Unravelling transmission of Mycobacterium avium subspecies paratuberculosis to dairy calves: results of a lifelong longitudinal study.

Johne's disease (JD) is a chronic disease of ruminants endemic in the UK and other countries and responsible for large economic losses for the dairy sector. JD is caused by Mycobacterium avium subspecies paratuberculosis (MAP), which typically infects calves that remain latently infected during a long period, making early detection of infection challenging. Cow to calf transmission can occur in-utero, via milk/colostrum or faecal-orally. Understanding of the different transmission routes to calves is important in informing control recommendations. Our aim in this longitudinal study was to measure the association between the transmission routes via the dam and the environment on a calf subsequently testing serologically positive for MAP. The study population comprised of 439 UK dairy calves from 6 herds enrolled between 2012 and 2013. These calves were followed up from birth until 2023. At birth individual calf data was captured. During follow-up, individuals entering the milking herd were quarterly tested for the presence of MAP antibodies using milk ELISA. Cox regression models were used to measure the association between exposure from the dam (in-utero and/or colostrum) or from the environment (long time in dirty yard) and time to first detection of MAP infection. An association between calves born to positive dams and probability of having a MAP positive test result remained after excluding potential MAP transmission via colostrum (Hazard ratio: 2.24; 95% CI: 1.14 - 4.41). Calves unlikely to be infected with MAP via the in-utero or colostrum route, had 3.68 (95% CI: 3.68 1.45-9.33) higher hazard of a positive test result when they stayed longer in a dirty calving area. The effect of the dam infection status on transmission to calves precedes the dam's seroconversion and persists after excluding the potential role of transmission via colostrum. The association between time spent in a dirty calving area and probability of a MAP positive test result highlights the role of environmental contamination as a source of infection in addition to the dam.

A Comparison of Dry Period Outcomes after Selective Dry Cow Therapy Carried Out by Farm Staff versus Veterinary Students in a Low-Cell-Count Dairy Herd.

(1) Background: Selective dry cow therapy is widely promoted in many countries worldwide, however, concerns have been raised about the consequences of the unhygienic application of preparations by untrained operators, especially if no antimicrobials are being used, risking deteriorating mastitis outcomes. (2) Method: This study follows up on cows being dried off by farm staff and those dried off by final-year veterinary students and first-year graduate interns in a supervised training session. Subsequent mastitis parameters and culling data in a single herd with a low somatic cell count were evaluated. (3) Results: A total of 316 dry periods were enrolled in the study. There was no significant difference in the percentage of cows showing at least one high SCC reading within 90 days of the following lactation or cows with at least one case of clinical mastitis within the same period, neither in the total nor in the subset of cows dried off without an antimicrobial. Dry period cure rates and dry period new infection rates were similar too, as was the percentage of cows surviving in the herd after six months. The risk of culling within twelve months post-drying off was lower in cows dried off by students, the difference in survival manifesting itself from 150 days post-drying off, which is an unexplained finding. (4) Conclusion: Well-supervised practical training sessions on drying off routine can be responsibly implemented on well-managed commercial dairy herds.

A systematic literature review on the economic impact of endemic disease in UK sheep and cattle using a One Health conceptualisation.

