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.

Le virus Lassa entraine une fièvre hémorragique endémique en Afrique de l’Ouest et représente un problème de santé publique. Les connaissances sur la pathogénèse et les réponses immunitaires associées à la maladie sont partielles. Nous avons suivi les paramètres pathologiques, virologiques et immunologiques associés aux infections létales et non létales du LASV chez le singe cynomolgus. Le tableau clinique a été caractérisé par une dépression, une anorexie, une perte de poids et une asthénie chez les animaux survivants, tandis que ces mêmes symptômes ont été accompagnés de fièvre, de difficultés respiratoires et d’épistaxis chez les animaux infectés par une dose létale. Seuls ces derniers ont montré une perturbation des paramètres de coagulation, une rhabdomyolyse et une hausse des marqueurs de lésions rénales. Nous avons observé un tropisme radicalement différent en fonction de la sévérité de la maladie, avec une dissémination virale dans les organes plus importante et plus rapide chez les animaux décédés, la présence de particules infectieuses plus nombreuses et des modifications anatomopathologiques plus sévères. Une réponse immunitaire innée et adaptative précoce et puissante a été associée avec le contrôle de l’infection et la survie tandis que les infections fatales ont été caractérisées par une réponse inflammatoire ressemblant au choc septique, une défaillance de la réponse immunitaire ainsi qu’une réplication virale incontrôlée. Cette étude permet d’améliorer nos connaissances de la pathogénèse de la fièvre de Lassa et d’apporter des marqueurs d’infection prédictifs de la maladie / Lassa virus causes a hemorrhagic fever endemic in West Africa and represents a threat for civilians. The pathogenesis and the immune responses associated with the disease are poorly understood. We followed pathological, virological and immunological parameters associated with fatal and non-fatal Lassa virus infection in the cynomolgus monkey. The clinical picture was characterized by depression, anorexia, weight loss and asthenia in survivors whereas the same symptoms were supported by fever, respiratory difficulties and epistaxis in animals infected with the lethal dose. Only fatalities have shown coagulation parameters dysfunction, rhabdomyolysis and an increase of renal function markers. We observed a different viral tropism in a function of the disease severity, with viral dissemination in organs that was more important and faster in fatalities, the appearance of numerous infectious particles number and more severe pathologic changes. Early and robust innate and adaptive immune response has been associated with the control of infection and recovery whereas fatal infections were characterized by a sepsis like inflammatory response, defective immune response as well as uncontrolled viral replication. This study sheds light on the pathogenesis of Lassa fever and reveals infection markers predictive of the disease outcome

Dengue fever (DF) and dengue hemorrhagic fever (DHF) are emerging infectious diseases which are endemic in many regions of the globe, many of which are resource-poor areas. DHF and DF impose a severe economic health burden in tropical and subtropical areas. Dengue virus causes an acute febrile illness that can be a self-limited febrile illness, as seen in most cases of DF, or a life-threatening illness with plasma leakage and shock, as seen in cases of DHF. A systematic review of the literature revealed gaps in the knowledge base of clinical laboratory findings of dengue illness with regards to longitudinal dynamics and classification and predictive modeling of disease severity. The objective of this thesis was to investigate the utility of clinical laboratory variables for classification and prediction of disease outcomes. The data used in this investigation was derived from a prospective study of Thai children presenting to either of two study hospitals within 72 hours of onset of an acute febrile illness. Systematic data collection, including clinical laboratory parameters, and routine clinical management continued each day until 24 hours after the fever had subsided. A final diagnosis of DHF, DF, or other febrile illness (OFI) was assigned by an expert physician after chart review. The first research objective of this study was to describe the temporal dynamics of clinical laboratory parameters among subjects with DHF, DF, or OFI. Data were analyzed using lowess curves and population-average models. Quadratic functions of clinical variables over time were established and demonstrated significantly divergent patterns between the various diagnostic groups. The second research objective was to establish and validate tools for classification of illness severity using easily obtained clinical laboratory measures. Bivariate logistic regression models were established using data from one hospital in an urban area of Thailand as a training data set and validated with a second data set from a hospital in a rural area of Thailand. The validated models maintained a high sensitivity and specificity in distinguishing severe dengue illnesses without using the hallmark indicators of plasma leakage. The third research objective used classification and regression tree (CART) analysis to established diagnostic decisions trees using data obtained on the day of study enrollment, within the first 3 days of acute illness. Decision trees with high sensitivity were established for severe dengue defined either as: 1) DHF with evidence of shock (dengue shock syndrome, DSS); or 2) DSS or dengue with significant pleural effusion. This study expands existing knowledge of the potential utility of clinical laboratory variables during different phases of dengue illness. The application of the results of these studies should lead to promising opportunities in the fields of epidemiological research and disease surveillance to reduce the health burden, and improve the clinical management, of dengue illness. Future directions involve application of these algorithms to different study populations and age groups. Additionally, other analytical techniques, such as those involving CART analysis, can be explored with these data.

