardsandclassificationoftuberculisinadultsand children.AmJRespirCritCareMed2000;161:1376–http://www.cdc.gov/tb/publications/PDF/1376.pdf.
- CDC.Treatmentftuberculosis.MMWR2003;52(RR-11). http://www.cdc.gv/mmwr/PDF/rr/rr5211.pdf.
