Thesis (Ph. D.)--University of Virginia, 1999. / Spine title: RSV & CTL responses. Includes bibliographical references (p. 143-185). Also available online through Digital Dissertations.

Orientador: Maria Rita Donalísio Cordeiro / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T16:23:15Z (GMT). No. of bitstreams: 1 Freitas_AndreRicardoRibasde_D.pdf: 4270845 bytes, checksum: 09078cb28a971b59a0103ccfbe6a3bee (MD5) Previous issue date: 2014 / Resumo: Introdução e objetivos: As infecções respiratórias estão entre as mais importantes causas de morbimortalidade no mundo. A sua alta incidência tem relevante impacto nos óbitos, como também na sobrecarga do sistema de saúde e absenteísmo no trabalho e escola Todas as faixas etárias são acometidas, porém, as mais afetadas são as crianças e os idosos. Também são particularmente susceptíveis os imunocomprometidos e os portadores de doenças crônicas em geral. Os vírus são os agentes responsáveis pela maior parte das infecções respiratórias, os principais vírus causadores de infecções respiratórias são o influenza A e B e o Vírus Sincicial Respiratório (VSR). Estes vírus têm comportamento biológicos distintos e o conhecimento de como estes vírus afetam a saúde da população é fundamental para embasar as ações de prevenção, profilaxia e tratamento de pacientes permitindo uma alocação adequada de recursos em quantidade e tempo adequados. No Brasil, no ano 2000, para monitorar a ocorrência destes vírus foi implantada a vigilância de síndromes gripais SIVEP-GRIPE, que através de 128 unidades sentinelas distribuídas em todas as regiões do país coletam semanalmente amostras de secreção de nasofaringe por semana de pacientes com síndromes gripais. Neste trabalho estudamos o impacto do influenza na mortalidade no estado de São Paulo, nas diferentes faixas etárias no período entre 2002 e 2011, incluindo o período da pandemia de 2009. Estudamos também a sazonalidade do VSR nas 5 diferentes regiões brasileiras e o impacto deste vírus nas internações por doenças respiratórias entre menores de 5 anos. Metodologia: Para o estudo da mortalidade associada ao influenza utilizamos o método de regressão de Serfling adaptado para dados semanais extraindo da série histórica os períodos de maior circulação viral a partir dos resultados do sistema de vigilância sentinela SIVEP-GRIPE. Comparar a mortalidade associada à pandemia de influenza de 2009, às epidemias prévias anuais de influenza nas diferentes faixas etárias e com diferentes subtipos de vírus influenza circulantes no estado de São Paulo. Para o estudo da sazonalidade do VSR utilizamos análise de Wavelets, análise de Fourier, análise simplificada de estações anuais comparando os resultados nas 5 regiões administrativas do Brasil. Para identificar possíveis correlações temporais entre a circulação dos vírus respiratórios utilizamos métodos de regressão de ranque de Spearman e de regressão parcial. Resultados e conclusões: A mortalidade por pneumonia e influenza associada à pandemia de 2009 no estado de São Paulo foi ligeiramente mais alta que nos outros anos de influenza sazonal, considerando a mortalidade geral, sem distinção de faixa etária. Houve diferenças no risco de morrer entre as faixas etárias. Entre os indivíduos de 5 a 19 anos, a mortalidade associada à pandemia de 2009 foi 2,6 maior (0,6 óbitos/100.000hab) que a de anos não pandêmicos. Na faixa etária de 20 a 59 anos, a mortalidade associada à pandemia de 2009 foi 5,1 maior (2,8 óbitos/100.000hab) que nos anos não pandêmicos. As taxas de mortalidade entre menores de 5 anos foi 0,9 óbitos/100.000hab e na população de mais 60 anos foi 13,1 óbitos/100.000hab, ou seja, foram menores que nos anos não pandêmicos. O método de análise utilizado permitiu a diferenciação entre a mortalidade associada a subtipos virais (A(H3N2), B ou sazonal A(H1N1) e A(H1N1) pdm 2009). Foi possível a comparação entre a mortalidade associada à pandemia de influenza de 2009 em São Paulo, às epidemias anuais de influenza nas diferentes faixas etárias e com diferentes subtipos de vírus influenza circulando. Isto é, o impacto da circulação do vírus pandêmico influenza A(H1N1) foi maior na mortalidade em adultos e jovens, enquanto em maiores de 65 anos foi discreto. Por outro lado, o excesso de mortalidade foi expressivo em maiores de 65 anos, nos anos de circulação do influenza A(H3N2). O modelo de Serfling adaptado a dados semanais com validação por meio de dados da vigilância sentinela de síndromes gripais (SIVEP-GRIPE) mostrou-se confiável para detectar picos de maior circulação viral do Influenza e supostos reflexos na mortalidade em diferentes faixas etárias em período pandêmico, epidêmico e de circulação sazonal do vírus Influenza. Sobre o VSR foi possível identificar padrões sazonais do VSR em todas as regiões administrativas do Brasil utilizando-se dados da vigilância de síndromes gripais (SIVEP-GRIPE). Houve diferenças entre os momentos de maior circulação do vírus em algumas das cinco regiões administrativas do Brasil. Os padrões sazonais de internação por doenças sabidamente relacionadas com o VSR [Pneumonia devida a vírus respiratório sincicial, Bronquite aguda devida a vírus sincicial respiratório, Bronquiolite aguda devida a vírus sincicial respiratório, Bronquiolite (aguda, não especificada),] foram semelhantes aos encontrados pela análise da circulação do VSR por meio de dados da vigilância de síndromes gripais (SIVEP-GRIPE). Houve correlação temporal entre a circulação do VSR e as taxas de internação por doenças do aparelho respiratório em geral (Capítulo-X da CID-10) entre menores de 5 anos, nas cinco regiões administrativas do Brasil. Houve