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1
Foster-Cuevas, Mildred. "Immunodeterminants of foot-and-mouth disease virus." Thesis, University of Hertfordshire, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338562.
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Puig, Arturo. "Lipopeptide vaccines against foot and mouth disease." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428103.
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Nayak, Arabinda. "Foot and mouth disease virus RNA replication." Thesis, University of Surrey, 2005. http://epubs.surrey.ac.uk/842873/.
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Infection of susceptible cells with foot and mouth disease virus (FMDV) results in multiplication of the RNA genome and assembly of mature virions. The entire process of genome replication is completed in a few hours and encompasses many intracellular events. Like other picornaviruses, FMDV uses a peptide primed RNA replication mechanism. The factors that are required to uridylylate each of the three FMDV VPg peptides and the role of the FMDV cis-acting replication element (cre) or 3B Uridylylation Site (bus) in VPg uridylylation have been determined. The native N-terminus of the FMDV 3Dpol enzyme is a pre-requisite for VPg uridylylation in vitro and the effects of mutations in the RNA template are consistent with a slide-back mechanism. The role of the poly(A) tail in uridylylating VPg was insignificant using full-length FMDV RNA transcripts suggesting the possibility of an alternative mechanism of VPg incorporation into negative strand RNA. The optimal RNA sequences required for VPg uridylylation were found to be within the 5' non-coding region (NCR). Furthermore, the results also showed evidence for RNA-RNA interactions between distinct structures from within the 5' NCR that influence VPg uridylylation. The polymerase precursor 3CDpro is also a prerequisite for uridylylation of each of the FMDV VPg peptides. However BCpro alone can substitute for 3 CD, but is much less efficient. It also appeared that the overall charge of the VPg peptides determines their recognition by the FMDV 3Dpol. The RNA binding activity of the 3C was found to be required for its stimulatory effects on VPg uridylylation. Unlike the poliovirus cloverleaf, the FMDV S-fragment (at the 5' end of the genome) does not interact with the FMDV 3CD precursor protein; however it binds specifically to a cellular factor p48. The crude replication complexes (CRCs) isolated from FMDV-infected cells were found to synthesize viral RNA very efficiently and an in vitro RNA replication system developed using these CRCs can be used to study the complete RNA replication events of FMDV.
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Cottam, Eleanor Myfanwy. "Micro-evolution of foot-and-mouth disease virus." Thesis, Connect to e-thesis. Move to record for print version, 2008. http://theses.gla.ac.uk/92/.
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Thesis (Ph.D.) - University of Glasgow, 2008.Ph.D. thesis submitted to the Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, 2008. Includes bibliographical references. Print version also available.
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Lea, Susan Mary. "Structural studies on foot-and-mouth disease virus." Thesis, University of Oxford, 1993. http://ora.ox.ac.uk/objects/uuid:438dc0ae-b899-40fd-84dc-03d3fc1a537f.
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Foot-and-mouth disease viruses (FMDVs) constitute the aphthovirus genus of the Picornaviridae. The structures of Oi subtype viruses OiK and G67 have been solved and comparisons reveal the structural basis of monoclonal antibody escape mutations in G67. Escape mutations are seen to occur at surface-exposed residues and to provoke structural changes limited to the altered side chains. Comparisons of the structures of O1 and O1BFS (Acharya et al., Nature 337, 709-716 (1989)) suggest that changes occurring 'in-the-field' in response to polyclonal antibody pressure may be subtly different from mutations produced by monoclonal antibody pressure in vitro. Field mutations are seen to alter less exposed residues and to have more far-reaching structural effects than the in vitro, monoclonal provoked mutations. Crystals of G67 are seen to be 'intimately twinned', the data possessing extra symmetry due to a mis-packing of the crystals. A protocol, based on current real-space averaging procedures with a novel constraint imposed, has been used successfully to deconvolute these data. This method might be more generally applied to deconvolute the wavelength overlaps that occur when using the Laue method. The structures of C-S8cl and mutant SD6-6 have been solved at a resolution of 3.5Å. These structures enable comparisons between members of different FMDV serotypes to be made for the first time, namely: serotype 0 (O1BFS) and serotype C (C-S8cl). Flexibility of the Arg-Gly-Asp containing G-H loop of VP1 is seen to be amongst the most conserved structural features. This loop is implicated in receptor binding and possible roles for the observed flexibility are discussed. The CS8cl structure also reveals more detail in previously disordered regions of the capsid, namely: the N-terminal residues of VP2 and potential myristate density under the 5-fold axis of the virion. Analysis of structures from the Protein Data Bank reveals different patterns of amino acid use in proteins involved in the two halves of the immune recognition event i.e. immunoglobulins and viruses. These patterns seem to be based not only on the characteristics of the most used amino acids but also on characteristics of the nucleotide codons used to code for them.
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Edacheril, Mathew. "Assessment of herd immunity to foot-and-mouth disease." Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314315.
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Howes, Emma Louise. "Investigating the foot-and-mouth disease virus 3A protein." Thesis, University of St Andrews, 2018. http://hdl.handle.net/10023/15521.
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Foot-and-Mouth Disease Virus (FMDV) is a globally important pathogen responsible for causing Foot-and-Mouth Disease (FMD) in wildlife and domestic livestock species and has significant economic impacts. FMD is difficult to control due to its highly infectious nature, wide diversity of host species and the existence of multiple serotypes; therefore, understanding the processes of FMDV infection and viral RNA replication are key to the development of improved diagnostics and vaccines. This thesis investigates the potential roles of the FMDV 3A non-structural protein using a combination of sub-genomic replicons, recombinant viruses and proteomics techniques. The picornavirus 3A protein has previously been linked with roles in replication complex formation, virulence and determining viral host range. This thesis presents findings showing that a naturally occurring deletion in 3A had differing effects on replication in cells lines derived from different natural hosts thereby supporting the conclusion that 3A has an important role in viral host range. Proteomic (immunoprecipitation and mass spectroscopy) investigations were carried out to identify potential cellular interaction partners of FMDV 3A, and the impact on infection and replication of reducing expression of two selected cellular proteins Rab7L1 and TBC1D20 was investigated. The 3A protein of FMDV was shown to include a conserved FFAT motif (which bind the ER resident protein VAP) in its N terminal domain. A role for this motif was also investigated with the results suggesting that the 3A FFAT motif is important for efficient viral replication. Finally, the potential role of 3A to act as the donor of 3B during replication was investigated. Key findings from experiments using FMDV replicons and recombinant viruses showed that full-length P3 and the processing intermediate 3ABBB are not required for viral RNA replication suggesting that the preferred donor of 3B for uridylation is likely a 3BC containing precursor protein.
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Mahdi, Ali Jafar. "Foot and mouth disease in Iraq: strategy and control." Kansas State University, 2010. http://hdl.handle.net/2097/4620.
