Meningitis registry of hospitalized cases in children: epidemiological patterns of acute bacterial meningitis throughout a 32-year period

<p>Abstract</p> <p>Background</p> <p>Bacterial meningitis remains a source of substantial morbidity and mortality in childhood. During the last decades gradual changes have been observed in the epidemiology of bacterial meningitis, related to the introduction of new polysaccharide and conjugate vaccines. The study presents an overview of the epidemiological patterns of acute bacterial meningitis in a tertiary children 's hospital during a 32-year period, using information from a disease registry. Moreover, it discusses the contribution of communicable disease registries in the study of acute infectious diseases.</p> <p>Methods</p> <p>In the early 1970s a Meningitis Registry (MR) was created for patients admitted with meningitis in Aghia Sofia Children's Hospital in Athens. The MR includes demographic, clinical and laboratory data as well as treatment, complications and outcome of the patients. In 2000 a database was created and the collected data were entered, analyzed and presented in three chronological periods: A (1974–1984), B (1985–1994) and C (1995–2005).</p> <p>Results</p> <p>Of the 2,477 cases of bacterial meningitis registered in total, 1,146 cases (46.3%) were classified as "probable" and 1,331 (53.7%) as "confirmed" bacterial meningitis. The estimated mean annual Incidence Rate (IR) was 16.9/100,000 for bacterial meningitis, 8.9/100,000 for <it>Neisseria meningitidis</it>, 1.3/100,000 for <it>Streptococcus pneumoniae</it>, 2.5/100,000 for <it>Haemophilus influenzae </it>type b (Hib) before vaccination and 0.4/100,000 for Hib after vaccination. <it>Neisseria meningitis </it>constituted the leading cause of childhood bacterial meningitis for all periods and in all age groups. Hib was the second most common cause of bacterial meningitis before the introduction of Hib conjugate vaccine, in periods A and B. The incidence of bacterial meningitis due to <it>Streptococcus pneumoniae </it>was stable. The long-term epidemiological pattern of <it>Neisseria meningitidis </it>appears in cycles of approximately 10 years, confirmed by a significant rise of IR in period C. The Case Fatality Rate (CFR) from all causes was 3.8%, while higher CFR were estimated for <it>Streptococcus pneumoniae </it>(7.5%, RR=2.1, 95% CI 1.2–3.7) and <it>Neisseria meningitidis </it>(4.8%, RR=1.7, 95% CI 1.1–2.5) compared to other pathogens. Moreover, overall CFR varied significantly among the three time periods (p = 0.0015), and was estimated to be higher in period C.</p> <p>Conclusion</p> <p>By using the MR we were able to delineate long-term changes in the epidemiology of bacterial meningitis. Thus the MR proved to be a useful tool in the study and the prevention of communicable diseases in correlation with prevention strategies, such as vaccinations.</p

Risk factors for nasopharyngeal carriage of drug-resistant Streptococcus pneumoniae: data from a nation-wide surveillance study in Greece

<p>Abstract</p> <p>Background</p> <p>A nation-wide surveillance study was conducted in Greece in order to provide a representative depiction of pneumococcal carriage in the pre-vaccination era and to evaluate potential risk factors for carriage of resistant strains in healthy preschool children attending daycare centers.</p> <p>Methods</p> <p>A study group was organized with the responsibility to collect nasopharyngeal samples from children. Questionnaires provided demographic data, data on antibiotic consumption, family and household data, and medical history data. Pneumococcal isolates were tested for their susceptibility to various antimicrobial agents and resistant strains were serotyped.</p> <p>Results</p> <p>Between February and May 2004, from a total population of 2536 healthy children, a yield of 746 pneumococci was isolated (carriage rate 29.41%). Resistance rates differed among geographic regions. Recent antibiotic use in the last month was strongly associated with the isolation of resistant pneumococci to a single or multiple antibiotics. Serotypes 19F, 14, 9V, 23F and 6B formed 70.6% of the total number of resistant strains serotyped.</p> <p>Conclusion</p> <p>Recent antibiotic use is a significant risk factor for the colonization of otherwise healthy children's nasopharynx by resistant strains of <it>S pneumoniae</it>. The heptavalent pneumococcal conjugate vaccine could provide coverage for a significant proportion of resistant strains in the Greek community. A combined strategy of vaccination and prudent antibiotic use could provide a means for combating pneumococcal resistance.</p

Molecular Epidemiology of Enterovirus in Children with Central Nervous System Infections

