Varicella vaccination coverage of children under two years of age in Germany

Background: Since July 2004, routine varicella vaccination is recommended by the German Standing Vaccination Committee in Germany. Health Insurance Funds started to cover vaccination costs at different time points between 2004 and 2006 in the Federal States. Nationwide representative data on vaccination coverage against varicella of children under two years of age are not available. We aimed to determine varicella vaccination coverage in statutory health insured children under two years of age in twelve German Federal States using data from associations of statutory health insurance physicians (ASHIPs), in order to investigate the acceptance of the recommended routine varicella vaccination programme. Methods: We analysed data on varicella vaccination from 13 of 17 ASHIPs of the years 2004 to 2007. The study population consisted of all statutory health insured children under two years of age born in 2004 (cohort 2004) or 2005 (cohort 2005) in one of the studied regions. Vaccination coverage was determined by the number of children vaccinated under 2 years of age within the study population. Results: Varicella vaccination coverage of children under two years of age with either one dose of the monovalent varicella vaccine or two doses of the measles, mumps, rubella, and varicella vaccine increased from 34% (cohort 2004) to 51% (cohort 2005) in the studied regions (p < 0.001). More than half of the vaccinated children of cohort 2004 and two third of cohort 2005 were immunised at the recommended age 11 to 14 months. The level of vaccination coverage of cohort 2004 was significantly associated with the delay in introduction of cost coverage since the recommendation of varicella vaccination (p < 0.001). Conclusions: Our study shows increasing varicella vaccination coverage of young children, indicating a growing acceptance of the routine varicella vaccination programme by the parents and physicians. We recommend further monitoring of vaccination coverage using data from ASHIPs to investigate acceptance of the routine vaccination programmes over time

Simian Varicella Virus Infection of Rhesus Macaques Recapitulates Essential Features of Varicella Zoster Virus Infection in Humans

Simian varicella virus (SVV), the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV). Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP) resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox) in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation

Spinal Astrocytic Activation Is Involved in a Virally-Induced Rat Model of Neuropathic Pain

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and “NO-Astrocyte-Cytokine-NMDAR-Neuron” pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN

Varicella-Zoster virus gene expression in latently infected rat dorsal root ganglia

Latent infection of human ganglia with Varicella-Zoster virus (VZV) is characterized by a highly restricted pattern of viral gene expression. To enhance understanding of this process we used in situ hybridization (ISH) in a rat model of VZV latency to examine expression of RNA corresponding to eight different VZV genes in rat dorsal root ganglia (DRG) at various times after footpad inoculation with wild-type VZV. PCR in situ amplification was also used to determine the cell specificity of latent VZV DNA. It was found that the pattern of viral gene expression at 1 week after infection was different from that observed at the later times of 1 and 18 months after infection. Whereas multiple genes were expressed at 1 week after infection, gene expression was restricted at the later time points when latency had been established. At the later time points after infection the RNA transcripts expressed most frequently were those for VZV genes 21, 62, and 63. Gene 63 was expressed more than any other gene studied. While VZV DNA was detected almost exclusively in 5-10% of neurons, VZV RNA was detected in both neurons and nonneuronal cells at an approximate ratio of 3:1. A newly described monoclonal antibody to VZV gene 63-encoded protein was used to detect this protein in neuronal nuclei and cytoplasm in almost half of the DRG studied. These results demonstrate that (1) this rat model of latency has close similarities in terms of viral gene expression to human VZV latency which makes it a useful tool for studying this process and its experimental modulation and (2) expression of VZV gene 63 appears to be the single most consistent feature of VZV latency

Antibodies to varicella-zoster virus modulate antigen distribution but fail to induce viral persistence in vitro.

Varicella-zoster virus (VZV) persists in human sensory ganglia. One of the hypotheses to explain the induction or the maintenance of VZV latency is that it could be promoted by the immune response itself. It is known that in the case of viruses which bud off the infected cell membrane, virus-specific antibodies can induce antigenic modulation, i.e., spatial redistribution of viral antigens and modulation of their synthesis. To determine whether antigenic modulation occurs during VZV infection in vitro and could possibly be involved in viral persistence, we have grown infected cells in the presence of anti-VZV antibodies either transiently or permanently. The distribution of immune complexes and viral proteins was then analyzed. In transient immunomodulation experiments, the distribution of one or more viral antigens was modified not only in the cytoplasmic membranes but also in the cytoplasm and nucleoplasm of infected cells. When infected cells were kept permanently in the presence of antibodies, the same pattern of redistribution of immune complexes was observed and the localization of internal viral glycoproteins was significantly modified. However, antibodies did not prevent the lytic effect of infection; they altered neither the infectious virus yield nor the Western immunoblot pattern of viral proteins, suggesting that immunomodulation is not the primary effector of viral persistence