Дисертації з теми "Infections infantiles"

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Respiratory infections account for more than 25% of the whole medical, pediatric, outpatient and hospital services. Around 90% of those infections are related with viral agents. RSV is an important agent identified in those diseases. This study aimed at assessing the frequency of Respiratory Syncytial Virus (RSV) in children aged from 0 to 6 years with upper respiratory infection diseases (URID) from a nursery school, and to associate the clinical and epidemic data of mild degree of URID with the viral agent. The children had a daily follow-up in the period from July 2003 to July 2004, and viral investigation for RSV by means of Polimerase Chain Reaction (PCR), in the children's nasopharyngeal secretions that presented signs of breathing infection. A total of 259 events of URID in 173 children have occurred. A hundred twenty-two (70.5%) children were over 2 years in the beginning of the follow-up and 94 (54.3%) were male. The monthly number of episodes ranged from 0 to 53. RSV was diagnosed in 27 (10.5%) samples, and it was more frequent between the months of July to September. The signs observed in the children with RSV infection were coryza in 26 (96.3%) episodes, nasal obstruction in 19 (70.4%), coughs in 15 (55.6%), wheezing in 3 (11.1%) and sneeze and fever in 2 (7.4%) episodes. Antibiotics were administered in 16 (6.2%) episodes of breathing infection. One (3.7%) infection episode by RSV received treatment with antibiotic. One (0.4%) serious episode had developed for hospitalization. A high frequency of RSV was observed among the children from nursery school with mild breathing infections, mainly from the beginning of the autumn to the spring; the most frequent signs in the infections for RSV were cough, coryza and nasal obstruction; there was association between nasal obstruction and infections by RSV.
As infecções respiratórias são responsáveis por mais de 25% de todo o atendimento médico pediátrico, ambulatorial e hospitalar. Em torno de 90% dessas infecções estão relacionadas com agentes virais. O Vírus Sincicial Respiratório (VSR) é um importante agente identificado nessas afecções. Esse estudo objetivou estimar a freqüência do VSR em crianças com idade entre 0 e 6 anos com infecção das vias aéreas superiores (IVAS), procedentes de uma creche e associar os dados clínicos e epidemiológicos da IVAS de grau leve com o agente viral. Foi realizado seguimento diário das crianças no período de julho de 2003 a julho de 2004 e investigação virológica para VSR através de Polimerase Chain Reaction (PCR), em secreções nasofaríngeas das crianças que apresentaram sinais de infecção respiratória. Ocorreram 259 episódios de IVAS em 173 crianças. Cento e vinte e duas (70,5%) crianças tinham mais de 2 anos de idade no início do segmento e 94 (54,3%) eram do sexo masculino. O número mensal de episódios variou de 0 a 53. O VSR foi diagnosticado em 27 (10,5%) amostras e foi mais freqüente nos meses de julho a setembro. Os sinais observados nas crianças com infecção por VSR foram coriza em 26 (96,3%) episódios, obstrução nasal em 19 (70,4%), tosse em 15 (55,6%),chiado em 3 (11,1%) e espirro e febre em 2 (7,4%) episódios. O uso de antibióticos ocorreu em 16 (6,2%) episódios de infecção respiratória. Um (3,7%) episódio de infecção por VSR recebeu tratamento com antibiótico. Houve 1 (0,4%) episódio grave que evoluiu para internação. Observou-se uma alta freqüência de VSR entre as crianças com infecções respiratórias leves, principalmente do início do outono ao início da primavera; os sinais mais freqüentes nas infecções por VSR foram tosse, coriza e obstrução nasal; houve associação entre obstrução nasal e infecções por VSR.

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Acute respiratory infections, especially upper respiratory tract infections (URTI), are the most frequent causes of infantile morbidity in the world. Day-care facilities are closed, with great circulation of people and infectious agents as well, being therefore prone to the spreading of viral respiratory infections. Mathematical epidemic models are quantitative analysis methods that might be used for understanding and predicting the transmission dynamics of infectious diseases. Objective: Verify the monthly incidence of URTI, of 8 respiratory viruses, and to simulate a mathematical model, evaluating its qualitative and quantitative behavior regarding true data from URTI in school of infantile education in integral period children. Casuistic and Methods: From July 2003 to July 2004, all children (173) in the school of infantile education in integral period were followed from 1.6 to 12 months. Them presenting signs of respiratory infections were examined and their nasopharyngeal aspirate specimen was collected, in a total of 255 analyses. Soon after, specific multiplex trial of reverse transcription, followed by the polymerase chain reaction (multiplex RT-PCR), was accomplished for identification of the 8 viruses related to respiratory infections. Results and Conclusions: The average incidence of URTI was 2.33 episodes per child-year. URTI was observed throughout the year of study, especially in the fall and winter, lowering during spring and presenting few cases in summer. Rhinovirus presented the greatest incidence, being observed throughout the period of study. Influenza B, respiratory syncytial virus (RSV), and metapneumovirus presented lower incidence, especially during fall and winter. URTI caused by other analyzed viruses - influenza A, parainfluenza 1, 2, and 3 were rare. The evaluation of the mathematical model through simulations has provided promising results, as it was possible to get true data reproduction. The model is promising. Having its suppositions adequate, it might be useful for understanding the dynamics and spreading of diseases, planning and evaluating prevention and immunization strategies in epidemics.
As infecções respiratórias agudas, em especial as infecções das vias aeríferas superiores (IVAS), são as causas mais freqüentes de morbidade infantil no mundo. As creches são ambientes fechados, onde há grande circulação de pessoas e também de agentes infecciosos, sendo então favoráveis à disseminação de infecções respiratórias virais. Os modelos epidemiológicos matemáticos são métodos de análise quantitativos e podem ser usados para compreensão e predição da dinâmica de transmissão de uma doença infecciosa. Objetivo: Verificar a incidência mensal de IVAS, de 8 vírus respiratórios, e simular um modelo matemático, avaliando seu comportamento qualitativo e quantitativo em relação aos dados reais de IVAS nas crianças da Escola de Educação Infantil em período integral. Casuística e Método: Todas as crianças (173) que freqüentaram a escola no período de julho de 2003 a julho de 2004 foram acompanhadas por 1,6 a 12 meses. Elas apresentaram sinais de IVAS foram examinadas e tiveram coletado espécime de aspirado de nasofaringe, perfazendo um total de 255 análises. Em seguida, foi realizado ensaio específico multiplex de transcrição reversa seguida da reação em cadeia de polimerase (multiplex RT-PCR) para identificação dos 8 vírus relacionados às IVAS. Resultados e Conclusões: A incidência média de IVAS foi de 2,33 episódios por criança-ano. As IVAS incidiram durante todo o período do estudo, principalmente no outono e inverno, decaindo na primavera e com poucos casos no verão. O rinovírus teve maior incidência tendo sido observado em todos os períodos em que ocorreram episódios de IVAS. Influenza B, vírus sincicial respiratório (VSR) e metapneumovírus ocorreram com menor incidência, principalmente no outono e inverno. IVAS causadas pelos outros vírus analisados influenza A, parainfluenza 1, 2 e 3 foram raras. A avaliação do modelo matemático, por meio de simulações, forneceu resultados animadores, visto que se conseguiu a reprodução dos dados reais. O modelo é promissor. Com a adequação das suas suposições, pode ser útil para a compreensão das dinâmicas de disseminação de doenças, planejamento e avaliação de estratégias de prevenção e de imunização em epidemias.

Le genre Entérovirus (EV) (famille des picornaviridae) est composé de petits virus à ARN non enveloppées classés en 12 espèces dont 7 sont pathogènes pour l'homme : 4 espèces (A-D) d'enterovirus humains (HEV) et trois espèces (A-C) de rhinovirus humains (HRV). Dans le genre enterovirus, les HRV et HEV sont reconnus comme des pathogènes respiratoires fréquemment responsables d'infections des voies aériennes supérieures et inférieures chez l'enfant et l'adulte. Entre 2009 et 2012, de nouveaux génotypes d'HEV à tropisme respiratoire (HEV-68, 104, 109, et le CVA-21) ont été décrits dans des cas isolés ou épidémiques démontrant la capacité des espèces A à D à induire des infections respiratoires basses humaines.La première phase de ce travail de thèse a eu pour objectifs de préciser le rôle étiologique des infections à EVs; d'identifier les génotypes potentiellement responsables des pathologies respiratoires pédiatriques nécessitant une hospitalisation, mais aussi d'analyser et de comparer les caractéristiques cliniques et épidémiologiques entre les différents groupes de génotypes identifiés. Nous avons réalisé une étude rétrospective sur une cohorte de 309 enfants hospitalisés au CHU de Reims entre septembre 2009 et juin 2010 pour une infection respiratoire aiguë non documentée microbiologiquement par la réalisation des tests virologiques et bactériologiques conventionnels. Nos résultats montrent que le génome des EVs (HEV et HRV) est retrouvé dans 60,5% (187/309) des aspirations naso-pharyngées des enfants hospitalisés, distinguant 15 infections à HEV (dont 10 souches HEV-68) et 172 à HRV. Les cas de bronchiolite et d'exacerbation de l'asthme (133/187) positifs pour la détection des souches HEV (12/133) étaient plus âgés (P=0,003) et plus fréquemment associés avec une détresse respiratoire (P=0,01) et un besoin en oxygénothérapie au moment de leur hospitalisation (P=0,01) que les cas infectés par un HRV. De plus, nous avons mis en évidence pour la première fois en France la circulation épidémique de souches d'HEV-68 (10/15 des souches d'HEV détectées) isolées au cours de l'automne 2009 chez des enfants hospitalisés pour une infection respiratoire aiguë. Nos résultats fournissent de nouvelles informations sur ce génotype ré-émergent qui semble présenter un tropisme respiratoire spécifique des voies respiratoires inférieures.La seconde phase de ce travail de thèse s'est intéressée à étudier les mécanismes liés au développent des processus inflammatoires de la muqueuse au cours de l'infection des voies respiratoires basses par HEV. A l'aide d'un modèle in vitro de cellules respiratoires humaines (A549) infectées par HEV-B (CVB5, Mitchell), nous avons observé que l'infection réplicative des HEV dans les cellules A549 induisait une augmentation dose et temps-dépendante des ARNm, et des protéines IL-8, MCP-1 et RANTES.En conclusion, nos résultats obtenus à partir de prélèvements respiratoires dans le cadre de notre étude de cohorte suggèrent que les EVs représentent une cause étiologique fréquente d'infections respiratoires basses chez l'enfant avec une pathogénicité supérieure des HEVs (principalement dans notre étude HEV-68) par rapport aux souches HRVs. De plus, nos résultats obtenus à partir d'expérimentation in vitro démontrent que les HEVs du groupe B sont capables d'induire au cours de l'infection des cellules épithéliales alvéolaires humaines (A459) une sécrétion spécifique d'IL-8, MCP-1 et RANTES. La production de ces chimiokines correspond à une réponse innée de la cellule épithéliale humaine infectée par les HEVs: nous avons montré pour la première fois que ce mécanisme était en partie régulé par l'activation de la voie non canonique de NF-kB via la protéine NIK dans la cellule épithéliale respiratoire humaine
The Enterovirus (EV) genus (picornaviridae family) consists of small non-enveloped positive RNA viruses classified in 12 species of which 7 are pathogenic for humans: four species (A-D) of human enterovirus (HEV) and three species (A-C) of human rhinovirus (HRV). Among the EV genus, HEV and HRV are recognized as leading causes of acute respiratory tract infections (ARTIs) in human. Between 2009 and 2012, new HEV respiratory genotypes (e. g. HEV-68, 104, 109, 117 and CVA-21) have been described in isolated cases or outbreaks supporting the ability HEV species A to D to induce lower respiratory tract infections. This supports the hypothesis of an underestimation of the prevalence and etiological role of EVs in pediatric acute respiratory tract infections (ARTIs) (more specifically bronchitis, bronchiolitis and asthma exacerbation).To assess the etiological role and the clinical characteristics of HRV and HEV infections in pediatric patients hospitalized for ARTIs, we conducted a retrospective study of 309 hospitalized pediatric patients in University Hospital Centre of Reims with microbiologically unexplained ARTIs from September 2009 to June 2010. Among the 309 ARTIs, 15 HEV and 172 HRV strains were identified. Among bronchiolitis and asthma exacerbation cases (n=133), HEV infected cases were older (P=0.003) and were more frequently associated with a respiratory distress (P=0.01) and a need for oxygen therapy at the time of admission (P=0.01) than cases infected by HRV strains. Interestingly, during this retrospective study, we provided evidence that during the fall 2009 in France, HEV-D68 strains were responsible for a low proportion of pediatric cases hospitalized for acute airway diseases including bronchiolitis and asthma exacerbation.To identify the mechanisms that can regulate the development of airway mucosa inflammation during HEV respiratory lower tract infections, we investigated the production of chemokines by HEV infected human alveolar epithelial cells (A549). Using in vitro model A549 cells infected by HEV-B (CVB5, Mitchell), we demonstrated that HEV-B strains isolated from upper respiratory tract of child with bronchiolitis could actively replicate in various human airway epithelial cells, and that this replicative infection induced specific dose and time-dependent increases in mRNA and protein secretion of IL-8, MCP-1 and RANTES, but not of all other CC and CXC human chemokines tested. The protein secretion of these chemokines appeared to be significantly increased at 48 and 72 hours post-infection in culture treated by low-doses of IFN-γ in comparison with mock-infected cells (P <0.001), and was correlated to the viral replication activity. In second time, we explore the pathogenic mechanisms that can regulate inflammatory responses to HEV in lower respiratory airways. We show that HEV infection induced a time-dependent increase of NIK protein accumulation that peaks at 16 hours post-infection (H P-I). NIK protein accumulation mediated the processing of p100 in p52, which association with Rel B was evidenced in nuclear compartment between 16 and 48 H P-I.In conclusion, our findings indicate that EVs are a common cause of lower respiratory tract infections in pediatric patients with a potential higher pathogenicity of HEV strains (mainly HEV-68) by comparison to HRV strains. Moreover, our in vitro results demonstrated that HEV are capable to induce the release of specific chemokines (IL -8, MCP-1 and RANTES) by alveolar epithelial cells during a replicative infection. Finally, we demonstrated for the first time that this innate airway epithelial cell response against HEV infection was partly regulated by the activation of the non-canonical NF-kB via NIK protein

