Simulation of animal disease spread is essential for understanding and controlling the outbreak of disease among herds of livestock (in particular cattle and poultry). Using a computerized system or simulator, animal health professionals or epidemiologists often spend many hours determining the set of input parameters that most accurately represent a disease spread or an outbreak scenario. A parameter can be a simple boolean value, or a scientific or often hypothetically derived range of real numbers. Many times, an epidemiologist chooses a value provisionally in a random fashion and repeats the simulation until a viable solution is achieved. This tedious process is inefficient and lengthy. To assist and improve this laborious practice in a concise and timely manner, a Genetic Algorithm is employed to determine a population based solution consisting of input parameters using the North American Animal Disease Spread Model (NAADSM).

Introduction: In the Archives of the University of Melbourne there are two black notebooks containing the handwritten reminiscences of William Tyson Kendall, the “founder of the veterinary profession in Australia”. In fact, Kendall makes very little reference to the veterinary college that he founded, his teaching or the trials that he was to confront, but out of that chance encounter with his notebooks I became interested in the early years of the profession in Victoria; the profession to which Kendall devoted so much of his incredible energy and enthusiasm. Further inquiry only served to enhance this interest, but revealed that there was a paucity not only of primary source material, but also of recorded history. During the course of conversations with both retired and active practitioners, I have frequently been told, and can verify, that veterinarians are great talkers, and many of them are keen to preserve their historical heritage, but are the worst procrastinators when it comes to the written word. (For complete introduction open document).

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2014-04-22T16:33:20Z No. of bitstreams: 1 Luciane Marieta Soares O uso da talidomida...2013.pdf: 1032465 bytes, checksum: 705c1f8374aee3a4f8a1b0f537cd33f6 (MD5) / Made available in DSpace on 2014-04-22T16:33:21Z (GMT). No. of bitstreams: 1 Luciane Marieta Soares O uso da talidomida...2013.pdf: 1032465 bytes, checksum: 705c1f8374aee3a4f8a1b0f537cd33f6 (MD5) Previous issue date: 2013 / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / A leptospirose é uma zoonose de importância global, causada por leptospiras patogênicas. Seu tratamento é limitado quando iniciado após quatro dias do surgimento de sintomas, portanto, novas terapias adjuvantes são necessárias. Objetivo. Testar a droga imunomoduladora talidomida como terapia adjuvante à ampicilina no modelo de tratamento tardio da leptospirose experimental em hamsters. Métodos. 60 hamsters foram infectados via intraperitoneal por Leptospirainterrogans cepa L1-130, e foram separados em grupos: nenhum tratamento (NONE), talidomida (TAL), ampicilina (AMP) e ambos (AMP-TAL). A talidomida foi administrada via sonda orogástrica na dosagem de 50 mg/Kg diluída em óleo de linhaça (2ml/Kg) por três dias. Já a ampicilina por via intramuscular: 100mg/Kg/bid por seis dias. Foram realizados dois desenhos experimentais. Experimento 1: o tratamento foi iniciado 48h após o início dos sinais clínicos da doença. Experimento 2: o tratamento foi iniciado imediatamente após a detecção do primeiro óbito entre os animais infectados. Resultados. Experimento1: todos os hamsters dos grupos AMP e AMP-TAL sobreviveram (n=8) enquanto todos os animais dos grupos NONE (n=6) e TAL (n=8) morreram. Os hamsters dos grupos AMP e AMP-TAL não mostraram lesões renais, pulmonares ou hepáticas. Baixa carga de leptospiras foi detectada nos órgãos alvo. Experimento 2: o desfecho letal foi observado em 6/6 hamsters no grupo NONE, 8/8 do grupo TAL, 6/8 do AMP e 6/8 do AMP-TAL. A talidomida usada como adjuvante não prolongou a sobrevida dos animais tratados com ampicilina. No entanto, o grupo TAL apresentou sobrevida