Work Package Livestock production, health, welfare and disease control
Introduction
Embedded within the overall theme of livestock production, health, welfare and disease control, is the science of epidemiology: the study of the occurrence of diseases within populations and ultimately seeks to provide better ways to preventing or control target diseases.The skills and resources to gather and analyse large data sets from a variety of sources provides us with the means to understand the epidemiology of given diseases. In this programme of research we use these skills to help with identification of threats, rapid disease detection, adoption of strategies to minimise the risk of infection, application of measures to prevent spread and these are adopted to a contribute to sustainable livestock systems and to explore potential threats to public health.
The ever-increasing global focus on our use of antimicrobials (AMU) in livestock systems and associated antimicrobial resistance (AMR) with the implications for human health, also fall within the remit of Research Deliverable 2.2.6. (RD 2.2.6). In addition to exploring behaviours in relation to AMU reasons for reluctance or failure by livestock producers to adopt alternative and recommended strategies for disease control are wide ranging.The work within RD 2.2.6 therefore recognises the need to better understand these socio/economic factors and seeks to identify pathways to break these barriers down.
Aim of Research
To advance our knowledge of how to improve disease control strategies through epidemiological and socio-economic approaches. This includes research into the spread of important, targeted, endemic pathogens and antimicrobial resistance (AMR) via livestock and the environment including transmission of such pathogens to humans.
In order to achieve this, we will more specifically:
- analyse existing, large data sets to improve knowledge of the threat of disease incursion and to aid the rapid detection of endemic livestock diseases.
- investigate new strategies for disease control and investigate two zoonotic pathogens (Verotoxigenic Escherichia coli (VTEC) and Cryptosporidium parvum) with the aim of minimising human exposure.
In addition, we will improve understanding of antimicrobial resistance and finally put recently developed, novel diagnostic tools to use in the spheres of identifying abundance of pathogen populations and provide methods to help treat internal parasites (worms) in lambs.
Progress
Our four Scottish partner Institutes worked with a wide range of collaborating scientists, including the EPIC Centre of Expertise and International collaborators from the EFSA funded STOC-FREE consortium, to improve measurement and control of animal diseases. This included epidemiological investigations into major emerging disease that might transmit from animals to humans. We developed approaches to specifically analyse existing, large data sets to help improve knowledge of the threat of disease incursion; to aid the rapid detection of endemic livestock diseases and we improved understanding of antimicrobial resistance in livestock. To achieve all this our research deliverable orchestrated an unusually wide range of science disciplines, both qualitative and quantitative as it must to provide practical impact. Despite the extension of the Covid19 pandemic the work has generally progressed well. The extension into year 2021-22 has provided the opportunity to complete field studies precluded in the previous year. The additional time allowed much of the research output to be reported to stakeholders to help protect human health and assist livestock keepers maintain Scotland’s deserved reputation for production of high quality, safe and environmentally sound products.
Highlights
- Improved analysis of large datasets helped enhance the design of targeted surveillance for endemic livestock diseases in Scotland.
- Advice about the need to modify sampling strategies was provided to survey providers, and the potential to investigate indirect impacts of sheep scab control policies was described.
- The need for behaviour change interventions to be cognisant of local context in order to be effective was identified in a qualitative study of the experiences of cattle farmers and vets in south-west Scotland with the Bovine Viral Diarrhoea Eradication Programme.
- Value was added to the research on improved disease control from earlier years of this programme with results delivered to stakeholders: new and refined strategies for disease detection (parasitic fluke, exotic pig disease), prevention and control (bovine viral diarrhoea in cattle, endemic and zoonotic pig diseases, antimicrobial resistance via reduction in antimicrobial use).
- Scientists demonstrated that there is sufficient evidence and industry engagement to warrant Government support for a porcine reproductive and respiratory syndrome control programme in the Scottish pig sector. This is now being implemented.
- Qualitative studies comparing the antibiotic prescribing behaviours of rural general practice doctors and veterinary surgeons highlighted both common and unique challenges for prescribers. Presented in a report to Scottish Government science-policy advisors, these provide an improved understanding of the vet’s role in facilitating antimicrobial usage from a remote and rural practice perspective.
