Subclinical VZV reactivation in immunocompetent children hospitalized in the ICU associated with prolonged fever duration*

AbstractA prospective observational study was conducted to examine whether asymptomatic VZV reactivation occurs in immunocompetent children hospitalized in an ICU and its impact on clinical outcome. A secondary aim was to test the hypothesis that vaccinated children have a lower risk of reactivation than naturally infected children. Forty immunocompetent paediatric ICU patients and healthy controls were enrolled. Patients were prospectively followed for 28 days. Clinical data were collected and varicella exposure was recorded. Admission serum levels of TNF-a, cortisol and VZV-IgG were measured. Blood and saliva samples were collected for VZV-DNA detection via real-time PCR. As a comparison, the detection of HSV-DNA was also examined. Healthy children matched for age and varicella exposure type (infection or vaccination) were also included. VZV reactivation was observed in 17% (7/39) of children. Children with VZV reactivation had extended duration of fever (OR = 1.17; 95% CI, 1.02–1.34). None of the varicella-vaccinated children or healthy controls had detectable VZV-DNA in any blood or saliva samples examined. HSV-DNA was detected in saliva from 33% of ICU children and 2.6% of healthy controls. Among children with viral reactivation, typing revealed wild-type VZV and HSV-1. In conclusion, VZV reactivation occurs in immunocompetent children under severe stress and is associated with prolonged duration of fever

Varicella-zoster virus seroprevalence in children and adolescents in the pre-varicella vaccine era, Germany

Background: In 2004, universal childhood varicella vaccination was introduced in Germany. We aimed to determine the age-specific prevalence of anti-varicella zoster virus (VZV) IgG-antibodies among children in the pre-varicella vaccine era in Germany, to identify factors associated with VZV seropositivity, and to assess the suitability of a commercially available ELISA for VZV seroepidemiological studies by comparing it with an in-house fluorescent antibody to membrane antigen test (FAMA) as the gold standard. Methods: Serum samples of 13,433 children and adolescents aged 1–17 years included in the population-based German Health Interview and Examination Survey for Children and Adolescents (KiGGS; conducted 2003–2006) were tested for anti-VZV IgG by ELISA. All samples with equivocal ELISA results and a random selection of ELISA-negative and -positive samples were tested by FAMA. Statistical analyses were conducted using a weighting factor adjusting the study population to the total population in Germany. Seroprevalences were calculated as percentages (%) with a 95% confidence interval (CI). Odds ratios (OR) were computed by multivariate logistic regression to determine the association between socio-demographic factors and VZV seropositivity. Results: The VZV seropositivity rate was 80.3% (95% CI: 79.3–81.3) in varicella-unvaccinated children and adolescents. VZV seropositivity rates differed significantly between age groups up to age 6 years, but not by gender. Of 118 retested serum samples with an equivocal ELISA result, 45.8% were FAMA-positive. The proportion of samples tested as false-negative in by ELISA varied by age group: 2.6% in children aged 1–6 and 9% in children aged 7–17 years. Multivariate analyses showed that age, having older siblings, and early daycare start were associated with seropositivity in preschoolers; migration background reduced the chance of VZV seropositivity in schoolchildren (OR: 0.65; 0.43–0.99) and adolescents (OR: 0.62; 0.4–0.97). Conclusion: In the pre-varicella vaccine era, most children in Germany contracted varicella by age six. Schoolchildren with a migration background and children without siblings have an increased risk of being VZV seronegative and should be targeted for catch-up vaccination, if they have no history of chickenpox. ELISAs are suitable for use in population-level serosurveys on VZV, but samples with equivocal ELISA results should be retested by FAMA

Epigenetic mechanisms regulating the transition from embryonic stem cells towards a differentiated neural progeny

The hippocampal formation and parahippocampal region are prominent components of the rat nervous system and play a crucial role in learning, memory, and spatial navigation. Many new details regarding the entorhinal cortex have been discovered since the previous edition, and the growing interest in the area of CA2 has been covered in this chapter. Emphasis is on a conceptual change: instead of perceiving the hippocampal circuit as the standard sequential processing network, current insights favor the concept that multiple parallel networks are present. Many new facts, combined with a thorough restructuring of information and inclusion of pointers to relevant (online) resources, make this chapter relevant to both the novice and senior readership