Interferon-gamma-release assays: Better than tuberculin skin testing?
ABSTRACTAlthough the tuberculin skin test has long been the standard for detecting latent tuberculosis infection, it has many limitations. Interferon-gamma-release assays are gaining acceptance as an alternative. In this paper we present cases to illustrate how these new tests can be used and how to interpret the results.
KEY POINTS
- Prior vaccination with bacille Calmette-Guérin can cause the results of skin testing to be falsely positive, but it does not affect interferon-gamma-release assays.
- In 2005, the US Centers for Disease Control and Prevention recommended that interferon-gamma-release assays be used in all situations in which skin testing is currently used. Updated guidelines were published on June 25, 2010.
- Successful implementation of interferon-gamma-release assay testing requires education of everyone involved—phlebotomists, laboratory personnel, occupational health workers, and clinicians.
CASE 4: AN INDETERMINATE RESULT IN A WOMAN AT LOW RISK
A 65-year-old woman, also from the United States, has an indeterminate QFT-GIT result on preemployment screening. She has no known contacts with tuberculosis.
Comment. An indeterminate result can mean either that the person is immunosuppressed (in which case her blood would show a low response to mitogen; Table 1), or that there could have been errors in the performance of the test, such as improper transport, handling, or storage of the blood specimen.6 Previously at our institution, 8% of the results in our health care workers were indeterminate, a finding that led to changes in specimen collection and laboratory analysis that significantly decreased the number of indeterminate results.12 We also found that using the newer QuantiFERON test, ie, the QFT-GIT, further decreased the indeterminate rate.12
A person with an indeterminate result should be tested again and be evaluated by a physician for underlying immunosuppression or to rule out active tuberculosis (eg, via chest radiography).
There are only limited data on the use of interferon-gamma-release assays in immunosuppressed people, such as patients with human immunodeficiency virus (HIV) infection. False-negative and indeterminate results are increasingly more common in HIV patients with declining CD4 counts.20 In immunocompromised patients at high risk of infection, use of both an assay and skin testing may be reasonable.16
CASE 5: SCREENING THE CONTACTS OF A MAN WITH ACTIVE TUBERCULOSIS
A 39-year-old male health care worker is diagnosed with active tuberculosis. The QFT-GIT test is then used to determine exposure in all possible contacts.
Comment. The CDC guidelines recommend using QuantiFERON tests in all circumstances in which the tuberculin skin test has been used, including contact investigation screening.9 The QFT-GIT test can be used to screen possible contacts of infected health care workers at baseline, and it is recommended that the test be repeated 8 to 10 weeks after the exposure.9 In our experience, contact investigation has been more efficient and easier to conduct with the use of the QFT-GIT than with the tuberculin skin test.21
THE FUTURE OF TUBERCULOSIS TESTING
Given the wide availability of interferon-gamma-release assays and laboratories that process them, more tuberculosis control programs will probably start using them rather than tuberculin skin testing. Successful implementation requires education of everyone involved—phlebotomists, laboratory personnel, occupational health workers, and clinicians. Further study is needed to evaluate the feasibility, utility, cost-effectiveness, and value of using these new tests.
