Inaug.-diss.-Bern. / "Literatur": p. 44-47.

Inaug.-diss.-Bern. / "Literatur": p. 44-47.

The causative agents of plague (Y. pestis), glanders (B. mallei) and melioidosis (B. pseudomallei) are included in critical agents of bioterrorisim. They belong to the most intensively studied agents during cold war, specially in the former Soviet Union (FSU). Mostly what is known about these agents, particularly (Y. pestis ) is not available in English language publications. Many of the studies are written in Russian language and published in Russian scientific journals. Thus, the work is designed to evaluate, published and unpublished Russian language written data obtained, in comparisions to the current state of global knowledge on the pathogens in concern.

Vaccination is one of the most effective public health interventions in the world, saving millions of lives and preventing the onset of debilitating diseases. With widespread emergence of multi-drug resistant pathogens, the importance of preventative medicine has become even more apparent. However, one of the limiting factors in developing novel vaccines that are both safe and highly immunogenic is the availability of adjuvant delivery systems licensed for human use. The purpose of this study was to investigate the role gold nanoparticles could play as an effective vaccine delivery system. A variety of coupling chemistries were explored for their ability to conjugate protein and polysaccharide antigens onto the surface of gold nanoparticles for the development of vaccines against a number of biologically important human pathogens including Y. pestis, B. mallei and S. pneumoniae. Retention of antigenicity and coupling efficiency of conjugated molecules was measured using characterisation techniques such as localised surface plasmon resonance and immunoblotting. Gold nanoparticle coupled antigens were then used to immunise mice and to measure the protective efficacy and the immunological response induced. The findings indicate antigen-specific immune responses are elevated when an antigen is coupled onto gold nanoparticles. Moreover, immunological data from nanoparticle coupled glycoconjugate vaccines against B. mallei and S. pneumoniae indicate the likely presence of a strong T cell immune response which is essential for providing immunological memory. Finally, an intracellular trafficking assay was carried out to identify some of the mechanisms that might be involved in uptake of gold nanoparticles into professional phagocytes. Confocal imaging of receptors associated with endosomal compartments revealed that gold nanoparticles may enter cells through multiple pathways. The findings reported in this study suggest that gold nanoparticles may be an excellent candidate for further investigation as a novel vaccine delivery system.

A thesis by Marc Ashley Bayliss entitled ‘Virus-like particles as a novel platform for delivery of protective Burkholderia antigens’ and submitted to the University of Exeter for the degree of Doctor of Philosophy. There is currently no licensed vaccine available for the global tropical pathogen Burkholderia pseudomallei which is the causative agent of melioidosis and a potential bio-threat agent. The capsule polysaccharide (CPS) expressed by B. pseudomallei has been shown to offer some protection against bacterial challenge. Polysaccharide immunogenicity can be enhanced by conjugation to a carrier protein and several licensed vaccines utilise this technology. Virus-like particles (VLPs) are non-infectious, non-replicating, viral proteins that self-assemble into viral structures and are in several licensed vaccines as primary antigens. VLPs are also effective delivery platforms for foreign antigens by genetic insertion or chemical conjugation. iQur, a collaborator on this project, has developed Tandem CoreTM that consists of two genetically linked hepatitis B core proteins that allow insertion of large proteins into each core whilst remaining assembly competent. The aim of this thesis was to assess the protective efficacy of Tandem CoreTM VLPs chemically conjugated to CPS and Tandem CoreTM Burkholderia protein fusion constructs. This involved three objectives; reduce the cost of CPS extraction; identify immunogenic Burkholderia proteins; and test candidate vaccine efficacy in an animal model of acute melioidosis against B. pseudomallei challenge. To reduce the cost of extraction, CPS was purified from B. thailandensis strain E555 and bacterial culture CPS concentration optimised which first required development of a quantitative ELISA. Immunogenic Burkholderia proteins were identified from the literature but Tandem CoreTM fusion constructs containing these proteins were not assembly competent. The Burkholderia proteins were added as co-antigens to the VLP CPS conjugate vaccine but did not improve efficacy. Tandem CoreTM VLPs conjugated to CPS were protective against B. pseudomallei challenge and were compared to CPS conjugated to Crm197: a commercially available carrier protein used in several licensed vaccines. At lower challenge doses, survival was greater in mice vaccinated with the VLP-CPS conjugate although at higher doses, Crm197-CPS efficacy was greater.

