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Over the last 20 years, pig production has been characterised by a rapid increase in the volume of pig meat produced, greater intensification of the pig-rearing process and much greater international movement of products. There have also been many novel viral diseases that challenge the industry. Are these two developments linked and, if so, how? To understand how changes in the industry may influence the evolution of viruses, it is important to understand something of evolutionary theory. For RNA viruses, the concept of 'quasispecies' has moved solidly from theory to fact. Such viruses do not exist as a single entity, but as a 'cloud' of viruses, whose degree of diversity is influenced by a number of factors. Chief among these are the size and rate of the replicating population, along with the availability and diversity of susceptible hosts. A feature of RNA viruses is a high level of mutation, due to lack of capability to correct errors on the part of the host cell. Both in vivo and in vitro, RNA viruses have been shown to accumulate and fix these mutations, leading to bottleneck events and fitness loss, the phenomenon known as 'Muller's ratchet'. Likewise, the opposite effect, fitness gain, can be achieved in an environment providing for high levels of replication and the generation of large populations of virus. This has been shown to be possible in vitro by high-volume passage. It is possible that the regular introduction of diverse viruses within large-scale pig production provides an in vivo equivalent that could drive quasispecies populations to increased fitness, and may explain why emergent viruses, either new to science or with new synergies and presentation, seem to be appearing more commonly. Source


Brown I.H.,Veterinary Laboratories Agency Weybridge
Avian Diseases | Year: 2010

Events during the period extending from 2006 to 2009 have been overshadowed by the ongoing panzootic with H5N1 (highly pathogenic notifiable avian influenza [HPNAI]), which has afflicted 63 countries and three continents (Africa, Asia, and Europe) during the review period. Two countries, Indonesia and Egypt, have formally declared the disease endemic to the World Organisation for Animal Health, while others have used a variety of approaches aimed at containment, control, and eradication. These approaches have achieved variable success, but in 2009 several countries that had previously declared themselves free of HPNAI became reinfected. In addition, the virus continued to be detected widely in wild bird populations, even in the absence of local poultry outbreaks. Other poultry outbreaks with HPNAI have been reported in South Africa (in ostriches with H5N2 in 2006) and the U.K. (in chickens with H7N7 in 2008). Also notable was the report of H5N2 HPNAI in wild bird populations in North Africa in 2007. Improved active surveillance systems and vigilance for notifiable avian influenza (NAI) in domestic poultry, especially in host groupings, in which clinical signs following infection may be inapparent (e.g., domestic waterfowl), have inevitably resulted in the detection and reporting of other activity. Low pathogenicity NAI H5 or H7 viruses were isolated/detected from poultry in Belgium (H5N2, 2008), Chinese Taipei (H5N2, 2008), Denmark (H5N2, 2006; H7N1, 2008), France (H5N2, 2007), Germany (H7N3, 2008), Italy (H7N7, 2006; H7N3, 2007-08), the Netherlands (H7N7, 2006), Portugal (H5N2, 2007; H5N3, 2007), the Republic of Korea (H7N8, 2007; H5N2, 2008), and the U.K. (H7N3, 2006; H7N2, 2007). In addition, there has also been significant activity with H6 and H9 viruses in poultry populations, especially in Asia. © 2010 American Association of Avian Pathologists. Source


Chalmers R.M.,Cryptosporidium Reference Unit | Smith R.,Veterinary Laboratories Agency Weybridge | Elwin K.,Cryptosporidium Reference Unit | Clifton-Hadley F.A.,UK Environment Agency | Giles M.,UK Environment Agency
Epidemiology and Infection | Year: 2011

