Screening for tuberculosis infection using whole-blood interferon-gamma and Mantoux testing among Japanese healthcare workers.

OBJECTIVE: To examine the hypothesis that results of the QuantiFERON-TB Gold assay (QFT-G), a whole-blood test for detection of tuberculosis infection, are more significantly related to known risk factors for tuberculosis infection in healthcare workers (HCWs) who have received bacille Calmette-Guerin vaccine than are results of the Mantoux tuberculin skin test (TST). DESIGN: All HCWs (approximately 510) from a 370-bed general hospital in Tokyo where patients with and patients without tuberculosis are treated were invited to participate in the study. All study participants completed a questionnaire about their Mycobacterium tuberculosis infection risk factors as HCWs at the general hospital. They were then tested for LTBI by means of the QFT-G, followed by the TST. Statistical analyses were performed to compare results of each test with M. tuberculosis infection risk factors (age, length of employment in the healthcare industry, history of working with tuberculosis-positive patients in a tuberculosis ward or in the outpatient department of the hospital's tuberculosis clinic for more than 1 year, chest radiograph evidence of healed tuberculosis, history of performing bronchoscope procedures, and job classification), and for TST-positive HCWs, to compare the QFT-G result with the TST induration diameter. RESULTS: A total of 332 HCWs (95% of whom had been vaccinated with BCG) participated in the study, and 33 had positive QFT-G results, suggesting a prevalence of LTBI of 9.9%. Of 304 HCWs who underwent TST, 283 (93.1%) had an induration diameter of 10 mm or more. Multiple logistic regression analysis revealed that positive QFT-G results were significantly associated with age and with a history of working in a tuberculosis ward or an outpatient department of a tuberculosis clinic. TST results were not correlated with any of the tuberculosis infection risk factors we evaluated. CONCLUSIONS: Positive QFT-G results were closely associated with the presence of risk factors for LTBI in a hospital setting, suggesting that the QFT-G can detect LTBI in a population composed predominantly of BCG vaccinees. Because most HCWs worldwide have been vaccinated with BCG, the QFT-G offers a significant improvement over the TST in tuberculosis screening programs and minimizes unwarranted use of tuberculosis prophylaxis.

[Basic characteristics of a novel diagnostic method (QuantiFERON TB-2G) for latent tuberculosis infection with the use of Mycobacterium tuberculosis-specific antigens, ESAT-6 and CFP-10].

PURPOSES: To determine the optimum cut-off level of a newly developed method for diagnosing tuberculosis infection based on whole-blood interferon-gamma measurement, and to study the basic characteristics of the method. STUDY SUBJECTS: 1) A total of 220 young, healthy individuals having no apparent exposure to tuberculosis infection, most of whom have had a vaccination with BCG vaccine. 2) One hundred eighteen tuberculosis patients who were diagnosed by positive Mycobacterium tuberculosis on culture. 3) A group of 75 youngsters exposed to an infectious tuberculosis patient and who showed a strong tuberculin reaction (with erythema diameter of 30 mm or more). METHOD: Whole-blood specimens of donors were stimulated with antigens, i.e., ESAT-6 and CFP-10, and then cultured. Plasma concentrations of interferon-gamma discharged were then determined with QuantiFERON-CMI. Correlation between interferon-gamma concentrations in response to ESAT-6 and CFP-10, and their correlation with Mantoux test results were analyzed for various categories of donors. The Receiver Operating Characteristics analysis was performed considering the loss due to misclassification. [ RESULTS AND DISCUSSION: The optimum cut-off level was determined as 0.35 IU/ml for both ESAT-6 and CFP-10. This gave the test a sensitivity of 89.0% and specificity of 98.1% in detecting tuberculosis infection. The correlation of interferon-gamma response with tuberculin tests among BCG-vaccinated individuals was low, which suggested that the test was not influenced by previous BCG vaccination. The low correlation between ESAT-6 and CFP-10 tests suggested that the simultaneous use of the two tests was beneficial. As in the case of clinical tests in general, the cut-off should be set at a lower level when the test is applied to high prevalence situation and vice versa.