Is moving from targeted culling to BCG-vaccination of badgers (Meles meles) associated with an unacceptable increased incidence of cattle herd tuberculosis in the Republic of Ireland? A practical non-inferiority wildlife intervention study in the Republic of Ireland (2011-2017).

Bovine tuberculosis (BTB) remains as a costly disease of cattle-herds in the Republic of Ireland (ROI). This persistence is partially attributable to the presence of M. bovis infection in a wildlife reservoir, the European badger (Meles meles). Thus, both area-wide and limited-area targeted-badger-culling have been part of the ROI-BTB control/eradication program to help reduce the future incidence of a cattle-herd BTB breakdown (i.e. a "new herd-level occurrence of BTB"). However, neither badger-culling practice can be sustained as a major component in the ongoing BTB eradication program in the ROI. Vaccination of badgers with Bacille Calmette-Guérin (BCG) has been proposed as an alternative to badger culling. Thus, in 2011, a five-year non-inferiority study was implemented in seven counties in the ROI. This study was designed to compare and contrast the cattle-herd-BTB-incidence in areas where intramuscular badger vaccination would be implemented versus the cattle-herd-BTB-incidence in the remaining area of the same county where targeted-badger-culling was maintained as the standard treatment response to probable badger-sourced BTB breakdowns. Our outcome of interest was a new cattle-herd-BTB-episode (breakdown) with a total of >2 standard skin-test (SICTT) reactors detected during the episode. Treatments (badger vaccination or targeted badger culling) were cluster allocated based on where the majority of the herd owner's land was located. To assess the impact of the two treatments, we compared the incidence-risk, of our defined outcome, for cattle herds in the area under vaccination to the outcome incidence-risk for cattle herds in the remainder of the same county after 4 and 5 years of having implemented badger vaccination. A random-effects logit model with adjustment for clustering by treatment, and statistical control of herd-type, herd-size and five-year prior-BTB-episode history was used for our analyses. Although not included in the logistic model, a relative badger density metric based on the annual number of badgers captured-per-sett-night of capturing effort was developed for each treatment area; this metric indicated that relative badger density was approximately 40 % higher in vaccination areas than in the targeted badger-culling areas during our study. Overall, our study results indicated that vaccination was not inferior to targeted badger-culling in four counties and badger vaccination was deemed to produce ambivalent results in one (County Cork North) of the seven study sites in the ROI. A post-study investigation, in County Galway, where vaccination was deemed inferior to target culling, revealed that widespread purchases of cattle from a nearby cattle mart, by herd owners in the vaccination-area, was associated with the increased herd and vaccination-area risk of BTB. No single "biasing hypothesis" was evident for the apparent vaccine inferiority in the second study site (County Monaghan) where vaccination was deemed inferior to targeted culling; hence no further investigations were conducted.

Molecular Dynamics Modeling of the Structure and Na+-Ion Transport in Na2S + SiS2 Glassy Electrolytes.

Solid-state sodium batteries, a relatively safe and potentially cost-effective energy-storage technology, have attracted increasing scientific attention recently for application in stationary grid-scale energy storage. Identifying solid electrolytes with high electrochemical stability and high Na+-ion conductivity at room temperature is critically important to enable high energy densities with enhanced rate capabilities. We evaluated sodium sulfide-silicon sulfide, xNa2S + (1- x)SiS2, glasses as potential glassy solid electrolytes (GSEs) using molecular dynamics (MD) simulations. We employed ab initio MD to determine ion conduction mechanisms, to calculate energy barriers for ion hops, and to correlate these to the local short-range structure of 0.50Na2S + 0.50SiS2 glass. To simulate much larger systems for accurately calculating the ionic conductivity, we parameterized empirical Buckingham-type potential and performed classical MD simulations. After validating these calculations by comparing the structure obtained from MD to that from X-ray scattering data, we calculated the ionic conductivity of these glasses for the range of 0.33 ≤ x ≤ 0.67 compositions. The calculated ionic conductivities at room temperature were in the range of ∼10-5 S/cm for the x = 0.50 composition and increased significantly with sodium sulfide ( x) content. These calculations provide theoretical insights into the role of Na2S content on the ionic conductivity of GSEs aiding in the selection of specific compositions to enhance the ionic conductivity.

