Submitted by LUCIA HELENA DE ALMEIDA TESTA null (luciatesta2011@gmail.com) on 2016-03-07T22:13:50Z No. of bitstreams: 1 Infecção viral respiratória comunitária e hospitalar em pacientes submetidos a transplante de células tronco hematopoiéticas.pdf: 1140941 bytes, checksum: 93b0313920244f35bff64660455608c7 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-03-09T14:00:14Z (GMT) No. of bitstreams: 1 testa_lha_me_bot.pdf: 1140941 bytes, checksum: 93b0313920244f35bff64660455608c7 (MD5) / Made available in DSpace on 2016-03-09T14:00:14Z (GMT). No. of bitstreams: 1 testa_lha_me_bot.pdf: 1140941 bytes, checksum: 93b0313920244f35bff64660455608c7 (MD5) Previous issue date: 2016-02-03 / As infecções por vírus respiratórios (VR) são causas importantes de mortalidade em pacientes submetidos a Transplante de Células-Tronco Hematopoiéticas (TCTH) especialmente no período anterior à pega do enxerto. Estas infecções também podem ser adquiridas dentro dos hospitais, possivelmente transmitida por contato com profissionais de saúde ou cuidadores infectados, ou com objetos ou superfícies contaminadas. Portanto, é importante caracterizar o tipo de transmissão para que medidas rigorosas de controle possam ser implantadas. Objetivos: Analisar os casos de infecção por vírus respiratórios (VR) nos pacientes submetidos a TCTH entre agosto de 2010 a dezembro de 2013 e caracterizar os tipos de transmissão durante esse período. Método: O presente estudo foi realizado no Hospital Amaral Carvalho de Jahu nas unidades de internação e ambulatório de TCTH e na unidade de hematologia, incluindo pacientes com diagnóstico comprovado de VR por imunofluorescência ou PCR multiplex em amostras de lavado nasal. A transmissão foi definida como hospitalar na ausência de sintomas respiratórios à admissão e diagnóstico de VR comprovado laboratorialmente após cinco dias da internação ou até cinco dias após a alta hospitalar. Resultados: Durante este período 187 pacientes tiveram 214 episódios de infecção por VR. Cento e oitenta e três (85,5%) foram considerados infecção comunitária e 31 (14,5%) episódios foram considerados infecção hospitalar, sendo que 17 (7,9 %) episódios ocorreram na unidade de TCTH e 21 (9,8 %) episódios na unidade de hematologia (p=NS). A permanência hospitalar por mais de 23 dias se associou a transmissão hospitalar (p=<0,001) e o ano de 2013 mostrou uma queda significante desse tipo de transmissão (p=0,04). O VSR foi o VR com maior frequência de progressão para pneumonia. Conclusão: Concluímos que a higienização das mãos, coleta de lavado nasal (LN) antes das internações para o transplante de células tronco hematopoiéticas (TCTH), isolamento de contato para os pacientes com vírus respiratório positivo, busca ativa de sintomas e a educação continuada para os pacientes, familiares e profissionais da saúde devem ser contínua para o controle das infecções por VR nas unidades de TCTH. A maioria dessas medidas são de baixo custo e altamente efetivas. Cuidadores, contactuantes domiciliares e profissionais de saúde devem aderir às medidas de controle para garantir a segurança dos pacientes. / Introduction: Community-acquired respiratory viruses (RV) are the most frequent etiologic agents causing acute respiratory infections (ARI) in humans. These agents have a wide antigenic range, universal distribution, affect people in all age groups, and may cause various clinical syndromes involving both the upper and lower respiratory tract. These respiratory infections are major causes of mortality in patients undergoing hematopoietic stem cell transplantation (HSCT), especially in the period prior to engraftment. These infections may also be acquired in hospitals, possibly transmitted by contact with infected health professionals or patient caregivers, or with contaminated objects or surfaces. Since 2008, a continued education program was started at the HSCT Program of Amaral Carvalho Foundation aiming to improve the control of RV transmission. Patients, caregivers, donors, family members and employees are invited to participate in the activities. Objectives: To review the cases of RV infections in patients undergoing HSCT from August 2010 to December 2013, characterize the type of transmission, if community- or hospital-acquired during this period, and determine the morbidity and mortality of RV infections. Methods: The study was conducted at the HSCT Service of Amaral Carvalho Hospital, analyzing the charts of HSCT recipients with RV infection diagnosed by immunofluorescent assay or multiplex PCR. Medical data and images from patients admitted to the HSCT and hematology wards, as well as from patients assisted at the outpatient clinic were retrospectively reviewed. Hospital transmission was defined when the interval between hospital admission and the first symptoms was more than five days, or when the interval between patient discharge and the first symptoms was up to five days. Results: During this period, 187 patients had 214 episodes of VRI. Thirty-one episodes (14.5%) were considered hospital-acquired. Rates of hospital transmission were similar between HSCT unit (7,9%) and the hematology ward (9,8%). Hospital stay for more than 23 days was associated with hospital transmission (p=0.001) and a significant decrease in this type of transmission was observed in 2013 (p=0.04). VSR was the RV with the highest frequency of progression to pneumonia (42%). Conclusion: We conclude that hand hygiene, nasal lavage collection (LN) before hospitalizations for hematopoietic stem cell transplantation (HSCT), contact isolation for patients with positive respiratory virus, active pursuit of symptoms and continuing education for patients, family and healthcare professionals should be continuous for the control of infections in HSCT VR units. Most of these policies have low cost and are highly effective. Caregivers, household contacts and health professionals must comply with the control policies to ensure the safety of patients.