Endemic sheep and cattle diseases represent a constant strain and impact to animal health and welfare, the environment, public health, and the economy. Quantifying this impact helps to inform decisions on surveillance and control of livestock diseases. This systematic literature review had two objectives; to describe the economic impact of endemic sheep and cattle diseases in the United Kingdom using a broad conceptualisation of impact, and to investigate what variables (e.g. medication costs, loss of production) and methods are included in these calculations. The Prisma protocol for systematic literature reviews was followed. Searches were performed in Pubmed, Scopus and Web of Science using selected and trialled search terms. A total of 1129 papers were identified and screened for relevancy; 38 papers were selected for full review extracting and analysing data on disease, impact and methods. From this final selection of papers it was found that; 1) research in this area is mainly focused on the dairy sub-sector, 2) the most mentioned diseases were mastitis and lameness in dairy cattle; bovine viral diarrhoea in beef cattle; and ectoparasites in sheep with reported animal-level costs of £ 77-£ 548/cow/year, £ 26-£ 185/bovine animal/year and £ 40-£ 47/ewe/year, respectively, 3) numerous methods and variables were used to calculate or estimate the economic impact with most studies focussing on the direct producer impacts and less on the wider implications and affected stakeholders; and 4) it was common for studies to look at one disease in isolation rather than consider disease impact on the farm as a whole. It is recommended that future economic impact calculations on livestock disease include wider implications to estimate the true cost of disease. To generate the necessary data, a wider, more inclusive conceptualisation of impact will be needed to support the collection of data and facilitate communication between stakeholders. Systematic health data recording combined with assessment calculations and metrics that allow comparability within or across livestock sub-sectors will increase the informative value of these impact calculations.

In Vitro Supplementation of Copper Modulates the Functional Th1/Th2 Phenotype of Peripheral Blood Mononuclear Cells in Cattle.

This study investigated the association of copper levels and monocyte plasticity between M1 (CD14+ CD16-) and M2 (CD14- CD16++) phenotypes. Five samples of female bovine PBMCs were incubated in 0, 4, 8 and 16 µM copper and stimulated (PPD-A, TLR- 2 ligand (Pam3CSK4), or media alone) before they were washed and stained for cell surface expression analysis by flow cytometry. M1 function was measured through nitric oxide production using a Griess assay. Flow cytometry analysis showed a significant reduction in viability with increased copper (p < 0.001). Increasing copper had a significant impact on CD14 expression (p = 0.026) and in cows older than 4 years copper levels positively affected CD14 expression (p = 0.001), whereas in animals of four years or younger, Cu did not affect the CD14 expression (p = 0.701 and 0.939, respectively). CD14 expression affected both CD16 expression and NO production. For CD16 expression, there was a further significant negative effect of copper levels in cows older than 4 years, NO was not affected by varying copper levels. In our small sample, monocytes in the presence of a higher copper environment showed a stronger M1 support for better cellular immunity which might contain intracellular infections more effectively. To test this, a randomised clinical trial will be required to determine whether copper supplementation could prevent progression to Johne's disease in MAP infected cows.

Closely related Lak megaphages replicate in the microbiomes of diverse animals.

Lak phages with alternatively coded ∼540 kbp genomes were recently reported to replicate in Prevotella in microbiomes of humans that consume a non-Western diet, baboons, and pigs. Here, we explore Lak phage diversity and broader distribution using diagnostic polymerase chain reaction and genome-resolved metagenomics. Lak phages were detected in 13 animal types, including reptiles, and are particularly prevalent in pigs. Tracking Lak through the pig gastrointestinal tract revealed significant enrichment in the hindgut compared to the foregut. We reconstructed 34 new Lak genomes, including six curated complete genomes, all of which are alternatively coded. An anomalously large (∼660 kbp) complete genome reconstructed for the most deeply branched Lak from a horse microbiome is also alternatively coded. From the Lak genomes, we identified proteins associated with specific animal species; notably, most have no functional predictions. The presence of closely related Lak phages in diverse animals indicates facile distribution coupled to host-specific adaptation.

Changing Veterinary Attitudes towards Delivering Biosecurity Advice to Beef Farmers.

Biosecurity advice is an important way veterinarians can help farmers to reduce disease burdens on their farms. Many different factors are at play when delivering this advice, one being veterinary competence and their communication skills. This study looked at the private veterinary practitioners' perceptions of their own competence to deliver biosecurity advice as part of a longitudinal biosecurity project. Their responses were collected in the form of a telephone questionnaire. The results showed significant increases in private veterinary practitioners' responses to comfort (p = 0.022), capability (p = 0.002), and consistency (p = 0.006) as well as an increase of uptake of advice (p = 0.015) as the project progressed. The mean time spent delivering biosecurity advice increased and dropped subsequently, suggesting an initially more thorough and later on a more efficient process. The overall perceptions of the veterinarians of the study were also assessed. The results suggest development of the participating veterinarians following the conscious-competence learning model showing a need to improve the knowledge and training of future generations of private veterinary practitioners in the area of biosecurity with, in particular, an increased focus on the importance of the veterinarian-farmer relationship.