correlação temporal entre as taxas de internação entre menores de 5 anos por doenças sabidamente relacionadas com o VSR [Pneumonia devida a vírus respiratório sincicial, Bronquite aguda devida a vírus sincicial respiratório, Bronquiolite aguda devida a vírus sincicial respiratório, Bronquiolite (aguda, não especificada),] e as taxas de internação por doenças respiratórias em geral nesta faixa etária nas cinco regiões administrativas do Brasil, indicando que este é o principal vírus associado às internações de crianças até 5 anos por doenças respiratórias. De acordo com as evidências encontradas neste estudo, os esquemas de profilaxia contra o VSR hoje utilizados precisam ser revistos e particularizados para cada região do país. Entre as ações a serem revistas estão a disponibilização do palivizumabe, bem como medidas de prevenção à circulação do VSR na comunidade / Abstract: Introduction and Objectives: Respiratory infections are amongst the most important causes of morbidity and mortality worldwide. Its high incidence has significant impact on deaths, but also burdens the health system and leads to absenteeism from work and school All age groups are affected, but the most affected are children and the elderly. Are also particularly susceptible immunocompromised and patients with chronic diseases in general. Viruses are the agents responsible for most respiratory infections, the main cause of respiratory virus infections are influenza A and B and Respiratory Syncytial Virus (RSV). These viruses have distinct biological behavior and knowledge of how these viruses affect people's health is fundamental to support the prevention, prophylaxis and treatment of patients allowing an adequate allocation of resources in quantity and adequate time. In Brazil, in 2000, to monitor the occurrence of these viruses was established surveillance of influenza-like syndromes SIVEP-FLU, which through 128 sentinel units distributed in all regions of the country collect weekly samples of nasopharyngeal secretions of patients per week with influenza-like illness. In this work we study the impact of influenza on mortality in the state of São Paulo , in different age groups between 2002 and 2011 , including the period of the 2009 pandemic. We also studied the seasonality of RSV in 5 different Brazilian regions and the impact of this virus in hospitalizations for respiratory diseases among children under 5 years. Methods: To study the mortality associated with influenza used the regression method of Serfling adapted for extracting weekly data of the time series periods of increased viral movement from the results of sentinel surveillance system SIVEP - FLU . Compare the mortality associated with pandemic 2009 influenza , annual epidemics of influenza prior at different ages and with different subtypes of influenza viruses circulating in the state of São Paulo . To study the seasonality of RSV , we use wavelet analysis , Fourier analysis , simplified analysis of annual seasons comparing the results in five administrative regions of Brazil . To identify possible temporal correlations between the circulation of respiratory viruses use regression methods of Spearman rank and partial regression. Results and Conclusions: The mortality from pneumonia and influenza associated with the 2009 pandemic in the state of São Paulo was slightly higher than in the other years of seasonal influenza, considering the overall mortality, irrespective of age. There were differences in the risk of dying between age groups. Among individuals 5-19 years, the mortality rate associated with the 2009 pandemic was 2.6 higher than that of non-pandemic years. (0.6 deaths /100,000 inhabitants) In the age group 20-59 years, the rate associated with the 2009 pandemic mortality was 5.1 higher than in non-pandemic years. (2.8 deaths /100,000 inhabitants). Mortality rates among children under five years was 0.9 deaths /100,000 inhabitants and in persons over 60 years was 13.1 deaths /100,000 inhabitants, ie were lower than in non- pandemic years . The method of analysis used allowed the differentiation between mortality associated with viral subtypes (A(H3N2), A(H1N1) and B or seasonal A(H1N1) pdm 2009) . It was possible to compare the mortality associated with the 2009 influenza pandemic in Sao Paulo, annual influenza epidemics in different ages and with different subtypes of influenza viruses circulating. That is, the impact of the circulation of influenza A(H1N1) pandemic virus was higher mortality in adults and children, while in adults over 65 years was low . On the other hand, the excess mortality was significant in adults over 65 years ago, in circulating influenza A H3N2. The Serfling model adapted to weekly data validation using data from sentinel surveillance of influenza-like illness (SIVEP - GRIPE) was reliable for detecting peaks of higher viral circulation of influenza and alleged impacts on mortality in different age groups in pandemic period , epidemic and seasonal circulation of influenza viruses . About RSV was possible to identify seasonal patterns of RSV in all administrative regions of Brazil using surveillance data of influenza syndromes (SIVEP -GRIPE). There were differences between the moments of greatest circulation of the virus in some of the five administrative regions of Brazil. Seasonal patterns of hospitalization for known diseases with RSV [ Pneumonia due to respiratory syncytial virus , acute bronchitis due to respiratory syncytial virus , acute bronchiolitis due to respiratory syncytial virus bronchiolitis ( acute , unspecified ) ] were similar to those found by analysis of the movement of data