Underreporting of viral encephalitis and viral meningitis, Ireland, 2005-2008.

Viral encephalitis (VE) and viral meningitis (VM) have been notifiable infectious diseases under surveillance in the Republic of Ireland since 1981. Laboratories have reported confirmed cases by detection of viral nucleic acid in cerebrospinal fluid since 2004. To determine the prevalence of these diseases in Ireland during 2005-2008, we analyzed 3 data sources: Hospital In-patient Enquiry data (from hospitalized following patients discharge) accessed through Health Intelligence Ireland, laboratory confirmations from the National Virus Reference Laboratory, and events from the Computerised Infectious Disease Reporting surveillance system. We found that the national surveillance system underestimates the incidence of these diseases in Ireland with a 10-fold higher VE hospitalization rate and 3-fold higher VM hospitalization rate than the reporting rate. Herpesviruses were responsible for most specified VE and enteroviruses for most specified VM from all 3 sources. Recommendations from this study have been implemented to improve the surveillance of these diseases in Ireland.

Rapid activation of poly(ADP-ribose) polymerase contributes to Sindbis virus and staurosporine-induced apoptotic cell death.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a chromatin-associated enzyme that is activated by DNA strand breaks and catalyzes the transfer of ADP-ribose groups from NAD to itself and other nuclear proteins. Although caspase-mediated PARP-1 cleavage occurs during almost all forms of apoptosis, the contribution of PARP-1 activation and cleavage to this cell death process remains unclear. Using immortalized fibroblasts from wild-type (PARP-1(+/+)) and PARP-1 knockout (PARP-1(-/-)) mice, and a mouse neuroblastoma cell line (N18), the role that poly(ADP-ribosyl)ation plays in Sindbis virus (SV)-induced apoptosis was examined. Robust PARP-1 activation occurred in SV-infected cells prior to morphologic changes associated with apoptotic cell death and PARP-1 activity ceased simultaneously with caspase-3 activation and PARP-1 proteolysis. PARP-1 activity was maximal before detectable DNA fragmentation, but was absent when DNA damage was most intense. SV and staurosporine-induced cell death was delayed in fibroblasts lacking PARP-1 activity, suggesting that PARP-1 activation contributes to apoptotic cell death induced by these stimuli. SV replication was not affected by lack of PARP-1 activity, but DNA fragmentation and caspase-3 activation were delayed and occurred at lower levels in PARP-1-deficient fibroblasts. Early virus-induced PARP-1 activation may represent a novel way by which cells signal to the nucleus to regulate protein function by poly(ADP-ribosyl)ation in response to virus infection.