- Environmental DNA analyses for liver fluke, rumen fluke and mud snail worked quite well in the laboratory, but proved not to be sufficiently robust when applied to field samples. Risk assessment is therefore still best done by testing faeces from grazing animals and identifying suitable mud snail habitat, species identity and fluke infection status.
- A vaccine trial based on the sheep scab transmission model was completed successfully following covid linked delays and the resulting report presents the implications for how the vaccine can best be used as part of a future coordinated control strategy for sheep scab.
- Research into the highly important problem of antimicrobial resistance (AMR)progressed on several fronts including: A new approach to AMR measurement “Quantitative Estimation of Population AMR” (QEPA) was developed and validated and has been presented to the scientific community. A longitudinal study exploring AMR transmission associated with use of sewage sludge as fertilizer was analysed and results so far indicate a low risk of spread.
This Research Deliverable combines the expertise of four partner Institutes working with a wide range of partners including the EPIC Centre of Expertise and International collaborators from the EFSA funded STOC-FREE consortium. The overall focus is on measuring and controlling animal diseases and epidemiological type investigations into major zoonotic pathogen risks plus antimicrobial resistance. The work orchestrates an unusually wide range of science disciplines, both qualitative and quantitative as it must to provide practical impact. Despite the Covid19 pandemic the work has generally progressed well. Field studies not completed by early 2020 have indeed been impeded but extension into year 2021-22 has provided the opportunity to complete these projects. Much of this research is in the process of being reported now to our stakeholders to help livestock keepers maintain Scotland’s deserved reputation for production of high quality, safe and environmentally sound products.
Highlights
- The method for measurement of AMR hugely affects results: a novel lab/statistical method that enumerates bacterial density and the proportion that are resistant was developed. The method was subsequently tested using faeces using structured studies involving two distinct groups of dairy calves. Very low within group but very high between group variation was demonstrated. Such differences may be due to group-level factors relating to previous antimicrobial exposure or within-group transfer of AMR. Interventions will now be explored to help minimise animal and human AMR exposures.
- Bayesian inference of on farm disease dynamics from mortality data: pathogens such as African swine fever virus (ASFV) are an increasing threat to global livestock production. Quantification of epidemiological parameters, such as within-farm transmission rates and latent and infectious periods is critical to inform efficient disease control. Routinely collected livestock mortality data is a potential source of readily available and representative information regarding disease transmission early in outbreaks. We develop methodology to make use of such data and test it by inferring epidemiological parameters for ASFV using data from outbreaks on 9 farms in the Russian Federation. Our methodology performs better than current methods, quantifies transmission within-farm and from external sources, and allows combination of data across multiple herds, improving inference. The approach could be applied to other outbreaks or pathogens.
- Advanced statistical methods were used to analyse data from the Scottish bovine viral diarrhoea (BVD) eradication programme to inform improved BVD Control. Farms close to each other are more likely to share staff, equipment, animals and grazing ground. There is an increased likelihood of the incidence of over the fence contact and mixing of animals from the different herds. The result of these and other management associated risk factors is that transmission of BVD virus is more likely across neighbouring farms resulting in clusters of farms with similar BVD infection status. Using data from the Scottish BVD eradication program, we investigated the existence of clusters of BVD positive farms and how the clusters developed and changed as the eradication program progressed. This has helped inform better targeted control.
- Difficulties arise for between farm trade because of the differences in disease status arising from non-European Union (EU) regulated national or regional disease-free programmes. The Pan European STOC FREE project uses bovine viral diarrhoea virus (BVDV) in cattle as an exemplar; and Scottish BVD eradication as a comparative case study. International trade in livestock is also hampered where informed comparison of animal BVD status by livestock traders is impossible. Variable eradication approaches have led to differences in definition of and in the way disease free status is assigned. STOC-FREE has explored these issues and aims to enable comparisons to be made between countries to facilitate trade. Statistical models using data from several European countries have been established and generated estimates for the confidence that trading herd might be truly free of BVD. The method is transferable to different diseases in multiple species
- Research demonstrates that some environmental E. coli associated with plants and soil contain virulence genes including antibiotic resistance and toxins that are encoded on mobile elements (plasmids; bacteriophage), which helps to explain the presence of zoonotic E. coli (STEC) on plants.
