The four serotypes of dengue virus (DENV 1-4) have a significant and growing impact on global health. Dengue disease encompasses a wide range of clinical symptoms, usually presenting as an uncomplicated febrile illness lasting 5-7 days; however, a small percentage of infections are associated with plasma leakage and bleeding tendency (called dengue hemorrhagic fever, DHF), which can result in shock. Epidemiological studies indicate that severe dengue disease most often occurs during secondary heterotypic DENV infection. Additionally, plasma leakage (the hallmark of DHF) coincides with defervescence and viral clearance, suggesting that severe disease arises from the immune response to infection rather than a direct effect of the virus. A number of studies have found increased levels of markers of immune cell activation in patients with DHF compared to patients with the less severe form of disease (DF). These markers include IFNγ, TNFα, soluble CD8, soluble IL-2 receptor, soluble TNF receptor, and CD69, which support a role for T cells in mediating immunopathology. Because of the high homology of DENV 1-4, some degree of serotype-cross-reactivity is seen for most T cell epitopes. A high percentage of DENV-specific T cells recognize multiple DENV serotypes, as demonstrated by peptide-MHC (pMHC) tetramer binding and in vitro functional assays performed on PBMC from subjects vaccinated with an experimental DENV vaccine or naturally-infected subjects with secondary (>1) DENV infection. This thesis sought to address several gaps in the literature, specifically whether T cell responses differ in primary versus secondary (natural) infection. We studied the frequency, phenotype, and function of DENV-specific T cells. We demonstrated substantial serotype-cross-reactivity of antigen-specific T cells generated in response to naturally-acquired primary as well as secondary DENV infection. The frequency of A11-NS3133 epitope-specific T cells during acute infection did not correlate with disease severity. However, the peak frequency occurred earlier in primary infection while the frequency of CD45RA+ T cells declined quicker in secondary infection, suggesting the expansion of DENV-specific memory T cells. DENV-immune T cells exhibited different functional capabilities that were dependent on the particular serotype of infection. Specifically, DENV-1 or -3 stimulation of A11-NS3133 epitope-specific T cell lines resulted in robust function that included IFNγ production, whereas DENV-2 stimulation resulted in limited function that often included MIP-1β but not IFNγ production. These data support a role for T cells in DENV infection and offer new insights into their potential contribution to dengue pathology.

The transmission of many infectious diseases is affected by climate variations, particularly for diseases spread by arthropod vectors such as malaria and dengue. Previous epidemiological studies have demonstrated statistically significant associations between infectious disease incidence and climate variations. Such research has highlighted the potential for developing climate-based epidemic early warning systems. To establish how much variation in disease risk can be attributed to climatic conditions, non-climatic confounding factors should also be considered in the model parameterisation to avoid reporting misleading climate-disease associations. This issue is sometimes overlooked in climate related disease studies. Due to the lack of spatial resolution and/or the capability to predict future disease risk (e.g. several months ahead), some previous models are of limited value for public health decision making. This thesis proposes a framework to model spatio-temporal variation in disease risk using both climate and non-climate information. The framework is developed in the context of dengue fever in Brazil. Dengue is currently one of the most important emerging tropical diseases and dengue epidemics impact heavily on Brazilian public health services. A negative binomial generalised linear mixed model (GLMM) is adopted which makes allowances for unobserved confounding factors by including spatially structured and unstructured random effects. The model successfully accounts for the large amount of overdispersion found in disease counts. The parameters in this spatio-temporal Bayesian hierarchical model are estimated using Markov Chain Monte Carlo (MCMC). This allows posterior predictive distributions for disease risk to be derived for each spatial location and time period (month/season). Given decision and epidemic thresholds, probabilistic forecasts can be issued, which are useful for developing epidemic early warning systems. The potential to provide useful early warnings of future increased and geographically specific dengue risk is investigated. The predictive validity of the model is evaluated by fitting the GLMM to data from 2001-2007 and comparing probabilistic predictions to the most recent out-of-sample data in 2008-2009. For a probability decision threshold of 30% and the pre-defined epidemic threshold of 300 cases per 100,000 inhabitants, successful epidemic alerts would have been issued for 94% of the 54 microregions that experienced high dengue incidence rates in South East Brazil, during February - April 2008.