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Master of ScienceDepartment of Diagnostic Medicine/Pathobiology
Gary A. Anderson
Foot-and-mouth disease (FMD) is a highly infectious viral disease of cattle, pigs, sheep, goats, buffalo, and artiodactyl wildlife species. Foot-and-mouth disease virus is endemic and periodic devastating epidemics have occurred and caused heavy economic losses in Iraq for a long time. The first official cases of FMD were recorded in 1937, while the first record of a specific FMD serotype in Iraq was serotype A in 1952. Other serotypes have been reported since then; serotypes O, SAT-1 and Asia1 were recorded in 1957, 1962, and 1975, respectively. Veterinary Services in Iraq has been severely weakened over the past two decades, and its infrastructure has been devastated as a consequence of previous political conflicts, wars and international sanctions. The breakdown of Veterinary Services led to the disruption of disease control strategies, collapse of disease surveillance and monitoring, and weakening of response systems. The destruction of the Al-Dora FMD laboratories for diagnosis and vaccine production by the United Nation in 1996, and the restrictions placed on the importation of vaccines have strongly affected the FMD control program. A severe epidemic of FMD occurred in Iraq in 1998, affecting 2.5 million ruminants and causing heavy losses in newly born animals. It is estimated to have killed about 550,000 animals. The outbreak was due to the serotype O1 Middle East strain which has affected large and small ruminants. In 2009, Iraq was severely affected by new serotype A (subtype A Iran 05). The major efforts of Veterinary Services in Iraq have been directed towards control of FMD by vaccination strategies. Two types of vaccine have been used, trivalent vaccine (O, A 22, and Asia 1) for cattle and buffalo and monovalent vaccine (O Manisa) for sheep and goats. Vaccination has been implemented once yearly on a voluntary basis. Sometimes other limited control measures have accompanied vaccination, which include quarantine, movement control, focused vaccination, disinfection, and public awareness programs. The FMD control program in Iraq has been confronted by many challenges: deficits in FMD surveillance and emergency preparedness, limited diagnostic capabilities, difficulties in restricting animal movement, and lack and irregular supply of appropriate vaccines.
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Sahle, Mesfin. "An epidemiological study on the genetic relationships of foot and mouth disease viruses in East Africa." Pretoria : [s.n.], 2010. http://upetd.up.ac.za/thesis/available/etd-08132008-095346/.
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O'Connor, Steven Patrick. "The production of foot-and-mouth disease virus-like particles in the plant Nicotiana benthamiana: a potential candidate vaccine for foot-and-mouth disease." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29378.
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Foot and mouth disease virus (FMDV) infects cloven-hoofed animals causing the highly contagious foot and mouth disease. It is spread by contact or through aerosol. The disease is often debilitating for infected animals and can be fatal. Severe measures are taken to contain outbreaks; quarantine and trade restrictions are imposed and herds with infected individuals are culled to prevent the spread of the disease. Consequently, outbreaks of the disease have drastic implications for agriculture and social economies which can be devastating for affected countries. There are seven serotypes of the virus; of which SAT1, SAT2, and SAT3 are endemic to Africa. South African buffalo populations such as those in the Kruger National Park, are natural carriers of FMDV (Thomson 1995). Careful monitoring and regular vaccination are necessary to detect and prevent outbreaks and the spread of the disease to livestock of neighbouring areas and farms. The vaccines currently used are inactivated FMDV virions. These are produced in cell culture, an expensive process that requires high levels of biosafety. Furthermore, inactivated virions present non-structural proteins (NSPs) and thus cannot be distinguished from the infectious virus by imported ELISA kits that utilise the NSPs as coating antigens and conventionally produced detecting antibodies. We aimed to use recombinant constructs encoding the FMDV capsid and protease genes, cloned into the different vectors; pRIC, pEAQ and pTRAc, for transient expression in Nicotiana benthamiana to generate virus-like particles as an alternative vaccine candidate. Using a plant based expression system presents numerous advantages over the traditional cell culture production of the vaccine currently used. After having synthesised the FMDV genes P12A and 3C, the fusion gene P1-2A-3C (required for the vaccine) was cloned into these different plant expression vectors available in our laboratory. With Agrobacteria mediated infiltration of N. benthamiana, we demonstrated expression of recombinant protein by western blotting; and Coomassie stain, for each of the different constructs. Analytical ultra-centrifugation through a sucrose gradient was used to purify protein extracts. Comparison against a dilution series of bovine serum albumin was used to quantify the yield for each respective vector construct by densitometry. Transmission Electron Microscopy (TEM) imaging was used to qualitatively determine virus-like particle (VLP) assembly. In conclusion, we demonstrate proof of concept for a viable alternative approach for the production of a candidate vaccine for FMDV.
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Fry, Elizabeth Evelyn. "The three dimensional structure of foot and mouth disease virus." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281130.
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Bessell, Paul R. "Spatial epidemiology of Foot and Mouth Disease in Great Britain." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4831.
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During 2007 the UK experienced outbreaks of three notifiable exotic livestock diseases; Foot and Mouth Disease (FMD), Highly Pathogenic Avian Influenza (HPAI) and bluetongue. Large epidemics of any of these diseases would have a serious impact on animal welfare, farming, food production and the economy. In light of this, understanding holdings which are most likely to acquire and spread infection and being able to identify areas at higher risk of an epidemic is valuable when preparing for and managing an epidemic. This thesis uses a spatial epidemiological framework and the detailed disease and demographic data from the 2001 Great Britain (GB) FMD epidemic to develop static models of the risk of FMD susceptibility and transmission. These models are used to develop maps of FMD risk. These methods are then applied to the outbreak of FMD in 2007. The inputs for this analysis comprised a set of data relating to the farms diagnosed with FMD and farms culled as part of the disease control measures. The cleaning of these data is described and data which were estimated relating to dates of infection and putative sources of infection are evaluated. The distribution of farm holdings and animals is taken from the June 2000 GB agricultural census, off-fields of farms in the agricultural census are recorded in other datasets and these have been identified and linked to census holdings. A model of holding level susceptibility is developed using both farm level variables and measures of animal numbers in the locality of the holding as well as the distance to the nearest farm infected before the ban on animal movements (seeds). The overall fit of the model was very good with an area under the Receiver Operator Characteristic (ROC) curve of 0.91. A further model was developed to describe the risk of FMD transmission. However, due to incompleteness of transmission data, this was a model of the risk of finding a subsequent Infected Premises (IP) within 3km of an IP. Risk factors were a combination of holding level variables and locality measures as well as data relevant to the infection, such as infectious period and the species initially infected. The area under the ROC curve for this model was 0.71, which is regarded as an acceptable fit. Geographical barriers to FMD transmission were investigated using a case-control methodology, linear barriers comprising rivers and railways had a significant protective effect with respect to disease transmission (odds ratio = 0.54, 95% CIs = 0.30,0.96, p=0.038). Modelled values for the transmission and susceptibility models were transformed to a raster surface in ESRI ArcMap for both the disease as it was seeded in the 2001 epidemic and a non-specific background risk surface independent of the distribution of seeds. A risk map generated for the outbreak of FMD in Surrey in August 2007 suggested that there was little risk of a large outbreak in Surrey. Potential disease introductions through livestock movements from Surrey into Scotland were identified and these suggested that if the disease were introduced into Scotland there was great danger of substantial local spread. These methods described in this thesis have been used to map risk of FMD and subsequently applied to inform the risk presented by a different outbreak of FMD. The study underlines the value of detailed data both disease and demographic, for epidemic management. Similar methods could and should be applied to other infectious diseases threats of livestock such as HPAI and bluetongue.
