Foreign animal disease can cause serious damage to the United States (US) agricultural sector and foot-and-mouth disease (FMD), in particular, poses a serious threat. FMD causes death and reduced fecundity in infected animals, as well as significant economic consequences. FMD damages can likely be reduced through implementing pre-planned response strategies. Empirical studies have evaluated the economic consequences of alternative strategies, but typically employ simplified models. This dissertation seeks to improve US preparedness for avoiding and/or responding to an animal disease outbreak by addressing three issues related to strategy assessment in the context of FMD: integrated multi region economic and epidemic evaluation, inclusion of risk, and information uncertainty. An integrated economic/epidemic evaluation is done to examine the impact of various control strategies. This is done by combining a stochastic, spatial FMD simulation model with a national level, regionally disaggregated agricultural sector mathematical programming economic model. In the analysis, strategies are examined in the context of California's dairy industry. Alternative vaccination, disease detection and movement restriction strategies are considered as are trade restrictions. The results reported include epidemic impacts, national economic impacts, prices, regional producer impacts, and disease control costs under the alternative strategies. Results suggest that, including trade restrictions, the median national loss from the disease outbreak is as much as $17 billion when feed can enter the movement restriction zone. Early detection reduces the median loss and the standard deviation of losses. Vaccination does not reduce the median disease loss, but does have a smaller standard deviation of loss which would indicate it is a risk reducing strategy. Risk in foreign animal disease outbreaks is present from several sources; however, studies comparing alternative control strategies assume risk neutrality. In reality, there will be a desire to minimize the national loss as well as minimize the chance of an extreme outcome from the disease (i.e. risk aversion). We perform analysis on FMD control strategies using breakeven risk aversion coefficients in the context of an outbreak in the Texas High Plains. Results suggest that vaccination while not reducing average losses is a risk reducing strategy. Another issue related to risk and uncertainty is the response of consumers and domestic markets to the presence of FMD. Using a highly publicized possible FMD outbreak in Kansas that did not turn out to be true, we examine the role of information uncertainty in futures market response. Results suggest that livestock futures markets respond to adverse information even when that information is untrue. Furthermore, the existence of herding behavior and potential for momentum trading exaggerate the impact of information uncertainty related to animal disease.

Thesis (M.A. in Security Studies (Homeland Security and Defense))--Naval Postgraduate School, March 2005. / Thesis Advisor(s): Christopher Bellavita. Includes bibliographical references (p. 133-139). Also available online.

