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1
Beek, Diederik van de. "Bacterial meningitis in adults." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2004. http://dare.uva.nl/document/72440.
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Atobe, Jane Harumi. "Amplificação de DNA de Neisseria meningitidis em amostras de líquido cefalorraquidiano pela reação em cadeia da polimerase-multiplex." Universidade de São Paulo, 1998. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-11082006-115017/.
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Padronizou-se a PCR-Multiplex para a detecção do DNA de Neisseria meningitidis. Para tanto os primers escolhidos foram: RW01, DG74 e COR28 baseados na subunidade menor do ribossomo (16S rRNA) que apresenta regiões de seqüências conservadas encontradas em todas as bactérias conhecidas. Os primers RW01 e DG74 amplificaram o fragmento universal bacteriano de 370 bp e, os primers RW01 e COR28, o fragmento específico de N. meningitidis de 279 bp em uma única etapa. Os resultados obtidos nas amostras de LCR de 168 pacientes pelos métodos de cultura e PCR-Multiplex quando comparados à bacterioscopia mostraram que tal técnica apresentou alta sensibilidade (91,3%) no estudo de amostras de LCR de bacterioscopia positiva, enquanto que a cultura apresentou resultados menores (19,7%). Nas amostras de LCR com bacterioscopia negativa a sensibilidade da PCR-Multiplex (57,8%) também foi mais elevada do que da cultura (10%). Estes dados sugerem que a técnica aqui padronizada é altamente promissora para ser utilizada como método diagnóstico da meningite meningocócica, especialmente nos casos de pacientes submetidos à terapia antibiótica prévia.The PCR-multiplex technique was standardized to detect N.meningitidis DNA. It was used universal primer for all bacteria showing sequence of minor subunit of 16S ribossome regions (RW01, DG74) by amplification of 370bp fragment and another (COR28) for specific sequence of N. meningitidis, amplifying 279bp fragment in one step. The results obtained in CSF samples of 168 patients by culture and PCR-Multiplex technique when compared with microscopy showed high sensitivity (91,3%) in samples with positive microscopy (81) to Gram negative diplococcus, however the culture presented only 19, 7% of positivity in the same samples. In other hand the CSF samples with negative bacterioscopy (67) the PCR-Multiplex sensitivity (57,8%) was higher to culture (10,0%) too. These data indicate a high sensitivity and specificity of PCR as a tool for a rapid diagnosis of meningococcal meningitis, mainly in that patient submitted to previous antibiotic therapy as in case of this work (90% of patients) besides the possibility of a rational practice of specific treatment.
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Al, Jindan Reem Yussuf. "Hearing loss and bacterial meningitis." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499828.
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Winter, Andrew John. "Hearing loss in experimental bacterial meningitis." Thesis, University of Birmingham, 1997. http://etheses.bham.ac.uk//id/eprint/32/.
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Experimental meningitis was induced in pigmented guinea pigs by subarachnoid inoculation of \(1 \times 10^9\) Escherichia coli K-12 or \(3 \times 10^7\) CFU Streptococcus pneumoniae serotype 2 D39 (NCTC 7466) or PLN-A, \(\Delta\)NA1 or \(\Delta\)HY1, defined isogenic derivatives of D39 deficient in pneumolysin, neuraminidase or hyaluronidase respectively. All animals developed a meningeal inflammatory response and a labyrinthitis. Hearing loss in pneumococcal meningitis was measured by recording the evoked auditory nerve compound action potential from the round window membrane. Animals infected with PLN-A sustained significantly less hearing loss than those infected with wild-type D39 (12 dB vs. 50 dB 12 h post inoculation; P<0.0001), Neuraminidase deficiency did not alter the course of the meningeal inflammatory response nor affect hearing loss. The \(\Delta\)HY1 mutant survived poorly in the cerebrospinal fluid and blood but still caused hearing loss. Both pneumococcal and E. coli meningitis induced specific ultrastructural lesions in the organ of Corti as judged by high-resolution scanning and transmission electron microscopy, and these lesions were most severe with pneumolysin-sufficient pneumococcal infection. Microperfusion of \(5\times10^6\) CFU S.pneumoniae D39 directly into the scala tympani of guinea pigs also resulted in electrophysiological and ultrastructural damage to the organ of Corti that could be diminished by pretreatment with antibiotics. The data confirm the cochlea as the site of meningogenic deafness. They suggest that pneumolysin expression is chiefly responsible for meningogenic deafness and that if pneumococci invade the inner ear during bacterial meningitis, cochlear deafhess will rapidly ensue.
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Alves, Danilo Antonini 1987. "Utilização de sílica mesoporosa como adjuvante em vacinas de vesícula de membrana externa de Neisseria meningitidis." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314457.
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Orientador: Marcelo LancellottiDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Vesículas da membrana externa ou outer membrane vesicles (OMV) são nanopartículas liberadas no meio de cultura durante o crescimento bacteriano resultantes de evaginações da membrana externa. A OMV é composta por antígenos presentes na membrana externa bacteriana, como porinas e lipo-oligossacarídeos - LOS, proporcionando a estas estruturas um efeito imuno-estimulatório, sendo alvo potencial para a produção de vacinas. Este trabalho teve como objetivo analisar a utilização de OMV de Neisseria meningitidis IAL 2443, linhagem pertencente ao sorogrupo B causadora de meningites no estado de São Paulo, com nanopartículas de sílica mesoporosa SBA-15 e SBA-16 no processo de imunização vacinal. Utilizou-se o processo fermentativo em estado semi-sólido para o crescimento bacteriano e um processo de ultracentrifugação para isolamento da OMV. Comparou-se a produção de OMV de linhagens de N. meningitidis selvagens IAL 2443 e C2135 e mutante knock-out para o gene responsável pela produção de pilina - C2135_pilE. A atividade imunológica foi verificada por meio da imunização em camundongos Swiss e a verificação da citotoxicidade foi realizada em cultura celular utilizando células VERO e NHI 3T3. Os resultados mostraram que as diferentes linhagens de N. meningitidis possuem cinéticas de produção de OMVs distintas em tempo e quantidade. A não expressão de pilE também afeta a cinética da produção dessas estruturas. O uso de adjuvantes de sílica mesoporosa SBA- 15 e SBA- 16 com a OMV IAL 2443 aumenta o reconhecimento pelo sistema imunológico, consequentemente elevando o número de anticorpos específicos frente a mesma cepa bacteriana e a outras linhagens do mesmo sorotipo e sorotipos diferentes. O teste de citotoxicidade em células VERO e NHI 3T3 demonstrou inocuidade nas preparações com SBA- 15 e SBA- 16, atestando a segurança no uso destas preparações como adjuvantes vacinais. O estudo demonstrou que a metodologia utilizada para produção de OMV é vantajosa do ponto de vista quantitativo e econômico e o uso de SBA- 15 e SBA- 16 apresenta potencial como adjuvante em vacinas baseadas em OMV
Abstract: Outer membrane vesicles or OMV are nanoparticles released into the culture medium during bacterial growth resulting from evaginations of the outer membrane. The OMV consists of antigens present in the bacterial outer membrane, like porins and lipooligosaccharides - LOS, these structures provide an immuno-stimulatory effect, and potential target for vaccine production. This study aimed to analyze the use OMV of Neisseria meningitidis IAL2443, belonging to serogroup B strain causing meningitis in São Paulo, as vaccine using the mesoporous silica SBA-15 and SBA-16 in the immunization process. Fermentation process was used in semi-solid state for bacterial growth and a process of ultracentrifugation for the isolation these OMV. It was compared to OMV production of strains of N.meningitidis strains IAL 2443 and C2135, and knock-out mutant for the gene responsible for producing pilin - C2135_pilE. The immunological activity was measured by immunization in Swiss mice and verification of cytotoxicity was performed in cell culture using VERO cells and NIH 3T3. The results showed that different strains of N. meningitidis have OMVs kinetics of production of different time and quantity. The expression does not pile also affects the kinetics of production of these structures. The use of adjuvants mesoporous silica SBA-15 and SBA-16 with the IAL2443 OMV increases the recognition by the immune system, thus bringing the number of specific antibodies against the same bacterial strain and other strains of the same serotype and different serotypes. The cytotoxicity test in NIH 3T3 cells showed VERO and safety in preparation adjuvanted with SBA-15 and SBA-16, confirming the safe use of these preparations as vaccine adjuvants. The study showed that the methodology used for the production of OMV is advantageous from the point of view of quantity and cost and use of SBA-15 and SBA-16 has potential as an adjuvant in vaccines based on OMV
Mestrado
Bioquimica
Mestre em Biologia Funcional e Molecular
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Richardson, Martin Paul. "Hearing loss during bacterial meningitis in children." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243780.
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Abdalla, Hana Khidir. "Modulation of inflammatory mediators during experimental bacterial meningitis /." Linköping : Department of Molecular and Clinical Medicine, Linköping university, 2005. http://www.bibl.liu.se/liupubl/disp/disp2005/med907s.pdf.
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Diab, Asim Eltayeb. "Experimental bacterial meningitis : studies on immunopathogenesis and immunoregulation /." Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-3008-2.
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Thomas, Karla Mari. "Bacterial meningitis in neonates and children South Africa." Master's thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/10743.
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Includes bibliographical references.Acute bacterial meningitis is defined as the inflammation of the meninges. It is caused by various bacteria and the specific aetiology is age dependant. In the neonatal period the causative organisms are: Group B streptococci, Gram - negative bacilli (e.g.: E. coli, Klebsiella spp, Enterobacter spp, Salmonella spp) and Listeria monocytogenes. In infants and children up to the age of 5 the most common causative organisms include: Streptococcus pneumoniae, Haemophilus influenzae type B (Hib)and Neiseria meningitidis. The two chief causes of bacterial meningitis in children older than 5 are S. pneumoniae and N. meningitidis. Various studies have been performed to look at the profile of meningitis among the paediatric population. Objective: To investigate the aetiology of acute bacterial meningitis in South African newborns and children from 2005 - 2010.
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Raza, Muhammad Waqar. "Viral infections as predisposing factors for bacterial meningitis." Thesis, University of Edinburgh, 1993. http://hdl.handle.net/1842/20135.
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Epidemiological data suggest that viral infections might be predisposing factors for bacterial meningitis and carriage of type b Haemophilus influenzae (Hib), Neisseria meningitidis or Streptococcus pneumoniae, the three pathogens most commonly associated with bacterial meningitis. Non-secretors of ABO blood group antigens are over-represented among patients with bacterial meningitis and in populations affected by some outbreaks. The first objective of the study was to examine the hypothesis that non-secretors were also over-represented among patients with respiratory viral infections. Compared with the local population, there was a significantly higher proportion of secretors among patients with disease due to respiratory syncytial virus (RSV), influenza A virus, rhinovirus and ECHO virus. The hypothesis that Leb and/or H-type 1 antigens present on cells or in body fluids of secretors might be receptor(s) for RSV was examined. Affinity purified molecules with Leb or H type 1 determinants or synthetic receptor analogues did not decrease the infectivity of RSV for HEp-2 cells. Bacterial attachment to mucosal surfaces is an important prerequisite for infection. The second major objective was to assess the effect of RSV infection of HEp-2 cells (a human epithelial cell line) on binding of bacteria responsible for meningitis. Binding of bacteria labelled with fluorescein isothiocyanate (FITC) to HEp-2 cells and RSV-infected HEp-2 cells was compared by flow cytometry. Strains of meningococci (3) and Hib (5) expressing antigens of different serogroups, serotypes and subtypes and a strain of Staphylococcus aureus bound significantly more effectively to virus infected cells. Similar patterns of increased binding of unlabelled meningococci to monolayers of RSV-infected cells were also observed. Studies to identify the changes on the cell surface associated with RSV infection responsible for enhanced binding were carried out with one strain of meningococcus. Viral infection of HEp-2 cells did not enhance the expression of Lewisa antigen, a proposed receptor for bacteria in non-secretors. Monoclonal antibodies to the attachment glycoprotein G of RSV decreased the bacterial binding to infected HEp-2 cells; but monoclonal antibodies to the fusion glycoprotein F did not affect binding.
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Trócoli, Maria Graziela Cavalcanti. "Epidemiologia das meningites bacterianas e virais agudas ocorridas no Instituto Estadual de infectologia Säo Sebastiäo (IEISS) - Rio de Janeiro - Período 11.11.96 a 10.06.97." reponame:Repositório Institucional da FIOCRUZ, 1998. https://www.arca.fiocruz.br/handle/icict/4650.
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Previous issue date: 1998Descreve um estudo de Coorte Descritivo Retrospectivo, realizado com dados obtidos através de prontuários de pacientes internados no Instituto Estadual de Infectologia Säo Sebastiäo, no período de 11/96 a 06/97, que tiveram diagnóstico definitivo de meningite bacteriana ou viral. Procedeu-se às estimativas das gravidade e letalidade, de ambas as meningites, comparando-as entre si, bem como dos respectivos agentes etiológicos específicos. Com base nos 204 pacientes, 141 dos quais, portadores de meningite bacteriana e 63, de meningite viral, viu-se que as primeiras se apresentaram mais graves e mais letais que estas últimas, com excessos de risco de 17,6 e 7,8 por cento, respectivamente. Também evidenciou-se que, apesar de todas as infecçöes bacterianas apresentarem casos graves e incidência de óbitos, a que teve maior número destes desfechos foi a meningite pneumocócica, enquanto que, dentre as virais, a meningite por Herpes simples vírus, foi a única a apresentar tais eventos. Os maiores preditores para a gravidade foram a meningite pneumocócica, a meningite por Herpes simples vírus e a idade de 15 anos ou mais. Já para a letalidade, os preditores, além destes patógenos, foram os menores de 1 ano e evoluçäo clínica para o coma, na meningite bacteriana, e a idade de 15 anos ou mais e evoluçäo para torpor ou coma na viral. Ainda constatou-se que as características liquóricas seguem um padräo bem definido para cada uma das meningites em estudo.
This is a Retrospective Descriptive Cohort study, accomplished through reference book, with patients interned at the São Sebastião State Institute of Infectology, in Rio de Janeiro City, Brazil, in the period from 11/96 to 06/97, with definitive diagnosis of bacterial or viral meningitis. It was proceeded to the estimates of the severity and mortality, of both meningitis, comparing them to each other, as well as the respective pathogens. Based on the 204 patients, 141 of the which, carriers of bacterial meningitis and 63, of viral meningitis, the first ones came more severe and more lethal than these last ones, with excesses of risk of 17,6 and 7,8%, respectively. It was also evidenced that, in spite of all the bacterial infections they present severe cases and obits incidence, the one that had larger number of these was the pneumococcal meningitis, while, of the viral ones, the meningitis for Herpes simplex virus, was the only to present such events. The most importants predictores for the severity were pneumococcal meningitis, herpes simplex virus meningitis and the 15 years-old age or more. Already for the mortality, the predictores, besides these pathogens, was last then 1 year old and clinical evolution for the coma, in the bacterial meningitis, and the 15 years-old age or more and evolution for torpor or coma, in the viral one. It was still verified that the cerebrospinal fluid (CSF) characteristic follows a pattern very defined for each one of the meningitis in study.