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Jochimsen, Aaron A. "The vulnerability of U.S. agriculture to foot and mouth disease." Thesis, Monterey, California: Naval Postgraduate School, 2015. http://hdl.handle.net/10945/45881.
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Approved for public release; distribution is unlimitedThe U.S. livestock industry represents a critical economic infrastructure, due to its size and influence on national and international agricultural systems. The high-concentration farming practices that allow the United States to be a world leader in agriculture also present a vulnerability to biological pathogens, particularly foot and mouth disease (FMD). The purpose of this thesis is to stimulate and broaden the discussion of the U.S. livestock industry’s susceptibility to an FMD outbreak, regardless of how it is introduced. It reviews case studies of prominent outbreaks in the United Kingdom (2001) and Taiwan (1997). The themes that emerged from these case studies—responsibility and response—informed a discussion of ways to increase U.S. efficiency when responding to an FMD outbreak. The case studies illustrate that FMD outbreaks in thriving livestock industries can have devastating economic, social, and political consequences. The United States should address these and other international FMD outbreaks to improve the preparedness and resilience of the U.S. livestock industry to an outbreak of FMD.
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Abrams, Charles C. "The biosynthesis of foot-and-mouth disease virus empty capsids." Thesis, University of Reading, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.332255.
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Flint, Mike. "A study of foot-and-mouth disease virus polyprotein processing." Thesis, University of Reading, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295238.
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Davidson, Freda Lynn. "Alternative strategies for foot-and-mouth disease control in pigs." Thesis, University of Hertfordshire, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361189.
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Chitray, Melanie. "Investigating potential factors affecting foot-and-mouth disease virus internalization." Pretoria : [s.n.], 2008. http://upetd.up.ac.za/thesis/available/etd-02192009-165513/.
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Knight-Jones, Theo. "Field evaluation of foot-and-mouth disease vaccination in Turkey." Thesis, Royal Veterinary College (University of London), 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.618321.
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Borley, Daryl W. "Epitope dominance studies with serotype O foot-and-mouth disease." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:4adc3373-1d89-41d9-b1ce-7d8cbb0e817a.
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Foot-and-mouth disease virus (FMDV) is an economically devastating and highly contagious livestock pathogen. It exists as seven serotypes, comprising numerous antigenically distinct subtypes. The large amount of antigenic heterogeneity has confounded attempts at developing broadly reactive vaccines. In order to overcome this issue the fundamentals of the interactions between the virus and the host humoral immune response must first be understood. Previous work in this area using monoclonal antibody (mAb) escape mutants has identified five antigenic sites for the O serotype and efforts have been made to quantify their relative importance. However, this does not represent a complete picture of serotype O antigenicity. The work conducted in this thesis demonstrates the role of a limited number of dominant substitutions in mediating the antigenic diversity of serotype O Foot-and-Mouth disease virus. Two alternative but complementary methods for identifying epitopes were developed. The first used a mathematical model to analyse newly generated serological and sequence data from 105 viruses, cultured for this purpose (and cross-reacted to 5 reference antisera), in the context of an existing crystallographic structure to identify and quantify the antigenic importance of sites on the surface of the virus. The second approach was purely structural, using existing B cell epitope prediction tools to develop a method for predicting FMDV epitopes using existing crystallographic structures of FMDV. These techniques were validated by the use of reverse genetics, which confirmed the impact on cross reactivity of two predicted novel serotype O antigenic residues, with a further four novel residues identified by looking in depth at the interactions between two genetically close, but antigenically distant viruses. This increased knowledge of the antigenic composition of serotype O FMDV contributes to our understanding of the nature of vaccine efficacy and the breadth of protection, which, in the longer term, will aid in the goal of developing vaccines to better protect livestock from such a highly antigenically variable disease.
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Ludi, Anna Barbara. "Antigenic variation of foot-and-mouth disease virus serotype A." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648211.
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Chitray, Melanie. "Investigating potential factors affecting foot-and-mouth disease virus internalisation." Diss., University of Pretoria, 2008. http://hdl.handle.net/2263/30391.
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Foot-and-mouth disease (FMD) is a highly contagious disease caused by the FMD virus (FMDV) belonging to the Picornaviridae family. The virus affects cloven-hoofed animals and occurs as seven immunologically distinct serotypes where six of the seven serotypes occur in Africa. This fact, as well as the role of wildlife in virus maintenance, makes eradication and control of FMDV in Africa difficult. Thus, it is imperative to attain more information regarding the genetic diversity of FMD viruses prevalent on the African continent to further our knowledge of the virus as well as to enable better control strategies and the development of improved vaccines. Sufficient genetic information regarding the Leader (L) and complete capsid-coding, P1, region of serotype A and O viruses prevalent on the African continent is lacking, although the SAT isolates have been extensively characterised in the past. In this study the sequence of the L/P1-coding region was successfully determined using a genome-walking approach for a small number of A and O viruses recovered from outbreaks isolated from various species in East and West Africa over the last 33 years. Phylogenetic analysis of the P1 and capsid-coding regions 1A, 1B, 1C and 1D revealed that the African isolates grouped strictly according to serotype and geographic region which indicated the possibility of transboundary spread of the virus within East and West African countries respectively. In contrast, phylogenetic analysis of the non-structural, Lpro-coding region revealed a different tree topology compared to the capsid-coding regions for the A and O isolates with sub-grouping according to serotype and geographic regions was less apparent. The relatedness between the serotype A and O L region might be the result of genetic recombination. The inter and intratypic nucleotide and amino acid variation of the A and O isolates revealed that the most variable capsid-coding region was the externally located VP1 whilst the internally located VP4 capsid protein was the most conserved. The observed variation is in agreement with other studies and reflects the selective pressures on these proteins which either allow or prevent the occurrence of genetic changes for structural constraints or immune escape. Surprisingly, the L protease-encoding region also displayed a high degree of variation. A detailed analysis of the L/P1 amino acid alignment of the A and O isolates revealed that although the extent of variation is high in these regions, the amino acids identified in previous studies as important for FMDV structure (for the capsid-coding regions) and function were found to be conserved, indicating that the virus has adapted itself to elude the host immune response without affecting its vital functional and structural abilities. Additionally, it was observed that the amino acid residues identified as being important for FMDV attaching to the host cell receptors e.g. the RGD amino acid motif of VP1 was highly conserved for all isolates. To further investigate the FMDV-receptor interaction, RT-PCRs were developed to examine the mRNA expression level of the known FMDV receptors. The â integrins that facilitate FMDV cell entry i.e. â1, â3, â6, â8 and heparan sulphate proteoglycans (HSPG) were investigated in susceptible cell lines used for FMDV vaccine production i.e. IB-RS-2 and BHK-21. The RT-PCRs were successfully developed and optimised. The results showed that the mRNA expression levels were variable for all receptor cDNAs tested across 36 passage levels of IB-RS-2 and BHK-21 cells. No distinct differences in virus susceptibility for three FMDV strains with continuous cell passage of IB-RS-2 and BHK-21 cells at passage levels 5, 21 and 36 could be found. The information gained from this study regarding the viral L and P1 region genetic diversity, and phylogenetic analysis has indeed impacted on our understanding of FMDV African viruses. Additionally, the investigation of the FMDV receptor mRNA expression levels and virus susceptibility on two cell lines with continuous cell passage has proved a vital starting point to determine the possible receptors expressed on the surface of cells used by the vaccine production division at the ARC-OVI-TADP and forms the basis for further investigations of the FMDV receptors on the protein level and the development of a real-time RT-PCR for FMDV receptor expression.Dissertation (Msc)--University of Pretoria, 2008.
