Epidemiology and evolution of Marek’s Disease virus

Abstract

Marek’s disease (MD) is an oncogenic disease affecting chickens and is estimated to cost the worldwide poultry industry $1-2 billion annually. The causative agent of MD, Marek’s disease virus (MDV), provides a welldocumented example of virus virulence evolution occurring over a period of sixty years. The reason behind this evolution is unknown, although certain untested hypotheses have been suggested. These include vaccination (with increasingly potent vaccines) and other aspects of industrialisation, such as the decreased cohort duration of successive generations and an increased stocking density of the broiler flocks. In this thesis, four sections of work are undertaken. First, estimation of epidemiological parameters is tackled: virulence of MDV is quantified by looking at host mortality and virus shedding rates in vaccinated and unvaccinated birds. This is achieved via maximum likelihood estimation and Bayesian McMC techniques. Second, viral fitness is quantified by defining multiple lifetime fitness functions using the parameters previously estimated to understand the direction and force of virulence selection for different farm environments. Third, the impact of an outbreak of MDV on a broiler flock is examined by simulating a whole flock of birds. This provides an epidemiological understanding of the virus at the flock level and can help elucidate methods for disease control and surveillance and can also give a fitness measure to understand on-farm evolution of the virus. Fourth, a between-farm model is analysed to evaluate which MDV strains are able to persist in a network structure of farms and how this might be affected by biosecurity measures, different farm networks, farm size, bird lifespan and vaccination. This provides insights into how quickly a different strain can invade a farm network and the plausibility of it becoming endemic. Parameter estimation results show that the time to death for an infected bird decreases and its virus shedding rate increases with previous definitions of virulence in the literature. Model results suggest that the choice of fitness measure alters the conclusions reached. Increasing the amount of demographic structure introduced into the fitness measure shows that neither vaccine introduction nor decreasing a bird’s lifespan changes the ability of more virulent virus strains to outcompete less virulent strains. In any environment, more virulent strains are always selected for. Epidemiological results suggest that vaccination allows a low prevalence of virus on a farm although there are no deaths from the disease itself. Analogous results for between-farm spread suggest that if on-farm cleaning efficiency is low enough, a high prevalence of disease throughout a network of vaccinated flocks can exist but the farms themselves show no signs of increased mortality from the disease. The hypotheses for explaining the increase in virulence of MDV may not be consistent with the results of this work. Despite previous arguments that vaccines are driving the evolution of virulence ofMDV, this first quantitative work on the subject demonstrates that this might not be the case. This work also formulates new hypotheses to explain why MDV virulence has increased over the past sixty years which will pave the way for ongoing research in the area of virulence evolution in farm environments.