Methods and Processes of Developing the Strengthening the Reporting of Observational Studies in Epidemiology - Veterinary (STROBE-Vet) Statement.

BACKGROUND: Reporting of observational studies in veterinary research presents challenges that often are not addressed in published reporting guidelines. OBJECTIVE: To develop an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement that addresses unique reporting requirements for observational studies in veterinary medicine related to health, production, welfare, and food safety. DESIGN: Consensus meeting of experts. SETTING: Mississauga, Canada. PARTICIPANTS: Seventeen experts from North America, Europe, and Australia. METHODS: Experts completed a pre-meeting survey about whether items in the STROBE statement should be modified or added to address unique issues related to observational studies in animal species with health, production, welfare, or food safety outcomes. During the meeting, each STROBE item was discussed to determine whether or not rewording was recommended and whether additions were warranted. Anonymous voting was used to determine consensus. RESULTS: Six items required no modifications or additions. Modifications or additions were made to the STROBE items 1 (title and abstract), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources/measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations), and 22 (funding). CONCLUSION: The methods and processes used were similar to those used for other extensions of the STROBE statement. The use of this STROBE statement extension should improve reporting of observational studies in veterinary research by recognizing unique features of observational studies involving food-producing and companion animals, products of animal origin, aquaculture, and wildlife.

Explanation and Elaboration Document for the STROBE-Vet Statement: Strengthening the Reporting of Observational Studies in Epidemiology-Veterinary Extension.

The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement was first published in 2007 and again in 2014. The purpose of the original STROBE was to provide guidance for authors, reviewers, and editors to improve the comprehensiveness of reporting; however, STROBE has a unique focus on observational studies. Although much of the guidance provided by the original STROBE document is directly applicable, it was deemed useful to map those statements to veterinary concepts, provide veterinary examples, and highlight unique aspects of reporting in veterinary observational studies. Here, we present the examples and explanations for the checklist items included in the STROBE-Vet statement. Thus, this is a companion document to the STROBE-Vet statement methods and process document (JVIM_14575 "Methods and Processes of Developing the Strengthening the Reporting of Observational Studies in Epidemiology-Veterinary (STROBE-Vet) Statement" undergoing proofing), which describes the checklist and how it was developed.

Explanation and Elaboration Document for the STROBE-Vet Statement: Strengthening the Reporting of Observational Studies in Epidemiology - Veterinary Extension.

The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement was first published in 2007 and again in 2014. The purpose of the original STROBE was to provide guidance for authors, reviewers and editors to improve the comprehensiveness of reporting; however, STROBE has a unique focus on observational studies. Although much of the guidance provided by the original STROBE document is directly applicable, it was deemed useful to map those statements to veterinary concepts, provide veterinary examples and highlight unique aspects of reporting in veterinary observational studies. Here, we present the examples and explanations for the checklist items included in the STROBE-Vet Statement. Thus, this is a companion document to the STROBE-Vet Statement Methods and process document, which describes the checklist and how it was developed.

Methods and Processes of Developing the Strengthening the Reporting of Observational Studies in Epidemiology - Veterinary (STROBE-Vet) Statement.

