Orientador: Paulo Fernando de Arruda Mancera / Resumo: A dengue é a doença viral de caráter febril que se espalha pelo mundo nos últimos anos. Os mosquitos fêmeas da espécie Aedes aegypti são os responsáveis por transmitir o patógeno conhecido como sendo responsável por uma extensa morbidade e mortalidade em cidades tropicais por todo o mundo. A dengue é causada por quatro sorotipos distintos DENV-1, DENV-2, DENV-3, DENV-4, sendo todos capazes de causar doença, e caracterizados como distintos entre si. Esses sorotipos determinam formas clínicas variadas como dengue febril (DV), ou nas formas graves da doença como a febre hemorrágica da dengue (DHF). O modelo matemático proposto neste trabalho considera lactentes nascidos de mãe imune ao vírus da dengue, ou seja, mãe que possui imunidade para dois ou mais sorotipos do DENV. A modelagem matemática é descrita por um sistema de equações diferenciais ordinárias não-lineares. O modelo descreve a quantidade de anticorpos do lactente transferidos pela mãe imune, a interação entre os monócitos infectados e não infectados e o vírus da dengue. O objetivo deste trabalho é investigar a ocorrência da dengue hemorrágica em lactentes com infecção primária. Para isso, obtemos o número reprodutivo básico, analisamos a positividade, a estabilidade local e global do modelo proposto. / Mestre

This work was supported by Cienciativa of CONCYTEC Peru, under contract number 164-2016-FONDECYT, and the Programa Nacional de Innovación para la Competitividad y Productividad (Innóvate Perú), under contract number 116-PNICP-PIAP-2015. / Background: Huánuco is a central eastern region of Peru whose geography includes high forest and low jungle, as well as a mountain range that constitutes the inter-Andean valleys. It is considered a region endemic for dengue due to the many favorable conditions that facilitate transmission of the virus. Methods: A total of 268 serum samples from patients in Huánuco, Peru with an acute febrile illness were assessed for the presence of dengue virus (DENV) via RT-PCR and NS1, IgM, and IgG ELISA during December 2015 and March 2016. Results: DENV was detected in 25% of samples via RT-PCR, 19% of samples by NS1 antigen ELISA, and 10.5% of samples by IgM ELISA. DENV IgG was detected in 15.7% of samples by ELISA. The most frequent symptoms associated with fever across all groups were headache, myalgia, and arthralgia, with no significant difference between the four test methods Conclusions: In this study, DENV was identified in up to 25% of the samples using the standard laboratory method. In addition, a correlation was established between the frequency of positive results and the serological tests that determine NS1, IgM, and IgG. There is an increasing need for point-of-care tests to strengthen epidemiological surveillance in Peru. / Revisión por pares / Revisión por pares

