Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection — United States, 2010

[Guest guest]

I found this article from last year interesting and helpful.It doesn't sound like CDC recommends using the TST as a screen and then following up (+)'s w/ an IGRA.But they do recommend considering the IGRA as primary for the groups below.

I always find the (+)'s in the BCG vaccinated confusing - despite article after article from the CDC saying a (+) is a (+) in these BCG vaccinated groups --> the CDC in the past has felt that >10 years, the TST should fade away and so a (+) reaction is a new exposure -- unrelated to the past BCG vaccination.

But...I still wonder.By screening these BCG vaccinated patients with an IGRA - is would seem to avoid these false (+)'s.Although cost and hassle of sending a blood sample overnight somewhere (if it isn't done in the local hospital) is a drawback.

See below for link to the article and the specifics of when to use IGRA vs TST.--------------------------------------------------------------------------------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. ------------------------------------------------------------------------------------

Locke, MD=======================================http://www.cdc.gov/mmwr/pdf/rr/rr5905.pdf

Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection — United States, 2010Test 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 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 followup 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 (113). 

TST conversion is defined as a change from negative to positive with an increase of ≥10 mm in induration within 2 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 2 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) or2) 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. 

• Repeating an IGRA or performing a TST might be useful when the initial IGRA result is indeterminate, borderline, or invalid and a reason for testing persists. A second test

initial test are unusual, such as when the Nil value is higher than typical for the population being tested (e.g., IFN-γ concentration for Nil by QFT-G or QFT-GIT >0.7 IU/ml for most of the U.S. populations), the Nil value is appreciably greater than the value obtained with M. tuberculosisantigen stimulation (e.g. when IFN-γ concentration for Nil by QFT-G is 0.35 IU/ml greater than the concentration obtained with either ESAT-6 or CFP-10 stimulation, or when the number of spots for Nil by T-Spot is four spots greater than the number with either ESAT-6 or CFP-10 stimulation), or the Mitogen value is lower than is expected for the population being tested (e.g., the Mitogen Response by QFT-G or QFT-GIT is <0.5 IU/ml, or the number of spots in the mitogen well by T-Spot is <20). If an IGRA is to be repeated, a new blood sample should be used. In such situations, repeat testing with another blood sample usually provides interpretable results.

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.