through RSV surveillance of influenza-like syndromes ( SIVEP - GRIPE) . There was a temporal correlation between the circulation of RSV and the rates of hospitalization for respiratory diseases in general (Chapter X of ICD- 10) among children under 5 diseases in the five administrative regions of Brazil . There was a temporal correlation between the rates of hospitalization among children under 5 years for known diseases with RSV [ Pneumonia due to respiratory syncytial virus , acute bronchitis due to respiratory syncytial virus , acute bronchiolitis due to respiratory syncytial virus bronchiolitis ( acute , unspecified ) ] and rates of hospitalization for respiratory diseases in general in this age group in the five administrative regions of Brazil , indicating that this is the main virus associated with hospitalizations of children under 5 years due to respiratory diseases . According to the evidence found in this study , the schemes of prophylaxis against RSV used today need to be reviewed and individualized for each region of the country . Among the actions to be reviewed are the availability of palivizumab , as well as measures to prevent the circulation of RSV in the community / Doutorado / Epidemiologia / Doutor em Saude Coletiva

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Master of Science in Medicine in the field of Clinical Microbiology and Infectious Diseases Johannesburg, 2018. / Background: Respiratory Syncytial Virus (RSV) is a common cause of upper and lower respiratory tract infections (LRTI), primarily in children having severe disease manifestation. In South Africa, RSV is identified in approximately 25-30% of children hospitalized for LRTI. There is a spectrum of RSV-associated LRTI severity. Understanding associations between immune mediators and RSV-LRTI severity could assist clinicians in the triaging for level of care. Several cytokines have been implicated in RSV-LRTI severity. Aim: Study the associations between cytokine levels from plasma and nasopharyngeal aspirate with RSV infection or RSV-associated LRTI severity in hospitalized infants ranging from 0-12 months of age. The correlation between plasma and nasopharyngeal aspirate cytokine concentrations was also evaluated. Methods: Paired plasma and nasopharyngeal aspirate (NPA) samples were collected from polymerase chain reaction confirmed RSV-infected infants without coinfection with other pathogens that we investigated for. Paired samples were also collected from RSV negative-control infants (n=31) who did not have any respiratory symptoms. Control-infants were scheduled for elective surgery; samples were collected before administration of medication and surgical procedure. RSV associated LRTI episodes were grouped into mild (n=89) and severe RSV-LRTI (n=113) using the Respiratory Index of Severity in Children (RISC) Score. Interferon gamma (IFN-γ), interleukins (IL) IL-1α, IL-1β, IL-4, IL5, IL-6, IL-8, IL-9, IL-10, IL-12(p70)IL-13, macrophage inducing protein (MIP-1α), monocyte chemo attractant protein (MCP-1), tumour necrosis alpha (TNF-α), Regulated on activation, normal T cell expressed and secreted (RANTES) and were measured with multiplex immunosorbent assay using Luminex® technology. Cytokine profiles were evaluated for association of RSV-LRTI severity and between RSV LRTI cases and controls. Results: Comparing hospitalized RSV-associated LRTI to control infants, RSV cases had elevated plasma TNF-α (0.7pg/ml vs. 0.5pg/ml; p=0.007), and IL-10 (1.0pg/ml vs. 0.6pg/ml; p=0.02) concentrations, and reduced plasma MIP-1α (12pg/ml vs. 28pg/ml; p=0.008) and IFN-γ (3pg/ml vs. 5pg/ml; p=0.02) levels. Nasopharyngeal aspirate TNF-α (8.0pg/ml vs. 1.0pg/ml; p=0.01), IL-8 (2682pg/ml vs. 184pg/ml; p=0.002), MCP-1 (287pg/ml vs. 66pg/ml; p<0.001), MIP-1α (27pg/ml vs. 6.7pg/ml; p=0.004) concentrations were elevated in RSV-LRTI cases compared to control infants. Infants hospitalized with severe RSV-associated LRTI (RISC score ≥2) were younger than mild cases (3.9 vs. 4.5 months; p=0.01). In RSV cases, severe RSV-LRTI was associated with increased plasma IFN-γ levels (4pg/ml vs. 3pg/ml) and NPA MIP-1α concentrations (88pg/ml vs. 50pg/ml, mean; all other values medians) compared to mild RSV-LRTI. In a multivariate analysis, NPA MIP-1α levels remained associated with RSV-LRTI (p=0.05), but could not predict RSV-LRTI severity. Conclusion: This study observed that during RSV-associated LRTI, immune response was directed at the respiratory tract. Reduced concentrations of plasma IFN-γ and elevated levels of cytokines in the NPA may suggest that the blood of RSV-LRTI cases had reduced number of IFN-γ producing cells. There was no evidence of distinct Th1 or Th2 type immune response and the cytokines associated with RSV-LRTI severity could not predict the outcome of severe RSV-associated LRTI. Key words: Respiratory Syncytial Virus, Lower respiratory tract infections, Severity, Plasma, Nasopharyngeal aspirate, IFN-γ, MIP-1α, Luminex® / LG2018