mais longa que o grupo que não recebeu tratamento algum. Os animais tratados apresentaram maior frequência de destrabeculação de hepatócitos. Conclusão: Esse estudo abre novas perspectivas no desenvolvimento de um tratamento tardio na leptospirose, contudo observou-se que a talidomida utilizada como terapia adjuvante não teve impacto na sobrevida de hamsters como modelo de início tardio de terapia antimicrobiana. / Leptospirosis is a zoonosis of global importance, caused by pathogenic leptospira. His treatment is limited when started after four days of onset of symptoms, increasing the risk of morbidity and mortality, so new adjuvant therapies are needed.Objectives.To test the immunomodulatory drug, thalidomide, as an adjuvant therapy to antibiotics in experimental leptospirosis. Methods. Hamsters were infected by Leptospirainterrogans strain L1-130, and groups were assigned based on no treatment (NONE), thalidomide only (TAL), ampicillin only (AMP) or both (AMP-TAL). Thalidomide was administered via a gastric tube: 50 mg/kg in linseed oil and 2 ml/kg for three days. Ampicillin was administered intramuscularly at the rate of 100 mg/kg/bid for six days. Treatment was started two days after the onset of symptoms (experiment 1) and immediately after detection of the first death (experiment 2). Results. Experiment 1: all hamsters from the groups AMP and AMP-TAL survived (n=8), while all hamsters from groups NONE (n=6) and TAL (n=8) died. The AMP and the AMP-TAL groups showed no renal, lung or liver pathology and absent or very low leptospiral burden in target organs. Experiment 2: lethal outcome was observed in 6/6 hamsters in the NONE group, 8/8 in the TAL group, and 6/8 in the AMP group and the AMP-TAL group. Thalidomide showed no survival benefit when compared to hamsters treated with ampicillin alone. The TAL group, however, had a longer interval between infection and death when compared to the NONE group. Treated animals had a higher frequency of liver plate disarray. The TAL, AMP and AMP-TAL groups had very low tissue leptospiral counts. Conclusion: This study may open new perspectives to assist the development of a delayed treatment in leptospirosis, however it was observed that thalidomide used as adjuvant therapy had no impact on the survival of hamsters as late onset of antimicrobial therapy model.

Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / Raymond R. R. Rowland / Classical swine fever virus (CSFV) is an enveloped, positive strand RNA virus, and member of the genus Pestivirus. It is a highly infectious and transmissible swine pathogen that threatens the global swine industry. The United States has been free of CSFV since 1977, however, monitoring the millions of domestic and feral pigs present in the US puts a significant strain on national surveillance efforts. There are no validated diagnostic techniques that can simultaneously sample multiple pigs (i.e. all pigs in a pen or barn). Similarly, there are no validated serological assays that can quickly test for CSFV without cross-reacting with other pestiviruses. The purpose of the first study was to establish a moderate CSFV-infectious model and determine how a single oral fluid sample from a pen of pigs can function as a diagnostic sample for detecting CSFV. Oral fluid (OF) and serum samples were collected from 10 pigs experimentally infected with CSFV Paderborn strain. Using RT-PCR, CSFV was detected in OF on 8 days post infection (dpi), and in the serum of one pig on 6 dpi. A single OF sample can, therefore, take the place of 10 serum samples to detect CSFV in a population. In a second study, monoclonal antibodies reactive to CSFV glycoproteins were generated in mice immunized with recombinant E2 and Erns antigens. Five E2-specific clones and two Erns-specific clones showed reactivity to CSFV-infected. Epitope mapping of the E2 clones showed that all reacted with the N-terminal portion of E2; a region highly variable among pestiviruses. Together with OF sampling, monoclonal antibodies can be used to develop new tools for improving CSF surveillance in large swine populations.

