Three studies showing the importance of quantitative methods in investigation of veterinary infectious disease.
MSc(R) thesis, University of Glasgow.
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Chapter 1 – EXAMINING THE EVOLUTIONARY HISTORY OF BOVINE PAPILLOMAVIRUS IN EQUINE SARCOIDS
The papillomavirus (PV) family consist of slowly evolving host-adapted DNA viruses. Bovine papillomaviruses (BPVs) -1 and -2 primarily cause warts in their natural host, the cow, but also lead to locally aggressive and invasive skin tumours in equids known as sarcoids. This chapter gives an account of the first phylogenetic analysis of BPV in equine sarcoids, undertaken in order to clarify the evolutionary history of the virus and its cross-species association with equine sarcoids. Phylogenetic trees were constructed for three different stretches of the BPV genome. Although two of these analyses used gene segments that proved too short to draw any firm conclusions, the phylogenetic analysis carried out on the BPV-1 transcriptional promoter region (LCR) from cattle and horse samples provided interesting insights into the evolution of the virus. The genetic diversity seen in the LCR variants was shown to be ancient, predating domestication of both equids and cattle. The phylogenetic tree shows clear geographic segregation, with an ancestral BPV-1 group consisting of African and Brazilian sequences and a more evolved European group of sequences. The distribution of the cattle samples within the phylogeny suggests the sequences originally evolved in ancestral cattle, and that the genetic diversity found in equine sarcoids is the result of multiple, relatively recent species jumps into horses from different seeding strains of the virus. In addition, a specific LCR sequence variant was isolated in equine samples from all countries sampled here, despite being absent from cattle samples, suggesting that viruses containing this sequence variant may have a selective advantage within the equine population.
Chapter 2 - SCOTTISH SHEEP MOVEMENTS AND THEIR POTENTIAL FOR DISEASE TRANSMISSION
Animal movements play a major role in the spread of livestock diseases. By identifying farms pivotal to the network of livestock movements, it may be possible to more efficiently curb the spread of disease. Diseases transmit over great ranges of timescale and infectiousness. Sheep are moved from premises to premises for a variety of different reasons and with widely varying residence times on the arrival premises, and different types of movement are important in the spread of different diseases. This report describes work identifying those sheep farms important in terms of the types of movements involved in both a fast-transmitting and a slowly-transmitting disease. In so doing it raises the possibility of achieving control of multiple infections by targeting just a single subset of farms. If this were possible it would provide a cost effective and efficient method to reduce the burden of disease in the national flock.
Chapter 3 – THE IMPLICATIONS OF POST-INFECTION IMMUNITY FOR THE EPIDEMIOLOGY AND CONTROL OF Escherichia coli O157 INFECTION OF CATTLE
This report describes the use of epidemiological modelling to investigate how a period of post-infection immunity impacts the transmission dynamics of E. coli O157. Shigatoxigenic strains of E. coli, including the O157 strain, cause severe disease in man despite being asymptomatic in cattle, their natural reservoir host. Previous work modelling the transmission dynamics of E. coli has assumed that an animal becomes immediately susceptible on recovery from an infection, but recent experimental evidence indicates this may not be the case. In this project, stochastic models were developed for E. coli in cattle, allowing comparison of the effects of a period of post-infection immunity with the previously used assumption of immediate return to susceptibility. The results show that post-infection immunity gives lower values for outbreak duration, and for mean and variance in prevalence, and that this is observed over a biologically plausible range of the basic reproduction number, Ro. This in turn indicates that E. coli infection is likely to be more difficult to control if post-infection immunity exists, especially at higher infection prevalences. This study also reveals that if the assumption of post-infection immunity is valid, an even higher degree of individual heterogeneity in transmission is needed to explain the degree of variance in E. coli O157 prevalence seen in the field, thus validating previous work which demonstrated the importance of supershedder animals and individual heterogeneity. This study provides the first steps in investigating how a period of immunity following E. coli infection of cattle affects conclusions drawn by previous work assuming an immediate return to susceptibility. Models allowing the incorporation of individual heterogeneity are needed to further investigate the subject.
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