- Using a combination of fluke egg counting in faecal samples taken from sentinel sheep, and mud snail PCR screening to determine species identification and fluke infection status, we have been able to show that the liver fluke risk to livestock associated with conservation grazing around wader scrapes at SRUC Kirkton & Auchtertyre, is currently relatively low, compared to neighbouring in-bye fields. This research features as a case study on the SEFARI website and is included in a Fluke Risk & Conservation Grazing Guide, currently in production.
- Researching farmer behaviour in relation to the livestock disease control: farmers views can be useful to inform how the government can best influence and support policy driven behaviour change and support eradication of diseases such as Johne’s disease and BVD. There is a lack of homogeneity on many topics (which reflects diversity within the sector), except for ‘advice and guidance’ which farmers want to be simple, concise, tailored, and respectful. In relation to government funding, some farmers felt this should prioritise stability while others wanted it to be used for practical measures to increase productivity and profit, reduce waste, and benefit health.
This Research Deliverable (RD) explores many facets of “Animal Disease Epidemiology” and demonstrates the wide ranging combined applied research capability within the Research Institutes collaborating on this RD. We are investigating the epidemiology of many important livestock endemic and epidemic diseases including external parasites (sheep scab) viral diseases (BVD, AI, ASF), bacterial infections (VTEC), and internal parasites (cryptosporidia, liver fluke). Beyond the specific diseases, research into new approaches and methodologies - such as the development of new tools (statistical models) to help measure and control animal diseases - are embraced within this important RD. Many of the diseases under exploration are considered zoonotic pathogens: cryptosporidia, salmonella, VTEC, plus antimicrobial resistance. The research involves four collaborating Scottish Institutes with some further Scottish level and European level interaction with for example, partners in the European Food Standard Agency funded STOC-FREE project and the EPIC Centre of Expertise on Disease Outbreaks. This Research Deliverable is now focussed in the fourth year, on delivery of applied outputs (including policy briefs and refereed journal publications plus the provision of: new methods; new vaccines and new tests) to help livestock stakeholders maintain Scotland’s deserved reputation for the production of high quality, safe and environmentally sound products.
Highlights
- Policy Brief : Critical control points for Scottish BVD Eradication Scheme: Retention of Bovine Viral Diarrhoea Virus (BVDV) positive bovines within cattle herds.
- Active collaboration EFSA Sound Control project featuring Scottish BVD control as case study for surveillance systems https://sound-control.eu/wp-content/uploads/2019/11/Deliverable-1.1-version-7.pdf coupled to our “overview of non-regulated cattle diseases in the European Union for which control programmes (CPs) are in place within member states (MS)" delivered to SG
- Policy brief delivered to SG complemented with a refereed paper "Use of sheep movement data to inform slaughterhouse based surveillance design and interpretation: the case of antimicrobial resistance" published in Frontiers in Veterinary Science.
- Social Science research has been escalated over the period and outputs include two reports on "The views of farmers and vets about BVD” and "The views of farmers and vets about Johne's disease" with examples of presentations: “Tackling Isolation and Fostering Connections" to the Scottish Rural Mental Health Conference at UHI Inverness and “Positive and negative health impacts of experiences associated with livestock veterinary practice” presented to the UK Mind Matters Symposium in London.
- A concerted focus of research on Antimicrobial Resistance (AMR) and Antimicrobial Usage (AMU) within the SEFARI SRP programme presented to key Scottish government staff at a Workshop in Perth complimented with briefing material such as the Science Brief - "Results of Analysis of novel method to determine level of anti-microbial resistance in a single sample"
- A dataset established to include Hutton-derived E. coli isolates combined with the UK samples, via a public database (www.enterobase.co.uk) to enable UK wide collaboration researching potentially zoonotic environmental E. coli.
- Guidelines, aimed and livestock keepers and other interested stakeholders, have been compiled and disseminated by internet and leaflet on the control of the zoonotic protozoa cryptosporidia.
- More academic, but highly critical research, that infers parameter values characterising within farm transmission of African Swine Fever including uncertainty quantification for use in subsequent analysis.
- A plethora of new tests have been developed for a wide range of livestock parasites within host and within the environment.