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Granert, Carl. "Modulation of the inflammatory response in experimental bacterial meningitis /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3852-0/.
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Ajdukiewicz, Katherine M. B. "Glycerol adjuvant therapy in adult bacterial meningitis in Malawi." Thesis, University of Liverpool, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.632134.
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Background: Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HN co-infection. Mortality exceeds 50%, even with appropriate antibiotic therapy, and is not improved with corticosteroids. Glycerol adjuvant therapy reduces long-term morbidity in bacterial meningitis in children, and its use is being promoted. We aimed to assess the effectiveness of glycerol as an adjuvant therapy for adults with bacterial meningitis in Africa In addition, we aimed to measure the effect of glycerol on reducing intracranial pressure and deafness. Methods: The study was done in two phases. First, in an open-label dose-finding study, 45 adult patients with symptoms, signs, and cerebrospinal fluid findings consistent with bacterial meningitis received 50, 75, or 100 ml of glycerol four times a day for 4 days. We then did a randomised, double-blind, placebo-controlled trial of oral glycerol in adults with bacterial meningitis. Patients with clinical and cerebrospinal fluid findings suggestive of bacterial meningitis were randomly assigned in blocks of 12 by use of a random number list produced by an independent statistician to receive either glycerol or an equivalent volume of sugar solution. Glycerol and placebo were indistinguishable by colour or taste. The primary outcome was mortality at 40 days, with secondary outcomes including disability and mortality restricted to pneumococcal disease; reduction in cerebrospinal fluid opening pressure and optic nerve sheath diameter measurement at Day 2 and hearing loss at Day 40. All patients were analysed for the primary outcome excluding those who were lost to follow-up. This trial is registered at controlled-trials. com, number ISRClN70121840. Findings: 75 mL glycerol four times a day was the highest tolerated dose, and was used for the main study. 265 patients were assigned treatment: 137 glycerol and 128 placebo. The trial wa.s stopped early on the advice of the data and safety monitoring board after a planned interim analysis. By Day 40,61 (49%) of 125 patients in the placebo group and 86 (63%) of 136 in the glycerol group had died (adjusted odds ratio 2-4,95% CI 1·3-4·2, p=0·003). There was no benefit from glycerol for death and disability by Day 40, and glycerol did not improve death and disability by Day 40 or death at Day 40 in patients with proven bacterial disease or pneumococcal disease. Two serious adverse events occurred that were possibly due to the study drug. Optic nerve sheath diameter and CSF opening pressure were not reduced by glycerol. There was a trend towards less hearing loss at Day 40 in the glycerol arm five (5.6%) compared with placebo 16 (21.3%) (p=0.026). Interpretation: Oral glycerol therapy cannot be recommended as an adjuvant therapy in adults with bacterial meningitis in resource-poor settings with a high HIV prevalence.
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Ala'Aldeen, Dlawer Abdul-Aziz. "Characterisation, regulation and vaccine potential of iron regulated proteins of Niesseria meningitidis." Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304738.
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Berkley, James Alexander. "Invasive bacterial infections in children at a sub Saharan district hospital." Thesis, University of Newcastle upon Tyne, 2002. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289202.
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Pereira, Rafaella Fabiana Carneiro 1985. "Estabelecimento de modelos celulares para análise in vitro dos mecanismos de virulência de neisseria meningitidis." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314458.
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Orientador: Marcelo LancellottiDissertação (mestrado) - Universidade Estadual de Campinas, Insituto de Biologia
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Resumo: Neisseria meningitdis, ou meningococo, é uma bactéria comensal da nasofaringe humana. Contudo, algumas linhagens meningocócicas ocasionalmente ultrapassam a mucosa respiratória e a barreira hematoencefálica e causam enfermidades como meningite e septicemia. Como a espécie humana é o único hospedeiro natural para esse patógeno, estudos in vitro com modelos celulares são uma ferramenta importante para a análise da interação entre o meningococo e seu hospedeiro. Este trabalho teve por objetivo avaliar a influência de diferentes linhagens de N. meningitidis na adesão celular, morfologia e expressão de quimiocinas inflamatórias em culturas in vitro de células humanas. Tais parâmetros também foram avaliados em um sistema in vitro de co-cultura celular entre células de origem nervosa e endotelial a fim de mimetizar a barrreira hematoencefálica humana. Os resultados obtidos indicam que a adesão de diferentes linhagens bacterianas em células humanas de sítios específicos do processo infeccioso do meningococo, como Hep-2 (laringe), NCIH460 (pulmão), Hec1b (endotelial) e NG97 (neuroglia) foi capaz de mimetizar o processo fisiopatológico deste microrganismo. Em condições in vitro, células de origem nervosa mostraram-se mais suscetíveis à infecção nos parâmetros avaliados como uma elevada expressão de TNF-?, quimiocina característica em infecções meningocócicas. A linhagem B4 destacou-se entre as linhagens meningocócicas estudadas, apresentando elevados percentuais de adesão em células humanas com valor máximo de adesão em NG97. Células HEp-2 apresentaram poucas alterações morfológicas significativas frente à infecção por N. meningitidis. Tais resultados podem estar associados ao fato do trato respiratório superior ser o habitat natural do meningococo, no qual a interação entre este patógeno e as células hospedeiras seja comensal e não-invasiva. O modelo mimético de barreira hematoencefálica, realizado em transwell, indicou comunicação entre as células que o compõem e uma maior expressão dos níveis de quimiocinas inflamatórias quando comparada à infecção desta bactéria por cada uma das células estudadas isoladamente. Tal modelo foi capaz de mimetizar a barreira hematoencefálica, fato o que torna possível sua aplicação em estudos da passagem de fármacos e outros patógenos por essa barreira.
Abstract: Neisseria meningitidis,or meningococci, is a commensal bacterium of the human nasopharynx. However, occasionally some meningococcal strains can cross the respiratory mucosa and the blood-brain barrier and cause life-threatening diseases such as meningitis and septicaemia. Since the human species is the only natural host for this pathogen, in vitro studies with cellular models are an important tool for the analysis of the meningococci and its host. The aim of this present work was to value the influence of several strains of N. meningitidis in cellular adhesion, morphology and inflammatory chemokines expression in human cells cultivated in vitro. These parameters were also evaluated in a co-cultivated cellular system with glial and endothelial cells aiming mimicking the human blood brain barrier. The results indicate that the adhesion of different bacterial strains from specific sites of infectious process of meningococci as Hep-2 (larynges), NCIH460 (lung), Hec1b (endothelial) and NG97 (glial cells) was capable of mimicking, partially, the pathophysiology of this microorganism. In in vitro conditions, cells from nervous origin showed more susceptibility to infection then others in this evaluated parameters such as a high TNF-? expression, a common chemokine in meningococcals diseases. The B4 strain distinguished from the others by presenting high rates of adhesion in human cells with maximum value on NG97. HEp-2 cells showed few expressives morphologic alterations after meningococcal infection. These results may be associated with the fact that the upper human respiratory tract is the meningoccci natural habitat, in which the interaction between this pathogen and host cells are commensal and not-invasive.The mimicking blood-brain barrier model, performed in transweel, has demonstrated some communication between the cells and greater expression of inflammatory chemokines when compared to the infection in isolated cells. This model was capable of mimicing the blood-brain barrier, which makes its application possible in studies of drugs and others pathogens who might crossover though this barrier.
Mestrado
Bioquimica
Mestre em Biologia Funcional e Molecular
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Sokhan, A. V. "Neurospecific markers - new opportunities in the diagnosis of bacterial meningitis." Thesis, Sumy State University, 2017. http://essuir.sumdu.edu.ua/handle/123456789/64505.
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У роботі представлені результати дослідження
рівнів нейроспецифічних маркерів NSE, протеїну S-100, GFAP
та MBP у цереброспінальній рідині хворих на менінгококовий та
пневмококовий менінгіти в динаміці хвороби. Визначено
наявність уражень нейронів, астрогліальних клітин та
мієлінових нервів у всіх хворих та визначена можливість
використання цих показників з діагностичною та
прогностичною метою.Diagnostic role of neuro specific proteins in assessing the degree of damage to the cells of the central nervous system currently confirmed. It proved that levels of neuron specific proteins in cerebrospinal fluid corresponds to the degree of the CNS cell damage in patients with stroke, injury, Alzheimer's disease, etc. However, the role and the diagnostic value of CSF neuron specific protein in patients with acute bacterial meningitis is almost unknown.
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Herbert, Mark A. "Signature tagged mutagenesis of Haemophilus influenzae." Thesis, Open University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340734.
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Ryder, Stephen J. "Studies on the recruitment of macrophages into the central nervous system." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309144.
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Bakshi, Sharmila. "Role of the NMB0342-NMB0348 locus in meningococcal pathogenesis and investigation of NMB0345 as a vaccine candidate." Thesis, University of Oxford, 2004. http://ora.ox.ac.uk/objects/uuid:9ab7045e-651b-4b6d-b06e-7b56619ef899.
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Neisseria meningitidis is the most common cause of bacterial meningitis in the Western world and the second leading cause of mortality in 1-5 year-olds in the United Kingdom. A signature-tagged mutagenesis screen of approximately 3,000 insertional mutants of a serogroup B isolate of N. meningitidis, C311⁺, identified 73 genes required for pathogenesis in an infant rat model of meningococcal septicaemia. Homology-based searches indicate that two of the genes identified, NMB0342 and NMB0345, have homologues in other pathogenic bacteria and exist within a potential operon of seven genes (NMB0342-NMB0348). NBM0342 is a homologue of ispA (intracellular septation protein) of Shigella flexneri, required for effective intercellular spread and plaque formation in epithelial cells. NMB0345 is a homologue of cbf, a Campylobacter jejuni gene that encodes a 29 kDa protein which is a major antigenic peptide. PCR and Southern analyses of genes in the NMB0342-NMB0348 locus show that they are conserved across a wide range of pathogenic isolates and serogroups of N. meningitidis. However, these genes are present only in a subset of commensal strains. N. meningitidis mutants with transpoon insertions in NMB0342 and NMB0345 are highly attenuated when directly competed with the wild-type bacterium in the infant rat model of infection. Mutations have been introduced into other genes within the locus and the resulting mutants analyzed for their ability to cause systemic disease. Mutants with transpoon insertions in the NMB0343 and NMB0344 genes are significantly attenuated, while mutants with insertions in NMB0347 and NMB0348 are attenuated to a lesser degree. Complementation of the NMB0342 mutation by ectopic chromosomal integration of a wild-type copy of NMB0342 almost completely restores the virulence of the bacterium. In vitro cell-culture analyses and microscopic analysis of mutants in association with host cells demonstrate that a mutant with a transpoon insertion in NMB0345 is significantly reduced in its adherence to Chang epithelial cells compared to the wild-type bacterium. Whole blood and serum-sensitivity assays show that the NMB0342 and NMB0345 mutants are highly serum-sensitive compared to the wild-type bacterium. Preliminary experiments have demonstrated that immunization of mice with recombinant NMB0345 protein confers protection against challenge with the serogroup B isolate MC58. In vitro assays demonstrate that recombinant NMB0345 is an active peptidyl polyl cistrans isomerase (PPIase). Together, the results from these investigations support a role for genes of the NMB0342-NMB0348 locus in the pathogenesis of N. meningitidis infections. Further investigation is needed to assess the potential of NMB0345 as a vaccine candidate.
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Okike, Ifeanyichukwu O. "The causes, presentation, outcome and management of bacterial meningitis in young infants." Thesis, St George's, University of London, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.754072.
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Background and objectives Bacterial meningitis (BM) is associated with significant morbidity and mortality The case fatality rates amongst neonates have declined but rates of sequelae have remained unchanged. This thesis aimed to define the current burden, management and outcome in young infants. Methods Two national surveillance studies conducted using national reporting systems by the Public Health England and neonatal unit infection network, in combination with prospective/ retrospective multi-centre observational studies were used. Results The incidence of BM is highest in infants <90 days compared to any other age group. In neonates, the incidence and aetiology has not changed since the 1980s. Group B streptococcus and E. coli remain the leading causes; neither are currently vaccine- preventable. Listeria meningitis occurred only in the first month of life with implications for national empiric antibiotic recommendations. The presenting features are non-specific and only half presented with fever, which could potentially lead to significant delays in initiating empiric antibiotics. In a subset of 97 infants, the time from triage to receipt of first antibiotic dose was 2.0 hours (IQR: 1.0-3.3) hours, significantly shorter in infants with fever or seizures at presentation compared to those without. Almost all symptoms reported by parents appeared at the onset of the illness, with very few new symptoms appearing subsequently. We have identified gaps in the current management of cases. 4 Dr. Ifeanyichukwu Ogbonnaya Okike 2017 8% died, and 20% of survivors suffered a serious central nervous system (CNS) complication at discharge. The independent risk factors for death were prematurity, low birthweight, coma at presentation and pneumococcal meningitis, whilst temperature instability, seizures, CSF protein >2275 mg/dl and pneumococcal meningitis were independently associated with serious CNS complications. Conclusion The incidence of BM in young infants and rates of serious CNS complications have not changed in more than three decades. Our e-leaming tool based on lessons from the course of illness and clinical management of cases in addition to our proposed management algorithm will be invaluable resources. An effective GBS vaccine is needed to reduce the burden of serious bacterial infection in young infants.
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Diallo, Kanny. "The molecular epidemiology and ecology of Neisseria species in the African meningitis belt." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:d7a7f86f-579f-4996-8984-c4831075f505.