Veterinary Tropical Diseases
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Di, Nardo Antonello. "Phylodynamic modelling of foot-and-mouth disease virus sequence data." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7558/.
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The under-reporting of cases of infectious diseases is a substantial impediment to the control and management of infectious diseases in both epidemic and endemic contexts. Information about infectious disease dynamics can be recovered from sequence data using time-varying coalescent approaches, and phylodynamic models have been developed in order to reconstruct demographic changes of the numbers of infected hosts through time. In this study I have demonstrated the general concordance between empirically observed epidemiological incidence data and viral demography inferred through analysis of foot-and-mouth disease virus VP1 coding sequences belonging to the CATHAY topotype over large temporal and spatial scales. However a more precise and robust relationship between the effective population size (Ne) of a virus population and the number of infected hosts (or 'host units') (N) has proven elusive. The detailed epidemiological data from the exhaustively-sampled UK 2001 foot-and-mouth (FMD) epidemic combined with extensive amounts of whole genome sequence data from viral isolates from infected premises presents an excellent opportunity to study this relationship in more detail. Using a combination of real and simulated data from the outbreak I explored the relationship between Ne, as estimated through a Bayesian skyline analysis, and the empirical number of infected cases. I investigated the nature of this scaling defining prevalence according to different possible timings of FMD disease progression, and attempting to account for complex variability in the population structure. I demonstrated that the variability in the number of secondary cases per primary infection Rt and the population structure greatly impact on effective scaling of Ne. I further explored how the demographic signal carried by sequence data becomes imprecise and weaker when reducing the number of samples are described, including how the extent of the size and structure of the sampled dataset impact on the accuracy of a reconstructed viral demography at any level of the transmission process. Methods drawn from phylodynamic inference combine powerful epidemiological and population genetic tools which can provide valuable insights into the dynamics of viral disease. However, the strict and sensitive dependency of the majority of these models on their assumptions makes estimates very fragile when these assumptions are violated. It is therefore essential that for these methods to be applied as reliable tools supporting control programs, more focused theoretical research is undertaken to model the epidemiological dynamics of infected populations using sequence data.
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Wong, Yim-ping, and 黃艷萍. "Development of a subunit vaccine against foot-and-mouth disease virus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B31221993.
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Wright, Caroline Frances. "Dissecting the molecular basis of foot-and-mouth disease virus evolution." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/4254/.
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Foot-and-mouth disease virus (FMDV) causes the most contagious transboundary disease of animals, affecting both wild and domestic cloven-hoofed animals. Similarly to other RNA viruses, FMDV is highly variable as a result of the inherent low fidelity of the viral RNA-dependent RNA polymerase. The accumulation of this variability and relatedness between FMDV sequences was used to provide evidence for modes of transmission (fomite) as well as a constant clock rate across two FMDV topotypes (~8.70 x 10-3 substitutions/site/year), during the 1967 UK FMD epidemic, using full genome consensus sequencing. However, during an epidemic, virus replicates within multiple animals, where it is also replicating and evolving within different tissues and cells. Each scale of evolution, from a single cell to multiple animals across the globe, involves evolutionary processes that shape the viral diversity generated below the level of the consensus. During this PhD project, next-generation sequencing (NGS) was used to dissect the fine scale viral population diversity of FMDV. Collaboration with the Institute of Biodiversity, Animal Health and Comparative Medicine at the University of Glasgow provided the specialist bioinformatic and statistical capabilities required for the analysis of NGS datasets. As part of this collaboration, a new systematic approach was developed to process NGS data and distinguish genuine mutations from artefacts. Additionally, evolutionary models were applied to this data to estimate parameters such as the genome-wide mutation rate of FMDV (upper limit of 7.8 x 10-4 per nt). Analysis of the mutation spectra generated from a clonal control study established a mutation frequency threshold of 0.5% above which there can be confidence that 95% of mutations are real in the sense that they are present in the sampled virus population. This threshold, together with an optimized protocol, was used for the more extensive investigation of within and between host viral population dynamics during transmission. Analysis of mutation spectra and site-specific mutations revealed that intra-host bottlenecks are typically more pronounced than inter-host bottlenecks. NGS analysis has distinguished between the population structure of multiple samples taken from a single host, which may provide the means to reconstruct both intra- and inter-host transmission routes in the future. A more sophisticated understanding of viral diversity at its finest scales could hold the key to the better understanding of viral pathogenesis and, therefore development of effective and sustainable disease treatment and control strategies.
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Hofner, Maureen Catherine. "A study of foot-and-mouth disease virus pathogenesis in cattle." Thesis, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338844.
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Freire, Antonio de Padua. "Epidemiological studies of foot-and-mouth disease in Minas Gerais Brazil." Thesis, University of Reading, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363661.
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McInerney, Gerald Michael. "Trans-encapsidation of capsid-defective foot-and-mouth disease virus replicons." Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301929.
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Collen, Trevor. "T cell responses of cattle to foot-and-mouth disease virus." Thesis, Open University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293303.
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Ali, Shireen. "Origin of replication complexes during foot and mouth disease virus infection." Thesis, University of Hertfordshire, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302421.
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Salt, Jeremy Simon. "The immunology of foot and mouth disease virus persistence in cattle." Thesis, University of Hertfordshire, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.358299.
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Wong, Yim-ping. "Development of a subunit vaccine against foot-and-mouth disease virus /." Hong Kong : University of Hong Kong, 1999. http://sunzi.lib.hku.hk/hkuto/record.jsp?B21080161.
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Malik, Nayab. "Structural characterisation of the foot-and-mouth disease virus uncoating pathway." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:1120387b-eeb1-4a66-a380-06cfe37c5a47.