Bacillus thuringiensis (B. thuringiensis) es una bacteria Gram positiva que forma un cristal paraesporal con actividad insecticida contra insectos de diferentesórdenes. Los bioinsecticidas fabricados con las esporas y cristales de B. thuringiensis son una alternativa frente a los pesticidas químicos sintéticos para el control de mosquitos que son vectores de enfermedades metaxénicas, como por ejemplo, malaria y dengue. Se caracterizaron 53 cepas nativas de B. thuringiensis, procedentes de suelos peruanos, de los departamentos de Junín, Lima (Huaral), Ica, Cuzco, Tacna, Arequipa, Chiclayo y Cajamarca; dos de ellas codificadas como Ica10 y Caj1 por su procedencia, presentaron actividad entomocida contra larvas de Aedes aegypti. Se observan cepas que presentan bandas (toxinas) con pesos moleculares en el órden de los 36 kDa y mayores a 116 kDa; otras cepas presentan bandas a 97 y 75 kDa, como las de, Cajamarca, Arequipa y Chiclayo, que serían entomocidas para dípteros, algunas cepas presentaron bandas de 130 kDa que corresponderían al gen cry1, tóxico para lepidópteros. El gen cry2 fue el más frecuente (92%), seguido de cry1 (45%) y cry4 (42%), lo cual significaría que las cepas tendrían principalmente, actividad entomocida contra dípteros. El secuenciamiento confirmó la presencia de genes cry en 62 de 67 cepas analizadas. Se determinó la cepa B. thuringiensis Cuz5 como variedad cry2Ab. El método del PCR fue efectivo para caracterizar rápidamente las cepas en base al contenido de genes que amplifican con secuencias de oligonucleótidos conocidos. El método REP-PCR mostró patrones de bandas diferentes en las cepas aisladas que podría significar variabilidad genética entre las cepas estudiadas, el dendograma permitió agruparlas en tres clusters y subclusters que podrían deberse a las variedades del gen cry. Palabras claves: Bacillus thuringiensis, cristal paraesporal, entomocida, gen cry, control de plagas. / *** Bacillus thuringiensis (B. thuringiensis), is a Gram-positive bacterium, that forms a parasporal crystals with insecticidal activity against different insect orders. Bioinsecticides manufactured with B. thuringiensis spores and crystals are a useful alternative to synthetic chemical pesticide in agriculture and for mosquito control. B. thuringiensis has also been used successfully to suppress the population levels of medically important dipteran pests. Examples include the mosquito vectors of malaria, virus diseases including dengue. It was characterized 53 strains peruanas of Bacillus thuringiensis with entomocidal properties from soil Peruvian’s farms of the deparments of Junín, Lima (Huaral), Ica, Cuzco, Tacna, Arequipa, Chiclayo y Cajamarca, two: Ica10 y Caj1 with activity against Aedes aegypti. There are strains with toxins betwen 36 y 116kDa. Strains with bands to 97 and 70KDa, as those of Arequipa, Cajamarca and Chiclayo, which would be entomocidal with band of 130 kDa that correspond to cry gen, toxic to Lepidoptera and Diptera. Cry2 gene was the most abundant (92%), followed by cry1 (45%) and cry 4 (42%), which means that the strains would have activity against Dipterans. The sequencing confirms the content of cry genes in most of the analyzed strains. The strain Cuz5 as variety cries 2Ab. The PCR method is effective to rapidly characterize the strains based on the content of genes that amplify with known sequences of oligonucleótidos and REP-PCR shows patterns of different bands in the isolated strains that could mean genetic variability among the studied strains, the dendogram allows to group them into three clusters and subclusters, that might be due to the varieties of the gene cry. Key words: Bacillus thuringiensis, parasporal crystal, entomocida, cry gene, crop pestes.