The foot-and-mouth disease (FMD) virus poses a considerable threat both to farmers and to the wider economy should there be a future incursion into the UK. The most recent large-scale FMD epidemic in the UK was in 2001. Mathematical models were developed and used during this epidemic to aid decision-making about how to most effectively control and eliminate it. While the epidemic was eventually brought to a halt, it resulted in a huge loss of livestock and is estimated to have cost the UK economy around ¿6 billion. The mathematical models predicted the overall spatial spread of FMD well, but had low predictive ability for identifying precisely which farm premises became infected over the course of the epidemic. This will in part have been due to the stochastic nature of the models. However, the transmission probability between two farm premises was represented as the Euclidean distance between their point locations, which is a crude representation of FMD transmission. Additionally, the premises' point location data contain inaccuracies, sometimes identifying the farmer's residential address rather than the farm itself which may be a long way away. Local FMD transmission occurs via contaminated fomites carried by people or vehicles between premises, or by infected particles being blown by wind between proximal fields. Given that these transmission mechanisms are thought to be related to having close field boundaries, it is possible that some of the inaccuracy in model predictions is also due to imprecisely representing such transmission. In this thesis I use fine-scale geographical data of farm premises' field locations to study the contiguity of premises (where contiguous premises (CPs) are defined as having field boundaries < 15m apart). I demonstrate that the distance between two premises' point locations does not accurately represent when they are CPs. Using an area of southern Scotland containing 4767 livestock premises, I compare the predictions of model simulations using two different model formulations. The first is one of the original models based on the 2001 outbreak, and the second is a new model in which transmission probability is related to whether or not premises were contiguous. The comparison suggests that the premises that became infected during the course of the simulations were more predictable using the new model. While it cannot be concluded that this will translate into more accurate predictions until this can be validated during a future outbreak, it does suggest that the new model is more predictable in its route through the landscape, and therefore that it may better reflect local transmission routes than the original model. Networks based on contiguity of premises were constructed for the same area of southern Scotland, and showed that 90.6% (n=4318) of the premises in the area were indirectly connected to one another as part of the Giant Component (GC). The network metric of 'betweenness' was used to identify premises acting as bridges between otherwise disconnected sub-populations of premises. It was found that removing 100 premises with highest betweenness served to fragment the GC. Model simulations indicated that, even with some longer-range transmission possible, removing these premises from the network resulted in a large decrease in mean number of infected premises and outbreak duration. In real terms, premises removal from the network would mean ensuring these premises did not become infected by enhanced biosecurity and/or vaccination depending on policy. In this thesis I also considered the role of biosecurity practices in shaping FMD spread. A sample of 200 Scottish farmers were interviewed on their biosecurity practices, and their biosecurity risk quantified using a biosecurity 'risk score' developed during the 2007 FMD outbreak in Surrey. Using Moran's I and network assortativity measures it was found that there did not appear to be any clustering of biosecurity risk scores on premises. Statistical analysis found no association between biosecurity risk and the mathematical model's premises' susceptibility term (which describes the increase in a premises' susceptibility with increasing numbers of livestock). This suggests that the model's susceptibility term is not indirectly capturing a general pattern in biosecurity on different sized farm premises. Thus, this body of work shows that incorporating a more realistic representation of premises location into mathematical models, in terms of area (i.e. as fields) rather than a point, alters predictions of spatial spread. It also demonstrates that targeted control at a relatively small number of farms could effectively fragment the farming landscape, and has the potential to considerably reduce the size of an FMD outbreak. It also demonstrates that variations in premises' FMD biosecurity risks are unlikely to be indirectly affecting the spatial or demographic components of the model. This increase in understanding of how geographic, social and demographic factors relate to FMD spread through the landscape may enable more effective control of an outbreak, should there be an incursion in the UK in future.

Doctor of Philosophy / Department of Agricultural Economics / Ted C. Schroeder / Concerns regarding management of animal disease and related perceptions about food safety have escalated substantially in recent years. Terrorist attacks of September 2001, discovery of bovine spongiform encephalopathy in a dairy cow in December 2003 in Washington state and subsequent discoveries of BSE infected animals in Texas in 2005 and Alabama in 2006, and recent worldwide outbreaks of highly contagious animal diseases (i.e., Foot-and-Mouth Disease and Avian Influenza A (H5N1)) have made apparent the need for animal traceability in U.S. livestock production and marketing. In addition, animal identification and trace-back systems are rapidly developing throughout the world increasing international trading standards. In recent years, increasing numbers of economic analyses of animal diseases have integrated epidemiological models into economic frameworks. However, there are only a few studies that have used this integrated framework to analyze the effects of animal traceability on highly contagious animal diseases. This study’s goal is to quantify and evaluate the economic impacts of different depths of animal identification/trace-back systems in the event of a hypothetical highly contagious foot-and-mouth disease outbreak that poses a threat to U.S. livestock competitiveness. Specifically, an epidemiological disease spread model is used to evaluate the impact of a foot-and-mouth disease outbreak in southwest Kansas. The information obtained from the disease spread model is then used in conjunction with an economic model to determine the changes in welfare of producers and consumers. Results obtained from the epidemiological model indicate that as the depth of animal identification in cattle is increased, the number of animals destroyed is reduced as are the associated costs. Also, the length of the outbreak is reduced by approximately two weeks. The economic results suggest that as surveillance is increased, decreases in producer and consumer welfare are smaller. Furthermore, as surveillance is increased, decreases in producer and consumer surplus measures can be reduced by approximately 60 percent.