Reproductive Performance and Partial Budget Analysis of a Prostaglandin or a Modified Ovsynch Protocol in Autumn Calving Dairy Herds.

In autumn calving dairy herds, treatment of cattle not observed in estrus prior to the breeding season is common. Routinely, a single prostaglandin or a modified Ovsynch (MOFT) protocol are used-without evidence of their relative effectiveness. This study compares the effects on conception, associated timing, and profitability of administering cows with prostaglandin or MOFT treatment. A hundred and ninety-two Holstein-Friesian cows from three herds without an observed estrus within 28-days before mating start date were randomly treated with d-cloprostenol (PGOD) or an 8-day MOFT protocol. The association of treatment and calving-breeding start-date interval (CBSI) on the risk of conception were investigated. Partial budget, sensitivity analysis, and Monte Carlo simulation was used to assess economic performance, identify critical input variables, and explore the effects of input uncertainties on model output. There was a significant association between MOFT treatment and conception during 21 and 84 days after mating start date, compared to PGOD. MOFT treatment was associated with a mean net benefit of £58.21 (sd £19.42) and £27.29 (sd £17.75) per cow for herds with a fixed or variable dry-off date, respectively. The relative profitability of an MOFT protocol is dependent on its effects on barren rate and herd dry-off strategy.

The Occurrence of Mycobacterium avium Subspecies paratuberculosis Positive Milk Antibody ELISA Results in Dairy Cattle under Varying Time Periods after Skin Testing for Bovine Tuberculosis.

Enzyme-linked immunosorbent assays (ELISA) are used to screen cows for Mycobacterium avium subspecies paratuberculosis (MAP) infections, informing Johne's disease (JD) management practices in dairy herds. The causative agent of bovine tuberculosis (bTB), Mycobacterium bovis, and MAP share multiple antigens. Moreover, Mycobacterium avium subspecies avium is used in the single intradermal cervical comparative tests (SICCT) that are routinely used in early detection of cows infected with bTB. Although these are different types of immune responses, potentially the SICCT may interfere with the levels of MAP antibodies. This study aimed to clarify the relationship between the SICCT-MAP milk ELISA testing interval and apparent prevalence of JD risk statuses. Data from 51 herds were used, totalling 46,738 cow observations. The Poisson models showed that MAP milk ELISA testing at 14 day intervals post-SICCT statistically significantly increased the odds of detecting JD-positive cows compared to JD testing 85+ days post-SICCT. The odds ratio (OR) started at 2.5 in the first 14 day interval post-SICCT, increasing each two-week period to an OR of 4.0 at 57-70 days, to subsequently drop. Additionally, a herd history of bTB increased the odds of detecting JD-positive cows (OR = 1.2); this was relatively limited compared to the magnitude of the post-SICCT effect.

Antimicrobial & antiparasitic use and resistance in British sheep and cattle: a systematic review.

