Esta tese tem por objetivo apresentar um estudo sistemático da resolução,em duas dimensões espaciais, de problemas de espalhamento de ondas eletromagnéticas por meios condutores e meios dielétricos homogêneos e heterogêneos, envolvendo fontes singulares, números de onda elevados e condições de contorno absorventes, modelados pela equação de Helmholtz. A resolução dessa classe de problemas pelo Método dos Elementos Finitos apresenta dificuldades de várias ordens. A primeira decorre da presença de fontes singulares, tendo sido superada pela adoção de uma técnica de remoção de singularidades. Uma outra decorre do caráter indefinido do operador de Helmholtz para números de onda elevados, o que resulta em um erro de aproximação denominado erro de poluição. A minimização desse erro foi obtida utilizando-se a nova formulação de Petrov-Galerkin, com funções peso quase ótimas, denominada método Quasi Optimal Petrov-Galerkin (QOPG). O método QOPG, originalmente desenvolvido para meios homogêneos, foi adaptado para tratar problemas em meios heterogêneos. Finalmente, consideram-se os efeitos das condições de contorno absorventes de Bayliss-Turkel sobre a qualidade das soluções obtidas. / This thesis aims at presenting a systematic study of resolution of two-dimensional problems of electromagnetic wave scattering, by conducting and homogeneous or non-homogeneous dielectric media, involving singular sources, large wavenumbers and absorbing boundary conditions, governed by the scalar Helmholtz equation. The resolution of this class of problems through the Finite Element Method, raises several orders of difficulty. The first one comes from the presence of singular sources, having been overcome by adopting a technique of singularity removal. Another one is related to the undefined character of the Helmholtz operator for large wavenumbers, which results in the so-called pollution error of the approximated solution. This error is minimized through a new formulation of Petrov-Galerkin, using quasi optimal weighting functions, called Quasi Optimal Petrov-Galerkin (QOPG) method. The QOPG method, originally developed for homogeneous media, is extended to treating problems with non-homogeneous media as well. Finally, the effects of Bayliss-Turkel absorbing boundary conditions on the quality of the numerical solutions is also evaluated.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of this study was to evaluate the natural infection of chickens of extensive breeding of an area considered endemic for spotted fever in the state of Rio Grande do Sul through serological survey, as well as to perform the experimental infection by Rickettsia parkeri these birds. In the first study, 300 blood samples were collected and the sera were tested by indirect immunofluorescence assay (IFA) to identify the presence of anti-Rickettsia spp. antibodies. The occurrence of anti-Rickettsia spp. antibodies observed was 1.33% (4/300), with titers ranging from 64 to 256 for R. parkeri, Rickettsia rickettsii and/or Rickettsia bellii. In the second step, was performed the experimental infection by R. parkeri. 