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Foot-and-mouth disease virus is a single-stranded RNA virus that belongs to the genus aphthoviruses, in the family Picornaviridae, and causes disease in cloven-hoofed animals. It is one of the biggest hindrances to the international trade of animals and animal products in the world. The virus capsids readily dissociate into pentamers at acidic pH. While there have been several studies on enterovirus uncoating, this process is poorly-understood for aphthoviruses, and there are no published structures elucidating how FMDV undergoes this transformation to infect cells. Furthermore, there are no structures available for a dissociated FMDV pentamer. Thus far, there has been only one paper claiming to show, at low resolution, a disassembly intermediate for another aphthovirus, Equine Rhinitis A Virus (ERAV). Here, a 5.2Å-structure of an FMDV assembly formed from acid dissociated pentamers, visualised using cryo-electron microscopy (cryo-EM), is presented. This inside-out assembly of the pentamers highlights the extensive conformational changes in the pentamers that may have lead to the disassembly of the native capsid. Also presented here is a lower-resolution structure of the isolated dissociated pentamer (8.2 Å), enabling a comparison of the differences between native FMDV particles, the dissociated- and the re-assembled pentamers. These analyses elucidate why the pentamers may have been unable to re-assemble properly. Together, these data suggest that the ERAV structure mooted to be a disassembly intermediate may have formed from re-assembled dissociated pentamers. Furthermore, it is concluded that there is still no hard structural evidence that aphthoviruses form an intermediate particle during disassembly. The thesis also includes high-resolution cryo-EM structures of the FMDV serotypes SAT1 and SAT3 (3.8 Å and 3.1 Å respectively), derived from inactivated virus-pellets, thus completing the repository of high-resolution structures for all SAT serotypes. The results provide an insight into the reasons for SAT3 being the most thermally-unstable picornaviruses, and also include predictions and comparative analyses with known antigenic sites of other FMDV serotypes.
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Quan, Melvyn. "Quantitative dynamics of foot-and-mouth disease virus infection in pigs." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/30663.
Full textAbstract:
The main objectives of this project were to provide an accurate quantitative description, and develop a mathematical model, of FMDV dynamics in infected pigs. Time-course studies were set up and the viral load in serum, nasal swabs and tissue samples were determined. Time after infection, mode of infection, inoculation dose and housing conditions were examined as possible determinants of viral load. Similar results were obtained from pigs infected with FMDV by the intravenous, intradermal or oro-nasal route. Initial models of the early viral dynamics of FMDV disagreed with the experimental data. Experimental data showed larger effects of dose on the temporal distribution of viraemia than was predicted by the models. This disagreement could be resolved by: i) limiting the rate of infection of epithelial cells at low FMDV concentrations; ii) converting the virus removal system (such as the mononuclear phagocyte system) into one of limited capacity; or iii) the addition of a virus removal system of limited capacity, such as non-specific binding of FMDV into the models. A hypothesis in which the rate of infection of epithelial cells was limited at low FMDV concentration could be supported by the literature. For FMDV to successfully infect and replicate within a cell, host protein synthesis has to be inhibited and anti-viral defences inactivated. The probability of a successful infection of a cell increases as the number of infecting viruses increases, suggesting that the rate of infection of cells at low FMDV concentrations is indeed limited. The experimental work has highlighted the strong relationship between inoculation dose and dynamics of FMDV in vivo and the modelling exercise has highlighted important determinants of viral dynamics, as well as areas where further research should be directed.
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Logan, Grace. "The molecular and genetic evolution of foot-and-mouth disease virus." Thesis, University of Glasgow, 2017. http://theses.gla.ac.uk/7877/.
Full textAbstract:
Foot-and-mouth disease virus (FMDV) (Family: Picornaviridae, Genus: Aphthovirus) is a significant global pathogen with extensive economic impact. FMDV has a low fidelity RNA-dependent RNA polymerase and lacks proof reading capability. This coupled with its relatively short generation time and large population sizes means it exists in a swarm of genetically closely related variants. The reservoir of diversity contained within this mutant spectrum allows the virus to adapt rapidly to new environments. Much of the previous work looking at virus evolution has focused on the consensus level genetic sequence. The advent of next generation sequencing (NGS) technologies enables evolutionary studies of the entire viral swarm. This PhD project uses NGS technologies to interrogate the swarm structure by investigating factors affecting the viral swarm and the dynamics of variants within it. Furthermore, this work shows how analysis of the swarm can reveal fundamental information about virus biology. A PCR-free NGS methodology was developed to create deep sequencing data sets of all genomes present within an FMDV viral swarm. The elimination of the PCR step results in less errors being introduced in the sequencing process thereby improving the resolution and reliability of the identification of low level variants. This optimised method was then used to define and compare the FMDV swarms of several wildtype isolates. This revealed differences in swarm structure from isolate to isolate and produced evidence of within swarm selection. Not all proteins known to be under selection at the consensus level were also under selection within the swarm. The diversity of viruses within the swarm was found to be dependent upon the host from which a virus was sampled, with African buffalo potentially able to maintain multiple infections. Subconsensus variants in these mixed samples had mutations at positions previously associated with immune escape. Investigation of the evolution of swarm structure when adapting to new cell type in vitro indicated that two distinct population structures can exist relative to the existence of adaptive pressure. These two population structures have different distributions of variable nucleotides but comparative total levels of variation (as measured by Shannon's entropy). Deep sequencing of the virus swarm enabled the discovery of conserved novel stem loop structures, which were hypothesized to be required for packaging of the virus genome. Mutating these sites produced a virus with decreased packaging efficiency. This thesis includes novel analysis techniques for considering the viral swarm. It demonstrates how investigating the diversity in the swarm can help us to understand virus molecular biology, its evolution and the limits upon this. Understanding viral evolution at this scale has the capacity to improve our fundamental understanding of the biology and evolution of FMDV which can in turn inform vaccine design and disease control strategies.
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Scott, Katherine Anne. "Improved stability of foot-and-mouth disease virus (FMDV) SAT2 capsid." Thesis, University of Pretoria, 2016. http://hdl.handle.net/2263/60130.
Full textAbstract:
The thermostability of vaccines is of crucial importance in Africa, where the
logistical process to get the vaccine from the manufacturer to the animal may take months,
and in many remote regions transport and storage is in the absence of a cold-chain.
Vaccines with improved stability and less reliance on a cold-chain are needed and could
improve the longevity of immune responses elicited in vaccinated animals. In South Africa,
cattle in the vaccination zone neighbouring the Kruger National Park have to be
vaccinated thrice annually because of declining antibody responses at three months postvaccination.
FMDV is known to be unstable, especially for O and SAT2 serotypes in mildly
acidic pH conditions or at elevated temperatures, leading to dissociation of the capsid
(146S particle) and loss of immunogenicity. The link between rapidly declining antibody
responses and capsid stability have been reported by Doel and Baccarini, 1981. We
hypothesized that more stable viruses, especially thermostability, will not only improve the
protective immune response in animals but also require less frequent booster
vaccinations.The residues at the capsid inter-pentamer interfaces, and their interactions, are important for the infectivity and stability of the virion and mutations adjacent to these interfaces have an effect on the conformational stability of FMDV. However, experimental studies on the relative importance of residues and molecular interactions in viral capsid assembly, disassembly, and/or stability are still very limited, especially for the SAT serotypes of FMDV. This study investigated the effects of potential residues at the pentameric interfaces that are responsible for increased thermostability and potentially improved stability candidates were tested in small (guinea pigs) and large (cattle) animal vaccination trials to understand the role of stabilised antigens on immune responses. The biological variation in biophysical stability in SAT2 viruses in the southern Africa region was investigated to determine if any naturally occurring viruses have greater capsid thermostability. Naturally occurring stable viruses could be used as prospective candidates in vaccine production and therefore potentially result in increased duration of immune responses.