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
O metapneumovÃrus humano (MPVh) à um vÃrus que tem se destacado como um dos agentes mais freqÃentes de infecÃÃes respiratÃrias agudas (IRA) virais na infÃncia. Este estudo teve como objetivos: observar a freqÃÃncia das infecÃÃes causadas pelo MPVh em crianÃas atendidas por IRA no Hospital Infantil Albert Sabin, hospital pediÃtrico de referÃncia do estado do CearÃ, no perÃodo de janeiro de 2006 a dezembro de 2007; descrever aspectos de sazonalidade dessas infecÃÃes relacionando-as com a ocorrÃncia de chuvas e a circulaÃÃo de outros vÃrus respiratÃrios; descrever as caracterÃsticas clÃnico-epidemiolÃgicas dos pacientes infectados pelo MPVh, comparando com os pacientes negativos e com os positivos para outros vÃrus e avaliar a tÃcnica de IFI como mÃtodo de diagnÃstico para a detecÃÃo do MPVh. Amostras de secreÃÃo de nasofaringe foram coletadas de crianÃas com sintomas de IRA e submetidas à tÃcnica de imunofluorescÃncia indireta para detecÃÃo dos seguintes vÃrus respiratÃrios: MPVh, vÃrus sincicial respiratÃrio (VSR), influenza A e B, adenovÃrus e parainfluenza 1, 2 e 3. Durante os 24 meses de estudo, foram colhidas amostras de 1276 crianÃas sendo detectado algum vÃrus respiratÃrio em 380 (29,78%) amostras. O MPVh foi o segundo vÃrus respiratÃrio mais encontrado representando um total de 8,69% de todas as amostras e de 29% dentre as amostras positivas para os vÃrus pesquisados. NÃo foi observado para o MPVh um padrÃo de sazonalidade nem correlaÃÃo com perÃodo chuvoso. A maioria dos pacientes positivos para MPVh foram atendidos na emergÃncia (89,2%). A mÃdia de idade dos pacientes positivos para o MPVh foi de 27 meses sendo significativamente superior que a das crianÃas infectadas pelo VSR (15 meses), adenovÃrus (14 meses) e vÃrus parainfluenza 3 (18 meses). Dentre os pacientes infectados pelo MPVh, 53,2% tiveram o diagnÃstico de infecÃÃes das vias aÃreas superiores e 46,7% tiveram o diagnÃstico de infecÃÃes das vias aÃreas inferiores. As infecÃÃes por MPVh apresentaram o mesmo espectro de infecÃÃes causadas pelos demais vÃrus pesquisados. O MPVh associou-se mais a casos de pneumonia que levaram à hospitalizaÃÃo das crianÃas infectadas do que outros vÃrus analisados. Mais da metade dos pacientes infectados pelo MPVh utilizaram o aerossol / salbutamol no seu tratamento (68,5%). A tÃcnica de IFI mostrou-se bastante eficaz como mÃtodo de diagnÃstico para a detecÃÃo do MPVh nesse estudo
The human metapneumovÃrus (hMPV) is a newly discovered virus that has been considered as one of the most common agents of acute respiratory infections (ARI) virus in childhood. The objectives of this study were: 1) to observe the frequency of infections caused by hMPV among children attending Hospital Infantil Albert Sabin, a major pediatric hospital in CearÃ, from January 2006 to December 2007; 2) to describe aspects of seasonality of these infections relating them to the occurrence of rain and the circulation of other respiratory viruses, 3) to describe the clinical and epidemiological characteristics of patients infected by hMPV, compared with positive and negative patients for other viruses; 4) to evaluate the IFI assay as a method of diagnosis for the detection of hMPV. Nasopharyngeal aspirates were collected from children with symptoms of ARI and submitted to indirect immunofluorescence assays for the detection of the following respiratory viruses: hMPV, respiratory syncytial virus (RSV), influenza A and B, adenovirus and parainfluenza 1, 2 and 3. During the 24 months of study, samples were collected from 1276 and respiratory viruses were demonstrated in 380 (29.78%) samples. The hMPV was the second most frequently detected respiratory viruses representing a total of 8.69% of all samples and 29% among the samples positive for the virus analyzed. It was not observed for hMPV a pattern of seasonality or correlation with the rainy season. Most patients positive for hMPV were attended in the emergence (89.2%). The mean age of patients infected by hMPV was 27 months, wich is significantly older than that for VSR (15 months), adenovirus (14 months) and parainfluenza virus 3 (18 months). Among patients infected by hMPV, 53.2% had a diagnosis of infections of the upper airways and 46.7% had a diagnosis of infections of the lower airways. The hMPV infections showed the same spectrum of infections caused by other viruses analyzed. The hMPV associated to more cases of pneumonia that led to the hospitalization of children infected than other viruses analyzed. More than half of these patients used the aerosol / salbutamol as conduct therapy (68.5%). The IFI assay proved to be quite effective as a method of diagnosis for the detection of hMPV in this study

Este estudo avaliou a incidência e distribuição de Candida spp. isoladas de casos de infecção hospitalar no período entre 2005 to 2007, em um hospital público infantil, em São Paulo. Brasil. As amostras foram isoladas de sangue, urina e outros materiais biológicos (36,6%, 37,12% e 26,52%, respectivamente). As análises micromorfológicas e bioquímicas revelaram que a distribuição por espécie foi 62,12% Candida albicans, 37,88% não-albicans. Uma maior incidência de amostras de C. albicans foi observada em casos de candidúria (53,62%) enquanto espécies não-albicans foram mais prevalentes em candidemia (71,43%) (p < 0.05). A respeito da produção enzimática, 68,94%, 47,73%, 65,91% e 66,67% foram positivas para proteínase, fosfolipase, lipase e hemolisina. Em relação aos antifúngicos, para Anfotericina B, 96,97% dos isolados mostraram e para 5- fluorcitosina foi observado o maior índice de resistência. Os fatores de risco identificados para candidemia hospitalar foram as doenças pré-existentes, terapia antibiótica de largo espectro e a presença de cateter venoso central.
This study evaluated the incidence and distribution of Candida spp. identified from cases of nosocomial infection in the period from 2005 to 2007, in a public children\'s hospital in São Paulo, Brazil. The strains were isolated from the blood, urine and other biological specimens (36,6%, 37,12% and 26,52%, respectively). Micromorphological and biochemical analyses revealed that the overall distribution by species was 62,12% Candida albicans, 37,88% non-albicans. A higher incidence of C. albicans strains was observed in cases of candiduria (53,62%) while non-albicans species were more prevalent in cases of candidemia (71,43%) (p < 0.05). Concernig the production of enzymes, 68,94%, 47,73%, 65,91% and 66,67% presented positive proteinase, phospholipase, lipase and hemolin activity. In relation to antifungal for the Amphotericin B, 96,97% of isolates showed sensitivity and for 5- fluorocytosine was observed the biggest index of resistence. The Risk factors identified for nosocomial candidemia was underlying disease, therapy with broad-spectrum antibiotics and the presence of a central venous catheter.