Limited recent molecular epidemiology data are available for pediatric Central Nervous System (CNS) infections in Europe. The aim of this study was to investigate the molecular epidemiology of enterovirus (EV) involved in CNS infections in children. Cerebrospinal fluid (CSF) from children (0&ndash;16 years) with suspected meningitis&ndash;encephalitis (ME) who were hospitalized in the largest pediatric hospital of Greece from October 2017 to September 2020 was initially tested for 14 common pathogens using the multiplex PCR FilmArray&reg; ME Panel (FA-ME). CSF samples positive for EV, as well as pharyngeal swabs and stools of the same children, were further genotyped employing Sanger sequencing. Of the 330 children tested with FA-ME, 75 (22.7%) were positive for EV and 50 different CSF samples were available for genotyping. The median age of children with EV CNS infection was 2 months (IQR: 1&ndash;60) and 44/75 (58.7%) of them were male. There was a seasonal distribution of EV CNS infections, with most cases detected between June and September (38/75, 50.7%). EV genotyping was successfully processed in 84/104 samples: CSF (n = 45/50), pharyngeal swabs (n = 15/29) and stools (n = 24/25). Predominant EV genotypes were CV-B5 (16/45, 35.6%), E30 (10/45, 22.2%), E16 (6/45, 13.3%) and E11 (5/45, 11.1%). However, significant phylogenetic differences from previous described isolates were detected. No unusual neurologic manifestations were observed, and all children recovered without obvious acute sequelae. Specific EV circulating genotypes are causing a significant number of pediatric CNS infections. Phylogenetic analysis of these predominant genotypes found genetic differences from already described EV isolates

Multi-targeted molecular therapeutic approach in aggressive neuroblastoma: the effect of Focal Adhesion Kinase-Src-Paxillin system

Introduction: Nonreceptor tyrosine kinases play key roles in the integrin system. Located at the focal adhesions, they consist of large protein complexes through which the cytoskeleton connects to the extracellular matrix. The focal adhesion kinase (FAK)-Src-paxillin complex, a major mediator of the integrin pathway, contributes to cell migration and motility. Its overexpression is increased in children with advanced neuroblastoma (NB), one of the most common malignancies of childhood, with poor survival. Areas covered: We review the most recent data on FAK-Src-paxillin and their implications in NB, the molecular structure and the regulatory mechanisms of each molecule and their interactions and up-to-date information on their use as the newest biomarkers and their potential use as therapeutic targets in NB. Expert opinion: Based on the current literature, we hypothesize that combined and concurrent inhibition of the FAK-Src-Paxillin system may result in significant tumor suppression and prevention or delay of metastasis

A Case-Control Study on the Risk Factors for Meningococcal Disease among Children in Greece.

The aim of this study was to identify environmental or genetic risk factors that are associated with invasive meningococcal disease (IMD) in children in Greece.A case-control study was performed in 133 children (44 cases and 89 controls) aged between 0-14 years, who were hospitalized in a children's hospital in Athens. Demographics and possible risk factors were collected by the use of a structured questionnaire. To investigate the association of mannose binding lectin (MBL) with IMD, a frequency analysis of the haplotypes of the MBL2 gene and quantitative measurement of MBL serum protein levels were performed using Nanogen NanoChipR 400 technology and immuno-enzyme techniques, respectively.The multivariate analysis revealed that changes in a child's life setting (relocation or vacation, OR = 7.16), paternal smoking (OR = 4.51), upper respiratory tract infection within the previous month (OR = 3.04) and the density of people in the house/100m2 (OR = 3.16), were independent risk factors associated with IMD. Overall 18.8% of patients had a MBL2 genotype with low functionality compared to 10.1% of healthy controls, but this was not statistically significant (p = 0.189).Prevention strategies aimed at reducing parental smoking and other risk factors identified in this study could decrease the risk of IMD among children in Greece

FAK-Src-paxillin system expression and disease outcome in human neuroblastoma

<p><b>Background:</b> Neuroblastoma (NB) often presents with metastatic disease and poor survival. The need for new prognostic markers remains invaluable. The FAK-Src-Paxillin protein system is associated with aggressive phenotype in adult malignancies but is largely unexplored in pediatric NB. <b>Objective:</b> To assess FAK-Src-Paxillin protein expression in human NB cell lines and clinical cytology material and to delineate its association with survival. <b>Design/Methods:</b> Western blot and immunohistochemistry were applied for FAK-Src-Paxillin expression in NB cell lines and 23 human cytology specimens, respectively. Protein expression in human clinical samples was correlated with clinicopathological parameters, <i>MYCN</i> amplification and survival. <b>Results:</b> FAK, Src and Paxillin proteins are expressed in human NB cells lines, and can be detected in clinical cytology specimens from NB patients, (59%, 32% and 33% respectively). Simultaneous FAK-Src-Paxillin expression was noted in 30% of NB patients. Children with concomitant positivity FAK, Src, and Paxillin tumors, as well as <i>MYCN</i> amplification, had increased mortality compared to those without. <b>Conclusions:</b> FAK-Src-Paxillin system is a marker of unfavorable prognosis for human NB patients but also a promising therapeutic target.</p

Multivariate analysis (logistic regression) of the risk factors for invasive meningococcal disease.

<p>Multivariate analysis (logistic regression) of the risk factors for invasive meningococcal disease.</p