Our first aim was to investigate the role of different amino acid changes at the interface and their effect on capsid stability using models derived by Oxford University. These changes were introduced by mutating the SAT2 ZIM7/83 infectious genome-length clone (pSAT2) to derive mutated chimeric SAT2 viruses. We quantified the stabilizing effects of these mutations by using various stability assays. We established the novel thermofluor shift assay that is able to quantify the capsid stability of viruses. The growth kinetics, antigenicity, genetic stability, pH and salt sensitivity were investigated for each of the genetically engineered viruses (Chapters 2 and 3).
The second aim was to further our understanding on the correlation between improved stability and immune responses by performing small animal (Chapter 2) and large animals trials in cattle (Chapter 4) and comparing stabilised and wild-type antigens. This study for the first time for SAT vaccines, determined differences in IgG1 and IgG2 profiles, interferon gamma (IFN-γ) responses and differences in total and neutralising antibodies of stabilised and wild-type antigens over a six month period in cattle (Chapter 4). Animals were intra-dermolingually challenged with live virus to determine levels of protection the antigens have afforded.
In addition, a third aim will be to better understand the inherent thermostability variation of SAT2 viruses in the Southern African region (Chapter 5) by establishing a protocol for screening field isolates as potential vaccine strains and correlating their stability to amino acid residues at the interface of the 146S particles.
Thesis (PhD)--University of Pretoria, 2016.
Agricultural Research Council
Veterinary Tropical Diseases
PhD
Unrestricted
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Sangare, Oumou. "Molecular epidemiology of foot-and-mouth disease virus in West Africa." Thesis, University of Pretoria, 2002. http://hdl.handle.net/2263/23010.
Full textAbstract:
The economy of West African countries is dependent mainly on agriculture. Livestock production is a vital source of providing dietary protein for the rapidly growing human population and it is therefore important to define strategies for controlling infectious diseases that are undermining the livestock industry. Although the foot-and-mouth disease (FMD) virus causes one of the most devastating economical diseases, it has been mainly ignored in West Africa due to low mortality rates in the face of other diseases that cause significant mortalities. This may explain the lack of interest for studying FMD infections in the region. However, the eradication of other diseases such as Rinderpest together with an increase in the number of outbreaks of FMD in recent years has caused a renewed interest in understanding the epidemiology of the disease. Foot-and-mouth disease is a highly contagious disease of cloven-hoofed animals. The causative agent, FMD virus, has a high rate of genetic variation in its single-stranded RNA genome. The genetic characterization of the surface capsid protein gene, VP1, is the most informative technique for studying the molecular epidemiology of FMD. The genetic profile of different serotypes of FMDV isolated across West Africa was investigated in this study using manual and automated nucleotide sequencing. A total number of 21 type O isolates from Ghana, Burkina Faso and South Africa (1992-2000), 23 SAT-1 viruses from Niger and Nigeria (1975-1981) and 30 SAT-2 viruses from Mali, Ivory Coast, Ghana, Nigeria, Liberia, Senegal and Gambia (1974-1991) were investigated. The sequence data was used to establish the phylogenetic relationships between the west African strains and those previously characterized from East, central and southern Africa as well as other regions of the world in the case of serotype O. Viruses from West Africa formed a single genotype while the isolates from South Africa clustered with the Pan-Asian topotype (Bangladesh 1997&Japan 2000). Sequence identity of 99 % and 95 % were found between Ghana-Burkina Faso and South Africa-Bangladesh type O viruses, respectively. Within SAT-2, the viruses characterized were isolated over 27 years from seven countries in West Africa and two indigenous topotypes (> 97 % sequence identity in the cluster) were identified. Of interest was the clustering of viruses Nigeria from 1982 and Eritrea in 1998, which has provided the first evidence of virus transmission between West and East Africa. For SAT-1, two distinct lineages (I-II) were identified. Lineage I consisted of viruses isolated between 1975-1976 from neighboring countries Niger and Nigeria, while lineage II was composed of viruses recovered from outbreaks between 1979-1981 in Nigeria. Furthermore, viruses from the latter lineage shared > 98 % sequence identity across the VP1 gene providing a clear indication of a long circulation of virus in the field in West Africa. For the serotypes investigated in this study viz. serotypes O, SAT-2 and SAT-1, it was shown that the year of isolation is more important in the epidemiology of FMD in West Africa than country of origin. The phylogenetic analysis demonstrated that viruses from each serotype grouped according to year of isolation rather than their geographical origin. This is in contrast of what was reported previously for FMDV strains in southern Africa. Results further revealed that FMD viruses from West Africa are evolving independently from viruses elsewhere on the continent and clustered in discrete genotypes. The genetic distinctiveness of west African FMD isolates is likely to be reflected antigenically and has implications in the selection of regionally appropriate field strains for use in vaccines to assist in the control of the disease.Thesis (PhD (Veterinary Tropical Diseases))--University of Pretoria, 2002.
Veterinary Tropical Diseases
unrestricted
37
Sabanathan, Saraswathy. "Neurodevelopmental outcomes following severe hand foot and mouth disease in Vietnam." Thesis, Open University, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.699826.
Full textAbstract:
In 2011, more than 160 children died in an unprecedented outbreak of Hand foot and mouth disease (HFMD) in Vietnam, predominantly associated with enterovirus 71 (EV-A71). The occurrence of encephalitis outbreaks in children at vulnerable developmental stages raised concerns of long-term consequences. Limited retrospective outcome studies in the literature lack either a healthy comparison group or a locally validated neurodevelopmental assessment tool. Brain MRI retrospective observations identified stereotypical patterns of brainstem lesions predominantly in severe EV-A71 HFMD cases with conflicting opinions on the prognostic role of MRI. I adapted the "Bayley Scales of Infant and Toddler development (3rd edition)" for Vietnam and demonstrated that the adaptation was reliable and valid. I conducted a prospective observational cohort study to test the hypothesis that children with severe HFMD, graded per Vietnam Ministry of Health classification, would have lower cognitive, language and motor Z scores than a healthy comparison group. All HFMD cases had virological samples taken and a sample of severe HFMD cases had brain MRI scans. All Z score 95% confidence intervals were within 2 standard deviations of the comparative healthy cohort mean suggesting outcomes at six months were not significantly lower than the healthy comparative group. I identified novel non- specific brain white matter abnormalities on MRI in all severity grades, lower motor Z scores in grade 2b children with MRI abnormalities and that Coxsackievirus A10 (CV-A10) was significantly associated with MRI abnormalities. These findings support surveillance of all enteroviruses during HFMD outbreaks and suggest MRI may be predictive of motor impairment in a subset of severe HFMD cases. No significant impairment was identified at six months follow-up, but more complex developmental skills are yet to emerge. Hence the study continues for an eighteen-month follow up to robustly determine emergence of long-term sequelae.