The Picornaviridae family contains a number of pathogens which are economically important including Poliovirus, Coxsakievirus, Hepatitis A Virus, and Foot-and-Mouth-Disease-Virus. Recently the emergence of novel picornaviruses associated with gastrointestinal, neurological and respiratory diseases in humans has been reported. Although effective vaccines for viruses such as FMDV, PV and HAV have been developed there are currently no antivirals available for the treatment of picornavirus infections. Picornaviruses proteins are classified as: the structural proteins VP1, VP2, VP3 and VP4 which form the subunits of the viral capsid and the replication proteins which function as proteases, RNA-polymerases, primers and membrane binding proteins. Although the host specificity and viral pathogenicity varies across members of the family, the icosahedral capsid is highly conserved. The capsid consists of 60 protomers, each containing a single copy of VP1, VP2 and VP3. A fourth capsid protein, VP4, resides on the internal side of the capsid. Capsid assembly is integral to life-cycle of picornaviruses; however the process is complex and not fully-understood. The overall aim of the study was to broaden the understanding of the evolution and function of the structural proteins across the Picornaviridae family. Firstly a comprehensive analysis of the phylogenetic relationships amongst the individual structural proteins was performed. The functions of the structural proteins were further investigated by an exhaustive motif analysis. A subsequent structural analysis of highly conserved motifs was performed with respect to representative enteroviruses, Foot-and-Mouth-Disease-Virus and Theiler’s Virus. This was supplemented by the in silico prediction of interacting residues within the crystal structures of these protomers. Findings in this study suggest that the capsid proteins may be evolving independently from the replication proteins through possible inter-typic recombination of functional protein regions. Moreover the study predicts that protomer assembly may be facilitated through a network of multiple subunit-subunit interactions. Multiple conserved motifs and principle residues predicted to facilitate capsid subunit-subunit interactions were identified. It was also concluded that motif conservation may support the theory of inter-typic recombination between closely related virus sub-types. As capsid assembly is critical to the viral life-cycle, the principle interacting motifs may serve as novel drug targets for the antiviral treatment of picornavirus infections. Thus the findings in the study may be fundamental to the development of treatments which are more economically feasible or clinically effective than current vaccinations.

The suitability of a plant-based transient expression system using the agro-infiltration technique was compared to an Escherichia coli (E. coli)-based expression system to produce the VP1 protein from Serotype O, South Korean strain, of the foot-and mouth disease virus (FMDV). The full-length VP1 coding sequence was expressed in Escherichia coli as a fusion protein and purified as a His-tagged VP1 fusion protein with a yield of 14 mg L-1 bacterial culture. For transient expression in tobacco, the VP1 coding sequence was cloned into binary vector pMYV497, containing a CTB (cholera toxin B subunit) signal peptide and SEKDEL ER retention signal, and transiently agro-infiltrated into non-transgenic N. benthamiana and transgenic N. tabacum plants constitutively expressing the rice cysteine protease inhibitor OC-I. A protein resembling VP1 was detected using immuno-blotting analysis in both N. benthamiana and OC-I N. tabacum plants seven days post agro-infiltration. Although a possible stabilizing effect on VP1 was found due to OC-I expression, protein yields were not significantly different between transformed OC-I and non-OC-I control plants. Also, simultaneous co-infiltration with a plasmid allowing additional transient OC-I expression did not significantly improve VP1 production. The average VP1 amount achieved in OC-I expressing plants was 0.75% of total soluble protein. Overall, this study has shown that transient VP1 expression in tobacco is possible, but requiring further optimization, and that OC-I might have a stabilizing effect against proteolytic degradation of VP1 during advanced stages of senescence in agro-infiltrated plants coinciding with peaks in protein expression. Copyright / Dissertation (MSc)--University of Pretoria, 2012. / Plant Science / unrestricted