The reporting of observational studies in veterinary research presents many challenges that often are not adequately addressed in published reporting guidelines. A consensus meeting of experts was organized to develop an extension of the STROBE statement to address observational studies in veterinary medicine with respect to animal health, animal production, animal welfare and food safety outcomes. The consensus meeting was held 11-13 May 2014 in Mississauga, Ontario, Canada. Seventeen experts from North America, Europe and Australia attended the meeting. The experts were epidemiologists and biostatisticians, many of whom hold or have held editorial positions with relevant journals. Prior to the meeting, 19 experts completed a survey about whether they felt any of the 22 items of the STROBE statement should be modified and whether items should be added to address unique issues related to observational studies in animal species with health, production, welfare or food safety outcomes. At the meeting, the participants were provided with the survey responses and relevant literature concerning the reporting of veterinary observational studies. During the meeting, each STROBE item was discussed to determine whether or not re-wording was recommended, and whether additions were warranted. Anonymous voting was used to determine whether there was consensus for each item change or addition. The consensus was that six items needed no modifications or additions. Modifications or additions were made to the STROBE items numbered as follows: 1 (title and abstract), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources/measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations) and 22 (funding). Published literature was not always available to support modification to, or inclusion of, an item. The methods and processes used in the development of this statement were similar to those used for other extensions of the STROBE statement. The use of this extension to the STROBE statement should improve the reporting of observational studies in veterinary research related to animal health, production, welfare or food safety outcomes by recognizing the unique features of observational studies involving food-producing and companion animals, products of animal origin, aquaculture and wildlife.

Methods and processes of developing the strengthening the reporting of observational studies in epidemiology - veterinary (STROBE-Vet) statement.

BACKGROUND: The reporting of observational studies in veterinary research presents many challenges that often are not adequately addressed in published reporting guidelines. OBJECTIVE: To develop an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement that addresses unique reporting requirements for observational studies in veterinary medicine related to health, production, welfare, and food safety. DESIGN: A consensus meeting of experts was organized to develop an extension of the STROBE statement to address observational studies in veterinary medicine with respect to animal health, animal production, animal welfare, and food safety outcomes. SETTING: Consensus meeting May 11-13, 2014 in Mississauga, Ontario, Canada. PARTICIPANTS: Seventeen experts from North America, Europe, and Australia attended the meeting. The experts were epidemiologists and biostatisticians, many of whom hold or have held editorial positions with relevant journals. METHODS: Prior to the meeting, 19 experts completed a survey about whether they felt any of the 22 items of the STROBE statement should be modified and if items should be added to address unique issues related to observational studies in animal species with health, production, welfare, or food safety outcomes. At the meeting, the participants were provided with the survey responses and relevant literature concerning the reporting of veterinary observational studies. During the meeting, each STROBE item was discussed to determine whether or not re-wording was recommended, and whether additions were warranted. Anonymous voting was used to determine whether there was consensus for each item change or addition. RESULTS: The consensus was that six items needed no modifications or additions. Modifications or additions were made to the STROBE items numbered: 1 (title and abstract), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources/measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations), and 22 (funding). LIMITATION: Published literature was not always available to support modification to, or inclusion of, an item. CONCLUSION: The methods and processes used in the development of this statement were similar to those used for other extensions of the STROBE statement. The use of this extension to the STROBE statement should improve the reporting of observational studies in veterinary research related to animal health, production, welfare, or food safety outcomes by recognizing the unique features of observational studies involving food-producing and companion animals, products of animal origin, aquaculture, and wildlife.

A quantitative systems pharmacology model of blood coagulation network describes in vivo biomarker changes in non-bleeding subjects.

Essentials Baseline coagulation activity can be detected in non-bleeding state by in vivo biomarker levels. A detailed mathematical model of coagulation was developed to describe the non-bleeding state. Optimized model described in vivo biomarkers with recombinant activated factor VII treatment. Sensitivity analysis predicted prothrombin fragment 1 + 2 and D-dimer are regulated differently. SUMMARY: Background Prothrombin fragment 1 + 2 (F1 + 2 ), thrombin-antithrombin III complex (TAT) and D-dimer can be detected in plasma from non-bleeding hemostatically normal subjects or hemophilic patients. They are often used as safety or pharmacodynamic biomarkers for hemostatis-modulating therapies in the clinic, and provide insights into in vivo coagulation activity. Objectives To develop a quantitative systems pharmacology (QSP) model of the blood coagulation network to describe in vivo biomarkers, including F1 + 2 , TAT, and D-dimer, under non-bleeding conditions. Methods The QSP model included intrinsic and extrinsic coagulation pathways, platelet activation state-dependent kinetics, and a two-compartment pharmacokinetics model for recombinant activated factor VII (rFVIIa). Literature data on F1 + 2 and D-dimer at baseline and changes with rFVIIa treatment were used for parameter optimization. Multiparametric sensitivity analysis (MPSA) was used to understand key proteins that regulate F1 + 2 , TAT and D-dimer levels. Results The model was able to describe tissue factor (TF)-dependent baseline levels of F1 + 2 , TAT and D-dimer in a non-bleeding state, and their increases in hemostatically normal subjects and hemophilic patients treated with different doses of rFVIIa. The amount of TF required is predicted to be very low in a non-bleeding state. The model also predicts that these biomarker levels will be similar in hemostatically normal subjects and hemophilic patients. MPSA revealed that F1 + 2 and TAT levels are highly correlated, and that D-dimer is more sensitive to the perturbation of coagulation protein concentrations. Conclusions A QSP model for non-bleeding baseline coagulation activity was established with data from clinically relevant in vivo biomarkers at baseline and changes in response to rFVIIa treatment. This model will provide future mechanistic insights into this system.

