African trypanosomiasis is a protozoan infection affecting tens of thousands of people and millions of livestock animals across sub-Saharan Africa. In humans the disease is fatal without chemotherapeutic intervention and in animals it causes a severe anaemia that greatly impairs productivity. Available drug compounds are difficult to administer and unacceptably toxic. A natural product, ascofuranone, inhibits a key trypanosome specific respiratory enzyme, trypanosome alternative oxidase, and was shown over a decade ago to be trypanocidal using both in vitro and in vivo experiments. The compound suffers from rapid metabolism and contains several functionalities undesirable in a drug compound. Despite the promising activity the lack of applicable synthetic methods available hampered the development of chemotherapeutics from ascofuranone. In this work, novel synthetic routes were completed to explore the lead compound. New synthetic methods were successfully developed using palladium catalysed Suzuki couplings and Lewis acid catalysed rearrangements. Ortho-lithiation approaches also afforded potent novel inhibitors. Of particular note is a benzisoxazole, which is expected to alleviate many of the metabolic issues associated with ascofuranone. Alternate heterocycle analogues were explored and an interesting indazole analogue obtained. Finally, chemical methods were developed towards the benzisoxazole and indazole motifs with carboxylic acids, amenable to diversification by amide coupling. A preliminary range of novel amide containing 5, 6-heterocycles were synthesized to begin SAR exploration of these structures.

This thesis examines the Influenza A/H5N1 virus in action through an ethnographic study focused on the entwined concepts of risk and modernity. The objective is to explain why the response to the virus has been challenged in Indonesia. Concerned with policy formulation, and everyday practice, the thesis argues that assemblages of historical, political, institutional and knowledge‐power processes create multiple hybrid constructions of risk and modernity, which challenge technical responses based on epistemological positions and institutional arrangements that do not allow for such hybridity. The thesis is organised into four sections. The first section (chapters 1 – 3) introduces the virus and its terrain, outlines a constructivist position, and argues that conceptually risk and modernity have multiple, dynamic, power‐laden forms. The second section (chapters 4 – 6) contrasts constructions of risk and modernity among the actors and networks responding to the emergence, spread and persistence of the H5N1 virus, with the constructions of affected people in Indonesia. The third section (chapters 7 – 9) investigates the multi‐directional processes that occur when ‘global' policies and practices encounter ‘local' social and political settings, and vice versa, through three empirical case studies of the response to H5N1 in Indonesia between 2005 and 2010. The final section (chapter 10) provides a set of reflections and conclusions. Given the conceptual plurality of risk and modernity, and the multiple overlapping interacting hybrid constructions that have been empirically demonstrated in the case of H5N1, it is concluded that reductive, science‐based, governmentally‐orientated responses which treat nature as a matter of separate, fixed identity do not allow for such hybridity. The virus in action in Indonesia shows that any divide between nature and society is artificial and deceiving. Technical disease control responses need to incorporate understandings which accept the dynamics of culture, politics, and power.

O gênero Brachyteles, endêmico do Brasil, é constituído por duas espécies, B. arachnoides e B. hypoxantus, e estudos recentes demonstraram que suas populações selvagens podem estar seriamente reduzidas. Na tentativa de reverter a situação atual, esforços têm sito realizados visando a conservação dos muriquis, no entanto, dados relativos à condição sanitária de Brachyteles são extremamente escassos. Sabe-se, que o estabelecimento de protocolos adequados de manejo é condição necessária para a manutenção das espécies em cativeiro, sobretudo as ameaçadas e/ou criticamente ameaçadas, como é o caso dos atelídeos em questão. Desse modo, o presente trabalho de pesquisa almejou investigar as principais alterações anátomo-patológicas e correspondentes causas de morte de 18 (10M:8F) espécimens de B. arachnoides, B .hypoxantus e híbridos mantidos em cativeiro junto ao Centro de Primatologia do Rio de Janeiro (CPRJ). Os animais foram necropsiados entre os anos de 1988 e 2010 sendo utilizados fragmentos de órgãos e tecidos colhidos e fixados em solução de formalina a 10%, sendo 9 exemplares de B. arachnoides, 3 B hypoxantus e 4 híbridos, totalizando 