Article

Repeat tuberculin skin testing leads to desensitisation in naturally infected tuberculous cattle which is associated with elevated interleukin-10 and decreased interleukin-1 beta responses

TB Research Group, Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom.
Veterinary Research (Impact Factor: 2.82). 10/2009; 41(2):14. DOI: 10.1051/vetres/2009062
Source: PubMed

ABSTRACT

The principal surveillance tool used to control bovine tuberculosis in cattle is the removal of animals that provide a positive response to the tuberculin skin-test. In this study we performed a longitudinal investigation of the immunological and diagnostic consequences of repeated short-interval skin-tests in cattle naturally infected with Mycobacterium bovis. Tuberculin skin-test positive cattle were subjected to up to four further intradermal comparative cervical skin-tests at approximately 60-day intervals. A significant progressive reduction in the strength of the skin-test was observed after successive tests. In contrast, the magnitude of interferon-gamma (IFN-gamma) responses was not influenced by repeat skin-testing either transiently around the time of each skin-test or longitudinally following repeated tests. A significant boost in blood interleukin-10 (IL-10) production was observed within 3 days following each skin-test although the magnitude of this boosted response returned to lower levels by day 10 post-test. The application of a novel multiplex assay to simultaneously measure seven cytokines and chemokines also identified that skin-testing resulted in a significant and progressive reduction in antigen specific interleukin-1beta (IL-1beta) whilst confirming stable IFN-gamma and elevated IL-10 responses in the blood. Therefore, we have demonstrated that in cattle naturally infected with M. bovis, repeat short-interval skin-testing can lead to a progressive reduction in skin-test responsiveness which has potential negative consequences for the detection of infected animals with marginal or inconclusive skin-test responses. The desensitising effect is associated with decreased IL-1beta and elevated IL-10 responses, but importantly, does not influence antigen specific IFN-gamma responses.

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    • "Furthermore, there is evidence that PPD inoculation may sensitise the animals, thereby affecting the result of a subsequent skin test in the same animal (Thom et al 2004). It is possible that repeated tuberculin testing may affect the results of other blood-based immune assays used to diagnose tuberculosis (Thom et al 2004, Coad et al 2010). The complexity of tuberculin, the presence of cross-reactive components, and the low specificity have fueled the search for new antigens and diagnostic assays specific to M. bovis (Pollock et al 2005, Aagaard et al 2010). "
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    • "We assessed the effect of pathogen genotype on skin test response (PPD-B – PPD-A) by comparing the influence of genotype with other potential sources of variation, extracting skin test results for animals that tested positive under the standard interpretation . We excluded animals that had an inconclusive result at the previous skin test because they might have become desensitised to tuberculin, characterised by a progressive decrease in response to each subsequent test by cattle undergoing repeated short interval testing (Coad et al., 2009) or those with advanced disease (de la Rua-Domenech et al., 2006). Following these exclusions , 11,799 animals remained, 78% of which were female. "
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    • "VeBus holds the individual measurements (a1, a2, b1 and b2) from all tests (failed or not) for a subset of animals, while VetNet holds data for the last test only of all cattle classified as reactors. Two important biases affect these measurements: (1) all reactors have, by definition, exceeded the prescribed threshold, so the expectation of any relationship with ‘22’ is unclear; (2) repeat testing can potentially lead to smaller swellings [22]. Consequently, for both consistency and to control for desensitisation we used the first non-reacting test results for each animal recorded in VeBus, regardless of whether that animal went on to become a reactor later in its life. "
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