Estimation of sensitivity and specificity of bulk tank milk PCR and 2 antibody ELISA tests for herd-level diagnosis of Mycoplasma bovis infection using Bayesian latent class analysis.

Mycoplasmosis (due to infection with Mycoplasma bovis) is a serious disease of beef and dairy cattle that can adversely affect health, welfare, and productivity. Mycoplasmosis can lead to a range of often severe, clinical presentations. Mycoplasma bovis infection can present either clinically or subclinically, with the potential for recrudescence of shedding in association with stressful periods. Infection can be maintained within herds because of intermittent shedding. Mycoplasma bovis is recognized as poorly responsive to treatment, which presents a major challenge for control in infected herds. Given this, particular focus is needed on biosecurity measures to prevent introduction into uninfected herds in the first place. A robust and reliable laboratory test for surveillance is important for both herd-level prevention and control. The objective of this study was to estimate the sensitivity (Se) and specificity (Sp) of 3 diagnostic tests (1 PCR and 2 ELISA tests) on bulk tank milk (BTM), for the herd-level detection of M. bovis using Bayesian latent class analysis (BLCA). In autumn 2018, BTM samples from 11,807 herds, covering the majority of the main dairy regions in Ireland had been submitted to the Department of Agriculture testing laboratory for routine surveillance and were made available for study. A stratified random sample approach was used to select a cohort of herds for testing from this larger sample set. A final study population of 728 herds had BTM samples analyzed using a Bio-X ELISA (ELISA 1), an IDvet ELISA (ELISA 2) and a PCR test. A BLCA was conducted to estimate the Se and Sp of the 3 diagnostic tests applied to BTM for the detection of herd-level infection. An overall latent class analysis was conducted on all herds within a single population (a 3-test, 1-population model). The herds were also split into 2 populations based on herd size (small herds had <82 cattle; a 3-test, 2-population model) and separately into 3 regions in Ireland (Leinster, Munster, and Connacht/Ulster; a 3-test, 3-population model). The latent variable of interest was the herd-level M. bovis infection status. In total, 363/728 (50%) were large herds, 7 (1.0%) were positive on PCR, 88 (12%) positive on ELISA 1, and 406 (56%) positive on ELISA 2. Based on the 2-population model, the Se (95% Bayesian credible interval [BCI] was 0.03 (upper and lower limits: 0.02, 0.05), 0.22 (0.18, 0.27), and 0.94 (0.88, 0.98) for PCR, ELISA 1, and ELISA 2, respectively. The Sp (95% BCI) was 0.99 (0.99, 1.0), 0.97 (0.95, 0.99), and 0.92 (0.86, 0.97) for PCR, ELISA 1, and ELISA 2, respectively. The herd-level true prevalence was estimated at 0.43 (BCI 0.35, 0.5) for smaller herds. The true prevalence was estimated at 0.62 (BCI 0.55, 0.69) for larger herds. The true prevalence was estimated at 0.56 (BCI 0.49, 0.463) in the 1-population model. For the 3-population model, the Se (95% BCI) was 0.03 (0.02, 0.05), 0.24 (0.18, 0.29), and 0.95 (0.9, 0.98) for PCR, ELISA 1, and ELISA 2 respectively. The Sp (95% BCI) was 0.99 (0.99, 1.0), 0.98 (0.96, 0.99), and 0.88 (0.79, 0.95) for PCR, ELISA 1 and ELISA 2, respectively. The herd-level true prevalence (95% BCI) was estimated at 0.65 (0.56, 0.73), 0.38 (0.28, 0.46), and 0.53 (0.4, 0.65) for populations 1, 2, and 3 respectively. Across all 3 models, the range in true prevalence was 38% to 65% of Irish dairy herds infected with M. bovis. The operating characteristics vary substantially between tests. The IDvet ELISA had a relatively high Se (the highest Se of the 3 tests studied) but it was estimated at 0.95 at its highest in 3-test, 3-population model. This test may be an appropriate test for herd-level screening or prevalence estimation within the context of the endemically infected Irish dairy cattle population. Further work is required to optimize this test and its interpretation when applied at herd-level to offset concerns related to the lower than optimal test Sp.

Seroprevalence of Mycoplasma bovis in bulk milk samples in Irish dairy herds and risk factors associated with herd seropositive status.

