The neurotoxic branch of the kynurenine pathway is highly activated in the central nervous system of patients with pneumococcal meningitis.

BACKGROUND: Acute bacterial meningitis (ABM) causes excessive activation of N-methyl-D-aspartate receptors (NMDAr), leading to cortical and hippocampal neuron death. As opposite, enteroviral meningitis is more frequently benign. The kynurenine (KYN) pathway is the major catabolic route of tryptophan (TRP) and some of its metabolites are agonists or antagonists of NMDAr. METHODS: In order to investigate the pathogen-specific patterns of KYN pathway modulation in the central nervous system of children with acute meningococcal (MM), pneumococcal (PM) or enteroviral (VM) meningitis, the cerebrospinal fluid (CSF) concentrations of TRP, KYN, kynurenic acid (KYNA) and quinolinic acid (QUINA) were evaluated by ultra-high performance liquid chromatography (uHPLC) coupled to mass spectrometry. In addition, CSF levels of IL-6, IL-10 and TNF-α were quantified by multi-analyte flow assay. The data was mined and integrated using statistical and machine learning methods. RESULTS: The three forms of meningitis investigated herein up-regulated the neurotoxic branch of the KYN pathway within the intrathecal space. However, this response, represented by the concentration of QUINA, was six and nine times higher in PM patients compared to MM or VM, respectively. CSF levels of IL-6, TNF-α, and IL-10 were increased in MM and PM patients when compared to controls. In VM, CSF IL-6 and IL-10, but not TNF-α were increased compared to controls, although not reaching the high levels found in bacterial meningitis. No correlation was found between the concentrations or the ratios of any pair of KYN metabolites and any cytokine or standard cytochemical parameter tested. CONCLUSIONS: CNS infection with meningococci, pneumococci, and enteroviruses intrathecally activate the KYN pathway, favoring its neurotoxic branch. However, in PM, higher CSF levels of QUINA, compared to MM and VM, may contribute to its poorer neurologic outcome.

Neurologic Manifestations of Noncongenital Zika Virus in Children.

We evaluated neurologic complications following noncongenital Zika virus infection in 11 children who presented with central nervous system signs. Zika virus RNA was detected by real-time reverse transcription-polymerase chain reaction in cerebrospinal fluid. Approximately one-quarter of patients required antiepileptic medication in follow-up, and 2 children progressed to learning difficulties or developmental delay.

The impact of viral infections on childhood central nervous system infections.

BACKGROUND: Viruses are a common cause of central nervous system (CNS) infections. However, studies of CNS viral pathogens in pediatric patients are poorly explored because viral infections are often erroneously diagnosed as bacterial infections. METHODS: 299 CNS samples were collected from pediatric patients aged from one month to 14 years old. A total of 140 viral meningitis cases that met the inclusion criteria were included in this study. In 38 of the 140 cerebral spinal fluid (CSF) samples (27.1%), conventional and real-time PCR were used to identify viruses commonly associated with CNS infections. RESULTS: Among them, 23 patients (16.5%) tested positive for flaviviruses such as dengue, Zika, and yellow fever virus, eight patients (5.7%) were positive for enterovirus (ENTV), and six patients (4.3%) were positive for human herpesvirus 1/2. We also identified one case of dengue virus and ENTV co-infection. CONCLUSIONS: A correlation between clinical symptoms and laboratory findings for the viruses was identified. Our study also reinforces the importance of including viruses in the laboratory diagnosis of CNS infections especially flaviviruses, which assists public health authorities in implementing early interventions.

Central and peripheral nervous system involvement in Zika virus infection in a child.

A 7-year-old boy that presented an encephalomyeloradiculitis and no classic symptoms of arboviruses. Zika virus (ZIKV) was confirmed by molecular analyses of cerebrospinal fluid and 1 year later by plaque reduction neutralization test. This case demonstrates that ZIKV can be associated with diffuse nervous system infection in children.

Meningitis Associated with Simultaneous Infection by Multiple Dengue Virus Serotypes in Children, Brazil.