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The objective of the present study was to delineate the epidemiological profile of pregnant women diagnosed with HIV/aids, syphilis and hepatitis B and C, notified in 2015, in a tertiary care regional referral service. As specific objectives: to present the epidemiological profile of the pregnant women notified in 2015 to the group responsible for the Maternal and Child Care Line of the hospital where the research was carried out, and to prepare a newsletter aiming at helping the visibility of the data to list the priorities of the team's actions. This is a cross-sectional retrospective study performed at a reference hospital in the central region of Rio Grande do Sul. Data collection took place in November and December 2016 and January 2017, through consultation in the system and notification forms of the Nucleus of Hospital Epidemiological Surveillance. From the survey, 179 cases of STI were identified in pregnant women in the year 2015. The age of women ranged from 15 to 41 years. The provenance of the pregnant women showed that many are coming from small municipalities of the central region of Rio Grande do Sul, considering that this hospital is a reference for this region. The product resulting from this work consisted of two articles of a newsletter, widely distributed and disseminated in the service in which the research was developed. As benefits, after the collection and analysis of the data, the results obtained were presented to the service, which allowed the knowledge of the situational diagnosis that could guide the planning of surveillance actions, prevention and control of the vertical transmission of STIs in municipalities of the 4th CRS, since HUSM is a reference in the hospital service for the region.
O presente trabalho teve por objetivo geral delinear o perfil epidemiológico das gestantes com diagnóstico de HIV/aids, sífilis e hepatites B e C, notificadas no ano de 2015, em um serviço de referência regional de atenção terciária. Como objetivos específicos: apresentar o perfil epidemiológico das gestantes notificadas no ano de 2015 ao grupo condutor da Linha de Cuidado Materno Infantil do hospital onde desenvolveu-se a pesquisa, e elaborar boletim informativo visando auxiliar a visibilidade dos dados para elencar prioridades de ações da equipe. Trata-se de um estudo transversal retrospectivo realizado em hospital de referência da região central do Rio Grande do Sul. A coleta de dados ocorreu de novembro e dezembro de 2016 e janeiro de 2017, por meio de consulta no sistema e fichas de notificação do Núcleo de Vigilância Epidemiológica Hospitalar. Do levantamento realizado, foram identificados 179 casos de IST em gestantes no ano de 2015. A idade das mulheres variou de 15 a 41 anos. A procedência das gestantes evidenciou que muitas são advindas de municípios de pequeno porte da região central do Rio Grande do Sul, tendo em vista que este hospital é referência para esta região. O produto resultante deste trabalho constou de dois artigos e boletim informativo, amplamente distribuído e divulgado no serviço no qual desenvolveu-se a pesquisa. Como benefícios, após o término da coleta e análise dos dados, os resultados obtidos foram apresentados ao serviço, o que permitiu o conhecimento do diagnóstico situacional que poderá balizar o planejamento de ações de vigilância, prevenção e controle da transmissão vertical das ISTs, nos municípios da 4ª CRS, visto que o HUSM é referência no serviço hospitalar para a região.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
O vÃrus influenza à o Ãnico com a habilidade de causar epidemias anuais recorrentes em curto espaÃo de tempo, atingindo todas as faixas etÃrias, ocorrendo com maior gravidade em crianÃas e idosos. Este estudo teve como objetivo conhecer os aspectos demogrÃficos e o padrÃo de sazonalidade das infecÃÃes respiratÃrias agudas (IRAs) causadas pelo vÃrus influenza em crianÃas atendidas no Hospital Infantil Albert Sabin, na cidade de Fortaleza â CearÃ, no perÃodo de janeiro de 2001 a julho de 2004. Foram coletadas 1950 amostras de aspirado de nasofaringe de crianÃas com sintomas de infecÃÃo respiratÃria aguda. Todas as amostras foram analisadas por reaÃÃo de imunofluorescÃncia indireta. A reaÃÃo de em cadeia da polimerase com transcriÃÃo reversa foi utilizada em 47 amostras positivas por imunofluorescÃncia indireta dos anos de 2003 e 2004 para anÃlise da variantes virais (H1 e H3 ) e influenza B. Um total de 156 amostras foram positivas para os vÃrus influenza A ou B, representando uma prevalÃncia de 8%. Entre as infecÃÃes causadas por vÃrus, aquelas causadas pelos vÃrus influenza A e B representaram 24,1%. O vÃrus influenza apresentou um padrÃo de ocorrÃncia anual regular, com surtos epidÃmicos durante o primeiro semestre de cada ano, correlacionados aos perÃodos chuvosos. Os picos dos perÃodos epidÃmicos de influenza antecederam ou ocorreram concomitantemente Ãs campanhas nacionais de vacinaÃÃo. Os vÃrus influenza A e B co-circularam em todos os anos de estudo, havendo uma predominÃncia significativa do vÃrus influenza A (91%) em relaÃÃo ao vÃrus influenza B (9%). Em relaÃÃo ao setor de atendimento das crianÃas com infecÃÃes por vÃrus influenza observouse a maioria delas foi atendida em ambulatÃrios (48,7%) e emergÃncia (39,7%). Dezoito crianÃas infectadas pelo vÃrus influenza foram atendidas nas enfermarias (11,5%). Com relaÃÃo à idade das crianÃas com influenza observou-se que essas infecÃÃes predominaram em crianÃas atà dos dois anos de idade (55%). InfecÃÃes de vias aÃreas inferiores predominaram em crianÃas atà dois anos de idade. Cerca de 65,4% das infecÃÃes pelo vÃrus influenza foram diagnosticadas como infecÃÃes de vias aÃreas superiores. InfecÃÃes de vias aÃreas inferiores predominaram em crianÃas atà dois anos de idade (68,5%). Nos anos de 2003 e 2004 foram identificadas as variantes virais A/H3 e B do vÃrus influenza, com predominÃncia da primeira (78,7%)
The influenza virus is unique with it is ability to cause recurring annual epidemics in a short time interval, affecting all ages, with larger gravity in children and elderly people. The aim of this study is to describe demographic features and the pattern of the seasonality of acute respiratory infections caused by influenza virus in children attended at Albert Sabin Children Hospital, in Fortaleza â CearÃ, over the period of January period 2001 at July 2004. A total of 1950 samples of nasopharyngeal aspirates were collected from chidren with symptoms of acute respiratory infection. All samples were analyzed by indirect imunofluorescense assay (IFA). Forty seven Influenza A or B positive samples by IFA, in 2003 and 2004, were submitted to polimerase chain reaction with reverse transcription (RTPCR) for analysis of viral variant H1 and H3 and influenza b. A total of 156 samples were influenza A or influenza B positive, representing a prevalence rate of 8%. Among the viral infections, those caused by influenza viruses represented 24,1%. The influenza virus showed a pattern of regular annual occurrence, observed during the first semester of each year, correlated to the rainy periods. The peak of the epidemic periods of influenza preceded or occurred concomitantly to the national campaigns of vaccination. Influenza virus A and B cocirculated in all years of the study, with a significant predominance of the virus influenza A (91%) over influenza B (9%). Regarding to the medical care setting, the majority of the children with influenza infection were attended in ambulatories (48,7%) and emergency (39.7%). Eighteen children with influenza were attended in wards (11,5%). Regarding to the age of the children with influenza these infections predominated in children until two years of age. About 65,4% of the influenza infections were diagnosed as upper respiratory tract infections. Lower respiratory tract infection predominated in children until two years of age. In 2003 and 2004 were identified the variants A/H3 and B, with predominance of the first (78,7%)

Investigamos a ocorrência de espécies de leveduras isoladas em um hospital infantil. Pesquisamos a presença de C. dubliniensis; investigamos as espécies do complexo Candida parapsilosis e estudamos as espécies deste complexo quanto a produção de biofilme. Pesquisamos os fatores relacionados a virulência e o perfil de sensibilidade pelo método Etest®. Dentre os anos em estudo C. albicans foi a levedura mais isolada com 36.45% seguida de C. tropicalis 23.36%, C. parapsilosis sensu stricto 21.49%, Pichia anômala 5.61%, C. guilliermondii 4.67%, C. krusei 2.80%; C. orthopsilosis 1.87%, C. glabrata 1.87%, C. metapsilosis 0.94%, C. pararugosa 0.94%. C. dubliniensis não foi isolada nesta pesquisa. No estudo do complexo Candida parapsilosis, C. parapsilosis sensu estricto foi a espécie mais prevalente. Produziram biofilme apenas oito amostras de C. parapsilosis sensu estricto e uma amostra de C. orthopsilosis. As espécies não-albicans produziram mais proteinase e hialuronidase do que C. albicans. No estudo da fosfolipase e hemolisina, C. albicans foi a espécie mais produtora. Todas as amostras foram sensíveis para anfotericina B e para fluconazol quatro amostras foram resistentes. Duas amostras foram resistentes para caspofungina.
We investigated the occurrence of yeast species isolated in a public hospital. We researched the presence of C. dubliniensis and investigated the species within the complex Candida parapsilosis and studied this complex in relation to biofilm´s production. We also investigated the factors related to virulence and studied the sensibility profile by the \"Etest ®\" method. During the years of study, C. albicans was the most isolated yeast with 36.45% followed by C. tropicalis 23,36%, C. parapsilosis sensu stricto 21,49%, Pichia anomala 5,61%, C. guilliermondii 4.67%, C. krusei 2.80%, C. orthopsilosis 1.87%, C. glabrata 1.87%, C. metapsilosis 0.94%, C. pararugosa 0.94%. C. dubliniensis was not isolated in this study. In the study of Candida parapsilosis complex, C. parapsilosis sensu stricto was the most prevalent species. Only eight strains of C. parapsilosis sensu stricto and one strain of C. orthopsilosis produce biofilm. The non-albicans species showed greater activity of the proteinase and hyaluronidase than C. albicans. In the study of hemolysin and phospholipase, C. albicans was the most producer. All strains were susceptible to amphotericin B and to fluconazole four were resistant. For caspofungin, two strains were resistant.

Introdução: O Protocol Aids Clinical Trial Group (PACTG 076), publicado em 1994, demonstrou que a utilização da zidovudina (ZDV) reduzia a taxa de transmissão materno-infantil do HIV (TMI HIV) de 25% para 8,3%. Atualmente a terapia antirretroviral (TARV) combinada associada a uma série de medidas pode reduzir a taxa de TMI HIV para menos de 2%. Embora o Ministério da Saúde preconize a adoção destas medidas, a TMI HIV ainda permanece acima dos níveis desejados, principalmente em nosso meio. De acordo com levantamento da Vigilância Epidemiológica do Município de Porto Alegre, no ano de 2012 a taxa TMI HIV foi de 2,9%. Objetivo: Avaliar os fatores que interferem na TMI HIV em um Hospital Universitário do Município de Porto Alegre/RS. Método: Trata-se de um estudo de coorte histórico, tendo como amostra 292 bebês nascidos de mulheres portadoras do HIV, cujos nascimentos ocorreram no Centro Obstétrico de um Hospital Universitário do Município de Porto Alegre/RS, entre 1º de janeiro de 2010 a 31 de dezembro de 2014. Resultados: Dos 292 bebês, cujas mães eram portadoras do HIV, 3,8% (n=11) foram contaminados. Destes 90,9% (n=10) nasceram por cesariana; 90,9% (n=10) tinham d37 semanas; 54,6% (n=6) receberam ZDV xarope isoladamente e 45,4% (n=5) receberam ZDV + nevirapina (NVP). Quatro gestantes cujos bebês foram contaminados apresentaram sífilis na gestação (36,4%). A má adesão a TARV (p<0,003), a carga viral d1.000 cópias/mL ou ignorada no 3º trimestre (p<0,001) e o CD4 <500 células/mm3 (p<0,046) no terceiro trimestre foram significativamente associados a maior TMI HIV. Conclusão: Os fatores associados significativamente a TMI HIV foram à má adesão a TARV, a presença de sífilis na gestação, a carga viral d1000 cópias e o CD4 <500 células/mm³ no terceiro trimestre.
Introduction: Protocol Aids Clinical Trial Group (PACTG 076), published in 1994, demonstrated that the use of zidovudine (ZDV) had reduced the rate of mother-tochild transmission (MTCT) of HIV from 25% to 8.3%. Currently, a combined antiretroviral therapy (HAART) associated with a number of measures can reduce the rate of MTCT to less than 2%. Although the Ministry of Health recommends the adoption of these measures, the MTCT still remains above desired levels, especially in our center. According to a survey of Epidemiological Surveillance of Porto Alegre, in 2012 the rate of MTCT was 2.9%. Objective: To evaluate the factors that interfere with MTCT from HIV-positive women who gave birth in a University Hospital of Porto Alegre/RS. Method: A historical cohort study, with a sample 292 babies from HIV infected mother whose delivery occurred at Obstetric Center of the University Hospital of Porto Alegre/RS, at period of January 2010 till December 2014. Results: Of 292 babies of women HIV positive, 3.8% (n=11) were infected. Of those 90.9% (n=10) was born by cesarean section; 90.9% (n=10) had d37 weeks; 54.6% (n=6) received only ZDV syrup and 45.4% (n=5) received ZDV+nevirapine (NVP). Four pregnant women whose babies were infected, mother had syphilis during pregnancy (36.4%). Poor adherence to HAART (p<0.003), viral load d1000 copies/mL or ignored in the third trimester (p<0.001) and CD4 <500 cells/mm3 (p<0.046) in the third trimester were significantly associated with higher MTCT. Conclusion: We conclude that the presence of syphilis in pregnancy, viral load d1000 copies/mL or ignored in the third trimester, the CD4 <500 cells/mm³ in the third trimester, poor adherence to HAART were significant factors for MTCT.