O Brasil possui o maior rebanho de equinos da América Latina e o terceiro do mundo, gerando um mercado de grande importância econômica para a sociedade brasileira. Esta complexa cadeia de negócios sofre também a influência de variáveis que orbitam as diversas relações estabelecidas. Entre elas, destacam-se as variáveis de ordem macroeconômica (influenciando o mercado e as relações de troca), ambientais e legais, derivadas da ação de órgãos reguladores (MAPA, ANVISA, entre outros). Recentemente, o estado brasileiro se viu refém de uma crise sanitária da zoonose do Mormo em equinos, que afetou diretamente o complexo do agronegócio do cavalo, incluindo dificuldades no âmbito internacional, como a realização das Olimpíadas do Rio 2016. Desta maneira, busca-se contribuir na análise dos pontos críticos ocasionados por esta ameaça de ordem legal/sanitária junto à cadeia de negócios, buscando respostas para melhoria da gestão estratégica entre os atores envolvidos, com base na proposta de gerenciamento de processos de negócios. A abordagem metodológica utilizada nesta pesquisa foi de natureza qualitativa e caracteriza-se como exploratória, quanto ao seu foco, e descritiva, quanto aos seus resultados e conclusões. Na descrição das etapas do Fluxograma de controle e erradicação do Mormo, foram observadas algumas atividades críticas para a consecução deste objetivo no Estado brasileiro. Todas essas atividades foram trabalhadas dentro uma matriz de priorização e, confirmados níveis altos de impacto e de probabilidade, passaram por uma análise de risco. Ao final são formuladas uma série de propostas de melhoria ao Fluxograma atual, buscando-se contribuir na mitigação de riscos para este importante segmento do agronegócio brasileiro. / Brazil has the largest equine population of Latin America and the third one in the world, generating a market of huge economic importance for Brazilian society. This complex business chain also suffers the influence of the variables surrounding these established relationships. Among them, the macroeconomics variables (affecting market and exchange relations), environmental and legal, resulting from the regulatory agencies\" (MAPA, ANVISA and others) actions, are highlighted. Recently the Brazilian state found itself taken into a health crisis of glanders zoonosis in horses, that affected directly the horse agrobusiness complex, including challenges of international context, related to Rio 2016 Olympic Games fulfilment. In this regard, the intention is to contribute towards the analysis of critical points related to this legal/health threat within the business chain, seeking answers for strategic management improvement among engaged actors, based on the propositions of business process management. The research\'s methodologic approach was of qualitative nature; characterized as exploratory regarding their focus, and descriptive in terms of outcomes and conclusions. In the description of the steps of control flowchart and glanders\'s eradication, were sighted some critical activities for the achievement of this goal in Brazil. All of them were worked out within a prioritizin matrix, and confirmed high levels of impact and probability, undergoing a risk analysis. Several improvement proposals for the current flowchart are offered, seeking to contribute towards the mitigation of risks for this fundamental segment of Brazilian agribusiness.

The causative agents of plague (Y. pestis), glanders (B. mallei) and melioidosis (B. pseudomallei) are included in critical agents of bioterrorisim. They belong to the most intensively studied agents during cold war, specially in the former Soviet Union (FSU). Mostly what is known about these agents, particularly (Y. pestis ) is not available in English language publications. Many of the studies are written in Russian language and published in Russian scientific journals. Thus, the work is designed to evaluate, published and unpublished Russian language written data obtained, in comparisions to the current state of global knowledge on the pathogens in concern.