16 indivíduos pertencentes ao acervo do CPRJ/FEEMA, e 2 B. arachnoides pertencentes ao Parque Municipal Quinzinho de Barros (FZQB). Destes, 2 (11,1 %) eram neonatos, 2 (11,1%) jovens, 13 (72,2%) adultos e 1 (5,6%) idosos. O peso dos B. arachnoides, B. hypoxantus e B. híbridos adultos, jovens e neonatos variou de 0,5 Kg até 14 Kg. O peso médio dos adultos foi 5,6 Kg. O peso médio dos adultos foi de 2,8 Kg para os caquéticos, 5,9 Kg para os magros, 8,25 Kg para os bem nutridos. Dados de histórico clínico, reprodutivo, comportamentais e análises clínicas foram avaliados visando auxílio na obtenção da causa de morte (CM). A diarréia foi a alteração clínica mais consistente observada no grupo pesquisado sendo que cinco mortes (27,8%) foram causadas por quadros de sepses, quatro por infecção viral (22,2%), três (17%) por pneumonias, dois (11%) por parasitismo. Distúrbio metabólico, peritonite e eutanásia decorrente de retrovirose foram responsáveis por 1 óbito cada (5,5%). Não foi possível determinar a CM de um (5,5%) neonato em avançado estado de putrefação. Destes 18 casos de óbito, três (17%) foram decorrentes das conseqüências da infecção por um agente viral da família Retroviridae. A análise histomorfométrica mostrou que a taxa de hemossiderose hepática (THH) variou entre 0.2% e 41.7%, não havendo diferenças significantes entre as THHs quando comparados os parâmetros sexo, idade, tempo de cativeiro, espécies e peso. A análise estatística revelou correlação entre as áreas de hemossideorse e reticulina pelo teste de Sperman com (P=0,0326, r= -0,5048) No entanto, não observou-se correlação ao avaliar a morfometria da reticulina e as graduações histopatológicas de necrose (P=0,1009, Sperman, r= 0,3991). O mesmo padrão foi observado ao avaliar a correlação entre as áreas de reticulina e os casos sépticos e não sépticos com (P= 0,6126, Mann-Whitney test). Os agentes etiológicos diagnosticados através de imuno-histoquímica, análise ultra-estrutural e/ou molecular foram: Herpes simplex, Vírus respiratório sincicial (RSV), vírus compatíveis com a família Retroviridae, Toxoplasma gondii, Entamoeba spp., Strongyloides spp., Candida spp. e Helicobacter pylori. O potencial zoonótico dos agentes infecciosos identificados reflete a importância da implantação de medidas preventivas rigorosas com o objetivo de preservar a saúde da comunidade humana e dos muriquis. Uma monitoração sanitária através de exame clínico e colheita de material biológico também foram realizadas em 10 espécimes cativos de muriquis. Pretende-se, de forma pioneira representar a sistematização de processos patológicos envolvendo espécimes do gênero Brachyteles cativos, contribuindo para a manutenção destes espécimens em cativeiro, assim como indiretamente na conservação destes em vida livre, sugerindo protocolos sanitários preventivos e favorecendo a reprodução e manutenção das populações. / The Brachyteles genus is endemic in Brazil, comprises two species, B. arachnoides and B. hypoxantus, and recent studies have shown that their wild populations can be seriously reduced. In an attempt to reverse the current scenario, efforts have been made to promote the conservation of muriquis, however, data on the sanitary condition of Brachyteles are extremely scarce. It is known that the establishment of appropriate management protocols is a prerequisite for the maintenance of the captive species, especially threatened and / or critically endangered, as is the case in question, atelids. Thus, the present research aimed to investigate the main anatomic-pathological and related causes of death in 18 (10M:8F) specimens of B. arachnoides, B. hypoxantus and hybrids in captivity at the Centro de Primatologia do Rio de Janeiro (CPRJ). The animals were autopsied between 1988 and 2010, being used fragments of organs and tissues removed and stained in formalin solution 10%, and 9 individuals of B. arachnoides, 3 B. hypoxantus and 4 hybrids, a total of 16 individuals belonging to the collection of CPRJ / FEEMA, and 2 B. arachnoides belonging to the Parque Municipal Quinzinho de Barros (FZQB). Of these, 2 (11.1%) were neonates, 2 (11.1%) youth, 13 (72.2%) adults and 1 (5.6%) elderly. The weight of adults, newborns and young B. arachnoides, B. hypoxantus and B. hybrid ranged from 0.5 kg to 14 kg average weight of adults was 5.6 kg average weight of adults was 2.8 kg for cachectic 5.9 kg for lean, 8.25 kg for well-nourished. Data from clinical history, reproductive, behavioral and medical tests were assessed for assistance in obtaining the cause of death (CD). Diarrhoea was the most consistent disease observed in this group and five deaths (27.8%) were caused by sepsis boards, four viral infection (22.2%), three (17%) for pneumonia, two ( 11%) of parasitism. Metabolic disorder, euthanasia and