Pediatric bacterial purulent meningitis (BPM) and viral encephalitis (VE) are significant medical and social problems due to their course severity, high frequency of death cases, and formation of neurologic deficiency at the disease outcome. Activation of hormonal regulation and severity syndrome of systemic inflammatory response are important factors to evaluate the character of BPM and VE course.Objective.To study the level of cortisol and laboratory indicators of systemic inflammation in children with various variants of BPM and VE course depending on the period of the disease (acute period, reconvalescence) to specify their role in the pathogenesis of acute neuroinfections.Object and methods.There were investigated hematological indicators, the level of cortisol, C-reactive protein in blood serum of 60 children, 39 of them had BPM and 21 ones VE. The comparison group included 14 children aged from 1 to 14 years old who were undergoing rehabilitation care due to neurologic problems at the Federal State-Financed Institution Pediatric Research and Clinical Center for Infectious Diseasesunder the Federal Medical Biological Agency.Results.The patients were divided into some subgroups according to the severity of their condition at the moment of hospitalization, i.e. urgent condition or critical condition requiring organ replacement therapy. The maximum increase of cortisol level and laboratory markers of systemic inflammation during the acute period was revealed in case of BPM in comparison with VE with a subsequent normalization to the stage of reconvalescence. Thelevel of cortisol during the acute period of BPM was reliably higher in the subgroup with urgent conditions, whereas in case of VE in the subgroup with critical conditions. There were no significant differences in the laboratory indicators of systemic inflammation response among the subgroups. There was established a correlation interrelation of cortisol level and the content of granulocytes and blood lymphocytes.Conclusion.There were identified characteristic features of cortisol content in children with bacterial and viral neuroinfections depending on the course of the disease.

Introduction of flow cytometry caused an increase in the investigation of liquor lymphocyte pool phenotype in the case of different brain disorders, including viral and bacterial meningitis, however this type of research in children has been relatively rare. Phenotype and lymphocyte functions are under cytokine control system, therefore detection of interconnections between lymphocyte pool subpopulation composition and cytokine level in blood and liquor of the patients concerns a great interest. The purpose of this research was to study lymphocyte subpopulation composition and the level of cytokines IL-1β, IL-6, IL-8, IL-10, IFNα, IFNγ and IL-4, and also IgG in liquor and blood of children with viral and bacterial meningitis. There was performed blood and liquor investigation in 46 children aged from 1 to 16 years old with viral (n = 35) and bacterial (n = 11) meningitis. Immunophenotyping of blood and liquor cells was performed by the method of flow cytometry with the use of monoclonal antibodies to CD3, CD4, CD8, CD19, CD16, CD56, CD25 and CD95. The content of cytokines was detected in ELISA, and that of IgG — by the method of quantitative immunoturbodimetry. During an acute period of viral meningitis there was detected a decrease in NK portion and activated CD25+ cells in the blood of patients accompanied by the increase in B-lymphocytes number, along with cytokine IFNγ, IL-8 and IL-10 serum level rise. There was determined T-lymphocytes accumulation in liquor with the prevalence of CD4+ Т-cells and, to a lesser degree, CD25+ and CD95+ cells, NK and B-lymphocytes. Intrathecally there was noted the predominance of IL-6 response accompanied by the growth of IL-8 and IL-10 concentration as well. During an acute period of bacterial meningitis there was noted a decrease in percentage of CD3+, CD4+, CD8+ Т-lymphocytes, NK, CD25+ and CD95+ cells, along with, on the contrary, sharp increase in B-cells pool, simultaneously with an expressed system response of IL-8 and IL-10. Liquor T-lymphocyte content was relatively correlated with blood indicators whereas the fraction of NK exceeded it, and B-lymphocyte content was 3–4 times higher than in patients with viral meningitis. There was IL-6, IL-10, IFNγ and IL-4 response intrathecally, and 10-multiply-growth of IgG level. Thus, the redistribution of lymphocyte subpopulations, and system and local cytokine response in children with meningitis have both common and special features depending on the aetiology and severity of disease. Phenotyping of lymphocytes and determination of both cytokines and immunoglobulins simultaneously in two biologic fluid allow to clear up the pathogenetic value of immunologic abnormalities in blood and cerebrospinal fluid of the patients in the aspect of interactions between cell and humoral factors of system and local immune response in neuroinfections of various aetiology.