64 chickens were used divided into eight groups which were inoculated with different amounts of the agent by several routes of administration. Group 1 (G1) - inoculated with 2,5 x 105 Vero cells infected with R. parkeri (1 ml) intramuscular (IM); G2 5,0 x 105 Vero cells infected with R. parkeri (2 ml) IM, G3 - 1 ml of inoculum subcutaneously (SC); G4 - 2 ml of inoculum SC; G5 - 1 ml of the inoculum intraperitoneally (IP); G6 - 2 ml of inoculum IP, and G7 and G8 1 ml and 2 ml of culture medium Vero cells IM respectively (negative control groups). The sera of chickens were evaluated at 3, 7, 14 and 21 days post infection (PI) by IFA, to verify the dynamics of antibodies in acute and chronic infection. To identify the multiplication of R. parkeri in tissues during the same period PI, PCR was performed from fragments of spleen and lung of chickens euthanized. Birds of G4 and G3, in order of importance, had the highest average antibody showing the highest levels at seven and 14 days PI. G2, G4 and G6 showed higher mean antibody compared to G1, G3 and G5 respectively, considering the infection dose-dependent. Rickettsial DNA was not detected in the tissues evaluated. The results of both studies suggest that chickens of extensive breeding from endemic area searched do not participate as a reservoir and/or amplifier host in the epidemiology of spotted fever of region and based in the experimental infection, it was verified that birds seroconverted by the challenge by R. parkeri, but no replication of the agent in the tissues analyzed, nor the presence of rickettsemia. / Este estudo teve como objetivo avaliar a infecção natural de galinhas de criação extensiva de uma área considerada endêmica para a febre maculosa no estado do Rio Grande do Sul através de pesquisa sorológica, bem como realizar a infecção experimental por Rickettsia parkeri nessas aves. No primeiro estudo, foram coletadas 300 amostras de sangue e os soros foram testados pela reação de imunofluorescência indireta (RIFI) para identificar a presença de anticorpos anti-Rickettsia spp. A ocorrência de anticorpos anti-Rickettsia spp. observada foi de 1,33% (4/300), com títulos variando de 64 a 256 para R. parkeri, Rickettsia rickettsii e/ou Rickettsia bellii. Na segunda etapa, foi realizada a infecção experimental por R. parkeri, o qual foram utilizadas 64 galinhas caipiras divididas em oito grupos, onde foram inoculadas diferentes quantidades do agente por diversas vias de administração. Grupo 1 (G1) - inoculado com 2,5 x 105 células Vero infectadas por R. parkeri (1 ml) via intramuscular (IM); G2 5,0 x 105 células Vero infectadas por R. parkeri (2 ml) via IM; G3 - 1 ml do inóculo via subcutânea (SC); G4 - 2 ml de inóculo via SC; G5 - 1 ml do inóculo via intraperitoneal (IP); G6 - 2 ml de inóculo via IP, e o G7 e G8 - 1 e 2 ml de meio de cultivo de células Vero via IM respectivamente (grupos controles negativos). Os soros das aves foram avaliados aos 3, 7, 14 e 21 dias pós infecção (PI) por meio de RIFI, para avaliar a dinâmica de anticorpos em infecção aguda e crônica. Para identificar a multiplicação de R. parkeri nos tecidos, no mesmo período PI, foi realizado o PCR a partir de fragmentos de baço e pulmão colhidos das galinhas eutanasiadas. As aves do G4 e G3, em ordem de importância, apresentaram as maiores médias de anticorpos apresentando os níveis mais elevados aos sete e 14 dias PI. Os grupos G2, G4 e G6 apresentaram médias de anticorpos superiores comparado ao G1, G3 e G5 respectivamente, sendo considerada a infecção dose-dependente. Não foi detectado DNA rickettsial nos tecidos avaliados. Os resultados de ambos os estudos sugerem que as galinhas de criação extensiva da área endêmica pesquisada não participaram como reservatório e/ou hospedeiro amplificador na epidemiologia da febre maculosa na região e baseado na infecção experimental, verificou-se que as aves soroconverteram mediante o desafio por R. parkeri, porém não houve a multiplicação do agente nos tecidos analisados, bem como a presença de rickettsemia.

