Role of transmission and pathogen components in virulence and disease pathogenesis for important endemic diseases of livestock in Scotland
Project Lead
Challenges
For the important infections and diseases affecting Scottish livestock production, we do not have a full understanding of how the pathogens are distributed or transmitted to their host animal, what key pathogens and components are important for infection and disease, and how these components interact with the host immune system. Two major diseases affecting cattle production in Scotland are bovine pneumonic pasteurellosis and Johne’s disease.
Pneumonic pasteurellosis
Pneumonic pasteurellosis is caused by Pasteurella multocida and results in significant production losses and mortality. No vaccines are available in Europe. Live vaccines in the United States provide a short duration of immunity and may exacerbate the disease. Extensive pulmonary damage occurs before clinical signs are evident. Therefore, an effective vaccine would offer more opportunities to instigate treatment to prevent lung damage.
Johne’s Disease
Johne’s Disease (JD) is caused by Mycobacterium avium subspecies paratuberculosis (MAP) and affects cattle, sheep, and goats. Ruminants often become infected in their first few months of life, via contaminated teats or the mother’s milk. MAP is shed in the faeces of infected livestock as well as wildlife reservoirs, contaminating the surrounding soil, water, and surfaces.
Infection can go undetected due to limited diagnostic testing. The current vaccine is only appropriate for sheep and does not stop infection or transmission. However, we can use it successfully as part of a JD control programme to mitigate introduction and spread in flocks. MAP is also controversially associated with Crohn’s disease in humans and so represents a potential public health threat.
Clinical mastitis
Intramammary infections causing mastitis are other important production-associated diseases in ruminants. Clinical mastitis is an important animal welfare issue and can lead to death or premature culling. It causes a reduction in milk quantity and quality, which influences weight gain and lamb production. Another pathogen affecting sheep productivity is Jaagsiekte retrovirus (JSRV), the cause of Ovine Pulmonary Adenocarcinoma (OPA), a contagious tumour of sheep. OPA remains a significant disease problem in the UK and worldwide. Disease control is problematic without a test for JSRV infection. Transthoracic ultrasound scanning (TUS) is an effective way to diagnose pre-clinical OPA, but it is expensive.
Questions
- For key diseases for livestock in Scotland, which pathogen component and host immune responses will prove useful to exploit as targets for potential vaccines or for accurate detection and diagnoses of infection?
Solutions
This project focuses on four of the most important infections and diseases affecting Scottish livestock production. This project is improving our understanding of (i) the transmission of Mycobacterium avium subspecies paratuberculosis (MAP), mastitis and Ovine Pulmonary Adenocarcinoma (OPA) in cattle and sheep; and (ii) identifying the processes involved in the virulence and infection of Pasteurella multocida.
Identifying antigens and immune responses associated with bovine P. multocida strains that differ in virulence
Our previous research compared bovine strains isolated in the UK and US. We found differences in the severity of the pathology and published the full genome sequences of virulent UK strains. We are extending this work to determine whether genetic differences between these strains are associated with known expressed virulence-associated factors. This could provide the first step in the design of a novel vaccine.
Understanding the drivers of MAP Transmission in the environment to livestock
We are investigating the drivers of environmental MAP transmission in the spread of infection within farmed and wildlife reservoirs, potential transmission routes from the environment to healthy livestock and the effectiveness of control programs to mitigate the spread of JD. We are developing a baseline of MAP in the farm environment in Scotland and determining the effectiveness of current mitigation strategies.
Exploring mastitis and OPA
We are modelling OPA transmission and evaluating different control scenarios, exploring the duration of virus production through analysis of JSRV in exhaled droplets from sheep with various stages of the disease, and evaluating virus infectiousness using cell and lung slice cultures. From these studies, we are assessing the risk of aerosol transmission of JSRV at different disease stages. Lastly, we are sequencing samples of JSRV from different farms over time to explore the influence of virus strain on infectiousness.
Longitudinal study of mammary health in a genetically characterized sheep flock
We are studying the health of a genetically characterized sheep flock over time. This involves genotyping three hundred age-matched ewes to provide information on their genetic background and their overall health. The insights from our study are informing mastitis control and intervention strategies. It will also provide information on the incidence of antimicrobial resistance affecting treatment options.
Project Partners
Progress
Objective 1 (Antigens and immune responses associated with bovine P. multocida strains differing in virulence): We have grown a low virulence P. multocida strain in culture and sequenced the genome using a combination of two short- and long-read sequencing technologies (Illumina and Nanopore). The sequences have been quality checked, assembled and annotated; ready for comparative analyses in Year 2.
Objective 2 (Drivers of MAP transmission in the environment to livestock): A multiplex MAP qPCR assay has been developed and its performance has been tested against soils and a commercial kit. Environmental samples for the spatial study have also been collected from most of the included farms. Quantification of MAP in these samples is slightly delayed. To compensate, aspects of the Year 2 longitudinal study have been delivered early, including a farmer questionnaire and farm recruitment.
Objective 3 (Longitudinal mammary health study in a genetically-characterized sheep flock): An archive of serum, white blood cells, genomic DNA and RNA has been generated from each ewe. The bacteriological analysis of milk samples collected over the first lactation from cases of clinical and subclinical mammary infections have been completed with bacterial isolates characterized to genus and species levels using a targeted sequence-based approach. To capture production data, the birth weight and weight gain till weaning for each lamb has been recorded.
Objective 4 (Control of OPA): Blood, exhaled breath condensate and nasal swab samples from different stages of experimental and clinical OPA were collected, RNA extracted and analysed by RT-qPCR. JSRV was not found to be detectable at the early stages of OPA, it was only detectable once the tumours could be observed by transthoracic ultrasound scanning.
Knowledge exchange: The OPA expert within the group drafted a working document for discussion with the Scottish Government Animal Health and Welfare Division working group on OPA, giving advice on surveillance and control for stakeholders, farmers and vets. This led to discussions on facilitating access to flock screening and developing potential assurance-type schemes. A similar presentation and discussion to DEFRA Sheep Health in England's Animal Health and Welfare Pathway expert group resulted in delegates from England and Wales joining the Scottish Government OPA working group in order to discuss progress towards a UK-wide approach to controlling the disease.
Direct Knowledge exchange to industry stakeholders was delivered through stakeholder events, including the Royal Highland Show, the NSA sheep event at Malvern and at project workshops to advise on specific disease problems, showcasing Moredun's research activities linked to this project and to specifically recruit farmers and vets to the Johne's project.
We have also presented project work at various national meetings, including talks to the Antimicrobial Resistance (AMR) Forum on AMR dynamics in farm livestock and the environment, on control measures for Johne's Disease at the annual Deer Society meeting, on OPA surveillance and control at the Vet Trust Conference and to the British Society of Pathology conference. We have also had discussions and presentations on the transmission and control of the diseases focused on in this project, including the identification of protein targets for vaccine development through proteomic approaches at the Biggar Science Festival, Scot Sheep 2022 and RHS.
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