Orientador: Clarisse Martins Machado / Resumo: As infecções por vírus respiratórios (VR) são causas importantes de mortalidade em pacientes submetidos a Transplante de Células-Tronco Hematopoiéticas (TCTH) especialmente no período anterior à pega do enxerto. Estas infecções também podem ser adquiridas dentro dos hospitais, possivelmente transmitida por contato com profissionais de saúde ou cuidadores infectados, ou com objetos ou superfícies contaminadas. Portanto, é importante caracterizar o tipo de transmissão para que medidas rigorosas de controle possam ser implantadas. Objetivos: Analisar os casos de infecção por vírus respiratórios (VR) nos pacientes submetidos a TCTH entre agosto de 2010 a dezembro de 2013 e caracterizar os tipos de transmissão durante esse período. Método: O presente estudo foi realizado no Hospital Amaral Carvalho de Jahu nas unidades de internação e ambulatório de TCTH e na unidade de hematologia, incluindo pacientes com diagnóstico comprovado de VR por imunofluorescência ou PCR multiplex em amostras de lavado nasal. A transmissão foi definida como hospitalar na ausência de sintomas respiratórios à admissão e diagnóstico de VR comprovado laboratorialmente após cinco dias da internação ou até cinco dias após a alta hospitalar. Resultados: Durante este período 187 pacientes tiveram 214 episódios de infecção por VR. Cento e oitenta e três (85,5%) foram considerados infecção comunitária e 31 (14,5%) episódios foram considerados infecção hospitalar, sendo que 17 (7,9 %) episódios oc... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Community-acquired respiratory viruses (RV) are the most frequent etiologic agents causing acute respiratory infections (ARI) in humans. These agents have a wide antigenic range, universal distribution, affect people in all age groups, and may cause various clinical syndromes involving both the upper and lower respiratory tract. These respiratory infections are major causes of mortality in patients undergoing hematopoietic stem cell transplantation (HSCT), especially in the period prior to engraftment. These infections may also be acquired in hospitals, possibly transmitted by contact with infected health professionals or patient caregivers, or with contaminated objects or surfaces. Since 2008, a continued education program was started at the HSCT Program of Amaral Carvalho Foundation aiming to improve the control of RV transmission. Patients, caregivers, donors, family members and employees are invited to participate in the activities. Objectives: To review the cases of RV infections in patients undergoing HSCT from August 2010 to December 2013, characterize the type of transmission, if community- or hospital-acquired during this period, and determine the morbidity and mortality of RV infections. Methods: The study was conducted at the HSCT Service of Amaral Carvalho Hospital, analyzing the charts of HSCT recipients with RV infection diagnosed by immunofluorescent assay or multiplex PCR. Medical data and images from patients admitted to the HSC... (Complete abstract click electronic access below) / Mestre

This thesis aims to describe the epidemiology of SARS-CoV-2 and other seasonal respiratory viruses (SRV) in the Ottawa region and determine if there are demographic or occupational risk factors associated with viral infection. This was accomplished in three articles: a rapid review of the literature evaluating SARS-CoV-2 seroprevalence in transit users, an account of SRV activity in Ottawa, Ontario from August, 2018 to January, 2022, and an analysis of coronavirus (CoV) incidence and prevalence in several at risk groups. Results indicated a reduction in SRV incidence during the COVID-19 pandemic correlated with the introduction of non-pharmaceutical public health measures. SARS-CoV-2 seroprevalence indicative of natural infection was not greater in population groups hypothesized to be at greater risk of infection, such as transit users and those exposed to children. Lower socioeconomic status and racial or ethnic minority were consistently associated with higher SARS-CoV-2 seroprevalence. SRVs are expected to resurge and co-circulate with SARS-CoV-2. Results from this thesis suggest those of ethnic minority, low income or immunocompromised individuals may at greater risk.

