ABSTRACT
OBJECTIVE: To evaluate Ontario's provincial varicella vaccination program through analysis of aggregate varicella cases in order to determine whether there has been a decrease in reportable disease burden; and to assess varicella vaccine adverse events following immunization (AEFIs). METHODS: Aggregate varicella cases (1993-2013) were extracted from the reportable disease databases. Pre-program (1993-2004) and post-program (2007-2013) periods were chosen according to implementation of the publicly funded vaccination program. AEFIs following administration of varicella vaccines (2010-2013) were also extracted. Reporting rates were calculated using net doses distributed as the denominator. Serious AEFIs were defined using World Health Organization standards. RESULTS: The incidence of aggregate varicella reports decreased significantly over the study period (from 311.4 to 22.2 cases per 100,000 population in 1993 and 2013, respectively). Incidence also decreased significantly in all age groups between the pre- and the post-program periods with a shift in age distribution towards older individuals in the post-program period. A total of 162 AEFIs following varicella vaccine were reported between 2010 and 2013 for an annualized reporting rate of 14.6 per 100,000 doses distributed. The most common events were rash (37.3%), including eight reports of varicella-like rash (0.7 per 100,000 doses distributed). Ten serious events were reported (0.9 per 100,000 doses distributed), and all vaccine recipients recovered. CONCLUSION: Significant reductions in varicella disease incidence and low AEFI reporting rates were observed with the introduction of the publicly funded varicella vaccine program in Ontario. Continued surveillance is indicated to further assess trends in varicella disease and vaccine safety.
ABSTRACT
Studies using animal models have shown that general anesthetics such as ketamine trigger widespread and robust apoptosis in the infant rodent brain. Recent clinical evidence suggests that the use of general anesthetics on young children (at ages equivalent to those used in rodent studies) can promote learning deficits as they mature. Thus, there is a growing need to develop strategies to prevent this injury. In this study, we describe a number of independent approaches to address therapeutic intervention. Postnatal day 7 (P7) rats were injected with vehicle (sterile PBS) or the NMDAR antagonist ketamine (20 mg/kg). After 8 h, we prepared brains for immunohistochemical detection of the pro-apoptotic enzyme activated caspase-3 (AC3). Focusing on the somatosensory cortex, AC3-positive cells were then counted in a non-biased stereological manner. We found AC3 levels were markedly increased in ketamine-treated animals. In one study, microarray analysis of the somatosensory cortex from ketamine-treated P7 pups revealed that expression of activity dependent neuroprotective protein (ADNP) was enhanced. Thus, we injected P7 animals with the ADNP peptide fragment NAPVSIPQ (NAP) 15 min before ketamine administration and found we could dose-dependently reverse the injury. In separate studies, pretreatment of P6 animals with 20 mg/kg vitamin D(3) or a nontoxic dose of ketamine (5 mg/kg) also prevented ketamine-induced apoptosis at P7. In contrast, pretreatment of P7 animals with aspirin (30 mg/kg) 15 min before ketamine administration actually increased AC3 counts in some regions. These data show that a number of unique approaches can be taken to address anesthesia-induced neurotoxicity in the infant brain, thus providing MDs with a variety of alternative strategies that enhance therapeutic flexibility.