Mestrado em Enfermagem, Área de especialização: Enfermagem em Saúde Infantil e Pediátrica
O presente relatório pretende dar a conhecer as aprendizagens e atividades desenvolvidas durante o Curso de Mestrado, particularmente em contexto de estágio no âmbito da aquisição e desenvolvimento de competências do Enfermeiro Especialista em Enfermagem de Saúde Infantil e Pediátrica e de mestre. A realização deste relatório permitiu-nos refletir sobre o percurso de aprendizagem e atividades realizadas, nomeadamente na área temática do projeto, inscrito na linha de investigação “necessidades em cuidados de Enfermagem em populações específicas”, que neste caso foram as crianças/jovens e famílias ao longo dos contextos de estágio. Desta forma, foram trabalhados temas diversos, como o desenvolvimento infantil, a enurese noturna, a higiene oral e a prevenção de doenças respiratórias, com intenção de desenvolver conhecimentos, aproveitar as oportunidades de aprendizagem e ressaltar a importância da maximização de saúde da criança, atendendo à finalidade de adequar toda a aprendizagem para ser aplicada em Timor-Leste.
The purpose of this report is to present the learning and activities developed during the Master's Course, particularly in the context of internship in the scope of acquisition and development of competences of the Nursing Specialist in Child and Pediatric Health Nursing and of master. The production of this report has enabled us to reflect on the journey of learning and activities, in particular in the thematic area of the project, inscribed in the line of research "needs nursing care in specific populations," which in this case were children / youth and families throughout the internship contexts. In this way, several themes, such as child development, nocturnal enuresis, oral hygiene and the prevention of respiratory diseases, were developed with the intention of developing knowledge, taking advantage of learning opportunities and highlighting the importance of health maximization the purpose of adjusting all learning to be applied in Timor-Leste.

This thesis looks at the social, political, and military effects of epidemic polio on America's war effort during World War II. The primary sources consulted include newspapers, military medical reports, photographs, memoirs, speeches, and archival collections. It looks at the effects of polio on the home front, more specifically how epidemics and the rising rates of polio were a detriment to the civilian war effort. It also focuses on the American military's preparation for and response to polio outbreaks among troops both at home and abroad. Finally, it discusses the experiences of the servicemen who contracted polio during the war. This work fills a major hole in the historiography of the disease and highlights the overlapping interests of the public, the medical community, and the military during a time of war.

Este relatório de estágio foi desenvolvido, no decorrer do Curso do Mestrado em Enfermagem em Associação na área de Especialização em Enfermagem de Saúde Infantil e Pediátrica, apresenta como objetivo primordial descrever e analisar a aquisição e desenvolvimento das competências comuns de Enfermeiro Especialista, competências de Enfermeiro Especialista em Enfermagem de Saúde Infantil e Pediátrica e competências de Mestre. Como título do presente relatório: “Prevenção de Infeção: Impacto na Criança e Jovem”, sendo articulado com o projeto desenvolvido ao longo dos estágios, tendo em conta a linha de investigação Segurança e Qualidade de Vida. Os enfermeiros apresentam um papel fulcral no sucesso da prevenção da infeção e o impacto que esta representa na criança / jovem e na sua família doente. Como futura enfermeira especialista em Enfermagem de Saúde Infantil e Pediátrica, os cuidados especializados a estas crianças que necessitam de cuidados especiais, devido a patologias já identificadas e com necessidades de um isolamento protetor específico, não criando um impacto negativo no modo da sua identificação. A escolha do tema surge com o interesse pessoal na área e com as necessidades identificadas diariamente na prática profissional. Após ser abordado com os enfermeiros orientadores, enfermeiros chefes e professor orientador, realçando a importância da realização deste projeto.
This internship report was developed during the Nursing Master Course in Association in the field of Specialization in Child and Pediatric Health Nursing, presents as primordial aim describe and analyze the acquisition and development of Specialized Nurse´s common abilities, abilities of Specialized Nurse in Child and Pediatric Nursing and Master´s abilities. As this report´s title “Infection prevention: Impact on children and young people”, being articulated with the project developed during the internships, in consideration of the research line Security and Quality of life. Nurses present a key role in the success of infection prevention and the impact that this represents in the child/ young person and their diseased family. As future specialist nurse in Child and Pediatric Health Nursing, the specialized care to these children that need special care, due to pathologies already identified and with needs of a specific protective isolation, not creating a negative impact on the way of their identification. The choice of theme arises with the personal interest in the area and with the needs daily identified on the professional practice. After being discussed with the guiding nurses, head nurses and guiding professor, lighting up the importance of this project´s realization.

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Co-infection Leishmania-HIV/Aids is a serious public health problem in almost of the world. The visceral leishmaniasis is the clinical form of leishmaniosis hat is most associated with HIV/Aids cases being the co-infection understated, since the leishmaniasis is not AIDS-defining illness. This was a descriptive cross sectional study from March 2006 to December 2008, aiming to investigate the occurrence of co-infection Leishmania-HIV in individuals living with HIV/Aids in a Reference Center in São Luís-MA. The population studied was composed of 287 individuals. It was used a questionnaire to collect demographic, epidemiological and socioeconomic data. The physical examination was performed and biological material for detection of infection by Leishmania chagasi was collected by indirect immunofluorescence technique (IIFT), and laboratory tests (blood count, CD4 and CD8, viral load, myelography) were found in charts. We used the chi-square test to assess association of demographic, socioeconomic and epidemiological variables between women and men, whereas p ≥ 0.05 for significance. Women and men had a statistically significant difference in color, destination of waste, occupation and family income. The presence of pen and near the residence showed statistically significant differences when comparing men and women. The prevalence of infection with Leishmania sp, detected by Montenegro Skin Test (MST) was 1,4%. All co-infected showed RIFI and as well as the bone marrow aspirate (myelogram) positives. This study helped identify the magnitude of the prevalence of co-infection Leishmania/HIV. Thus, we suggest that the anti-Leishmania has to be part of the differential diagnosis of individuals with HIV / AIDS and those public policies are increased for this problem.
A co-infecção Leishmania-HIV/Aids é um sério problema de saúde pública em quase todo o mundo. A Leishmaniose Visceral é a forma clínica das leishmanioses que está mais associada ao HIV/Aids, sendo os casos de co-infecção considerados subestimados, uma vez que, a leishmaniose não se constitui doença definidora de Aids. Foi realizado um estudo descritivo transversal de março de 2006 a dezembro de 2008, com o objetivo de investigar a ocorrência de co-infecção Leishmania-HIV em indivíduos convivendo com HIV/Aids, atendidas em um Centro de Referência em São Luís-MA. A população do estudo foi constituída por 287 indivíduos. A coleta de dados foi feita por meio de um questionário para a obtenção de dados demográficos, socioeconômicos e epidemiológicos, bem como foi realizado exame físico e coleta de material biológico para detecção da infecção por Leishmania sp , por meio da Intradermorreação de Montenegro (IDRM), Reação de Imunofluorescência Indireta (RIFI) e os exames laboratoriais (hemograma, contagem de CD4 e CD8, carga viral, mielograma) foram consultados nos prontuários. Através do teste qui-quadrado foi avaliado as variáveis demográficos, socioeconômicas e epidemiológicas entre mulheres e homens convivendo com HIV/Aids, considerando p ≥ 0,05 de significância. Houve diferença estatística significante na cor da pele, no destino dos dejetos, na ocupação e na renda familiar; como também na presença de chiqueiro em local próximo à residência. A prevalência da infecção por Leishmania sp detectada pela Intradermorreação de Montenegro (IDRM) foi de 1,4% e a prevalência da co-infecção Leishmania-HIV/Aids foi de 4,2%. Todos os co-infectados apresentaram RIFI e o aspirado de medula óssea (mielograma) positivos. Este estudo permitiu conhecer a magnitude da prevalência da co-infecção Leishmania/HIV. Assim, sugerimos que o teste anti-Leishmania seja realizado em todos os indivíduos com HIV/Aids, e que sejam incrementadas políticas públicas voltadas para essa problemática.

Objetivou-se, com o presente estudo, verificar a ocorrência de Cryptosporidium spp entre crianças do município de Taubaté-SP e realizar a genotipagem de isolados clínicos do parasito. Foram selecionadas 13 creches municipais, que atendiam crianças de 4 a 72 meses de idade, realizando-se implantação de um programa para busca ativa de casos de diarréia, com acompanhamento da população durante o ano de 2002. Para se conhecer o perfil coproparasitológico, realizou-se estudo transversal em quatro das 13 creches selecionadas. Foram examinadas 483 amostras fecais processadas pelo método de concentração em formalina-acetato de etila e, para a visualização de oocistos, esfregaços fecais foram corados pelo método de Kinyoun. No estudo prospectivo, Cryptosporidium spp foi encontrado em 11,1 % (3/27) das amostras, não se evidenciando outras espécies parasitárias. No estudo transversal, foram detectados oocistos em 0,2% (1/456) das amostras e a freqüência para outras espécies parasitárias foi de 30,5% (139/456). No estudo de genotipagem, foram analisadas 14 amostras de humanos, uma de bovino e uma de cão. Dentre os isolados de humanos, quatro eram de crianças de Taubaté-SP, cinco de crianças de uma favela de São Paulo-SP e cinco de pacientes HIV positivos, de Sorocaba-SP. O DNA extraído a partir das amostras fecais foi submetido a Nested-PCR, amplificando-se um segmento de 553pb de um gene que codifica proteína de parede de Cryptosporidium (COWP). Os produtos amplificados foram submetidos a processo de digestão enzimática (RPLP-PCR), e os perfis obtidos por eletroforese evidenciaram três espécies: Cryptosporidium hominis em oito amostras, Cryptosporidium parvum em quatro e Cryptosporidium meleagridis em duas. Dos isolados de Taubaté, dois foram correspondentes a C. hominis e dois a C. parvum. As amostras de bovino e de cão foram positivas para C. parvum. O genótipo dos isolados de Taubaté, humanos e de animais, foram confirmados por análise da sequência do fragmento de 553pb do gene COWP, comparando-se com as sequências disponíveis no GenBank.
The aims of this study were to investigate the occurrence of infection by Cryptosporidium spp in children living in Taubaté, São Paulo, Brazil, and to realize the molecular characterization of the parasite isolates. Thirteen day-care centers were selected and 4-72 months old children were involved in prospective study to detect diarrhea, during the 2002 year. In four of these day-care centers, a transversal study was performed in the beginning of the study to know the prevalence of intestinal parasites of children\'s community. A total of 483 stool samples were examined by the modified formalin-etil acetate concentration method, and the acid-fast Kinyoun stain was used to visualize oocysts. In the prospective study Cryptosporidium spp were detect in 11.1 % (3/27) of stool samples and no other parasites were found. In the transversal study oocysts were detected in 0.2% (1/456) of the samples and the frequency of infection by other parasites was 30.5% (139/456). In the genotyping study, 14 stool samples from humans and one sample from bovine and another from dog were analyzed. Among the human isolates, four were from children of Taubaté, five were from children living in a slum of São Paulo city and the other five from HIV-positive patients of Sorocaba, São Paulo. The animal samples were collected in Taubaté region. A DNA fragment of 553 pb of the Cryptosporidium oocyst wall protein (COWP) gene was amplified from stool samples by Nested-PCR, and Restriction Fragment Length Polymorphism analysis identified three species: Cryptosporidium hominis in eight samples, Cryptosporidium parvum in four samples and Cryptosporidium meleagridis in two samples. Among samples from Taubaté, two were positive for C. hominis and two for C. parvum. The bovine and dog samples were positive for C. parvum. The findings trom Taubaté were confirmed by sequence analysis of the 553bp amplicons and comparison of the COWP gene available in the GenBank.