Pathogen-containing droplets expelled into the air as infected individuals speak, cough, sneeze, or laugh may infect proximal secondary hosts. Facemasks are an effective, low-cost method to help prevent airborne transmission mediated by pathogen-laden droplets in the environment. To understand the testing of facemask materials to protect against airborne pathogens, we followed the American Society for Testing and Materials (ASTM) standard F2101-12 and built an in-house test platform. However, the standard lacks clear guidelines. To address this, we built an aerosol platform at McMaster University to generate and test droplets containing viable bacteria, allowing us to assess the filtration performance of different facemask materials. We created optimized procedures to ensure the generation and sampling of infectious aerosols are consistent and reliable. The operation, maintenance, and sterilization of the platform were also detailed. Airborne disease transmission is a complex phenomenon influenced by multiple factors. Conditions such as muco-obstructive airway disorders can increase the viscosity and solute content of airway lining fluid. Therefore, individual variability in airway mucus composition and initial droplet size may influence transmission dynamics. Thirdly, environmental conditions such as temperature and humidity can change the aerosol microenvironment and alter encapsulated pathogen viability. Evidence suggests infectious aerosols originate from the breakup of the airway lining fluid, and the site of origin within the airways can affect the size of pathogen-laden droplets. Using the bacteriophage Phi6 as a stand-in for the SARS-CoV-2 virus, we examined how droplet size, mucus composition, pathogen load, and environmental conditions (temperature and humidity) affect pathogen survival. Our findings may provide insight into the dynamics of airborne transmission and can help improve strategies to reduce the spread of respiratory infections. Lastly, we adapted the platform to conduct in vitro lung exposure studies of deposition, safety, and efficacy of bactericidal agents. The human airway epithelial cell line, Calu-3, cultured in an air-liquid interface system, was used to recapitulate the physiological characteristics of the respiratory mucosa. Pseudomonas aeruginosa biofilms cultured for 24 hours were placed within the impactor and exposed to aerosolized bactericidal agents. Preliminary results show that our cell-integrated exposure platform can assess in vitro safety, efficacy, and dosage of inhaled therapeutics. This setup can potentially help gather pre-clinical data to support in vivo studies of treatments for respiratory diseases. This platform has significant potential for expanding aerosol research at McMaster University to evaluate the effectiveness of personal protective equipment, study how infectious aerosols spread, and explore inhaled delivery of therapeutic agents to the lungs. These findings contribute to our understanding of airborne transmission and may inform strategies to reduce the spread of infections. / Thesis / Doctor of Philosophy (PhD) / Many respiratory infections are spread through the air by pathogen-containing droplets released from the airways of infected individuals as they breathe, talk, cough, sneeze, or laugh. Facemasks are an easy-to-adopt infection control strategy to guard against airborne infectious agents. An aerosol platform was built at McMaster University amidst the coronavirus pandemic to perform facemask material filtration tests using information from the American Society for Materials and Testing standard F2101-19. However, we soon identified ambiguous aspects of the standard that can potentially prevent the reliable operation of the test platform and the gathering of reproducible test results. The first objective was to modify the test setup and develop precise procedures to address ambiguities of the standard. Modifications of the platform and detailed procedures ensured more accurate and consistent testing of facemask materials. Next, we used the platform to study how long pathogens stay viable within aerosol droplets. Droplets containing the bacteriophage Phi6, a surrogate for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were used to study how droplet size, mucus composition, and environmental conditions (like temperature and humidity) affect pathogen survival. Lastly, we adapted our aerosol platform to investigate the inhaled delivery of antibacterial agents to target lung infections. Using cultures of human airway epithelial cells and Pseudomonas aeruginosa biofilms, we tested the antibacterial efficacy of aerosolized antibiotics and bacteriophages (viruses that kill bacteria). In summary, this thesis work has developed an aerosol platform for conducting reliable material filtration efficiency tests, probing virus stability within airborne droplets, and modelling inhaled drug delivery to the lungs.