Foot-and-mouth disease (FMD) is a viral disease endemic in Africa, the Middle East, South America, Asia and parts of Eastern Europe. It is a major constraint to international trade in livestock and livestock products in many African countries. In southern Africa, African buffaloes (Syncerus caffer) are reservoirs of the South African Territories (SAT) 1, SAT 2 and SAT 3 FMD viruses, and cattle raised in the vicinity of wildlife conservation areas are at constant risk of becoming infected with FMD viruses. In Mozambique, control of FMD is fundamentally based on vaccination of cattle in zones around protected areas. However, the vaccination protocol recommended by the vaccine producer (two primary vaccinations followed by four- to six-monthly boosters) is logistically impractical and financially not suitable for most countries. As a result, the double primary vaccination is usually not implemented. A commercially available bivalent FMD vaccine, containing the SAT 1 and SAT 2 serotypes, was assessed for its ability to induce and sustain immunity in cattle for at least 6 months following a single primary inoculation. The study was conducted with cattle reared in Limpopo National Park (LNP), Mozambique, and adjacent areas. One hundred and seventy five seronegative cattle aged between 6 and 18 months were vaccinated and 42 others from the same areas were left unvaccinated, as controls. A group of 39 vaccinated cattle were revaccinated 4 months after initial vaccination and 63 others were revaccinated 6 months after initial vaccination. The vaccinated and unvaccinated cattle were bled at predefined intervals (at vaccination, and at 1, 4, 5, 6, 8, 10 and 12 months post vaccination) and sera were tested with a liquid phase blocking ELISA to measure the antibody level against FMD virus. A high proportion (73%) of vaccinated cattle had seroconverted (log10 titre ≥1.6 for any SAT serotype) at one month after vaccination with a single primary dose and there was no significant difference between the proportions of animals that seroconverted to SAT 1 compared to SAT 2. A higher proportion of animals within LNP (82%) than outside LNP (50%) had seroconverted at one month after vaccination (P = 0.001). Overall, however, only relatively few animals (27% for SAT 1, 35% for SAT 2 and 7% for SAT 3) had protective antibody titres (log10 titre ≥2). At 4 months after vaccination, a very low proportion (8.3%) of vaccinated cattle had antibody titres ≥1.6 to any of the SAT serotypes, and there was no significant difference between the proportions of animals with antibodies to SAT 1 (2.1%) compared to SAT 2 (7.3%) (P = 0.17). No cattle had a protective titre (≥2) to SAT 1 at 4 months and only 4.2% to SAT 2. The revaccination at 4 months after initial vaccination elicited antibody titres ≥1.6 in 22% of vaccinated animals at one month after revaccination; this rose two months later to 90% and remained high (91%) at 10 months post first vaccination before dropping to 65% at 12 months. However, only 15% of cattle had protective titres (≥2) to any of the SAT serotypes at 12 months. For cattle revaccinated at 6 months after first vaccination the percentage of cattle that had a titre ≥1.6 two months after revaccination was also high (80%), remained high (89%) at 10 months post first vaccination and dropped to 54% at 12 months after first vaccination. Only 11% of cattle had protective titres (≥2) at 12 months. The research findings indicate that, although the vaccine is able to induce production of antibodies against SAT 1 and 2 in a significant percentage of cattle within one month after a single primary vaccination, these antibodies are short lived and have largely disappeared by 4 months post vaccination. This suggests that a protocol of a single primary vaccination is inadequate in naïve animals, even if revaccination takes place four months later. Revaccination improved the immune response for a longer period, resulting in detectible titres in the majority of animals for 6-8 months post revaccination. This can be used in disease control programmes to ensure some protection of cattle particularly when it is applied immediately before identified high risk periods of occurrence of FMD outbreaks. However, it seems unlikely that six-monthly revaccination is sufficient to maintain adequate levels of protective immunity. The study highlighted several difficulties associated with the vaccination of livestock under field conditions and the conduction of field trials. These included difficulties with cold chain maintenance, poor infrastructure for animal handling, and loss of follow-up due to loss of animal identification or poor owner/herder compliance. Copyright / Dissertation (MSc)--University of Pretoria, 2012. / Production Animal Studies / unrestricted

The majority of the world’s most widespread and problematic pathogens evade host immune responses by inducing strain-specific immunity. The host immune system seems to induce a vigorous immune response towards hypervariable epitopes, seemingly attracting less attention to more highly conserved vital regions. The South African Territory (SAT)-2 foot-and-mouth disease virus (FMDV) is the most prevalent and antigenic diverse of the SAT serotypes with the occurrence of multiple antigenic and genetic subtypes. Identification of the fine antigenic structure of the capsid of these viruses remains essential in the design and engineering of a vaccine seed strain that confers cross-protection against intra-typic viruses. Towards refocusing the antigenicity of SAT2/ZIM/07/83 virus, two strategies were utilised, (1) replacement of predicted antigenic determinants to corresponding sites of the antigenic distant SAT2/EGY/09/12 virus and (2) charge-dampening of previously identified epitope regions with alanine residues. The antigenic distance of refocused mutants was evaluated by (1) virus neutralisation assays using parental and heterologous convalescent bovine sera and (2) through antigenic profiling with non-neutralising SAT2-specific murine monoclonal antibodies (mAbs). One antigenic site on VP1 (Site 3) was identified using bovine polyclonal antibodies, whereas an additional three epitope regions were elucidated using the murine mAbs. Furthermore, the cell culture-adapted vSAT2 was shown to utilise a third FMDV alternate receptor to infect integrin- and heparin sulphate-deficient cell lines. Comprehensive knowledge on the antigenic structure of these viruses will assist in the fundamental design of engineered vaccines by incorporating critical antigenic sites that confer increased antigenicity and cross-protective immune response against myriad SAT2 field strains. Furthermore, this information will not only improve design of vaccine seed viruses, but will also contribute towards novel vaccine constructs or even empty nanoparticles as a vaccine strategy in the future. / Thesis (PhD)--University of Pretoria, 2020. / Agricultural Research Council / National Research Foundation / Red Meat Industry Trust / Poliomyelitis Research Foundation / Microbiology and Plant Pathology / PhD / Unrestricted