In order to monitor epidemiological trends, Cryptosporidium-positive samples (n=4509) from diarrhoeic patients were typed. Compared to the previous 4 years, the proportion of Cryptosporidium hominis cases in 2004-2006 increased to 57·3%, while 38·5% were C. parvum. The remaining 4·2% cases included mixed C. parvum and C. hominis infections, C. meleagridis, C. felis, C. ubiquitum and a novel genotype. When the typing results were combined with enhanced surveillance data to monitor risk exposures, C. hominis was linked to urban dwelling, previous diarrhoea in the household, any travel especially abroad, and using a swimming or paddling pool. C. parvum was linked to having a private water supply, contact with surface water, visiting or living on a farm, and contact with farm animal faeces. The proportion of laboratory-confirmed indigenous cases acquired from direct contact with farm animals was estimated to be 25% for C. parvum and 10% of all reported Cryptosporidium cases. © Copyright Cambridge University Press 2010. Source


Jones G.J.,Veterinary Laboratories Agency Weybridge | Gordon S.V.,Veterinary Laboratories Agency Weybridge | Gordon S.V.,University College Dublin | Hewinson R.G.,Veterinary Laboratories Agency Weybridge | Vordermeier H.M.,Veterinary Laboratories Agency Weybridge
Infection and Immunity | Year: 2010

Results of previous studies utilizing bioinformatic approaches in antigen-mining experiments revealed that secreted proteins are among the most frequently recognized antigens from Mycobacterium bovis. Thus, we hypothesized that the analysis of secreted proteins is likely to reveal additional immunogenic antigens that can be used to increase the specificity of diagnostic tests or be suitable vaccination candidates for mycobacterial infections. To test this hypothesis, 382 pools of overlapping peptides spanning 119 M. bovis secreted and potentially secreted proteins were screened for the ability to stimulate a gamma interferon response in vitro using whole blood from tuberculin-positive reactor (TB reactor) cattle. Of the 119 proteins screened, 70 (59%) induced positive responses in the TB reactor animals to various degrees. Strikingly, all but one of the 15 ESAT-6 proteins tested were recognized by at least 30% of the TB reactor animals, with 12 of the 22 most commonly recognized antigens belonging to this protein family. Further analysis of these data demonstrated that there was no significant difference in immunogenicity between the ESAT-6 proteins that were components of potentially intact ESX secretory systems and those corresponding to additional partial esx loci. Importantly for vaccine design, antigenic epitopes in some highly conserved regions shared by numerous ESAT-6 proteins were identified. However, despite this considerable homology, peptide-mapping experiments also revealed that immunodominant peptides were located in regions of amino acid variability. Copyright © 2010, American Society for Microbiology. All Rights Reserved. Source


Johnson N.,Veterinary Laboratories Agency Weybridge | Cunningham A.F.,University of Birmingham | Fooks A.R.,Veterinary Laboratories Agency Weybridge
Vaccine | Year: 2010

Infection with rabies virus causes encephalitis in humans that has a case fatality rate of almost 100%. This inability to resolve infection is surprising since both pre-exposure vaccination and, if given promptly, post-exposure vaccination is highly effective at preventing encephalitic disease. The principal immunological correlate of protection produced by vaccination is neutralizing antibody. T-helper cells contribute to the development of immunity whereas cytotoxic T cells do not appear to play a role in protection and may actually be detrimental to the host. One reason for a failure to protect in humans may be the poor immunological response the virus provokes, despite the period between exposure to virus and the development of disease being measured in months. Few individuals have measurable neutralizing antibody on presentation with disease, although in many cases this develops as symptoms become more severe. Furthermore, when antibody is detected in serum it rarely appears in cerebrospinal fluid suggesting limited penetration into the CNS, the site where it is most needed. The role of the modest mononuclear cell infiltrate into the brain parenchyma is unclear. Some studies suggest the virus can suppress cell-mediated immunity early during the infection although there is little mechanistic evidence to support this beyond suppression of intracellular interferon production by the viral phosphoprotein. In contrast, levels of antibody in the CNS correlate to the peak virus production within the CNS. Here we review the current understanding of immune responses to rabies infection and vaccination against this disease. This article identifies a need to understand how rabies antigens are initially presented and how this can influence the subsequent development of antibody responses. This could help identify ways in which the response to prophylactic vaccination can be enhanced and how the natural immune response to infection can be boosted to combat neuroinvasion. Crown Copyright © 2010. Source

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