Doctor of Philosophy / Department of Animal Sciences and Industry / Curtis Kastner / The U.S. agriculture industry is diverse and dynamic, plays a vital role in the nation’s economy, and serves as a critical component in providing the global food supply. Agriculture has and always will be susceptible to threats such as pests, disease, and weather, but it is also threatened by intentional acts of agroterrorism. One specific area of concern is foreign animal diseases (FAD) and the danger these diseases create for the U.S. livestock industry. Whether a disease outbreak is intentional or accidental, it could devastate animal agriculture and the food infrastructure and have a lasting impact on state, national, and global economies. One of the most economically devastating diseases that raise fear and anxiety in the livestock industry is foot and mouth disease (FMD). A number of administrative, regulatory, and legislative actions have been implemented at state and federal levels designed to protect the agriculture industry and to prevent, prepare for, and respond to an accidental or intentional introduction of an FAD. However, the consistency, clarity, and long-term commitment of these policy approaches remains in question. Effective policy decisions require a multidisciplinary approach that consider and balance science, economics, social factors, and political realities. A significant number of policy analysis tools exist and have been applied to animal emergency scenarios but few actually address the complexity of these policy dilemmas and provide information to policymakers in a format designed to help them make better decisions. Policy development needs to take a more multidisciplinary approach and better tools are needed to help decision makers determine the best policy choices. This dissertation analyzes three FAD policy dilemmas: mass euthanasia and depopulation, carcass disposal, and vaccination. Policy tools are developed to address the multidisciplinary nature of these issues while providing the information necessary to decision makers in a simple and useful format.

Pela utilização de métodos bioquímicos, biofísicos, de tipagem sorológica e de visualização das proteínas totais bacterianas, isolados de surubim Pseudoplatystoma corruscans, tilápia Oreochromis niloticus e pacu Piaractus mesopotamicus, foram caracterizados, identificados e sua virulência determinada. Dentre as linhagens de referência, o isolado de surubim caracterizou-se como sendo Plesiomonas shiguelloides e os demais isolados de tilápia e pacu foram identificados como Aeromonas hydrophila, todos pertencentes à família Vibrionaceae. Os isolados de tilápia e pacu caracterizaram-se como linhagens virulentas, resistentes aos antibióticos ampicilina, amoxicilina, lincomicina, novobiocina, oxacilina, penicilina, rifampicina e trimetoprim+sulfametoxazol, em ensaios de antibiograma realizados em meio YEA que evidenciaram que as linhagens isoladas de peixes são resistentes a oito das dezessete substâncias antimicrobianas testadas pelo método de difusão em disco. Essas características são compatíveis com as apresentadas pelo espécime tipo de A. hydrophila. Ambas as linhagens quando cultivadas em meio YEA compartilharam a mesma banda de aproximadamente 33,61kDa com o espécime tipo para A. hydrophila. Em meio enriquecido com glucose, a banda compartilhada entre elas teve peso molecular aproximado de 144,28kDa. Os testes de aglutinação sorológica evidenciaram nestas duas linhagens a presença de antígenos estáveis ao calor do tipo O. A técnica de dupla imunodifusão de Ouchterlony demonstrou que o antígeno preparado a partir do isolado de tilápia é a linhagem de A. hydrophila mais indicada para ser utilizada em estudos visando o desenvolvimento de uma vacina polivalente. / Bacteria isolated from surubim Pseudoplatystoma corruscans, tilapia Oreochromis niloticus e pacu Piaractus mesopotamicus, were characterized and identified by biochemical, biophysical, serology, and SDS-PAGE, and their virulence observed. The strain isolated from surubim was characterized as Plesiomonas shigelloides. The other strains isolated from tilapia and pacu were Aeromonas hydrophila. The isolated A. hydrophila strains presented virulence and resistance against the follow antibacterial substances: ampicillin, amoxicillin, lincomicin, novobiocin, oxacillin, penicillin, rifampin and trimetoprim+sulfametoxazole. Both strains when cultivated in YEA medium shared with the A. hydrophila type strain a similar protein band of 33,61kDa. In a medium supplemented with glucose, only one protein exhibiting relative molecular mass of 144.28 kDa, was shared by the type strains isolated from fish and the type strain. The serology tests revealed that all isolated strains presented heat-stable O-antigens. The Ouchterlony double-immunodiffusion showed that the antigen prepared from the tilapia strain possessed surface antigens similar to A. hydrophila type strain and the strains isolated from pacu. This suggested the possibility of development and usage of a common or polyvalent vaccine for A. hydrophila among tilapia and pacu or other freshwater fish species.

