Evaluation of the diagnostic utility of a whole-blood interferon-gamma assay for determining the risk of exposure to Mycobacterium tuberculosis in Bacille Calmette-Guerin (BCG)-vaccinated individuals

Abstract

We evaluated the utility of the "QuantiFERON-TB Gold In-Tube" (QuantiFERON) test that uses tuberculosis (TB)-specific antigens for the diagnosis of latent infection in such individuals. We also examined the correlation between the interferon (IFN)-gamma response to these antigens and the exposure risk to TB by evaluating antigen-specific IFN-gamma release in comparison with IFN-gamma release in response to purified protein derivative (PPD) in 3 groups: medical students, nurses in a TB hospital, and TB patients. All nurses and TB patients responded to PPD, whereas 52% (P < 0.0001) and 79.2% (P = 0.04) responded to QuantiFERON, respectively. In the medical students, only 10.4% responded to QuantiFERON, whereas 85.2% were positive to PPD (P < 0.0001). There was also a significant correlation between the levels of IFN-gamma production and the duration of employment in the group of nurses at the TB hospital, suggesting ongoing exposure in this high-risk group. Thus, these results demonstrate that Mycobacterium tuberculosis-specific IFN-gamma release assay accurately discriminates low- and high-risk healthy subjects and might therefore be a useful diagnostic tool for the diagnosis of latent infection in Bacille Calmette-Guerin (BCG)-vaccinated individuals.

Figure 1

Whole blood response to PPD in different groups. Group A : Medical students (low risk); Group B : nurses at TB hospital (high risk); Group C : TB patients. Whole blood was stimulated with PPD for 5 days. IFN-γ release was determined by ELISA. Broken line shows the cut-off value for positive responders (62 pg/ml). Horizontal bars represent mean IFN-γ value. The significant difference of IFN-γ production levels was analyzed between two groups and P value less than 0.05 was considered significant. N.S. : not significant.

Figure 2

IFN-γ assay by “QuantiFERON®-TB Gold in tube” test in different groups. Group A : Medical students (low risk); Group B : nurses at TB hospital (high risk); Group C : TB patients. Whole blood were stimulated in a tube containing a mixture of ESAT-6, CFP-10, and a portion of TB antigen TB 7.7 for 20 h. IFN-γ release was determined by ELISA. Broken line shows the cut-off value for positive responders (0.35 IU/ml). Horizontal bars represent mean IFN-γ value. The significant differences of IFN-γ production levels were analyzed between two groups and P value less than 0.05 was considered significant. N.S. : not significant.

Figure 3

The correlation analysis in high risk individuals (Group B) between the exposure period to M. tuberculosis and the secretion levels of IFN-γ in response to PPD (A) or to a mixture of M. tuberculosis-specific antigens (B). Each point represents each individual value. A significant correlation (r = 0.424, p = 0.035) was found by M. tuberculosis-specific antigens. N.S. : not significant.