A model-based longitudinal meta-analysis of FEV1 in randomized COPD trials.

A model-based, longitudinal meta-analysis of the efficacy on morning trough forced expiratory volume in 1 second (FEV1 ) in chronic obstructive pulmonary disease (COPD) is presented. Literature data from 142 randomized maintenance trials were included, comprising 106,422 patients who received 19 compounds. 1982 morning trough FEV1 observations were available, each representing the mean FEV1 for a study arm at a specific timepoint. The final model for absolute FEV1 included baseline, disease progression, placebo effect, and drug effect estimates for all compounds, with interstudy variability on all model components and additional interarm variability on baseline. A dose-response relationship was identifiable for 10 of the 19 compounds. Drug-drug interactions among direct bronchodilators and the effect of concomitant background COPD treatment were included. Covariates were identified on baseline. Disease progression was proportional to the baseline FEV1 , and a mean baseline of <1.2 L resulted in a lower efficacy, in particular for antiinflammatory treatments.

Methods and Processes of Developing the Strengthening the Reporting of Observational Studies in Epidemiology-Veterinary (STROBE-Vet) Statement.

Reporting of observational studies in veterinary research presents challenges that often are not addressed in published reporting guidelines. Our objective was to develop an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement that addresses unique reporting requirements for observational studies in veterinary medicine related to health, production, welfare, and food safety. We conducted a consensus meeting with 17 experts in Mississauga, Canada. Experts completed a premeeting survey about whether items in the STROBE statement should be modified or added to address unique issues related to observational studies in animal species with health, production, welfare, or food safety outcomes. During the meeting, each STROBE item was discussed to determine whether or not rewording was recommended, and whether additions were warranted. Anonymous voting was used to determine consensus. Six items required no modifications or additions. Modifications or additions were made to the STROBE items 1 (title and abstract), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources and measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations), and 22 (funding). The methods and processes used were similar to those used for other extensions of the STROBE statement. The use of this STROBE statement extension should improve reporting of observational studies in veterinary research by recognizing unique features of observational studies involving food-producing and companion animals, products of animal origin, aquaculture, and wildlife.

Spatial and temporal analyses of metrics of tuberculosis infection in badgers (Meles meles) from the Republic of Ireland: Trends in apparent prevalence.

Badgers are a wildlife host of Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), and an important contributor to the epidemiology of bTB in cattle in Ireland and Britain. Repeated culling of badgers in high prevalence cattle bTB areas has been used in the Republic of Ireland as one tool to reduce intra- and interspecific transmission of M. bovis. We assessed factors that influenced infection prevalence of culled badgers from 2009 to 2012 (n=4948) where spatial, temporal and intrinsic factor data were available using multivariable modelling. Prevalence appeared higher in western areas than eastern areas of Ireland and badgers were more likely to be test-positive if caught at a sett (burrow system) which was close to other infected setts (spatial clustering of infection). There was a significant positive association between badger test-status and cattle prevalence of M. bovis infection at a spatial scale of 1km around setts. Badgers were more likely to be deemed test positive if they were male (OR: 1.9) or a parous female (OR: 1.7), compared to a female who had never conceived. Our results are consistent with different groups within badger populations having differential exposures and therefore infection risk (for example, parous vs. non-parous females). Furthermore, bTB clusters within the badger population, with greater risk to badgers in setts that are closest to other infected setts. The effective scale of the association of bTB risk between badger and cattle populations may be relatively large in Ireland. Our data indicate that the overall trend in prevalence of M. bovis infection in badgers has decreased in Ireland (P<0.001) while controlling for significant confounders over the study period, and follows a longer temporal trend from 2007 to 2013, where unadjusted apparent prevalence declined from 26% to 11% during 2007 to mid-2011, followed by a stable trend between 9 and 11% thereafter (n=10,267).