Made available in DSpace on 2014-07-29T15:07:32Z (GMT). No. of bitstreams: 1 Dissertacao Denizard Andre de Abreu Delfino.pdf: 922702 bytes, checksum: f27146bc0b024ae0d79c5f4cfec679f6 (MD5) Previous issue date: 2011-03-30 / The objective of this study was to carry out and analyze the actions taken to control the yellow fever epizootic in non-human primates, recorded in November 2007 to March 2010 in Aparecida de Goiania, Goias Brazil. The primary epidemiological information on the disease was obtained from the Municipal Health Secretariat, by the local Center for Zoonosis Control. Data were analyzed from the outbreak reports. In A descriptive study, the control actions, such as blocking vaccine against yellow fever by the municipal health department and the evaluation of physical barriers to contain the virus, were verified. The inspection of 58 dead nonhuman primates, representing 100% of the animals found in the period previously mentioned, was used. From these, 34.48% (20/58) were able to have samples collected, according to the specifications of the Epizooty Handbook Of this amount (58), 27.59% (16/58) of monkeys were collected and3.45% (2/58) presented positivity for yellow fever virus. By evaluating the actions that contributed to the epidemiological assessment at the city, it is emphasized the occurrence of three deaths among genera and species of nonhuman primates, Alouatta caraya, Cebus apella and Callithrix spp, with the circulation of yellow fever virus in two cities with epidemiological distinct characteristics. The areas which showed the highest incidence of deaths of monkeys had also the greatest degree of urban growth, characterized by recent environmental changes and residual maintenance of natural areas. / O presente estudo constituiu na condução e análises de ações desenvolvidas no controle da epizootia de febre amarela em primatas não-humanos, registrada nos meses de novembro 2007 a março de 2010 em Aparecida de Goiânia, Goiás. As informações epidemiológicas primárias relativas à enfermidade foram obtidas junto à Secretaria Municipal de Saúde, pelo Centro de Controle de Zoonoses local. A partir das fichas de notificação para epizootia os dados foram analisados. Foi realizado estudo descritivo, que estudou as ações de controle, como bloqueio vacinal contra a FA pela secretaria municipal de saúde do município e a avaliação das barreiras físicas na contenção do vírus amarílico. Foi utilizada a inspeção de 58 primatas não-humanos mortos, que representaram 100% dos animais encontrados no período acima citado, sendo que destes 34,48% (20/58) estavam aptos para colheita de amostras, segundo as especificações do com o Manual de Epizootia. Deste montante, foram coletados 27,59% (16/58) de macacos, com uma positividade para o vírus amarílico de 3,45% (2/58). Avaliando as ações que contribuíram para realização da investigação epidemiológica no município, destaca-se que ocorreram mortes entre três gêneros e espécies de primatas não-humanos, Alouatta caraya, Cebus spp. e Callithrix spp., com a circulação do vírus da FA em duas localidades com características epidemiológicas distintas. As áreas de maior ocorrência de mortes de macacos foram aquelas com maior grau de antropização, caracterizadas por alterações ambientais recentes e manutenção residual de áreas naturais.

Made available in DSpace on 2014-07-29T15:30:35Z (GMT). No. of bitstreams: 1 Dissertacao de Benigno Alberto Moraes Rocha.pdf: 429604 bytes, checksum: e7166c606b960cf25df199a5ddc928fd (MD5) Previous issue date: 2008-02-29 / In Brazil, dengue is present in almost all states and territories, with a circulation of three different serotypes (DEN 1, DEN 2 and DEN 3), resulting in about 500 000 cases reported in 2007 (PAHO 2008; MS / SVS 2008a). This dissertation consists of a literature review, with emphasis on the epidemiology of dengue in Brazil and two articles that are designed to analyze the clinical and epidemiological characteristics of this condition, focusing on children under 15 years old, in Goiânia. The first article provides a profile analysis 59. 157 reported cases of dengue (SINAN), in Goiania, from 2001 to 2006. It also presents a reliability evaluation of the clinical classification of dengue, as recorded in the SINAN, compared with a revised classification proposed by the authors. There was an increase of dengue fever with complications or Dengue hemorrhagic fever in all age groups (p <0.05), children showed more hemorrhagic manifestations, however, no difference in the proportion of severe cases among adults and children. The results showed a low capacity of the surveillance system for classifying cases potentially serious in children under 15 years old (Kappa = 0.22; 95% CI 0.20 to 0.24). The second article examines 162 children under 15 years with acute febrile illness