Introdução: As infecções virais do trato respiratório (IVTR) têm sido freqüentemente identificadas em associação com asma aguda (AA) em crianças, porém poucos estudos têm mostrado resultados similares em adultos com asma. Objetivos: Avaliar a prevalência de infecção viral na asma aguda em pacientes atendidos no setor de adultos do departamento de emergência (DE), comparando as características entre os grupos com amostras positivas e negativas para os vírus respiratórios. Material e Métodos: Conduzimos um estudo transversal de pacientes que se apresentaram com AA no setor de adultos do DE (idade igual ou maior que 12 anos) do Hospital de Clínicas de Porto Alegre. Um aspirado nasofaríngeo foi obtido para detecção de antígeno com a técnica de coloração de imunofluorescência indireta (vírus sincicial respiratório, adenovírus, influenza e parainfluenza tipo 1, 2, 3 e 4). Foram coletados dados referentes a características demográficas, medicações regulares, história médica pregressa, crise que levou à atual visita ao DE e desfechos da crise. Resultados: No período de março de 2004 a novembro de 2005, 111 pacientes foram examinados para IVTR. Foram identificados vírus respiratórios em 15 pacientes (8 com Adenovírus, 1 com RSV, 2 com Influenza A, e 4 com Parainfluenza tipo 1). Utilizando a análise de regressão logística, as variáveis com (p < 0,10), índice de massa corporal (IMC) e febre no domicilio, foram significativamente associados à identificação de vírus respiratório. Sessenta e seis por cento dos pacientes com IVTR apresentaram febre no domicílio, enquanto que somente 27% dos pacientes sem infecção viral apresentaram febre a domicílio, (p = 0,006). Não houve outra diferença significativa nas características clínicas, tempo de permanência e desfechos. Conclusão: Este estudo mostra uma prevalência de 13,5% de IVTR na AA em pacientes com idade igual ou maior que 12 anos atendidos na sala de emergência, confirmando a infecção viral como importante desencadeante nesta faixa etária. Dentre as características clínicas estudadas, febre no domicílio e IMC elevado, apresentam maior chance de identificação viral positiva. / Introduction: Respiratory tract viral infections (RTVI) have been frequently identified in association with acute asthma (AA) in children, but few studies have shown similar results in adults with asthma. Objectives: Evaluate the prevalence of viral infection with acute asthma in patients presented to the adult sector of the Emergency Department (ED), comparing the characteristics among the groups with positive and negative samples for respiratory viruses. Materials and Methods: It was conducted a cohort study of patients with AA that presented themselves to the adult sector of the ED (age 12 or older) at Hospital de Clínicas in Porto Alegre. A nasopharyngeal aspirate was obtained for detection of viral by indirect immunofluorescence technique (respiratory syncytial virus, adenovirus, influenza, and parainfluenza type 1, 2, 3, and 4). Data related to demographic characteristics, regular medication, previous medical history, the exacerbation that resulted in coming to the ED, and the outcomes of the crisis. Results: From March 2004 to November 2005, 111 patients were examined for RTVI. Respiratory viruses were identified in 15 patients (8 with Adenoviruses, 1 with RSV, 2 with Influenza A, and 4 with Parainfluenza type 1). Using the logistic regression analysis, the variables (p < 0.10) Body Mass Index (BMI) and fever at home were significantly associated to the identification of respiratory virus. Sixty-six percent of the patients with RTVI had fever at home while only 27% of the patients without viral infection presented fever a home (p = 0.006). There was not another significant difference in the clinical characteristics, time of stay, and outcomes. Conclusion: This study shows a prevalence of 13.5% of RTVI in AA in patients 12 years or older treated at the emergency room, which confirms viral infection as an important asthma-triggering factor in this age bracket. Among the clinical characteristics studied, fever at home and high BMI present the highest chance of positive viral identification.

