An Upgraded Blood Test That Identifies Tuberculous Infection

By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.

Synopsis: The CDC recommends that QuantiFERON®-TB Gold (QFT-G) may be used in all circumstances in which the TST is currently used, including contact investigations, evaluation of recent immigrants, and sequential-testing surveillance programs for infection control (e.g., those for health-care workers).

Source: Mazurek GH, et al. Guidelines for Using the QuantiFERON®-TB Gold Test for Detecting Mycobacterium tuberculosis Infection, United States. MMWR Recomm Rep. 2005;54(RR15):49-55. Erratum in: MMWR Morb Mortal Wkly Rep. 2005;54:1288.

Tuberculin skin testing is a crude procedure, fraught with potential error at every step, from application to interpretation, and requires 2 visits to a health care provider. Its use has persisted, nonetheless, because it remained, until recently, the only means of detection of latent infection with Mycobacterium tuberculosis. The introduction of an in vitro test, QuantiFERON, several years ago did provide an alternative, but it suffered from the same problems of cross-reactivity with other mycobacteria, especially BCG, as did the PPD skin test. An advanced and much improved version of this test, the QuantiFERON®-TB Gold (QFT-G) test was approved by the US FDA in May of this year, and has replaced the older version which is no longer available.

The QFT-G test utilizes an ELISA test to quantify IFN-release in fresh, heparinized, whole blood incubated with mixtures of synthetic peptides representing 2 proteins of M. tuberculosis, culture filtrate protein-10 (CFP-10) and early secretory antigenic target-6 (ESAT-6). These antigens are absent from BCG vaccine strains, as well as from most non-tuberculous mycobacteria with the exception of the photochromogens, M. kansasii and M. szulgai, and the scotochromogen, M. marinum. This relative antigenic selectivity allows improved specificity of QFT-G relative to the discontinued QFT or to PPD skin testing. Of particular importance is that QFT-G results are not affected by prior BCG vaccination; its specificity in BCG-vaccinated individuals has been reported to be 96% to 98%, which compares very favorably to PPD skin testing with a specificity reported to be 49%. At the same time, it appears to have good sensitivity, reported in patients with culture-positive active tuberculosis to be similar to that of PPD skin testing, at approximately 80%.

An important drawback to the use of QFT-G is that incubation with the test antigens (which continues for 16-24 hours) must be initiated within 12 hours of phlebotomy. This requires relatively close proximity to the laboratory performing the test. The performance of the test in immunocompromised patients, such as those with AIDS, has not been evaluated, but its sensitivity is likely to be reduced, as is true for PPD skin testing. QFT-G, of course, in contrast to PPD skin testing, produces no boosting effect—which may be a good or a bad thing, depending on your point of view and circumstance.

The CDC states that the QFT-G test can be used in all circumstances in which PPD skin testing is currently utilized. These include contact investigation, evaluation of recent immigrants with a history of BCG vaccination (in whom QFT-G would appear to have particular value), and screening of health care workers and other undergoing serial screening. In each of these circumstances, the QFT-G may replace the skin test; there is no reason to follow a positive QFT-G with a PPD skin test.