Dynamics of Susceptibility and Transmission of Campylobacter jejuni in Chickens

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Campylobacter jejuni is the leading cause of bacterial food poisoning in the UK, the largest source of which is believed to be contaminated poultry products. For this reason, the primary focus of regulatory authorities is directed towards measures that will limit the numbers of campylobacter-positive birds in commercial flocks. Studies that observe the burden of Campylobacter within different flocks provide important insights into the dynamics of transmission at the flock level. In particular it is almost impossible to distinguish whether flocks have lower levels of Campylobacter due to the individuals being more difficult to colonise or due to the rate of transmission between individuals being lower. However, from observational data alone it is difficult to distinguish the mechanisms responsible for any observed differences. Controlled animal challenge experiments can resolve these questions systematically. Traditionally this would require separate controlled experiments to be carried out to assess transmission and susceptibility independently. Recent statistical models - based on mathematical models of transmission and developed by the CIDC - offer a new approach whereby susceptibility and transmission can be simultaneously estimated from a single experiment. In this project we will develop this theory further and promote this approach that should lead to reductions in the number of experimental animals required to be killed to achieve a given scientific objective. Although this research is being developed specifically with regards to the colonisation of chickens with Campylobacter, we anticipate that this theory will be more generally applicable and has the potential to reduce the number of animals used in the investigation of a broad range of host-pathogen systems. Mathematical models are also useful for helping us to understand and utilise surveillance data more effectively and inform our understanding of the biological mechanisms in action with colonised flocks. A unique data set generated by our collaborators at the University of Oxford suggests that birds may naturally begin to clear Campylobacter when they have grown beyond the average slaughter-age of 30-40 days in Broiler production. We set out to use mathematical models to assess this hypothesis and determine the simplest possible set of mechanisms that can explain this fascinating new data set. This data set also provides a snapshot of the diversity of different strains of Camyplobacter and how it changes over time. Understanding the within- and between-host competition of different strains of bacteria will allow the development of new rational interventions to reduce colonisation. We will use this unique resource to begin to develop a framework by which the competition dynamics of different strains can be described, and the design of future studies improved. High-throughput sequencing is rapidly becoming fast and cheap enough that we will be able to study how the population of different strains evolves over time under natural transmission conditions. We propose to begin the development of theory that will facilitate the collection and analysis of such data to improve our understanding of the basic colonisation biology of this important zoonotic pathogen.