A equinocultura é uma atividade de grande importância no Brasil, e no Rio Grande do Sul (RS) se soma sua relevância cultural, no trabalho, esporte e no lazer. A partir disso, este trabalho tem o objetivo de dimensionar e caracterizar a atividade da equinocultura no RS, a partir de dados cedidos pela Secretaria da Agricultura, Pecuária e Irrigação, do período de 2010 a 2016. O rebanho equino gaúcho é composto por em torno de 90% de animais com mais de 6 meses de idade, e por aproximadamente 60% de fêmeas. Houve um crescimento de 105.572 animais no período, com um rebanho de 360.257 cavalos em 2010 e de 465.829 em 2016. Quarenta por cento dos equinos estão concentrados na mesorregião sudoeste, que é responsável também pelo maior número de nascimentos anuais. Vem ocorrendo uma queda no número de nascimentos no RS desde 2013, mas, ao mesmo tempo, um aumento expressivo no número de eventos equestres, especialmente os de esporte, assim como no trânsito de cavalos com essa finalidade. No referido período, observou-se um aumento no número de doenças notificadas ao Serviço Veterinário Oficial, especialmente os casos de anemia infecciosa equina e mormo. O aumento no número de eventos, trânsito e doenças notificadas está diretamente relacionado com a maior fiscalização e obrigatoriedade de apresentação de exames negativos para transporte. Diante dos dados analisados, conclui-se que há um crescimento no número de equinos e na circulação dos mesmos dentro do Estado, que a equinocultura é uma atividade importante no RS e que o fluxo de informações sobre a atividade é díficil. / The equine activities and breeding are very important for economy in Brazil, and in Rio Grande do Sul (RS) it is added their cultural, in work and in leisure relevance. Based on that, this study aims to scale out and characterize equine activities and breeding in RS, through data from 2010 to 2016 given by the Secretaria da Agricultura, Pecuária e Irrigação. Horse herd in RS is composed by 90% of horses older than 6 months and 60% of mares. There was an increase of 105.572 animals during the referred period, with a herd of 360.257 horses in 2010 and 465.829 in 2016. Forty percent of the horses are located in southweast mesoregion, which is where the majority of annual equine births occur. There is a decrease in birth numbers in RS since 2013 but at the same time, an expressive increase in equestrian events, specially related to sports events, and an increase in horse transportation for sporting purpose. It was possible to observe a raise in number of diseases reported to the Oficial Veterinary Service, especially in equine infectious anemia and glanders cases. The increase in the number of events, transit and notified diseases is directly related to the greater surveillance and obligatory presentation of negative exams for transportation. Considering the analyzed data, it is concluded that there is an increase in the number of equines and their circulation within the State, that the equine breeding is an important activity in RS and that the information flow about the activity is difficult.

A equinocultura é uma atividade de grande importância no Brasil, e no Rio Grande do Sul (RS) se soma sua relevância cultural, no trabalho, esporte e no lazer. A partir disso, este trabalho tem o objetivo de dimensionar e caracterizar a atividade da equinocultura no RS, a partir de dados cedidos pela Secretaria da Agricultura, Pecuária e Irrigação, do período de 2010 a 2016. O rebanho equino gaúcho é composto por em torno de 90% de animais com mais de 6 meses de idade, e por aproximadamente 60% de fêmeas. Houve um crescimento de 105.572 animais no período, com um rebanho de 360.257 cavalos em 2010 e de 465.829 em 2016. Quarenta por cento dos equinos estão concentrados na mesorregião sudoeste, que é responsável também pelo maior número de nascimentos anuais. Vem ocorrendo uma queda no número de nascimentos no RS desde 2013, mas, ao mesmo tempo, um aumento expressivo no número de eventos equestres, especialmente os de esporte, assim como no trânsito de cavalos com essa finalidade. No referido período, observou-se um aumento no número de doenças notificadas ao Serviço Veterinário Oficial, especialmente os casos de anemia infecciosa equina e mormo. O aumento no número de eventos, trânsito e doenças notificadas está diretamente relacionado com a maior fiscalização e obrigatoriedade de apresentação de exames negativos para transporte. Diante dos dados analisados, conclui-se que há um crescimento no número de equinos e na circulação dos mesmos dentro do Estado, que a equinocultura é uma atividade importante no RS e que o fluxo de informações sobre a atividade é díficil. / The equine activities and breeding are very important for economy in Brazil, and in Rio Grande do Sul (RS) it is added their cultural, in work and in leisure relevance. Based on that, this study aims to scale out and characterize equine activities and breeding in RS, through data from 2010 to 2016 given by the Secretaria da Agricultura, Pecuária e Irrigação. Horse herd in RS is composed by 90% of horses older than 6 months and 60% of mares. There was an increase of 105.572 animals during the referred period, with a herd of 360.257 horses in 2010 and 465.829 in 2016. Forty percent of the horses are located in southweast mesoregion, which is where the majority of annual equine births occur. There is a decrease in birth numbers in RS since 2013 but at the same time, an expressive increase in equestrian events, specially related to sports events, and an increase in horse transportation for sporting purpose. It was possible to observe a raise in number of diseases reported to the Oficial Veterinary Service, especially in equine infectious anemia and glanders cases. The increase in the number of events, transit and notified diseases is directly related to the greater surveillance and obligatory presentation of negative exams for transportation. Considering the analyzed data, it is concluded that there is an increase in the number of equines and their circulation within the State, that the equine breeding is an important activity in RS and that the information flow about the activity is difficult.

