Bovine Tuberculosis: Effect of the Tuberculin Skin Test on the Interferon Gamma Assay

Authors: SCHILLER, I - Federal Veterinary Office; VORDERMEIER, M - Veterinary Laboratories Agency (VLA); Waters, Wade; OESCH, B - Prionics Ag

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 12/3/2009
Publication Date: 12/3/2009
Citation: Schiller, I., Vordermeier, M., Waters, W.R., Oesch, B. 2009. Bovine Tuberculosis: Effect of the Tuberculin Skin Test on the Interferon Gamma Assay [abstract].

Interpretive Summary:

Technical Abstract: Introduction Bovine tuberculosis (bTB) is a disease of zoonotic and economic importance. Despite intensive eradication efforts over decades, bTB continues to be a problem with global perspective. The control of bTB is based on a test and slaughter policy and/or abattoir surveillance. Two types of tuberculin skin tests (TST), the caudal fold test (CFT) and the comparative cervical skin test (CCT), are used as primary screening tests. The interferon gamma (IFN-gamma) assay (Bovigam®, Prionics, Switzerland) constitutes a laboratory-based test which is widely used complementary to the tuberculin skin test. The combined use of the in vivo and in vitro assays rises the question whether the IFN-gamma responses are influenced by the TST. In fact, the CFT has been described to boost the IFN-gamma responses and these results formed the basis to apply the IFN-gamma assay between 3 and 30 days after CFT in the USA. In contrast, no significant boost has been attributed to the CCT. Aim Published data on the influence of the TST, both the CFT and the CCT, on the IFN-gamma assay are contradictory. Our communication addresses this issue by reviewing published data and by drawing conclusions from these studies including additional data. Results The CCT does neither significantly boost nor depress IFN-gamma production. These data are based on responses in naturally infected cattle. Even repeated CCTs in experimentally infected cattle did not show any significant increases between the repeat CCT and the control groups. Although IFN-gamma responses in experimentally infected cattle were reduced 3 days after CCT, this effect could not be verified in naturally infected animals, emphasizing the importance to confirm findings in cattle naturally infected with bTB. In contrast, the CFT boosted the IFN-gamma responses in cattle experimentally infected with Mycobacterium bovis. The boost was shorter as originally anticipated and lasted only from 3 to 7 days after the CFT. Importantly, there was no effect on the relative response to tuberculin, calculated as optical density values obtained with bovine tuberculin minus avium tuberculin. Consequently, the boosting effect of the CFT did not influence the final test interpretation. In uninfected cattle, however, it cannot be excluded that the CFT induces a mild boost of the responses to either bovine or avian tuberculin shortly after applying the CFT and thus decreases the specificity of the IFN-gamma assay. Further studies taking into account different mycobacterial background situations (infections with environmental, non-tuberculous mycobacteria) are needed to verify this effect. Conversely to its boosting effect, the CFT induced a mild depression of the IFN-gamma responses in experimentally infected cattle about 7 to 10 days after the CFT. This depression was without effect on test interpretation in strong positive cattle. More data are needed to conclude on its influence in weak positive animals. Conclusion The influence of the TST on in vitro IFN-gamma response depends on the location of in vivo application of tuberculins. No significant effect can be observed after CCT. Boost and depression of IFN-gamma production associated with CFT in experimentally infected cattle require further investigation in naturally infected cattle, thereby sharpening the use of the IFN-gamma assay as excellent tool for the control and eradication of bTB.