suggestive of dengue fever, attended from 2005 to 2006. We collected blood samples for detection of IgM anti-dengue (MAC-ELISA), molecular biology test (RT-PCR) and virus isolation. Half the cases were laboratory confirmed by serology and 84 and five by RT-PCR and / or virus isolation and identification of DEN 3 in all. Myalgia, arthralgia, rash, thrombocytopenia and leukopenia were more frequent among confirmed cases (p <0.05). PPV and NPV for suspected dengue cases, by clinical criteria, were respectively 54.8% and 40.0%. Recommended clinical criteria for diagnosis of dengue were reluctant for this specific age group, even in a region of high endemicity. / No Brasil, a dengue esta presente em quase todos os estados e territórios, com circulação de três sorotipos diferentes (DEN 1, DEN 2 e DEN 3), resultando em cerca de 500 mil casos notificados, em 2007 (PAHO 2008; MS/SVS 2008a). A presente dissertação de mestrado é composta por uma revisão da literatura, com ênfase na epidemiologia da dengue no Brasil e por dois artigos que se propõem analisar as características clínicas e epidemiológicas desse agravo, com enfoque em menores de 15 anos de idade, em Goiânia. O primeiro artigo traz uma análise do perfil de 59. 157 casos notificados de dengue (SINAN), em Goiânia, de 2001 a 2006. Apresenta, também, uma avaliação da confiabilidade da classificação clínica de dengue, conforme registrada no SINAN, em comparação com uma classificação revisada, propostas pelos autores. Houve aumento de dengue com complicação ou dengue hemorrágica, em todas as faixas etárias (p<0,05), Crianças apresentaram mais manifestações hemorrágicas, entretanto, não houve diferença na proporção de formas graves entre adultos e crianças. Foi evidenciada uma baixa capacidade do sistema de vigilância para classificar casos potencialmente graves, em menores de 15 anos de idade (Kappa = 0,22; IC95% 0,20-0,24). O segundo artigo analisa 162 menores de 15 anos, com quadro febril agudo, sugestivo de dengue, atendidas entre 2005 a 2006. Foram colhidas amostras de sangue para detecção de IgM anti-dengue (MAC-ELISA); teste de biologia molecular (RT-PCR) e isolamento viral. Metade dos casos foram confirmados laboratorialmente, sendo 84 por sorologia e cinco por RT-PCR e/ou isolamento viral, com identificação de DEN 3 em todos eles. Mialgia,artralgia, exantema, plaquetopenia e leucopenia foram mais freqüentes entre os casos confirmados (p< 0,05). VPP e VPN para casos suspeitos de dengue, pelos critérios clínicos, foram, respectivamente, de 54,8% e 40,0%. Critérios clínicos preconizados para o diagnóstico de dengue mostraram-se pouco específicos para esta faixa etária, mesmo em região de alta endemicidade.

Neste trabalho foi feito uma investigação sorológica em moradores na região amazônica e moradores rurais do sudeste brasileiro, através do teste de inibição da hemaglutinação (HI) para a cepa vacinal da Febre Amarela mais 17 sorotipos diferentes de arbovírus, sendo quatro do gênero Alphavirus (ALP), nove do gênero Flavivirus (FLA) e cinco do gênero Orthobunyavirus (ORT), para verificar qual desses vírus estão circulando nessas regiões. Os resultados do HI foram divididos em quatro áreas: na cidade Machadinho dOeste (Rondônia) (N=285) tivemos para ALP=50 (17,54%), FLA=270 (94,74%), ORT=58 (20,35%) e negativos (NEG)=12 (4,20%). Nas pessoas que moram ao longo do Rio Machado (Rondônia) (N=343) tivemos ALP=99 (28,86%), FLA=229 (66,76%), ORT=41 (11,95%) e NEG=93 (27,10%). Na cidade Teodoro Sampaio (São Paulo) (N=78) tivemos FLA=55 (70,51%) e NEG=23 (29,5%). Na cidade Jacupiranga (São Paulo) (N=149) tivemos ALP=7 (4,7%), FLA=50 (33,56%), ORT=20 (13,42%) e NEG=84 (56,4%). Concluímos que os resultados obtidos sugerem a circulação desses vírus nas regiões estudadas. / In this work we performed a serological investigation in residents of Amazon region and country people who lives in Southeastern of Brazil, by hemagglutination inhibition (HI) for Yellow fever vaccine and 17 different serotype of arboviruses: four from the genus Alphavirus (ALP), nine from the genus Flavivirus (FLA), and five from the genus Orthobunyavirus (ORT), to try to ascertain which of these arboviruses are circulating in these areas. The results of HI were divided into four areas: In Machadinho dOeste city (Rondônia) (N=285) we had to ALP=50 (17,54%), FLA=270 (94,74%), ORT=58 (20,35%) and negatives (NEG)=12 (4,20%). In people who live along the Machado River (Rondônia) (N=343) we had to ALP=99 (28,86%), FLA=229 (66,76%), ORT=41 (11,95%) and NEG=93 (27,10%). In Teodoro Sampaio City (São Paulo) (N=78) we had to FLA=55 (70,51%) and NEG=23 (29,5%). In Jacupiranga City (São Paulo) (N=149) we had to ALP=7 (4,70%), FLA=50 (33,56%), ORT=20 (13,42%) and NEG=84 (56,4%). In conclusion, the obtained data suggest the circulation of these viruses in these regions.