A equinocultura é uma atividade de grande importância no Brasil, e no Rio Grande do Sul (RS) se soma sua relevância cultural, no trabalho, esporte e no lazer. A partir disso, este trabalho tem o objetivo de dimensionar e caracterizar a atividade da equinocultura no RS, a partir de dados cedidos pela Secretaria da Agricultura, Pecuária e Irrigação, do período de 2010 a 2016. O rebanho equino gaúcho é composto por em torno de 90% de animais com mais de 6 meses de idade, e por aproximadamente 60% de fêmeas. Houve um crescimento de 105.572 animais no período, com um rebanho de 360.257 cavalos em 2010 e de 465.829 em 2016. Quarenta por cento dos equinos estão concentrados na mesorregião sudoeste, que é responsável também pelo maior número de nascimentos anuais. Vem ocorrendo uma queda no número de nascimentos no RS desde 2013, mas, ao mesmo tempo, um aumento expressivo no número de eventos equestres, especialmente os de esporte, assim como no trânsito de cavalos com essa finalidade. No referido período, observou-se um aumento no número de doenças notificadas ao Serviço Veterinário Oficial, especialmente os casos de anemia infecciosa equina e mormo. O aumento no número de eventos, trânsito e doenças notificadas está diretamente relacionado com a maior fiscalização e obrigatoriedade de apresentação de exames negativos para transporte. Diante dos dados analisados, conclui-se que há um crescimento no número de equinos e na circulação dos mesmos dentro do Estado, que a equinocultura é uma atividade importante no RS e que o fluxo de informações sobre a atividade é díficil. / The equine activities and breeding are very important for economy in Brazil, and in Rio Grande do Sul (RS) it is added their cultural, in work and in leisure relevance. Based on that, this study aims to scale out and characterize equine activities and breeding in RS, through data from 2010 to 2016 given by the Secretaria da Agricultura, Pecuária e Irrigação. Horse herd in RS is composed by 90% of horses older than 6 months and 60% of mares. There was an increase of 105.572 animals during the referred period, with a herd of 360.257 horses in 2010 and 465.829 in 2016. Forty percent of the horses are located in southweast mesoregion, which is where the majority of annual equine births occur. There is a decrease in birth numbers in RS since 2013 but at the same time, an expressive increase in equestrian events, specially related to sports events, and an increase in horse transportation for sporting purpose. It was possible to observe a raise in number of diseases reported to the Oficial Veterinary Service, especially in equine infectious anemia and glanders cases. The increase in the number of events, transit and notified diseases is directly related to the greater surveillance and obligatory presentation of negative exams for transportation. Considering the analyzed data, it is concluded that there is an increase in the number of equines and their circulation within the State, that the equine breeding is an important activity in RS and that the information flow about the activity is difficult.