Is multistrain infection by Dichelobacter nodosus important in the severity of footrot and in the management of disease?

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Footrot, caused by Dichelobacter nodosus (Dn), costs the UK sheep industry >£80million pa: 98% of flocks have footrot and 3 million ewes are diseased pa. The current licensed vaccine includes 9/10 Dn FimA serogroups, offering 60% efficacy for 4 months. As vaccines contain fewer serogroups efficacy increases; flocks often have several serogroups.

Dn isolates are defined as benign or virulent based on specific virulence genes. Disease is also defined as benign or virulent, however, disease and isolate virulence are not well correlated: virulent isolates are detected in benign disease and vice versa. We propose that confusion has arisen because culturable isolates rather than whole community Dn have been studied and because isolate virulence has not been studied in longitudinal studies where disease dynamics would inform on temporal relationships between virulence of bacteria and disease.

Recent work in our group indicated that Dn load drives pathogenesis and that flocks with no disease still have detectable Dn. We hypothesise that total load and the whole community of virulent and benign Dn strains are key to understanding disease dynamics and to identify effective flock specific managements that provide resilience to disease. We will study total community, FimA and virulence of Dn using non-culture techniques: PCR, qPCR, MLVA fingerprinting and high-throughput sequencing. We will combine lab results with disease and management data from 3 epidemiological studies and use competing risks models to elucidate strain and virulence factors that drive disease progression and severity. A framework of stochastic mathematical models will be used to simulate optimal control strategies including the role of varying number of serogroups / vaccine. Should our hypothesis be correct then in 3-5 years the sheep industry will have a strategy to control footrot using a combination of flock specific vaccine together with other managements to reduce load and increase resilience.

Please see attached documents from the lead (University of Warwick)