peritonitis resulting from a retrovirus were responsible for one each death (5.5%). We were unable to determine the CD of one (5.5%) neonate in an advanced state of putrefaction. Of these 18 deaths, three (17%) resulted from the consequences of infection by a viral agent of the family Retroviridae. Histomorphometric analysis showed that the hepatic hemosiderosis rate (HHR) ranged between 0.2% and 41.7%, with no significant differences between the HHR compared the parameters sex, age, time in captivity, species and weight. Statistical analysis revealed a correlation between areas of reticulin hemossideorse and with the Spearman test (P = 0.0326, r = -0.5048). However, no correlation was seen when evaluating the morphometry of reticulin and histopathological grades of necrosis (P = 0.1009, Spearman r = 0.3991). The same pattern was observed to evaluate the correlation between areas of reticulin and cases with septic and non septic (P = 0.6126, Mann-Whitney test). The etiologic agents diagnosed by immunohistochemistry, ultrastructural analysis and molecular were: Herpes simplex, Respiratory Syncytial Virus (RSV), consistent with the virus family Retroviridae, Toxoplasma gondii, Entamoeba spp., Strongyloides spp., Candida spp. and Helicobacter pylori. The zoonotic potential of the infectious agents identified reflects the importance of strict implementation of preventive measures in order to preserve the health of human communities in contact with the muriquis. A health monitoring by clinical examination and collection of biological material were also performed in 10 specimens of captive muriquis. We aim, in a pioneering way, represent the systemization of processes involving pathological specimens of the genus Brachyteles captives, contributing to the maintenance of these specimens in captivity, as well as indirectly on the conservation of these in the wild, suggesting preventive health protocols and encouraging the breeding and maintenance of populations

This research work is on time-delayed models of infectious diseases dynamics. The dynamics of infectious diseases are studied in the presence of time delays representing temporary immunity or latency. We have designed and analysed time-delayed models with various parameters to simulate disease dynamics, in a view to gaining insight into the behaviour of a population in the presence of infectious diseases, and the reaction of the population to changes in the management procedure of such infections.

O gênero Brachyteles, endêmico do Brasil, é constituído por duas espécies, B. arachnoides e B. hypoxantus, e estudos recentes demonstraram que suas populações selvagens podem estar seriamente reduzidas. Na tentativa de reverter a situação atual, esforços têm sito realizados visando a conservação dos muriquis, no entanto, dados relativos à condição sanitária de Brachyteles são extremamente escassos. Sabe-se, que o estabelecimento de protocolos adequados de manejo é condição necessária para a manutenção das espécies em cativeiro, sobretudo as ameaçadas e/ou criticamente ameaçadas, como é o caso dos atelídeos em questão. Desse modo, o presente trabalho de pesquisa almejou investigar as principais alterações anátomo-patológicas e correspondentes causas de morte de 18 (10M:8F) espécimens de B. arachnoides, B .hypoxantus e híbridos mantidos em cativeiro junto ao Centro de Primatologia do Rio de Janeiro (CPRJ). Os animais foram necropsiados entre os anos de 1988 e 2010 sendo utilizados fragmentos de órgãos e tecidos colhidos e fixados em solução de formalina a 10%, sendo 9 exemplares de B. arachnoides, 3 B hypoxantus e 4 híbridos, totalizando 16 indivíduos pertencentes ao acervo do CPRJ/FEEMA, e 2 B. arachnoides pertencentes ao Parque Municipal Quinzinho de Barros (FZQB). Destes, 2 (11,1 %) eram neonatos, 2 (11,1%) jovens, 13 (72,2%) adultos e 1 (5,6%) idosos. O peso dos B. arachnoides, B. hypoxantus e B. híbridos adultos, jovens e neonatos variou de 0,5 Kg até 14 Kg. O peso médio dos adultos foi 5,6 Kg. O peso médio dos adultos foi de 2,8 Kg para os caquéticos, 5,9 Kg para os magros, 8,25 Kg para os bem nutridos. Dados de histórico clínico, reprodutivo, comportamentais e análises clínicas foram avaliados visando auxílio na obtenção da causa de morte (CM). A diarréia foi a alteração clínica mais consistente observada no grupo pesquisado sendo que cinco mortes (27,8%) foram causadas por quadros de sepses, quatro por infecção viral (22,2%), três (17%) por pneumonias, dois (11%) por parasitismo. Distúrbio metabólico, peritonite e eutanásia decorrente de retrovirose foram responsáveis por 1 óbito cada (5,5%). Não foi possível determinar a CM de um (5,5%) neonato em avançado estado de putrefação. Destes 18 casos de óbito, três (17%) foram decorrentes das conseqüências da infecção por um agente viral da família