Introdução e Objetivo: No Brasil, procedimentos valvares representam no mínimo 30% das cirurgias cardíacas realizadas no país. Em nosso meio ainda predominam as lesões valvares decorrentes da febre reumática e doenças degenerativas. Nos pacientes reumáticos, a valva mitral é a mais acometida, predominando a estenose devido à fusão comissural e lesões no plano subvalvar; porém espessamento e retração de cúspides também são comuns, determinando dupla lesão ou insuficiência desta valva. Em processos degenerativos, as cordas tendíneas podem se apresentar alongadas. Na tentativa de utilização futura do laser como método auxiliar na correção cirúrgica dessas valvopatias, iniciamos estudo experimental com o objetivo de comparar histologicamente o tecido valvar mitral de suínos (cordas tendíneas e cúspides) submetido com e sem o laser de alta potência (LAP). Métodos: Foram estudadas cordas tendíneas e cúspides mitrais de suínos jovens e saudáveis, divididos em 6 grupos: G1-Aplicação do laser em cordas tendíneas com o tempo de 15 s; G2- Aplicação do laser em cordas tendíneas com o tempo de 20 s; G3- Aplicação do laser em cordas tendíneas com o tempo de 30 s; G4- Grupo controle relacionado a G1, G2 e G3; G5- Grupo cúspide submetido a corte com lâmina de bisturi; G6- Grupo cúspide submetido a corte com laser. As cordas tendíneas dos grupos G1, G2 e G3 receberam tratamento com laser de diodo (=980 nm, P=3,0 W) e o grupo G6 com laser de diodo em outros parâmetros (=980 nm, P=9,0 W, T=12s). Termografia e tomografia por coerência óptica foram utilizadas durante o experimento. Parte da amostra foi preservada em formaldeído e glutaraldeído para análise microscópica e a outra parte foi preservada em solução fisiológica 0,9% para análise mecânica. Resultados: Houve um decréscimo significante no comprimento das cordas tendíneas após aplicação do laser quando comparado ao comprimento inicial (p=0,005 em G1 e G2 e p=0,004 em G3). À microscopia óptica, G1, G2 e G3 apresentaram áreas hialinas ocupando quase a totalidade da espessura da corda, quando coradas pela Hematoxilina-Eosina (HE), áreas vermelho-escura na região central da corda quando coradas pelo Tricrômico de Masson e áreas com birrefringência diminuída quando coradas pelo Picrosírius vermelho. Na avaliação mecânica, os grupos lasers apresentaram diminuição da rigidez do material, assim como na força máxima durante a ruptura, entretanto o deslocamento foi maior em relação ao grupo controle (p=0,005). No G5, evidenciamos ausência de qualquer alteração histológica. No G6 foram identificadas áreas de menor birrefringência do colágeno quando corado pelo Picrosírius vermelho, áreas estas que apresentavam aspecto basofilico hialino no HE e coloração vermelho-escura ao Tricrômico de Masson. Conclusão: As cordas tendíneas de valvas mitrais de suínos submetidas ao laser de alta potência apresentaram redução do seu comprimento final, diminuição na birrefringência e alteração na distribuição dos feixes de colágeno. Além disso, apresentaram queda da rigidez, maior fragilidade de rotura e maior deslocamento ao teste de tração mecânica quando comparada ao grupo controle. Com relação às cúspides, os danos térmicos encontrados no grupo corte com laser de alta potência foram maiores do que em relação ao bisturi de lâmina, quando evidenciados pela microscopia óptica / Introduction and Objective: In Brazil, valvar procedures represent at least 30% of cardiac surgeries performed in the country. It still predominate valvar lesions resulting from rheumatic fever and degenerative diseases. In rheumatic patients, the mitral valve is the most affected, predominantly stenosis due to commissural fusion and lesions in the subvalvar plane, however, thickening and retraction of the leaflets are also common, causing double lesion or mitral insufficiency. In degenerative process, the chordae tendineae may present elongated. In an attempt to further use of the laser as an auxiliary method in the surgical correction of valvar heart disease, we started experimental study with the purpose of comparing the histological swine tissue mitral valve (chordae tendineae and cusps) with and without high-power laser (HPL) application. Methods: Normal porcine mitral valve chordae and cups were studied and divided randomly into the following 6 groups: G1- Laser in the chordae tendineae with time of 15s; G2- Laser in the chordae tendineae with time of 20s; G3- Laser in the chordae tendineae with time of 30s; G4- Control Group; G5- Cusp group cut with a scalpel blade; G6- Cusp group