jdelvall@upc.edu.pe / Acute respiratory infections are responsible for high morbi–mortality in Peruvian children. However, the etiological agents are poorly identified. This study, conducted during the pandemic outbreak of H1N1 influenza in 2009, aims to determine the main etiological agents responsible for acute respiratory infections in children from Lima, Peru. Nasopharyngeal swabs collected from 717 children with acute respiratory infections between January 2009 and December 2010 were analyzed by multiplex RT-PCR for 13 respiratory viruses: influenza A, B, and C virus; parainfluenza virus (PIV) 1, 2, 3, and 4; and human respiratory syncytial virus (RSV) A and B, among others. Samples were also tested with direct fluorescent-antibodies (DFA) for six respiratory viruses. RT-PCR and DFA detected respiratory viruses in 240 (33.5%) and 85 (11.9%) cases, respectively. The most common etiological agents were RSV-A (15.3%), followed by influenza A (4.6%), PIV-1 (3.6%), and PIV-2 (1.8%). The viruses identified by DFA corresponded to RSV (5.9%) and influenza A (1.8%). Therefore, respiratory syncytial viruses (RSV) were found to be the most common etiology of acute respiratory infections. The authors suggest that active surveillance be conducted to identify the causative agents and improve clinical management, especially in the context of possible circulation of pandemic viruses

Ypač svarbią reikšmę Lietuvos žemės ūkiui turi viena iš gyvulininkystės šakų – galvijininkystė. Jos plėtrai didelę žalą daro galvijų užkrečiamosios, ypač virusinės, ligos, todėl būtina greitai, tiksliai ir efektyviai diagnozuoti galvijų virusines ligas, užkirsti kelią jų plitimui Lietuvoje. Kvėpavimo ir virškinimo trakto ligomis galvijų prieauglis serga visose pramoninės gyvulininkystės šalyse, dėl šių ligų galvijai gaišta žymiai dažniau, nei nuo reprodukcijos, medžiagų apykaitos ligų ar mastitų. Didesnį veršelių susirgimų skaičių ir gaišimą nuo enteritų bei respiratorinių ligų galima būtų paaiškinti dideliu virusinių ligų – GVD, IGR, PG-3, RSV, adenovirusų ,RV, CV ir bakterinių infekcijų išplitimu. Mūsų darbo tikslas buvo atlikti galvijų užkrečiamųjų virusinių ligų paplitimo analizę, ištirti CV, RV, RSV ir adenovirusų paplitimą galvijų bandose. Dėl rota ir korona virusų buvo ištirti 56 išmatų mėginiai, dėl antikūnų prieš adenovirusą – 20, RS virusą 28 kraujo serumo mėginiai. Šiems tyrimams buvo naudojami komerciniai standartizuoti imunofermentinės analizės (IFA) rinkiniai. Veršelių 30 kraujo serumo mėginių buvo ištirti pusiau kiekybiniu natrio sulfito precipitacijos metodu, dėl imunoglobulinų kiekio nustatymo. Tyrimai atlikti LSMU VA Užkrečiamųjų ligų katedroje ir Nacionalinio maisto ir veterinarijos rizikos vertinimo instituto Virusologijos skyriuje 2013 metais. Įvertinus padėtį 3 ūkiuose, kur buvo atlikti ligų tyrimai, nustatyta, kad rotavirusine infekcija vidutiniškai... [toliau žr. visą tekstą] / Cattle take a very important place in Lithuanian agriculture. Since the development of livestock can be seriously affected by contagious diseases, especially viral ones, it is highly important quickly, accurately and efficiently diagnose viral disease of cattle, and to prevent its spreading in Lithuania. In all livestock farming industry countries, cattle offspring are suffering from respiratory and digestive tract diseases. They are dying from these diseases more often than from reproductive, metabolic diseases and mastitis. Increasing calves’ cases and mortality rate from enteritis and respiratory diseases can be explained by the high viral diseases such as GVD, IGR, PG-3, RSV, adenovirus, RV, CV and bacterial infections spread. The goal of our study was to analyze the spread of livestock infectious viral diseases and examine the CV, RV, RVS and adenovirus prevalence in the cattle herds. 56 fecal samples were tested for the rotavirus and coronavirus, 20 – for antibodies against adenovirus, and 28 blood serum samples for RS virus. To test these samples, we used standardized commercial enzyme-linked immunosorbent assay (ELISA) kits. 30 blood serum samples of calves were analyzed by quantitative sodium sulfite precipitation method for the determination of immunoglobulin. The tests took place at LSMU VA Department of Infectious Diseases and National Food and Veterinary Risk Assessment Institute, Department of Virology in 2013. Cattle from 3 farms were assessed for anticipated... [to full text]

INTRODUÇÃO: As infecções do aparelho respiratório inferior (IARI) constituem importante causa de morbi-mortalidade nas crianças abaixo dos cinco anos de idade e são responsáveis por um grande número de hospitalizações. Os vírus são os seus principais agentes causadores. A maioria das IARI, na criança, tem um único agente viral identificado. Com o advento de técnicas moleculares, tornou-se possível a identificação de mais de um agente viral numa mesma amostra de secreção respiratória. No que diz respeito à gravidade da doença entre crianças infectadas por um único vírus em relação às crianças infectadas por dois ou mais vírus (coinfecção), a literatura científica revela-se conflitante. No presente estudo, os autores comparam a gravidade da infecção entre um ou mais agentes virais em crianças até 24 meses de idade hospitalizadas com infecção aguda do aparelho respiratório inferior e os possíveis fatores associados à evolução clinica. CASUÌSTICA E MÉTODOS: em estudo de coorte retrospectivo foram analisadas 304 crianças hospitalizadas com infecção respiratória aguda no período de fevereiro a novembro de 2005. Foram avaliadas as características demográficas dos pacientes (idade, sexo), diagnóstico de alta, presença de fatores de risco para gravidade (prematuridade, displasia broncopulmonar, cardiopatia, imunodepressão, neuropatia) e os seguintes desfechos de gravidade: tempo de internação, necessidade e tempo de oxigênio, necessidade e tempo de internação em UTI, necessidade e tempo de ventilação mecânica. A técnica de PCR ou RT-PCR foi utilizada para identificação de oito vírus respiratórios: vírus sincicial respiratório (VSR), metapneumovírus humano (MPV-h), parainfluenza 1, 2 e 3 (PIV), Influenza A e B (IV A e B) e adenovírus (AdV). RESULTADOS: Foram identificados agentes virais em 219 (72%) crianças sendo que 158 (72%) crianças apresentaram infecção por um único agente