To determine the causes of viral meningitis, we analyzed 22 cerebrospinal fluid samples collected during the 2014-2015 dengue epidemics in Brazil. We identified 3 serotypes of dengue virus (DENV-1, -2, and -3), as well as co-infection with 2 or 3 serotypes. We also detected the Asian II genotype of DENV-2.

Impacto de fatores clínicos e laboratoriais no ganho de peso em uma coorte de pacientes com Fibrose Cística diagnosticados pela triagem neonatal / Impact of clinical and laboratory weight gain in a cohort of patients with cystic fibrosis diagnosed by newborn screening factors

Introdução: A Fibrose Cística é uma doença genética autossômica recessiva de caráter progressivo que acomete as glândulas exócrinas. Vários fatores podem interferir no ganho de peso e determinar a qualidade de vida desses pacientes. Objetivo: Avaliar os fatores clínicos e laboratoriais que influenciem na evolução do ganho de peso dos pacientes com Fibrose Cística. Método: Coorte híbrida, retrospectiva de 2003 a 2009. Questionário padronizado foi elaborado para coleta de dados dos prontuários. O programa utilizado foi SPSS 16.0 para armazenamento e análises estatísticas. Por se tratar de dados longitudinais, as análises univariadas consistiram em desenvolver modelos preliminares da variação peso em função do tempo para cada uma das covariáveis separadamente (sexo, insuficiência pancreática, colonização crônica por Pseudomonas aeruginosa (PA), Stafilococcus aureus sensível (MSSA) e resistente à meticilina (MRSA), nível sérico de albumina, íleo meconial e mutação genética). Para essa análise longitudinal do peso, foi utilizado o software R. Nível de significância de 5%. Resultados: Foram acompanhados 43 pacientes com mediana de idade ao diagnóstico de 41 dias, sendo 80% com mutação ΔF508 (22,5% homozigotos). 58% sexo masculino. Das variáveis analisadas, insuficiência pancreática, colonização crônica por PA, MSSA, MRSA e hipoalbuminemia influenciaram, do ponto de vista estatístico, o ganho longitudinal de peso. Nesta coorte, as variáveis, íleo meconial, mutação genética e sexo não tiveram influência no ganho ponderal. Conclusão: A insuficiência pancreática, colonização crônica por PA, MSSA, MRSA e hipoalbuminemia tiveram influência negativa no ganho ponderal, reforçando a necessidade de maior atenção com a assistência destes pacientes.

Introduction: Cystic fibrosis is an autosomal recessive genetic disorder of progressive affecting the exocrine glands. Several factors can interfere with weight gain and determine the quality of life of these patients. Objective: To evaluate the clinical and laboratory factors that influence the evolution of weight gain in patients with Cystic Fibrosis. Methods: Hybrid Cohort, retrospective from 2003 to 2009 standardized questionnaire was designed to collect data from medical records. The program SPSS 16.0 was used for storage and statistical analyzes. Because it is longitudinal data, univariate analyzes consisted develop preliminary models of weight change versus time for each of the covariates separately (sex, pancreatic insufficiency, chronic colonization with Pseudomonas aeruginosa (PA), Staphylococcus aureus sensitive (MSSA) and methicillin-resistant (MRSA), serum albumin, meconium ileus and genetic mutation). For this longitudinal analysis of weight R. Software level of significance of 5% was used. Results: 43 patients were followed with a median age at diagnosis of 41 days, of which 80% DF508 mutation (22.5% homozygous). 58% male, the variables analyzed, pancreatic insufficiency, chronic colonization by PA, MSSA, MRSA and hypoalbuminemia influenced, the statistical point of view, the longitudinal weight gain. In this cohort, variables, meconium ileus, genetic mutation and sex had no influence on weight gain. Conclusion: Pancreatic insufficiency, chronic colonization by PA, MSSA, MRSA and hypoalbuminemia had a negative influence on weight gain, reinforcing the need for greater attention to the care of these patients.