The progress for the research undertaken on the Research Deliverable is wide ranging, involving disease threats to cattle, sheep and pigs as well as to humans, so to ease comprehension the strands are presented together as follows:
Zoonotic diseases (infectious diseases that can be transmitted between animals and humans and vice versa) includes research into verocytotoxigenic E. coli (VTEC) and cryptosporidium. We have explored the genetic basis as to why some VTEC isolates are more successful at surviving and persisting in the environment. Genetically divergent E. coli isolates were identified, so providing evidence of an extensive E.coli gene pool. Research into the parasite Cryptosporidium parvum suggested that adult cattle might not be a major source of transmission of to their calves as was previously believed.
Antimicrobial resistance (AMR) in livestock is seen as a potential hazard to human health. On a positive note, AMR levels in bacteria from clinical cases of mastitis in sheep were found to be low. The geographic picture of AMR created from analysis of soil samples collected from across Scotland (Yrs 1 and 2) was overlaid with soil metadata and land management providing a reflection of the impact of agricultural practices on resistance. Research into methods that quantify the variation of AMR at different levels, for example animal compared to farm, were shown to help identify likely causes of AMR. In addition, a comparison of different methods used to test for AMR were extended to samples from different species and confirmed that there are differences in prevalence between host species.
Exploring ways to control diseases currently found/present in Scottish livestock, endemic diseases, focussed on viral and parasitic diseases of both cattle and sheep. The researchers help support the government’s strategy to eradicate bovine viral diarrhoea virus (BVD) from our cattle herd. Spatial cluster models developed to inform detection of the source of BVD virus in positive herds towards the end of the eradication scheme have been accepted for publication. The Scottish BVD eradication scheme has been used as an exemplar to help develop a Europe-wide framework to assist in providing confidence for disease-free cattle trading between certain countries and funding is matched to work in this RD. Linked to this work a more general survey targeting vets and farmers to identify barriers to disease control was conducted.
Research into endemic parasitic diseases of sheep included analyses of data from the sheep scab transmission study trials previously reported with a model on the transmission dynamics constructed to allow novel interventions to be tested. Samples from lambs infected with gastrointestinal nematode worms were separated for a “high” or “low” wormer need (to deal with a specific worm challenges) and the results were analysed and compared. Liver fluke are an increasing problem so the application of methods developed in this RD, associated with the stages to target in the liver fluke life cycle have been presented and discussed with Stakeholders. Environmental DNA assays were evaluated and shown to hold great promise for environmental applications.
Data derived at population level has also been analysed including farm mortality data associated with disease outbreaks– specifically African Swine Fever (ASF) in pigs – and has been shown to give reliable estimates for potential outbreak characteristics. Sheep movement data has identified key options for future surveillance strategies.
Analysis of research data suggested that sampling for E.coli O157 pre-slaughter is not a reliable indicator of the identification of high contamination of cattle or sheep carcases for human consumption. Progress was made on distinguishing if environmental verocytotoxigenic E. coli (VTEC) is of a bovine or human source. The Salmonella model developed in Year 1 was used to identify the most effective intervention to reduce bacterial shedding. Different methods used to test for antimicrobial AMR in both fresh and stored (cattle) faecal samples produced different results, suggesting freezing and long term storage of samples was of limited value. Using a range of soil samples collected from across Scotland, a model was developed to explore AMR in the environment. A ‘Resistant Gene’ atlas for Scotland was created identifying hot spots. Widespread resistance to Vancomycin detected.
Research into endemic disease provided information to Scottish Government in relation to the distribution of the retention time of BVD positive cattle to assist with the administration of the latter stages of the Scottish BVD eradication scheme. The team increased the number of environmental sampling techniques to quantify the risk of liver fluke to grazing livestock. Developed prototype environmental DNA assays for liver fluke and the associated mud snail. Developed methods for extracting and amplifying fluke DNA. Developed methods to assess the viability of liver fluke cysts in forage. Other work differentiated Cryptosporidium parvum species from a range of farmed animal sources. Targeted Selective Treatment (TST) studies demonstrated that anthelmintic support for lambs within a flock to reach similar liveweight gains varied significantly. By transmission study trials, we increased our understanding of the transmission of Psoroptes ovis – the mite responsible for sheep scab. Methodology developed in Year 1 to model TB control was trialled and it is now possible for analysis to account for individual animals and their life history events.