Introdução: As infecções virais do trato respiratório (IVTR) têm sido freqüentemente identificadas em associação com asma aguda (AA) em crianças, porém poucos estudos têm mostrado resultados similares em adultos com asma. Objetivos: Avaliar a prevalência de infecção viral na asma aguda em pacientes atendidos no setor de adultos do departamento de emergência (DE), comparando as características entre os grupos com amostras positivas e negativas para os vírus respiratórios. Material e Métodos: Conduzimos um estudo transversal de pacientes que se apresentaram com AA no setor de adultos do DE (idade igual ou maior que 12 anos) do Hospital de Clínicas de Porto Alegre. Um aspirado nasofaríngeo foi obtido para detecção de antígeno com a técnica de coloração de imunofluorescência indireta (vírus sincicial respiratório, adenovírus, influenza e parainfluenza tipo 1, 2, 3 e 4). Foram coletados dados referentes a características demográficas, medicações regulares, história médica pregressa, crise que levou à atual visita ao DE e desfechos da crise. Resultados: No período de março de 2004 a novembro de 2005, 111 pacientes foram examinados para IVTR. Foram identificados vírus respiratórios em 15 pacientes (8 com Adenovírus, 1 com RSV, 2 com Influenza A, e 4 com Parainfluenza tipo 1). Utilizando a análise de regressão logística, as variáveis com (p < 0,10), índice de massa corporal (IMC) e febre no domicilio, foram significativamente associados à identificação de vírus respiratório. Sessenta e seis por cento dos pacientes com IVTR apresentaram febre no domicílio, enquanto que somente 27% dos pacientes sem infecção viral apresentaram febre a domicílio, (p = 0,006). Não houve outra diferença significativa nas características clínicas, tempo de permanência e desfechos. Conclusão: Este estudo mostra uma prevalência de 13,5% de IVTR na AA em pacientes com idade igual ou maior que 12 anos atendidos na sala de emergência, confirmando a infecção viral como importante desencadeante nesta faixa etária. Dentre as características clínicas estudadas, febre no domicílio e IMC elevado, apresentam maior chance de identificação viral positiva. / Introduction: Respiratory tract viral infections (RTVI) have been frequently identified in association with acute asthma (AA) in children, but few studies have shown similar results in adults with asthma. Objectives: Evaluate the prevalence of viral infection with acute asthma in patients presented to the adult sector of the Emergency Department (ED), comparing the characteristics among the groups with positive and negative samples for respiratory viruses. Materials and Methods: It was conducted a cohort study of patients with AA that presented themselves to the adult sector of the ED (age 12 or older) at Hospital de Clínicas in Porto Alegre. A nasopharyngeal aspirate was obtained for detection of viral by indirect immunofluorescence technique (respiratory syncytial virus, adenovirus, influenza, and parainfluenza type 1, 2, 3, and 4). Data related to demographic characteristics, regular medication, previous medical history, the exacerbation that resulted in coming to the ED, and the outcomes of the crisis. Results: From March 2004 to November 2005, 111 patients were examined for RTVI. Respiratory viruses were identified in 15 patients (8 with Adenoviruses, 1 with RSV, 2 with Influenza A, and 4 with Parainfluenza type 1). Using the logistic regression analysis, the variables (p < 0.10) Body Mass Index (BMI) and fever at home were significantly associated to the identification of respiratory virus. Sixty-six percent of the patients with RTVI had fever at home while only 27% of the patients without viral infection presented fever a home (p = 0.006). There was not another significant difference in the clinical characteristics, time of stay, and outcomes. Conclusion: This study shows a prevalence of 13.5% of RTVI in AA in patients 12 years or older treated at the emergency room, which confirms viral infection as an important asthma-triggering factor in this age bracket. Among the clinical characteristics studied, fever at home and high BMI present the highest chance of positive viral identification.