Made available in DSpace on 2016-12-23T13:47:02Z (GMT). No. of bitstreams: 1 Creuza Rachel Vicente.pdf: 3384838 bytes, checksum: c3eca90bf4886725c29d5e5904662f2b (MD5) Previous issue date: 2012-03-15 / Introdução: A ocorrência da dengue sofre influência do comportamento, estrutura social e distribuição da população e sua transmissão pode variar de acordo com as áreas do município. Seu prognóstico depende do diagnóstico precoce e da imediata instituição do tratamento. Este estudo avalia fatores associados à ocorrência da dengue, enfatizando a distribuição territorial e os relacionados à dengue grave. Métodos: Foram realizados dois estudos, sendo um transversal e outro retrospectivo, sobre a totalidade dos casos de dengue que ocorreram em Vitória no ano de 2011, com base nos dados do Sistema de Informações de Agravos de Notificação. Resultados: Entre os casos confirmados, 53,4% ocorreram em mulheres, 74,7% em maiores de 15 anos e 6,3% evoluíram para gravidade. Os territórios de saúde de Jardim Camburi, Maruípe, Ilha das Caieiras, Santa Martha e Santo André responderam por 41,6% das notificações. Quase metade dos casos foram concluídos por critério laboratorial e, destes, 80% realizaram sorologia. Em todos os territórios, mais de 20% dos notificados realizaram sorologia e, na maioria, mais de 51% tiveram resultado positivo. Nas regiões de São Pedro, Maruípe e Santo Antônio, os afetados eram principalmente jovens, enquanto nas regiões Continental e Forte São João, eram pessoas mais velhas. Dos 371 casos de dengue grave, 78,7% foram de dengue com complicações e 21,3% de febre hemorrágica da dengue. Sessenta e sete por cento dos casos ocorreram em pessoas com idade superior a 15 anos. As Regiões de Saúde de Maruípe e São Pedro foram responsáveis por mais da metade dos casos de dengue grave (56,35%). Houve associação estatisticamente significante entre ocorrência de febre hemorrágica da dengue com idades mais jovens (menores de 15 anos) e maior tempo decorrido na procura por atendimento. Também houve associação estatisticamente significante entre maior tempo decorrido na procura pelo atendimento e idade menor que 15 anos. Os casos de dengue grave estavam concentrados em faixas etárias mais jovens na região de São Pedro. Conclusão: A distribuição territorial não foi uniforme, e pode ser determinada pela alta densidade populacional e pelas condições socioeconômicas. As diferenças de idade entre as regiões podem estar relacionadas à incidência da doença nestes locais. A grande proporção de sorologias positivas e o número de exames realizados possibilitaram uma boa detecção e acompanhamento dos casos de dengue. Os resultados corroboram os de outras pesquisas que apontam uma mudança no perfil da febre hemorrágica da dengue nas Américas e no Brasil, com crescente acometimento de jovens, e apontam a demora no tempo de procura por atendimento, baixa qualidade urbana e alta endemicidade como possíveis fatores de risco. / Introduction: The incidence of dengue, influenced by human behavior, social structure and population distribution, may vary with respect to the geographical areas of a given city. Its prognosis depends on early diagnosis and prompt initiation of treatment. This study evaluates factors related to the occurrence of dengue, emphasizing the territorial distribution and risk factors for severe dengue. Methods: A cross-sectional and a retrospective study on all cases were conducted with dengue cases of Vitória in 2011, based on data from the Information System of Notifiable Diseases (SINAN). Results: 53.4% of confirmed cases occurred in women, 74.7% were 15 years old or older, and 6.3% were severe forms. The health territories of Jardim Camburi, Maruípe, Ilha das Caieiras, Santa Martha and Santo André accounted for 41.6% of reported cases. Almost half of the cases had final classification based on laboratory tests, and of these, 80% were submitted to serological tests. Of all territories, more than 20% of those reported cases had been submitted to serological tests, and more than 51% of them had a positive result. In the regions of São Pedro, Santo Antônio e Maruípe, the affected individuals were younger, while in Continental Region and Forte São João Region, they were older. Of the 371 cases of severe dengue, 78.7% were classified as dengue with complications and 21.3% were classified as dengue hemorrhagic fever, whose age distribution disclosed a frequency of 67.1% in individuals 15 years old or older. Regions of Maruípe and São Pedro were responsible for over half of cases of severe dengue (56.3%). There was a statistically significant association between the occurrence of dengue hemorrhagic fever and younger ages (under 15 years) and longer time interval between the beginning of symptoms and seeking for care. People younger than 15 years old take longer to seek for care. The frequencies of cases of severe dengue were concentrated in younger age groups in the region of São Pedro. Conclusion: The geographical distribution was not uniform, and can be influenced by the high population density and socioeconomic conditions. The age differences between regions may be related to disease incidence in these locations. A large proportion of positive tests and a great number of tests performed allowed a good detection and monitoring of dengue cases. The results corroborate those of other studies that indicate a change in the profile of dengue hemorrhagic fever in the Americas and Brazil, with growing involvement of young people, and indicate the time delay in seeking treatment, urban poor quality and high endemic scenario as possible risk factors.