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Neisseria meningitidis (Nm) is one of the major causes of bacterial meningitis in the African meningitis belt (AMB). This organism is part of the genus Neisseria, which includes ten human restricted species, mostly harmless commensals of the nasopharynx; however, Nm is capable of causing invasive meningococcal disease. The transition from carriage to pathogenic state remains perplexing, and strict virulece factors have yet to be identified. It has been hypothesised that non-pathogenic Neisseria (NPN) carried asymptomatically in the oroopharynx could play a role in modulating carriage of Nm, and therefore, its likelihood of invasion. In chapter 3, the diversity of the genus was characterised within a collection of 46 034 nasopharyngeal samples obtained across the AMB: five different species were identified, with Nm and NPNs displaying inversely related risk factors fo carriage. Chapter 5 presents the whole genome sequence (WGS) analysis of 107 Neisseria isolates unclassified by other methods. This higher genetic resolution, complemented with the use of a novel speciation approach, revealed seven novel Neisseria species, mostly collected in African countries. The invasive potential may also be due to the presence of particular genetic factors in the meningococcal genome. Chapter 4 presents the WGS comparison of 23 carried and invasive serogroup A Nm collected in Chad during the 2011 meningitis epidemic. Isolates from both phenotypic groups were found to be part of the same bacterial populations; however, discrete clusters were identified, associated with distinct age groups. These results indicate that genomic analyses are essential to appropriately study Neisseria diversity, and that lower resolution methods have greatly underestimated the diversity of the genus in Africa. The identification of Nm clusters associated with certain niches and of the differences in carriage risk factors suggests that variation in the environment, including the presence of NPNs, may be key in modulating carriage of Nm.
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Bush, Victoria Louise. "The interaction of Neisseria meningitidis with host cells." Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361473.
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Torres, Vitor Félix. "Receptor desencadeador expresso nas células mielóides Tipo 1 (TREM-1) no diagnóstico e prognóstico na meningite bacteriana em crianças." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/129631.
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Base teórica: A meningite bacteriana é uma causa importante de morbidade e mortalidade na infância. Análise do líquido cefalorraquidiano (LCR) continua a ser a ferramenta de diagnóstico padrão ouro, porém novos biomarcadores para o diagnóstico e prognóstico ainda são necessários. Receptor Desencadeador Expresso nas Células Mielóides Tipo 1 (TREM-1) é um receptor transmembrana expresso em neutrófilos e monócitos, que desempenha um papel importante na modulação da resposta inflamatória. A sua fração solúvel (sTREM-1) também é aumentada na infecção, inflamação ou doenças imunológicas. Neste estudo nós avaliamos, prospectivamente, o valor do TREM-1 como um biomarcador de meningite bacteriana aguda em pacientes pediátricos e sua possível utilização como uma ferramenta de prognóstico neste cenário. Objetivos: O objetivo primário do presente estudo é caracterizar os níveis líquóricos solúveis de TREM-1 (sTREM-1) em pacientes admitidos por suspeita clínica de meningite. Analisamos também os níveis de sTREM-1 nos casos de meningite bacteriana e viral, além de medir a sensibilidade e especificidade deste biomarcador no LCR e estudar se esse biomarcador pode ser um fator associado ao prognóstico em meningite bacteriana aguda. Métodos: Sessenta e um pacientes pediátricos, de 0 a 10 anos foram avaliados quanto à meningite e foram prospectivamente incluídos neste estudo. Na admissão, após a suspeita clínica de meningite foram submetidos à análise do LCR para o diagnóstico e uma amostra do LCR inicial foi utilizado também para análise do sTREM-1. Os pacientes foram acompanhados durante a sua internação com o registro de seu tratamento e desfecho clínico para posterior análise dos dados. Resultados: Dentre os 61 pacientes, 38 (62%) foram negativos para a meningite, 7 (11%) pacientes foram diagnosticados com meningite viral e 16 (27%) pacientes foram diagnosticados com meningite bacteriana aguda e recebeu tratamento direcionado. Sexo (p = 0,15), presença de fatores de risco identificados (p = 0,17), presença de convulsões (p = 0,31), outras complicações clínicas (p = 0,11) e mortalidade (p = 0,66) não diferiram entre os grupos. Anormalidades sensoriais (p <0,0001) e presença de cefaléia (p = 0,003) foram mais prevalentes em pacientes com meningite. Como esperado, a contagem de leucócitos, glicose e proteína no LCR foram significativamente diferentes entre pacientes com meningite e pacientes sem meningite. As concentrações de sTREM-1 no LCR de pacientes com meningite bacteriana foi superior quando comparada com pacientes com meningite viral e com controles (1204,67 pg/ml, 39,34 pg/ml e 12,09 pg/ml, respectivamente; p <0,0001). Quando sTREM-1 foi usado como um determinante de diferenciação entre pacientes com ou sem meningite bacteriana, a análise da área sob a curva ROC foi de 0,95 (IC de 95% = 0,89-1,00; p <0,0001). A presença de fatores de risco para a meningite bacteriana (p = 0,04), anormalidades sensoriais (p <0,0001), contagem de leucócitos no LCR (p = 0,01), níveis de glicose no LCR (p = 0,002), níveis de proteína no LCR (p = 0,032) e os níveis de sTREM-1 no LCR (p = 0,004) foram associados com meningite bacteriana, incluindo os níveis sTREM-1 acima do ponto de corte estabelecido de 68,0 pg/ml (p <0,0001). A meningite bacteriana (p = 0,02) e os valores de sTREM-1 maior do que o ponto de corte (68,0 pg/ml) (p = 0,04) foram associados com sequelas neurológicas graves e morte neste grupo de pacientes. Conclusão: Avaliamos os níveis sTREM-1 de crianças com suspeita clínica de meningite. Os níveis de s-TREM-1 foram aumentados nos casos de meningite bacteriana e correlacionados com o prognóstico. Os nossos resultados sugerem que níveis elevados de sTREM-1 no LCR podem ser utilizados como um biomarcador para o diagnóstico de meningite bacteriana aguda em crianças e que pode ser útil na determinação do prognóstico do paciente nesse cenário.Background: Bacterial meningitis is an important cause of morbidity and mortality in infancy. Cerebrospinal fluid (CSF) analysis remains the gold standard diagnostic tool, however new biomarkers for diagnosis and prognosis are still required. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a transmembrane receptor expressed on neutrophils and monocytes that plays an important role on the immune response. Its soluble fraction (sTREM-1) is also increased in infection, inflammation or immune diseases. In this study we evaluate the value of sTREM-1 as a biomarker of acute bacterial meningitis in pediatric patients and its possible use as a prognostic tool prospectively. Methods: Sixty-one pediatric patients, from 0 to 10 years of age were evaluated for meningitis and were prospectively included in this study. At admission, following clinical hypothesis of meningitis patients were submitted to CSF analysis for diagnosis and a sample of initial CSF was also used for TREM-1 analysis. Patients were followed during hospitalization and clinical evaluation and treatment outcome were recorded for posterior analysis. Results: Thirty-eight (62%) out of 61 patients were negative for meningitis, 7 (11%) patients were diagnosed with viral meningitis and 16 (27%) patients were diagnosed with and received treatment for acute bacterial meningitis. Sex (p = 0.15), presence of identified risk factors (p = 0.17), presence of seizures (p = 0.31), other clinical complications (p = 0.11), and mortality (p = 0.66) did not differ among groups. Sensorial abnormalities (p<0.0001) and presence of headache (p= 0.003) were more prevalent in patients with meningitis. As expected, leukocyte count, glucose, and protein levels were significantly different between patients with meningitis and patients without meningitis. Concentrations of sTREM-1 in CSF from patients with bacterial meningitis was higher when compared to patients with viral meningitis and with controls (1204.67 pg/ml, 39.34 pg/ml and 12.09 pg/ml, respectively; p<0.0001). When sTREM-1 was used as a determinant to differentiate between patients with or without bacterial meningitis, the analysis of the area under the ROC curve (AUC) was 0.95 (95% CI=0.89-1.00; p<0.0001). Presence of risk factors for bacterial meningitis (p = 0.04), sensorial abnormalities (p<0.0001), CSF leukocyte count (p = 0.01), CSF glucose levels (p = 0.002), CSF protein levels (p = 0.032) and CSF sTREM-1 levels (p = 0.004) were all associated with bacterial meningitis, including sTREM-1 levels above the established cut-off point of 68.0 pg/ml (p<0.0001). Bacterial meningitis (p = 0.02) and values of sTREM-1 higher than the cut-off point (68.0 pg/ml) (p = 0.04) were associated with death and severe neurological disabilities in this patient cohort. Conclusion: We evaluated sTREM-1 levels in CSF of children with clinical hypothesis of meningitis. The sTREM-1 levels were increased in bacterial meningitis and correlated with prognosis. Our results suggest that CSF sTREM- 1 levels can be used as a biomarker for diagnosis of acute bacterial meningitis in children and it might be useful in determining patient’s prognosis in this scenario.
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Попов, Сергій Віталійович, Сергей Витальевич Попов, Serhii Vitaliiovych Popov, and О. В. Корниенко. "Оценка эффективности применения гормонотерапии у детей с бактериальным менингитом." Thesis, Изд-во СумГУ, 2005. http://essuir.sumdu.edu.ua/handle/123456789/6714.
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Coutinho, Leonam Gomes. "Estudo do papel da prote?na multifuncional APE1/Ref-1 sobre a resposta inflamat?ria na meningite bacteriana." Universidade Federal do Rio Grande do Norte, 2013. http://repositorio.ufrn.br:8080/jspui/handle/123456789/12649.
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Previous issue date: 2013-03-19Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-?. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition
A meningite bacteriana (MB) ? uma doen?a infecciosa que permanece com altas taxas de mortalidade e morbidade em todo o mundo, principalmente em pa?ses subdesenvolvidos, apesar dos avan?os na antibioticoterapia. Um dos principais mecanismos associados ?s sequelas durante a MB ? a elevada resposta inflamat?ria, que promove uma exacerbada quantidade de esp?cies reativas de oxig?nio (ERO) levando ?s c?lulas a apoptose ou necrose. A ativa??o de enzimas de reparo de DNA durante o estresse oxidativo tem sido demonstrada nas mais diversas desordens. Uma importante enzima envolvida neste processo ? a endonuclease apur?nica/apirimidinica1/fator redox-1 (APE1/Ref-1). Ela ? uma prote?na multifuncional envolvida no reparo de DNA e na redu??o de fatores envolvidos com a resposta inflamat?ria, tais como o fator nuclear kappa B (NFkB) e prote?na ativadora 1 (AP-1). Este estudo teve como objetivo identificar o envolvimento de APE1/Ref-1 na resposta inflamat?ria visando a possibilidade de sua utiliza??o como alvo terap?utico na redu??o de sequelas durante a MB. Para isto, inicialmente foi realizado uma an?lise no perfil de express?o de citocinas em l?quor de pacientes com meningite causada por Streptococcus pneumoniae e Neisseriae meningitidis visando selecionar moduladores inflamat?rios de interesse para ensaios em cultura de c?lula subsequentes. Em seguida, utilizando um modelo celular de indu??o com LPS foi avaliado o efeito da inibi??o da atividade de reparo e redox de APE1 sobre a express?o de citocinas inflamat?rias. Por fim, foi observada a express?o de APE1 no c?rtex (CX) e hipocampo (HC) de ratos com MB frente a uma terapia adjuvante com vitamina B6. Nossos resultados mostraram um perfil de moduladores inflamat?rios muito semelhante no l?quor dos pacientes com MB causada pelos pat?genos estudados, embora interferon gama (IFNy) tenha sido VI significativamente mais expresso em pacientes com S. pneumoniae do que N. meningitidis. Quanto ao uso dos inibidores das fun??es, redox e de reparo, de APE1/Ref-1 no modelo in vitro, houve redu??o significativa na express?o de algumas citocinas, principalmente o fator de necrose tumoral-alfa (TNF-?). Al?m disso, os inibidores demonstraram uma redu??o nos n?veis de ERO nas c?lulas estimuladas com LPS. No modelo animal, a express?o prot?ica de APE1/Ref-1, no CX e HC dos ratos, foi modulada ap?s introdu??o da vitamina B6. Portanto, esses dados fornecem um novo olhar para a fisiopatologia da MB, em que citocinas como IFNy podem ser usadas em um diagn?stico diferencial entre meningites causadas por S. pneumoniae e N. meningitidis. A prote?na de reparo de DNA, APE1/Ref-1, parece ser um alvo potencial na modula??o da resposta inflamat?ria e do estresse oxidativo, bem como a terapia adjuvante com vitamina B6 mostra ter um papel sobre a express?o de APE1/Ref-1. Consequentemente, o conhecimento obtido neste estudo pode ser importante na melhoria do progn?stico da MB, al?m de contribuir para entender a associa??o entre o reparo de DNA e inflama??o
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Scarborough, M. "Dexamethasone adjuvant therapy and intramuscular ceftriaxone in adult bacterial meningitis in Malawi, Central Africa." Thesis, University of Liverpool, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501732.
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In sub-Saharan Africa bacterial meningitis is common and carries a high mortality, Steroid adjuvant therapy reduces mortality in aduhs in the developed world but has not been adequately tested in developing countries or in the context of advanced HIV. The mechanism of action of adjunctive steroids in bacterial meningitis is incompletely understood but may involve down regulation of the host's proinflammatory cytokine response. Bacterial meningitis in this setting presents late and is strongly associated with HIV co-infection. Dexamethasone adjuvant therapy for bacterial meningitis in aduhs did not reduce mortality or morbidity. Intramuscular ceftriaxone was not inferior to intravenous ceftriaxone for the treatment of bacterial meningitis. Cytokine expression was unaffected by the use of steroid adjuvant therapy.
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Abués, Mohanna Damasceno. "Perfil etiológico da meningite bacteriana no estado do Tocantins." Universidade Federal do Tocantins, 2018. http://hdl.handle.net/11612/1026.
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A meningite bacteriana continua sendo um problema de saúde pública no Brasil, estudá-la em
todos seus aspectos faz com que as chances de intervenções possam ser descobertas a fim de
diminuir seus altos índices de mortalidade e sequelas dentre as pessoas acometidas. O
presente trabalho teve por finalidade caracterizar o perfil etiológico da meningite bacteriana
no estado do Tocantins, no período de 2010 a 2017, através de um estudo retrospectivo,
transversal, de natureza quantitativa, realizado a partir de dados provenientes do Laboratório
Central de Saúde Pública do Estado do Tocantins (LACEN-TO), em relação à realização de
culturas de líquido cefalorraquidiano (LCR) para o diagnóstico laboratorial de meningite
bacteriana. Este estudo constatou que foram realizadas 2041 culturas de LCR e um baixo
crescimento microbiológico dentre elas. O grupo bacteriano com maior crescimento dentre as
culturas positivas foram o Staphylococcus coagulase negativos (SCN), principalmente o S.
epidermides. Dentre as bactérias de importância a saúde pública, a de maior incidência foi
Streptococcus pneumoniae (sorotipo 3 e 19A), acometendo principalmente indivíduos do sexo
masculino e as faixas etárias abaixo de 60 anos, não havendo distinção considerável entre
crianças, adolescentes e adultos, seguido de Neisseria meningitides (sorogrupo C) e
Haemophilus influenzae (sorotipo b); a maioria dos sorotipos de S. pneumoniae apresentaram
susceptibilidade aos antimicrobianos, exceto sorotipo 19A, que apresentou multirresistência.