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Ngu, Duy Nghia. "Epidemiology and dynamic of hand, foot and mouth disease in Vietnam." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT099/document.
Full textAbstract:
Ce travail a analysé tous les cas de HFMD déclarés à Hai Phong pendant l’épidémie de 2011 et 2012 qui a été la plus importante au Vietnam et la première enregistrée dans le nord du pays. Hai Phong a connu la plus forte incidence au Nord Vietnam. C’était donc un bon modèle pour étudier la dynamique de cette maladie sans interférence et reliquats de précédentes épidémies ou de patients immunoadaptés.La première section est consacrée à une revue de la littérature sur EV-A71 et les entérovirus. La seconde section est divisée en trois chapitres, chacun abordant un aspect spécifique du projet.Le premier chapitre aborde la dynamique de la maladie et le rôle des directives officielles pour la gestion de l’épidémie de 2011-2012. Outre les éléments de base, cette étude apporte des résultats sur l’influence des directives HFMD durant l’épidémie, ce qui n’avait pas encore été fait. La publication des directives a conduit à un accroissement du score de sévérité et d’une réduction du délai entre le premier pic de fièvre et l’admission. Cet effet est associé à un accroissement de la sensibilisation qui a conduit à déclarer la plupart des patients avec des symptômes sévères pour assurer de meilleurs traitements et suivis. Le travail décrit dans ce chapitre a aussi démontré que trois vagues avec des caractéristiques différentes et causées par trois virus différents s’étaient succédées. La vague 1 et la vague 3 ont été causées respectivement par EV-A71 et par une combinaison de CV-A6 et CV-A16 alors que la vague 2 a été causée par un virus inconnu. Ce travail est aussi une analyse intégrative incluant une analyse spatiotemporelle. La maladie semble s’être étendue vers l’est en suivant les rivières pour atteindre les des zones plus peuplées à partir desquelles elle s’est répandue par les routes secondaires locales. Etant donné l’âge moyen des patients, environ 2 ans, la source de contamination doit être cherchée chez les adultes asymptomatiques contaminés lors de leurs activités professionnelles et des mobilités locales.Le deuxième chapitre aborde la phylogénie et la distribution spatiotemporelle de EV-A71 dans le nord du Vietnam et apporte un éclairage sur l’évolution et la dynamique de cet entérovirus. La protéine de capside VP1 a été ciblée. La première conclusion de ce chapitre est que l’épidémie de 2011 et 2012 n’a pas été causée par une souche exogène mais par des souches d’EV-A71 déjà présentes au Nord Vietnam. Ceci indique qu’elles peuvent se maintenir à faible niveau, asymptomatique, en stase génomique et avec une structuration géographique. La cause de l’épidémie devrait donc être recherchée dans le tissu socio-économique plutôt que dans une émergence extérieure. Une autre conclusion de ce chapitre est la corrélation observée ente les groupes de variants I/V et phylogénie, pathogénicité et groupe ethnique. Les profils des mutations I/V aux positions 249, 262 et 284 sur la protéine VP1 pourraient jouer un rôle dans la pathogénicité, ce qui est appuyé par la corrélation entre variants I/V et sévérité/ethnicité.Le dernier chapitre aborde la modélisation mathématique d’une maladie multiphases telle que HFMD. Il est essentiel de détecter aussi tôt que possible une nouvelle vague associée à un nouvel agent. Grace à la grande taille de la cohorte disponible pour ce travail (environ 9000 patients), nous avons pu développer un système d’équations différentielles apportant une forte correspondance avec les données observées. Le modèle a confirmé l’existence de trois vagues en 2011-2012, ayant des niveaux de virulence différents. Il permet aussi de caractériser chaque vague, de détecter l’apparition d’une nouvelle vague et d’associer des groupes patients à un tableau clinique.En conclusion, ce travail de thèse a permis de souligner plusieurs éléments clés à aborder de façon coordonnée afin de faciliter une surveillance efficace de l’HFMD au VietnamThis work analyzed all HFMD cases reported in Hai Phong in 2011 and 2012 outbreak which was the largest to have ever occurred in Vietnam and the first recorded in the northern part of the country. Hai Phong city experienced the highest HFMD incidence in North Vietnam. It was thus a good model for investigating the dynamic of the disease without interference and potential remains from previous outbreaks or patient immunological adaptation.The first section is dedicated to a review of the literature on EV-A71 and enteroviruses. The second section is divided in three chapters, each one addressing a specific issue of the project.The first chapter addresses the dynamic of the disease and the role of official guidelines in the handling of the 2011-2012 epidemic. Beside basic epidemiological features, the study also provides findings relating to the influence of HFMD guidelines during the outbreak period that has never been described before. The guideline release led to a significant increase of the severity score and reduced delay between onset and admission. This effect is linked to an increased awareness leading to patients being mostly declared with severe symptoms in order to ensure a better treatment and surveillance. The work presented in this chapter also demonstrated that three waves occurred with different characteristics and caused by three different viruses. Wave 1 and wave 3 were caused by EV-A71 and a combination of CV-A6 and CV-A16, respectively while Wave 2 was caused by an unknown virus. This work is also an integrative analysis including a spatiotemporal analysis. The disease seems to have expanded following the eastbound river system to reach densely populated settlements from where it secondarily expanded through local roads. Owing to the average age of the patients, around 2, the source of contamination must be sought for within asymptomatic adults being contaminated during their occupational activities and in local movements.The second chapter addresses the phylogeny and spatiotemporal distribution of EV-A71 in North Vietnam and provides an insight on the evolution and dynamic of the EV-A71 enterovirus. The VP1 capsid protein was used as target. The first conclusion of this chapter is that the 2011-2012 outbreak was not caused by an incoming strain but by EV-A71 strains which were already present in North Vietnam. This indicates that they can remain in a low level, asymptomatic state, in genomic stasis and with a geographic structuration. The cause for outbreaks should thus be sought for in the socio-economic patterns rather than in exogenous emergence. Another outcome of this chapter is the observed correlation between I/V variant groups and phylogeny, pathogenicity and ethnicity. The I/V pattern at positions 249, 262 and 284 on the VP1 protein might play a role in pathogenicity. The observed correlation of the I/V variant populations with severity and ethnicity strengthen this hypothesis.The last chapter addresses the mathematical modelling of a multiphase disease such as HFMD. It is essential to detect as soon as possible the emergence of new wave, associated to a novel agent. Owing to the large size of the cohort available for this work (ca. 9000 patients), we have been able to develop a differential equation model providing a very high fit with the observed data. The model confirmed that three waves were present in 2011-2012 with differing virulence. It also allows to characterize each wave, detect the start of a new one and associate groups of patients with specific patterns of symptoms.As a conclusion, this PhD work as underlined some key issues to be addressed in a coordinated way in order help developing an efficient surveillance and monitoring system for HFMD in Vietnam
39
Berryman, Stephen John. "Early events in cell entry by foot-and-mouth disease virus." Thesis, University of Surrey, 2005. http://epubs.surrey.ac.uk/842711/.
