Dataset Information

Differential gene expression segregates cattle confirmed positive for bovine tuberculosis from antemortem tuberculosis test-false positive cattle originating from herds free of bovine tuberculosis.

ABSTRACT: Antemortem tests for bovine tuberculosis (bTB) currently used in the US measure cell-mediated immune responses against Mycobacterium bovis. Postmortem tests for bTB rely on observation of gross and histologic lesions of bTB, followed by bacterial isolation or molecular diagnostics. Cumulative data from the state of Michigan indicates that 98 to 99% of cattle that react positively in antemortem tests are not confirmed positive for bTB at postmortem examination. Understanding the fundamental differences in gene regulation between antemortem test-false positive cattle and cattle that have bTB may allow identification of molecular markers that can be exploited to better separate infected from noninfected cattle. An immunospecific cDNA microarray was used to identify altered gene expression (P ? 0.01) of 122 gene features between antemortem test-false positive cattle and bTB-infected cattle following a 4-hour stimulation of whole blood with tuberculin. Further analysis using quantitative real-time PCR assays validated altered expression of 8 genes that had differential power (adj??P ? 0.05) to segregate cattle confirmed positive for bovine tuberculosis from antemortem tuberculosis test-false positive cattle originating from herds free of bovine tuberculosis.

SUBMITTER: Lim A

PROVIDER: S-EPMC3373196 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Differential gene expression segregates cattle confirmed positive for bovine tuberculosis from antemortem tuberculosis test-false positive cattle originating from herds free of bovine tuberculosis.

Lim Ailam A Steibel Juan P JP Coussens Paul M PM Grooms Daniel L DL Bolin Steven R SR

Veterinary medicine international 20120604

Antemortem tests for bovine tuberculosis (bTB) currently used in the US measure cell-mediated immune responses against Mycobacterium bovis. Postmortem tests for bTB rely on observation of gross and histologic lesions of bTB, followed by bacterial isolation or molecular diagnostics. Cumulative data from the state of Michigan indicates that 98 to 99% of cattle that react positively in antemortem tests are not confirmed positive for bTB at postmortem examination. Understanding the fundamental diffe ...[more]

PMID: 22701814

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Project description:Bovine tuberculosis (bTB) outbreaks, caused by Mycobacterium bovis infection, are a costly animal health challenge. Understanding factors associated with the duration of outbreaks, known as breakdowns, could lead to better disease management policy development. We undertook a retrospective observational study (2012-2018) and employed Finite Mixture Models (FMM) to model the outcome parameter, and to investigate how factors were associated with duration for differing subpopulations identified. In addition to traditional risk factors (e.g., herd size, bTB history), we also explored farm geographic area, parcels/farm fragmentation, metrics of intensity via nitrogen loading, and whether herds were designated controlled beef finishing units (CBFU) as potential risk factors for increased duration. The final model fitted log-normal distributions, with two latent classes (k) which partitioned the population into a subpopulation around the central tendency of the distribution, and a second around the tails of the distribution. The latter subpopulation included longer breakdowns of policy interest. Increasing duration was positively associated with recent (<3 years) TB history and the number of reactors disclosed, (log) herd size, beef herd-type relative to other herd types, number of land parcels, area, being designated a CBFU ("feedlot") and having high annual inward cattle movements within the "tails" subpopulation. Breakdown length was negatively associated with the year of commencement of breakdown (i.e., a decreasing trend) and non-significantly with the organic nitrogen produced on the farm (N kg/hectare), a measure of stocking density. The latter finding may be due to confounding effects with herd size and area. Most variables contributed only moderately to explaining variation in breakdown duration, that is, they had moderate size effects on duration. Herd-size and CBFU had greater effect sizes on the outcome. The findings contribute to evidence-based policy formation in Ireland.