Le genre Flavivirus regroupe plus de 70 espèces dont plusieurs sont des pathogènes humains de première importance responsables dans les formes les plus graves de manifestations hémorragiques ou d’encéphalites parfois mortelles. L’absence de traitements antiviraux spécifiques et l’augmentation croissante des flaviviroses, surtout dans les régions tropicales, justifient un effort de recherche et développement pour lutter contre ces maladies.Ce travail a abordé deux aspects de l’infection à flavivirus : un aspect épidémiologique et un aspect plus fondamental sur l’immunité innée et les contremesures flavivirales. L’étude épidémiologique a été menée en collaboration avec le CENETROP (Centro national de enfermedades tropicales) de Bolivie grâce à la contribution de l’IRD. De par l’analyse des différentes souches circulantes dans ce pays, elle a permis une meilleure compréhension de l’épidémiologie de la dengue et de la fièvre jaune et nous a fait prendre conscience de la variabilité génétique de ces virus. Devant le peu de données répertoriées en Bolivie, nos travaux serviront de référence pour comprendre les épidémies futures, peut-être améliorer les techniques de diagnostic et permettre le développement de stratégies de prévention adaptées et l’amélioration des politiques de lutte contre la fièvre jaune en Amérique du Sud. La cohabitation entre le virus et l’hôte immunocompétent est le résultat d’un équilibre subtil entre le taux de réplication virale et la clairance du système immunitaire pour garantir la survie des deux espèces. Chacun a évolué en développant des mécanismes de défenses contre l’autre. Notre second travail visait à analyser l’influence de la protéine flavivirale non structurale NS1 sur la réponse interféron de l’hôte. L’identification de stratégies virales d’évasion face à l’immunité de l’hôte et l’analyse de leurs fonctions dans l’infection virale permettrait de mieux comprendre le système immunitaire ainsi que l’interaction virus–hôte. Ceci aiderait au développement de nouvelles stratégies antivirales afin de traiter les pathologies associées à ces arbovirus. / The Flavivirus genus consists of sevevral human pathogens responsible for hemorragic syndrome or encephalitis. The absence of specific antiviral treatment and an increase in Flavivirus incidence has led to a greater research effort in fighting these diseases. The study takes an epidemiological and a fundamental approach in its analysis of the innate immune response to flavivirus infection as well as flaviviral adaptation to evade this response. The analysis of circulating strains in Bolivia has led to a better understanding of dengue and yellow fever and also an awareness of their genetic variability. Given the limited information available in Bolivia, our studies could be used as a reference to understand future epidemics, improve diagnostic methods and allow the development of prevention strategies to fight against yellow fever in south Africa. The relationship between virus and host results from a subtle balance between viral replication and immunity clearance allowing the survival of both species. Each one as developed defence mechanisms against the other. We also examined the role of the non structural protein NS1 in the interferon respons to Flaviviral infection. Knowledge on viral escape strategies from host immunity could help to develop antiviral treatment for these arbovirus diseases

Objetivos. Evaluar los conocimientos, actitudes y prácticas sobre dengue, medidas de prevención y control, e identificar los factores asociados a su desconocimiento, en alumnos de una institución educativa estatal. Diseño. Estudio observacional transversal. Lugar. Institución educativa estatal en Chorrillos, Lima, Perú. Participantes. Alumnos de educación primaria. Métodos. En el año 2013, se encuestaron 142 alumnos del quinto y sexto grado de educación primaria y se exploró la percepción en 12 brigadieres en base a la técnica proyectiva. Principales medidas de resultados. Conocimientos, actitudes y prácticas sobre dengue. Resultados. El 53,5 % (76) era varón y el promedio de edad fue 11,2 con ± 1,05 años. El 33,1 % (47; IC95% 25,4 a 41,4) de los estudiantes tenía un conocimiento básico de dengue y 53,5% (76) identificaron la forma de transmisión vectorial del dengue. El 29,6 % (42; IC95% 22,2 a 37,8) de los escolares reconocieron las larvas y 54,2% (77) la forma adulta del vector. El 5,6% (8) y 2,1% (3) de los encuestados identificaron el larvicida y el cambio de arena húmeda de los floreros como medidas de prevención de la infestación domiciliaria. El 75,4% (75; IC95% 67,4 a 82,2) de los niños aceptarían participar en la búsqueda del vector, con diferencias significativas entre los niños y las niñas (p=0,049238). El no haber recibido información previa se asoció a no tener conocimiento básico de dengue (OR=3,7; IC95% 1,7 a 8,3; p= 0,0004676). Conclusiones. Los conocimientos de los estudiantes sobre los signos y síntomas y la forma de transmisión del dengue, las características del vector y las medidas de prevención del dengue fueron bajos y el no recibir información se asoció al desconocimiento del dengue. / Objectives. To assess the knowledge, attitudes and practices on dengue fever, measures for prevention and control, and to identify factors related to unawareness in public elementary school students in the district of Chorrillos, Lima, Peru. Design. Cross sectional observational study. Setting. State elementary institution in Chorrillos district, Lima, Peru. Participants. Students of elementary school. Methods. In the year 2013, 142 students from fifth and sixth grade answered a survey questionnaire. We explored the perception among 12 school brigadiers using the projective technique. Main outcome measures. Knowledge, attitudes and practices about dengue. Results. In the study, 53.5% students were boys (76), mean age 11.2 ± 1.05 years old; 33.1% (47; CI95% 25.4-41.4) had basic knowledge about dengue; 53.5% (76) were able to identify dengue virus’ mechanism of vertical transmission; 29.6% of students (42; CI95% 22.2-37.8) were able to identify the larvae and 54.2% (77) identified the adult flying mosquito. Only 5.6% (8) and 2.1% (3) knew respectively of larvicides and using wet sand in flower vases as measures of control at home; 75.4% of the boys (75; CI95% 67.4-82.2) were willing to participate in active control of the mosquito vector, with statistical difference between boys and girls (p = 0.049238). Not having previous information led to not having basic knowledge about dengue (OR = 3.7; CI95% 1.7–8.3) (p = 0.0004676) Conclusion. The knowledge among students about clinical features, mode of transmission, vector and measures of prevention and control of the dengue virus were low because they had not received appropriate information.