ObjectivesVertical transmission of hepatitis C virus (HCV) is rare compared with other chronic viral infections, despite that newborns have an immature, and possibly more susceptible, immune system. It further remains unclear to what extent prenatal and perinatal exposure to HCV affects immune system development in neonates.DesignTo address this, we studied B cells, innate immune cells and soluble factors in a cohort of 62 children that were either unexposed, exposed uninfected or infected with HCV. Forty of these infants were followed longitudinally from birth up until 18 months of age.ResultsAs expected, evidence for B cell maturation was observed with increased age in children, whereas few age-related changes were noticed among innate immune cells. HCV-infected children had a high frequency of HCV-specific IgG-secreting B cells. Such a response was also detected in some exposed but uninfected children but not in uninfected controls. Consistent with this, both HCV-exposed uninfected and HCV-infected infants had evidence of early B cell immune maturation with an increased proportion of IgA-positive plasma cells and upregulated CD40 expression. In contrast, actual HCV viraemia, but not mere exposure, led to alterations within myeloid immune cell populations, natural killer (NK) cells and a distinct soluble factor profile with increased levels of inflammatory cytokines and chemokines.ConclusionOur data reveal that exposure to, and infection with, HCV causes disparate effects on adaptive B cells and innate immune cell such as myeloid cells and NK cells in infants.

Regardless of viral genotype we found no association between IL28B genotype and the risk of HCV-VT. The IL28B genotype CC, which has been shown to be favourable in other settings, was not protective of HCV-VT. Thus, other factors possibly associated with the risk of HCV-VT need to be explored.

Introduction. The analysis of current literature data indicates insufficient understanding of subpopulation composition of lymphocytes in blood and cerebrospinal fluid (CSF) during neuroinfectious diseases in children. It has been established that cells of the main lymphocyte populations are divided into many small (minor) subpopulations. The purpose of this research was to study the relative content of major and minor subpopulations of blood and CSF lymphocytes in children with aseptic viral meningitis (AM) or bacterial purulent meningitis (BM). Materials and methods. Phenotyping of blood and CSF lymphocytes of children aged from 4 months to 17 years with the diagnosis of AM (n=86) and BM (n=39) was carried out by the method of flow cytometry. To make a comparison, we assessed blood and CSF samples of the children with acute respiratory viral infections (ARVI) with the syndrome of meningism (n=27). There was investigated the relative content of the major subpopulations: (CD3+ T-lymphocytes, T-helpers - CD3+CD4+  Th, cytotoxic T-lymphocytes - CD3+ CD8+ CTL, natural killer cells - CD3-CD16+CD56+ NK, B-cells - CD3-CD19+); and the minor lymphocyte subpopulations: (double positive/DP/(CD3+CD4+CD8+), double negative/DN/(CD3+CD4-CD8-) T-cells, NKT (CD3+CD16+CD56+), CD3-CD8+ NK, CD3+CD8dim and CD3+CD8bright). Results. In the acute period of BM and AM in the blood and CSF there were found significant differences in the content of major and minor lymphocyte subpopulations in contrast with the comparison group (ARVI). The predominance of T-cells, Th, CTL, NK, NKT, DN, CD3-CD8+ NK, CD3+CD8bright and CD3+CD8dim with a significantly lower B-cell content compared to BM was characteristic for lymphocyte subpopulation composition of blood in AM. In the CSF of children with AM, T-cells and Th prevailed, while the number of B-cells and CD3-CD8 + NK was lower compared to those in BM. The dynamics of the disease revealed differences in CSF and blood subpopulation composition depending on the nosological form, while maintaining differences of some major and minor lymphocyte subpopulations from the comparison group. The calculation of the ratio of CSF/blood for the major and minor lymphocyte subpopulations revealed the prevalence of most subpopulations (the coefficients ranged from 1.2 to 16.4) in the CSF of the comparison group (ARVI), except B-cells, NK and CD3-CD8+ NK (coefficients ranged from 0.07 to 0.31). In AM and BM there occurred various changes in the CSF/blood ratio for most of the studied subpopulations in the acute period and in the recovery phase with characteristic features for each nosological form. Conclusion. The results indicate the presence of specific features in the activation of systemic and intrathecal immune response in viral and bacterial meningitis in children and can be used as an additional differential diagnostic criterion.