Enquadramento Em lactentes de países de baixo e médio rendimento, Giardia lamblia, Cryptosporidium e Entamoeba hystolitica são agentes prevalentes em infeções intestinais. As interações hospedeiro-parasita podem levar a uma resposta inflamatória da mucosa e aumento da permeabilidade intestinal. Clinicamente, isto pode refletir-se por impacto negativo no crescimento e neurodesenvolvimento. Os efeitos destas infeções intestinais subclínicas na saúde infantil têm sido pouco estudado. Objetivo Analisar, em crianças assintomáticas de São Tomé, as associações entre infeções por parasitas intestinais e a função da barreira intestinal, o estado nutricional e o neurodesenvolvimento. Métodos Foi realizado um estudo coorte de nascimento com seguimento até aos 24 meses de idade. A antropometria foi avaliada mensalmente e incluiu o crescimento atingido (zscores para peso/comprimento, comprimento/idade – CIzs e diferença do comprimento-para-idade – DCI), a velocidade do crescimento (z-scores para velocidade ponderal – VPzs e linear – VLzs) e o risco de desnutrição (aguda e crónica, definida como <-1DP). O neurodesenvolvimento foi rastreado em idades-chave usando o “Bayley Infant Neurodevelopmental Screening”. Os biomarcadores fecais para inflamação (S100A12) e permeabilidade intestinais (alfa-1-antitripsina - A1AT) foram medidos aos 24 meses. A presença de protozoários e helmintas intestinais foi avaliada trimestralmente por técnicas microscópicas Foram usados diferentes modelos estatísticos para estudar associações entre infecções por parasitas intestinais e os resultados das avaliações da função da barreira intestinal, estado nutricional e neurodesenvolvimento. Resultados Foram incluídos 475 recém-nascidos, representado 8,6% dos nados-vivos em São Tomé; 280 (58,9%) completaram os 24 meses de seguimento. Giardia lamblia e helmintas foram os parasitas mais prevalentes. A análise multivariável revelou que: 1) lactentes infetados com Giardia lamblia e helmintas tiveram tendência para aumento de 23,6% e 24,1% no marcador de inflamação intestinal, respectivamente; os infetados por qualquer parasita tiveram tendência para aumento de 33,6% no marcador de permeabilidade; além disso, os níveis de A1AT foram 100% superiores em lactentes com desnutrição aguda e 50% superiores nos com desnutrição crónica; 2) lactentes infetados com Giardia lamblia e helmintas tiveram associação significativa com diminuição no crescimento linear (-0,10 e -0,16 CIzs; e -0,32 e -0,48 de DCI, respectivamente); os infetados com Cryptosporidium spp. tiveram associação significativa com diminuição na velocidade de crescimento ponderal e linear (-0,43 VPzs e -0,55 VLzs); 3) a infecção por Giardia lamblia e a desnutrição crónica associaram-se independentemente e significativamente com 1,69 e 2,37 maior probabilidade de atraso no desenvolvimento, respectivamente. Conclusões Este é o primeiro estudo de coorte de nascimento em São Tomé, pioneiro em estudar associações entre infeções por parasitas intestinais e a função da barreira intestinal, estado nutricional e neurodesenvolvimento. Foi confirmado o papel subestimado dos protozoários e helmintas como agentes etiológicos de infecções intestinais subclínicas. Estas infecções revelaram uma tendência para associação com a disfunção da barreira intestinal e associações significativas com restrição do crescimento linear e neurodesenvolvimento. Estas associações são problemáticas em São Tomé, endémico para Giardia lamblia e helmintas, em contexto de proporção não negligenciável de lactentes marginalmente desnutridos. Estes poderão ter capacidade limitada para reparar lesões da mucosa, com impacto negativo no crescimento e neurodesenvolvimento, ficando comprometido o atingimento do seu pleno potencial.
Background Giardia lamblia, Cryptosporidium and Entamoeba hystolitica are prevalent etiologic agents of enteric infections in infants from low- and middle-income countries. Hostparasite interactions may lead to mucosal inflammatory response and increased intestinal permeability. Clinically this can result in a negative impact on growth and neurodevelopment. The effects of these subclinical enteric protozoa infections on infant health are poorly explored. Aim To analyze the associations between enteric parasitic infections and intestinal barrier function, nutritional status and neurodevelopment in asymptomatic infants in São Tomé. Methods A birth cohort study with a follow-up until 24 months of age was implemented. Anthropometry was assessed monthly and included attained growth (weight-for-length z-score, length-for-age z-score – LAZ, and length-for-age difference – LAD), growth velocity (weight velocity z-score – WAVZ, and length velocity z-score – LAVZ), and risk for undernutrition (wasting and stunting, using the <-1SD cut-off). Neurodevelopment was screened at key ages using the “Bayley Infant Neurodevelopmental Screening” score. Fecal biomarkers for intestinal inflammation (S100A12) and permeability (alpha 1 anti-trypsin - A1AT) were measured at 24 months of age. Enteric protozoa and intestinal helminths were examined quarterly in stool samples using microscopic techniques. Different statistical models were used to explore associations between enteric parasitic infections and the three outcomes: intestinal barrier function, nutritional status, and neurodevelopment. Results A total of 475 neonates were enrolled, representing 8.6% of live-births in São Tomé; 280 (58.9%) infants completed 24 months of follow-up. Giardia lamblia and helminths were the most prevalent parasites. The multivariable analysis showed that: 1) infants with Giardia lamblia and helminths infections had a tendency toward an increase of 23.6 % and of 24.1 % in the inflammatory biomarker, respectively; those infected by any enteric parasite had a tendency toward an increase of 33.6% in the permeability biomarker; additionally, this biomarker was 100% higher in wasted infants and 50% higher in those stunted; 2) infants with Giardia lamblia and helminths infections showed a significant association with a decrease in linear growth (by - 0.10 and -0.16 of LAZ and by -0.32 and -0,48 of LAD, respectively); those with Cryptosporidium spp. infection displayed a significant association with a decrease in weight and length velocities (-0.43 WAVZ and -0.55 LAVZ); 3) Giardia lamblia infection and stunting were independently and significantly associated with a 1.69 and 2.37 increased risk of poor development, respectively. Conclusions This first birth cohort ever performed study in São Tomé is innovative in exploring associations between enteric parasitic infections and the intestinal barrier function, nutritional status and neurodevelopment in infants. The underestimated role of protozoa and helminths as etiologic agents of subclinical enteric infections was confirmed. These parasitic infections showed a tendency of association with intestinal barrier dysfunction and significant associations with decreased linear growth and risk of poor neurodevelopment. In the context of São Tomé, an endemic area for Giardia lamblia and helminths with a non-negligible proportion of marginally undernourished infants such associations are problematic. Affected infants may have a limited capacity to repair mucosal damage, with a negative impact on growth and neurodevelopment, thus jeopardizing the achievement of their full potential.

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Para avaliar fatores de risco para hospitalizações por infecções respiratórias agudas (IRA), desenvolveu-se um estudo caso-controle com crianças de 4 a 24 meses de idade hospitalizadas devido a estas infecções, de julho de 2008 a julho de 2011, em instituições públicas/SUS de seis municípios brasileiros. Um grupo controle formado por crianças da mesma faixa etária hospitalizadas por doença não infecciosa e outro constituído por crianças que desde o nascimento tiveram, no máximo, apenas uma hospitalização por doenças respiratórias. Banco de Dados de um estudo sobre efetividade da vacina contra rotavírus, IBGE e Ministério da Saúde foram as fontes de dados. Variáveis individuais (relativas à mãe e à criança) e contextuais foram os fatores de risco examinados. As análises foram realizadas mediante Regressão Logística, assumindo p<0,05. Baixo peso ao nascer (OR=2,0), número total de internações desde o nascimento (OR=1,3), número de internações por doenças do aparelho respiratório (OR=3,2) e uso de cigarro na gestação (OR=1,5) mostraram-se associadas com o desfecho, na análise bivariada. Na análise estratificada, os grupos de municípios apresentaram-se como modificador de efeito para peso ao nascer, número de internações e fumo na gestação. A análise multinível indicou correlação linear entre as variáveis, as variáveis contextuais Índice de Gini<0,46 e temperatura média anual < 24 graus Celsius, mostraram-se associadas ao desfecho. Esses achados revelam a necessidade de investimentos sociais, tais como redução da desigualdade de renda e melhoria da qualidade da assistência prestada à gestante e à criança de modo a contribuir para reduzir as internações por IRA em crianças.
Salvador

Made available in DSpace on 2016-08-19T18:15:58Z (GMT). No. of bitstreams: 1 MARIA NEUSA SOUSA CAVALCANTE.pdf: 559402 bytes, checksum: 722392cbe89c47e945c68e6b760c003b (MD5) Previous issue date: 2009-09-25
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Visceral Leishmaniasis is a zoonosis that attacks man in an accidental way and in the present decade presents itself in a wide geographic expansion, attacking urban and peri-urban spaces of large Brazilian cities. The precarious social/economic and environmental conditions, as well as life habits are relevant to the epidemiology of the disease and seem to favor the maintaining of the transmission cycle. A Cohort study was accomplished during the period of August 2006 to January 2008, with the objective of investigating the occurrence of non-symptomatic infection by Leishmania chagas in humans in the villages of Maresia, Pantoja and Marisol in the municipal area of Raposa, MA. The study was delineated in three phases: in the first phase, a population census was taken; in the second phase, demographic, social/economic and epidemiologic data was collected using a questionnaire, as well as a physical examination and tests to detect the infection by Leishmania chagasi in 1371 individuals by the immune enzymatic test (ELISA), and in 1356 individuals by the Montenegro skin test (IDRM); and in the third phase, the physical exam as well as the ELISA test was performed on 958 individuals. In the statistical analysis of the risk factors, a logistic regression and Poisson test in the Stata 9.0 program was used, having a significant level p<0,05 (95%). The initial and final prevalence and the incidence of infection by Leishmania chagasi by means of the ELISA test was 19,8%, 16,6% and 8,4% respectively, and the prevalence by means of the IDRM test was 82%. The following variables were found to be associated with the incidence of infection by Leishmania chagasi by the ELISA test: over 15 years of age (p<0,001) and the presence of more than 4 dwellers in a residence (p=0,039); and association with the prevalence of infection by Leishmania chagasi by the IDRM test were: over 15 years of age (p=0,003), straw or adobe walls (p=0,0014), a poultry-gard present (p=0,004) and reference to mosquito-breeders in the peridomiciliar (p=0,026). The high prevalence detected by the IDRM in the localities studied indicates a large exposure of the dwellers to the vetor of LV, and the incidence detected by the ELISA demonstrates the vulnerability of the individuals to the risk of contracting the disease.
A leishmaniose visceral é uma zoonose que acomete o homem de forma acidental e apresenta-se em franca expansão geográfica com o acometimento de espaços urbanos e periurbanos de grandes cidades brasileiras. As precárias condições socioeconômicas, ambientais e hábitos de vida são relevantes na epidemiologia da doença e parecem favorecer a manutenção do ciclo de transmissão. Realizou-se um estudo de coorte, no período de agosto de 2006 a janeiro de 2008, com objetivo de investigar a ocorrência de infecção assintomática por Leishmania chagasi em humanos nas Vilas Maresia, Pantoja e Marisol no município de Raposa-MA. O estudo foi delineado em três fases: na primeira fase, realizado o censo populacional; na segunda fase, coleta dos dados demográficos, socioeconômicos, epidemiológicos utilizando um questionário, como também a realização do exame físico e de testes para detecção da infecção por Leishmania chagasi em 1371 indivíduos pelo método de Ensaio imunoenzimático (ELISA) e, em 1356 indivíduos pela Intradermorreação de Montenegro (IDRM); na terceira fase, realização em 958 indivíduos o exame físico bem como o teste de ELISA. Na análise estatística dos fatores de risco, utilizou-se a regressão logística e o teste Poisson no programa Stata 9.0, e, com nível de significância p<0,05 (95%). A prevalência inicial e final, e a incidência da infecção por L.chagasi por meio do teste ELISA foram de 19,8%, 16,6% e 8,4% respectivamente, e a prevalência por meio do teste IDRM de 82%. Encontrou-se associação com a incidência da infecção por L.chagasi pelo teste ELISA as seguintes variáveis: idade acima de 15 anos (p<0,001) e a presença de mais de 4 moradores na residência (p=0,039); e associação com a prevalência de infecção por L.chagasi pelo teste IDRM foram: idade maior que 15 anos (p=0,003), parede de palha/taipa ou adobe (p=0,0014), presença de galinheiro (p=0,004) e referência a criadouros do mosquito no peridomicílio (p=0,026). A alta prevalência detectada pelo IDRM nas localidades estudadas indica a grande exposição dos moradores ao vetor da LV, e a incidência detectada pelo ELISA demonstra a vulnerabilidade dos indivíduos ao risco de contrair a doença.