A variety of antimicrobials and antiparasitics are used to treat British cattle and sheep to ensure animal welfare, a safe food supply, and maintain farm incomes. However, with increasing global concern about antimicrobial resistance in human and animal populations, there is increased scrutiny of the use of antimicrobials in food-producing animals. This systematic review sought to identify and describe peer and non-peer reviewed sources, published over the last ten years, detailing the usage of, and resistance to, antimicrobials and antiparasitics in sheep and cattle farming systems in Britain as well as identify knowledge gaps. Applying the PRISMA review protocol and guidelines for including grey literature; Scopus, Web of Science, Medline, and government repositories were searched for relevant articles and reports. Seven hundred and seventy titles and abstracts and 126 full-text records were assessed, of which 40 scholarly articles and five government reports were included for data extraction. Antibiotic usage in sheep and cattle in Britain appear to be below the UK average for all livestock and tetracyclines and beta-lactam antibiotics were found to be the most commonly used. However, the poor level of coverage afforded to these species compared to other livestock reduced the certainty of these findings. Although resistance to some antibiotics (using Escherichia coli as a marker) appeared to have decreased in sheep and cattle in England and Wales over a five-year period (2013-2018), levels of resistance remain high to commonly used antibiotics. The small number and fragmented nature of studies identified by this review describing anthelmintic usage, and the lack of available national sales data, prevented the identification of trends in either sheep or cattle. We recommend that additional efforts are taken to collect farm or veterinary level data and argue that extraction of this data is imperative to the development of antimicrobial and antiparasitic resistance strategies in Britain, both of which are needed to reduce usage of these anti-infective agents, curb the development of resistance, and safeguard national agricultural production. Finally, metrics produced by this data should be generated in a way to allow for maximum comparability across species, sectors, and countries.

The Effect of Iron Dextran Injection on Daily Weight Gain and Haemoglobin Values in Whole Milk Fed Calves.

Anaemia caused by iron deficiency has long been reported in dairy calves. This study investigated iron deficiency anaemia on UK dairy farms feeding whole milk and evaluated the effect of iron supplementation on the daily weight gain (DG) and haemoglobin (Hb) levels of these calves. Two-hundred-and-thirty-seven calves were enrolled across six farms. At enrolment, calves were randomly allocated to either receive treatment with iron injection (INJ; n = 120) consisting of 5 mL (1 g iron) of iron dextran (Uniferon 20% Injection, Pharmacosmos) or no injection, control (CON; n = 117). Calves were blood-sampled for Hb and total proteins and weighed at weeks one, six and 12 of age. Iron had a significant effect on DG from one to six weeks, with an average 78 g/d (SD 18 g/d, n = 188, 95% Confidence interval: 44-112 g/d, p < 0.001) DG increase in the INJ calves. Iron had a significant effect on Hb concentration at six weeks between the INJ group and CON group (110.7 (SD 12.4) versus 94.9 g/L (SD 13.2), respectively). Calves with a higher growth rate from one to six weeks were more likely to have low Hb levels at six weeks. There was farm variation in both Hb levels and DG, however, despite this, there was an effect of iron across all farms.

Minimally Invasive Markers of Stress and Production Parameters in Dairy Cows before and after the Installation of a Voluntary Milking System.

Automatic milking systems (AMS) are a low-labour alternative to conventional parlours, with previous studies demonstrating that cows vary in their ability to cope with the change to AMS. Cortisol expression can be combined with other measures to assess stress: saliva and hair have the advantage of requiring minimally invasive sampling. No work has investigated the long-term impact of introduction of AMS. The aims of the study were to assess short-term and chronic stress associated with a change in milking system by measuring salivary and hair cortisol levels and to assess the impact on health and production parameters. Cows from one farm changing their milking system were recruited to the study and sampled for saliva (n = 10) and hair (n = 12) before and after installation. Cortisol levels were measured using a salivary cortisol enzyme immunoassay kit. Body condition, lameness and milk parameters of the whole herd were regularly assessed. Salivary cortisol showed no diurnal pattern but was affected by lameness and gestation. Non-lame cows showed a reduction in salivary cortisol after AMS introduction (p < 0.001). Hair cortisol levels increased after AMS, but it was unclear if this change was seasonal. Milk yield increased by 13% and somatic cell count reduced by 28%. Body condition score was consistently good, but lameness remained high throughout the study. Production values alone do not represent high welfare. The high lameness and associated cortisol levels suggest that cow stress requires consideration when changing milking systems.