Using a Systems Pharmacology Model of the Blood Coagulation Network to Predict the Effects of Various Therapies on Biomarkers.

A number of therapeutics have been developed or are under development aiming to modulate the coagulation network to treat various diseases. We used a systems model to better understand the effect of modulating various components on blood coagulation. A computational model of the coagulation network was built to match in-house in vitro thrombin generation and activated Partial Thromboplastin Time (aPTT) data with various concentrations of recombinant factor VIIa (FVIIa) or factor Xa added to normal human plasma or factor VIII-deficient plasma. Sensitivity analysis applied to the model revealed that lag time, peak thrombin concentration, area under the curve (AUC) of the thrombin generation profile, and aPTT show different sensitivity to changes in coagulation factors' concentrations and type of plasma used (normal or factor VIII-deficient). We also used the model to explore how variability in concentrations of the proteins in coagulation network can impact the response to FVIIa treatment.

A multiscale model of interleukin-6-mediated immune regulation in Crohn's disease and its application in drug discovery and development.

In this study, we have developed a multiscale systems model of interleukin (IL)-6-mediated immune regulation in Crohn's disease, by integrating intracellular signaling with organ-level dynamics of pharmacological markers underlying the disease. This model was linked to a general pharmacokinetic model for therapeutic monoclonal antibodies and used to comparatively study various biotherapeutic strategies targeting IL-6-mediated signaling in Crohn's disease. Our work illustrates techniques to develop mechanistic models of disease biology to study drug-system interaction. Despite a sparse training data set, predictions of the model were qualitatively validated by clinical biomarker data from a pilot trial with tocilizumab. Model-based analysis suggests that strategies targeting IL-6, IL-6Rα, or the IL-6/sIL-6Rα complex are less effective at suppressing pharmacological markers of Crohn's than dual targeting the IL-6/sIL-6Rα complex in addition to IL-6 or IL-6Rα. The potential value of multiscale system pharmacology modeling in drug discovery and development is also discussed.CPT: Pharmacometrics & Systems Pharmacology (2014) 3, e89; doi:10.1038/psp.2013.64; advance online publication 8 January 2014.

Model-based drug development: a rational approach to efficiently accelerate drug development.

The pharmaceutical industry continues to face significant challenges. Very few compounds that enter development reach the marketplace, and the investment required for each success can surpass $1.8 billion. Despite attempts to improve efficiency and increase productivity, total investment continues to rise whereas the output of new medicines declines. With costs increasing exponentially through each development phase, it is failure in phase II and phase III that is most wasteful. In today's development paradigm, late-stage failure is principally a result of insufficient efficacy. This is manifested as either a failure to differentiate sufficiently from placebo (shown for both novel and precedented mechanisms) or a failure to demonstrate sufficient differentiation from existing compounds. Set in this context, this article will discuss the role model-based drug development (MBDD) approaches can and do play in accelerating and optimizing compound development strategies through a series of illustrative examples.

Non-Arrhenius ionic conductivities in glasses due to a distribution of activation energies.

