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Title: Bovine Tuberculosis: Effect of the Tuberculin Skin Test on In vitro Interferon gamma Responses

item SCHILLER, IRENE - Federal Veterinary Office
item VORDERMEIER, H - Veterinary Laboratories Agency (VLA)
item Waters, Wade
item WHELAN, ADAM - Veterinary Laboratories Agency (VLA)
item COAD, MICHAEL - Veterinary Laboratories Agency (VLA)
item GORMLEY, EAMONN - University College - Ireland
item BUDDLE, BRYCE - Agresearch
item Palmer, Mitchell
item Thacker, Tyler
item MCNAIR, JIM - Agri-Food And Biosciences Institute
item WELSH, MICHAEL - Agri-Food And Biosciences Institute
item HEWINSON, R - Veterinary Laboratories Agency (VLA)
item OESCH, BRUNO - Prionics Ag

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/5/2010
Publication Date: 7/1/2010
Citation: Schiller, I., Vordermeier, H.M., Waters, W.R., Whelan, A.O., Coad, M., Gormley, E., Buddle, B.M., Palmer, M.V., Thacker, T.C., Mcnair, J., Welsh, M., Hewinson, R.G., Oesch, B. 2010. Bovine Tuberculosis: Effect of the Tuberculin Skin Test on In vitro Interferon gamma Responses. Veterinary Immunology and Immunopathology. 136(1-2):1-11.

Interpretive Summary: Bovine tuberculosis (bTB), caused by Mycobacterium bovis, accounts for up to 10% of human TB cases in developing countries and is increasing in cattle in the US and UK. Control of bTB is hindered by the presence of numerous wildlife reservoirs such as white-tailed deer, European badgers, and brush-tailed possums. Reasons for the failure to eradicate the disease are multi-factorial. Limitations in the sensitivity and specificity of diagnostic tests are factors contributing to the persistence of bTB. The Bovigam™ assay is approved for use within the United States as a complimentary test for bovine tuberculosis. Effects of tuberculin testing, the other approved test for bTB, confound interpretation and accuracy of the Bovigam™ assay. In the present study, conclusions on the effects tuberculin administration for skin test on the Bovigam™ assay are drawn based upon previously published reports and new data. Knowledge obtained from this study may lead to an improved test for tuberculosis, thereby, advancing the national tuberculosis eradication program.

Technical Abstract: Bovine tuberculosis (bTB) is a disease of zoonotic and economic importance. In many countries, control is based on test and slaughter policies and/or abattoir surveillance. For testing, cell mediated immune- (CMI-) based assays (i.e., Tuberculin skin test (TST) supplemented by the interferon gamma (IFN-g) assay) are the primary surveillance and disease control tests for bTB. The combined use of the in vivo and in vitro CMI assays to increase overall sensitivity has raised the question of whether the IFN-g response is influenced by injection of purified protein derivatives (PPD) for TST. Published data on the influence of the TST, applied as the caudal fold test (CFT) or the comparative cervical test (CCT), on the IFN-g assay are contradictory. Reviewing published data and including additional data, the following conclusions can be drawn: (1) In naturally infected cattle, PPD administration for the single or repeated-short interval CCT neither boosts nor depresses PPD-specific IFN-g production. Disparate results have been concluded from some studies using experimental infections, emphasizing the importance of confirming initial experimental-based findings with studies using cattle naturally infected with Mycobacterium bovis. (2) In cattle experimentally infected with M. bovis, PPD administration for CFT boosts PPD-specific IFN-g production for up to 7 days without any effect on test interpretation. Importantly, in naturally infected cattle, CFT-related boosting selectively increases the in vitro M. bovis PPD (PPD-B) response 3 days after CFT, resulting in an increased PPD-B response relative to the response to M. avium PPD (PPD-A). In non-infected cattle, it cannot be excluded that the CFT induces a mild boost of the PPD-specific response, particularly in animals sensitized to environmental, non-tuberculous mycobacteria, thus decreasing the specificity of the IFN-g assay. Further studies are required to clearly describe the effects of CFT in non-infected animals and in low reacting infected cattle.