Randomised Control Trial Comparing Cypermethrin-Based Preparations in the Prevention of Infectious Bovine Keratoconjunctivitis in Cattle.

Infectious bovine keratoconjunctivitis (IBK) caused by Moraxella bovis is commonly seen in the summer months spread by face flies. This trial investigated the difference in incidence of IBK cases from natural exposure between two groups of animals, one treated with Cypermethrin pour-on preparation (PON, n = 98) and one with Cypermethrin impregnated ear tags (TAG, n = 99). Daily Live Weight Gain (DLWG) difference was investigated between animals with cases and those without and between treatment groups. A randomised positive control study, enrolled 197 animals split into two treatment groups. Cases of IBK and DLWG were recorded over the grazing season (April-November 2018). Fifty-four cases of IBK were recorded. There was no association between the two treatment groups (p = 0.362) and case status. Breed and under 12 months old were significant factors for having a case; (OR 2.3, p = 0.014 and OR 3.5, p < 0.001 respectively). There was no difference in DLWG between animals that had a case and animals that had not (p = 0.739) or between the two treatment groups (p = 0.215). Based on our results, there is no significant difference between PON or TAG preparations in the prevention of IBK. Younger animals and white-faced breeds are significantly more likely to suffer with IBK.

Mycobacterium avium subspecies paratuberculosis seroconversion in dairy cattle and its association with raised somatic cell count.

This retrospective case-control study investigates the relationship between seroconversion to Mycobacterium avium subspecies paratuberculosis (MAP) and raised somatic cell count (SCC). The study consists of 112 case cows from three dairy farms in the UK; for each case cow with a positive antibody titre, there was a seronegative control cow for comparison. Seroconversion was monitored using milk ELISA antibody titres for MAP taken at quarterly intervals. SCCs were recorded at the time a positive antibody titre was first recorded as well as at the previous and subsequent milk recording in order to explore a temporal relationship between the two events. The previous and subsequent milk recordings were a month before and after seroconversion was identified. The results showed that cows that were infected with MAP had an increased SCC around the time that they first became seropositive, providing evidence for a temporal relationship between the two events; high SCCs were particularly prevalent before and at the time of first detecting seroconversion. The explanation is being discussed that potentially an underlying, currently not studied, factor may be predisposing both events, the progression of paratuberculosis is predisposing the host to mastitis, or indeed intramammary infections help initiate paratuberculosis progression.

Risk of Lameness in Dairy Cows with Paratuberculosis Infection.

Johne's disease (JD) is an important disease affecting the UK dairy industry, as is cattle lameness. An association between JD and lameness has been suggested; however, little evidence exists to support this. The purpose of this study was to determine if cows affected by JD were more likely to be lame and if so, what the temporal association is. Retrospective dairy cow mobility and JD status (based on milk ELISA) data were obtained from two farms of 98 JD cows (49 high and 49 medium positive) and their matched controls. We evaluated the timing and the proportion of (chronic) lameness in JD-positive cows versus controls and proportion of lameness before and after the first ELISA positive test. Compared to their controls, JD cows are lame more often (Odds Ratio = 2.7 (95% Confidence Interval = 1.2-6.0) p = 0.017) and became lame on average three months earlier (p = 0.010). High positive cows were more likely to develop lameness after seroconversion (OR = 2.8 (95% CI = 1.1-7.5), p = 0.038) versus medium positive cows. Results of this study suggest that there is a link between JD and lameness and that JD precedes lameness. The underlying mechanisms for this association remain unknown and were not the scope of this study.

Development of clinical sign-based scoring system for assessment of omphalitis in neonatal calves.