Assim, o principal agente etiológico da meningite bacteriana no estado do Tocantins, de
importância a saúde pública, no período estudado foi o Streptococcus pneumoniae, porém
devido à baixa positividade de culturas e isolamento desses agentes, é necessário que haja
melhorias no diagnóstico laboratorial dessa doença desde o ato da punção, para minimizar o
crescimento de bactérias da microbiota, à liberação de resultados, inclusive introdução de
novas tecnologias, como a reação em cadeia da polimerase (PCR), que poderá diminuir o
tempo de resposta do resultado e aumentar o conhecimento da etiologia deste agravo, devido
sofrer menos influência em relação a qualidade de amostra e tempo de processamento.The bacterial meningitis is still a public health problem in Brazil, studying it in all its aspects causes that the chances of interventions can be discovered in order to reduce their high mortality rates and sequelae among people affected. The present study aimed to characterize the etiological profile of bacterial meningitis in the state of Tocantins, from 2010 to 2017, through a retrospective cross-sectional study of a quantitative nature, based on data from the Central Laboratory of Public Health of the State of Tocantins (LACEN-TO), in relation to cerebrospinal fluid cultures (CSF) for the laboratory diagnosis of bacterial meningitis. This study found that 2041 cultures of CSF and low microbiological growth were performed among them. The bacterial group with the highest growth among the positive cultures were coagulase negative Staphylococcus (SCN), mainly S. epidermides. Among the bacteria of public health importance, Streptococcus pneumoniae (serotype 3 and 19A) was the most prevalent, affecting mainly male individuals and the age groups below 60 years, with no significant distinction among children, adolescents and adults, followed Neisseria meningitides (serogroup C) and Haemophilus influenzae (serotype b); the majority of serotypes of S. pneumoniae showed antimicrobial susceptibility, except for serotype 19A, which presented multiresistance. Thus, the main etiological agent of bacterial meningitis in the State of Tocantins, of importance to public health, during the period studied was Streptococcus pneumoniae, but due to the low positivity of cultures and isolation of these agents, it is necessary to have improvements in the laboratory diagnosis of this disease since the puncture act to minimize the growth of bacteria in the microbiota, the release of results, including introduction of new technologies, such as polymerase chain reaction (PCR), which may decrease the response time of the result and increase knowledge of the etiology of this less influence on sample quality and processing time.
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Coutinho, Leonam Gomes. "Ativa??o local da rota da quinurenina por moduladores inflamat?rios durante a meningite bacteriana." Universidade Federal do Rio Grande do Norte, 2008. http://repositorio.ufrn.br:8080/jspui/handle/123456789/16760.
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Previous issue date: 2008-03-18Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Activation of the kynurenine (KYN) pathway (KP) by modulators of immune system has been observed during several neurological diseases. Here we assessed the association of chemo-/cytokine levels with the concentration of KP metabolites in cerebrospinal fluid (CSF) and plasma samples from patients with bacterial meningitis (BM). All samples were collected from 42 patients diagnosed with acute bacterial meningitis (ABM), aseptic meningitis, tuberculous meningitis and patients without infection neurological disorders. CSF and plasma concentration of metabolites from the KP was assessed by high pressure liquid chromatography (HPLC) and cytokines and chemokines by Bio-plex 200 suspension array system. Concentrations of the KP metabolites KYN and kynurenic acid (KYNA) were significantly higher in CSF of patients with ABM compared to other groups. Tryptophan (TRP), anthranilic acid (AA), 3-hydroxykynurenine (3HK) and 3-hydroxyanthranilic acid (3HAA) did not show statistical significance, although some of them presented a good accumulation during ABM. The expression of TNF-alpha, IL-6, IL-1beta, IFN-gamma, IL-10, IL-1 receptor antagonist (IL-1Ra), MIP-1alpha, MIP-1beta, MCP-1 and G-CSF was about 100-fold higher in CSF from ABM patients than other infected groups. In all CSF and plasma samples, the concentration of IL-2, IL-12(p70), IL-4, IL-8 and GM-CSF was not significant. ABM still showed significant concentrations of IL-6, IL-10, IL-1Ra and MCP-1 in plasma samples. Based on the comparison of KP metabolites concentrations between plasma and CSF samples we conclude that the activation of the tryptophan pathway upon BM occurs within the brain. This increase in KP metabolites is most due to activation of the KP by molecules as IFN-gamma and TNF-alpha in response to infection.
A ativa??o da rota da quinurenina por moduladores do sistema imune tem sido observada durante diversas doen?as neurol?gicas. Neste trabalho foi avaliado a associa??o entre os n?veis de citocinas e quimiocinas com a concentra??o dos metab?litos da rota da quinurenina ( Kynurenine pathway KP) em amostras de l?quor e plasma de pacientes com meningite bacteriana. Todas as amostras foram coletadas de 42 pacientes hospitalizados com o diagn?stico de meningites bacteriana aguda, tubercul?sica, ass?ptica e pacientes cujo diagn?stico excluiu infec??o no sistema nervoso central. As concentra??es dos metab?litos da quinurenina foram avaliadas pela cromatografia l?quida de alta press?o enquanto os n?veis de citocinas e quimiocinas foram medidos pelo Bio-plex 200 suspension array system. Concentra??es de quinurenina e ?cido quinur?nico foram significativamente mais elevadas no l?quor de pacientes com meningite bacteriana aguda do que nos outros grupos. Ainda no l?quor, os n?veis de triptofano, ?cido antran?lico, 3-hidroxiquinurenina e ?cido 3-hidroxiantran?lico n?o mostraram signific?ncia estat?stica, embora alguns deles apresentaram um bom ac?mulo durante meningite bacteriana aguda. No l?quor dos pacientes com meningite bacteriana foram observados n?veis mais elevados de TNF-alfa, IL-6, IL-1beta, IFN-gama, IL-10, IL-1Ra, MIP-1alpha, MIP-1beta, MCP-1 e G-CSF do que os outros grupos infectados. Em todas as amostras, as concentra??es de IL-2, IL-12(p70), IL-4, IL-8 e GM-CSF n?o variaram significativamente. No grupo com meningite bacteriana aguda foram tamb?m observadas elevadas concentra??es de IL-6, IL-10, IL-1Ra e MCP-1 no plasma. Baseado na compara??o das concentra??es dos metab?litos da via quinurenina no l?quor e no plasma, conclui-se que a ativa??o desta via metab?lica durante a meningite ocorre primordialmente dentro do c?rebro. O aumento na concentra??o dos metab?litos da quinurenina durante a infec??o deve-se ativa??o da enzima idoleamina 2,3 dioxigenase por prote?nas da resposta imune hospedeira principalmente pelo IFN-gama, IL1beta e TNF-alfa.
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Drew, Shelley Jean. "Hearing loss induced by bacterial meningitis : investigations into the possible involvement of: i) Bacterial ototoxins; ii) Nitric oxide, excitotoxicity, and reactive oxygen species." Thesis, University of Birmingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393838.
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Qarani, Sozan. "Investigation of the role of the non-integrin laminin receptor in the pathogenesis of bacterial meningitis." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/31739/.
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The human non-integrin laminin receptor (LamR) is a multifunctional protein which is localised to a number of sub-cellular locations. LamR is a component of the ribosome and has a number of intracellular functions; it also acts as an extracellular receptor for laminin, growth factors, pathogenic microorganisms, prion proteins, toxins and the anticarcinogen epigallocatechin gallate (ECGC). Although LamR is present in most cellular compartments, its overexpression in many types of cancer cells suggests a vital role for LamR in tumor-cell migration and invasion. There are two isoforms of laminin receptor: the monomeric 37-kDa laminin receptor precursor (37LRP) and the mature 67-kDa laminin receptor (67LR). Although the precise molecular nature of 67LR is unclear, accumulating evidence strongly suggest that 37LRP can undergo homo- and/or hetero-dimerization with Galectin-3 (Gal-3) to form mature 67LR. A recent study demonstrated that both homo- and heterodimer LamR forms are present on the cell surface, where they form distinct populations. Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) are major causes of bacterial meningitis. The contribution of LamR in traversal of the blood brain barrier (BBB) by neurotropic viruses is well established and interaction with LamR was recently found to be critical for initiation of bacterial contact with the blood brain barrier (BBB). These bacteria bind LamR via the surface protein adhesins: meningococcal PilQ and PorA; pneumococcal CbpA; and H. influenzae OmpP2. Further investigations showed that the fourth and second extracellular loops of meningococcal PorA and OmpP2 of H. influenzae, respectively, are responsible for LamR binding. The work presented here consists of two complementary projects in which a number of approaches were taken to characterise the ligand-binding domains of LamR. The first project aimed to identify sites on LamR that are critical for binding the ligands of bacterial meningeal pathogens. The second project aimed to identify residues that contribute to the stability of LamR homodimers and the heterodimer with Gal-3. Several mutations were introduced into full-length human LamR, either by deletion mutations within the C-terminal domain (CTD) of LamR using inverse polymerase chain reaction (IPCR), or by single-amino acid substitution in the N-terminal domain (NTD) of LamR using site-directed mutagenesis. Protocols for large-scale expression of full-length and truncated LamR proteins in human cells were developed, as well as non-denaturing purification protocols. We hypothesised that bacteria-binding domains could be located on both the NTD and CTD of LamR. In vivo examination using ELISA assays, in which the interaction of LamR and whole bacteria or purified recombinant PorA or PilQ were tested identified several novel sites on LamR that contributed significantly to binding of the bacterial ligands. These sites include amino acids 206-229 and 263-282, located within the CTD, and Tyrosine 156 in the NTD, each of which contributed to the binding of meningococcal PorA, and more specifically it’s fourth extracellular loop. Furthermore, three sites on LamR comprising amino acids 206-229 and 263-282 within the CTD and Tyrosine 139 in the NTD were shown to contribute to binding pneumococcal CbpA, OmpP2 and Loop two of OmpP2 of H. influenzae. These results indicate that the three neuroinvasive bacteria share the same binding sites on LamR. Bimolecular fluorescence complementation (BifC) coupled with flow cytometry and confocal microscopy revealed the vital contribution of amino acid residues Arginine 155, Tyrosine 156 and Lysine 166 (all within the NTD of LamR) for the homodimerization and heterodimerization of LamR with Gal-3. The dimerization of two meningococcal host receptors, LamR and Gal-3, may help to extend spectrum of their bacterial adhesins, which may act cooperatively or synergistically at different stages of infection. Information about the residues in LamR that contribute to the stabilization of LamR dimers has implications for the role of LamR dimers in the pathogenesis of bacterial meningitis. Identification of bacteria-binding domains on LamR is of particular interest for development of vaccines or therapeutic interventions that provide protection against the three major meningitis-causing bacteria. The aim of the current work was first to localise the domains of LamR responsible for binding with PorA and PilQ of N. meningitidis; CbpA and OmpP2 of S. pneumonia, and OmpP2 of H. influenzae. Also, previous studies have shown conspicuous homodimerisation of 37LRP and heterodimerisation with Gal-3. Our second aim was to identify of amino acid residues involved in 37LRP self-association and heterodimer formation with Gal-3. In current work, several regions of LamR were hypothesised to constitute the binding site for the bacterial ligands; these predictions were based on previous studies on LamR binding domains and the crystal structure of laminin receptor. Also, to investigate both homo and heterodimerisation of LamR, the involvement of several putative amino acid residues within 37LRP in LamR dimerisation was was hypothesised.
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Gudina, Esayas Kebede [Verfasser], and Hans-Walter [Akademischer Betreuer] Pfister. "Assessment of Treatment Strategies in Acute Bacterial Meningitis in Ethiopia / Esayas Kebede Gudina ; Betreuer: Hans-Walter Pfister." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/1121507956/34.
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Gjini, Ardiana. "Community acquired bacterial meningitis and meningococcal septicaemia amongst adults in England and Wales : epidemiology and clinical management." Thesis, Open University, 2009. http://oro.open.ac.uk/54215/.
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Background: Bacterial meningitis and meningococcal septicaemia are important causes of morbidity and mortality in the UK and elsewhere. There have been achievements in paediatric care, including vaccination; however mortality amongst otherwise healthy young adults remains high. Objective: I undertook this study to examine the way by which the public health burden of meningitis in adults can be reduced. Methods: I used routine surveillance data (laboratory reports, clinical notifications, hospital activity, mortality data) to examine the epidemiology and determine the changing trends. I undertook a capture-recapture study to quantify the underreporting through the routine surveillance. I conducted a retrospective review of clinical management of adult patients with meningitis in England and Wales using medical records of patients diagnosed with meningitis or meningococcal septicaemia. I examined the association of clinical management with the outcome of the disease (CABM and MS). Findings: The epidemiology of adult meningitis in England and Wales is changing. Overall forms of CABM show no significant changing trend, whilst meningococcal septicaemia shows an increasing trend. Tubercular meningitis is increasing significantly, whilst pneumococcal, HiB and Listeria meningitis are falling. Mortality generally remains in a steady trend. There are differences by age-group and causative organisms. There is considerable (-50%) underreporting of both, incidence and mortality from all major routine surveillance systems. Hospital management of meningitis is largely sub-optimal. Main areas of deficiency in clinical care are: timely diagnosis and consequently administration of antibiotics, assessment of severity, and record keeping; and these appeared to vary between the hospitals. It is difficult to examine the association between clinical with the outcome of meningitis primarily due to confounding by severity of illness which in my study was further jeopardised by the lack of recorded data and study power. Conclusion: This study has identified areas within public health interventions, such as vaccination policies, and clinical care, such as improved diagnosis and severity assessment, where there is potential for improvement towards a reduced public health burden of adult meningitis in England and Wales.
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Malerbi, Andréa Felice dos Santos. "Implante auditivo de tronco encefálico em pacientes com perda auditiva neurossensorial profunda por meningite e ossificação coclear total bilateral." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5143/tde-25082017-094437/.