Today, infectious animal diseases and the propagation speeds of these diseaseshave been threatening the human health. Threats from animal disease outbreakssuch as Avian Influenza have increased in both number and complexity. So, it is extremely important to determine the animal diseases at first appearances and totake precautions according to propagation speeds of the diseases. Geographic Information Systems (GIS) have become an important tool inveterinary epidemiology, surveillance and monitoring of animal diseases. Such approaches can be used for public health planning and predicting disease risks. This study aims to build a GIS web-based animal health surveillance system in Turkey in order to monitor and analyse disease outbreaks. Different sources of data / geographical data, animal holding locations, disease outbreak recordings, reporting information and special GIS functions have been incorporated in the application. It enables to determine the first, second and third degree risk zones of a disease, query the animals, holdings and disease events, create thematic maps and show the results of explored landscape features associated with Avian Influenza outbreak of 2006 and present graphically illustrated reports. This study will make the management of the disease outbreak situation easier, enhance the response mechanism of the decision makers, help to make better decisions, control the disease as quickly as possible, protect both the animals and humans against diseases, also provide a tool to evaluate different strategies to prevent the spread of infectious diseases. So, in an infectious disease case, emergency precautions can be taken and control strategies can be planned.

The introduction of FMD into the US would have serious economic and societal effects on the livelihoods and sustainability of affected livestock producers. Livestock producers serve as an important line of defense in both detecting an introduction of FMD as well, helping to prevent disease spread. However, due to the complexity of moral, social, and economic issues surrounding the control of highly contagious diseases, producer cooperation during an outbreak may not be assured. This study was conducted using a mixed-methods approach, including qualitative analysis of interviews and quantitative analysis of a postal survey, in order to explore the factors likely to influence producer cooperation in FMD detection and control in Texas. Reporting of cattle with clinical signs of FMD in the absence of an outbreak was related to producers´ beliefs about the consequences of reporting, beliefs about what other producers would do, trust in agricultural agencies, and their perception of the risk posed by FMD. During a hypothetical outbreak, intentions to report were determined by beliefs about the consequences of reporting, and perception of the risk posed by FMD. Intentions to gather and hold cattle when requested during an outbreak were determined by beliefs about the consequences of gathering and holding, beliefs about barriers to gathering and holding, trust in other producers, and perception of the risk posed by FMD. Compliance with animal movement restrictions was determined by experiential attitudes, beliefs about the availability of feed, space, and disinfection procedures, beliefs about what other producers would do, and perception of the risk posed by FMD. Recommendations for improving producer cooperation include targeting specific beliefs in both planning and communication, increasing transparency in the post-reporting process, planning for and communicating plans for maintaining business continuity in order to better inform risk perception, and partnering with organizations to ensure sustained and meaningful communication that supports trust between producers within the affected agricultural community.

Pela utilização de métodos bioquímicos, biofísicos, de tipagem sorológica e de visualização das proteínas totais bacterianas, isolados de surubim Pseudoplatystoma corruscans, tilápia Oreochromis niloticus e pacu Piaractus mesopotamicus, foram caracterizados, identificados e sua virulência determinada. Dentre as linhagens de referência, o isolado de surubim caracterizou-se como sendo Plesiomonas shiguelloides e os demais isolados de tilápia e pacu foram identificados como Aeromonas hydrophila, todos pertencentes à família Vibrionaceae. Os isolados de tilápia e pacu caracterizaram-se como linhagens virulentas, resistentes aos antibióticos ampicilina, amoxicilina, lincomicina, novobiocina, oxacilina, penicilina, rifampicina e trimetoprim+sulfametoxazol, em ensaios de antibiograma realizados em meio YEA que evidenciaram que as linhagens isoladas de peixes são resistentes a oito das dezessete substâncias antimicrobianas testadas pelo método de difusão em disco. Essas características