Epidemiology and evolution of Marek’s Disease virus
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Date
2010Author
Atkins, Katherine E.
Metadata
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.