CDC: Use judgment when interpreting IGRAs
In new guidelines for Interferon Gamma Release Assays (IGRAs), the Centers for Disease Control and Prevention offers these recommendations.
General recommendations for use of IGRAs
Tuberculin skin tests (TSTs) and IGRAs (QFT-G, QFT-GIT, and T-Spot) should be used as aids in diagnosing infection with M. tuberculosis. These tests may be used for surveillance purposes or to identify persons likely to benefit from treatment, including persons who are or will be at increased risk for M. tuberculosis infection or for progression to active tuberculosis if infected.
IGRAs should be performed and interpreted according to established protocols using FDA-approved test formats. They should be performed in compliance with Clinical Laboratory Improvement Amendment (CLIA) standards.
Both the standard qualitative test interpretation and the quantitative assay measurements should be reported together with the criteria used for test interpretation. This will permit more refined assessment of results and promote understanding of the tests.
Arrangement for IGRA testing should be made prior to blood collection to ensure that the blood specimen is collected in the proper tubes, and that testing can be performed within the required timeframe.
Prior to implementing IGRAs, each institution and tuberculosis-control program should evaluate the availability, overall cost, and benefits of IGRAs for their own setting. In addition, programs should consider the characteristics of the population to be tested.
As with the TST, IGRAs generally should not be used for testing persons who have a low risk for both infection and progression to active tuberculosis if infected (except for those likely to be at increased risk in the future). Screening such persons diverts resources from higher priority activities and increases the number of false-positive results. Even with a test specificity approaching 99%, when the prevalence of M. tuberculosis infection is ≤1%, the majority of positive results will be false positives. If persons at low risk for both infection and progression are to be tested, selection of the test with the greatest specificity will minimize false-positive results, reduce unnecessary evaluation and treatment, and minimize the potential for adverse events from unnecessary treatment.
Test selection
Selection of the most suitable test or combination of tests for detection of M. tuberculosis infection should be made on the basis of the reasons and the context for testing, test availability, and overall cost effectiveness of testing. Results of studies examining sensitivity, specificity, and agreement for IGRAs and TST vary with respect to which test is better. Although data on the accuracy of IGRAs and their ability to predict subsequent active tuberculosis are limited, to date, no major deficiencies have been reported in studies involving various populations. As use of these tests increases, greater understanding of their value and limitations will be gained.
An IGRA may be used in place of (but not in addition to) a TST in all situations in which CDC recommends tuberculin skin testing as an aid in diagnosing M. tuberculosis infection, with preferences and special considerations noted below. Despite the indication of a preference in these instances, use of the alternative test (FDA-approved IGRA or TST) is acceptable medical and public health practice.
Situations in which an IGRA is preferred but a TST is acceptable
An IGRA is preferred for testing persons from groups that historically have low rates of returning to have TSTs read. For example, use of an IGRA might increase test completion rates for homeless persons and drug-users. The use of IGRAs for such persons can increase test completion rates, so control efforts can focus on those most likely to benefit from further evaluation and treatment.
An IGRA is preferred for testing persons who have received BCG (as a vaccine or for cancer therapy). Use of IGRAs in this population is expected to increase diagnostic specificity and improve acceptance of treatment for LTBI.
Situations in which a TST is preferred but an IGRA is acceptable
A TST is preferred for testing children aged <5 years. Use of an IGRA in conjunction with TST has been advocated by some experts to increase diagnostic sensitivity in this age group. Recommendations regarding use of IGRAs in children have also been published by the American Academy of Pediatrics.
Situations in which either a TST or an IGRA may be used without preference
An IGRA or a TST may be used without preference to test recent contacts of persons know or suspected to have active tuberculosis with special considerations for follow-up testing. IGRAs offer the possibility of detecting M. tuberculosis infection with greater specificity than with a TST. Also, unlike TSTs, IGRAs do not boost subsequent test results and can be completed following a single patient visit. However, data on the ability of IGRAs to predict subsequent active tuberculosis are limited. If IGRAs are to be used in contact investigations, negative results obtained prior to 8 weeks after the end of exposure typically should be confirmed by repeat testing 8-10 weeks after the end of exposure. This recommendation is similar to one used for TST, because data on the timing of IGRA conversion after a new infection are not currently available. Use of the same test format for repeat testing will minimize the number of conversions that occur as a result of test differences.
An IGRA or a TST may be used without preference for periodic screening of persons who might have occupational exposure to M. tuberculosis (e.g., surveillance programs for health-care workers) with special considerations regarding conversions and reversions. For serial and periodic screening, IGRAs offer technical, logistic, and possible economic advantages compared with TSTs but also have potential disadvantages. Advantages include the ability to get results following a single visit. Two-step testing is not required for IGRAs, because IGRA testing does not boost subsequent test results. Disadvantages of IGRAs in this setting include a greater risk of test conversion due to false-positive IGRA results with follow-up testing of low-risk health-care workers who have tested negative at prior screening. CDC has published criteria for identifying conversions for TSTs and IGRAs. TST conversion is defined as a change from negative to positive with an increase of ≥10 mm in induration within two years. TST conversion is associated with an increased risk for active tuberculosis. An IGRA conversion is defined as a change from negative to positive within two years without any consideration of the magnitude of the change in TB Response. Using this lenient criterion to define IGRA conversion might produce more conversions than are observed with the more stringent criteria applied to TSTs. Furthermore, an association between an IGRA conversion and subsequent disease risk has not been demonstrated. The criteria for interpreting changes in an IGRA that identify new infections remain uncertain. CDC encourages institutions and programs in which IGRAs are used to publish their experiences, particularly in regard to rates of conversion, reversion, and progression to active tuberculosis over time.
Situations in which testing with both an IGRA and a TST may be considered
Although routine testing with both a TST and an IGRA is not generally recommended, results from both tests might be useful when the initial test (TST or IGRA) is negative in the following situations: 1) when the risk for infection, the risk for progression, and the risk for a poor outcome are increased (e.g., when persons with HIV infection or children aged <5 years are at increased risk for M. tuberculosis infection) or 2) when clinical suspicion exists for active tuberculosis (such as in persons with symptoms, signs, and/or radiographic evidence suggestive of active tuberculosis) and confirmation of M. tuberculosis infection is desired. In such patients with an initial test that is negative, taking a positive result from a second test as evidence of infection increases detection sensitivity. However, multiple negative results from any combination of these tests cannot exclude M. tuberculosis infection.
Using both a TST and an IGRA also might be useful when the initial test is positive in the following situations: 1) when additional evidence of infection is required to encourage compliance (e.g., in foreign-born health-care workers who believe their positive TST result is attributable to BCG) or 2) in healthy persons who have a low risk for both infection and progression. In the first situation, a positive IGRA might prompt greater acceptance of treatment for LTBI as compared with a positive TST alone. In the latter situation, requiring a positive result from the second test as evidence of infection increases the likelihood that the test result reflects infection. For the second situation, an alternative is to assume, without additional testing, that the initial result is a false positive or that the risk for disease does not warrant additional evaluation or treatment, regardless of test results. Steps should be taken to minimize unnecessary and misleading testing of persons at low risk.
[Editor's note: The CDC guideline on IGRAs is available at www.cdc.gov/mmwr/preview/mmwrhtml/rr5905a1.htm?s_cid=rr5905a1_w.]
In new guidelines for Interferon Gamma Release Assays (IGRAs), the Centers for Disease Control and Prevention offers these recommendations.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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