The new ex vivo interferon – gamma release assays (IGRAs), such as the QuantiFERON – TB Gold and T-Spot.TB tests, can detect a latent TB infection (LTBI) more accurately than tuberculin skin tests (TSTs).
IGRAs were more specific than TSTs in populations vaccinated with Bacillus of Calmette-Guerin (BCG). IGRAs also do not require a return visit for reading as is needed for patients who have had TSTs. They are available in 24 hours, do not boost (see booster phenomenon), and they are not subject to a reader bias. Most atypical mycobacterial infections do not cause a reaction in IGRA testing. The results of IGRAs and TSTs are often discordant. Although these tests have many limitations and there is no gold standard for the diagnosis of LTBI, the new IGRAs have good specificity, and show promise for detecting LTBI, particularly in BCG–vaccinated patients.
Reading a TB Test: Nucleic Acid Amplification (NAA)
NAA tests are United States Food and Drug Administration (FDA) approved tests that are performed on at least one respiratory specimen, and preferably on the first one, and use a polymerase chain reaction (PCR). Each commercial NAA test uses a different method to amplify different nucleic acid regions of Mycobacterium tuberculosis complex (e.g. a portion of 16S rRNA) and then employs a detection probe specific for Mycobacterium tuberculosis. NAA tests can be used to identify identical mycobacterial DNA and RNA of Mycobacterium tuberculosis in sputum and produce immediate confirmation that a person has active tuberculosis.
NAA test results need to be interpreted in relationship to the results of acid fast bacillus (AFB) smears of sputum:
If sputum specimen is NAA test positive and AFB smear positive, patient can be presumed to have TB.
If sputum specimen is NAA test positive and AFB smear negative, additional specimens (not to exceed three) should be tested. If a second NAA test is positive, the patient can be presumed to have TB.
If sputum specimen is NAA test negative and the AFB smear is positive, a test for inhibitors should be performed.
If inhibitors are detected, the NAA test is not useful for diagnosis.
If inhibitors are not detected, additional specimens (not to exceed three) should be tested. clinical judgment should be used to determine if treatment should be started before AFB culture results are available.
If a second sputum specimen is NAA test negative and AFB smear positive and no inhibitors are detected, then the patient may be presumed to have a nontuberculous mycobacterium (NTM).
If sputum specimen is NAA test negative and AFB smear negative, additional specimens (not to exceed three) should be tested. If a subsequent specimen is NAA negative and AFB smear negative, patient can be presumed not to be infectious.
Reading a TB Test: Further Notes on NAA Testing
Current NAA tests are not sufficiently sensitive to exclude the diagnosis of tuberculosis in patients with AFB smear negative results and who are suspected of having tuberculosis.
The Communicable Disease Center (CDC) recommends NAA testing to be done on at least one representative specimen of sputum from each patient who has signs or symptoms of pulmonary TB and for whom a diagnosis of TB is being considered, but has not been established, when the test result would change the case management or TB control activities, such as contact investigations.
(Updated Guidelines for the Use of Nucleic Acid Amplification Tests in the Diagnosis of Tuberculosis, Mortality and Morbidity Weekly Reports, Volume 58, pp 7 – 10, 2009).