What really causes footrot in sheep: a national cohort study of the microbial diversity of Dichelobacter nodosus in sheep in sickness and in health

Lead Research Organisation: University of Warwick
Department Name: School of Life Sciences

Abstract

There are a plethora of virulent factors in Dicelobacter nodosus, the causal agent of ovine footrot, but these do not clearly define benign and virulent strains. The disease itself is endemic or epidemic in different climates suggesting a complex aetiology. We consider that only by studying D. nodosus using non-culture methods will we understand the dynamic relationship between colonisation, bacterial virulence and disease episodes in sheep. Given the persistent nature of D. nodosus, understanding this relationship is essential to develop strategies for control of disease, including better vaccines. This PhD will explore the range of virulence factors in the community of D. nodosus in flocks of sheep, to test the hypothesis that in endemic situations a community of D. nodosus strains are distributed nationally and that control can be obtained by targeted management of strains at a national level.

Experimental approaches
The student will source swab samples from farmers throughout England who will also send data from their sheep, including estimated level of footrot and ID.

Methodology and study design
1. Use epidemiological principles to design the sampling protocol and study to collect a sample of swabs from a representative number of English sheep farmers who responded to our recent study (700 farmers) in years 1 and 2, conduct the study and receive the swab samples (24 months)
2. Learn molecular methods and investigate serogroup and virulence factors in the community of D. nodosus strains collected (30 months)
3. Use modelling to test the hypothesis that serogroup and virulence are associated with spatial clustering of sheep in England and farmer behaviour in terms of biosecurity and purchase of sheep. ( 36 months)
4. Identify the most prevalent serogroups and test the hypothesis that a serogroup specific vaccine could be used to control footrot in England.

The ultimate aim is to identify the relative proportion of to 10 serogroups of D. nodosus and to investigate whether a vaccine with fewer serogroups could be used to control footrot in sheep.

Molecular training
The student will extract DNA from interdigital matter on stored swabs. They will identify all serogroups and fimbrial load of each serogroup by qPCR and use specific primers to investigate the presence of virulence factors (e.g. fimA, aprV2; Keenan et al., 2011).

Statistical and epidemiological modelling
The student will use mixed effect multistate models and latent class models in a Bayesian framework, that allows prediction and inference, to identify patterns within the community of D. nodosus virulence factors and distribution of D. nodosus nationally.

Originality: The national community of D. nodosus has never been studied before with analysis of strains of bacteria using epidemiological data, this is highly novel for any disease.
Difficulties: Developing skills to do the molecular biology will take time and having several strains in a sample will require consideration on how to summarise the data for further analysis.
Challenges: How to analyse the data from the community strain analysis so that they can be used in statistical modelling of the study.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M017281/1 05/10/2015 04/10/2019
1645284 Studentship BB/M017281/1 05/10/2015 30/09/2019 Naomi Prosser
 
Description The prevalence of lameness in ewes in a cohort of 154 flocks rose slightly between 2013 and 2015. Four managements were associated with lameness in these flocks, three of these managements had been previously associated with lameness (time to treatment of lame sheep, causing bleeding during routine foot trimming and mixing the flock with other flocks) and one was novel (duration of vaccination programme against footrot). Between 2013 and 2015 farmers changed their practices in four managements that were associated with lameness in sheep in 2013. Most changes were towards best practice recommendations with the exception of one: farmers were taking longer to treat lame sheep in 2015 than in 2013.

This study was also the largest and most representative study of the serogroups of Dichelobacter nodosus (the cause of the most common form of lameness, footrot) in England to date. All serogroups A - I were detected, at different prevalence, but distributed randomly between flocks, and there was heterogeneity in the serogroup communities between flocks. Serogroups H and B were the most common serogroups, and it was common for > 1 serogroup to infect feet and flocks. Analysis demonstrated that it is unlikely that a footrot vaccine tailored for England will be more effective than the commercial vaccine, as many flocks will not be protected.
Exploitation Route Knowledge of what managements are associated with lameness in sheep, by how much, and how farmers are responding to messages about how to manage lame sheep will help to both improve our knowledge of how to best prevent and treat lameness in sheep, and to tailor communications to farmers to promote uptake of these managements. These findings can be used to improve the welfare and profitability of sheep in the UK and help achieve the Farm Animal Welfare Council target for the prevalence of lameness to be 2% by 2021.