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Introdução: O implante auditivo de tronco encefálico (ABI) é indicado para pacientes com perda auditiva neurossensorial severa a profunda quando há impossibilidade de realização do implante coclear. Em pacientes com surdez por meningite e ossificação coclear total bilateral, o ABI é a opção para a reabilitação auditiva. Objetivos: O estudo tem por objetivo avaliar a contribuição do ABI para os limiares audiométricos e para a percepção de fala após no mínimo 12 meses de uso em pacientes com ossificação coclear total por surdez pós-meningite, bem como descrever as complicações do procedimento. Material e métodos: Dez pacientes com surdez pósmeningite foram submetidos ao ABI por via retrolabiríntica ampliada em um centro terciário de assistência e ensino. Todos os pacientes foram operados pela mesma equipe cirúrgica e a avaliação audiológica foi realizada pelo mesmo fonoaudiólogo. Foram realizados audiometria tonal e testes de percepção de fala no pré-operatório e no mínimo 12 meses após a ativação do implante. Foram descritas as complicações associadas ao procedimento. Resultados: Oito de dez pacientes implantados permaneceram usuários. Dois pacientes não apresentaram respostas auditivas e abandonaram o seguimento. Os oito pacientes apresentaram melhora estatisticamente significativa nos limiares audiométricos, bem como nos testes de discriminação de palavras e vogais comparando pré e pós-operatório com média de seguimento de 3,3 anos. Em dois pacientes, a discriminação de sentenças em formato fechado somente no modo auditivo foi de 30% e 40%. Todos os oito usuários referiram benefício com o uso do ABI. Não houve complicações relacionadas ao procedimento. Conclusão: O ABI via retrolabiríntica ampliada é uma opção terapêutica segura para pacientes com surdez pós-meningite e com presença de ossificação coclear total bilateral, contribuindo para melhora nos limiares audiométricos e nos testes de percepção de fala. Embora a melhora nos testes audiológicos seja inferior à do implante coclear, a maioria dos pacientes do estudo usa o ABI diariamente por um período superior a 8 horas e refere benefício em seu cotidianoIntroduction: The Auditory Brainstem Implant (ABI) is an option to auditory restoration in patients with severe to profound sensorineural hearing loss who cannot be fitted with a cochlear implant. This is the only option in patients with post meningitis hearing loss presenting with bilateral total cochlear ossification. Objectives: The main objective of the study is to evaluate the hearing contribution in audiometry and speech perception tests at least 12 months after ABI implantation in patients with post-meningitis profound hearing loss. The complications of the procedure were also described. Materials and Methods: Ten patients with post-meningitis hearing loss went an ABI through extended retrolabyrinthine approach in a tertiary center by the same surgeons. The same audiologist was responsible for audiological follow-up. Tonal audiometry and speech perception tests were made before and at least 12 months after the ABI activation. The procedure complications were described for all patients. Results: Eight of ten patients became ABI users. Two patients had no auditory response and abandoned the treatment. Eight users showed benefit in tonal audiometry, word and vowels perception tests after an average follow up of 3.3 years. Two patients were able to recognize 30 and 40% of closed sentences without lip reading. There were no complications due to the ABI procedure. Conclusion: The extended retrolabyrinthine approach for the ABI is a safe surgical option for patients with post-meningitis hearing loss and totally ossified cochleae. It contributes to hearing performance in audiometry and speech perception tests. Even though the ABI results are poorer than the cochlear implants, in this study the majority of patients use their ABI more than eight hours a day and report benefits in daily activities
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Moraes, José Cassio de. "Epidemiologia das meningites bacterianas por Haemophilus influenzae, Streptococcus pneumoniae e enterobactérias no município de São Paulo, 1960-77." Universidade de São Paulo, 1988. http://www.teses.usp.br/teses/disponiveis/6/6132/tde-18122017-115821/.
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As meningites bacterianas constituem um sério problema de Saúde Pública em todo mundo, por sua incidência, sua letalidade e pela frequência das sequelas que os sobreviventes apresentam. Os agentes etiológicos Haemophilus influenzae, Neisseria meningitidis e Streptococcus pneumoniae são responsáveis por cerca de 60 a 80 por cento dos casos. O presente estudo tem como objetivo conhecer o comportamento epidemiológico das meningites por H.influenzae, S. pneumoniae e por bacilos Gram-negativo, especialmente as enterobactérias 1 no Município de São Paulo no pertodo 1960- 77. O levantamento foi realizado por uma equipe formada por professores do Departamento de Medicina Social da Faculdade de Ciências Médicas da Santa Casa de São Paulo, por médicos sanitaristas e por acadêmicos de medicina. Os dados, colhidos diretamente do prontuário dos pacientes, foram anotados em uma ficha pré-codificada. A meningite por H.influenzae somente foi confirmada quando se identificava o agente na cultura. A confirmação da meningite por S.pneumoniae se dava pela bacterioscopia e/ou pela cultura do líquor. As meningites por bacilo Gram-negativo foram subdivididas em 3 grupos. No primeiro, incluíram-se os casos em que a bacterioscopia e/ou cultura revelaram a presença de um bacilo Gram-negativo sem, contudo, haver a especificação do agente. No segundo, classificaram-se os casos em que, na cultura, foi isolada uma bactéria do gênero Salmonella. O último grupo correspondeu áquele em que se identificou a presença de uma outra enterobactéria. Os subdistritos ou distritos do Municipio de São Paulo foram agrupados de 3 maneiras. As duas primeiras corresponderam às 3 ou 6 áreas homogêneas especificadas pela Fundação SEADE. A última se baseou na distibuição da população economicamente ativa segundo sua participação nos diferentes setores da economia. A população dos subdistritos e distritos do Município de São Paulo segundo faixa etária para os anos compreendidos no estudo foi estimada pelo método geométrico modificado. No período estudado foram confirmados 900 casos de meningite por H.influenzae com um coeficiente médio de 0,89 por 100000 habitantes. Os menores de 5 anos contribuíram com 91,2 por cento dos casos, dos quais 63 por cento eram em menores de um ano. O coeficiente médio para menores de um ano foi de 23,3 por 100000 habitantes. As zonas central, intermediária e periférica não apresentaram incidências significantemente diferentes. Os coeficientes de morbidade padronizados segundo idade foram 0,8, 0,8 e 0,9 para as zonas central, intermediária e periférica, respectivamente. A letalidade média no período de 1960-77 foi de 31 por cento . As crianças menores de um ano apresentaram a maior taxa de letalidade, 40 por cento . No período 1960-77 foram confirmados 1951 casos de meningite por S.pneumoniae com um coeficiente médio de 1,9 por 100000 habitantes. As crianças menores de 5 anos contribuíram com 52 por cento dos casos dos quais 38.5 por cento eram menores de um ano. Os coeficientes médio por 100000 habitantes, para os menores de um ano, foram 37,1 e 29,7 para 1960-69 e 1970-77, respectivamente. A incidência por 100000 habitantes na zona periférica (2,2) na primeira década foi, praticamente, o dobro da zona central, (1,2). Os coeficientes padronizados segundo idade foram 1,6, 1,5 e 2,0 para as zonas central, intermediária e periférica, respectivamente. No período seguinte estes valores foram 1,4, 1,5 e 2,0. A letalidade média no período foi de 44 por cento . Ela foi inversamente proporcional ao número de leucócitos no llquor de entrada. A letalidade na faixa etária menores de um ano foi de 60 por cento no período estudado. No período estudado foram identificados 290 casos de meningite por Salmonella dos quais 10 por cento o foram na primeira década. O coeficiente médio por 100000 habitantes foi de 0,3. A S.typhimurium foi a espécie mais frequente com 112 casos. Os menores de um ano contribuíram com 91 por cento dos casos, dos quais 52 por cento ocorreram no primeiro trimestre de vida. A incidência média por zona não mostrou diferencas estatisticamente significantes. A letalidade média foi de 87 por cento . Os menores de um ano apresentaram um valor ainda maior, 89 por cento . No período estudado foram identificados 211 casos de meningite por outras enterobactérias com um coeficiente médio de 0,2. A primeira década contribuiu com 32 por cento dos casos. Os gêneros Escherichia e Enterobacter foram os mais frequentes sendo responsáveis por 71 por cento dos casos. Os menores de um ano contribuiram com 57 por cento dos casos, com coeficiente de 4.0 e 4.5 para os períodos 1960-69 e 1970-77 respectivamente. A letalidade média foi de 65 por cento sendo o grupo etário maior de 60 anos o de maior letalidade. A incidência por zona não diferiu significantemente. A meningite por bacilo Gram-negativo apresentou um comportamento epidemiológico distinto da meningite por H.influenzae e das enterobactérias, revelando ser composto por uma miscelânea de agentes. No período de estudo foram identificados 25455 casos de meningite bacteriana, com coeficiente médio de 25 por 100000 habitantes. O coeficiente passaria a ser de 36 por 100000 habitantes se acrecentássemos as meningites bacterianas de etiologia indeterminada. Este índice representou 1 caso para 2782 habitantes. A meningite por N.meningitidis ocupou o primeiro lugar, com 84 por cento dos casos e um coeficiente médio de 21 por 100000. Na primeira década ocorreram 2657 casos, com um coeficiente médio de 5,4 por 100000 habitantes. As três principais etiologias foram responsáveis por 89 por cento dos casos. No octênio seguinte a meningite por meningococo foi responsável por 90 por cento dos casos. No ano de 1974, acme da epidemia de meningite meningocócica, foram identificados 18069 casos de meningite representando um coeficiente de 264 por 100000. Este valor representaria que 1 em cada 379 habitantes foi acometido pela doença naquele ano.Bacterial meningitis is an intectious disease of major public health throughout the world because of its high incidence and case fatality rates and the permanent sequelae that are seen in the survivors. Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae are the etiologic agents responsible for 60 to 80 per cent of cases. The purpose of this study is to better understand the epidemiology of meningitis caused by H. influenzae, S. pneumoniae and gram-negative bacilli, especially, the Enterobacteriaceae, in the city of São Paulo during the period 1960-77. The survey was performed by a group of professors from the Department of Social Medicine of the \"Faculdade de Ciências Médicas da Santa Casa de São Paulo\", public health physicians and medical students. Data were obtained directly from the patient\'s records and registered on a pre-coded form. Cases of H.influenzae meningitis were confirmed by culture while S.pneumoniae cases were confirmed by gram stain and/or culture of the cerebrospinal fluid (CSP). The cases of gram negative bacillary meningitis were divided into three groups. The first included the cases that were diagnosed by gram stain and culture; the second, the cases where salmonella species were isolated in the culture: and the third, the cases where the presence of other Enterobacteriaceae were identified. The districts of the city of São Paulo were grouped in three ways: two corresponding to the homogenous areas specified by the \"Fundação SEADE\", and the third one based on the distribution of the economically active population according to its participation in the different branches of economic activity. The population of São Paulo by districts included in the study was estimated by the modified geometric method. During the study, 900 cases ot H. influenzae meningitis were confirmed, giving an average rate ot 0.89 cases per 100,000 population. Children <5 years old represented 91 per cent ot the cases, 63 per cent of them being less than one year old . The average rate for children <1 year old was 23.3 cases per 10O,OOO population. The average case fatality rate for the period 1960-77 was 31 per cent . The hightest case fatality rate ocurred in children <1 year old and was 40 per cent . The central, intermediate and peripheria zones didn\'t show significant different rates of incidence. The age standartized morbidity rates for these zones were, respectively, 0.8, 0.8 and 0.9. During 1960-77, 1,951 cases of S.pneumoniae meningitis were confirmed, giving an average rate of 1.9 per 100,000 population. Children <5 years old accounted for 52.4 per cent ot cases and 38.5 per cent were
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Koutangni, Thibaut. "Modélisation des méningites bactériennes dans la ceinture africaine des méningites pour l’évaluation de la vaccination préventive Incidence, Carriage and Case-Carrier Ratios for Meningococcal Meningitis in the African Meningitis Belt : A Systematic Review and Meta-Analysis Compartmental Models for Seasonal Hyperendemic Bacterial Meningitis in the African Meningitis Belt." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS159.
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Une dynamique saisonnière régulière (hyperendémie) et épidémique est observée pour les méningites à méningocoques et pneumocoques dans la ceinture africaine des méningites. Comprendre cette dynamique est essentiel pour une meilleure prévention et modélisation. Les hyperendémies serait liées à un risque accru de méningite chez les porteurs sains du méningocoque et du pneumocoque ; ou une transmission accrue de ces bactéries par les porteurs sains et les personnes malades en saison sèche. Nous avons développé trois modèles mathématiques des méningites, incluant l’une ou la combinaison des deux hypothèses. Les modèles étaient paramétrés sur base des connaissances actuelles de la biologie et la physiopathologie des méningocoques et des pneumocoques. Nous avons comparé les performances des modèles à prédire les cas de méningites bactérienne aiguë notifiés par des formations sanitaires au Burkina Faso entre 2004-2010, dans le cadre de la surveillance des méningites. Les prédictions des modèles étaient satisfaisantes (R2, 0.72, 0.86, 0.87). Forcer la saisonnalité de la transmission seule ou et du risque de méningite permettent de mieux prédire l'amplitude des hyperendémies saisonnières. Cependant, le modèle incluant la saisonnalité de la transmission seule nécessitait un taux d'invasion constant plus élevé. Ces résultats suggèrent que des variations saisonnières du risque de méningite et de transmission des bactéries contribuent aux hyperendémies saisonnières. En conséquence, des interventions réduisant le risque de transmission et d’invasion bactériennes, pendant la saison sèche, seraient nécessaires pour limiter la saisonnalité de la méningite bactérienne en AfriquePathophysiological mechanisms underlying the seasonal dynamic and epidemic occurrence of bacterial meningitis in the African meningitis belt remain unknown. Regular seasonality (hyperendemicity) is observed for meningococcal and pneumococcal meningitis. Understanding this is critical for better prevention and modelling. The two main hypotheses for hyperendemicity during the dry season imply an increased risk of invasive disease given asymptomatic carriage of meningococci and pneumococci; or an increased transmission of these bacteria from carriers and ill individuals. We developed three mathematical models of seasonal hyperendemicity, featuring one or a combination of the two hypotheses. Models were parameterized based on current knowledge on meningococcal and pneumococcal biology and pathophysiology. We compared the models’ performance in reproducing weekly incidences cases of acute bacterial meningitis reported by health centres in Burkina Faso during 2004–2010, through meningitis surveillance. All models performed well (R2, 0.72, 0.86, 0.87). Seasonal forcing transmission only or and risk of meningitis better captured amplitude of seasonal incidence. However, seasonal forcing transmission alone required a higher constant invasion rate. These results suggest a combination of seasonal changes of the risk of invasive disease and carriage transmission is involved in hyperendemic bacterial meningitis in the African meningitis belt. Consequently, interventions reducing the risk of nasopharyngeal invasion and the bacteria transmission, especially during the dry season are believed to be needed to limit the recurrent seasonality of bacterial meningitis in the meningitis belt
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Bellac, Caroline. "Pathomechanisms of bacterial meningitis based on transcriptome analysis : role of kynurenine 3-hydroxylase and galectin-3/-9 in brain injury /." [S.l.] : [s.n.], 2007. http://www.zb.unibe.ch/download/eldiss/07bellac_c.pdf.