Mycoplasma bovis is a serious disease of cattle worldwide; mastitis, pneumonia, and arthritis are particularly important clinical presentations in dairy herds. Mycoplasma bovis was first identified in Ireland in 1994, and the reporting of Mycoplasma-associated disease has substantially increased over the last 5 years. Despite the presumed endemic nature of M. bovis in Ireland, there is a paucity of data on the prevalence of infection, and the effect of this disease on the dairy industry. The aim of this observational study was to estimate apparent herd prevalence for M. bovis in Irish dairy herds using routinely collected bulk milk surveillance samples and to assess risk factors for herd seropositivity. In autumn 2018, 1,500 herds out of the 16,858 herds that submitted bulk tank milk (BTM) samples to the Department of Agriculture testing laboratory for routine surveillance were randomly selected for further testing. A final data set of 1,313 sampled herds with a BTM ELISA result were used for the analysis. Testing was conducted using an indirect ELISA kit (ID Screen Mycoplasma bovis). Herd-level risk factors were used as explanatory variables to determine potential risk factors associated with positive herd status (reflecting past or current exposure to M. bovis). A total of 588 of the 1,313 BTM samples were positive to M. bovis, providing an apparent herd prevalence of 0.45 (95% CI: 0.42, 0.47) in Irish dairy herds in autumn 2018. Multivariable analysis was conducted using logistic regression. The final model identified herd size, the number of neighboring farms, in-degree and county as statistically significant risk factors for herd BTM seropositivity to M. bovis. The results suggest a high apparent herd prevalence of seropositivity to M. bovis, and evidence that M. bovis infection is now endemic in the Irish dairy sector. In addition, risk factors identified are closely aligned to what we would expect of an infectious disease. Awareness raising and education about this important disease is warranted given the widespread nature of exposure and likely infection in Irish herds. Further work on the validation of diagnostic tests for herd-level diagnosis should be undertaken as a matter of priority.

Geographical distribution of Angiostrongylus vasorum in foxes (Vulpes vulpes) in the Republic of Ireland.

The reported incidence of the metastrongylid nematode Angiostrongylus vasorum, that infects dogs and other canids, is increasing worldwide outside recognized endemic foci. This apparent expansion of the parasite's range is causing concern to veterinary clinicians as the disease caused in dogs can be life threatening and its treatment is not straightforward. The red fox is thought to be a reservoir host for dogs. To investigate the spatial distribution of infection in foxes in Ireland, the hearts and lungs of 542 foxes from all over Ireland were examined. The incidence of infection was found to be 39·9% [95% confidence interval (CI) 35·7-44·1] with positive samples occurring in each of the country's 26 counties. This report confirms that the parasite is endemic in Ireland and the overall prevalence is the second highest in Europe. This is the first survey of A. vasorum infection in Irish foxes and highlights the potential exposure of the Irish dog population to high risk of cross-infection. Additionally, Crenosoma vulpis was found in seven of the foxes, a parasite not previously reported in the Irish fox.

Prevalence and distribution of exposure to Schmallenberg virus in Irish cattle during October 2012 to November 2013.

BACKGROUND: Schmallenberg virus (SBV) was first identified in November 2011. It is a novel Orthobunyavirus (family Bunyaviridae) whose main ill effect is congenital malformation of the musculoskeletal and central nervous systems. It is borne by Culicoides spp., and has spread extensively in western Europe. The first case of SBV in Ireland was diagnosed in October 2012. It was anticipated that once the virus emerged in Ireland that there would be wide scale or nationwide spread over the course of the 2013 vector season. The objectives of this study were to determine the seroprevalence and distribution of exposure to Schmallenberg virus in Irish cattle from November 2012 to November 2013. METHODS: Samples of brain for the pathology based surveillance were collected from malformed bovine and ovine foetuses submitted for post mortem examination. These samples were tested for SBV using RT-qPCR. Three serological surveys were carried out on sera submitted for the national brucellosis eradicartion programme. A spatial analysis of both sets of data was carried out. RESULTS: Between October 2012 and 10th May 2013, SBV was confirmed by RT-qPCR in brain tissues from malformed foetuses obtained from 49 cattle herds and 30 sheep flocks in Ireland. In national serosurveys conducted between November 2012 until November 2013 the herd-level and animal-level SBV seroprevalences in cattle were 53 and 36 % respectively for the first survey, 51 and 35 % for the second survey and 53 and 33 % for the third survey. The herd level seroprevalence in counties ranged from 0 to 100 %, with the counties in the south and southeast having the highest seroprevalence (>50 %), the midlands a moderate herd level seroprevalence (10-50 %) while northern and north western counties had a low herd level seroprevalence (0-10 %). There was close spatial agreement between the results of the two different targeted surveillance strategies. CONCLUSIONS: At the end of the 2012 vector season, there was widespread exposure to SBV among herds in southern and south eastern Ireland. During 2013, there was little or no evidence of further outward spread, unlike the situation in several other European countries. Given the lack of evidence for circulation of the virus since 2012, it is likely that the younger age cohort in herds previously exposed to SBV and substantial proportions of animals of all ages on the margins of affected areas are immunologically naïve to SBV, and would be susceptible to infection if the virus were to re-emerge.

