HWN Suggests

A Better Test for TB infection

Then you want a TB blood test! The TB blood test is more specific than a TB skin test (less likely to cause a false positive) and it requires only one visit, while a TB skin test may require several visits (four visits over a 10 to 21 day period for a two-step test). TB blood tests (also called interferon-gamma release assays or IGRAs) measure how the immune system reacts to the bacteria that cause TB. An IGRA is a laboratory test that measures how strongly a person’s immune system reacts to TB bacteria.

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 Challenges related to TB testing and diagnosis

IGRAs are next-generation diagnostic tools for assessment of TB infection. They assess surrogate markers of M. tuberculosis (MTB) infection as indicated by a cellular immune response to purified membrane antigens of MTB. IGRA results can be available in 24 to 48 hours and do not require a follow-up visit for reading of results. MTB-specific antigens include early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), which are encoded by genes located within the region of difference 1 segment of the MTB genome. The antigens are more specific for MTB than PPD as they are not expressed by any BCG vaccine strains or most species of NTM, other than M. marinum, M. kansasii and M. szulgai. More importantly, M. avium complex (MAC), the most common nontuberculous mycobacteria worldwide, does not express either ESAT-6 or CFP-10, and thus patients with MAC infection are IGRA test-negative.

 Weighing Gold or Counting Spots Which Is More Sensitive to Diagnose Latent Tuberculosis Infection?

In the United States, the Food and Drug Administration has approved the QuantiFERON-TB Gold test for diagnosis of LTBI and is evaluating the T-SPOT.TB test. The Centers for Disease Control and Prevention have recommended that the QuantiFERON-TB Gold test can generally be substituted for the tuberculin skin test. I agree with this recommendation, except that I favor continued use of the tuberculin skin test in populations with depressed cell-mediated immune responses. In Europe, where both IFN-γ–based tests are available, I believe that the T-SPOT.TB test should be used for persons in whom cell-mediated immunity may be depressed. For immunocompetent persons, either IFN-γ–based test can be used. Clinical laboratories are likely to prefer the QuantiFERON-TB Gold test because it is simpler to perform than the T-SPOT.TB test.

Articles of Interest

Interferon-Gamma Release Assays versus Tuberculin Skin Testing for the Diagnosis of Latent Tuberculosis Infection: An Overview of the Evidence

We conclude that both tests are accurate to detect latent tuberculosis, although interferon-gamma release assays have higher specificity than tuberculin skin testing in BCG-vaccinated populations, particularly if BCG is received after infancy. However, both tests perform poorly to predict risk for progression to active tuberculosis.

A Three-Way Comparison of Tuberculin Skin Testing, QuantiFERON-TB Gold and T-SPOT.TB in Children

Although a high level of agreement between the IGRAs was observed, they are commonly discordant with the TST. The correct interpretation of a negative assay in a child with a positive skin test in clinical practice remains challenging and highlights the need for longitudinal studies to determine the negative predictive value of IGRAs.

Can you trust the TB blood test? Questions linger

After years of struggling with the vagaries of the tuberculosis skin test, you might think that hospitals would embrace a new technology. But the blood test has been slow to catch on. Cost and laboratory barriers likely will be resolved as new versions of the test obtain wider distribution. But TB experts want to know: Would you put more faith in this test than the skin test to detect seroconversions without producing false-positives?

Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model

Health care workers (HCWs) are at risk for exposure to tuberculosis (TB) and are routinely tested for latent TB infection (LTBI) as part of most infection control programs in North American hospitals. Traditionally, HCWs have been screened with the Tuberculin Skin Test (TST) and preventive therapy provided for those testing positive, but over the last decade, interferon-gamma release assays (IGRAs) have been introduced as an alternative to the TST. IGRAs–including the QuantiFERON-TB Gold In-Tube (QFT, Qiagen, Valencia, USA) and T-SPOT.TB (Oxford Immunotec, Oxfordshire, UK)–offer several advantages over the TST, including improved specificity (particularly in BCG vaccinated populations), in vitro testing and the requirement that patients make only a single visit.

Resources

CDC

Interferon-Gamma Release Assays (IGRAs) are whole-blood tests that can aid in diagnosing Mycobacterium tuberculosis infection. They do not help differentiate latent tuberculosis infection (LTBI) from tuberculosis disease. Two IGRAs that have been approved by the U.S. Food and Drug Administration (FDA) are commercially available in the U.S: QuantiFERON®-TB Gold In-Tube test (QFT-GIT); T-SPOT®.TB test (T-Spot)