This literature review will discuss Zika virus and the salient research on antibody dependent enhancement and how this mechanism may lead to congenital defects. Specific objectives include: the mechanism of antibody dependent enhancement, Zika and dengue virus pathogenesis, placenta pathophysiology, and how changes in viral virulence may play a role the pathogenesis of neurologic congenital defects seen in infants infected with Zika virus in utero. While some cohort studies have examined the relationship between prior dengue immunity, Zika virus infection in pregnancy, and effects on neonatal outcomes further prospective studies using large cohorts and more detailed lab testing and imaging is essential to better understand this relationship. A proposed study enrolling a large cohort of women in the 6th- 8th week of pregnancy from Northeastern Brazil will seek to further describe what additional risk dengue immunity may pose in the context of Zika virus. This risk is essential to understand, as Zika and Dengue viruses co-circulate in many regions of the world. Furthermore, participants in the proposed study will undergo bi-weekly screening for Zika virus through laboratory and ultrasound testing until their delivery. Infants will then have full neurologic testing and MRI scanning for the following year after birth to characterize any congenital defects. Neonates born to mothers with prior dengue immunity who contract Zika virus during pregnancy will be compared to neonates not exposed to Zika virus in utero. This experiment will illuminate the associated risk and evidence of ADE occurring with prior dengue immunity and Zika virus infection during pregnancy. Results from this study will not only help define risks of congenital defects with Zika virus, it will inform vaccine research and elucidate challenges in the administration of the current tetravalent dengue vaccine.

Submitted by PPG Biotecnologia Farmac?utica (mpbf@pucrs.br) on 2017-12-20T19:17:22Z No. of bitstreams: 1 ANA_SOFIA_OLIVEIRA-DIS.pdf: 959707 bytes, checksum: 29ee77d841ca692f44c6db51a03d5a23 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-12-26T17:46:20Z (GMT) No. of bitstreams: 1 ANA_SOFIA_OLIVEIRA-DIS.pdf: 959707 bytes, checksum: 29ee77d841ca692f44c6db51a03d5a23 (MD5) / Made available in DSpace on 2017-12-26T17:48:46Z (GMT). No. of bitstreams: 1 ANA_SOFIA_OLIVEIRA-DIS.pdf: 959707 bytes, checksum: 29ee77d841ca692f44c6db51a03d5a23 (MD5) Previous issue date: 2017-06-20 / Dengue fever is an arboviral infection highly common in Brazil, and it corresponds to a major public health problem. Annually, its incidence overcomes 50,000,000, from which about 25,000 are associated to death cases. Due to this high incidence and number of death, it is of great urgency to identify this disease while in an early state. That way, would be possible to avoid any progression of the disease to more severe cases. A major problem related to dengue is that the virus is represented by four subtypes, which are phylogenetically distinct (DENV1, DENV2, DENV3 and DENV4). This means that, although the manifestations and the forms of dissemination are the same, an infection caused by one of the serotypes will not protect against the others. In fact, an infection caused by one of the four serotypes may intensify even more the disease caused by a secondary infection by the three others. One hypothesis that could explain this relationship between heterotypic infections and severe cases of the disease is the ADE hypothesis (antibody-dependent enhancement), which suggests that a secondary infection would cause a cross-reaction between antigen and antibody, preventing the virus of being inactivated. As a consequence, it would result in an increase of the production of inflammatory mediators and vascular permeability that would intensify the disease. Therefore, it?s very important to identify the disease while it is still in an initial stage. However, this early identification is hard and its diagnosis is still limited. Thus, a serological marker would be highly valuable. Recently, serological biomarkers for early diagnosis have become a topic of great interest. These biomarkers have advantages of not being invasive to the patient and inexpensive to produce and analyze. Thus, in this project, we introduce a new technology for the search of such markers, the peptoids. Peptoids are synthetic oligomers, composed of N-substituted glycine units, and can