Orientador: Liciana Vaz de Arruda Silveira / Resumo: Introdução: As arboviroses geram grandes preocupações em saúde pública globalmente, devido sua ampla distribuição e disseminação. Neste cenário, dengue tem maior importância epidemiológica, vista que é uma doença grave e pode ocasionar o óbito rapidamente, além de estar associada fortemente com variáveis climáticas. Objetivos: Verificar associação do perfil epidemiológico da dengue com variáveis climáticas no município de Bauru. Método: Pesquisa ecológica, analítica com estudo de tendências ou séries temporais, a partir de dados retrospectivos dos casos de Dengue notificados no Município de Bauru – SP, entre 01/01/2000 à 31/12/2017. Utilizou-se o Software STATA 14 for Windows onde foi ajustado um modelo de séries temporais, tipo auto-regressivo (AR), modelo auto-regressivo integrado de média móvel (ARIMA) e modelo auto-regressivo integrado de média móvel com sazonalidade (SARIMA), sem transformação. Resultados: Foram confirmados 24.883 casos de dengue entre 2000 e 2017. Predominou casos em pessoas brancas, na faixa etária entre 20 e 59 anos, sexo feminino. Maior incidência dos casos ocorreu no outono. A velocidade média do vento em 55 Km/h (DP ± 18 km/hora), protege a cidade, reduzindo a incidência de dengue em 10%. A associação entre o aumento da chuva e a temperatura mínima, proporciona o aumento da umidade do ar na cidade e consequente proliferação de mosquitos, implicando assim no número de casos da doença. Conclusões: O índice pluviométrico e a temperatura influenciam d... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Arboviruses raise major public health concerns globally because of their distribution and dissemination. In this context, dengue has greater epidemiological importance, since it is a serious disease and can cause death soon, in addition to it is highly associated to weather variables. Objectives: To verify the association of the epidemiological profile of dengue with weather variables in the city of Bauru. Method: Ecological, analytical research with the study of trends or time series, based on retrospective data of Dengue cases reported in the city of Bauru - SP, between 01/01/2000 to 12/31/2017. The software STATA 14 for Windows, was used to fit an autoregressive (AR) time series model, an autoregressive integrated model of moving average (ARIMA) and a seasonal autoregressive integrated model of moving average (SARIMA) without transformation. Results: 24,883 cases of dengue were confirmed between 2000 and 2017. Predominant cases were white women, aged between 20 and 59 years. The highest incidence occurred in the autumn.The average wind speed at 55 km / h (DP ± 18 km / h), protects the city, reducing the incidence of dengue in 10%. The association between increased rainfall and minimum temperature provides increased humidity in the city and consequent mosquitoes proliferation, thus implying the number of cases of the disease. Conclusions: The rainfall index and temperature directly influence the incidence of the disease, while the wind speed causes a protectiv... (Complete abstract click electronic access below) / Mestre

Weltweit leben ca. 2,5 Mrd. Menschen im Dengue Virus Verbreitungsgebiet. Dengue Virus Infektionen führen zum Dengue Fieber und können bei Re-Infektionen mit anderen Serotypen das sog. Dengue Schocksyndrom mit einer Letalität von 10% verursachen. Momentan stehen jedoch weder Impfstoffe noch antivirale Substanzen zur Verfügung. In der vorliegenden Arbeit sollten DENV2-Proteaseinhibitoren entwickelt werden. Dazu wurde ein in vitro DENV Proteasetest etabliert, für den die DENV Protease in Bakterien exprimiert und anschließend gereinigt wurde. Mit diesem System wurden 144 Verbindungen getestet und Diaryl-Thioether, Thiazole und Zimtsäurederivate als Dengue PIs charakterisiert. Ein Diarythioether (FM 47) wurde an die Proteasestruktur modelliert und nach den Strukturdaten zielgerichtet derivatisiert. Diese Derivate ihibierten die Protease im mikromolaren Bereich und wurden anschließend in einer Zellkultur getestet. Drei Substanzen - HWu 11, HWu 51, HWu 62 - zeigten gute bis sehr gute Hemmung in vivo bei 2,5 μM. Die Charakterisierung der Inhibitoren zeigte eine nicht-kompetitive Hemmung. Die gefundenen Substanzen bilden eine gute Grundlage für die weitere Inhibitorforschung. / About 2,5 billion people live in dengue virus endemic area. There is neither a established medical treatment or vaccine for dengue virus infection. The Dengue virus protease represents a prime target for rational drug design. Here, I report the development of a fluorometric dengue virus protease test and the screening of a library of potential dengue virus protease inhibitors, which resulted in the identification of several substances inhibiting the dengue protease with IC50 values in the low micromolar range. Among these, three diaryl thioethers were shown to be potent non-competitive inhibitors, which blocked DENV replication in cell culture in the submicromolar range