cut with laser. Chordae tendineae from G1, G2 e G3 received diode laser (=980 nm, P=3,0 W) and G6 diode laser with other parameters (=980 nm, P=9,0 W, T=12s). Termography and optical coherence tomography were included during the procedure. Part of the sample was preserved in formaldehyde and glutaraldehyde for microscopic analysis and another part was stored in 0.9% saline for mechanical analysis. Results: There was a significant decrease in chordae length after laser application when compared to the initial length (p=0,005 to G1 and G2; p=0,004 to G3). In laser groups, histological analysis revealed a typical hyaline areas occupying almost the entire thickness of the chordae, when stained with Hematoxylin-Eosin (HE); dark red central areas when stained with Masson Trichrome and a birefringence decrease when stained with Picrocirius red. In mechanical analysis, we found lower stiffness, maximum rupture force decrease and larger displacement compared with the Control Group (p=0,005). In G5, was evidenced absence of any histological abnormality and a homogeneous blue appearance, typical of the cusp. However in G6, a basophilic hyaline aspect was found focally when stained with HE, dark red areas when stained with Masson Trichrome and a birefringence decrease when stained with Picrocirius Red. Conclusion: Chordae tendineae of normal porcine submitted to a high-power laser presented with reduced length, birefringence decrease and the collagen bundles organized into different orientations. Besides, presented lower stiffness, maximum rupture force decrease and larger displacement compared with the control group. Regarding cups, thermal changes were bigger in the cusp group cut with laser compared cusp group cut with scalpel blade, observed by optical microscopy

The fever response, besides being part of host defense response to infection or inflammation, is associated with discomfort and anxiety and may constitute a risk for febrile seizures in children. Therefore, antipyretic therapy is routinely prescribed for febrile patients. The animal models of fever using the systemic injection of lipopolysaccharide (LPS) and Baker yeast, described in the literature, are suitable for screening of novel antipyretics, but they do not provide information regarding the mechanism of action of these compounds. Therefore, the present study aimed to describe and validate a model of fever induction by prostaglandin (PG) E2, the final mediator of febrile response in the central nervous system, in young male Wistar rats (25-30 days of age). In this protocol, PGE2 was injected intrathecally without implantation of cannula. Rectal temperature (TR) was recorded every thirty minutes for three hours after PGE2 injection (08:00 11:00 h). The intrathecal (i.t.) injection of PGE2 10 ηg in 100 μL/animal induced fever in the animals, which was prevented by administration of EP1 and EP3 receptors antagonists, but did not by antagonist of EP4 receptor. In addition, the classic antipyretics dipyrone and acetaminophen, at doses that had no effect per se on TR of animals, did not revert the fever induced by i.t. injection of PGE2. This model seems suitable to investigate whether the action of antipyretics occurs upstream or downstream the prostaglandin coupling in EP receptors. In addition, this protocol is advantageous from the technical, ethical and economical point of view compared to others PGE2-induced fever protocols described in the literature, because trepanation for cannula implantation is not required, reducing the inflammatory response, animals suffering and experimental costs. / A febre, apesar de fazer parte da resposta de defesa do hospedeiro à infecção ou inflamação, está associada com desconforto e ansiedade, além de representar um risco iminente de convulsões febris em crianças. Por isso, terapia antipirética é rotineiramente prescrita a pacientes febris. Os modelos animais de febre empregando a injeção sistêmica de lipopolissacarídeo (LPS) e fermento de padeiro, descritos na literatura, são úteis para a triagem de novos antipiréticos, mas não fornecem informações a respeito do mecanismo de ação desses compostos. Diante disso, o presente estudo objetivou padronizar e validar um modelo de indução de febre por prostaglandina (PG) E2, o mediador final da resposta febril no sistema nervoso central, em ratos machos jovens da raça Wistar (25-30 dias). Neste protocolo, a PGE2 foi injetada pela via intratecal (i.t.), não necessitando a implantação de cânula. A temperatura retal (TR) foi registrada a cada