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Pelegrín, Senent Iván. "Clinical approach and management of bacterial infections of the central nervous system related to hydrocephalus." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/585886.
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INTRODUCTION: Community-acquired bacterial meningitis is a relevant entity related to a high morbidity and mortality, despite of the adjuvant and antibiotic treatments available. Morbidity and mortality are caused by neurological complications, being hydrocephalus one of the less investigated one and related to Listeria monocytogenes meningoencephalitis episodes, which increase have been reported in the last decade. Moreover, the devices used for treatment of hydrocephalus have a high risk of infection. These infections have a high personal and economic costs, and their prevention and treatment management can be optimised.
HYPOTHESIS: Studying certain aspects of community-acquired bacterial and device-related infections of the central nervous system might improve management and outcome of these patients.
OBJECTIVES: 1. To describe the impact on outcome with hydrocephalus complicating community acquired bacterial meningitis patients. 2. To evaluate prognostic factors related to sequelae and mortality in L. monocytogenes meningoencephalitis. 3. To assess efficacy of different treatment strategies on a cohort of patients with ventriculoperitoneal shunt infections. 4. To evaluate, in vitro, a new antibiotic-impregnated external ventricular drainage catheter to prevent Acinetobacter baumannii infections.
METHODS: Observational clinical study of a cohort of community-acquired bacterial meningitis and ventriculoperitoneal shunt infection patients during more than 35 years in a university reference hospital. Experimental study of efficacy of an antibiotic-impregnated external ventricular catheter tested by a dynamic in vitro model.
RESULTS: Among 790 community-acquired bacterial meningitis patients, 22 (3%) presented complicating hydrocephalus. 7/22 (32%) episodes were caused by L. monocytogenes and Streptococcus pneumoniae. Mortality of patients with complicating hydrocephalus was 50%. Age, time to illness and L. monocytogenes aetiology were risk factors related to development of hydrocephalus. L. monocytogenes episodes increased in the last decade (from 0.73 episodes/1000 admissions to 1.02/1000 admissions per year). Mortality was 24% and neurological sequelae 18%. Seizures were present in 14% and hydrocephalus in 16% of patients. The addition of gentamicin to ampicillin, use of adjuvant dexamethasone and antiepileptic prophylaxis with phenytoin did not influence outcome. Risk factors related to a worse outcome were the presence of hydrocephalus and the inappropriate empirical antibiotic treatment. Among 86 episodes of ventriculoperitoneal shunt infections: 6 received only antibiotic therapy; 24 were managed with a shunt removal without replacement; 37 were managed with a shunt replacement in 2 steps; and 19 with a shunt replacement in one step. The most effective strategy was shunt replacement in 2 steps (89% cure). 6/9 (67%) external ventricular drainage catheters impregnated with trimethoprim, rifampin and triclosan were free of colonisation at least for 3 weeks after several inoculations with 104 A. baumannii in an in vitro model.
CONCLUSIONS: The development of hydrocephalus complicating an episode of community acquired bacterial meningitis causes a worse rate of mortality and sequelae. The outcome of L. monocytogenes patients could be improved if the empirical antibiotic treatment is accurate and if a precise suspicion and management of potential hydrocephalus occurs. Shunt removal, particularly in 2 steps when the patient is not shunt-dependant, is the best strategy in the treatment of a ventriculoperitoneal shunt infection, without increasing morbidity. A new external ventricular drainage catheter impregnated with triclosan, rifampin and trimethoprim might prevent multirresistant A. baumannii ventriculitis.INTRODUCCIÓN: La meningitis bacteriana adquirida en la comunidad es una enfermedad asociada a una elevada morbimortalidad a pesar de los tratamiento adyuvantes y antibióticos disponibles. Su principal causa son las complicaciones neurológicas. La hidrocefalia secundaria es de las menos estudiadas y además está asociada a la etiología Listeria monocytogenes, de reciente incremento en países desarrollados. Por otra parte, los dispositivos utilizados para el tratamiento de la hidrocefalia, drenajes ventriculares temporales y permanentes, tienen alto riesgo de infección. Cuando esto sucede, las consecuencias de la infección, tanto en el paciente como en el sistema sanitario, son importantes, siendo las estrategias de prevención y tratamiento de estas infecciones mejorables. Hipótesis: Estudiar aspectos concretos de las infecciones bacterianas del sistema nervioso central, tanto comunitarias como asociadas a dispositivos, puede ayudar a mejorar el manejo y pronóstico de los pacientes. OBJETIVOS: 1. Determinar el impacto de la hidrocefalia secundaria en el pronóstico de los pacientes con meningitis bacteriana adquirida en la comunidad. 2. Analizar los factores pronósticos de mortalidad y secuelas en la meningoencefalitis por L. monocytogenes. 3. Evaluar la eficacia de diferentes estrategias de tratamiento en una cohorte de pacientes con infecciones de shunt ventriculoperitoneal. 4. Evaluación in vitro de un nuevo drenaje ventricular externo impregnado con antibióticos para prevenir las infecciones por Acinetobacter baumannii multiresistente. MÉTODOS: Estudio clínico observacional de una cohorte de pacientes con meningitis bacteriana adquirida en la comunidad e infecciones de shunt ventriculoperitoneal durante más de 35 años en un Hospital universitario de referencia para infecciones del sistema nervioso central. Estudio experimental de la evaluación de la eficacia de un drenaje ventricular externo impregnado en antibióticos en un modelo dinámico in vitro. Resultados: De 790 pacientes con meningitis bacteriana adquirida en la comunidad, 22(3%) presentaron hidrocefalia como complicación. 7/22(32%) episodios fueron causados por L. monocytogenes y Streptococcus pneumoniae. La mortalidad de los pacientes que presentaron hidrocefalia fue del 50%. La edad, un tiempo de enfermedad avanzado y la etiología L. monocytogenes fueron factores de riesgo asociados a desarrollar hidrocefalia. Los episodios de meningoencefalitis por L. monocytogenes se incrementaron en los últimos 10 años (de 0.73 episodios/1000 admisiones a 1.02/1000 admisiones). La mortalidad fue 24% y las secuelas neurológicas 18%. La frecuencia de crisis comicial fue del 16% y de hidrocefalia del 14%. La adicción de gentamicina al tratamiento con ampicilina no modificó el pronóstico, al igual que el uso de dexametasona ni de profilaxis con fenitoína. Los factores asociados a mal pronóstico fueron la presencia de hidrocefalia y el tratamiento antibiótico empírico inadecuado. De 86 episodios de infección de shunt ventriculoperitoneal: 6 episodios se manejaron sólo con antibióticos; en 24 se retiró el shunt sin recambio; en 37 se realizó un recambio en 2 tiempos del shunt; y en 19 un recambio en un tiempo. La estrategia más efectiva fue el recambio en 2 tiempos (89% de curación). 6/9(67%) drenajes ventriculares externos impregnados en trimetroprim, rifampicina y triclosan permanecieron libre de colonización al menos 3 semanas tras varias inoculaciones con 104 A. Baumannii en un modelo in vitro. CONCLUSIONES: La hidrocefalia secundaria a un episodio de meningitis bacteriana adquirida en la comunidad conlleva una mayor gravedad neurológica y un peor pronóstico en cuanto a mortalidad y secuelas. El pronóstico de la meningoencefalitis por L. Monocytogenes podría mejorar si se administra un tratamiento antibiótico empírico adecuado y si se sospecha y se maneja correctamente la potencial hidrocefalia secundaria. La retirada del shunt , concretamente en dos tiempos cuando el paciente es shunt dependiente, es la estrategia de elección en el tratamiento en una infección de shunt ventriculoperitoneal, sin aumentar la morbilidad. Un nuevo drenaje ventriuclar externo impregnado con triclosan, rifampicina y trimetroprim podría prevenir las ventriculitis por A. baumannii multiresistente.
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Ільїна, Ніна Іванівна, Нина Ивановна Ильина, Nina Ivanivna Ilina, Вікторія Валеріївна Ільїна, Виктория Валерьевна Ильина, and Viktoriia Valeriivna Ilina. "Етіологія і клінічні ознаки бактерійного менінгіту в Сумській області." Thesis, Тернопільський державний медичний університет імені І. Я. Горбачевського, 2017. http://essuir.sumdu.edu.ua/handle/123456789/65034.
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За останнє десятиріччя відбувається тенденція до зростання захворюваності на гострі серозні менінгіти неуточненої етіології. У структурі БГМ при встановленій етіології (76,4%) переважали захворювання, спричинені менінгококовою та стрептококовою інфекціями. Переважна більшість БГМ, спричинених іншими мікроорганізмами, а також нез’ясованої етіології, були вторинними.За последнее десятилетие произошла тенденция к повышению заболеваемости острыми серозными менингитами неуточненной этиологии. В структуре бактериального гнойного менингита установленной этиологии (76,4%) преобладали заболевания, вызванные менингококковой и стрептококковой инфекциями. Преимущественное большинство БГМ, вызванных другими микроорганизмами, а также невыясненной этиологии, были вторичными.
Over the past decade, there has been a trend towards an increase in the incidence of acute serous meningitis, unspecified etiology. The structure of bacterial purulent meningitis of established etiology (76.4%) was dominated by diseases caused by meningococcal and streptococcal infections. The predominant majority of BMS, caused by other microorganisms, as well as unexplained etiology, were secondary.
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Пипа, Л. В., Р. В. Свістільник, Ю. М. Лисиця, and В. В. Бавровський. "Нейронсентитична енолаза - маркер нейродеструкції при менінгітах у дітей." Thesis, Сумський державний університет, 2015. http://essuir.sumdu.edu.ua/handle/123456789/43133.
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Хвороби центральної нервової системи інфекційної природи займають друге місце серед причин
первинної інвалідизації населення, поступаючись лише судинній патології головного мозку. За даними Гузевой В. И. та співавт. (2004), частота менінгітів серед всіх органічних уражень нервової системи становить 27-29 %. Незважаючи на сучасні досягнення в лікуванні менінгітів із застосуванням сучасної етіологічної та патогенетичної терапії, летальність від них залишається досить високою (10-60 %) і за
останні 20 років суттєво не змінилась. За даними Emonts M. et al. (2004), летальність від менінгококового менінгіту складає 4-6 %, тоді як від ускладненого септичним шоком – до 40 %.
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Braun, Benedikt Johannes [Verfasser]. "The formyl peptide receptor like-1 and scavenger receptor MARCO are involved in glial cell activation in bacterial meningitis / Benedikt Johannes Braun." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2014. http://d-nb.info/1051428076/34.
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Khumalo, Jermaine. "The use of molecular diagnostic methods to improve the detection of the common bacterial and viral causes of community acquired meningitis in children in South Africa." Master's thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/15539.
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With conventional methods of diagnosis, substantial overlaps are common due to an absence of the expected CSF findings clearly aligning to bacterial or viral infection. Reduced sensitivity is commonly observed chiefly due to empiric antibiotic treatment leading to bacterial culture negative results. This leads to costly hospital admissions and unnecessarily prolonged treatment for the unexplained aetiology, further compounded by routine viral diagnostics not being commonly implemented for meningitis diagnosis. We developed and validated in-house quantitative real-time (qPCR) multiplex assays to test for bacterial causes namely: Neisseria meningitidis (ctrA gene), Haemophilus influenzae (hpd gene) and Streptococcus pneumoniae (lytA gene) and viral causes namely: enterovirus (5' UTR), herpes simplex (UL30 gene) and mumps virus (Fusion protein gene). The qPCR assays were carried out on the Biorad CFX 96 real-time instrument. These validated assays were used to screen a cohort of suspected meningitis cases. The retrospective study included 300 paediatric patients aged from 60 days-12 years, over a 1-year period (November1, 2012 to November 30, 2013) with suspected meningitis presented to the outpatient departments of the Red Cross War Memorial Children‟s Hospital (RCCH) in Cape Town. Cerebrospinal fluid with abnormal chemistry and cell counts was selected and total nucleic acid was extracted with the QIAsymphony virus/bacterial DSP kit (QIAGEN, Valencia, CA). The median age of children was 19 months (IQR: 6-65 months). Among the screened 291 CSF samples, 7 (2.4%) cases Gram stain results were obtained along with relatively few cases with positive bacterial culture growth 4/291 (1.4%). Based on bacterial qPCR results, 8 (2.7%), 3 (1%) and 1 (0.3%) were positive for S. pneumoniae, N. meningitidis and H. influenzae respectively. A majority of cases were viral positives with enteroviruses being the dominant at 91/291 (31.3%) and mumps virus 3/291 (1%). No herpes simplex DNA was detected. The bacterial qPCR showed a sensitivity and specificity of 85.7% and 97.7% respectively when compared against a composite reference standard (CRS). We report an improvement with additional detected causes of bacterial meningitis and highlight the burden of the common viral causes. However, a large proportion of cases (63.6 %) have aetiology still unknown. PCR shows valuable in concluding viral aetiology in routine diagnosis.
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Costa, Gleise Aparecida Moraes. "Comportamento da meningite bacteriana neonatal de acordo com o peso de nascimento." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5141/tde-06022007-095913/.