Full textAbstract:
The studies presented in this thesis demonstrate that foot-and-mouth disease virus (FMDV) infection mediated by the integrin ?v?6 takes place through clathrin-dependent endocytosis. Inhibition of clathrin-dependent endocytosis by sucrose treatment or transient expression of a dominant-negative version of AP180 inhibited virus entry and infection. Similarly, inhibition of endosomal acidification inhibited an early step in infection. Blocking endosomal acidification did not interfere with surface expression of alphavbeta6, virus binding to the cells, uptake of the virus into endosomes, or cytoplasmic virus replication. These observations suggest that the low pH within endosomes is required for a post-entry step of infection, most likely capsid uncoating and delivery of viral RNA into the cytosol. FMDV infection occurred in the absence of caveolae and inhibition of lipid-raft dependent endocytosis did not inhibit virus uptake or infection. Using immunofluorescence confocal microscopy, FMDV colocalised with alphavbeta6 at the cell surface but not with the B subunit of cholera toxin, a marker for lipid rafts. At 37°C, virus was rapidly taken up into the cells and colocalised with markers for early and recycling endosomes but not with a marker for lysosomes, suggesting that infection occurs from within the early or recycling endosomal compartments. This conclusion was supported by the observation that FMDV infection is not inhibited by nocodazole, a reagent that inhibits vesicular trafficking between early and late endosomes (and hence trafficking to lysosomes). Internalisation of alphavbeta6 and its accumulation in early and recycling endosomes was triggered by virus binding, suggesting that the integrin serves not only as an attachment receptor but also to deliver the virus to the acidic endosomes.
40
Birtley, James Robert. "Crystal structure of the 3C protease from foot-and-mouth disease virus." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413578.
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Knox, Stephen Richard. "Investigating the substrate specificity of foot and mouth disease virus 3C protease." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445242.
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Ryan, Eoin Denis. "The Pathogenesis of Foot-and-Mouth Disease in Foetal and Neonatal Lambs." Thesis, Royal Veterinary College (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.522721.
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Lau, Ming-ho, and 劉明昊. "Risk factors of hand foot mouth diseases outbreaks in kindergartens inHong Kong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42994901.
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Hingley, P. J. "Problems in modelling responses of animals to foot and mouth disease vaccine." Thesis, University of Reading, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356751.
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Miller, Laura Caldwell. "Penetration of the host cell membrane by foot-and-mouth disease virus." Thesis, University of Reading, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366045.
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Strong, Rebecca Marian. "Modification of protein synthesis initiation by foot-and-mouth disease virus proteases." Thesis, University of Surrey, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421325.
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Samuel, Alan Richard. "Genetic and antigenic studies on foot-and-mouth disease virus type O." Thesis, University of Hertfordshire, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245397.
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Munoz-Repiso, Mercedes Garcia-Valcarcel. "Cellular immune recognition of foot-and-mouth disease virus and derived antigens." Thesis, University of Hertfordshire, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283858.
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Lenman, Morag May. "Synthetic and structural studies of foot-and-mouth disease virus polyprotein processing." Thesis, University of St Andrews, 1996. http://hdl.handle.net/10023/15436.
Full textAbstract:
The 2A region of the foot-and-mouth disease virus (FMDV) polyprotein is only 16 amino acids in length. During synthesis of the FMDV polyprotein, a primary proteolytic processing event occurs between the 2A and 2B regions of the polyprotein at a Gly-Pro junction. Since the 2A region is too small to be an enzyme, and there is evidence to rule out host protease involvement, it is proposed that the 2A segment represents a self-cleaving system. Synthetic oligopeptides containing the 2A sequence have been prepared using solid phase peptide synthesis and their three-dimensional structures in different solvents have been investigated, using NMR and CD techniques. Computer modelling studies of the 2A region have been carried out and have indicated the presence of a cis prolyl bond. Short peptide fragments containing the sequence of the 2A region around the scissile bond have also been prepared by solution phase peptide synthesis and their conformations examined, using NMR spectroscopy. In particular, the NPGP tetrapeptide, which is alleged to possess cleavage activity was prepared and its reactivity investigated. The influence of prolyl cis/trans isomerism on the structure of polypeptides is poorly understood and a synthetic approach has been used to prepare cis X-Pro peptides. The strategy involved the formation of bicyclic compounds containing a hydrazide linkage with a view to breaking the N-N bond under mild conditions to give the natural cis X-Pro peptide. The design, synthesis and reactivity of various novel, bicyclic cis X-Pro dipeptides is described. These compounds represent a new class of type VI beta-turn mimetics and as it has been shown that they can be easily extended at the amino and carboxy termini for incorporation into larger peptides. X-ray crystal structures for some of the compounds and intermediates are presented. Investigations into the reductive cleavage of these compounds were carried out and some were found to display unusual reactivity with the chosen reduction method. In particular, a novel intramolecular transamidation reaction is reported and its mechanism has been investigated by the use of various substituted derivatives.
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McReynolds, Sara W. "Modeling management of foot and mouth disease in the central United States." Diss., Kansas State University, 2013. http://hdl.handle.net/2097/16872.
Full textAbstract:
Doctor of PhilosophyDepartment of Diagnostic Medicine and Pathobiology
Michael W. Sanderson
The last outbreak for Foot and Mouth Disease (FMD) in the United States (U.S.) was in 1929. Since that time the U.S. has not had any exposure to the disease or vaccination, creating a very susceptible livestock population. The central U.S. has a large susceptible livestock population including cattle, swine, sheep, and goats. The impact of FMD in the U.S. would be devastating. Simulation modeling is the only avenue available to study the potential impacts of an introduction in the U.S. Simulation models are dependent on accurate estimates of the frequency and distance distribution of contacts between livestock operations to provide valid model results for planning and decision making including the relative importance of different control strategies. Due to limited data on livestock movement rates and distance distribution for contacts a survey was conducted of livestock producers in Colorado and Kansas. These data fill a need for region specific contact rates to provide parameters for modeling a foreign animal disease. FMD outbreaks often require quarantine, depopulation and disposal of whole herds in order to prevent the continued spread of the disease. Experts were included in a Delphi survey and round table discussion to critically evaluate the feasibility of depopulating a large feedlot. No clearly acceptable method of rapidly depopulating a large feedlot was identified. Participants agreed that regardless of the method used for depopulation of cattle in a large feedlot, it would be very difficult to complete the task quickly, humanely, and be able to dispose of the carcasses in a timely fashion. Simulation models were developed to assess the impact of livestock herd types and vaccination on FMD outbreaks in the central U.S. using the North American Animal Disease Spread Model (NAADSM), a spatially explicit, stochastic state-transition simulation model. Simulation scenarios with large vaccination zones had decreased outbreak length and number of herds destroyed. Vaccination did not provide additional benefit to control compared to depopulation alone when biosecurity and movement controls were high, however the ability to achieve high levels of biosecurity and movement control may be limited by labor and animal welfare concerns.