viral (IU) e 61 (28%) apresentaram co-infecção (CI). O VSR foi o vírus mais freqüente em ambos os grupos. No grupo IU, o VSR esteve presente em 121 amostras (76,6%), seguido do AdV em 20 amostras (12,6%) e pelo MPV-h em 11 amostras (7%). No grupo CI, o agente mais identificado em associação com o VSR foi o AdV, presente em 24 amostras (39%) seguido do MPV-h em 16 amostras (26%). Não foi encontrada diferença entre os grupos IU e CI quanto à idade (p=0,66), sexo (p=0,84), história de prematuridade (p=0,87). A distribuição das infecções virais, segundo o mês de ocorrência, foi semelhante nos grupos IU e CI, predominando nos meses de abril, maio e junho. As infecções virais foram mais frequentes nas crianças menores de 1 ano de idade tanto no grupo IU como no grupo CI. A bronquiolite foi o diagnóstico mais freqüente em ambos os grupos (42% IU e 33% CI). Não houve diferença, entre os dois grupos, quanto à necessidade de UTI (p=0,12), necessidade de oxigênio (p=0,71), necessidade de ventilação mecânica (p=0,35), tempo de internação (p=0,18), tempo de UTI (p=0,8), tempo de ventilação mecânica (p=0,8), tempo de oxigênio (p=0,81). CONCLUSÃO: A gravidade das infecções virais do aparelho respiratório inferior em lactentes hospitalizados foi semelhante tanto em pacientes com coinfecção como nos pacientes com infecção por um único agente. / BACKGROUND: Lower acute respiratory tract infections are a major cause of morbidity and mortality in children under five years of age and lead to a large number of hospitalizations. Acute bronchiolitis and pneumonia correspond to the main manifestations of these infections and viruses are the major ethiologic agents. Whether the infections caused by one or more virus are associated with the disease severity is still controversial . OBJECVIVES: to compare the severity of the infection by one or more viral agents in children up to 24 months of age hospitalized with acute lower respiratory tract infection and the possible associated factors with clinical outcome. PATIENTS AND METHODS: A retrospective study of 304 children hospitalized with acute respiratory disease from February to November 2005. We evaluated the demographics (age, sex), disease severity risk factors (prematurity, bronchopulmonary dysplasia, heart disease, immunosuppression, neuropathy, absence of breastfeeding) and the following outcomes: lengh of hospitalization, oxygen therapy, admission in the ICU, need of mechanical ventilation. The PCR or RT-PCR was used to identify eight respiratory viruses: respiratory syncytial virus (RSV), human metapneumovirus (h- MPV), parainfluenzavirus 1, 2 and 3 (PIV), influenza A and B (IV A and B) and adenovirus (AdV). RESULTS: Viral agents were identified in 219 (72%) children. Among them 158 (72%) were infected with a single viral agent and 61 (28%) had co-infection. RSV was the main ethiologic agent in 121 samples (76.6%) in the patients with a single agent , followed by AdV in 20 samples (12.6%) and the h-MPV in 11 samples (7%). In the patients with co-infection, the most common association was the RSV and AdV (39%) followed by the RSV and h-MPV (26%). There was no statistically significant difference between the group with single viral agent and the group with co-infection regarding age (p=0.66), gender (p=0.84), history of prematurity (p=0.87) and history of breastfeeding until 6 months of age (p=0.36). The monthly distribution of viral infections was similar in both groups, predominantly in April, May and June. Children under one year of age were the most afected by acute lower respiratory tract infection in both groups. Bronquiolitis was the most frequent diagnosis in both groups. There was no difference between the groups regarding the need for ICU (p=0.12), oxygen requirement (p=0.71), need for mechanical ventilation (p=0.35), length of hospitalization (p= 0.18), ICU stay (p= 0.8), duration of mechanical ventilation (p=0.8), oxygen therapy (p=0.81). CONCLUSION: In children hospitalized with acute respiratory low tract infection caused by one or more type of virus configure the same disease severity profile.

INTRODUÇÃO: As infecções do aparelho respiratório inferior (IARI) constituem importante causa de morbi-mortalidade nas crianças abaixo dos cinco anos de idade e são responsáveis por um grande número de hospitalizações. Os vírus são os seus principais agentes causadores. A maioria das IARI, na criança, tem um único agente viral identificado. Com o advento de técnicas moleculares, tornou-se possível a identificação de mais de um agente viral numa mesma amostra de secreção respiratória. No que diz respeito à gravidade da doença entre crianças infectadas por um único vírus em relação às crianças infectadas por dois ou mais vírus (coinfecção), a literatura científica revela-se conflitante. No presente estudo, os autores comparam a gravidade da infecção entre um ou mais agentes virais em crianças até 24 meses de idade hospitalizadas com infecção aguda do aparelho respiratório inferior e os possíveis fatores associados à evolução clinica. CASUÌSTICA E MÉTODOS: em estudo de coorte retrospectivo foram analisadas 304 crianças hospitalizadas com infecção respiratória aguda no período de fevereiro a novembro de 2005. Foram avaliadas as características demográficas dos pacientes (idade, sexo), diagnóstico de alta, presença de fatores de risco para gravidade (prematuridade, displasia broncopulmonar, cardiopatia, imunodepressão, neuropatia) e os seguintes desfechos de gravidade: tempo de internação, necessidade e tempo de oxigênio, necessidade e tempo de internação em UTI, necessidade e tempo de ventilação mecânica. A técnica de PCR ou RT-PCR