Introdução: As infecções virais do trato respiratório (IVTR) têm sido freqüentemente identificadas em associação com asma aguda (AA) em crianças, porém poucos estudos têm mostrado resultados similares em adultos com asma. Objetivos: Avaliar a prevalência de infecção viral na asma aguda em pacientes atendidos no setor de adultos do departamento de emergência (DE), comparando as características entre os grupos com amostras positivas e negativas para os vírus respiratórios. Material e Métodos: Conduzimos um estudo transversal de pacientes que se apresentaram com AA no setor de adultos do DE (idade igual ou maior que 12 anos) do Hospital de Clínicas de Porto Alegre. Um aspirado nasofaríngeo foi obtido para detecção de antígeno com a técnica de coloração de imunofluorescência indireta (vírus sincicial respiratório, adenovírus, influenza e parainfluenza tipo 1, 2, 3 e 4). Foram coletados dados referentes a características demográficas, medicações regulares, história médica pregressa, crise que levou à atual visita ao DE e desfechos da crise. Resultados: No período de março de 2004 a novembro de 2005, 111 pacientes foram examinados para IVTR. Foram identificados vírus respiratórios em 15 pacientes (8 com Adenovírus, 1 com RSV, 2 com Influenza A, e 4 com Parainfluenza tipo 1). Utilizando a análise de regressão logística, as variáveis com (p < 0,10), índice de massa corporal (IMC) e febre no domicilio, foram significativamente associados à identificação de vírus respiratório. Sessenta e seis por cento dos pacientes com IVTR apresentaram febre no domicílio, enquanto que somente 27% dos pacientes sem infecção viral apresentaram febre a domicílio, (p = 0,006). Não houve outra diferença significativa nas características clínicas, tempo de permanência e desfechos. Conclusão: Este estudo mostra uma prevalência de 13,5% de IVTR na AA em pacientes com idade igual ou maior que 12 anos atendidos na sala de emergência, confirmando a infecção viral como importante desencadeante nesta faixa etária. Dentre as características clínicas estudadas, febre no domicílio e IMC elevado, apresentam maior chance de identificação viral positiva. / Introduction: Respiratory tract viral infections (RTVI) have been frequently identified in association with acute asthma (AA) in children, but few studies have shown similar results in adults with asthma. Objectives: Evaluate the prevalence of viral infection with acute asthma in patients presented to the adult sector of the Emergency Department (ED), comparing the characteristics among the groups with positive and negative samples for respiratory viruses. Materials and Methods: It was conducted a cohort study of patients with AA that presented themselves to the adult sector of the ED (age 12 or older) at Hospital de Clínicas in Porto Alegre. A nasopharyngeal aspirate was obtained for detection of viral by indirect immunofluorescence technique (respiratory syncytial virus, adenovirus, influenza, and parainfluenza type 1, 2, 3, and 4). Data related to demographic characteristics, regular medication, previous medical history, the exacerbation that resulted in coming to the ED, and the outcomes of the crisis. Results: From March 2004 to November 2005, 111 patients were examined for RTVI. Respiratory viruses were identified in 15 patients (8 with Adenoviruses, 1 with RSV, 2 with Influenza A, and 4 with Parainfluenza type 1). Using the logistic regression analysis, the variables (p < 0.10) Body Mass Index (BMI) and fever at home were significantly associated to the identification of respiratory virus. Sixty-six percent of the patients with RTVI had fever at home while only 27% of the patients without viral infection presented fever a home (p = 0.006). There was not another significant difference in the clinical characteristics, time of stay, and outcomes. Conclusion: This study shows a prevalence of 13.5% of RTVI in AA in patients 12 years or older treated at the emergency room, which confirms viral infection as an important asthma-triggering factor in this age bracket. Among the clinical characteristics studied, fever at home and high BMI present the highest chance of positive viral identification.

