GUIDELINESS FOR TB TESTING

June 30, 2010 — The US Centers for Disease Control and Prevention (CDC) have issued updated guidelines for testing for Mycobacterium tuberculosis infection in adults and children using interferon gamma release assays (IGRAs), approved by the US Food and Drug Administration (FDA). The updated recommendations, published in the June 25 issue of Morbidity and Mortality Weekly Report, offer guidance to US public health officials, healthcare providers, and laboratory workers.

"Before 2001, the tuberculin skin test (TST) was the only practical and commercially available immunologic test for Mycobacterium tuberculosis infection approved in the United States," write Gerald H. Mazurek, MD, and colleagues from the Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, CDC. "Recognition that interferon gamma (IFN-γ) plays a critical role in regulating cell-mediated immune responses to M. tuberculosis infection led to development of ...IGRAs for the detection of M. tuberculosis infection. IGRAs detect sensitization to M. tuberculosis by measuring IFN-γ release in response to antigens representing M. tuberculosis."

Since the CDC published 2005 guidelines for use of the QuantiFERON-TB Gold test (QFT-G), 2 new IGRAs were FDA approved to assist in diagnosing latent and active M tuberculosis infection: QuantiFERON-TB Gold In-Tube test (QFT-GIT) and the T-SPOT.TB test (T-Spot). For these assays, the antigens, methods, and interpretation criteria are different from those for previously FDA-approved IGRAs.

The updated recommendations for IGRA use were developed by a group of experts convened by the CDC to review available evidence including data submitted to FDA, published reports, and expert opinion concerning IGRAs. Studies of sensitivity, specificity, and agreement for IGRAs and tuberculin skin test yielded varying results regarding superiority of any of these tests.

"In brief, TSTs and IGRAs (QFT-G, QFT-GIT, and T-Spot) may be used as aids in diagnosing M. tuberculosis infection," the guidelines authors write. "They may be used for surveillance purposes and to identify persons likely to benefit from treatment. Multiple additional recommendations are provided that address quality control, test selection, and medical management after testing."

Recommendations for use of IGRAs in these guidelines include the following:

* To assist in diagnosing infection with M tuberculosis, tuberculin skin tests and IGRAs may be used for surveillance or to identify persons likely to benefit from treatment (those who are or will be at increased risk for M tuberculosis infection or for progression to active tuberculosis if infected).
* Established protocols using FDA-approved test formats are required for performance and interpretation of IGRAs in compliance with Clinical Laboratory Improvement Amendment standards.
* To facilitate more refined evaluation of test results and better understanding of implications and limitations of the tests, both the standard qualitative test interpretation and the quantitative assay measurements should be reported along with the criteria used for test interpretation.
* Before blood draw, arrangements for IGRA testing should be made so that the specimen is collected in the proper tubes and so that testing can be performed within the required timeframe.
* Before implementing testing with IGRAs, each institution and tuberculosis-control program should consider availability, overall cost, potential benefits of IGRAs, and characteristics of the test population in their own setting.
* Neither the tuberculin skin test nor the IGRAs should typically be used to test persons at low risk for both infection and progression to active tuberculosis if infected, unless they are likely to be at increased risk in the future. Screening such persons is likely to cause a higher number of false-positive results and diversion of resources from higher-priority activities. When testing low-risk patients, the test with the greatest specificity should be chosen.
* The most suitable test or combination of tests to diagnose M tuberculosis infection should be chosen based on the reasons and the context for testing, test availability, and overall cost effectiveness.
* An IGRA may be used instead of a tuberculin skin test in all situations in which the CDC recommends the tuberculin skin test as an aid in diagnosing M tuberculosis infection.
* An IGRA is preferred for testing persons from groups that typically have low rates of returning to have tuberculin skin tests read and for those who have received Bacille Calmette-Guérin (BCG) as a vaccine or as cancer treatment. In the latter group, the tuberculin skin test has a higher false-positive rate.
* IGRAs or the tuberculin skin test (without preference) may be used to test recent contacts of persons with infectious tuberculosis.
* IGRAs or the tuberculin skin test (without preference) may be used for periodic screening for occupational exposure.
* For testing children younger than 5 years, the tuberculin skin test is preferred vs the IGRA. To increase diagnostic sensitivity in this age group, however, some experts recommend using an IGRA as well as the tuberculin skin test.

"Although substantial progress has been made in documenting the utility of IGRAs, additional research is needed that focuses on the value and limitations of IGRAs in situations of importance to medical care or tuberculosis control," the guidelines authors write.

MMWR Morb Mortal Wkly Rep. 2010;59(RR-5):1-28.