In recent decades, a number of foot-and-mouth disease (FMD) outbreaks have occurred in countries that had been FMD-free for many years. The last FMD outbreak in the United States occurred in 1929 and the country contains a naïve livestock population, meaning it is susceptible to an outbreak. In the event of an FMD outbreak in the United States, the speed at which the source and contacts between livestock can be identified impacts both the implementation and effectiveness of mitigation strategies. The purpose of this thesis was to analyze the impact of higher levels of animal traceability on the immediate welfare losses resulting from an FMD outbreak originating in Utah. An epidemiological model was used to simulate the spread of the disease throughout the livestock population of Utah and estimate a mean number of animals depopulated over 1000 iterations for low, medium and high levels of trace intensity. This number of animals depopulated was then used to create supply shocks in an equilibrium displacement model. This model revealed the welfare losses across four marketing levels for beef, three for pork and two for pork. The research contained in this thesis determined that the adoption of a high intensity trace system can prevent immediate welfare losses of between $131 and $190 million for the United States beef industry, including $49 million to the Utah fed cattle, feeder cattle and market hog marketing levels

Picornaviruses are responsible for some of the most common and debilitating diseases affecting humans and animals worldwide. The objectives of this dissertation research were (1) estimate phylogenetic relationships among 11 picornavirus genera and within three species: foot-and-mouth disease virus (FMDV: Aphthovirus) which afflicts cloven-hoofed animals and human rhinovirus A and B (HRV: Enterovirus) which cause the common cold; (2) better understand the impact recombination has on genomic organization and evolution; (3) characterize where positive and purifying selection has occurred in proteins and how selection has influenced phenotype. The dissertation includes four studies. The first chapter provides an overview of the evolutionary significance of recombination, its detection and estimation, and its effect on phylogenetic analysis in four biological systems: bacteria, viruses, mitochondria, and the human genome. Chapter two investigates the inter- and intra-serotypic relationships within FMDV by examining 12 genes. Gene sequences were analyzed to assess recombination breakpoint locations, genetic diversity, and natural selection in FMDV. Recombination breakpoints were located throughout the genome. Paraphyletic relationships among serotypes were not as prevalent as previously reported, suggesting that convergent evolution was prevalent. Purifying selection was the dominant evolutionary force influencing both genotype and phenotype. Chapter three examines inter- and intra-specific relationships of HRV using 11 genes. Similar hypotheses were tested as in chapter two. No recombination was detected and phylogenetic relationships among enteroviruses, HRV-A, and HRV-B remain unresolved. The evolution of HRV-A major serotypes appeared to be under extensive purifying selection, HRV-A minor serotypes under predominantly positive selection, and a nearly equal influence from both kinds of selection was evident for HRV-B serotypes. Chapter four examines phylogenetic relationships among genera using three conserved genes. The hypothesis of cospeciation between picornaviruses and their hosts was also tested. The deepest split in the family separated Hepatovirus, ‘Tremovirus’, Parechovirus, and seal picornavirus type 1 from the remainder of the family. Enterovirus and ‘Sapelovirus’ were sister taxa. Cardiovirus, ‘Senecavirus’, Aphthovirus, Erbovirus, Teschovirus, and Kobuvirus were derived from a common ancestor with Kobuvirus occupying a basal position relative to the other genera in this clade. My analyses suggest that picornaviruses have not cospeciated with their known hosts.