Estimating the extent of spatial association of Mycobacterium bovis infection in badgers in Ireland.

Mycobacterium bovis infects the wildlife species badgers Meles meles who are linked with the spread of the associated disease tuberculosis (TB) in cattle. Control of livestock infections depends in part on the spatial and social structure of the wildlife host. Here we describe spatial association of M. bovis infection in a badger population using data from the first year of the Four Area Project in Ireland. Using second-order intensity functions, we show there is strong evidence of clustering of TB cases in each the four areas, i.e. a global tendency for infected cases to occur near other infected cases. Using estimated intensity functions, we identify locations where particular strains of TB cluster. Generalized linear geostatistical models are used to assess the practical range at which spatial correlation occurs and is found to exceed 6 in all areas. The study is of relevance concerning the scale of localized badger culling in the control of the disease in cattle.

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.

Herd-level factors associated with detection of calves persistently infected with bovine viral diarrhoea virus (BVDV) in Irish cattle herds with negative herd status (NHS) during 2017.

A compulsory national BVD eradication programme commenced in Ireland in 2013. Since then considerable progress has been made, with the animal-level prevalence of calves born persistently infected (PI) falling from 0.67 % in 2013 to 0.06 % in 2018. The herd-level prevalence fell from 11.3 % in 2013 to 1.1 % in 2018. In the Irish programme, herds in which all animals have a known negative status and which have not contained any PI animals for 12 months or more are assigned a negative herd status (NHS). While considerable progress towards eradication has been made, PI calves have been identified in a small proportion of herds that had previously been assigned NHS. Given this context, a case-control study was conducted to investigate potential risk factors associated with loss of NHS in 2017. 546 herds which had NHS on 1 January 2017 and lost that status during 2017 (case herds) were matched with 2191 herds (control herds) that retained their NHS status throughout 2017. Previous history of BVD infection, herd size, herd expansion, the purchase of cattle including potential Trojan cattle and the density of BVD infection within 10 km of the herd emerged as significant factors in a multivariable logistic regression model. This work adds to the evidence base in support of the BVD eradication programme, particularly establishing why BVD re-emerged in herds which had been free of BVD for at least the previous 12 months prior to the identification of a BVD positive calf. This information will be especially important in the context of identifying herds which may be more likely to contain BVD positive animals once the programme moves to herd-based serology status for trading purposes in the post-eradication phase.

Targeted badger removal and the subsequent risk of bovine tuberculosis in cattle herds in county Laois, Ireland.

We investigated the impact of targeted removal of badgers on the subsequent bovine tuberculosis (BTB) risk in cattle herds in county Laois, Ireland. The study period was 1989-2005. For each of 122 targeted badger-removal licenses (permit to remove badgers in the proximity of cattle herds undergoing a serious BTB episode), the herd number (index herd) for which the license was given was obtained. The herds in the proximity of the index herd were identified from another database. The main "exposure" in our study was the geographical location of herds relative to the area in which targeted badger removal was conducted. We categorized herds into five different exposure groups: herds were classified as non-exposed and denoted as group 0 (reference group) if they were located 500 m or more from the edge of any parcel of land of the index herd; group 1, was the index herds, group 2 the immediate (contiguous) neighbors of the index herd, group 3 herds were not immediate neighbors but within 150 m and group 4 herds were between 150 m and 500 m distance from the edge of any parcel of land of the index herd, respectively. We conducted a survival analysis (allowing multiple failures per herd) to compare the hazard of having a BTB episode in any of the four groups of exposed herds vs. the hazard in herds in the reference group. We controlled for other known risk factors as well taking into account a temporal component. Our analysis showed that the hazard ratio for the index herds (group 1) were non-significantly increased, indicating that there was no difference in the hazard of failing a BTB test (after the targeted badger removal was conducted) between index herds and reference herds. For the rest of the herds farther away from badger removal activities the hazards were lower than herds in areas not under badger removal. The hazard in the reference group decreased over the study period.