A very diverse RD deals predominantly with using epidemiological methods to evolve new ways of measuring disease in livestock populations and epidemiological approaches to establishing improved control. Research was initiated into zoonotic diseases and to establish barriers to farmer and veterinary behaviours that impede better adoption of control strategies. Initial effort was focussed on developing epidemiological tools to control zoonotic diseases, to determine if the presence of E.coli O157 in an animal prior to slaughter can be an indicator of a later risk to human health and to investigate the hypothesis that the environmental persistence of E.coli is dependent upon a specific set of gene. In addition, developing verified Cryptosporidium parvum DNA based control material for use in diagnostic tests and adapting a within-herd Salmonella transmission model for use under Scottish pig production systems. Steps were taken to identify the prevalence of antimicrobial resistance in samples from Scottish cattle populations.
In relation to endemic livestock disease, information was provided to Scottish Government to assist with the development of the Scottish bovine viral diarrhoea (BVD) eradication scheme. Different methods to determine liver fluke risk were evaluated including a method of testing environmental samples for liver fluke infection on pastures. Big data approaches were used to describe Scottish sheep movement relating to the slaughter population and acknowledging that diagnostic test results for TB do not take historical or movement data into account, outbreak data was used to develop a model that gives better estimates for disease transmission.
Future Activities
Much of the word from RD 2.2.6 will now be progressed and continued within the next Strategic Programme (2022-2027). Areas such as antimicrobial resistance and usage will be researched within defined Topics within specific Research Questions along with elements of farmer behaviors; zoonotic disease (involving ticks and fluke) and food hygiene.
Selected Outputs
- Report: “The Pig Industry Medicines Hub”.
- Relating growth potential and biofilm formation of Shigatoxigenic Escherichia coli to in planta colonisation and the metabolome of ready-to-eat crops doi: https://doi.org/10.1101/523175
- Influence of Plant Species, Tissue Type, and Temperature on the Capacity of Shiga-Toxigenic Escherichia coli To Colonize, Grow, and Be Internalized by Plants doi: https://doi.org/10.1128/AEM.00123-19
- An empirical comparison of isolate-based and sample-based definitions of antimicrobial resistance and their effect on estimates of prevalence. https://www.sciencedirect.com/science/article/pii/S0167587717300272
- Difficulties arising from the variety of testing schemes used for bovine viral diarrhoea virus (BVDV). http://dx.doi.org/10.1136/vr.103329
- Insights for the assessment of the economic impact of endemic diseases: specific adaption of economic frameworks using the case of bovine viral diarrhoea. https://doi.org/10.20506/rst.36.1.2624
- Research Brief to Scot Gov on 23/08/17 – “Retention of BVDV persistently infected bovines on farms: consequences for BVD eradication scheme.”
- Research Brief "Where do PI bovines die? Analysis of the BVD eradication scheme data" sent to Scot Gov on 1/12/17.
- Draft Policy Brief, “Determining herd level disease status by spot test screening young stock for antibodies - optimising the number of animals to test and cut points for BVDV" sent to Scot Gov on 15/8/2107.
- Strategies for screening young stock for antibodies - optimising numbers to test, cut-points, & predictive values for bovine viral diarrhoea virus. https://doi.org/10.1038/s41598-018-27870-
- Patchy promiscuity: machine learning applied to predict the host specificity of Salmonella enterica and Escherichia coli. https://dx.doi.org/10.1099%2Fmgen.0.000135
- Publication: A description and qualitative comparison of the elements of heterogeneous bovine viral diarrhea control programs that inflence confidence of freedom.
- Publication: Standardizing output-based surveillance to control non-regulated cattle diseases: Aspiring for a single general regulatory framework in the European Union.
- Publication: Genetic diversity and shedding profiles for Cryptosporidium parvum in adult cattle and their calves.
- Publication: Antimicrobial resistance in ovine bacteria: A sheep in wolf's clothing?
- Preprint: A modelling framework for the prediction of the herd-level probability of infection from longitudinal data.
- Animation: Ectoparasite informative animation Stop the Creeps on Sheep
- https://sefari.scot/blog/2021/04/12/why-we-need-to-consider-the-role-of-plants-in-the-spread-of-zoonotic-pathogens
- Government Briefing document: Can the Stoc Free model be used for the analysis of paratuberculosis data JI Eze, RW Humphry, M Henry, GJ Gunn