Quantitative scoring of an interferon-gamma assay for differentiating active from latent tuberculosis.

The aim of this study was to assess the contribution of an interferon-gamma release assay (T-SPOT.TB) to the differentiation of active tuberculosis (TB) from latent TB infection by quantifying spot-forming units (sfu). The investigation was a prospective study of contacts exposed to a case of contagious TB and cases of HIV-negative culture-proven TB referred over a 16-month period. Tuberculin skin tests (TSTs) and T-SPOT.TB were performed in 310 contacts 8-12 weeks after exposure. In subjects with culture-proven TB, T-SPOT.TB was performed within 2 weeks of initiation of treatment. The analysis included all contacts with a positive T-SPOT.TB result and all subjects with TB. TB contacts (n = 127) and cases (n = 58) were included. Mean+/-sd T-SPOT.TB results were 107+/-56 (range 1-207) sfu for TB, 54+/-60 (7-239) sfu for contacts with positive T-SPOT.TB results and a TST induration diameter of >5 mm, and 19+/-27 (7-143) sfu for contacts with positive T-SPOT.TB results and a TST induration diameter of < or =5 mm. By receiver operating characteristic curve analysis, a threshold value of 49.5 sfu showed a sensitivity of 83% and specificity of 74% for distinguishing latent TB infection from TB. Although T-SPOT.TB results were significantly related to disease activity, the test cannot be recommended for the diagnosis of tuberculosis.