Project description:BackgroundDespite rigorous controls placed on herds which disclose ante-mortem test positive cattle to bovine tuberculosis, caused by the infection of Mycobacterium bovis, many herds in Northern Ireland (NI) experience prolonged breakdowns. These herds represent a considerable administrative and financial burden to the State and farming community.MethodsA retrospective observational study was conducted to better understand the factors associated with breakdown duration, which was modelled using both negative binomial and ordinal regression approaches.ResultsSix explanatory variables were important predictors of breakdown length in both models; herd size, the number of reactors testing positive in the initial SICCT test, the presence of a lesioned animal at routine slaughter (LRS), the count of M. bovis genotypes during the breakdown (MLVA richness), the local herd-level bTB prevalence, and the presence of herds linked via management factors (associated herds). We report that between 2008 and 2014, mean breakdown duration in NI was 226 days (approx. seven months; median: 188 days). In the same period, however, more than 6% of herds in the region remained under movement restriction for more than 420 days (13 months); almost twice as long as the mean. The MLVA richness variable was a particularly important predictor of breakdown duration. We contend that this variable primarily represents a proxy for beef fattening herds, which can operate by purchasing cattle and selling animals straight to slaughter, despite prolonged trading restrictions. For other herd types, the model supports the hypothesis that prolonged breakdowns are a function of both residual infection within the herd, and infection from the environment (e.g. infected wildlife, contiguous herds and/or a contaminated environment). The impact of badger density on breakdown duration was assessed by including data on main sett (burrow) density. Whilst a positive association was observed in the univariate analysis, confounding with other variables means that the contribution of badgers to prolonged breakdowns was not clear from our study. We do not fully reject the hypothesis that badgers are implicated in prolonging bTB breakdowns via spillback infection, but given our results, we posit that increased disease risk from badgers is unlikely to simply be a function of increasing badger density measured using sett metrics.

Project description:Bovine tuberculosis is endemic in cattle herds in Great Britain, with a substantial economic impact. A reservoir of Mycobacterium bovis within the Eurasian badger (Meles meles) population is thought to have hindered disease control. Cattle herd incidents, termed breakdowns, that are either 'prolonged' (lasting ? 240 days) or 'recurrent' (with another breakdown within a specified time period) may be important foci for onward spread of infection. They drain veterinary resources and can be demoralising for farmers. Randomised Badger Culling Trial (RBCT) data were re-analysed to examine the effects of two culling strategies on breakdown prolongation and recurrence, during and after culling, using a Bayesian hierarchical model. Separate effect estimates were obtained for the 'core' trial areas (where culling occurred) and the 'buffer' zones (up to 2 km outside of the core areas). For breakdowns that started during the culling period, 'reactive' (localised) culling was associated with marginally increased odds of prolongation, with an odds ratio (OR) of 1.7 (95% credible interval [CI] 1.1-2.4) within the core areas. This effect was not present after the culling ceased. There was no notable effect of 'proactive' culling on prolongation. In contrast, reactive culling had no effect on breakdown recurrence, though there was evidence of a reduced risk of recurrence in proactive core areas during the culling period (ORs and 95% CIs: 0.82 (0.64-1.0) and 0.69 (0.54-0.86) for 24- and 36-month recurrence respectively). Again these effects were not present after the culling ceased. There seemed to be no effect of culling on breakdown prolongation or recurrence in the buffer zones. These results suggest that the RBCT badger culling strategies are unlikely to reduce either the prolongation or recurrence of breakdowns in the long term, and that reactive strategies (such as employed during the RBCT) are, if anything, likely to impact detrimentally on breakdown persistence.

Project description:Persistence of bovine tuberculosis (bTB) in cattle is an important feature of Mycobacterium bovis infection, presenting either as herd recurrence or local persistence. One risk factor associated with the risk of recurrent episodes is the severity of a previous bTB episode (severity reflecting the number of bTB reactors identified during the episode). In this study, we have sought to identify predictors that can distinguish between small (less severe) and large (more severe) bTB episodes, and to describe nationally the severity of bTB episodes over time. The study included descriptive statistics of the proportion of episodes by severity from 2004 to 2015 and a case-control study. The case-control study population included all herds with at least one episode beginning in 2014 or 2015, with at least two full herd tests during the episode and a minimum herd-size of 60 animals. Case herds included study herds with at least 13 reactors whereas control herds had between 2 to 4 (inclusive) reactors during the first 2 tests of the episode. A logistic regression model was developed to identify risk factors associated with a large episode. Although there has been a general trend towards less severe herd bTB episodes in Ireland over time (2004-2015), the proportion of large episodes has remained relatively consistent. From the case-control study, the main predictors of a large episode were the year the episode started, increasing herd-size, previous exposure to bTB, increasing bTB incidence in the local area, an animal with a bTB lesion and a bTB episode in an associated herd. Herds that introduced more animals were more likely to have a smaller bTB episode, reflecting the reduced risk of within-herd transmission when an episode was due to an introduced infected bTB animal. Some of the risk factors identified in this study such as reactors in previous bTB episodes, herds with an associated herd undergoing a bTB episode, herds in high incidence areas etc. may help to target future policy measures to specific herds or animals for additional surveillance measures. This information has important policy implications.

Dataset Information

Differential gene expression segregates cattle confirmed positive for bovine tuberculosis from antemortem tuberculosis test-false positive cattle originating from herds free of bovine tuberculosis.

Publications

Differential gene expression segregates cattle confirmed positive for bovine tuberculosis from antemortem tuberculosis test-false positive cattle originating from herds free of bovine tuberculosis.

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