An all-island approach to mapping bovine tuberculosis in Ireland.

This study used techniques in Geographical Information Systems (GIS) to explore the spatial patterns of bovine tuberculosis (TB) in the whole island of Ireland over an 11-year period. This is the first time that data pertaining to TB from the Republic of Ireland and Northern Ireland have been collated and examined in an all-Ireland context. The analyses were based on 198, 156 point locations representing active farms with cattle in Northern Ireland and the Republic of Ireland between the years 1996 and 2006. The results consist of a series of maps giving a visual representation of cattle populations and associated detected bTB levels on the island of Ireland over this time interval.

Survival and dispersal of a defined cohort of Irish cattle.

An understanding of livestock movement is critical to effective disease prevention, control and prediction. However, livestock movement in Ireland has not yet been quantified. This study has sought to define the survival and dispersal of a defined cohort of cattle born in Co. Kerry during 2000. The cohort was observed for a maximum of four years, from January 1, 2000 to December 31, 2004. Beef and dairy animals moved an average 1.31 and 0.83 times, respectively. At study end, 18.8% of the beef animals remained alive on Irish farms, including 6.7% at the farm-of-birth, compared with 48.6% and 27.7% for dairy animals respectively. Beef animals werae dispersed to all Irish counties, but mainly to Cork, Limerick, Tipperary and Galway. Dairy animals mainly moved to Cork, Limerick, and Tipperary, with less animals going to Galway, Meath and Kilkenny. The four-year survival probability was 0.07 (male beef animals), 0.25 (male dairy), 0.38 (female beef), and 0.72 (female dairy). Although there was considerable dispersal, the number of moves per animal was less than expected.

Risk factors for disclosure of additional tuberculous cattle in attested-clear herds that had one animal with a confirmed lesion of tuberculosis at slaughter during 2003 in Ireland.

All the Irish cattle herds considered "clear" of bovine tuberculosis (BTB) having a single animal with a tuberculous lesion at slaughter during 2003 were identified. We performed a descriptive and logistic regression analysis to investigate whether selected risk factors had an association with the result of the herd test immediately after the tuberculous lesion was found ("Factory Lesion Test", FLT). At the FLT, only 19.7% (n=338) of these 1713 herds had 1 or more standard reactors. The lesioned animal was home-bred in 46% of the "source" herds; these herds had an increased risk (23.4%) of having at least 1 standard reactor animal relative to herds with a purchased-lesioned animal (16.6%) (RR=1.41). Our logistic models identified a number of important risk factors; two that appeared most important in predicting the FLT outcome were the time spent (residency) by the lesioned animal in the "source" herd, and the presence, or not, of the lesioned animal in a previous BTB episode in either the "source" herd, or the seller's herd in the case the lesioned animal was purchased. Our models fit the data well based on the Hosmer-Lemeshow test, however their sensitivity and specificity were very low (57% and 61% respectively). Surveillance of the cattle population for BTB using lesions found at slaughter is an essential component of an overall control program. Nonetheless, due to the poor predictability of the variables we measured, complete herd investigations are needed to help explain the FLT outcome of a herd.

Quantification of Mycobacterium bovis transmission in a badger vaccine field trial.