Omphalitis contributes significantly to morbidity and mortality in neonatal calves. Diagnosis of omphalitis is based on the local signs of inflammation-pain, swelling, local heat and purulent discharge. An abattoir trial identified an optimal, sign-based, scoring system for diagnosis of omphalitis. A sample of 187 calves aged between 7 and 15 days old were clinically examined for signs of umbilical inflammation and compared with postmortem examination of navels. On postmortem findings, 64 calves (34.2 per cent) had omphalitis. In the examined omphalitis cases, the most commonly affected umbilical structure was the urachus (78.1 per cent). Multivariable logistic regression revealed that thickening of the umbilical stump over 1.3 cm (P<0.001), discharge (P<0.001), raised local temperature (P=0.003) and the presence of umbilical hernia (P=0.024) were correlated and positive predictors of omphalitis. Discharge from the umbilical stump was associated with intra-abdominal inflammation (P=0.004). Assigning weights based on the multivariable logistic regression coefficients, a clinical scoring algorithm was developed. The cumulative score ranged from 0 to 9. Using this scoring system, calves were categorised as positive if their total score was ≥2. This scoring method had a sensitivity of 85.9 per cent, specificity of 74.8 per cent and correctly classified 78.6 per cent of all calves.

Herd-level prevalence of selected endemic infectious diseases of dairy cows in Great Britain.

To implement appropriate and effective disease control programs at the national level, up-to-date and unbiased information on disease frequency is needed. The aim of this study was to estimate the prevalence of selected endemic infectious diseases in the population of dairy herds in Great Britain. Bulk milk tank (BMT) samples from 225 randomly selected dairy farms, stratified by region and herd size, were tested for antibodies against bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1, Mycobacterium avium ssp. paratuberculosis, Leptospira Hardjo, Salmonella spp., Coxiella burnetii, Fasciola hepatica, Neospora caninum, and Ostertagia ostertagi. Furthermore, the presence of BVDV, C. burnetii, and Chlamydia-like organisms was determined by PCR. The apparent herd prevalence was estimated as a weighted proportion of positive herds. The true prevalence was calculated when a test was used with known test characteristics for the cut-off value used. Among unvaccinated herds, the true prevalence of BMT antibodies against BVDV was estimated at 66% [95% confidence interval (CI): 56-77%], M. avium ssp. paratuberculosis 68% (95% CI: 59-77%), bovine herpesvirus type 1 62% (95% CI: 52-73%), Leptospira Hardjo 47% (95% CI: 34-60%), and Salmonella spp. 48% (95% CI: 39-56%). The apparent prevalence of BMT antibodies against C. burnetii was 80% (95% CI: 75-85%), F. hepatica 55% (95% CI: 48-62%), N. caninum 46% (95% CI: 38-54%), and O. ostertagi 95% (95% CI: 91-98%). The BVDV, C. burnetii, and Chlamydia-like antigens were detected in 5 (95% CI: 2-9%), 29 (95% CI: 21-36%), and 31% (95% CI: 24-38%) of herds, respectively. Our results show that dairy cows across GB are frequently exposed to the studied pathogens, which are endemic at high levels with some geographical variations. These prevalence estimates provide a much-needed basis to assess whether nationwide control programs for the studied pathogens are justified by their potential economic, environmental, and public health implications. Should surveillance and control programs be initiated, the estimates presented here are a baseline against which progress can be assessed.

Erratum to: Monitoring cow comfort and rumen health indices in a cubicle-housed herd with an automatic milking system: a repeated measures approach.

[This corrects the article DOI: 10.1186/s13620-015-0040-7.].

Monitoring cow comfort and rumen health indices in a cubicle-housed herd with an automatic milking system: a repeated measures approach.

