A molecular epidemiological approach to combating footrot an endemic disease of sheep

Lameness in sheep is painful. In Great Britain over 95% of flocks have approximately 10% of sheep lame at any one time and 80% of this lameness is caused by footrot. There are approximately 1.6 million lame sheep in GB at any time. Footrot is estimated to cost the UK industry £31 million per year and is a huge worry to sheep farmers who do not feel that advice to manage this disease is successful. Footrot is an infectious disease caused by invasion of the skin between the claws of the foot with a bacterium called Dichelobacter nodosus. Surprisingly little is known about how this bacterium causes disease and how it survives (on the sheep or in the environment) when it is not causing disease. Over the past 7 years we have studied practical aspects of control of footrot. The key results were that farmers who treated lame sheep promptly with injectable antibiotics had low levels of lame sheep in their flocks (4% versus 12%) and also that trimming feet (traditionally used to control footrot) was associated with high levels of disease. These facts suggest that the bacteria may be much more widely spread in the environment than previously suspected from research in Australia. We know that the environment plays a role in disease occurrence. D. nodosus survives better in warm wet weather. We also know that there are several strains of the bacterium that can affect the severity of disease. However, we do not know which aspects of the environment or the bacterial strains are important in determining disease severity and persistence on farms. The bacteria may survive in pasture, in the gut or on feet of the non-diseased sheep. During our work we collected a large store of D. nodosus from swabs of sheep with and without disease and also stored bacterial DNA from the feet of sheep. We also have two years data from approximately 800 ewes and their lambs. Every occurrence of lameness has been recorded and investigated and samples taken to investigate whether D. nodosus was present. From these data we can form mathematical models that describe when a sheep became lame, how long she was lame for and factors that influenced the speed with which she recovered and, unfortunately for some, became lame again. The plan of work we propose is to analyse the data above as described and to add in new findings about D. nodosus from laboratory studies into the ability of strains to cause disease and their survival in the environment. Using results from these studies and our models we will be able to work out which strains of D. nodosus cause most disease and how important the environment and host are in their survival. The ultimate aim is to provide better advice on control of footrot and so lower the occurrence of this disease.

Footrot, caused by the bacterium Dichelobacter nodosus, is an endemic disease of enormous economic and welfare importance that has undermined the sustainability of the sheep industry for centuries. Little progress has been made in the understanding of disease persistence and a multidisciplinary approach using state-of-the-art molecular techniques and mathematical models is very timely. Farmers identify footrot as their greatest cause of concern in sheep health and recent advances in molecular tools and epidemiological analyses, particularly approaches to strain variation and predictive modelling, make this a feasible project. Current understanding of the relationship between D. nodosus and FR cannot distinguish between 4 hypotheses. These differ in terms of whether D. nodosus survives in the foot or the environment, whether such survival is short or long-term, and hence how transmission occurs. The involvement of other saprophytic, commensal and pathogenic bacteria and the genetic and virulence variation within D. nodosus are other variables to be considered. The over-arching aim is to study the population dynamics and population genetics of D. nodosus with a view to enhancing FR control strategies. We propose a multidisciplinary research programme that uses existing datasets (epidemiological and biological) and exploits recent scientific developments in epidemiology and molecular biology to further our understanding of FR in sheep. Our aim is to use these original data and new molecular biological categorisations and generate mathematical and statistical models to test the hypotheses and eliminate all but one. We will conclude the programme of work by using the remaining hypothesis to design a cohort study in year 4 of the proposal. Healthy and clinically affected sheep will be sampled, collecting data that will be determined from the first three years work. Biological and epidemiological analysis will be used to further our understanding from years 1-3.