Made available in DSpace on 2016-08-19T18:15:58Z (GMT). No. of bitstreams: 1 ELIONORA DE JESUS CARNEIRO JANSEN DE MELLO.pdf: 1110156 bytes, checksum: 21ebd7627a73f6cf7dc192f934be47e1 (MD5) Previous issue date: 2009-11-18
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
The human papillomavirus (HPV) is the agent of most common sexually transmitted infection in adolescence worldwide. The cervical cancer, related to this infection, is the leading cause of death in Maranhão. The biomolecular diagnosis used to HPV detection is the polymerase chain reaction (PCR). It is proposed to investigate the frequency of the HPV genotypes in high school students from a public school in Sao Luis by different diagnostic methods. We conducted a cross-sectional study, descriptive at adolescents in high school, totaling 39 female students aged 15 to 19 years in the period July 2008 to June 2009. A questionnaire covering socio-demographic and sexual behavior was used. It was carried out cytopathology, colposcopy, cervical biopsy and genotyping by Nested PCR in each sample. The inclusion criteria were presence of sexual activity and we excluded women who had no sexual activity, those with positivity for HIV and pregnant. The data were transferred to a spreadsheet in the software Excel 2007 and evaluated using Epi-Info 6.04. The socio-demographic data showed that most female adolescents studied was 15 to 17 years old, they lived in urban area and they were full-time students, they were white and had schooling from 12 to 14 years. In 25 (64.1%) adolescents, the first sexual intercourse occurred before age 16 (p = 0.240), half said to have among one and four sexual intercourses per week (p = 0.082), one partner (51.3%), and two to three partners (38.5%), 82% reported ever having had STDs (p = 0.704). Three reported abortion (p = 0.463). One reported having given birth to 17 years. As for gynecologic complaints, the main were leukorrhea (79.5%, p = 0.016) and pruritus (23.1%, p = 0.928). Eight (20.5%) reported family history of cancer. At colposcopy, there were no vulvar or vaginal lesions and we diagnosed minor injury in seven adolescents (17.0%). The Pap smear result showed inflammation in 37 (94.9%) and LSIL / HPV in a test. Histopathology was performed in 15 students (38.5%), and seven had changes suggestive of HPV. Genotyping was positive in 29 students (74.3%), predominantly to 14 high-risk genotypes in 21 (72.4%) adolescents, namely: 16, 18, 31, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 82, distributed in multiple coexisting and simple infections. In assessing the accuracy of Nested PCR, positive predictive value was 85.7% (true positives), and negative predictive value was 12.5% (true negatives), Nested PCR provides useful diagnostic information to the study of human papillomavirus, as multiple and simple infections diagnosis.
O papilomavírus humano (HPV) é o agente da infecção sexualmente transmissível mais comum na adolescência em âmbito mundial. O câncer do colo do útero, relacionado a esta infecção, é a principal causa de morte no Maranhão. O diagnóstico biomolecular usado é a reação em cadeia de polimerase (PCR) para detecção do HPV. Propõe-se investigar a frequência dos genótipos de HPV em adolescentes do ensino médio de uma escola pública de São Luís-MA, por diferentes métodos diagnósticos. Realizou-se um estudo transversal, descritivo, em adolescentes, cursando o ensino médio, totalizando 39 alunas com idade entre 15 a 19 anos no período julho de 2008 a junho de 2009. Utilizou-se questionário abordando variáveis sócio-demográficas e comportamento sexual. Realizou-se citopatologia, colposcopia, colpobiópsia e genotipagem por PCR-Nested em toda amostra. O critério de inclusão compreendeu presença de atividade sexual e os de não inclusão foram mulheres que não tiveram atividade sexual, positividade para HIV e gravidez. Os dados foram avaliados e transferidos para uma planilha no software Excel 2007 e Epi-Info 6.04. Os dados sóciodemográficos mostraram que a maioria das adolescentes estudadas tinha de 15 a 17 anos, era de procedência urbana e estudantes em tempo integral, cor branca e escolaridade entre 12 e 14 anos. Em 25 (64,1%) adolescentes, a sexarca ocorreu antes dos 16 anos (p=0,240), a metade disse ter de uma a quatro relações sexuais semanais (p=0,082); um parceiro (51,3%), e dois a três parceiros (38,5%); 82% disseram nunca ter tido DST (p=0,704). Três relataram abortamento (p=0,463). Uma informou parto aos 17 anos. Quanto às queixas ginecológicas, as principais foram leucorréia (79,5%; p=0,016) e prurido (23,1%; p=0,928). Oito (20,5%) relataram antecedentes de câncer familiar. À colposcopia, nenhuma apresentou lesões vulvares ou vaginais, tendo sido diagnosticado lesão menor em sete adolescentes (17,0%). O exame citopatológico apresentou resultado inflamatório em 37 (94,9%) e LSIL/HPV em um exame. A histopatologia foi realizada em 15 alunas (38,5%), sendo que sete apresentaram alterações sugestivas de HPV. A genotipagem foi positiva em 29 alunas (74,3%), com predomínio para 14 genótipos de alto risco em 21 (72,4%) adolescentes, sendo eles: 16, 18, 31, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 82, distribuídos em infecções múltiplas coexistentes e simples. Na avaliação da acurácia por PCR - Nestad o valor preditivo positivo foi de 85,7% (verdadeiros positivos), e o valor preditivo negativo foi de 12,5% (verdadeiros negativos), técnica que fornece informações diagnósticas úteis ao estudo do papilomavírus como infecção múltipla e simples.

Introduction: At the end of 2015, zika virus became the protagonist of an epidemic of congenital anomalies never observed. The northeastern region of Brazil was the most affected. Congenital Zika Syndrome is characterized by severe microcephaly, critical brain damage, ophthalmologic, auditory, cardiac and orthopedic anomalies, as well as severe developmental delay with irritability, spasticity and convulsions. Owning to the fact that it is a new pathology, little is known about its long-term evolution, since affected children are aged around 3 years. Goal: To follow-up of a cohort of infants born with microcephaly and / or anomalies associated with congenital zika virus infection, from birth to 18 months of age, evaluating their growth, development, feeding and occurrence of associated morbidities. Methodology: This was a longitudinal, observational and descriptive study of a cohort of infants born in Sergipe during the outbreak of microcephaly and referred to two public health services. The children were followed up through 18 months of age in childcare consultations, together with expert evaluations and complementary examinations. The data was collected from August / 2017 to January / 2018 with using a research form. Statistical analyzes were carried out in R Core Team 2018 software. Results: The cohort comprised 84 children with Congenital Zika Syndrome. There was a predominance of females (53.8%) and only 9 newborns had no diagnosis of microcephaly but had other alterations compatible with Congenital Zika Syndrome. The Z scores for head circumference, weight and length remained stable over time, remaining below the expected standard for the three anthropometric indexes. The evolution of Z scores for weight / length showed a downward trend, although the average remained in the eutrophic pattern. In addition to the occurrence of other neurological impairments, such as seizures (69%), spasticity (48,8%), and irritability (64,3%), the infants presented severe developmental delays with delayed acquisition of all markers. The prevalence of exclusive breastfeeding until 6 months was law (14.3%) and a significant percentage of feeding difficulty (57,1%). This aspect reflected the delay in the introduction of complementary feeding (mean age of 7.1 months) and non-progression to the family diet in 22.6%. As to the complementary evaluation, cerebral malformations compatible with congenital Zika infection were detected in all children, ocular involvement was diagnosed in 42 infants (54.5%), and in half (50.7%) cardiac anomalies were observed. The main clinical morbidity observed was upper airways infection, followed by intestinal constipation. Conclusions: Infants with Congenital Zika Syndrome exhibited anthropometric growth impairment, as well as a severe delay in the acquisition of neuromotor development markers. It was found low prevalence of exclusive breastfeeding until 6 months, with a high frequency of feeding difficulties. There was also a significant number of infants who presented irritability, convulsion and spasticity. This study reinforces the need for specialized multiprofessional follow-up aimed at rehabilitation therapies and support to the family members involved.
Introdução: Ao final de 2015, o Zika vírus tornou-se protagonista de uma epidemia de anomalias congênitas jamais observada, sendo a região nordeste do Brasil a mais atingida. A Síndrome da Zika Congênita caracteriza-se por microcefalia com grave dano ao tecido cerebral, alterações oftalmológicas, auditivas, cardíacas e ortopédicas, além de crítico atraso do desenvolvimento, com irritabilidade, espasticidade e convulsões. Tratando-se de nova condição clínica, pouco se sabe sobre sua evolução em longo prazo, uma vez que as crianças acometidas estão com média de 3 anos de idade. Objetivo: Realizar o acompanhamento de uma coorte de bebês com Síndrome da Zika Congênita, do nascimento aos 18 meses de vida, avaliando seu crescimento, desenvolvimento, evolução da alimentação e ocorrência de morbidades. Metodologia: Trata-se de estudo longitudinal, observacional e descritivo do acompanhamento de uma coorte de lactentes nascidos em Sergipe durante o surto de microcefalia e referenciados para dois serviços públicos de saúde. As crianças foram avaliadas até os 18 meses de vida em consultas de puericultura somadas a interconsultas com especialistas e realização de exames complementares. Os dados foram coletados de agosto/2017 a janeiro/2018 através de um formulário de pesquisa. As análises estatísticas foram realizadas com o auxílio do software R Core 2018. Resultados: Compuseram a coorte 84 crianças com características clínicas da Síndrome da Zika Congênita. Houve predomínio do sexo feminino (53,8%) e somente 9 recém-nascidos não tiveram diagnóstico de microcefalia, mas apresentavam outras alterações compatíveis com a Síndrome da Zika Congênita. Os escores Z para perímetro cefálico (PC), peso e comprimento apresentaram pouca variação ao longo do tempo. As médias de escore Z na primeira e última consulta foram as seguintes: PC (-6,0; -5,9); Peso (-1,9; -1,6) e Comprimento (-2,5; -1,7). A evolução dos escores Z para peso/comprimento, revelou tendência de queda, apesar da média ter se mantido no padrão de eutrofia. As crianças manifestaram grave atraso do desenvolvimento com retardo na aquisição de todos os marcos pesquisados, além da ocorrência de outros comprometimentos neurológicos tais quais convulsão (69%), espasticidade (48,8%) e irritabilidade (64,3%). Encontrou-se baixa prevalência de aleitamento materno exclusivo até os 6 meses (14,3%) e percentual significativo de relatos de dificuldade alimentar (57,1%), aspecto que refletiu no atraso da introdução da alimentação complementar (idade média de 7,1 meses) e na não progressão para a alimentação da família em 22,6%. Quanto aos exames e avaliações complementares, em todos os lactentes foram detectadas malformações cerebrais compatíveis com a infecção congênita pelo Zika vírus, em 54,5% foi diagnosticado comprometimento ocular e em metade (50,7%) foi observado alguma alteração cardíaca. A principal morbidade clínica apresentada pelas crianças foram as infecções das vias aéreas superiores, seguido de constipação intestinal. Conclusões: Os lactentes com Síndrome da Zika Congênita exibiram comprometimento do crescimento antropométrico, além de grave atraso na aquisição de marcos do desenvolvimento neuromotor. Constatou-se baixa prevalência de aleitamento materno exclusivo até os 6 meses, com alta frequência de dificuldades alimentares. Observou-se também número significativo de lactentes que evoluíram com irritabilidade, convulsão e espasticidade. Os achados deste estudo reforçam a necessidade de acompanhamento multiprofissional especializado para estas crianças, voltado para terapias de reabilitação e apoio aos familiares envolvidos.
Aracaju