BACKGROUND: Cow rumination and lying behaviour are potentially useful and interrelated indicators of cow health and welfare but there is conflicting evidence about how reliable these measures are. The objective of this study was to quantify the variation of indices of cow comfort and rumen health in a herd with an automatic milking system for which husbandry was relatively constant, in order to propose an alternative approach to optimising the use of these indices when continuous monitoring is not available. During a period of 28 days, standing index, cud chewing index and rumination index were observed. RESULTS: The daily mean standing index ranged between 9.0 and 18.0 per cent, cud chewing index between 43.5 and 74.0 per cent, and rumination index between 49.0 and 81.0 per cent. The point of lowest variation in the indices was determined as that with the lowest coefficient of variation. The coefficient of variation was lowest for data collected between 240 and 270 minutes after refreshing of the bedding material on the cubicles for both the standing index and rumination index, and for data collected between 120 and 150 minutes after refreshing of the bedding material on the cubicles for the cud chewing index. CONCLUSIONS: In spite of relative constant husbandry practices in a herd with an automatic milking system, the variation in the standing index, cud chewing index and rumination index was still considerable. This suggests these measures should be repeated on several consecutive days, according to population size and wanted margin of error, to be representative and useful.

Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent.

BACKGROUND: Various clinical protocols have been developed to aid in the clinical diagnosis of classical bovine spongiform encephalopathy (BSE), which is confirmed by postmortem examinations based on vacuolation and accumulation of disease-associated prion protein (PrPd) in the brain. The present study investigated the occurrence and progression of sixty selected clinical signs and behaviour combinations in 513 experimentally exposed cattle subsequently categorised postmortem as confirmed or unconfirmed BSE cases. Appropriate undosed or saline inoculated controls were examined similarly and the data analysed to explore the possible occurrence of BSE-specific clinical expression in animals unconfirmed by postmortem examinations. RESULTS: Based on the display of selected behavioural, sensory and locomotor changes, 20 (67%) orally dosed and 17 (77%) intracerebrally inoculated pathologically confirmed BSE cases and 21 (13%) orally dosed and 18 (6%) intracerebrally inoculated but unconfirmed cases were considered clinical BSE suspects. None of 103 controls showed significant signs and were all negative on diagnostic postmortem examinations. Signs indicative of BSE suspects, particularly over-reactivity and ataxia, were more frequently displayed in confirmed cases with vacuolar changes in the brain. The display of several BSE-associated signs over time, including repeated startle responses and nervousness, was significantly more frequent in confirmed BSE cases compared to controls, but these two signs were also significantly more frequent in orally dosed cattle unconfirmed by postmortem examinations. CONCLUSIONS: The findings confirm that in experimentally infected cattle clinical abnormalities indicative of BSE are accompanied by vacuolar changes and PrPd accumulation in the brainstem. The presence of more frequently expressed signs in cases with vacuolar changes is consistent with this pathology representing a more advanced stage of disease. That BSE-like signs or sign combinations occur in inoculated animals that were not confirmed as BSE cases by postmortem examinations requires further study to investigate the potential causal relationship with prion disease.

Farm practices to control E. coli O157 in young cattle--a randomised controlled trial.

A randomised controlled trial was used to investigate the effect of three complex management intervention packages to reduce the burden of E. coli O157 in groups of young-stock on cattle farms in England and Wales. All intervention farms were assigned measures to avoid buying in new animals and having direct contact or sharing water sources with other cattle. Furthermore, package A (7 farms) aimed to keep a clean environment and closed groups of young-stock; package B (14 farms) aimed for improved water and feed hygiene, whilst package C was assigned both A and B. The control farms (26 farms) were asked not to alter their practices. Farms, which were assigned intervention package A, exhibited a 48% reduction in E. coli O157 burden over the 4.5 months (average) of observation, compared to 18% on the control farms. The effect of package A compared to the control farms in a crude intention-to-treat model was RR = 0.26 (p=0.122). When the risk ratio was adjusted for actual application of the different measures, the effect of intervention package A became stronger and statistically significant (RR = 0.14 p=0.032). Statistical evidence (p< 0.05) showed that dry bedding and maintaining animals in the same groups were the most important measures within the package and weak evidence (p< 0.1) showed that a closed herd policy and no contact with other cattle may also be of importance. Compliance with the other measures in package A had no influence on the effect of the package. No evidence of effect of the other two intervention packages was found.