A putative role for homocysteine in the pathophysiology of acute bacterial meningitis in children.

BACKGROUND: Acute bacterial meningitis frequently causes cortical and hippocampal neuron loss leading to permanent neurological sequelae. Neuron death in acute bacterial meningitis involves the excessive activation of NMDA receptors and p53-mediated apoptosis, and the latter is triggered by the depletion of NAD + and ATP cellular stores by the DNA repair enzyme poly(ADP-ribose) polymerase. This enzyme is activated during acute bacterial meningitis in response to DNA damage induced, on its turn, by reactive oxygen and nitrogen species. An excess of homocysteine can also induce this cascade of events in hippocampal neurons. The present work aimed at investigating the possible involvement of homocysteine in the pathophysiology of meningitis by comparing its concentrations in cerebrospinal fluid (CSF) samples from children with viral or acute bacterial meningitis, and control individuals. METHODS: Homocysteine and cysteine concentrations were assessed by high-performance liquid chromatography in CSF samples from nine patients with acute bacterial meningitis, 13 patients with viral meningitis and 18 controls (median age: 4 years-old; range: <1 to 13) collected by lumbar puncture at admission at the Children's Hospital Joao Paulo II - FHEMIG, from January 2010 to November 2011. RESULTS: We found that homocysteine accumulates up to neurotoxic levels within the central nervous system of patients with acute bacterial meningitis, but not in those with viral meningitis or control individuals. No correlation was found between homocysteine and cysteine concentrations and the cerebrospinal fluid standard cytochemical parameters. CONCLUSIONS: Our results suggest that HCY is produced intrathecally in response to acute bacterial meningitis and accumulates within the central nervous system reaching potentially neurotoxic levels. This is the first work to propose a role for HCY in the pathophysiology of brain damage associated with acute bacterial meningitis.

The impact of highly active antiretroviral therapy on the survival of vertically HIV-infected children and adolescents in Belo Horizonte, Brazil.

The use of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected patients has reduced the number of acquired immune deficiency syndrome-related deaths worldwide. This study assessed the impact of HAART on the survival and death rates of vertically HIV-infected children and adolescents in Belo Horizonte, Brazil. Data were obtained from a historic cohort of vertically HIV-infected children and adolescents aged zero-19 years old who were admitted from March 1989-December 2004 and were followed until June 2006. Patients who used HAART were included if they were treated for at least 12 weeks. Of 359 patients, 320 patients met the inclusion criteria. The overall mortality rate was 9.7% [31/320; 95% confidence interval (CI): 6.0-13%]. The median survival for the non-HAART and HAART groups was 31.5 and 55.9 months, respectively (log rank = 22.11, p < 0.0001). In the multivariate analysis, the statistically significant variables were HAART and the weight-for-age Z score < -2, with HAART constituting a protective factor [relative risk (RR): 0.13; CI 95%: 0.05-0.33] and malnutrition constituting a risk factor (RR: 3.44; CI 95%: 1.60-7.40) for death. The incidence of death was 5.1/100 person-years in the non-HAART group and 0.8/100 person-years in the HAART group (p < 0.0001).

The impact of highly active antiretroviral therapy on the survival of vertically HIV-infected children and adolescents in Belo Horizonte, Brazil

The use of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected patients has reduced the number of acquired immune deficiency syndrome-related deaths worldwide. This study assessed the impact of HAART on the survival and death rates of vertically HIV-infected children and adolescents in Belo Horizonte, Brazil. Data were obtained from a historic cohort of vertically HIV-infected children and adolescents aged zero-19 years old who were admitted from March 1989-December 2004 and were followed until June 2006. Patients who used HAART were included if they were treated for at least 12 weeks. Of 359 patients, 320 patients met the inclusion criteria. The overall mortality rate was 9.7% [31/320; 95% confidence interval (CI): 6.0-13%]. The median survival for the non-HAART and HAART groups was 31.5 and 55.9 months, respectively (log rank = 22.11, p < 0.0001). In the multivariate analysis, the statistically significant variables were HAART and the weight-for-age Z score < -2, with HAART constituting a protective factor [relative risk (RR): 0.13; CI 95%: 0.05-0.33] and malnutrition constituting a risk factor (RR: 3.44; CI 95%: 1.60-7.40) for death. The incidence of death was 5.1/100 person-years in the non-HAART group and 0.8/100 person-years in the HAART group (p < 0.0001).