trinta minutos durante três horas após a injeção da PGE2 (08:00-11:00 h). A injeção i.t. de PGE2 10 ηg em 100 μL/animal induziu febre nos animais, a qual foi prevenida pela administração de antagonistas dos receptores EP1 e EP3, mas não por antagonista do receptor EP4. Além disso, os antipiréticos clássicos dipirona e paracetamol, em doses que não tiveram efeito per se na TR dos animais, não reverteram a febre induzida por PGE2 i.t. Este modelo parece útil para investigar se a ação dos antipiréticos ocorre antes ou depois da ligação da PGE2 em seus receptores EP. Além disso, este protocolo é vantajoso do ponto de vista técnico, ético e econômico em relação aos outros protocolos de indução de febre por PGE2 descritos na literatura, porque a trepanação para implantação de cânula não é necessária, reduzindo a resposta inflamatória, o sofrimento dos animais e os custos experimentais.

Rift Valley fever (RVF) is an emerging viral zoonosis that causes frequent outbreaks in east Africa and on the Arabian Peninsula. The likelihood of RVF global expansion due to climate change and human anthropogenic factors is an important issue. The causative agent, RVF virus, is an arbovirus that is transmitted by several mosquito species and is able to infect a wide range of livestock as well as people. The infection leads to mass abortions and death in livestock and a potentially deadly hemorrhagic fever in humans. RVF has severe socio-economic consequences such as animal trade bans between countries, disruption of food security, and economic disaster for farmers and pastoralists as well as for countries. Human behavior such as direct contact with infected animals or their fluids and exposure to mosquito bites increases the risk for contracting the disease. To better understand the challenges associated with RVF outbreaks and to explore prevention and control strategies, we used the One Health approach. The local community had to be involved to understand the interaction between the environment, animals, and humans. We focused on Sudan, Saudi Arabia, and Kenya. First, we systematically reviewed the literature and then we performed cross sectional community-based studies using a special One Health questionnaire. Climatic and remote sensing data were used in combination with statistics to develop a sub-region predictive model for RVF. For both Saudi Arabia and Sudan, the ecology and environment of the affected areas were similar. These areas included irrigation canals and excessive rains that provide an attractive habitat for mosquito vectors to multiply. The surveillance systems were unable to detect the virus in livestock before it spread to humans. Ideally, livestock should serve as sentinels to prevent loss of human lives, but the situation here was reversed. Differences between countries regarding further spread of RVF was mainly determined by better economic and infrastructure resources. In Sudan, there was a lack of knowledge and appropriate practices at the studied community regarding RVF disease symptoms and risk factors for both animals and humans. The community was hesitant in notifying the authorities about RVF suspicion in livestock due to the lack of a compensation system. The perceived role of the community in controlling RVF was fragmented, increasing the probability of RVF transmission and disease. In Kenya, our study found that better knowledge about RVF does not always translate to more appropriate practices that avoid exposure to the disease. However, the combination of good knowledge, attitudes, and practices may explain why certain communities were less affected. Strategies to combat RVF should consider socio-cultural and behavioral differences among communities. We also noticed that RVF outbreaks in Kenya occurred in regions with high livestock density exposed to heavy rains and wet soil fluxes, which could be measured by evapotranspiration and vegetation seasonality variables. We developed a RVF risk map on a sub-regional scale. Future outbreaks could be better managed if such relevant RVF variables are integrated into early warning systems. To confront RVF outbreaks, a policy is needed that better incorporates ecological factors and human interactions with livestock and environment that help the RVF pathogen spread. Early detection and notification of RVF is essential because a delay will threaten the core of International Health Regulations (IHR), which emphasizes the share of information during a transboundary disease outbreak to avoid unnecessary geographical expansion.