be used for several biological utilities that provide an alternative technology for the investigation and the elucidation of the immune response. Moreover, they have been used and reported as a potential candidate for the search of serological biomarkers due to their chemical stability in fluids where degradative enzymes can be found. In addition to that, the fact that there is no need for a prior knowledge about the target only make them even more attractive for such ?job?. In this project, a combinatorial library of about one million of peptoids was screened in sera from dengue positive patients, as well as negative patients. Hereby we report the potential of this synthetic molecules for the identification of antibodies with clinical relevance present in the patients' serum. The results here reported were generated by 3 consecutive screening steps, where 33 reactive peptoids were identified as potential biomarkers. Because of the impartiality of this technique, we believe that at least one of these 33 peptoids are extremely specific for the studied disease. Currently, they have been sent for the sequencing and re-synthesis step, so that new experiments can be done and the study can continue. We are very excited and we don?t expect nothing less than promising results in the field of diagnosis and dengue. / A dengue ? uma arbovirose de alta incid?ncia no Brasil, e corresponde a um grande problema de sa?de p?blica. Ela possui uma incid?ncia anual de mais de 50.000.000 e resulta num elevado n?mero de casos de ?bito, cerca de 25.000. Devido a isso, ? de grande urg?ncia que possamos identificar esta doen?a enquanto ela ainda se encontra em um estado inicial, para que, deste modo, possamos evitar a progress?o da doen?a para casos mais severos. Um grande problema relacionado a dengue ? que o v?rus ? representado por quatro subtipos, os quais s?o filogen?ticamente distintos (DENV1, DENV2, DENV3 e DENV4). Isso quer dizer que, por mais que as manifesta??es e formas de dissemina??o sejam iguais, a contamina??o por um dos sorotipos n?o ir? proteger contra as demais. Ao contr?rio do que muitos acreditam, a infec??o por um sorotipo pode at? assentuar uma infec??o secund?ria pelos demais. Uma hip?tese para explicar casos mais severos da doen?a devido a infec??es heterot?picas ? a hip?tese de ADE (antibody-dependent enhancement), a qual sugere que a rea??o cruzada resulta na falta da inativa??o viral, aumentando assim a produ??o de mediadores inflamat?rios e permeabilidade vascular devido a uma estimula??o da replica??o do v?rus. Devido a isso, ? de grande necessidade a identifica??o da doen?a antes das manifesta??es severas, e, porque essa identifica??o cl?nica, principalmente no est?gio inicial da doen?a, ? dif?cil, um marcardor sorol?gico seria muito valioso. Marcadores sorol?gicos para diagn?stico de doen?as v?m se tornando um t?pico de recente interesse. Esses biomarcadores t?m a vantagem de n?o serem invasivos para o paciente e baratos de produzir e analizar. Sendo assim, aqui, apresentamos uma nova tecnologia para a busca desses marcadores, os pept?ids. Pept?ids s?o olig?meros sint?ticos, compostos por unidades de glicina N-substitu?da e possuem uma variada utilidade biol?gica que proporcionam uma tecnologia alternativa para a investiga??o e elucida??o da resposta imune. O mesmo, v?m se destacando para busca de biomarcadores sorol?gicos devido a sua estabilidade qu?mica em flu?dos onde enzimas degradativas podem estar presentes e devido a resultados promissores sem a necessidade de um conhecimento pr?vio sobre o ant?geno natural e o seu anticorpo correspondente. Neste projeto, foi realizado a triagem de uma biblioteca combinatorial com cerca de um milh?o de pept?ids, os quais passaram por etapas de triagens em soros de pacientes positivos para dengue, bem como para pacientes negativos. Aqui provamos o potencial dessas mol?culas sint?ticas na identifica??o de anticorpos com relev?ncia cl?nica presente no soro dos pacientes. Os resultados obtidos foram gerados atrav?s de 3 etapas de triagem consecutivas, onde 33 pept?ids reativos foram identificados. Devido a imparcialidade desta t?cnica, acreditamos que pelo menos um desses 33 pept?ids seja extremamente espec?fico para a doen?a estudada. Os mesmos foram enviados para sequenciamento e re-s?ntese para que novos experimentos sejam feitos e para que os estudos continuem. Espera-se resultados muito promissores na ?rea de diagn?stico para dengue.