Also, further projects can investigate the feasibility of flock-specific vaccines as another possible method of improving the efficacy of vaccination against footrot.
Sectors Agriculture, Food and Drink

 
Description Cambridge University Veterinary Students Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact I made arrangements with the University of Cambridge for a workshop on lameness and mastitis in sheep for final year students at Cambridge University which has been taken by somebody from the University of Warwick for the past few years. I co-presented the section of the workshop on treating and managing lameness in sheep and how to apply this knowledge when talking to or visiting farmers as a veterinarian. This will have an impact on how the students treat and advise farmers on lameness and mastitis issues in their sheep once they have graduated and a practicing veterinarians. One student in 2017 had a further discussion with me afterwards as they were carrying out a project on footrot and I sent them a paper that was useful for their project.
Year(s) Of Engagement Activity 2017,2018
 
Description Farmer sign-up webpage 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact I have created a sign-up webpage for farmers to receive information about both the results from lameness and mastitis in sheep projects at the University of Warwick, and to be invited to participate in future research projects. The sign-up form has not been advertised yet however three farmers have signed up so far.
Year(s) Of Engagement Activity 2017,2018
URL https://warwick.ac.uk/fac/sci/lifesci/research/greengroup/farmersandvets/signup
 
Description Knowledge Transfer Day for University of Warwick Research Participants 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact I presented a poster of my research to recruit farmers to participate in my study at an event to disseminate the latest research results in how to manage and treat lameness in sheep from the University of Warwick. The audience were farmers who had taken part in sheep research for the University of Warwick in the past. I also assisted with leading a small discussion group of farmers. I gave invites to most of the farmers present and many expressed an interest in participating in my project
Year(s) Of Engagement Activity 2016
 
Description Recent research results webpage 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact I have written summaries of three recent research papers on sheep lameness and created a webpage for both these summaries and summaries written by others. These summaries are written for farmers, taking the most useful information for them out of the research papers that results from their participation in studies. The farmers then can see the outputs of their participation which encourages them to participate in future studies, and gives them results that can be applied on farm to make improvements to lameness and mastitis.
Year(s) Of Engagement Activity 2015,2016,2017
URL https://warwick.ac.uk/fac/sci/lifesci/research/greengroup/farmersandvets/latestresearch/
 
Description Sheep Breeders Round Table 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact I presented a poster of my research to farmers and sheep professionals and advised farmers on how best to treat and manage lame sheep. Some farmers reported that they were going to change lameness treatment and management practices as a result of the discussion.
Year(s) Of Engagement Activity 2017
URL https://www.nationalsheep.org.uk/sbrt/
 
Description University of Warwick Open Days 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact I talked with potential undergraduate students and their parents or friends at a stand about the research into lameness in sheep carried out at the University of Warwick. I answered both questions on sheep lameness and about studying in the University of Warwick. Occasionally the students and their parents would be sheep farmers and would be particularly interested in how best to treat their lame sheep.
Year(s) Of Engagement Activity 2017,2018
 
Description University of Warwick Public Science Evenings 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I talked to the general public about lameness research at the University of Warwick at two of the public science evenings (with topics of antibiotics and epidemics). Sometimes a sheep farmer would be present and I would discuss with them how they currently manage lameness and what best practice treatments they could start doing. In addition to a poster detailing the wide variety of methods we use to research lameness, I had various props (healthy and diseased feet of sheep, leaflets that have been produced to advise farmers on how best to treat and manage lameness in their sheep flocks, and some interactive quizzes on detecting lame sheep and the lesions that they suffer from) to engage with the event attendees.
Year(s) Of Engagement Activity 2017,2018
 
Description e-Portfolio and Research webpage 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I have created an e-Portfolio and research webpage explaining my research, which I regularly update. These pages include links to other webpages giving information on best practice to treat lameness in sheep.
Year(s) Of Engagement Activity 2015,2016,2017,2018
URL https://warwick.ac.uk/fac/sci/lifesci/research/greengroup/currentresearch/dnodosuscohortstudy