The incidence of varicella and herpes zoster in Massachusetts as measured by the Behavioral Risk Factor Surveillance System (BRFSS) during a period of increasing varicella vaccine coverage, 1998–2003

BACKGROUND: The authors sought to monitor the impact of widespread varicella vaccination on the epidemiology of varicella and herpes zoster. While varicella incidence would be expected to decrease, mathematical models predict an initial increase in herpes zoster incidence if re-exposure to varicella protects against reactivation of the varicella zoster virus. METHODS: In 1998–2003, as varicella vaccine uptake increased, incidence of varicella and herpes zoster in Massachusetts was monitored using the random-digit-dial Behavioral Risk Factor Surveillance System. RESULTS: Between 1998 and 2003, varicella incidence declined from 16.5/1,000 to 3.5/1,000 (79%) overall with ≥66% decreases for all age groups except adults (27% decrease). Age-standardized estimates of overall herpes zoster occurrence increased from 2.77/1,000 to 5.25/1,000 (90%) in the period 1999–2003, and the trend in both crude and adjusted rates was highly significant (p < 0.001). Annual age-specific rates were somewhat unstable, but all increased, and the trend was significant for the 25–44 year and 65+ year age groups. CONCLUSION: As varicella vaccine coverage in children increased, the incidence of varicella decreased and the occurrence of herpes zoster increased. If the observed increase in herpes zoster incidence is real, widespread vaccination of children is only one of several possible explanations. Further studies are needed to understand secular trends in herpes zoster before and after use of varicella vaccine in the United States and other countries

Viral Load, Clinical Disease Severity and Cellular Immune Responses in Primary Varicella Zoster Virus Infection in Sri Lanka

BACKGROUND: In Sri Lanka, varicella zoster virus (VZV) is typically acquired during adulthood with significant associated disease morbidity and mortality. T cells are believed to be important in the control of VZV replication and in the prevention of reactivation. The relationship between viral load, disease severity and cellular immune responses in primary VZV infection has not been well studied. METHODOLOGY: We used IFNgamma ELISpot assays and MHC class II tetramers based on VZV gE and IE63 epitopes, together with quantitative real time PCR assays to compare the frequency and phenotype of specific T cells with virological and clinical outcomes in 34 adult Sri Lankan individuals with primary VZV infection. PRINCIPAL FINDINGS: Viral loads were found to be significantly higher in patients with moderate to severe infection compared to those with mild infection (p&lt;0.001) and were significantly higher in those over 25 years of age (P&lt;0.01). A significant inverse correlation was seen between the viral loads and the ex vivo IFNgamma ELISpot responses of patients (P&lt;0.001, r = -0.85). VZV-specific CD4+ T cells expressed markers of intermediate differentiation and activation. CONCLUSIONS: Overall, these data show that increased clinical severity in Sri Lankan adults with primary VZV infection associates with higher viral load and reduced viral specific T cell responses

Hospitalizations for varicella in children and adolescents in a referral hospital in Hong Kong, 2004 to 2008: A time series study

Background: Varicella accounts for significant morbidities and remains a public health issue worldwide. Climatic factors have been shown to associate with the incidence and transmission of various infectious diseases. We describe the epidemiology of varicella in paediatric patients hospitalized at a tertiary referral hospital in Hong Kong from 2004 to 2008, and to explore the possible association between the occurrence of varicella infection and various climatic factors. Methods. The hospital discharge database of Princess Margaret Hospital was retrospectively analyzed for admissions associated with varicella from 2004 to 2008. Meteorological data were obtained from the monthly meteorological reports from the Hong Kong Observatory website. Time series analysis was performed with Poisson regression using a Generalized Estimating Equation (GEE) approach. Results: During the study period, 598 children were hospitalized for varicella. The mean age on admission was 57.6 months, and the mean duration of hospitalization was 3.7 days. The overall complication rate was 47%. The mean monthly relative humidity, especially in cool seasons, was inversely correlated with the monthly varicella cases of the same month. Conclusions: Varicella can lead to serious complications and prolonged hospitalization, even in previously healthy children. Lower relative humidity in cool seasons is associated with higher number of paediatric varicella hospital admissions. These findings are useful for a better understanding of the pattern of paediatric varicella hospitalization in Hong Kong. © 2011 Chan et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex

Genome-Wide Mutagenesis Reveals That ORF7 Is a Novel VZV Skin-Tropic Factor

The Varicella Zoster Virus (VZV) is a ubiquitous human alpha-herpesvirus that is the causative agent of chicken pox and shingles. Although an attenuated VZV vaccine (v-Oka) has been widely used in children in the United States, chicken pox outbreaks are still seen, and the shingles vaccine only reduces the risk of shingles by 50%. Therefore, VZV still remains an important public health concern. Knowledge of VZV replication and pathogenesis remains limited due to its highly cell-associated nature in cultured cells, the difficulty of generating recombinant viruses, and VZV's almost exclusive tropism for human cells and tissues. In order to circumvent these hurdles, we cloned the entire VZV (p-Oka) genome into a bacterial artificial chromosome that included a dual-reporter system (GFP and luciferase reporter genes). We used PCR-based mutagenesis and the homologous recombination system in the E. coli to individually delete each of the genome's 70 unique ORFs. The collection of viral mutants obtained was systematically examined both in MeWo cells and in cultured human fetal skin organ samples. We use our genome-wide deletion library to provide novel functional annotations to 51% of the VZV proteome. We found 44 out of 70 VZV ORFs to be essential for viral replication. Among the 26 non-essential ORF deletion mutants, eight have discernable growth defects in MeWo. Interestingly, four ORFs were found to be required for viral replication in skin organ cultures, but not in MeWo cells, suggesting their potential roles as skin tropism factors. One of the genes (ORF7) has never been described as a skin tropic factor. The global profiling of the VZV genome gives further insights into the replication and pathogenesis of this virus, which can lead to improved prevention and therapy of chicken pox and shingles

Assessing the introduction of universal varicella vaccination in the Netherlands.

Although varicella is seen as a benign disease in the Netherlands, about 40,000 visits to a general practitioner (GP) are made, over 200 hospital admission occur, and 2.3 persons die on average each year. Most of this burden of disease can be prevented by universal varicella childhood vaccination. Ten years after the introduction of the single-shot, single-component varicella childhood vaccination in the USA, a major reduction in hospitalization, mortality, and burden of disease has been reported. Using our recently vaccine evaluation model for the introduction of a new vaccine in our national immunization program, we have analyzed the feasibility of universal varicella vaccination by replacing the measles-mumps-rubella (MMR) vaccine with a measles-mumps-rubella-varicella (MMRV) vaccine. After structuring and reviewing the available data, two major points of uncertainty remain: (1) the influence of universal childhood vaccination on the incidence of zoster later in life; (2) the cost-effectiveness ratio for the Dutch situation. Despite these uncertainties it is clear that universal childhood vaccination will prevent most of the varicella related GP-visits, hospitalizations, and deaths