Previously observed non-Arrhenius behavior in fast ion conducting glasses [J. Kincs and S. W. Martin, Phys. Rev. Lett. 76, 70 (1996)] occurs at temperatures near the glass transition temperature, T(g), and is attributed to changes in the ion mobility due to ion trapping mechanisms that diminish the conductivity and result in a decreasing conductivity with increasing temperature. It is intuitive that disorder in glass will also result in a distribution of the activation energies (DAE) for ion conduction, which should increase the conductivity with increasing temperature, yet this has not been identified in the literature. In this Letter, a series of high precision ionic conductivity measurements are reported for 0.5Na(2)S + 0.5[xGeS(2) + (1-x)PS(5/2)] glasses with compositions ranging from 0 ≤ x ≤ 1. The impact of the cation site disorder on the activation energy is identified and explained using a DAE model. The absence of the non-Arrhenius behavior in other glasses is explained and it is predicted which glasses are expected to accentuate the DAE effect on the ionic conductivity.

Integrated pharmacometrics and systems pharmacology model-based analyses to guide GnRH receptor modulator development for management of endometriosis.

Endometriosis is a gynecological condition resulting from proliferation of endometrial-like tissue outside the endometrial cavity. Estrogen suppression therapies, mediated through gonadotropin-releasing hormone (GnRH) modulation, decrease endometriotic implants and diminish associated pain albeit at the expense of bone mineral density (BMD) loss. Our goal was to provide model-based guidance for GnRH-modulating clinical programs intended for endometriosis management. This included developing an estrogen suppression target expected to provide symptomatic relief with minimal BMD loss and to evaluate end points and study durations supportive of efficient development decisions. An existing multiscale model of calcium and bone was adapted to include systematic estrogen pharmacologic effects to describe estrogen concentration-related effects on BMD. A logistic regression fit to patient-level data from three clinical GnRH agonist (nafarelin) studies described the relationship of estrogen with endometrial-related pain. Targeting estradiol between 20 and 40 pg/ml was predicted to provide efficacious endometrial pain response while minimizing BMD effects.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e11; doi:10.1038/psp.2012.10; advance online publication 17 October 2012.

Predictors of the first between-herd animal movement for cattle born in 2002 in Ireland.

Movement of animals between farms represents a potential risk of bovine tuberculosis (BTB) and other disease transmission. The objectives of this study were to identify and quantify risk factors associated with the first between-herd movement of animals (denoted as risk move). A random sample of 1 percent of Irish calf births registered for 2002 (20,182 animals) was selected. Descriptive and survival analysis on movement over the period 2002-2005 was performed. A total of 12,119 (60%) of animals experienced a risk move over the 4-year study period. Among those that moved, 57% did so within the first 12 months of age. For animals in dairy herds, an early peak in risk move events was observed within the first 12 weeks of age; whereas in animals from suckler herds, a later risk move peak was observed between 21 and 36 weeks of age. The survival models identified a number of risk factors: two that appeared most important in predicting a risk move were gender and enterprise type. Males had a hazard ratio of 2.6 times that of females. The hazards for enterprise type, varied over time, thus a time-varying covariate (ent_type×ln(time)) was included in the Cox model. At 7 days of age, females in suckler herds were at 0.14 times the hazard of females in dairy herds for risk move, and over time, the hazards converged, equalised by day 140, and then diverged, so that by 4 years of age, females in suckler herds were at 4.64 times the hazard of females in dairy herds. Herds with a history of selling animals in previous years maintained that record during the study period with increased hazard of risk move. Enterprise type interacted with gender so that relative to females, males from dairy herds were at greater hazard of risk move than males from suckler herds. Hazard of risk move was also a function of ln (herd area), so that each doubling of farm area was accompanied by a 30.6% decrease in the hazards. The main conclusion was that risk of movement related disease transmission also depends on the purpose of the movement whether for breeding or for beef finishing. While males were at greater hazard of movement than females, they would have a shorter lifespan, thus limiting the opportunity for further transmission post-movement.

Prevalence of Yersinia enterocolitica shedding and bioserotype distribution in Ontario finisher pig herds in 2001, 2002, and 2004.