Fatores prognósticos socioeconômicos associados ao estado nutricional ao final do primeiro ano de vida em uma coorte de crianças com fibrose cística / Prognostic factors associated with socioeconomic nutritional status at the end of the first year of life in a cohort of children with cystic fibrosis

Objetivos: Avaliar a associação de fatores socioeconômicos no estado nutricional em uma coorte de pacientes com fibrose cística. Métodos: Estudo observacional de parte de uma coorte com pacientes selecionados pelo programa de triagem neonatal do Estado de Minas Gerais. Foi realizada análise dos prontuários de 54 crianças no período de 2003 a 2008 e avaliados fatores demográficos, nutrição ao nascimento, número de cômodos do domicílio, residência rural ou urbana, distância do centro de tratamento, renda familiar, número de irmãos, idade e escolaridade maternas. Foi realizado o escore Z de peso/idade, peso/altura e altura/idade, na idade entre 10 e 14 meses. Resultados: Entre os pacientes estudados, não houve diferença quanto ao sexo, a maioria nasceu no interior do estado, em região urbana. Vinte e oito por cento das mães tiveram seu filho em idade inferior a vinte anos, 40% não completaram o primeiro grau e 52% residem em moradia com menos de 5 cômodos. Das famílias estudadas, 16,7% viviam com menos de 1 salário mínimo mensal. Nenhum fator analisado apresentou relação estatisticamente significativa com o estado nutricional no primeiro ano de vida. Conclusões: A renda familiar e outros fatores socioeconômicos não foram preditores de desnutrição ao final do primeiro ano de vida, o que difere de resultados encontrados na literatura. Esta diferença foi atribuída ao fato das crianças seguirem um protocolo e receberem suporte terapêutico, fórmulas infantis, suplementos alimentares e medicações, o que pode atenuar o impacto da baixa renda familiar na evolução da doença.(AU)

Objectives: To evaluate the association of socioeconomic factors on nutritional status in a cohort of patients with cystic fibrosis. Methods: Observational study of part of a cohort of patients selected by the neonatal screening program of the State of Minas Gerais. Analysis was performed of medical records of 54 children in the period 2003 to 2008 and assessed demographic factors, nutrition at birth, number of rooms in the home, urban or rural residence, distance from treatment center, family income, number of siblings, age and education mother. We carried out the Z score for weight / age, weight / height and height / age, age between 10 and 14 months. Results: Among the patients studied, there was no gender difference, most born in the state, in urban areas. Twenty-eight percent of mothers had their son at the age of twenty, 40% had not completed elementary school and 52% live in housing with less than five rooms. Of the families studied, 16.7% lived on less than one minimum monthly wage. None of the analyzed factors showed a statistically significant relationship with nutritional status in the first year of life. Conclusions: Family income and other socioeconomic factors were not predictors of malnutrition at the end of the first year of life, which differs from results found in literature. This difference was attributed to the fact that children follow a protocol and receive therapeutic support, infant formulas, food supplements and medications, which can mitigate the impact of low family income in the evolution of the disease.(AU)

Fundação Hospitalar do Estado de Minas Gerais (FHEMIG): protocolo-guia de atendimento domiciliar e hospitlar de casos suspeitos ou confirmados de Influenza A (H1N1) / Fundação Hospitalar do Estado de Minas Gerais (FHEMIG): guide-line for home and hospital care monitoring suspect or confirmes cases of Influenza A (H1N1)

Este protocolo, de elaboração continuada, foi realizado pela Fundação Hospitalar do Estado de Minas Gerais como instrumento de organização e atualização do atendimento, em diversos níveis hierarquizados do Sistema Único de Saúde, desde a sua indicação de internação até a alta hospitalar, para garantir o melhor atendimento para os pacientes, o sucesso das ações de abordagem de casos clínicos e a biossegurança dos profissionais envolvidos no manejo dos pacientes.

