Determination of decisional cut-off values for the optimal diagnosis of bovine tuberculosis with a modified IFNγ assay (Bovigam®) in a low prevalence area in France

The Bovigam (R) gamma interferon (IFN gamma) assay was used to complement official skin-test screening in a low bovine tuberculosis (bTB) prevalence region in France. The aim of our work was to determine decisional cut-off values for protein purified derivatives (PPD) and ESAT6-CFP10 antigens (R) in order to optimize the efficacy of the modified Bovigam (R) test, in this low-prevalence area, for optimal classification of infected or non-infected herds following positive skin tests. The sensitivity of the IFN gamma assay relative to post-mortem bTB-positive animals (Se-r) was studied in 60 cattle from 20 bTB-infected herds. Its absolute specificity (Sp) was studied in 492 cattle from 25 bTB-free herds from a bTB-free zone. Its operational specificity (relative to the positive skin test) (Sp(r)) was also studied in 547 skin-test positive cattle from 172 bTB-free herds from an infected zone. Using normalized interpretations for individual (PPD or R) results, the cut-off values at 0.02 for PPD and 0.01 for R were obtained with a view to employ them in low prevalence areas with no previously observed non-specific reactions to SITT. Concerning its use after positive skin tests, cut-off values were set at 0.05 for PPD and at 0.03 for R. The choice of an interpretation method considering positive results with PPD and/or R (PPDUR), justified in a high risk context, provided a test Se-r of 93% [84-98] and Sp(r) of 71.8%[67.9-75.6]. Analysis of positive results with PPD and R (PPD boolean AND R), ideal for low-risk contexts, provided a test Sp(r) of 94.3% [92.0-96.1] and Se-r of 77% [64-87]. Thus, adapting the criteria to the region's infection status and to the conditions for its application is essential for the appropriate use of the IFN gamma assay. (C) 2011 Elsevier B.V. All rights reserved.