We investigated characteristics of Yersinia enterocolitica infection in Ontario finisher pig herds. Our specific objectives were to estimate or test: prevalence of Y. enterocolitica shedding in finisher pigs, bioserotype distribution, agreement between the herd-level tests based on sampling pig and pooled fecal samples, whether bioserotypes cluster by farms, and whether Y. enterocolitica-positive herds cluster spatially. In total, 3747 fecal samples were collected from 100 farms over the years 2001, 2002, and 2004 (250 total herd visits). Fecal samples were tested by culture and positive isolates were biotyped and serotyped. Apparent pig-level prevalence of Y. enterocolitica was 1.8%, 3.2%, and 12.5% in 2001, 2002, and 2004, respectively. Estimated true pig-level prevalence of Y. enterocolitica was 5.1%, 9.1%, and 35.1% in 2001, 2002, and 2004, respectively. Herd-level prevalence was 16.3%, 17.9%, and 37.5% in 2001, 2002, and 2004, respectively. In all years, the most common bioserotype was 4, O:3, followed by bioserotype 2, O:5,27. Kappa between herd-level status based on pig and pooled samples ranged between 0.51 and 0.68 for biotype 1A and bioserotype 4, O:3, respectively. For 4, O:3, a significant bias in discordant pairs was detected, indicating that pig samples were more sensitive than pooled samples in declaring a herd as positive. Farms tended to be repeatedly positive with the same bioserotype, but positive study farms did not cluster spatially (suggesting lack of between herd transmission and lack of a common geographic risk factor).

The risk of a positive test for bovine tuberculosis in cattle purchased from herds with and without a recent history of bovine tuberculosis in Ireland.

A retrospective cohort study was conducted to assess if cattle sold from Irish dairy herds within 7 months of herd de-restriction (clearance to trade) from a bovine-tuberculosis (BTB) episode had an excess risk of testing positive for BTB during the following 2 years, and to determine other risk factors associated with this outcome. If possible, a predictive metric for herds at high risk of selling future BTB-positive cattle would be generated. The unexposed cohort included all cattle sold within 7 months of the annual herd test in a random sample of dairy herds that did not test positive for BTB in 2003. The exposed cohort consisted of all cattle sold within 7 months of the date of de-restriction in all dairy herds that cleared a BTB episode in 2003. Only cattle sold from herds that were initially found to test positive for BTB using the single intradermal comparative tuberculin test (SICTT)-and not due to discovery of a BTB-positive animal at slaughter-were included as exposed cattle. To aid in the development of a predictive metric, the exposed cohort was subcategorized based on the number of reactors to the SICTT in the herd of origin during the BTB episode immediately prior to sale. The final exposure categories of 0 (unexposed), 1-7, and >or=8 total reactors were considered the unexposed, mildly exposed, and severely exposed cohorts, respectively. A multivariable logistic regression model was fit to the final BTB status of the animal using a generalized estimating equation method (GEE), assuming an exchangeable correlation structure of animals within herds, and using robust standard errors. Exposure level and the other available herd- and animal-level information were modeled. After controlling for other risk factors including the size of the herd of origin and the sex and age of the animal, the three-level exposure variable significantly improved the model (based on a change in Quasi-Akaike Information Criteria of 2.2) and demonstrated a trend of increasing risk of a future positive BTB test with increasing exposure category. The severely exposed cohort of animals had significantly higher risk of a future positive BTB test than the unexposed cohort (OR=1.78, p=0.030).

A multi-level approach for investigating socio-economic and agricultural risk factors associated with rates of reported cases of Escherichia coli O157 in humans in Alberta, Canada.

Using negative binomial and multi-level Poisson models, the authors determined the statistical significance of agricultural and socio-economic risk factors for rates of reported disease associated with Escherichia coli O157 in census subdivisions (CSDs) in Alberta, Canada, 2000-2002. Variables relating to population stability, aboriginal composition of the CSDs, and the economic relationship between CSDs and urban centres were significant risk factors. The percentage of individuals living in low-income households was not a statistically significant risk factor for rates of disease. The statistical significance of cattle density, recorded at a higher geographical level, depended on the method used to correct for overdispersion, the number of levels included in the multi-level models, and the choice of using all reported cases or only sporadic cases. Our results highlight the importance of local socio-economic risk factors in determining rates of disease associated with E. coli O157, but their relationship with individual risk factors requires further evaluation.