Typhoid disease, caused by infection with S. Typhi, is a significant cause of mortality and morbidity in resource–poor countries. Efforts have been made to generate a new generation of vaccines that are efficacious and can be given to infants, but have been hindered by a poor understanding of the protective immune response to S. Typhi infection, and in particular by the absence of a correlate of protection. Controlled human infection studies (‘challenge studies’) provide a model for investigating infectious diseases and appraising novel vaccines, including in typhoid disease. This DPhil described the development of a human challenge model of typhoid fever using <en>S. Typhi Quailes strain administered to healthy adults in a sodium bicarbonate buffer. The careful characterisation and manufactured of the strain is described. Following ingestion of 10³ CFU of S. Typhi 55% of participants developed typhoid disease, whilst ingestion of 10⁴ CFU gave a higher attack rate of 65%. At this attack rate vaccine efficacy against human challenge should be demonstrable with a modest sample size. Validity of the model in the appraisal of vaccines was demonstrated using Ty21a, a live, oral, attenuated vaccine. Protective efficacy of Ty21a compared to placebo against challenge was 35%, comparable to that observed in some endemic settings, and the estimated protection in the first year after vaccination in Cochrane meta-analysis. Clinical, microbiological and humoral immune responses were investigated in participants challenged during model development. Typhoid disease was associated with a high fever in most, but not all participants, and a range of symptoms. Severity of disease was variable, and included asymptomatic bacteraemia, as well as fever and symptoms in participants in whom bacteraemia could not be demonstrated. Typhoid disease was associated with a strong humoral immune response to the flagellin and lipopolysaccharide antigens of S. Typhi but not the Vi polysaccharide capsule. Humoral immune responses were not demonstrated in participants without typhoid fever. There was a dose-response relationship to the clinical, microbiological and humoral responses with participants challenged with 10⁴ CFU having more marked responses than those challenged with 10³ CFU. Future success of challenge studies relies on the willing participation of healthy adult volunteers. The motivations for participation, and experiences of participants, were appraised by questionnaire. Whilst financial compensation was an important motivator, it was not the sole motivator. Participants were positive about their experiences, and most would participate again.

Philosophiae Doctor - PhD / The study outlines five areas of intervention in the development of women studies and politics on the continent. Firstly, it examines the problematic construction and the inclusion of women in the narratives of the liberation struggle in South Africa. Secondly, the study identifies the sphere of intellectual debates as one of the crucial sites in the production of historical knowledge about the legacies of liberation struggles on the continent. Thirdly, it traces the intellectual trajectory of Charlotte Maxeke as an embodiment of the intellectual contributions of women in the struggle for liberation in South Africa. In this regard, the study traces Charlotte Maxeke as she deliberated and engaged on matters pertaining to the welfare of the Africans alongside the prominent intellectuals of the twentieth century. Fourthly, the study inaugurates a theoretical departure from the documentary trends that define contemporary studies on women and liberation movements on the continent. Fifthly, the study examines the incorporation of Maxeke's legacy of active intellectual engagement as an integral part of gender politics in the activities of the Women's Section of the African National Congress. In the areas identified, the study engages with the significance of the intellectual inputs of Charlotte Maxeke in South African history. / South Africa