Dengue fever is an arthropod-borne transmit disease, caused by dengue virus.The principal vectors are Aedes aegypti and Aedes albopictus. Induce Dengue fever (DF) and a more severe form of dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS). Dengue virus is the most prevalent arbovirus in tropical and subtropical regions. There is no specific drug and vaccine available for treatment and prevention. Therefore, DF is an important disease among transmit diseases in humans. For the effective control and prevention of DF transmission, rapid quantitative molecular biological methods are very important for the diagnosis of dengue fever. At present, there are many methods to isolate the RNA of Dengue virus; however, the new developed magnetic method has not been used for the Dengue virus isolation yet. At first, we evaluated various methods for Dengue virus isolation. The result indicate that the best method of RNA extraction for dengue virus is the QIAamp® Viral RNA kit manual extraction. There are no apparent differences of the effect for Dengue virus RNA isolation between filting film and magnetic bead method. Furthermore, DHF caused by Dengue virus is a very serious disease and the pathologic mechanism of DHF has not been elucidated completely. Both clinical and experimental trials have confirmed that the liver cell is one of the target infected by Dengue virus. And, the mechanism of Dengue virus-induced liver cell apoptosis remains poorly understood.Furthermore, there are free radical and cytokines production in patient¡As serum in the acute phase of DF. Therefore, the role of antioxidant and p21 in the mechanisms should be elucidcited. Our preliminary data show that p21 mRNA expression increase in HepG2 after Dengue virus infection. NAC, GSH, and DPI all can attenuate Dengue-induced cell apoptosis. Howerer, the relationship between p21 expression and liver cell apoptosis should be further clarified in the near future.

Thesis (Ph. D.)--Case Western Reserve University, 2008. / [School of Medicine] Department of Pathology. Includes bibliographical references.

Thesis (Ph.D. (Microbiology))--Mahidol University, 1973.

Thesis (M.Sc. (Public Health))--Mahidol University, 1979.

Doutor -- Universidade Federal da Bahia, Salvador, 2000.

La investigación tiene como objetivo identificar los factores de riesgo intrínsecos y extrínsecos que predisponen a los pobladores del Asentamiento Humano San Francisco a contraer Dengue. El Asentamiento Humano San Francisco pertenece a la jurisdicción sanitaria del Centro de Salud Santiago Apóstol, de la Red de Salud VI Tupac Amaru de la Dirección de Salud Lima Ciudad. El estudio es aplicativo de enfoque cuantitativo, tipo descriptivo, de corte transversal; la población estuvo compuesta por los pobladores del Asentamiento Humano San Francisco, contando con un total de 121 personas. Los instrumentos que se aplicaron fueron el formulario y la lista de chequeo. En relación a los factores de riesgo, se obtuvo que las características físicas de la comunidad y de las viviendas, el inadecuado abastecimiento de agua intradomiciliaria, así como el desconocimiento de la mayoría de los pobladores sobre aspectos importantes de la enfermedad como el hábitat, los criaderos del mosquito y alguna de sus medidas preventivas; y las inadecuadas prácticas de éstas, predispone al poblador a contraer dengue con el consecuente rebrote de la enfermedad. La presencia de factores extrínsecos e intrínsecos que limitan el control vectorial favorece la presencia del mosquito y su permanencia en la comunidad. / The investigation has as aim identify the intrinsic and extrinsic factors of risk that predispose to the settlers of the Human Accession San Francisco to contract Fastidiousness. The Human Accession San Francisco Apostle belongs(concerns) to the sanitary jurisdiction of the Center of Health Santiago, of the Network(Net) of Health the VIth Tupac Amaru of the Direction of Health Lima City The study is aplicativo of quantitative approach, descriptive type, of transverse court; the population was composed by the settlers of the Human Accession San Francisco, possessing (relying on) a whole of 121 persons. The instruments that were applied were the form and the list of checkup. In relation to the factors of risk, there was obtained that the physical characteristics of the community and of the housings, the inadequate supply of water intradomiciliaria, as well as the ignorance of the majority of the settlers on important aspects of the disease like the habitat, the breeding-places of the mosquito and someone of his(her,your) preventive measures; and the inadequate practices of these, it(he,she) predisposes the settler to contract fastidiousness with the consistent new shoot of the disease. The presence of extrinsic and intrinsic factors that limit the vectorial control favors the presence of the mosquito and his permanency in the community.