In the UK and Ireland, Bacille Calmette-Guérin (BCG) vaccination of badgers has been suggested as one of a number of strategies to control or even eradicate Mycobacterium bovis infection in badgers. In this manuscript, we present the results of a badger field trial conducted in Ireland and discuss how the novel trial design and analytical methods allowed the effects of vaccination on protection against infection and, more importantly, on transmission to be estimated. The trial area was divided into three zones North to South (A, B and C) where vaccination coverages of 0, 50 and 100%, respectively, were applied. Badgers were trapped over a 4year period. Badgers were assigned to either placebo or vaccine treatment, with treatment allocation occurring randomly in zone B. Blood samples were collected at each capture, and serology was performed in these samples using a chemiluminescent multiplex ELISA system (Enfer test). The analysis aimed to compare new infections occurring in non-infected non-vaccinated badgers to those in non-infected vaccinated ones, while accounting for the zone in which the badger was trapped and the infection pressure to which this individual badger was exposed. In total, 440 records on subsequent trappings of individual non-infected badgers were available for analysis. Over the study period, 55 new infections occurred in non-vaccinated (out of 239=23.0%) and 40 in vaccinated (out of 201=19.9%) badgers. A Generalized Linear Model (GLM) with a cloglog link function was used for analysis. Statistical analysis showed that susceptibility to natural exposure with M. bovis was reduced in vaccinated compared to placebo treated badgers: vaccine efficacy for susceptibility, VES, was 59% (95% CI=6.5%-82%). However, a complete lack of effect from BCG vaccination on the infectivity of vaccinated badgers was observed, i.e. vaccine efficacy for infectiousness (VEI) was 0%. Further, the basic reproduction ratio as a function of vaccination coverage (p) (i.e. R(p)) was estimated. Given that the prevalence of M. bovis infection in badgers in endemic areas in Ireland is approximately 18%, we estimated the reproduction ratio in the unvaccinated population as R(0)=1.22. Because VES was now known, the reproduction ratio for a fully vaccinated population was estimated as R(1)=0.50. These results imply that with vaccination coverage in badgers exceeding 30%, eradication of M. bovis in badgers in Ireland is feasible, provided that the current control measures also remain in place.

Eradicating BVD, reviewing Irish programme data and model predictions to support prospective decision making.

Bovine Viral Diarrhoea is an infectious production disease of major importance in many cattle sectors of the world. The infection is predominantly transmitted by animal contact. Postnatal infections are transient, leading to immunologically protected cattle. However, for a certain window of pregnancy, in utero infection of the foetus results in persistently infected (PI) calves being the major risk of BVD spread, but also an efficient target for controlling the infection. There are two acknowledged strategies to identify PI animals for removal: tissue tag testing (direct; also known as the Swiss model) and serological screening (indirect by interpreting the serological status of the herd; the Scandinavian model). Both strategies are effective in reducing PI prevalence and herd incidence. During the first four years of the Irish national BVD eradication programme (2013-16), it has been mandatory for all newborn calves to be tested using tissue tag testing. During this period, PI incidence has substantially declined. In recent times, there has been interest among stakeholders in a change to an indirect testing strategy, with potential benefit to the overall programme, particularly with respect to cost to farmers. Advice was sought on the usefulness of implementing the necessary changes. Here we review available data from the national eradication programme and strategy performance predictions from an expert system model to quantify expected benefits of the strategy change from strategic, budgetary and implementation points of view. Key findings from our work include (i) drawbacks associated with changes to programme implementation, in particular the loss of epidemiological information to allow real-time monitoring of eradication progress or to reliably predict time to eradication, (ii) the fact that only 25% of the herds in the Irish cattle sector (14% beef, 78% dairy herds) would benefit financially from a change to serosurveillance, with half of these participants benefiting by less than EUR 75 per annum at herd level or an average of EUR 1.22 per cow, and (iii) opportunities to enhance the effectiveness of the current programme, particularly in terms of time to eradication, through enforced compliance with PI removal as currently outlined in programme recommendations. The assembled information provides scientific arguments, contributing to an informed debate of the pros and cons of a change in eradication strategy in Ireland.

Does reactive badger culling lead to an increase in tuberculosis in cattle?

The conclusion from the randomised badger culling trial was that localised badger culling not only fails to control but can actually increase the incidence of bovine tuberculosis in cattle. Professor Simon More and colleagues from University College Dublin question that conclusion, arguing that the data do not provide sufficient evidence to rule out alternative hypotheses.

Quantifying badger exposure and the risk of bovine tuberculosis for cattle herds in county Kilkenny, Ireland.