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
Estudo de prevalÃncia (estudo transversal) sobre infecÃÃo por HPV em colo uterino de gestantes, avaliando o(s) subgrupo(s) de HPV mais prevalentes e a associaÃÃo quanto ao desenvolvimento de lesÃes intraepiteliais escamosas. A metodologia constituiu-se de questionÃrio aplicado diretamente a 272 gestantes, independente da idade gestacional e de estarem sintomÃticas ou nÃo na primeira consulta de prÃ-natal, alÃm da coleta de material cÃrvico-vaginal (paredes vaginais, ectocÃrvice e endocÃrvice) para realizaÃÃo de Citologia oncÃtica convencional pelo mÃtodo de coloraÃÃo proposto por Papanicolaou e do teste de Captura HÃbrida IIÂ. Procedeu-se a seguir a identificaÃÃo das lesÃes intraepiteliais escamosas e da presenÃa do vÃrus HPV de alto, baixo e mÃdio risco oncogÃnico. Os achados da Captura HÃbrida IIÂ foram correlacionados com os achados citolÃgicos, comparando-se a freqÃÃncia dos resultados anormais nos dois mÃtodos. Procedeu-se tambÃm a associaÃÃo com aspectos biossociais que pudessem interferir na infecÃÃo produzida pelo HPV e no possÃvel desenvolvimento de lesÃes intraepiteliais escamosas. Realizaram-se anÃlises de correlaÃÃo univariada e bivariada, com cÃlculo do Qui-quadrado de Pearson e valor p< 0,05. Utilizou-se tambÃm de regressÃo logÃstica para estimar a magnitude das associaÃÃes. A prevalÃncia de infecÃÃo por HPV e citologias oncÃticas anormais foi de 32,3% e 14,0 % respectivamente. Os subgrupos de HPV de alto risco foram mais prevalentes (27,6%) do que os de baixo e mÃdio risco (18,4%) e a sua associaÃÃo mostrou-se estatisticamente significativa (p<0,05). A associaÃÃo da infecÃÃo genital por HPV de alto risco com lesÃes intraepiteliais escamosas descritas na Citologia oncÃtica convencional foi mais prevalente (8,5%) do que com HPV de baixo de mÃdio risco (5,6%) e teve significÃncia estatÃstica (p<0,05)
This work studies the prevalence (cross sectional) on infection by HPV in uterine cervical of pregnant women evaluating the subgroups of HPV more prevalents and the association in relation to the development of squamous intraepithelial lesions. The methodology was constituted of questionary applied to 272 pregnant women independent of pregnant age and of being symptomatic or not in the first medical advice of prenatal besides the collect of cervico vaginal material (vaginal walls, ectocervix and endocervix) to the achievement of conventional oncotic cytology by the method of coloration proposed by Papanicolaou and the test of Capture Hybrid IIÂ. Then it was proceeded the identification of squamous intraepithelial lesions and the presence of HPV virus of high, low and medium oncogenic risk. The results of Capture Hybrid IIÂ were correlated with the cytologic discoveries comparing the frequency of anormal results in both methods. It was also proceeded the association with biosocial aspects which could interfere in the possible development of squamous intraepithelial lesions. The analysis of univariable and bivariable correlations were accomplished with calculus of Qui-squared of Pearson and value p<0,05. The logistic regression was used to estimate the importance of associations. The prevalence of infection by HPV and anormal oncotic cytologies was about 32,3% and 14,0% respectively. The sub groups of HPV of high risk were more prevalent (27,6%) than the ones of low and medium risk. (18,4%) and their association showed to be statistically significant (p< 0,05). The association of genital infection by HPV of high risk with squamous epithelial lesions described on conventional oncotic cytology was more prevalent (8,5%) than with HPV of low and medium risk (5,6%) and had statistical importance (p< 0,05)

PhD (Microbiology)
Department of Microbiology
Diarrhoea is still a major problem worldwide. Enteric pathogens such as Enteroaggregative E. coli (EAEC), Enteropathogenic E. coli (EPEC) and Enterotoxigenic E. coli (ETEC) have been reported to cause diarrhoea in children under the age of 5 years. The incidences of these pathogens are due to factors such as poor water quality, sanitation and hygiene practices. Infections with these pathogens result in diarrhoea and have been reported to result in severe disease outcomes more especially in children under 2 years of age. EPEC infections have been well studied using in vitro analyses, with studies highlighting the adherence traits, proteins and virulence genes involved in pathogenesis and inflammatory responses. EPEC is characterized by localized adherence with microcolony formation at the site of infection. In vivo studies have reported on human EPEC infection. However, the current animal models have not been able to replicate clinical outcomes (such as diarrhoea and weigh loss) of EPEC infection similar to humans. Therefore, there is still a need for a suitable small animal model that mimic clinical outcomes of human EPEC infections in vivo. Children living in poor environmental conditions are more susceptible to diarrhoeal pathogens. Furthermore, the incidences of children being exposed to co-infections (more than one pathogen at the same time) is relatively high. The EAEC/EPEC (A/P) and EPEC/ETEC (P/T) co-infections have been increasingly detected in children with and without diarrhoea. It has been suggested that patients infected with these co-infections might result in severe disease outcome than those infected with single pathogens. Pathogens are constantly evolving and the microbe-microbe interaction in the host can result in these pathogens competing for the same niche and thus result in increased virulence. Interaction of co-infections can lead to increased inflammatory responses thus affecting the infected host. The first objective of this study was to develop an EPEC murine model using weaned C57BL/6 mice that have been pretreated with antibiotic cocktail. Mice were orally infected with wild-type (WT) typical EPEC, bfp- and escN mutant strains. The WT had transient weight loss and wet stools with mucous; and the bfp- infected mice also had transient weight loss and bloody stool appearance. Increase in inflammatory biomarkers MPO, LCN-2, CRP, IL-6 and SAA were observed in the WT and bfp- infected mice. The mice infected with escN mutant did not exhibit any weight changes and the stools were similar to the uninfected mice. Furthermore, no inflammatory biomarkers were observed in mice infected with the escN mutant. Metabolic perturbations were observed in WT EPEC infected mice at day 3 post infection with the TCA cycle metabolites (reduced succinate, citrate, fumarate, cis-aconitate) being excreted at lower quantities indicating that the energy production in the infected mice was greatly affected. The second objective of this study was to determine the interaction between the P/T coinfections using in vitro and in vivo analyses. In vitro, human colorectal tumour 8 (HCT-8) cells were infected with single strains of ETEC, EPEC and both the pathogens and incubated for 3 hours. After infection the cells were analysed for bacterial adherence using real-time PCR. The single strains adhered at the same rate similar to the P/T coinfected cells. IL-8, as a marker of inflammatory response, was measured using ELISA. The results indicated that the P/T co-infected cells had a significant increase in IL-8 response higher than the single infections. The P/T co-infections were further analysed in vivo using the EPEC murine model developed in this study. Interestingly, mice infected with P/T co-infections developed severe diarrhoea accompanied with significant increased weight loss and some mice died during the 3-day infection period. The inflammatory responses MPO, LCN-2 and SAA were higher in the co-infected mice indicating a synergistic effect. The bfp and eltA virulence genes were significantly increased in the P/T co-infections. The third objective of this study was to determine the interaction between A/P coinfections using in vitro and in vivo analyses. HeLa cells and HCT-8 cells were infected with EAEC, EPEC and both the pathogens at the same time in order to determine adherence and inflammatory responses. EAEC adherence was higher than EPEC and A/P co-infections adherence. A/P co-infections did not have increased IL-8 response in HCT-8 cells when compared to EAEC alone. The virulence genes involved in EPEC adherence and Type 3 Secretion System (bfp, eae, tir, ler, per, espB and espA) were significantly reduced in A/P co-infected cells. An interesting adherence trait was observed between the A/P co-infections in HeLA cells, EAEC was found to adhere around EPEC altering the localized adherence pattern. The A/P co-infections were further analysed using the EPEC murine model developed in this study. The A/P infected mice had diminished weight changes and EAEC shedding was enhanced when EPEC was present. Faecal inflammatory biomarkers MPO and LCN-2 in A/P infected mice did not have any additive effect. The findings of this study contributed significantly to the knowledge of human EPEC infection in weaned C57BL/6 mice, highlighting clinical outcomes, inflammatory responses and metabolic perturbations. Furthermore, this study also highlighted the interaction of P/T and A/P co-infections using in vitro and in vivo analyses in order to determine the disease severity and outcomes. It was observed in this study that coinfections can result in either synergistic or antagonistic effects. Further studies are therefore, required in order to understand the underlying mechanisms that are involved during co-infections and this can further assist in the development of therapeutic interventions.
NRF

To determine the relationship between infant-feeding practices and diarrhoeal infections, a descriptive survey was conducted to infants between six to 12 months of age. A guided interview was conducted to 105 mothers of infants who attended the health facilities of Mbabane, Swaziland. The results show that breast-feeding is routinely practiced by the majority of mothers and exclusive breast-feeding is very low, but supplementary feed in the form of formula or solids are introduced by the majority of respondents within the first three months of life. Infants who were given colostrum and breast milk had fewer diarrhoeal attacks. Other factors, for example education and cultural factors influenced the feeding practices and number of diarrhoeal attacks. It is recommended that breast-feeding should be promoted as an important intervention in the control of diarrhoea
Health Studies
M.A. (Nursing Science)