foi utilizada para identificação de oito vírus respiratórios: vírus sincicial respiratório (VSR), metapneumovírus humano (MPV-h), parainfluenza 1, 2 e 3 (PIV), Influenza A e B (IV A e B) e adenovírus (AdV). RESULTADOS: Foram identificados agentes virais em 219 (72%) crianças sendo que 158 (72%) crianças apresentaram infecção por um único agente viral (IU) e 61 (28%) apresentaram co-infecção (CI). O VSR foi o vírus mais freqüente em ambos os grupos. No grupo IU, o VSR esteve presente em 121 amostras (76,6%), seguido do AdV em 20 amostras (12,6%) e pelo MPV-h em 11 amostras (7%). No grupo CI, o agente mais identificado em associação com o VSR foi o AdV, presente em 24 amostras (39%) seguido do MPV-h em 16 amostras (26%). Não foi encontrada diferença entre os grupos IU e CI quanto à idade (p=0,66), sexo (p=0,84), história de prematuridade (p=0,87). A distribuição das infecções virais, segundo o mês de ocorrência, foi semelhante nos grupos IU e CI, predominando nos meses de abril, maio e junho. As infecções virais foram mais frequentes nas crianças menores de 1 ano de idade tanto no grupo IU como no grupo CI. A bronquiolite foi o diagnóstico mais freqüente em ambos os grupos (42% IU e 33% CI). Não houve diferença, entre os dois grupos, quanto à necessidade de UTI (p=0,12), necessidade de oxigênio (p=0,71), necessidade de ventilação mecânica (p=0,35), tempo de internação (p=0,18), tempo de UTI (p=0,8), tempo de ventilação mecânica (p=0,8), tempo de oxigênio (p=0,81). CONCLUSÃO: A gravidade das infecções virais do aparelho respiratório inferior em lactentes hospitalizados foi semelhante tanto em pacientes com coinfecção como nos pacientes com infecção por um único agente. / BACKGROUND: Lower acute respiratory tract infections are a major cause of morbidity and mortality in children under five years of age and lead to a large number of hospitalizations. Acute bronchiolitis and pneumonia correspond to the main manifestations of these infections and viruses are the major ethiologic agents. Whether the infections caused by one or more virus are associated with the disease severity is still controversial . OBJECVIVES: to compare the severity of the infection by one or more viral agents in children up to 24 months of age hospitalized with acute lower respiratory tract infection and the possible associated factors with clinical outcome. PATIENTS AND METHODS: A retrospective study of 304 children hospitalized with acute respiratory disease from February to November 2005. We evaluated the demographics (age, sex), disease severity risk factors (prematurity, bronchopulmonary dysplasia, heart disease, immunosuppression, neuropathy, absence of breastfeeding) and the following outcomes: lengh of hospitalization, oxygen therapy, admission in the ICU, need of mechanical ventilation. The PCR or RT-PCR was used to identify eight respiratory viruses: respiratory syncytial virus (RSV), human metapneumovirus (h- MPV), parainfluenzavirus 1, 2 and 3 (PIV), influenza A and B (IV A and B) and adenovirus (AdV). RESULTS: Viral agents were identified in 219 (72%) children. Among them 158 (72%) were infected with a single viral agent and 61 (28%) had co-infection. RSV was the main ethiologic agent in 121 samples (76.6%) in the patients with a single agent , followed by AdV in 20 samples (12.6%) and the h-MPV in 11 samples (7%). In the patients with co-infection, the most common association was the RSV and AdV (39%) followed by the RSV and h-MPV (26%). There was no statistically significant difference between the group with single viral agent and the group with co-infection regarding age (p=0.66), gender (p=0.84), history of prematurity (p=0.87) and history of breastfeeding until 6 months of age (p=0.36). The monthly distribution of viral infections was similar in both groups, predominantly in April, May and June. Children under one year of age were the most afected by acute lower respiratory tract infection in both groups. Bronquiolitis was the most frequent diagnosis in both groups. There was no difference between the groups regarding the need for ICU (p=0.12), oxygen requirement (p=0.71), need for mechanical ventilation (p=0.35), length of hospitalization (p= 0.18), ICU stay (p= 0.8), duration of mechanical ventilation (p=0.8), oxygen therapy (p=0.81). CONCLUSION: In children hospitalized with acute respiratory low tract infection caused by one or more type of virus configure the same disease severity profile.

Orientadores: Emilio Carlos Elias Baracat, Clarice Weis Arns / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T23:20:49Z (GMT). No. of bitstreams: 1 Riccetto_AdrianaGutLopes_D.pdf: 18036035 bytes, checksum: 951a577babe97ac325d8f7e4a0ea459c (MD5) Previous issue date: 2006 / Resumo: Infecções respiratórias agudas são a causa mais comum de internação hospitalar em pediatria.O Vírus Sincicial Respiratório (VSR) é o principal agente destas infecções, com apresentação clínica de bronquiolite ou pneumonia. Os casos graves ocorrem principalmente em pacientes prematuros, com pneumopatias crônicas, cardiopatias e imunodeficiências. Uma proporção de pacientes internados necessita de ventilação pulmonar mecânica invasiva (VPMI). O acompanhamento após a fase aguda mostra frequentemente obstrução respiratória recorrente. Objetivos: Descrever as características epidemiológicas e clínicas de lactentes menores de 12 meses, hospitalizados com doença respiratória aguda baixa, determinando fatores associados à ventilação mecânica e à infecção pelo VSR, e as características evolutivas tardias desta população. Casuística e métodos: Estudo de corte prospectivo, realizado de 01 de abril a 30 de setembro de 