The objectives of the study were to quantify the levels of badger exposure for cattle and to test the hypothesis that increased badger exposure does not increase the risk of bovine tuberculosis (BTB) in a herd. Information that became available from the targeted removal of badgers over the study period, and from a badger-removal project in county Kilkenny, during 1996-1999 was used. The specific location of cattle within each farm, and the length of time that cattle spent in each farm field during the grazing season, and in the barnyard during winter, was used to build an exposure coefficient to quantify the amount of badger exposure that cattle encountered either on pasture or in the barn. The study design was a matched case-control study in which the control herds were selected using incidence density sampling. During the 4-year study period, 543 badgers were removed and of these 96 badgers were classified as tuberculosis positive; 96 BTB herd breakdowns occurred. There was a significant association between case herds and having a higher badger sett exposure coefficient during 1996-1998. No significant association between case herds and having a higher exposure coefficient based on the number of badgers, or the number of tuberculous badgers, during September 1997-December 1999 was found.

Genotyping of Mycobacterium bovis isolates from badgers in four areas of the Republic of Ireland by restriction fragment length polymorphism analysis.

An analysis of the molecular epidemiology of Mycobacterium bovis in badgers was made in four selected areas of the Republic of Ireland in which an intensive badger removal programme was being carried out over a period of five years. Tissue samples from 2310 badgers were cultured. Restriction fragment length polymorphism (RFLP) analysis with IS6110, polymorphic GC-rich sequence (PGRS) and direct repeat sequence (DR) probes was applied to the isolates from 398 badgers, and 52 different rflp types were identified. Most of the isolates belonged to seven predominant types, and the other 45 types were represented by few isolates. An analysis suggests that some of these 45 types may have been introduced by the inward migration of badgers and others may have been the result of genetic changes to one of the prevalent types. The badgers were divided into groups on the basis of the sett at which they were captured, and RFLP typing was applied to isolates from two or more badgers from 85 groups. Multiple RFLP types were identified among isolates from 50 of these groups, suggesting that badgers probably moved frequently between group territories.

Quantifying the risk of spread of bovine viral diarrhoea virus (BVDV) between contiguous herds in Ireland.

The control of bovine viral diarrhoea virus (BVDV) mainly focuses on the identification and restriction of persistently infected (PI) animals. However, other transmission pathways can also result in new breakdowns, including the movement of animals pregnant with PI calves (Trojan animals) and the spread of infection between contiguous farms. Contiguous spread is likely an important problem in the BVD eradication programme in Ireland, given the spatial distribution of residual infection, and the highly fragmented nature of land holdings on many Irish farms. In this study, we seek to quantify the risk of BVD spread between contiguous herds in Ireland. Multivariable logistic models were used to estimate the risk of a herd having BVD positive calves in January to June 2014 (the study period) when contiguous to a herd that had at least one BVD positive calf born in 2013. The models included risk factors relating to the study herd and to neighbouring herds. Separate multivariable models were built for each of four "PI-neighbour" factors relating to the presence of BVD+ animals and/or the presence of offspring of PI breeding animals. In total, 58,483 study herds were enrolled. The final model contained the province, the log of the number of calf births born during the study period, the number of cattle purchased between January 2013 and January 2014, and with a two-way interaction between the number of animals of unknown BVD status in the study herd and the PI-neighbour risk factor. When the number of PI-neighbour herds was used as the PI-neighbour risk factor, the odds ratio (OR) associated with the number of PI-neighbour herds ranged from 1.07 to 3.02, depending on the number of unknown animals present. To further explore the risk associated with PI-neighbour factors, the models were repeated using a subset of the study herds (n=7440) that contained no animals of unknown status. The best fitting model including "any PI-neighbour" as the PI-neighbour factor and also contained the log of the number of calf births born during the study period and the number of cattle purchased. The OR associated with "any PI-neighbour" was 1.92 (95% C.I. 1.37-2.70). This study provides the first quantitative information on the risks posed by the presence of BVD+ animals in neighbouring herds and also highlights the importance of clarifying the BVD status of animals that have not yet been tested in the context of the Irish eradication programme.

Temporal trends in the retention of BVD+ calves and associated animal and herd-level risk factors during the compulsory eradication programme in Ireland.