são compatíveis com as apresentadas pelo espécime tipo de A. hydrophila. Ambas as linhagens quando cultivadas em meio YEA compartilharam a mesma banda de aproximadamente 33,61kDa com o espécime tipo para A. hydrophila. Em meio enriquecido com glucose, a banda compartilhada entre elas teve peso molecular aproximado de 144,28kDa. Os testes de aglutinação sorológica evidenciaram nestas duas linhagens a presença de antígenos estáveis ao calor do tipo O. A técnica de dupla imunodifusão de Ouchterlony demonstrou que o antígeno preparado a partir do isolado de tilápia é a linhagem de A. hydrophila mais indicada para ser utilizada em estudos visando o desenvolvimento de uma vacina polivalente. / Bacteria isolated from surubim Pseudoplatystoma corruscans, tilapia Oreochromis niloticus e pacu Piaractus mesopotamicus, were characterized and identified by biochemical, biophysical, serology, and SDS-PAGE, and their virulence observed. The strain isolated from surubim was characterized as Plesiomonas shigelloides. The other strains isolated from tilapia and pacu were Aeromonas hydrophila. The isolated A. hydrophila strains presented virulence and resistance against the follow antibacterial substances: ampicillin, amoxicillin, lincomicin, novobiocin, oxacillin, penicillin, rifampin and trimetoprim+sulfametoxazole. Both strains when cultivated in YEA medium shared with the A. hydrophila type strain a similar protein band of 33,61kDa. In a medium supplemented with glucose, only one protein exhibiting relative molecular mass of 144.28 kDa, was shared by the type strains isolated from fish and the type strain. The serology tests revealed that all isolated strains presented heat-stable O-antigens. The Ouchterlony double-immunodiffusion showed that the antigen prepared from the tilapia strain possessed surface antigens similar to A. hydrophila type strain and the strains isolated from pacu. This suggested the possibility of development and usage of a common or polyvalent vaccine for A. hydrophila among tilapia and pacu or other freshwater fish species.

INTRODUÇÃO: Apesar do amplo uso da medida da saturação central de oxigênio como meta terapêutica em pacientes de terapia intensiva, diferenças absolutas em relação à saturação venosa mista existem. As causas desses gradientes, bem como o comportamento das mesmas ao longo do tempo nas doenças graves não foram completamente esclarecidas. Considerando que a maioria das intervenções atualmente empregadas para reverter desequilíbrios de oxigenação tecidual presentes nos pacientes graves é direcionada, direta ou indiretamente, ao coração; a situação particular de elevada taxa de extração de oxigênio basal do miocárdio e a ausência de ferramentas de monitorização do impacto miocárdico dessas intervenções, o presente estudo, diante da possibilidade teórica da participação do efluente do seio coronário nessas diferenças centrais para pulmonares, não só para a saturação de oxigênio (SO2), analisou o comportamento da SO2, pressão parcial de dióxido de carbono (PCO2), lactato e glicose, em diferentes modelos de hipóxia e compartimentos vasculares, com ênfase na avaliação do metabolismo miocárdico e seu impacto nos gradientes centrais para pulmonares. MÉTODOS: 37 porcos, machos, com peso em torno de 35 Kg, sedados e ventilados mecanicamente, foram estudados após indução de quatro diferentes tipos de injúria hipóxica (hipóxia anêmica, estagnante, hipóxica e sepse), sendo 8 animais por grupo e mais 5 controles. Além de variáveis hemodinâmicas e de oxigenação, SO2, PCO2, lactato e glicose foram medidos, em diferentes momentos, em 9 compartimentos vasculares distintos, incluindo o seio coronário (artéria femoral, veia cava inferior e superior, átrio direito, ventrículo direito, artéria pulmonar, veia suprahepática direita e veia porta). PRINCIPAIS RESULTADOS: As concentrações de O2, lactato e glicose no efluente do seio coronário apresentaram padrões distintos entre os grupos: troca de substrato energético de lactato por glicose nos grupos hipóxia hipóxica e anêmica, aumento no consumo de ambos os substratos na sepse e ausência de tendência clara no grupo da hipóxia estagnante. Os gradientes de PCO2 entre seio coronário e artéria femoral mantiveram-se estáveis com tendência de alargamento tardio em todos os modelos. Na análise dos demais gradientes regionais, o seio coronário apresentou a menor SO2 do organismo, as menores concentrações de lactato, os maiores níveis de PCO2, e esses padrões variaram ao longo do tempo. Mesma tendência evolutiva foi percebida entre os gradientes centrais para pulmonares de O2, lactato, CO2 e glicose e a medida desses mesmos parâmetros no seio coronário. CONCLUSÕES: As concentrações de O2, lactato e glicose no efluente do seio coronário estão relacionadas ao tipo de injúria e não apenas à disponibilidade de