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A meningite bacteriana no período neonatal é uma doença grave, associada à mortalidade elevada e seqüelas em cerca de 12 a 29% dos sobreviventes. Nos recém-nascidos com peso ao nascimento < 2500 g, o risco de adquirir meningite é três vezes superior àqueles com peso >= 2500 g e, entre neonatos de muito baixo peso (< 1500 g), o risco é 17 vezes maior. Objetivo: Geral: descrever o quadro clínico e as complicações da meningite bacteriana em dois grupos de recém-nascidos, considerados de acordo com o peso de nascimento (= 2500 g). Específico: descrever e comparar os agentes etiológicos, a freqüência de sinais e sintomas neurológicos e de complicações, a mortalidade e a duração do tratamento nos dois grupos. Métodos: Estudo observacional de 87 recém-nascidos com meningite bacteriana, admitidos na Unidade de Cuidados Intensivos Neonatais do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 11 anos (janeiro de 1994 a dezembro de 2004). Os dados foram obtidos através da análise de prontuários. Na análise estatística foram utilizados o teste exato de Fisher e teste não paramétrico de Mann Whitney. Resultados: Foram identificadas bactérias no líquor em 39% dos pacientes, sendo 50% bactérias Gram-positivas e 50% Gram-negativas. A maioria dos neonatos apresentou sinais e sintomas inespecíficos: febre (63,2%), irritabilidade (31%), letargia (26,4%). Os achados neurológicos ocorreram em 35,3% dos casos. As complicações ocorreram em 48,2% dos neonatos, principalmente convulsões (23%), hemorragia intracraniana (14,9%) e hidrocefalia (13,8%) com mortalidade de 11,5 %. Na comparação entre evolução clínica e peso de nascimento observou-se associação entre peso >= 2500 g e convulsão (p=0,047), peso >= 2500 g e fontanela abaulada (p=0,019), bactéria no LCR e complicações (p=0,008) e bactéria no LCR e óbitos (p=0,043). Conclusões: Os agentes etiológicos mais freqüentemente identificados no LCR foram as enterobactérias (41%), seguidas de Streptococcus B (17,5%), Streptococcus não B (17,5%), Staphylococcus aureus (11,7%), Neisseria meningitidis (8,8%) e Enterococcus faecalis (3,0%), não havendo diferença entre tipo de bactérias e peso de nascimento. Os sinais e sintomas predominantes foram inespecíficos, com achados neurológicos em 35% dos casos. A freqüência maior de sintomas neurológicos nos recém-nascidos com peso >= 2500 g, sugere maior grau de maturidade do sistema nervoso central nestas crianças. Embora a mortalidade tenha sido inferior à observada em estudos anteriores no mesmo Serviço, a freqüência de complicações foi alta, independentemente do peso de nascimento. A presença de bactéria no LCR associou-se à maior freqüência de convulsões e mortalidade. A necessidade de manutenção do tratamento por tempo mais prolongado nos recém-nascidos de baixo peso sugere maior gravidade da doença neste grupo de neonatos.Bacterial meningitis in the neonatal period is a severe disease, associated to elevated mortality and sequelae in around 12 to 29% of the survivors. Newborns whose birth weight is < 2,500g have a 3-fold increase in the risk of acquiring meningitis when compared to those whose weight is >= 2,500; among those with very low birth weight (< 1,500g), the risk increases 17-fold. Objectives: General: to describe the clinical picture and the complications of bacterial meningitis in two groups of newborns, considered according to birth weight (< 2,500g or >= 2,500g). Specific: to describe and compare the etiological agents, the frequency of neurological signs and symptoms and complications, mortality rate and duration of treatment in both groups. Methods: Observational study of 87 newborns with bacterial meningitis, admitted at the Neonatal Intensive Care Unit (NICU) of Instituto da Criança of Hospital das Clínicas of the University of São Paulo School of Medicine, during an 11-year period (January 1994 to December 2004). The data were obtained through the analysis of hospital files. Statistical analysis was carried out with Fisher\'s exact test and the non-parametric Mann Whitney test. Results: Bacteria were identified in the cerebrospinal fluid (CSF) of 39% of the patients, with 50% of them being Gram-positive and 50%, Gram-negative. Most neonates presented unspecific signs and symptoms: fever (63.2%), irritability (31%), and lethargy (26.4%). The neurological findings occurred in 35.3% of the cases. Complications occurred in 48.2% of the neonates, and were mainly seizures (23%), intracranial hemorrhage (14.9%) and hydrocephalus (13.8%) with a mortality rate of 11.5%. At the comparison between clinical evolution and birth weight, associations between weight >= 2,500g and seizures (p=0.047), weight >= 2,500g and concave fontanel (p=0.019), bacteria in the CSF and complications (p=0.008) and bacteria in the CSF and death (p=0.043) were observed. Conclusions: The etiological agents most often identified in the CSF were enterobacteria (41%), followed by B Streptococcus (17.5%), non-B Streptococcus (17.5%), Staphylococcus aureus (11.7%), Neisseria meningitidis (8.8%) and Enterococcus faecalis(3.0%), with no statistical difference between the type of bacteria and birth weight. The predominant signs and symptoms were unspecific, with neurological findings in 35% of the cases. The higher frequency of neurological signs and symptoms in newborns with birth weight >= 2,500g suggest a higher degree of central nervous system maturity in these infants. Although the mortality was lower than that observed in previous studies at the same Service, the frequency of complications was high, regardless of birth weight. The presence of bacteria in the CSF was associated to a higher frequency of seizures and mortality. The need for prolonged treatment in newborns with low birth weight suggests higher disease severity in this group of neonates.
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NEVES, Jane Marcia Brito das. "Meningites Bacterianas Agudas em crianças e adolescentes: Fatores de risco para óbito ou seqüelas precoces." Universidade Federal de Goiás, 2005. http://repositorio.bc.ufg.br/tede/handle/tde/1829.
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Previous issue date: 2005-11-26Objetive: To identify possible risk factors associate with poor prognosis among children and teenagers with acute bacterial meningitis Methods: Prevalence study with casecontrol analysis by review of medical records of patients aged 1 month to 19 years admitted to Tropical Disease Hospital in Goiânia Goiás with acute bacterial meningitis from 1 january 1998 to 31 december 2001 Patients who died or had one or more neurological sequelae at discharge were cosidered cases and patients with the same diagnosis but discharged with healthy recoveries as controls Risk factors for adverse outcome such as age sex proceeding area period between onset of symptoms and hospital admission history of antibiotic use etiologic agent meningeous signs level of consciousness convulsion circulatory and respiratory distress and laboratory values including peripheral white blood cels counts cerebrospinal fluid (CSF) protein level CSF glucose level and CSF white blood cels count were analysed Univariate analysis and logistics regression was used to evaluate the association between death or neurologic sequelae (depedents variables) and each risk factors (independent variable) Results: Of the 409 children and 117 teenagers admitted during the period of study 430 discharged with healthy recoveries 43 (8,2%) died and 53 (10,1%) had at least one sequelae at discharge (motor deficit, seizure hydrocephalus hearing impairment, cranial nerve deficits cerebral palsy and ataxia) Age < 24 months circulatory and respiratory distress torpor or coma seizure absence of meningeous signs proceeding area and peripheral white blood cels count < 5000/ mm³ were associated with poor prognosis However, age <24 months respiratory distress and torpor or coma were independently associated with adverse outcome Conclusion: Age < 24 months respiratory distress and torpor or coma were the main risk factors independently associated with poor prognosis Early identification of the all risk factors is very important to select the patients who need special care during of stay in hospital and after discharge at least until school age
Objetivo: Identificar os possíveis fatores de risco associados à evolução desfavorável em crianças e adolescentes com meningite bacteriana aguda (MBA) Casuística e métodos: Estudo de prevalência com análise tipo caso-controle mediante revisão dos prontuários de pacientes com idade de 1 mês a 19 anos internados com MBA no Hospital de Doenças tropicais (HDT) em Goiânia-Goiás durante o período de janeiro de 1998 a dezembro de 2001 Foram considerados casos os pacientes que faleceram ou apresentaram seqüelas evidentes na alta atribuíveis a MBA (n = 96) e controles os pacientes que receberam alta aparentemente com total recuperação (n = 430) Como possíveis fatores de risco para evolução desfavorável foram analisadas as variáveis: idade sexo procedência tempo de doença até a internação uso prévio de antibiótico agente etiológico sinais meníngeos nível de consciência ocorrência de convulsão de disfunção cardiorrespiratória e de alterações laboratoriais referentes a leucometria glicorraquia proteinorraquia e celularidade liquórica A análise univariada e a de regressão logística foram utilizadas para avaliar a associação entre evolução fatal e seqüela neurológica diagnosticada na alta (variáveis dependentes) e cada fator considerado como de risco (variáveis independentes) Resultados: Das 409 crianças e 117 adolescentes com MBA que participaram do estudo 430 evoluíram para cura (81,7%) sem seqüelas aparentes 43 (8,2%) faleceram e 53 (10,1%) apresentaram pelo menos uma seqüela evidente na alta: déficit motor em 23 (43,4%) convulsão em 21 (39,6%) hidrocefalia em 9 (17%) hipoacusia em 7 (13,2%) ptose palpebral em 4 (7,5%), estrabismo em 3 (5,7%) diplopia em 2 (3,8%) ataxia paralisia cerebral, e paralisia facial em 1 (2%) paciente Idade < 2 anos disfunção cardiorrespiratória torpor ou coma convulsão ausência de sinais meníngeos procedência e leucopenia foram os fatores de risco associados a mau prognóstico No entanto idade < 2 anos disfunção respiratória e torpor ou coma mostraram-se independentemente associados com óbito e seqüelas Conclusões: Idade < 2 anos disfunção respiratória e torpor ou coma foram os principais fatores de risco associados independentemente a mau prognóstico A identificação precoce de todos fatores de risco associados a óbito ou seqüelas é importante para a seleção de pacientes que necessitam de cuidados especiais para sustentação das funções vitais durante a internação bem como de acompanhamento após a alta sobretudo até a idade escolar
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Coelho, José Celso Cunha Guerra Pinto. "Papel da colonoscopia com magnificação de imagem associada à cromoscopia no diagnóstico diferencial entre lesões neoplásicas e não-neoplásicas do intestino grosso." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/5/5154/tde-06022007-084813/.
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O Câncer colorretal (CCR) é um problema de saúde importante devido a sua incidência e mortalidade elevadas. O rastreamento e o diagnóstico precoce são a principal estratégia para diminuir a mortalidade pelo CCR. A colonoscopia convencional (CC), constitui o melhor método para o diagnóstico precoce do CCR e para o diagnóstico e tratamento das lesões precurssoras. Entretanto a CC apresenta taxas de falha de detecção não desprezíveis. A colonoscopia com magnificação de imagem (CM), vem sendo utilizada com o intuito de melhorar a performance da CC. A sua principal vantagem é a possibilidade de diferenciar lesões neoplásicas de não-neoplásicas, de maneira que apenas lesões neoplásicas seriam retiradas, diminuindo custos e riscos relacionados ao rastreamento por colonoscopia. O objetivo deste estudo é determinar a acurácia da CM para o diagnóstico diferencial entre lesões neoplásicas e não-neoplásicas do intestino grosso por meio da comparação entre o diagnóstico endoscópico e o fornecido pelo exame histopatológico convencional. Entre abril de 2002 e outubro de 2003, cento e vinte pacientes foram incluídos no estudo, tendo-se encontrado 200 lesões. Todas as lesões foram classificadas endoscopicamente através da CM com alta magnificação (até 200X), associada a cromoscopia com índigo carmim, de acordo com a classificação proposta por Kudo, e em seguida excisadas ou biopsiadas para estudo histopatológico. A acurácia da determinação do diagnóstico diferencial endoscópico em relação à histopatologia entre lesões neoplásicas e não-neoplásicas foi de 78,5%. A diferença da CM em relação ao exame histopatológico foi estatisticamente significativa (p<0,0001). Conclui-se que, no atual estágio de desenvolvimento, a CM, pela sua acurácia, não permite excluir o exame histopatológico para o diagnóstico diferencial entre as lesões neoplásicas e não-neoplásicas do intestino grosso.Bacterial meningitis in the neonatal period is a severe disease, associated to elevated mortality and sequelae in around 12 to 29% of the survivors. Newborns whose birth weight is < 2,500g have a 3-fold increase in the risk of acquiring meningitis when compared to those whose weight is > or = 2,500; among those with very low birth weight (< 1,500g), the risk increases 17-fold. Objectives: General: to describe the clinical picture and the complications of bacterial meningitis in two groups of newborns, considered according to birth weight (< 2,500g or > or = 2,500g). Specific: to describe and compare the etiological agents, the frequency of neurological signs and symptoms and complications, mortality rate and duration of treatment in both groups. Methods: Observational study of 87 newborns with bacterial meningitis, admitted at the Neonatal Intensive Care Unit (NICU) of Instituto da Criança of Hospital das Clínicas of the University of São Paulo School of Medicine, during an 11-year period (January 1994 to December 2004). The data were obtained through the analysis of hospital files. Statistical analysis was carried out with Fisher\'s exact test and the non-parametric Mann Whitney test. Results: Bacteria were identified in the cerebrospinal fluid (CSF) of 39% of the patients, with 50% of them being Gram-positive and 50%, Gram-negative. Most neonates presented unspecific signs and symptoms: fever (63.2%), irritability (31%), and lethargy (26.4%). The neurological findings occurred in 35.3% of the cases. Complications occurred in 48.2% of the neonates, and were mainly seizures (23%), intracranial hemorrhage (14.9%) and hydrocephalus (13.8%) with a mortality rate of 11.5%. At the comparison between clinical evolution and birth weight, associations between weight > or = 2,500g and seizures (p=0.047), weight > or = 2,500g and concave fontanel (p=0.019), bacteria in the CSF and complications (p=0.008) and bacteria in the CSF and death (p=0.043) were observed. Conclusions: The etiological agents most often identified in the CSF were enterobacteria (41%), followed by B Streptococcus (17.5%), non-B Streptococcus (17.5%), Staphylococcus aureus (11.7%), Neisseria meningitidis (8.8%) and Enterococcus faecalis (3.0%), with no statistical difference between the type of bacteria and birth weight. The predominant signs and symptoms were unspecific, with neurological findings in 35% of the cases. The higher frequency of neurological signs and symptoms in newborns with birth weight > or = 2,500g suggest a higher degree of central nervous system maturity in these infants. Although the mortality was lower than that observed in previous studies at the same Service, the frequency of complications was high, regardless of birth weight. The presence of bacteria in the CSF was associated to a higher frequency of seizures and mortality. The need for prolonged treatment in newborns with low birth weight suggests higher disease severity in this group of neonates.
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Halle, Annett. "Streptococcus pneumoniae induziert Apoptose in zerebralen Endothelzellen." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2005. http://dx.doi.org/10.18452/15193.
