TB Notes Newsletter
No. 3, 2006
TUBERCULOSIS EPIDEMIOLOGIC STUDIES CONSORTIUM
New TBESC Study to Be Launched: Evaluation of New
Interferon-gamma Release Assays in the Diagnosis of Latent TB Infection
in Health Care Workers
Principal Investigator: Chuck Daley
Co-Principal Investigators: Nick Deluca, Jerry Mazurek, Susan
The TBESC is planning a new study titled “Evaluation of New
Interferon-gamma Release Assays in the Diagnosis of Latent Tuberculosis
Infection in Health Care Workers.” The study will evaluate
the test characteristics, feasibility, and cost-effectiveness of
interferon-gamma release assays (IGRAs) and the tuberculin skin
test (TST) when testing for LTBI in health care workers (HCWs) at
4 to 6 TBESC sites.
HCWs make up a critical study population for IGRAs. According to
the Labor Department, there are approximately 14 million HCWs in
the United States, most of whom undergo serial skin testing. HCWs
represent a diverse yet stable and accessible population with a
wide range of rates of LTBI and risks of TB exposure. Testing them
is costly and time consuming, but detection of new infection is
necessary for discovering M. tuberculosis transmission and for preventing
occupation-related TB. The consequences of missing TB in a HCW are
potentially disastrous (CDC. MMWR 2004: MMWR 2005).
Until recently the only method for detecting infection was the
TST, which requires two-step testing for the initial evaluation.
The TST has a number of important deficiencies: it lacks sensitivity
and specificity, its results are influenced by BCG vaccination,
and it requires two health care visits to obtain results. IGRAs
have excellent sensitivity and specificity and provide some advantages
over the TST. IGRAs require one health care visit, the result can
be available within one day, and interpreting the test results is
less subjective than for the TST. Many HCWs in the United States
were born in countries where the incidence of TB is high and where
BCG vaccination is routine. IGRAs using region-of-difference 1 antigens
are not influenced by BCG vaccination, which may increase HCW confidence
in the result.
IGRAs must be evaluated longitudinally in HCWs to determine the
frequency of reversion and conversion, to determine the optimal
definition of conversion, and to study the repeatability and reproducibility
of these new tests. Because a switch from skin testing to IGRAs
will represent a major change in our approach to testing HCWs, it
is important to assess the utilization and acceptability of these
new tests among patients and providers. Given the large number of
HCWs in the United States, it is important to evaluate the cost-effectiveness
of the different testing methods in health care settings.
aims of the study are as follows:
- To determine and compare the test characteristics (estimated
sensitivity and specificity) of two IGRAs (QuantiFERON TB Gold
[QFT-G] and T-Spot.TB) compared with each other and to the TST
at initial testing.
- To determine and compare the repeatability and reproducibility
of the results.
- To determine and compare the test characteristics of the two
IGRAs compared with the TST in detecting the phenomena of “conversion”
- To determine and compare the costs, cost differences, and cost-effectiveness
of the three methods.
- To determine and compare the feasibility of the three methods
for serial testing of HCWs.
- To determine and compare the acceptability and usability of
the IGRAs compared with the TST among patients and providers.
- To determine the extent to which, if any, the TST causes boosting
of results from the IGRAs.
- To observe how treating LTBI influences test results longitudinally.
After providing written consent, approximately
3000 HCWs from four to six TBESC sites will undergo a standardized
interview and will be tested serially with all three tests, except
for subjects who have 15 mm or greater of induration; they will
be tested with the two IGRAs. Test results will be recorded as currently
recommended by manufacturers’ and national guidelines (MMWR,
December 2005) and numerical output (i.e., the number of spot-forming
cells and amount of interferon gamma produced) from the IGRAs will
be recorded in order to determine the optimal definition for conversion.
For HCWs who have two-step testing, two IGRAs will be repeated with
the TST to observe whether the initial TST influences results from
the IGRAs. A sample of HCWs will have each test performed twice
at the initial testing in order to assess the repeatability of the
assays. HCWs will be retested every 6 months after the initial testing
until they have been retested at least three times (a total of four
testings). The influence of treating LTBI will be studied by comparing
longitudinal test results in HCWs who do and do not receive treatment.
Direct and indirect costs will be calculated for each test method
for comparing costs for each strategy and determining cost-effectiveness.
The acceptability and usability of the IGRAs by providers and the
acceptability of the testing procedures by the patients will be
assessed using qualitative methodology.
Submitted by Chuck Daley and Rachel Albalak
Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of Tuberculosis Elimination - http://www.cdc.gov/tb
Please send comments/suggestions/requests
CDC/Division of Tuberculosis Elimination
Communications, Education, and Behavioral Studies Branch
1600 Clifton Rd., NE - Mailstop E-10, Atlanta, GA 30333