<p>Asthma is a chronic immune-inflammatory disease of the airways, characterized by reversible airflow obstruction and airway hyperresponsiveness (AHR), and is associated with the development of airway remodeling. While our understanding of the pathophysiology of allergic asthma has increased remarkably in the last few decades, the origins of the disease remain elusive. Indeed, studies indicate that the prevalence of allergic asthma, has increased dramatically over the last 30 years. Within this context, a number of environmental factors including respiratory viral infections have been associated with the onset of this disease but causal evidence is lacking. The work presented in this thesis examines the interactions between a respiratory viral infection, specifically influenza A, and the common aeroallergen house dust mite (HDM) in an experimental murine model. To this end, we investigated the impact of an acute influenza A infection on the exposure to a subclinical dose of HDM (Chapter 2) and addressed potential underlying immune mechanisms using a global, genomic approach (Chapter 3). Our data demonstrate an enhancement of immune inflammatory responses to HDM and reveals multiple immune pathways by which influenza A may enhance the response to subsequent allergen exposure. Collectively these immune pathways are capable of lowering the threshold of HDM responsiveness. Lastly, as allergic asthma develops in most instances during infancy, we investigated the impact of an influenza A infection on allergen responses in infant mice (Chapter 4). In this setting, acute influenza A infection subverts constitutive allergen hyporesponsiveness thus resulting in sensitization, airway inflammation and, ultimately, structural and functional alterations persisting into adulthood.</p> / Doctor of Philosophy (PhD)

Orientador: Fátima Pereira de Souza / Banca: José Luiz Proença Módena / Banca: Maria Elisabete Jorge Amaral / Resumo: As infecções do trato respiratório estão associadas com mortalidade significativa no mundo inteiro e afetam principalmente crianças menores de cinco anos de idade. A maioria das infecções respiratórias é causada por agentes virais como: Vírus Sincicial Respiratório (RSV), Influenzavírus tipo A e B (FLUA e FLUB), Parainfluenza tipo 1, 2 and 3 (PIV-1, PIV-2 e PIV-3), Rhinovirus (HRV) e Metapneumovirus Humano (hMPV). O conhecimento da epidemiologia e prevalência desses vírus é importante para que metodologias terapêuticas possam ser aplicadas apropriadamente e saber como esses vírus estão circulando. O objetivo deste trabalho foi investigar a incidência de 8 tipos de vírus respiratórios em 279 amostras de aspirado nasofaríngeo obtidas de Julho/2004 a Setembro de 2005 de 120 crianças (73 do sexo masculino e 47 do sexo feminino) com idade entre 0 a 6 anos com sintomas de infecção respiratória aguda. A análise foi realizada pela técnica de RT-PCR e seqüenciamento direto. Nossos resultados mostraram que 27,2% (76/279) das amostras foram positivas para pelo um dos vírus respiratórios, sendo 84,2% (64/76) de Picornavírus, 76,3% (58/76) de Rhinovírus e 7,9% de Enterovírus (6/76), 7,9% (6/76) de RSV, 1,3% (1/76) de hMPV, 2,6% (2/76) de FLUA, 2,6% (2/76) de PIV-1 e 1,3% (1/76) de PIV-2. As infecções repetidas acometeram 29% (22/76) das crianças com infecção respiratória. A maioria das re-infecções, 82% (18/22), foram pelo gênero Rhinovírus. Os sintomas mais freqüentes foram coriza diagnosticada em 89,5% dos casos (68/76) seguido de tosse em 67,1% (51/76). Os Rhinovírus foram detectados em todo o período de estudo, com picos de infecção nos meses de inverno e outono, porém não houve associação significativa entre a presença viral e a sazonalidade. Neste estudo houve prevalência de infecção e re-infecção por Rhinovírus. Portanto, este estudo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Respiratory tract infections are associated with significant mortality worldwide and affect mostly children under five years of age. Most respiratory infections are caused by viral agents such as: Respiratory Syncytial Virus (RSV), the viruses of Influenza type A and B (FLUA and FLUB), Parainfluenza type 1, 2 and 3 (PIV-1, PIV-2 and PIV-3), Rhinovirus (HRV) and Human Metapneumovirus (hMPV). Knowledge of the epidemiology and prevalence of these viruses is important for therapeutic methods can be applied as appropriate and to know how these viruses are circulating. The aim of this work was to investigate the incidence of 8 types of respiratory viruses in 279 samples of nasopharyngeal aspirated obtained from July/2004 to September/2005 of 120 children (73 male and 47 female) with age between 0 to 6 years with symptoms of acute respiratory infection. The analysis was performed by RT-PCR and direct sequencing. Our results showed that 27,2% (76/279) of samples were positive at least for a type of the respiratory viruses, with 84,2% (64/76) of Picornaviruses, with 76,3% (58/76) of