Retroviridae. A análise histomorfométrica mostrou que a taxa de hemossiderose hepática (THH) variou entre 0.2% e 41.7%, não havendo diferenças significantes entre as THHs quando comparados os parâmetros sexo, idade, tempo de cativeiro, espécies e peso. A análise estatística revelou correlação entre as áreas de hemossideorse e reticulina pelo teste de Sperman com (P=0,0326, r= -0,5048) No entanto, não observou-se correlação ao avaliar a morfometria da reticulina e as graduações histopatológicas de necrose (P=0,1009, Sperman, r= 0,3991). O mesmo padrão foi observado ao avaliar a correlação entre as áreas de reticulina e os casos sépticos e não sépticos com (P= 0,6126, Mann-Whitney test). Os agentes etiológicos diagnosticados através de imuno-histoquímica, análise ultra-estrutural e/ou molecular foram: Herpes simplex, Vírus respiratório sincicial (RSV), vírus compatíveis com a família Retroviridae, Toxoplasma gondii, Entamoeba spp., Strongyloides spp., Candida spp. e Helicobacter pylori. O potencial zoonótico dos agentes infecciosos identificados reflete a importância da implantação de medidas preventivas rigorosas com o objetivo de preservar a saúde da comunidade humana e dos muriquis. Uma monitoração sanitária através de exame clínico e colheita de material biológico também foram realizadas em 10 espécimes cativos de muriquis. Pretende-se, de forma pioneira representar a sistematização de processos patológicos envolvendo espécimes do gênero Brachyteles cativos, contribuindo para a manutenção destes espécimens em cativeiro, assim como indiretamente na conservação destes em vida livre, sugerindo protocolos sanitários preventivos e favorecendo a reprodução e manutenção das populações. / The Brachyteles genus is endemic in Brazil, comprises two species, B. arachnoides and B. hypoxantus, and recent studies have shown that their wild populations can be seriously reduced. In an attempt to reverse the current scenario, efforts have been made to promote the conservation of muriquis, however, data on the sanitary condition of Brachyteles are extremely scarce. It is known that the establishment of appropriate management protocols is a prerequisite for the maintenance of the captive species, especially threatened and / or critically endangered, as is the case in question, atelids. Thus, the present research aimed to investigate the main anatomic-pathological and related causes of death in 18 (10M:8F) specimens of B. arachnoides, B. hypoxantus and hybrids in captivity at the Centro de Primatologia do Rio de Janeiro (CPRJ). The animals were autopsied between 1988 and 2010, being used fragments of organs and tissues removed and stained in formalin solution 10%, and 9 individuals of B. arachnoides, 3 B. hypoxantus and 4 hybrids, a total of 16 individuals belonging to the collection of CPRJ / FEEMA, and 2 B. arachnoides belonging to the Parque Municipal Quinzinho de Barros (FZQB). Of these, 2 (11.1%) were neonates, 2 (11.1%) youth, 13 (72.2%) adults and 1 (5.6%) elderly. The weight of adults, newborns and young B. arachnoides, B. hypoxantus and B. hybrid ranged from 0.5 kg to 14 kg average weight of adults was 5.6 kg average weight of adults was 2.8 kg for cachectic 5.9 kg for lean, 8.25 kg for well-nourished. Data from clinical history, reproductive, behavioral and medical tests were assessed for assistance in obtaining the cause of death (CD). Diarrhoea was the most consistent disease observed in this group and five deaths (27.8%) were caused by sepsis boards, four viral infection (22.2%), three (17%) for pneumonia, two ( 11%) of parasitism. Metabolic disorder, euthanasia and peritonitis resulting from a retrovirus were responsible for one each death (5.5%). We were unable to determine the CD of one (5.5%) neonate in an advanced state of putrefaction. Of these 18 deaths, three (17%) resulted from the consequences of infection by a viral agent of the family Retroviridae. Histomorphometric analysis showed that the hepatic hemosiderosis rate (HHR) ranged between 0.2% and 41.7%, with no significant differences between the HHR compared the parameters sex, age, time in captivity, species and weight. Statistical analysis revealed a correlation between areas of reticulin hemossideorse and with the Spearman test (P = 0.0326, r = -0.5048). However, no correlation was seen when evaluating the morphometry of reticulin and histopathological grades of necrosis (P = 0.1009, Spearman r = 0.3991). The same pattern was observed to evaluate the correlation between areas of reticulin and cases with septic and non septic (P = 0.6126, Mann-Whitney test). The etiologic agents diagnosed by immunohistochemistry, ultrastructural analysis and molecular were: Herpes simplex, Respiratory Syncytial Virus (RSV), consistent with the virus family Retroviridae, Toxoplasma gondii, Entamoeba