A dengue é uma infecção viral sistêmica, autolimitada, transmitida para os humanos através da picada de mosquitos fêmeas infectadas do gênero Aedes sp. Trata-se de uma doença com grandes impactos na economia e na saúde pública, e estima-se que entre 50 a 100 milhões novas infecções ocorram anualmente em mais de 100 países. A dengue é causada pelo Dengue virus (DENV), um vírus pertencente à família Flaviviridae, com genoma composto de uma única molécula de RNA, fita simples com polaridade positiva. A infecção pelo DENV pode ser assintomática ou apresentar diferentes manifestações clínicas, como febre do dengue (FD), febre hemorrágica do dengue (FHD) e Síndrome do Choque do dengue (SCD). Dados da literatura indicam que algumas infecções virais podem causar alterações epigenéticas em seus hospedeiros, principalmente a metilação do DNA. Assim, o propósito deste trabalho foi investigar a influência da infecção pelo DENV no perfil global de metilação dos pacientes, através da técnica de MethELISA, e analisar o padrão de metilação no promotor dos genes fator de necrose tumoral alfa (TNF-α) e interferon gama (IFN-γ). Os resultados obtidos indicam uma tendência na diminuição do percentual relativo de metilação após a infecção pelo DENV, sugerindo uma influência da infecção viral nos mecanismos epigenéticos do hospedeiro. Observou-se também uma maior taxa de desmetilação do promotor do TNF-α dos pacientes infectados em relação ao grupo controle. Em relação ao IFN-γ, não foi observada diferença no padrão de metilação do gene entre os dois grupos analisados. A meta-análise de microarranjos de DNA obtidos de pacientes infectados pelo DENV indica um aumento na expressão dos genes da Timina DNA Glicosilase (TDG) e das DNA Metiltransferases 1 e 3 (DNMT1 e DNMT3) nos pacientes infectados. Estes dados sugerem que o DENV é capaz de interferir com os mecanismos epigenéticos do hospedeiro. / Dengue fever is a systemic viral infection, self-limited, transmitted to humans through the bite of infected female mosquito from Aedes genus. It is a disease with major impacts on the economy and public health, and it is estimated that between 50 to 100 million new dengue infections occur annually in more than 100 countries. Dengue fever is caused by Dengue virus (DENV), a single strand positive sense RNA virus belonging to the Flaviviridae family. The DENV infection may be asymptomatic or present different clinical manifestations, such as dengue fever (DF), hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Published data indicate that some viral infections can cause epigenetic changes in their hosts, especially in the DNA methylation. Thus, the aim of this study was to investigate the influence of DENV infection in global methylation profile of DENV infected patients by MethELISA technique, and analyze the pattern of methylation in the promoter of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) genes. The results obtained show a decrease the relative methylation percentage after DENV infection, suggesting an influence of viral infection in the epigenetic mechanisms of the host. There was also detected a higher rate of demethylation of TNF-α promoter in infected patients if compared to the control group. No difference was found in the methylation frequency between the two analyzed groups regarding the IFN-γ promoter. Meta-analysis of DNA microarray indicates that patients infected with DENV shows an increase in the expression of Thymine DNA Glycosylase (TDG) and DNA methyltransferases 1 and 3 (DNMT1 and DNMT3) genes, all involved in epigenetic regulation. So, these data indicated that DENV is able to interfere with the host epigenetic mechanisms. / Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG

Submitted by Dominick Jesus (dominickdejesus@hotmail.com) on 2015-11-06T18:12:42Z No. of bitstreams: 2 Dissertação_Joelma Soares da Silva.pdf: 3973131 bytes, checksum: e2d308bc76b0d2e137227d73bfb0719f (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-11-06T18:12:43Z (GMT). No. of bitstreams: 2 Dissertação_Joelma Soares da Silva.pdf: 3973131 bytes, checksum: e2d308bc76b0d2e137227d73bfb0719f (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2011-02-23 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / In Amazonas state have been isolated 57 strains of Bacillus thuringiensis, these five have shown toxicity to Aedes aegypty. Isolates did not show the genes of Cry toxins 4AA; 4ba; 10Aa; 11Aa and 11Ba, except BtAM- 27 lineage that showed all genes analyzed. Data from the larvicidal activity of Amazonian isolates were not superior to those obtained with the standard strain Bti IPS-82, entrtanto BtAM 27 showed similar toxicity to this, the isolated enters obtained in this work, IBt-07 and IBt-28 were the most toxic . / No estado do Amazonas foram isolados 57 estirpes de Bacillus Thuringiensis, destas, cinco mostraram toxicidade às larvas de Aedes aegypty. Os isolados não apresentaram os genes das toxinas Cry 4Aa; 4Ba; 10Aa; 11Aa e 11Ba, com exceção da linhagem BtAM- 27 que apresentou todos os genes analisados. Os dados da atividade larvicida dos isolados do Amazonas não foram superiores aos obtidos com a estirpe padrão Bti IPS-82, entrtanto BtAM 27 mostrou toxicidade similar á esta, entra os isolados obtidos neste trabalho, IBt-07 e IBt-28 foram os mais tóxicos.

Tese (doutorado)—Universidade de Brasília, Instituto de Ciências Humanas, Departamento de Geografia, Programa de Pós-Graduação em Geografia, 2018. / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). / A dengue é uma doença vetorial bastante estudada em diversos campos como geografia e epidemiologia. Nos últimos anos a dengue avançou em vários países. Segundo o Ministério da Saúde (MS), no ano 2013 foram registrados, no Brasil, 1.452.673 casos, sendo considerada uma das maiores epidemias de dengue registrada no país; e a região centro-oeste a segunda maior em número de casos. O Distrito Federal, situado na região centro-oeste, teve um aumento significativo dos casos entre 2007 e 2014; em paralelo, a urbanização avançou sem planejamento urbano e infraestrutura adequada (COSTA,2011). Para Reis (2011) a forma da organização urbana pode favorecer a disseminação e proliferação da dengue, potencializando o contato entre o vetor, o vírus e o homem. Assim, esta tese tem por objetivo analisar a dinâmica espaço-temporal da dengue no Distrito Federal entre 2007 e 2014, a fim de verificar as relações entre seu padrão de ocorrência e os tipos de padrões urbanos encontrados no território. A metodologia consistiu em realizar a análise espaço-temporal da persistência e da intensidade da dengue, através da análise espacial, por meio de Sistemas de Informações Geográficas. Em seguida, procedeu-se classificação do uso do solo, análise da expansão urbana e cálculo das métricas de paisagem, por meio de técnicas sensoriamento. Por último, a partir das informações geradas nas etapas anteriores, foi realizado o mapeamento de síntese, quando foram analisadas as relações espaciais entre o padrão espaço-temporal da dengue e os padrões urbanos. Os resultados mostram que o comportamento espaço-temporal da dengue entre 2007 e 2014 se caracterizou por clusters de alta incidência e persistência em algumas regiões, as quais apresentaram padrões urbanos heterogêneos, caracterizado por trechos de áreas urbanas desagregadas e intercaladas por fragmentos de vegetação e com baixa cobertura de serviços de água, esgoto e lixo. Foi observado que tal padrão ocorre tanto em áreas de baixa renda, quanto de renda média-alta. Os resultados alcançados não permitem apontar, no momento, de que maneira estes tipos de padrões contribuem para as altas taxas de dengue em determinadas regiões do Distrito Federal, demandando a realização de estudos futuros. No entanto, eles contribuem para demonstrar como os padrões urbanos são importantes na análise da dengue e quanto podem contribuir para os programas locais de controle, apontando as áreas prioritárias para implementação de medidas de prevenção e controle da doença. / Dengue fever is a vector disease that has been extensively studied in several fields such as geography and epidemiology. In recent years, dengue fever has spread in several countries. According to the Brazilian Ministry of Health, in the year 2013 1.452.673 cases were registered in Brazil, being this one of the largest dengue epidemics in the country and the central-west region the second largest in number of cases. The Federal District, located in the central-west region, had a significant increase in cases between 2007 and 2014; in parallel, urbanization advanced without urban planning and adequate infrastructure (COSTA, 2011). For Reis (2011), the form of urban organization can favor the spread and proliferation of dengue, enhancing the