substrato energético. Padrões de gravidade, comuns às fases tardias de todos os grupos, puderam ser identificados: qualquer redução da SO2 coronariana; incremento do metabolismo de glicose; produção de lactato pelo miocárdio e surgimento de igualdade ou inferioridade dos níveis da PCO2 coronariana em relação aos valores dos demais compartimentos vasculares do organismo (independentemente da trajetória). A tendência dos gradientes de PCO2 transmiocárdicos seguiu a do débito cardíaco e, certamente, deve refletir fluxo coronariano. A análise dos gradientes regionais se mostrou capaz de permitir a avaliação de contextos orgânicos regionais específicos, como na avaliação do metabolismo hepático, na qual foi possível demonstrar que na hipóxia, a produção de glicose hepática é mantida até o óbito, diferentemente do padrão descrito para a sepse. Por fim, com a análise dos dados do grupo sepse, foi possível demonstrar que: a) assim como os gradientes centrais para pulmonares de SO2 e lactato já foram descritos, gradientes de glicose e PCO2 também existem; b) o seio coronário participa, significativamente, na formação desses gradientes de lactato, CO2 e glicose / INTRODUCTION: Despite of the widespread use of the central venous oxygen saturation measurement as a therapeutic goal in critically ill patients, absolute differences between this measurement and the mixed venous oxygen exist. Causes of these differences, as well the behavior of these gradients in critical illness, are not completely understood. Considering current therapeutic interventions aimed to reverse tissue oxygenation impairment are mediated by increases in cardiac output; the particular scenario in which the heart is not physiologically able to further increase oxygen extraction and the absence of tools to monitoring the myocardium impact of those interventions, the present study, facing the theoretical possibility of the coronary sinus effluent participation in those central to mixed venous differences, has analyzed the oxygen saturation (SO2), carbon dioxide partial pressure (PCO2), lactate and glucose concentrations behaviors over time, in different models of tissue hypoxia and in different vascular sites. Emphasis on the myocardial energetic metabolism and its impact over central to mixed venous gradients was placed. METHODS: 37 pigs, males, weighting about 35 Kg, sedated and mechanically ventilated, were studied after induction of four different hypoxic injury models (sepsis, and anemic, stagnant, hypoxic hypoxia), eight for group and five controls. In addition to hemodynamic and oxygen variables, SO2, PCO2, lactate and glucose were measured in different phases, in 9 distinct vascular sites, including coronary sinus (femoral artery, inferior and superior vena cava, right atria, right ventricle, pulmonary artery, right suprahepatic vein and portal vein). MAIN RESULTS: Concentrations of O2, lactate and glucose in the coronary sinus effluent presented distinctive patterns among groups: shift from lactate to glucose consumption in hypoxic hypoxia and anemic hypoxia groups, increase in both glucose and lactate consumption in sepsis and absence of clear trend in stagnant hypoxia group. PCO2 gradients from systemic artery to coronary sinus presented late enlargement trend in all groups. In the regional gradients analysis comparisons, coronary sinus presented the lowest SO2, the lowest lactate concentrations, the highest PCO2 levels, and these patterns changed over time. Similar evolution trends were observed between central to mixed venous O2, PCO2, lactate and glucose gradients and the same parameters measured in coronary sinus. CONCLUSIONS: Different concentrations of O2, PCO2, lactate and glucose in coronary sinus are related to the type of hypoxic injury and not only to energetic substrate availability. Severity-related patterns, common to all groups in late phases, were identified: any reduction of coronary SO2, shift to glucose consumption, net lactate myocardial production and equality or inferiority of PCO2 levels related to other vascular compartments (independently of trend). Trends in transmyocardial PCO2 gradients followed cardiac output ones and, certainly, should mirror coronary blood flow. Regional gradients analysis showed suitable to explore specific regional metabolic settings, as in the described example of liver metabolism, in which production of glucose were maintained in all phases by this organ in hypoxic hypoxia groups, differently from the impaired production described in literature for sepsis. At last, data from sepsis group have showed: a) as to the previously known central to mixed venous SO2 and lactate gradients, PCO2 and glucose gradients also exist; b) coronary sinus has participated significantly in formation of central to mixed venous lactate, PCO2 and glucose gradients