Rhinovírus e 7,9% of Enterovírus (6/76), 7,9% (6/76) of RSV, 1,3% (1/76) of hMPV, 2,6% (2/76) of FLUA, 2,6% (2/76) of PIV-1 and 1,3% (1/76) of PIV-2. The recurrent infections affect 29% (22/76) of children with respiratory infection. Most re-infections, 82% (18/22), were by Rhinovírus genus. The most frequent symptoms were runny nose diagnosed in 89.5% (68/76) followed by cough in 67.1% (51/76). Rhinovírus were detected throughout the study period, with peaks of infection during the winter and autumn, but there was no significant association between viral presence and seasonality. In this study there was prevalence of infection and re-infection by Rhinovírus. Therefore, this study provided better understanding of the circulation of respiratory viruses in a population of day care in the region... (Complete abstract click electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:27:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-03-05Bitstream added on 2014-06-13T19:55:51Z : No. of bitstreams: 1 bonfim_cm_me_sjrp.pdf: 483201 bytes, checksum: ee7e5d0928d4f0c7dcb6b57d4216ed16 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / As infecções do trato respiratório estão associadas com mortalidade significativa no mundo inteiro e afetam principalmente crianças menores de cinco anos de idade. A maioria das infecções respiratórias é causada por agentes virais como: Vírus Sincicial Respiratório (RSV), Influenzavírus tipo A e B (FLUA e FLUB), Parainfluenza tipo 1, 2 and 3 (PIV-1, PIV-2 e PIV-3), Rhinovirus (HRV) e Metapneumovirus Humano (hMPV). O conhecimento da epidemiologia e prevalência desses vírus é importante para que metodologias terapêuticas possam ser aplicadas apropriadamente e saber como esses vírus estão circulando. O objetivo deste trabalho foi investigar a incidência de 8 tipos de vírus respiratórios em 279 amostras de aspirado nasofaríngeo obtidas de Julho/2004 a Setembro de 2005 de 120 crianças (73 do sexo masculino e 47 do sexo feminino) com idade entre 0 a 6 anos com sintomas de infecção respiratória aguda. A análise foi realizada pela técnica de RT-PCR e seqüenciamento direto. Nossos resultados mostraram que 27,2% (76/279) das amostras foram positivas para pelo um dos vírus respiratórios, sendo 84,2% (64/76) de Picornavírus, 76,3% (58/76) de Rhinovírus e 7,9% de Enterovírus (6/76), 7,9% (6/76) de RSV, 1,3% (1/76) de hMPV, 2,6% (2/76) de FLUA, 2,6% (2/76) de PIV-1 e 1,3% (1/76) de PIV-2. As infecções repetidas acometeram 29% (22/76) das crianças com infecção respiratória. A maioria das re-infecções, 82% (18/22), foram pelo gênero Rhinovírus. Os sintomas mais freqüentes foram coriza diagnosticada em 89,5% dos casos (68/76) seguido de tosse em 67,1% (51/76). Os Rhinovírus foram detectados em todo o período de estudo, com picos de infecção nos meses de inverno e outono, porém não houve associação significativa entre a presença viral e a sazonalidade. Neste estudo houve prevalência de infecção e re-infecção por Rhinovírus. Portanto, este estudo... / Respiratory tract infections are associated with significant mortality worldwide and affect mostly children under five years of age. Most respiratory infections are caused by viral agents such as: Respiratory Syncytial Virus (RSV), the viruses of Influenza type A and B (FLUA and FLUB), Parainfluenza type 1, 2 and 3 (PIV-1, PIV-2 and PIV-3), Rhinovirus (HRV) and Human Metapneumovirus (hMPV). Knowledge of the epidemiology and prevalence of these viruses is important for therapeutic methods can be applied as appropriate and to know how these viruses are circulating. The aim of this work was to investigate the incidence of 8 types of respiratory viruses in 279 samples of nasopharyngeal aspirated obtained from July/2004 to September/2005 of 120 children (73 male and 47 female) with age between 0 to 6 years with symptoms of acute respiratory infection. The analysis was performed by RT-PCR and direct sequencing. Our results showed that 27,2% (76/279) of samples were positive at least for a type of the respiratory viruses, with 84,2% (64/76) of Picornaviruses, with 76,3% (58/76) of Rhinovírus e 7,9% of Enterovírus (6/76), 7,9% (6/76) of RSV, 1,3% (1/76) of hMPV, 2,6% (2/76) of FLUA, 2,6% (2/76) of PIV-1 and 1,3% (1/76) of PIV-2. The recurrent infections affect 29% (22/76) of children with respiratory infection. Most re-infections, 82% (18/22), were by Rhinovírus genus. The most frequent symptoms were runny nose diagnosed in 89.5% (68/76) followed by cough in 67.1% (51/76). Rhinovírus were detected throughout the study period, with peaks of infection during the winter and autumn, but there was no significant association between viral presence and seasonality. In this study there was prevalence of infection and re-infection by Rhinovírus. Therefore, this study provided better understanding of the circulation of respiratory viruses in a population of day care in the region... (Complete abstract click electronic access below)