Tuberculosis testing: Which patients, which test?
The most appropriate test to identify latent TB depends on the patient’s risk for developing active TB and other factors. This review provides practical guidance on who to test, how, and when.
Use of TST is well established
To perform a TST, inject 5 tuberculin units (0.1 mL) of purified protein derivative (PPD) intradermally into the inner surface of the forearm using a 27- to 30-gauge needle. (In the United States, PPD is available as Aplisol or Tubersol.) Avoid the former practice of “control” or anergy testing with mumps or Candida antigens because this is rarely helpful in making TB treatment decisions, even in HIV-positive patients.12
To facilitate intradermal injection, gently stretch the skin taut during injection. Raising a wheal confirms correct placement. The test should be read 48 to 72 hours after it is administered by measuring the greatest diameter of induration at the administration site. (Erythema is irrelevant to how the test is interpreted.) Induration is best read by using a ballpoint pen held at a 45-degree angle pointing toward the injection site. Roll the point of the pen over the skin with gentle pressure toward the injection site until induration causes the pen to stop rolling freely (FIGURE). The induration should be measured with a rule that has millimeter measurements and interpreted as positive or negative based on the individual’s risk factors (TABLE 3).3
Watch for these 2 factors that can affect TST results
Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is (or has been) used as a routine childhood immunization in many parts of the world, although not in the United States.13 It is ordinarily given as a single dose shortly after birth, and has some utility in preventing serious childhood TB infection. The antigens in PPD and those in BCG are not identical, but they do overlap.
BCG administered after an individual’s first birthday resulted in false positive TSTs >10 mm in 21% of those tested more than 10 years after BCG was administered.14 However, a single BCG vaccine in infancy causes little if any change in the TST result in individuals who are older than age 10 years. When a TST is performed for appropriate reasons, a positive TST in people previously vaccinated with BCG is generally more likely to be the result of LTBI than of BCG.15 Current guidelines from the Centers for Disease Control and Prevention (CDC) recommend that previous BCG status not change the cutoffs used for interpreting TST results.16
Booster phenomenon. In many adults who have undiagnosed LTBI that they acquired in the distant past, or who received BCG vaccination as a child, immunity wanes after several decades. This can result in an initial TST being negative, but because the antigens in the PPD itself stimulate antigenic memory, the next time a TST is performed, it may be positive.
In people who will have annual TST screenings, such as health care workers or nursing home residents, a 2-step PPD can help discriminate this “booster” phenomenon from a new LTBI acquired during the first year of annual TST testing. A second TST is placed 1 to 2 weeks after the initial test, a time interval during which acquisition of LTBI would be unlikely. The result of the second test should be considered the person’s baseline for evaluation of subsequent TSTs. A subsequent TST would be considered positive if the induration is >10 mm and has increased by ≥6 mm since the previous baseline.17
IGRA offers certain benefits
IGRA uses antigens that are more specific for Mycobacterium tuberculosis than the TST, and as a result, this test is not influenced by previous BCG vaccination. It requires only one blood draw, and interpretation does not depend on the patient’s risk category or interpretation of skin induration. The primary disadvantage of IGRAs is high cost (currently $200 to $300 per test), and the need for a laboratory with adequate equipment and personnel trained in performing the test. IGRAs must be collected in special blood tubes, and the samples must be processed within 8 to 16 hours of collection, depending on the test used.5
Currently, 2 IGRAs are approved for use in the United States—the QuantiFERON-TB Gold In-Tube (QFT-GIT) and the T-SPOT.TB assay. Both tests may produce false positives in patients infected with Mycobacterium marinum or Mycobacterium kansasii, but otherwise are highly specific for Mycobacterium tuberculosis. IGRA results may be “boosted” by recent TST (ie, a TST given within the previous 3 months may cause a false positive IGRA result), and this effect may begin as early as 3 days after a TST is administered.18 Therefore, if an IGRA is needed to clarify a TST result, it should be drawn on the day the TST is read.19