The national BVD eradication programme in Ireland started on a voluntary basis in 2012, becoming compulsory in 2013. The programme relies on accurate identification and prompt removal of BVD+ calves. However, a minority of herd owners have chosen to retain BVD+ animals (defined as still being alive more than seven weeks after the date of the initial test), typically with a view to fattening them to obtain some salvage value. During each year of the programme, additional measures have been introduced and implemented to encourage prompt removal of BVD+ animals. The objective of this study was to describe temporal trends in the retention of BVD+ calves and associated animal and herd-level risk factors during the first three years of the compulsory eradication programme in Ireland. The study population included all BVD+ calves born in Ireland in 2013-2015. A parametric survival model was developed to model the time from the initial BVD test until the animal was slaughtered/died on farm or until 31 December 2015 (whichever was earlier). A total of 29,504 BVD+ animals, from 13,917 herds, were included in the study. The proportion of BVD+ animals that were removed from the herd within 7 weeks of the initial test date increased from 43.7% in 2013 to 70.3% in 2015. BVD+ animals born in 2015 had a much lower survival time (median=33days) compared to the 2013 birth cohort (median=62days), with a year on year reduction in survival of BVD+ calves. In the initial parametric survival models, all interactions with herd type were significant. Therefore, separate models were developed for beef and dairy herds. Overall the results of the survival models were similar, with birth year, BVD+ status, herd size, county of birth and birth month consistently identified as risk factors independent of herd type (beef or dairy) or the numbers of BVD+ animals (single or multiple) in the herd. In addition, the presence of a registered mobile telephone number was identified as a risk factor in all models except for dairy herds with a single BVD+, while the sex of the BVD+ calf was only identified as a risk factor in this model. Significant progress has been made in addressing the issue of retention of BVD+ calves, however, there is a need for further improvement. A number of risk factors associated with retention have been identified suggesting areas where future efforts can be addressed.

A functional and ultrastructural analysis of experimental diabetic rat myocardium. Manifestation of a cardiomyopathy.

The effects of experimental diabetes on cardiac function and ultrastructure were studied in rats that had been diabetic for 6-24 wk. Experimental diabetes was produced by the intravenous (i.v.) injection of 65 mg/kg streptozocin (STZ) into rats 42-43 days old. Diabetic rat hearts perfused at 15 cm H2O on the working heart apparatus demonstrated depressed cardiac function (i.e., lower left ventricular pressure and +/- dP/dt) at 6, 12, and 24 wk of diabetes. Electron microscopic analysis of ventricular myocardium revealed increased lipid deposition from 6 to 24 wk of diabetes and progressive deterioration of the myocardial cell integrity at 12 and 24 wk of diabetes. This deterioration was characterized by loss of contractile protein, vacuolization (swollen sarcoplasmic reticulum), myelin formations, myocytolysis, and contracture bands. These alterations paralleled the depression of cardiac function at 12 and 24 wk of diabetes. There was, however, depressed function at 6 wk of diabetes but no observable alterations in myocardial ultrastructure. Therefore, experimental diabetes produced ultrastructural alterations in the rat heart that manifested themselves only after a demonstrable depression in cardiac function.

Cost-effectiveness of brief psychodynamic-interpersonal therapy in high utilizers of psychiatric services.

BACKGROUND: It is known that a small number of patients with mental health problems have chronic disorders and account for a disproportionate amount of mental health costs. This randomized controlled trial evaluated the cost-effectiveness of psychodynamic-interpersonal therapy vs treatment as usual in patients with mental health problems who were unresponsive to usual treatment. METHOD: Subjects (N = 110) with nonpsychotic disorders unresponsive to 6 months of routine specialist mental health treatment were enrolled in a randomized controlled trial. Sixty-three percent were women, the mean age was 41.4 years, the median duration of illness was 5 years, 68% were unemployed or receiving state benefits because of illness, and 75.5% had a depressive illness. Intervention patients received 8 weekly sessions of psychodynamic-interpersonal psychotherapy. Control patients received usual care from their psychiatrist. Outcome measures included ratings of psychological distress and health status and a detailed economic evaluation. Analysis was conducted on an intent-to-treat basis. RESULTS: Subjects randomized to psychotherapy had a significantly greater improvement than controls in psychological distress and social functioning 6 months after the trial. Baseline treatment costs were similar for both groups. Subjects who received psychotherapy showed significant reductions in the cost of health care utilization in the 6 months after treatment compared with controls. The extra cost of psychotherapy was recouped within 6 months through reductions in health care use. CONCLUSION: These preliminary findings suggest that brief psychodynamic-interpersonal therapy may be cost-effective relative to usual care for patients with enduring nonpsychotic symptoms who are not helped by conventional psychiatric treatment.