2004, em dois hospitais universitários da região de Campinas, São Paulo, Brasil. Foram avaliados 152 lactentes de 0 a 12 meses internados com diagnóstico inicial de doença respiratória aguda baixa. Realizou-se avaliação clínica e pesquisa do VSR, por imunofluorescência direta (EFD), em secreção nasofaríngea Os pacientes foram divididos em dois grupos, de acordo com a necessidade de VPMI e presença do VSR, comparando-se os fatores prognósticos. Seis a 12 meses após a internação hospitalar, os pacientes com IFD positiva para VSR e os submetidos à VPMI foram convocados e avaliados quanto à presença de sibilância recorrente. A associação entre fatores de risco e desfecho estudado foi analisada por Risco Relativo (RR) e intervalos de confiança (IC95%). Para comparação de proporções foi utilizado o teste Qui-quadrado e teste Exato de Fischer. Para comparação das medidas contínuas entre dois grupos foi aplicado o teste de Mann-Whitney. O nível de significância adotado para os testes estatísticos foi de 5%. Resultados. A pesquisa de VSR foi realizada em 149 lactentes, com positividade de 17,4% (26 pacientes) Vinte e um pacientes (13,8%) foram submetidos à VPMI e os fatores significativamente associados ã VPMI foram: idade menor de 3 meses (RR=2,35, IC95%: 1,06-5,22) e tempo de aleitamento materno menor que um mês (RR=3,15, IC95%: 1,35-7,35). Na comparação dos grupos com e sem a presença de VSR os fatores associados à infecção foram: idade gestacional abaixo de 35 semanas (RR=4,17, IC95%:2,21-7,87), peso ao nascer menor de 2500g (RR=2,69, IC95%: 1,34-5,37) e escolaridade materna menor que 5 anos (RR=2,28, IC 95%: 1,13-4,59). Na evolução clínica em seguimento ambulatorial, 26 de 41 convocados compareceram (63,4%), destes 19,2% eram não sibilantes, 57,7% eram sibilantes intermitentes e 23,1% sibilantes persistentes. Na comparação entre os grupos não sibilantes e sibilantes intermitentes, ocorreu diferença significativa na variável hospitalização após a alta, ocorrendo apenas no segundo grupo de pacientes. Na comparação entre os grupos não sibilantes e sibilantes persistentes leves/moderados, não ocorreram diferenças significativas nas variáveis analisadas. Conclusões: A incidência do VSR foi de 17,5% entre os lactentes internados com doença respiratória aguda baixa. Os fatores associados à VPM1 foram: idade menor que 3 meses e tempo de aleitamento materno menor que 1 mês Os fatores associados à aquisição do VSR foram idade gestacional abaixo de 35 semanas, peso ao nascer menor de 2500g e escolaridade materna menor que 5 anos. Na evolução clínica tardia, os lactentes com pesquisa positiva para VSR e os lactentes submetidos à VPMI apresentaram-se como sibilantes intermitentes, sem necessidade de corticoterapia inalatória e com maior número de hospitalizações após a alta / Abstract: In pediatrics, acute respiratory infections are the most common cause of hospitalization. The Respiratory Syncytial Virus (RSV) is the main agent responsible for these infections that are clinically manifested as bronchiolitis or pneumonia Severe cases occur mostly in premature patients who have chronic pneumopathies, cardiopathies and immunodeficiencies. Some of the hospitalized patients require invasive mechanical ventilation (IMV) Follow up after the acute phase often demonstrates recurring respiratory obstruction. Objectives: to describe the epidemiological and clinical characteristics of infants under the age of 12 months hospitalized with acute lower respiratory tract infections, determine factors related to mechanical ventilation and RSV as well as delayed evolutional characteristics of this population. Methods and Cases: This was a prospective cohort study conducted from 2001 April to 2001 September at two university hospitals in the region of Campinas, Sao Paulo. An evaluation was performed of 152 infants aged 0 to 12 months, hospitalized with an initial diagnosis of acute lower respiratory tract diseases Direct Immunofluorescence Assay (DFA) was used to perform a clinical research and assess RSV in the nasopharyngeal secretion. The patients were divided into two groups according to the need for IMV as well as the presence of RSV and their prognostic factors were compared. Six to twelve months after hospitalization, patients with DFA positive for RSV as well as patients who were subjected to IMV were recalled and checked for the presence of recurrent wheezing. The relation between risk factors and outcome was analyzed by applying Relative Risk (RR) and Confidence Intervals (CI 95%). The chi-square test and the Fisher Exact test were used for comparing proportions. Continuous measures were compared using the Mann Whitney test. The significance level adopted for statistical tests was 5%. Results: RSV research was conducted on 149 infants, revealing 17.4% positivity (26 patients). Twenty-one patients (13 8%) were subjected to IMV' and factors significantly associated were age below three months (RR=2.35, IC 95%: 1.06-5.22) and breastfeeding period less than one month (RR=3.15; IC95%: 1.35-7.35). When both groups were compared with and without the presence of RSV, the factors associated with infection were: gestational age less than 35 weeks (RR=4 17, IC95%: 2.21-7.87), birth weight less than 2,500g (RR=2.69, 1C95%: 1.34 -5.37) and maternal education less than five years (RR=2 28, IC 95%: 1 13-4.59). Only 26 (63.4%) out of 41 patients reported for follow up of clinical evolution. Of these, 19.2% were non-sibilants, 57.7% were intermittent sibilants and 23.1% were persistent sibilants When the non-sibilant groups were compared with the intermittent sibilants, a significant difference was observed in