Adult encephalitis surveillance: experiences from an Australian prospective sentinel site study.

Few countries routinely collect comprehensive encephalitis data, yet understanding the epidemiology of this condition has value for clinical management, detecting novel and emerging pathogens, and guiding timely public health interventions. When this study was conducted there was no standardized diagnostic algorithm to aid identification of encephalitis or systematic surveillance for adult encephalitis. In July 2012 we tested three pragmatic surveillance options aimed at identifying possible adult encephalitis cases admitted to a major Australian hospital: hospital admissions searches, clinician notifications and laboratory test alerts (CSF herpes simplex virus requests). Eligible cases underwent structured laboratory investigation and a specialist panel arbitrated on the final diagnosis. One hundred and thirteen patients were initially recruited into the 10-month study; 20/113 (18%) met the study case definition, seven were diagnosed with infectious or immune-mediated encephalitis and the remainder were assigned alternative diagnoses. The laboratory alert identified 90% (102/113) of recruited cases including six of the seven cases of confirmed encephalitis suggesting that this may be a practical data source for case ascertainment. The application of a standardized diagnostic algorithm and specialist review by an expert clinical panel aided diagnosis of patients with encephalitis.

Changes in severity of 2009 pandemic A/H1N1 influenza in England: a Bayesian evidence synthesis.

OBJECTIVE: To assess the impact of the 2009 A/H1N1 influenza pandemic in England during the two waves of activity up to end of February 2010 by estimating the probabilities of cases leading to severe events and the proportion of the population infected. DESIGN: A Bayesian evidence synthesis of all available relevant surveillance data in England to estimate severity of the pandemic. DATA SOURCES: All available surveillance systems relevant to the pandemic 2009 A/H1N1 influenza outbreak in England from June 2009 to February 2010. Pre-existing influenza surveillance systems, including estimated numbers of symptomatic cases based on consultations to the health service for influenza-like illness and cross sectional population serological surveys, as well as systems set up in response to the pandemic, including follow-up of laboratory confirmed cases up to end of June 2009 (FF100 and Fluzone databases), retrospective and prospective follow-up of confirmed hospitalised cases, and reported deaths associated with pandemic 2009 A/H1N1 influenza. Main outcome measures Age specific and wave specific probabilities of infection and symptomatic infection resulting in hospitalisation, intensive care admission, and death, as well as infection attack rates (both symptomatic and total). The probabilities of intensive care admission and death given hospitalisation over time are also estimated to evaluate potential changes in severity across waves. RESULTS: In the summer wave of A/H1N1 influenza, 0.54% (95% credible interval 0.33% to 0.82%) of the estimated 606,100 (419,300 to 886,300) symptomatic cases were hospitalised, 0.05% (0.03% to 0.08%) entered intensive care, and 0.015% (0.010% to 0.022%) died. These correspond to 3200 (2300 to 4700) hospital admissions, 310 (200 to 480) intensive care admissions, and 90 (80 to 110) deaths in the summer wave. In the second wave, 0.55% (0.28% to 0.89%) of the 1,352,000 (829,900 to 2,806,000) estimated symptomatic cases were hospitalised, 0.10% (0.05% to 0.16%) were admitted to intensive care, and 0.025% (0.013% to 0.040%) died. These correspond to 7500 (5900 to 9700) hospitalisations, 1340 (1030 to 1790) admissions to intensive care, and 240 (310 to 380) deaths. Just over a third (35% (26% to 45%)) of infections were estimated to be symptomatic. The estimated probabilities of infections resulting in severe events were therefore 0.19% (0.12% to 0.29%), 0.02% (0.01% to 0.03%), and 0.005% (0.004% to 0.008%) in the summer wave for hospitalisation, intensive care admission, and death respectively. The corresponding second wave probabilities are 0.19% (0.10% to 0.32%), 0.03% (0.02% to 0.06%), and 0.009% (0.004% to 0.014%). An estimated 30% (20% to 43%) of hospitalisations were detected in surveillance systems in the summer, compared with 20% (15% to 25%) in the second wave. Across the two waves, a mid-estimate of 11.2% (7.4% to 18.9%) of the population of England were infected, rising to 29.5% (16.9% to 64.1%) in 5-14 year olds. Sensitivity analyses to the evidence included suggest this infection attack rate could be as low as 5.9% (4.2% to 8.7%) or as high as 28.4% (26.0% to 30.8%). In terms of the probability that an infection leads to death in the second wave, these correspond, respectively, to a high estimate of 0.017% (0.011% to 0.024%) and a low estimate of 0.0027% (0.0024% to 0.0031%). CONCLUSIONS: This study suggests a mild pandemic, characterised by case and infection severity ratios increasing between waves. Results suggest low ascertainment rates, highlighting the importance of systems enabling early robust estimation of severity, to inform optimal public health responses, particularly in light of the apparent resurgence of the 2009 A/H1N1 strain in the 2010-11 influenza season.

Purification and partial characterisation of an alpha-tocopherol-binding protein from rabbit heart cytosol.

An alpha-tocopherol-binding protein has been isolated and purified from rabbit heart cytosol. The purified protein had an apparent molecular mass of 14,200, as derived from SDS-PAGE. The content of the protein in rabbit heart was around 11.8 micrograms per g of tissue. The binding of alpha-tocopherol to the purified protein was rapid, reversible, and saturable. Neither gamma nor delta tocopherol could displace the bound alpha-tocopherol from the protein, suggesting a high specificity for alpha-tocopherol. alpha-Tocopherol-binding protein did not bind oleate. Transfer of alpha-tocopherol from liposomes to mitochondria was stimulated 8-fold in the presence of the binding protein, suggesting that this protein may be involved in the intracellular transport of alpha-tocopherol in the heart.

Prostaglandin-E1-binding sites in rabbit erythrocyte membranes.

Prostaglandin E1 (PGE1) binding sites have been identified on rabbit erythrocyte membranes. The binding of PGE1 to the membranes was found to be highly specific, reversible, and saturable. The high-affinity binding sites had a dissociation constant (Kd.1) of 5.6 +/- 1.2 nM with a binding capacity of 210 +/- 51 fmol/mg protein, whereas the low-affinity binding sites had a dissociation constant (Kd.2) of 22 +/- 6.4 microM, and a binding capacity of 321 +/- 78 pmol/mg protein. Incubation with PGE1 did not activate adenylate cyclase in the membranes. Preincubation of rabbit erythrocyte membranes with physiological amounts of insulin (1.5 nM) resulted in an increase of PGE1 binding to the membranes from 241 +/- 65 to 429 +/- 85 fmol/mg protein. The insulin-induced increase in PGE1 binding was due to an increase in binding sites (both high-affinity and low-affinity binding sites) rather than to an increase in the affinity of the binding sites. Treatment of erythrocyte membranes with PGE1 at concentrations (4.0-7.5 nM) which were within the Kd.1 value of the high-affinity binding sites, resulted in a significant reduction in membrane fluorescence anisotropy (0.27 +/- 0.005-0.21 +/- 0.003). Use of higher concentrations (> 15 nM) of PGE1 reversed the effect of its lower concentration on the membrane anisotropy.