Hospital Foundation of Minas Gerais State has conducted continual development of this protocol, as an instrument for care organization and updating in several hierarchical levels of the Unified Health System, since its statement of admission to the hospital to ensure better care for patients, the successful actions for dealing with cases, and biosecurity for the professionals involved in the patients? management.

Perfil de sensibilidade em infecções pneumocócicas e análise da conduta terapêutica em hospital de referência em doenças infecciosas / Management of pneumococal infectious according to the sensibility profile in a state reference hospital for infectious disease

Com o advento da resistência do Streptococcus pneumoniae (pneumococo) à penicilina, o tratamento empírico inicial tornou-se complexo, sendo fundamental a determinação do perfil de sensibilidade em cada instituição, visando à adequada abordagem terapêutica deste agente. Objetivo: Analisar, em hospital de referência em doenças infecciosas, a conduta terapêutica instituída diante das infecções por Streptococcus pneumoniae, avaliando a influência do conhecimento do perfil de sensibilidade deste agente e das condições clínicas dos pacientes. Método: Estudo observacional de crianças hospitalizadas no Centro Geral de Pediatria (FHEMIG-BH), no período de 2000 a 2001. Resultado: Isolou-se o pneumococo em 33 crianças (57,6% com pneumonia e 42,4% com meningite). A infecção por pneumococo resistente à penicilina (MIC≥2,0 mg/ml) ocorreu em 9,1%, nos quais o tratamento foi modificado diante da piora clínica e do padrão de sensibilidade. Em 27,3% dos casos, isolou-se cepa com sensibilidade intermediária (MIC:0,1 a 1,0 mg/ml). Entre estes, 55,6% mantiveram o tratamento com penicilina na dose habitual, com boa evolução clínica. Nos demais com sensibilidade intermediária, houve alteração da antibioticoterapia. Cepas de pneumococos foram sensíveis (MIC≥ 0,06 mg/ml) em 63,6% das infecções e o uso da penicilina obteve bons resultados. Conclusões: A prevalência de cepas resistentes foi relativamente baixa (9,1%). Dos pacientes infectados por pneumococos com sensibilidade intermediária à penicilina, 55,6% apresentaram resposta clínica satisfatória com dose habitual deste antibiótico.

Management of pneumococcal infections according to the sensibility profile in State reference hospital for infectious disease. In troduction: The prevalence of infections due to Streptococcus pneumoniae with reduced susceptibiliry to penicillin is increasing what makes the empiric treatment a complex issue. Each institution should determine the sensibililty profile of this bacteria to estabilish the best management of these infections. Objectives: To know, in a State reference hospital for infectious disease, the sensibility profile of S. pneumoniae and to estabilish its correlation with clinical aspects. Methods: retrospective study of inpatients in Centro Geral de Pediatria (CGP - FHEMIG- Brazil) during the period of 2000 to 2001. Results: Pneumococcus was isolated in 33 children; 57.6% with pneumonia and 42.4% with meningitis. Penicillin resistant pneumococci (MIC > 2 µg/mIL were found in 9.1%. The therapy was changed according to the sensibility profile and clinical course of the illness. In 27.3% of the children, S. pneumoniae with reduced susceptibility to penicillin (MIC 0.1- 1,0 µg/mL) was isolated: 55.6% of the patients improved with penicillin in usual doses and the others had the antibiotic changed. In 63.6% of the patients. S. pneumoniae was sensitive to penicillin (MIC< 0.1µg/mL.]). Most of them used penicillin and the outcome was uneventful. Conclusions: The prevalence of penicillin resistant pneumococcus was relatively low (9.1%). Most patients with infections with pneumococcus with reduced susceptibility to penicillin (55.6%) got well using the standard therapy with this antibiotic.