spp., Strongyloides spp., Candida spp. and Helicobacter pylori. The zoonotic potential of the infectious agents identified reflects the importance of strict implementation of preventive measures in order to preserve the health of human communities in contact with the muriquis. A health monitoring by clinical examination and collection of biological material were also performed in 10 specimens of captive muriquis. We aim, in a pioneering way, represent the systemization of processes involving pathological specimens of the genus Brachyteles captives, contributing to the maintenance of these specimens in captivity, as well as indirectly on the conservation of these in the wild, suggesting preventive health protocols and encouraging the breeding and maintenance of populations

The data herein described is a compilation of retrospective and prospective studies of diseases in goats diagnosed at the Laboratório de Anatomia Patologica at the Universidade Federal de Mato Grosso do Sul. This investigation examined 74 necropsy reports of goats obtained for the period between January 2012 and August 2015. The results yielded 72 conclusive diagnoses (in 6 cases there was more than one diagnosis by necropsy), and 16 it was not possible to conclude for a diagnosis.. Of the 72 conclusive diagnoses, 65.3% were infectious and parasitic diseases, 25.0% were intoxications and toxinfections, and 8.3% were metabolic and nutritional diseases. Other disorders were diagnosed on one occasion only (1.4%). Haemonchosis was the most prevalent condition in all diagnoses (27.8%), followed by bilateral bronchopneumonia (20.8%) and poisoning by Brachiaria decumbens (18.1%). Four scientific papers resulted from this study: (1) Spontaneous poisoning by Brachiaria decumbens in goats; (2) Renal encephalopathy due to acute renal failure in a goat; (3) Granulomatous leptomeningitis in a goat associated with infection by Cryptococcus neoformans and (4) Hepatogenous chronic copper toxicosis associated with grazing Brachiaria decumbens in a goat. These four papers are already published and attached to this thesis. / Esta tese envolveu o estudo retrospectivo e prospectivo de doenças de caprinos diagnosticadas no Laboratório de Anatomia Patológica da Universidade Federal de Mato Grosso do Sul. Para isso, foram examinados os laudos de necropsias de caprinos realizadas de Janeiro de 2012 a Agosto de 2015. Durante o período estudado foram realizadas necropsias de 74 caprinos, que resultaram em 72 diagnósticos conclusivos (em 6 necropsias houve mais de um diagnóstico) e em 16 não foi possível concluir por um diagnóstico. Do total de 72 diagnósticos conclusivos, 65,3% eram de doenças infecciosas e parasitárias, 25,0% eram de intoxicações e toxinfecções e 8,3% eram de doenças metabólicas e nutricionais. Outros distúrbios foram diagnosticados em menor proporção (1,4%). Hemoncose foi a condição mais prevalente sobre o total de diagnósticos (27,8%), seguida de broncopneumonia bilateral (20,8%) e de intoxicacao por Brachiaria decumbens (18,1%). Este estudo resultou em quatro trabalhos científicos: (1) Spontaneous poisoning by Brachiaria decumbens in goats; (2) Renal encephalopathy due to acute renal failure in a goat; (3) Granulomatous leptomeningitis in a goat associated with infection by Cryptococcus neoformans e (4) Hepatogenous chronic copper toxicosis associated with grazing Brachiaria decumbens in a goat. Esses quatros trabalhos já estão publicados e estão anexados a esta tese.

The specifics of Argentina in mortality from infectious and parasitic diseases in the context of Latin America Abstract This work deals with mortality from infectious and parasitic diseases in Argentina at the turn of the 20th and 21st centuries. During this period, there was a high level of mortality from infectious diseases in Argentina, which is not common in countries where an epidemiological transition has already taken place. This thesis tries to theoretically explain the higher level of mortality from infectious diseases by describing the situation of infectious diseases in the Latin American region. It deals with the course of the demographic revolution and the epidemiological transition in the Latin American region, which had a significant impact on changes in mortality and describes the development of the incidence of specific infectious diseases in Argentina. The theoretical part is followed by an analytical explanation of mortality from infectious and parasitic diseases using the resulting indicators of mortality tables and decomposition methods used in the work. The main aim of this work was to find out what influenced the high and almost constant level of mortality from infectious diseases in Argentina at the turn of the century. The analysis was also made for selected Latin American...