relation to the variable - hospitalization after discharge, which only occurred in the second group. No significant difference was observed regarding the variables analyzed when non-sibilant groups were compared with moderate/mild persistent sibilants. Conclusions: The incidence of RSV was 17.5% in infants hospitalized with acute lower respiratory tract infections. Factors associated with IMV were age below three months and breastfeeding period less than one month Factors associated with acquisition of RSV were: gestational age less than 35 weeks, birth weight below 2,500 gm; maternal education level less than five years. Delayed clinical evolution revealed that infants who were positive for RSV and infants subjected to IMV demonstrated intermittent wheezing with no need for inhalation corticotherapy and also a higher number of hospitalizations after discharge / Doutorado / Saude da Criança e do Adolescente / Doutor em Saude da Criança e do Adolescente

Ma Shuang-Cheng. / "March 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 289-324). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Ho, Wing Shan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 116-137). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / Abstract (Chinese Version) --- p.v / Table of Contents --- p.vii / List of Figures --- p.x / List of Tables --- p.xi / List of Abbreviations --- p.xii / Chapter Chapter One: --- General Introduction / Chapter 1.1 --- Respiratory Syncytial Virus (RSV) --- p.1 / Chapter 1.2 --- RSV biology --- p.2 / Chapter 1.3 --- RSV strains --- p.10 / Chapter 1.4 --- RSV pathogenesis and host antiviral responses --- p.11 / Chapter 1.5 --- Prevention of RSV infection --- p.13 / Chapter 1.5.1 --- Vaccines --- p.13 / Chapter 1.5.2 --- Passive anti-RSV antibodies --- p.17 / Chapter 1.6 --- Treatment for RSV infections --- p.20 / Chapter 1.6.1 --- Ribavirin (Virasole®) --- p.20 / Chapter 1.6.2 --- Other antiviral strategies --- p.21 / Chapter 1.6.2.1 --- Attachment inhibitors --- p.22 / Chapter 1.6.2.2 --- Fusion inhibitors --- p.23 / Chapter 1.6.2.3 --- Replication inhibitors --- p.25 / Chapter 1.6.2.4 --- Ethnobotanic medicines --- p.28 / Chapter 1.6.2.4.1 --- Anti-RSV medicinal plant components --- p.31 / Chapter 1.6.2.4.1.1 --- Phenolics and polyphenols --- p.31 / Chapter 1.6.2.4.1.2 --- Flavonoids --- p.32 / Chapter 1.6.2.4.1.3 --- Terpenoids and essential oils --- p.34 / Chapter 1.6.2.4.1.4 --- Lectins --- p.34 / Chapter 1.6.2.4.1.4.1 --- General introduction to lectins --- p.34 / Chapter 1.6.2.4.1.4.2 --- Historical aspects of lectins --- p.35 / Chapter 1.6.2.4.1.4.3 --- Applications of lectins --- p.36 / Chapter 1.7 --- Objectives of the project --- p.37 / Chapter Chapter Two: --- Screening of medicinal plants and phytochemicals for antiviral activity against RSV / Chapter 2.1 --- Introduction --- p.39 / Chapter 2.2 --- Materials and methods --- p.47 / Chapter 2.2.1 --- Medicinal plants and phytochemicals --- p.47 / Chapter 2.2.2 --- Plant extracts preparation --- p.48 / Chapter 2.2.2.1 --- Aqueous extracts --- p.48 / Chapter 2.2.2.2 --- Ethanol extracts --- p.48 / Chapter 2.2.3 --- Cell and virus --- p.49 / Chapter 2.2.4 --- Endpoint titration of RSV infectivity --- p.50 / Chapter 2.2.5 --- Cytotoxicity test --- p.50 / Chapter 2.2.6 --- Antiviral assay --- p.52 / Chapter 2.3 --- Results --- p.53 / Chapter 2.4 --- Discussion --- p.58 / Chapter Chapter Three: --- "Mechanistic studies of anti-RSV actions of various fractions of Adina pilulifera, and daphnoretin, a purified compound from Wikstroemia indica" / Chapter 3.1 --- Introduction --- p.60 / Chapter 3.2 --- Materials and methods --- p.65 / Chapter 3.2.1 --- Fractionation of A. pilulifera ethanol extract --- p.65 / Chapter 3.2.2 --- Cell and virus --- p.65 / Chapter 3.2.3 --- Cytotoxicity test --- p.65 / Chapter 3.2.4 --- Endpoint titration of RSV by TCID50 method --- p.66 / Chapter 3.2.5 --- Antiviral study by CPE reduction assay --- p.66 / Chapter 3.2.6 --- Endpoint titration of RSV by plaque assay --- p.66 / Chapter 3.2.7 --- Antiviral study by plaque reduction assay --- p.67 / Chapter 3.2.8 --- Mode of antiviral action study --- p.68 / Chapter 3.3 --- Results --- p.70 / Chapter 3.4 --- Discussion --- p.76 / Chapter Chapter Four: --- Antiviral activity of Narcissus tazetta proteins / Chapter 4.1 --- Introduction --- p.81 / Chapter 4.2 --- Materials and methods --- p.88 / Chapter 4.2.1 --- Crude proteins extraction from Narcissus tazetta cultivar --- p.88 / Chapter 4.2.2 --- Separation of proteins with affinity column --- p.88 / Chapter 4.2.3 --- Gel filtration of protein fractions on Superose column --- p.89 / Chapter 4.2.4 --- Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) --- p.89 / Chapter 4.2.5 --- Electroblotting and N-terminal amino acid sequence analysis --- p.90 / Chapter 4.2.6 --- Protein concentration determination --- p.90 / Chapter 4.2.7 --- Isolation and purification of N. tazetta lectin (NTL) --- p.91 / Chapter 4.2.8 --- Antiviral activities of N. tazetta proteins and NTL --- p.92 / Chapter 4.2.8.1 --- Cell and virus --- p.92 / Chapter 4.2.8.2 --- Cytotoxicity test --- p.92 / Chapter 4.2.8.3 --- Endpoint titration of RSV by TCID50 method --- p.92 / Chapter 4.2.8.4 --- Antiviral study by CPE reduction assay --- p.92 / Chapter 4.2.8.5 --- Endpoint titration of RSV by plaque assay --- p.92 / Chapter 4.2.8.6 --- Antiviral study by plaque reduction assay --- p.93 / Chapter 4.2.8.7 --- Mode of antiviral action study --- p.93 / Chapter 4.3 --- Results --- p.94 / Chapter 4.4 --- Discussion --- p.107 / Chapter Chapter Five: --- General Discussion and Conclusions --- p.111 / References --- p.116