contact between vector, virus and man. Thus, this thesis aims to analyze the spatial-temporal dynamics of dengue in the Federal District between 2007 and 2014, to verify the relationships between its pattern of occurrence and the types of urban patterns found in the territory. The methodology consisted in performing the spatiotemporal analysis of dengue persistence and intensity, through spatial analysis, through Geographic Information Systems. Then, classification of the land use, analysis of the urban expansion and the calculation of the landscape metrics, by means of sensing techniques. Finally, from the information generated in the previous steps, the mapping of synthesis was carried out, where the spatial relationships between the dengue space-time pattern and the urban patterns were analyzed. The results show that the spatial-temporal behavior of dengue between 2007 and 2014 was characterized by clusters of high incidence and persistence in some regions, which presented heterogeneous urban patterns, characterized by stretches of disaggregated urban areas and interspersed by fragments of vegetation and low coverage of water, sewage and garbage services. It was observed that this pattern occurs in both low-income and middle-high income areas. The results do not allow us to point out now, how these types of patterns contribute to the high rates of dengue in certain regions of the Federal District, demanding future studies. However, they contribute to demonstrate how urban patterns are important in the analysis of dengue and can contribute to local control programs, pointing out the priority areas for implementation of disease prevention and control measures. / La dengue est une maladie vectorielle largement étudiée dans plusieurs domaines tels que la géographie et l'épidémiologie. Ces dernières années, la dengue s'est répandue dans plusieurs pays. Selon le ministère brésilien de la Santé, dans l'année 2013 ont été enregistrés au Brésil 1.452.673 cas de dengue, étant une des épidémies enregistrées les plus importantes dans le pays et la région du centre-oueste est la deuxième plus grande en nombre de cas. Le District fédéral, situé dans la région centre-ouest, a connu une augmentation significative du nombre de cas entre 2007 et 2014; parallèlement, l'urbanisation augmenté sans planification urbaine et infrastructures adéquates (COSTA, 2011). Selon Reis (2011), la forme d'organisation urbaine peut favoriser la propagation et la prolifération de la dengue, renforçant le contact entre le vecteur, le virus et l'homme. Ainsi,l’objectif de cette thèse est d'analyser la dynamique spatiotemporelle de la dengue dans le District fédéral entre 2007 et 2014, afin de vérifier la relation entre leur modèle d'occurrence et les types de modèles urbains trouvés sur le territoire. La méthodologie a consisté à effectuer l’analyse spatio-temporelle de la persistance et de l’intensité de la dengue, par l’analyse spatiale, à travers de systèmes d’information géographique. Ensuite, classification de l’utilisation des sols, analyse de l’expansion urbaine et calcul des métriques du paysage, au moyen de techniques télédétection. Enfin, à partir de l'information générée dans les étapes précédentes, la synthèse de cartographie a été effectuée, oú les relations spatiales entre la dengue et les modèles urbains ont été analysés. Les résultats montrent que le comportement spatio-temporel de la dengue entre 2007 et 2014, a été caractérisée par élevée l'incidence et persistance de la dengue, dans certaines régions, qui ont montré des modèles urbains hétérogènes, caractérisé par des portions de zones urbaines fragmentées et des fragments de végétation, avec couverture faible de l'eau, des égouts et des services d'ordures. Il a été observé que cette tendance se produit à la fois, dans les zones à revenu faible et à revenu intermédiaire-élevé. Les résultats obtenus ne permettent pas de pointer dans le moment, comment ces types de normes contribuent aux taux élevées de dengue dans certaines régions du District fédéral, exigeant la réalisation d'études futures. Cependant, ils contribuent à démontrer comment les formes urbaines sont importantes dans l'analyse de la dengue et comment elles peuvent contribuer aux programmes de contrôle locaux, en soulignant les domaines prioritaires pour la mise en oeuvre de mesures visant à prévenir et à lutter contre la maladie.