Trabalho de Projeto do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
Report on the Internship of Child Health carried out in the International Mobility period, within the framework of the 6th year of the Integrated Master's Degree in Medicine, Faculty of Medicine, University of Coimbra, Portugal. This training period lasted for 4 weeks at the Lauro Wanderley University Hospital in João Pessoa, State of Paraíba, Brazil. It is a project that intends to reflect the main aspects of a vast learning through a model that encompasses the clinical, theoretical and personal experience . Four clinical cases were selected for which a case report, theoretical review of the related topic, discussion and personal reflection were presented. The first theme, Congenital Cytomegalovirus Infection (ICCMV), aims to alert the growing global prevalence of this infection, promote a reflection on its importance in terms of long-term morbidity and mortality as well as emphasize the essential preventive resources in this clinical setting. Familial Mediterranean Fever (FFM), the second theme, portrays a disease with a characteristic distribution around the Mediterranean basin that is spreading worldwide and which it had never contacted despite the greater geographically close prevalence. The penultimate theme, Sexual Abuse (AS), arises in the follow-up of the most demanding clinical case on a personal level with the subsequent need to understand what procedures and actions should be developed in the event of suspicion of child maltreatment, especially in the case of AS. The last issue, Pediatric Palliative Care (CPP), deals with a current theme, globally discussed, which is a deficient clinical reality in most of the regions of the Globe, and which urges a public discussion capable of altering this reality.The order of approach of the themes was thought as a continuum from birth to death, mirroring a progressive growth and maturation in the discussion of increasingly complex themes.At the end of each topic I make a brief discussion and reflection that collects different teachings, lessons or conclusions that I have acquired. I will conclude with a final reflection and conclusion.
Relatório referente a Estágio de Saúde Infantil realizado em período de Mobilidade Internacional, no âmbito do 6º ano curricular do Mestrado Integrado em Medicina da Faculdade de Medicina, Universidade de Coimbra, Portugal. Este período formativo decorreu durante 4 semanas no Hospital Universitário Lauro Wanderley, em João Pessoa, Estado da Paraíba, Brasil.É um projeto que pretende espelhar as principais vertentes de uma aprendizagem vasta através de um modelo que engloba a experiência clínica, teórica e pessoal vivenciada. Foram selecionados quatro casos clínicos relativamente aos quais se apresenta um relato de caso, revisão teórica de tema relacionado, discussão e reflexão pessoal. O primeiro tema, a Infeção Congénita a Citomegalovírus (ICCMV), pretende alertar para a crescente prevalência global desta infeção, promover uma reflexão sobre a sua importância em termos de morbilidade a longo prazo e mortalidade bem como enfatizar os recursos preventivos essenciais neste âmbito clínico. A Febre Familiar do Mediterrâneo (FFM), o segundo tema, retrata uma doença com uma distribuição característica à volta da bacia do Mediterrâneo que se vem a disseminar mundialmente e com a qual nunca tinha contactado apesar da maior prevalência geograficamente próxima. O penúltimo tema, o Abuso Sexual (AS), surge no seguimento do caso clínico mais exigente a nível pessoal com posterior necessidade de entender que procedimentos e ações devem ser desenvolvidos perante uma situação de suspeita de maus tratos infantis, nomeadamente em caso de AS. O último tema, Cuidados Paliativos Pediátricos (CPP), trata uma temática atual, globalmente discutida, que constitui uma realidade clínica deficitária na maioria das regiões do Globo e relativamente à qual urge uma discussão pública capaz de alterar tal realidade. A ordem de abordagem dos temas foi pensada como um contínuo desde o nascimento até à morte espelhando um crescimento e amadurecimento progressivos na discussão de temáticas cada vez mais complexas. No final de cada tema faço uma breve discussão e reflexão que coleta diferentes ensinamentos, lições ou conclusões que fui adquirindo. Termino com uma reflexão final e conclusão.

PhD (Microbiology)
Department of Microbiology
Background: Diarrheal diseases have a major effect on human health, Globally; it is second only to pneumonia as a leading cause of death among children under five. They are due to a variety of infectious and non-infectious agents; including Entamoeba spp. Entamoeba histolytica is an invasive enteric protozoan parasite that causes amebiasis. Amebiasis is frequent in communities without clean water and poor sanitation, which include low-income South African populations in Giyani and Pretoria. In these populations, the amount of diarrhea caused by Entamoeba histolytica inclusive of all ages, sexes and HIV status is uncertain. Diagnosis of the parasite is usually by microscopy. However, microscopy lacks sensitivity and specificity, therefore it is not reliable. Fortunately, molecular diagnostic tests have been developed to detect different Entamoeba species in humans. It is known that the parasite E. histolytica causes asymptomatic and symptomatic diseases. However, the transition from colonization to disease is still unclear. While parasite and host factors, as well as environmental conditions influence the infection outcome, there is currently no clear explanation of wide variation in the presentation of the disease. This could suggest that there are other factors affecting the disease outcome. A better understanding of these factors as well as their role in disease remains target objectives of modern scientists and it will definitely help in the fight against the disease. In spite of the emerging evidence that the host microbiome, parasite burden and the inflammatory response contribute to the virulence of E. histolytica, their roles have never been defined in developing regions such as Giyani and Pretoria. In addition, the present study hypothesized that co-infections with E. histolytica and secretion of extracellular vesicles/exosomes have a significant impact on the virulence of E. histolytica. Little has been explored or elucidated about responses triggered by other enteropathogens/ameba interplay that could be important in the induction of tissue invasion and disease and also how E. histolytica/enteropathogens interplay in these infections has not been determined. Therefore, the knowledge of this interplay could help in understanding how this modifies disease manifestations by modulating pathogen virulence and the host response. The use of secretion systems is an essential biological process exploited by pathogenic microorganisms to promote survival and spread of the pathogen, which in turn exacerbate the infection. The study of extracellular vesicles (EVs) released by pathogens is a new and exciting field that may realistically contribute to a better understanding of the pathogenic process of E. histolytica and provide alternate control strategies. Aim and objective of the study: The overall aim of the study was to determine the impact of enteric pathogens and secreted extracellular vesicles on amebic virulence and the outcome of infection. This aim was addressed in through a series of six primary objectives, which were: a. To investigate the distribution and prevalence of protozoan parasites in South Africa. b. To investigate novel species of Entamoeba circulating in the South African population. ix c. To elucidate the impact of gut microbiota and immune response during amebic infection. d. To determine the role of Entamoeba histolytica macrophage inhibitory factor (EhMIF) during amebic infection. e. To investigate the impact of co-infections on the outcome of amebiasis. f. To determine the presence of secreted extracellular vesicles/exosomes in Entamoeba histolytica. Brief methodology and results: A modified and validated Taqman qPCR assay (with taqman probes and genus specific primers) was used for amplification and target detection. This assay was used to investigate the distribution and prevalence of protozoan parasites (Cryptosporidium spp and Giardia lamblia) in South Africa, the assay was considered superior for this project because it is more sensitive than conventional PCR and it can be used to detect multiple infection targets. This assay allows fast, accurate, and quantitative detection of a broad spectrum of enteropathogens and is well suited for surveillance or clinical purposes. A total of 484 stool samples collected from diarrheal and non-diarrheal patients from rural and urban communities of South Africa were studied. The overall prevalence of parasites (Giardia lamblia and Cryptosporidium spp) in rural and urban patients were found to be 49% (112/227) and 21% (54/257) respectively (p= < 0.0001). The distribution of specific pathogens in rural areas was Cryptosporidium spp (20%) and Giardia lamblia (14%). Our findings showed no significant difference in parasitic infections between gender and the age of the participants (Chapter 3). The discovery of novel species is of great importance to human health. We have recently discovered stools positive for Entamoeba organisms by microscopy but PCR negative for known Entamoeba species. This led to the hypothesis that novel species of Entamoeba are present in the South African population. A comprehensive assay was used which included probes to identify Entamoeba bangladeshi from diarrheal and non-diarrheal participants. A sensitive qPCR assays and amplicon sequencing was used to detect Entamoeba spp, Prevotella copri and Enterobacteriaceae. Interestingly, E. bangladeshi was identified in the South African population. Entamoeba was present in 27% (E. histolytica 8.5% (41/484), E. dispar 8% (38/484), and E. bangladeshi 4.75% (23/484) E. moshkovskii was not detected in the present study. We were also able to observe changes in the host microbiome and the parasite burden associated with E. histolytica infections in S. African diarrhea cases versus asymptomatic controls but not with E. bangladeshi or E. dispar. In E. histolytica positive samples the level of both parasite and P. copri were lower in non-diarrheal samples (p=0.0034) (Chapter 4). There is accumulating evidence that the inflammatory response contributes to injury. Little is known about the key parasite mediators of host mucosal immunopathology. This study hypothesized that migration inhibitory factor (MIF) mediates the destructive host inflammatory response seen in amebic colitis. To determine the role of EhMIF during amebic infection, we used a genetic approach to test the effect of EhMIF on mucosal inflammation. We found that EhMIF induces IL-8 secretion from intestinal epithelial cells. Mice treated with antibodies that specifically block EhMIF had reduced chemokine expression and neutrophil infiltration in the mucosa. In addition to antibody-mediated neutralization, mice infected with parasites overexpressing EhMIF had increased chemokine expression, neutrophil influx and mucosal damage. We also found that the concentration of EhMIF correlated with the level of intestinal inflammation in persons with intestinal amebiasis. Together, our results reveal a novel parasite mediator of mucosal inflammation and support MIF homologs as potential immunomodulatory targets (Chapter 5). To investigate the impact of co-infections on the outcome of amebiasis, we analyzed the co-occurence of E. histolytica with other enteropathogens known to cause diarrheal infections, such as Shigella/EIEC (IpaH), Campylobacter (cadf), Enterotoxigenic E. coli (STh), Norovirus GII and Adenovirus (Hexon). The results were compared with those obtained with E. histolytica that were not interacted with enteropathogens and with E. histolytica interacted with enteropathogens. The impact of multiple infections on the outcome of the infection was compared between nondiarrheal and diarrheal stool samples. It was found that co-infections with two pathogens were associated with diarrhea compared to single infections. Moreover, Norovirus GII, Campylobacter (Cadf) and co-infections were associated with diarrhea in the study population. This study did not show any significant impact of pathogens co-infecting with E. histolytica on the outcome of amebic infection (Chapter 6). The presence of secreted extracellular vesicles/Exosomes in Entamoeba histolytica was determined by using the Pathogenic ameba strains (HM-1:IMSS or HM-1:IMSS (Sub-strain-US) from petri’s lab to purify exosomes using the commercially available kit to isolate exosomes (total exosomes isolation kit). Our study for the first time revealed that E. histolytica does secrete Evs. This finding increases the appreciation that all organisms are likely to secrete these EVs (Chapter 7). However, the impact of these EVs on the pathogenesis of E. histolytica needs further investigations. Conclusion: This study has contributed significantly to our knowledge on infectious diarrhea and the diversity of Entamoeba species by providing new data on the rate and prevalence of Entamoeba diarrheal infections and their distribution in the South African population. Our study describes for the first time the presence of E. bangladeshi in the South African population. Furthermore, our results reveal a novel parasite mediator of mucosal inflammation and support MIF homologs as potential immunomodulatory targets. This study also, for the first time revealed that E. histolytica does secrete EVs. The results from this work will undoubtedly open an exciting research to establish a deeper understanding of the function and role of these vesicles in amebic infection. We encourage public health interventions like health education programs and improvement of sanitation and hygiene in these populations. Molecular diagnostics should be used for specific diagnostic in clinical settings.
NRF

A resistência aos antimicrobianos é um problema crescente de saúde pública, para o qual contribui a prevalência das infeções associadas aos cuidados de saúde e que têm maior prevalência em idade pediátrica, sendo o controlo de infeção fundamental e imperativo para a segurança e qualidade dos cuidados. Na linha de investigação da “Segurança e Qualidade de vida” e através da adoção da metodologia de trabalho de projeto, foram realizadas intervenções adaptadas às necessidades e particularidades de quatro contextos distintos, com o objetivo de contribuir para a promoção de um efetivo controlo de infeção em pediatria. Para um efetivo controlo de infeção, conclui-se que é fundamental sensibilizar os profissionais para a problemática e incentivar a participação dos pais, através do estabelecimento de uma verdadeira parceria de cuidados, no cumprimento das medidas necessárias. As intervenções centraram-se na resolução de problemas específicos de cada contexto, o que se demonstrou importante e motivador para os enfermeiros. Todo o percurso formativo é enunciado ao longo do relatório, bem como a reflexão sobre o seu contributo para a aquisição das competências de mestre, comuns e específicas do enfermeiro especialista em enfermagem de saúde infantil e pediátrica.
Antimicrobial resistance is a growing problem of public health, which contributes to the prevalence of infections associated with health care and which are more prevalent in the pediatric age, being infection control fundamental and imperative for the safety and quality of care. In the line of research on "Safety and Quality of Life", and through the adoption of the methodology of project work, interventions were made adapted to the needs and particularities of four distinct contexts, with the aim of contributing to the promotion of effective infection control in pediatrics. For effective infection control, it is concluded that it is essential to raise awareness among professionals about the problem and to encourage parental participation, through the establishment of a true partnership of care, in the fulfillment of the necessary measures. The interventions focused on solving specific context problems, which proved to be important and motivating for nurses. The entire training course is articulated throughout the report, as well as the reflection on its contribution to the acquisition of the master competences, common and specific of the specialist nurse in child and pediatric health nursing.