Evaluation of the tuberculin gamma interferon assay: potential to replace the Mantoux skin test

Abstract

We evaluated an in vitro test of cell-mediated immunity, the tuberculin gamma interferon assay, QuantiFERON-TB (QIFN), in 455 individuals from three groups: group I, 237 immigrants from high-risk countries; group II, 127 health care workers undergoing Mantoux testing; group III, 91 patients being investigated for possible active tuberculosis (79 patients) or Mycobacterium avium-Mycobacterium intracellulare complex infection (12 patients). The QIFN results were compared either to those of the Mantoux test or to microbiological and clinical diagnosis, as appropriate. In each group the correlation between the diameter of induration for the skin test and the magnitude of QIFN response was significant and of moderate strength (Spearman's rank correlation coefficient; rho = 0.59 to 0.61; P < 0.001). For group I, the agreement between QIFN and Mantoux results was 89% for Mantoux-negative and 64% for Mantoux-positive individuals. For group II, when >/=10-mm-diameter induration was taken as positive, the agreement was 81% for Mantoux-negative and 67% for Mantoux-positive individuals. For group III, agreement was 81% for Mantoux-negative and 86% for Mantoux-positive patients. For patients being evaluated for active tuberculosis, the performance of the Mantoux test was not statistically different from that of the QIFN assay. In patients with active tuberculosis, the assay had a sensitivity of 77%, not significantly higher for extrapulmonary than pulmonary cases (83% versus 74%). QIFN sensitivity was not significantly different for smear-negative or smear-positive cases (80% versus 71%). The QIFN assay is a potential replacement for the Mantoux test. The acceptability of these performance values and those of similar evaluations will determine the place this test will have in detecting evidence of mycobacterial infection.

FIG. 1

Correlation between percent QIFN response and Mantoux induration diameter in patients being evaluated for active tuberculosis. The percent QIFN response versus the Mantoux induration diameter is stratified as either 0, 1 to 9, 10 to 19, or ≥20 mm of induration. The solid bars represent medians, the boxes indicate the interquantile ranges, and the lines show the most extreme observations within 1.5 times the interquantile range. There was one extreme outlier with a value of 1,043% QIFN response in the 0-mm Mantoux group. The correlation between the QIFN result and Mantoux induration diameter was significant and of moderate strength (Spearman’s rank correlation coefficient = 0.61; P < 0.001).