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Die bakterielle Meningitis ist trotz der Anwendung modernster Antibiotika mit einer hohen Letalität und neurologischen Spätkomplikationen verbunden. Ein entscheidendes Ereignis ist dabei der Zusammenbruch der Blut-Hirn-Schranke (BHS). Die genauen Mechanismen, die zu ihrer Schädigung führen, sind bis heute unklar. In dieser Arbeit wurde untersucht, ob lebende Pneumokokken in einem Zellkulturmodell der BHS zu einer apoptotischen Zellschädigung von zerebralen Endothelzellen, als wichtigstem zellulären Bestandteil der BHS, führen und damit zu ihrer strukturellen Schädigung beitragen. Mittels verschiedener Detektionsmethoden (TUNEL, Fluoreszenzmikroskopie, Elektronenmikroskopie) konnte nachgewiesen werden, daß Streptococcus pneumoniae zu einem apoptotischen endothelialen Zelltod führt. Eine Beteiligung von Caspasen konnte weder mit direkter Aktivitätsmessung noch mittels Inhibitionsexperimenten oder dem Nachweis von Caspase-spezifischen Substraten gezeigt werden. Insgesamt sind die Morphologie der Zellkerne und die spezifische Degradation der endothelialen DNS hinweisend für einen Apoptosis-Inducing-Factor-vermittelten Zelltod ohne Caspasenbeteiligung. Diese Form des Zelltodes ist bereits in anderen Zellmodellen, bisher jedoch nicht bei zerebralen Endothelzellen beschrieben worden. Auf Seiten des Bakteriums konnten Wasserstoffperoxid und Pneumolysin als Auslöser der Apoptose identifiziert werden. Die zytotoxische Potenz des Pneumolysins ist dabei an dessen Poren-formende Aktivität gebunden. Die Ergebnisse sind von potentieller klinischer Relevanz, da es bei einer Bakteriämie und während der Invasion der Pneumokokken in das ZNS zu einem direkten Kontakt zwischen Bakterien und zerebralen Endothelzellen kommt und sich daraus eine Möglichkeit zur Entwicklung adjuvanter Therapien ergeben könnte.Despite sufficient antibiotic treatment, pneumococcal meningitis has remained a disease associated with high mortality and neurological sequelae. The disruption of the blood brain barrier (BBB) is regarded a key event in the initial phase of pneumococcal meningitis. However, the exact molecular mechanisms involved in this process are still unknown. The aim of this study was to determine if living pneumococci are able to induce apoptosis in cerebral endothelial cells - the main cellular component of BBB - and therefore might contribute to its damage. Using several different detection methods (TUNEL, fluorescence and electron microscopy), induction of apoptotic cell death of endothelial cells by pneumococci could be verified. An accompanying activation of caspases was not detectable, despite the use of specific detection techniques such as inhibition experiments, direct enzyme measurements and detection of caspase-specific protein cleavage. These results as well as the specific nuclear morphology and degradation of endothelial DNA suggest an involvement of the mitochondrial protein Apoptosis inducing factor (AIF). This is the first time this specific form of apoptotic, AIF-driven cell death has been described to be engaged in endothelial cells. On the part of the bacterium, pneumolysin and hydrogen peroxide were identified as the two main inducers of apoptosis. The cytotoxic potency of pneumolysin is related to its pore-forming activity. These results are of clinical relevance since pneumococci are known to reside in close proximity to cerebral endothelial cells during bacteriemia and their entry into the CNS. These findings could contribute to the development of adjuvant treatment of bacterial meningitis.
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Ільїна, Ніна Іванівна, Нина Ивановна Ильина, Nina Ivanivna Ilina, Вікторія Валеріївна Ільїна, Виктория Валерьевна Ильина, Viktoriia Valeriivna Ilina, and Н. В. Клименко. "Етіологічна структура та клінічні прояви бактеріальних гнійних менінгітів." Thesis, Сумський державний університет, 2015. http://essuir.sumdu.edu.ua/handle/123456789/43102.
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Актуальність вивчення бактеріальних гнійних менінгітів (БГМ) визначається тяжкістю перебігу, розвитком загрозливих життю церебральних та екстрацеребральних ускладнень, стійких резидуальних наслідків, високою летальністю, яка сягає в деяких вікових групах від 15 до 70 %. Щорічно захворюваність на БГМ складає 4-6 випадків на 100 тис. населення. За даними літератури, в етіологічній структурі БГМ ведуча роль належить менінгококовій, пневмококовій та гемофільній інфекціям. Епідеміологічне значення проблеми БГМ зумовлене постійною загрозою спалахів менінгококової інфекції.
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Albuquerque, Renata Chaves. "Avaliação de um ensaio utilizando-se MULTIPLEX-PCR para a detecção de meningites por diferentes agentes bacterianos." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-24012017-102958/.
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No presente trabalho, foi realizada uma MULTIPLEX-PCR para a detecção do DNA bacteriano de S. agalactiae, S.pneumoniae, N. meningitidis, H. influenzae e outros possíveis agentes etiológicos bacterianos das meningites. Este ensaio combina cinco diferentes iniciadores que detectam simultaneamente o gene crtA de N. meningitidis, o gene p6 de H. influenzae, o gene fbsA de S. agalactiae, o gene lytA de S. pneumoniae e o gene universal 16S rDNA para identificar a presença de agente bacteriano. Foram analisadas 447 amostras de LCR, o ensaio detectou 27 amostras positivas para cultura bacteriana e 13 amostras com resultado de cultura negativa. Estas amostras com cultura negativa apresentavam alterações bioquímicas, hematológicas, imunológicas ou microbiológicas (bacterioscopia) sugestivas de meningite, estes dados auxiliaram na análise dos resultados do MULTIPLEX-PCR. Este ensaio não apresentou reações inespecíficas com fungos, vírus e com outros agentes bacterianos testados (amplificando somente o gene 16S rDNA). A MULTIPLEX-PCR é um ensaio rápido, confiável, de fácil execução e facilmente implementável para a confirmação de meningite bacteriana. E este método pode auxiliar no diagnóstico de meningite com cultura de LCR negativa, particularmente para pacientes que previamente iniciaram antibioticoterapia e no diagnostico diferencial de meningite bacteriana ou viral.In this work, a MULTIPLEX-PCR has conducted for the bacterial DNA detection of S. agalactiae, S.pneumoniae, N. meningitidis, H. influenza and other possible etiologic bacterial meningitis agents. This test combines five different primers that detect simultaneously the crtA gene of N. meningitides, the p6 gene of H. influenza, the fbsA gene of S. agalactiae, the lytA gene of S. pneumoniae and the 16S rDNA universal gene to identify the presence of bacterial agent. From the 447 samples of CSF that were analyzed, the test detected 27 positive samples for bacterial culture and 13 samples with the result of negative culture. These negative culture samples presented biochemical changes, hematological, immunological or microbiological (bacterioscopy) suggestive of meningitis, these data helped in the analysis of the MULTIPLEX-PCR results. This test showed no nonspecific reactions with fungi, viruses and other bacterial agents tested (only amplifying the gene 16S rDNA). The MULTIPLEX-PCR test is a fast, reliable, easy to implement and easily implementable for of bacterial meningitis confirmation. And this method can aid in the meningitis diagnosis with negative culture of CSF, particularly for patients who previously started antibiotic therapy and in the differential diagnosis of bacterial or viral meningitis.
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Lundvall, Linn. "Synergistische, TLR- und NLR-vermittelte IL-1beta-Sekretion in Gliazellen sowie in Östrogen-inkubierten Peritonealmakrophagen." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2015. http://dx.doi.org/10.18452/17334.
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Toll-like Rezeptoren (TLR) und Nod-like Rezeptoren (NLR) sind Muster-erkennende Rezeptoren des angeborenen Immunsystems, die bakterielle Zellwandbestandteile erkennen können. Interleukin (IL)-1beta ist ein streng reguliertes Zytokin. Durch eine erste Stimulation wird der TLR-Rezeptor ausgelöst und führt zur Expression des Vorläuferproteins proIL-1beta. Durch einen zweiten Stimulus wird ein zytoplasmatischer NLR-Rezeptor zur Caspase1-Aktivierung angeregt. Dies führt zur post-translationalen Reifung von proIL-1beta zu reifem IL-1beta und zur Aktivierung weiterer Mechanismen der Pathogen-Eliminierung während einer bakteriellen Meningitis. Im ersten Teil dieser Arbeit wurde die synergistische Beziehung zwischen TLRs und NOD2 in Bezug auf die IL-1beta-Sekretion in Astrozyten und Mikroglia untersucht. Primäre murine WT-Astrozyten und eine humane Zelllinie, die mit Lipopolysaccharid (LPS) oder Lipopeptid sowie Muramyldipeptid (MDP) stimuliert wurden, zeigten signfikant erhöhte IL-1beta-Werte. IL-1beta war in NOD2-/- Astrozyten nicht erhöht. NOD2 trägt demnach als MDP-ausgelöster Rezeptor in Astrozyten, vermutlich zusammen mit dem Inflammasom-Komplex, zur Caspase-1-Aktivierung bei. In Mikrogliazellen lässt sich der bei Astrozyten gezeigte Effekt nicht reproduzieren. Zum ersten Mal wurde gezeigt, dass die TLR-abhängige IL-1beta-Antwort durch NOD2-Beteiligung in murinen und humanen Astrozyten synergistisch erhöht wird. In einem weiteren Versuchsteil wurde in primären murinen Peritonealmakrophagen von adulten Mäusen der TLR/NLR-Synergismus untersucht. Es stellte sich überraschenderweise heraus, dass weibliche NOD2-/- Mäuse zu einer synergistisch erhöhten IL-1beta-Sekretion fähig waren. SiRNA-Versuche mit in Östrogen vorinkubierten RAW264.7-NOD2-/- Zellen zeigten eine eindeutige Synergie der TLR4- und NOD2-Rezeptoren in der IL-1beta-Ausschüttung. Östrogen scheint weiblichen Individuen einen protektiven Vorteil vor Infektionen bei NOD2-Defizienz zu verschaffen.Toll-like receptors (TLR) and nod-like receptors (NLR) are pattern-recognition receptors that recognize lipopolysaccharide (LPS), lipopeptides and myramyldipeptide (MDP) derived from bacterial cell wall. We focus our question on the regulation of the pro-inflammatory cytokine interleukin (IL)-1beta during bacterial meningitis in primary murine astrocytes and microglia as well as cell lines and the synergism of TLR4 or TLR2 and NOD2 to amplify IL-1beta-expression. ProIL-1beta is expressed by TLR-stimulation and activation of NF-kB signal transduction. Through the activation of Caspase-1, possibly through NOD2 and the inflammasome, proIL-1beta is cleaved on post-translational level and obtains its activated status, leading to pathogen elimination during bacterial meningitis. Primary murine WT-astrocytes and a human cell line primed with LPS or lipopeptide and stimulated with MDP show significantly increased IL-1beta levels in the supernatant. NOD2-/- astrocytes do not show elevated IL-1beta levels. After screening of cytoplasmic proCaspase-1 and activated Caspase-1 by Western blot it became clear, that stimulation of NOD2 with MDP led to Caspase-1 activation and thus to IL-1beta maturation in primary murine WT-astrocytes. We demonstrate for the first time that the synergism between TLR4 and NOD2 leads to significantly elevated IL-1beta levels and that NOD2 is capable of activating caspase-1 in primary murine astrocytes. Another part of the work was to test the TLR/NLR-synergism on primary peritoneal macrophages from adult mice. Surprisingly, female NOD2-/- mice showed significantly elevated IL-1beta levels. SiRNA- and stimulation-experiments with RAW264.7-NOD2-/- cells pre-incubated in estrogen show a clear synergy in IL-1beta secretion through TLR4 and NOD2 receptors. Estrogen seems to protect females from infection when having a NOD2 deficiency.
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Dorneles, Aracélli Gnatta. "Hidrolise de nucleotideos da adenina em pacientes com meningite asseptica e bacteriana." Universidade Federal de Santa Maria, 2007. http://repositorio.ufsm.br/handle/1/11080.
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The meningitis is a serious inflammatory illness of meninges, the membranes that recover and protect encephalo and the spinal cord. The main causing agents of the meningitis are the viruses and the bacteria. Some works affirm that the adenosine, the final product of ATP hydrolysis (when degraded by ectonucleotidases), have an important protective role in brain disorders. Breakdown of extracellular ATP to adenosine is catalyzes by ecto-nucleotidases family, the NTPDase hydrolyze extracellular nucleotide tri and diphosphates (ATP and ADP) to nucleotide monophosphate (AMP) and the 5'-nucleotidase catalyzes the hydrolysis of AMP to adenosine. In this work we verified adenine nucleotides hydrolysis in the CSF of aseptic and bacterial meningitis patients, in order to compare with adenine nucleotides hydrolysis in controls patient (absence of neural inflammatory process). Were used patients with age between 18 and 59 years of both the sex in a sampling of 15 patient controls, 15 patients with aseptic meningitis and 15 patients with bacterial meningitis. For the criteria of inclusion and exclusion had been analyzed parameters like, aspect of the CSF, total counting of leukocytes, distinguishing counting of leukocytes, values of protein, glucose and lactate. We got as resulted a significant reduction of hydrolysis of the ATP in the patients with aseptic and bacterial meningitis when compared with patient controls. In contrast we got a significant increase of hydrolysis of the ADP and the AMP in the two groups of meningitis when compared with the controls. The increase in ADP and AMP hydrolysis maybe means the attempt of increase the adenosine production, that have a recognized neuroprotective actions in brain insults.A meningite é uma grave doença inflamatória das meninges, as membranas que recobrem e protegem o encéfalo e a medula espinhal. Os principais agentes causadores da meningite são os vírus e as bactérias. Vários trabalhos afirmam que a adenosina, produto final da degradação do ATP (quando degradado pelas ectonucleotidases), possui um importante papel protetor nas desordens cerebrais. A degradação do ATP até adenosina é catalisada pela família das ecto-nucleotidases, a NTPDase hidrolisa nucleotídeos extracelulares tri e di-fosfatados (ATP e ADP) até nucleotídeos mono-fosfatados (AMP), e a 5'-nucleotidase catalisa a hidrolise do AMP até adenosina. Neste trabalho verificou-se a hidrólise dos nucleotídeos de adenina no líquor de pacientes com meningite asséptica e bacteriana, a fim de comparar a hidrólise destes nucleotídeos com pacientes controles (ausência de processo inflamatório neural). Foram utilizados pacientes com idade entre 18 e 59 anos de ambos os sexos em uma amostragem de 15 pacientes controles, 15 pacientes com meningite asséptica e 15 paciente com meningite bacteriana. Para os critérios de inclusão e exclusão foram analisados parâmetros tais como: aspecto do líquor, contagem total de leucócitos, contagem diferencial de leucócitos, valores de proteína, glicose e lactato. Obtivemos como resultado uma diminuição significativa da hidrólise do ATP nos pacientes com meningite asséptica e bacteriana quando comparados com pacientes controles. Ao contrário obtivemos um aumento significativo da hidrólise do ADP e do AMP nos dois grupos de meningites quando comparados com os controles. A hidrólise aumentada do ADP e do AMP refere-se talvez a tentativa de aumentar a produção de adenosina, que por sua vez possui um conhecido papel neuroprotetor frente a insultos cerebrais.