A single 15-microg dose of 2009 H1N1 vaccine was immunogenic in adults, with mild-to-moderate vaccine-associated reactions. (ClinicalTrials.gov number, NCT00938639).

HE DISEASE BURDEN OF SEAsonal influenza in the pediatric population is generally attributed to a combination of immunologic naivety, prolonged virus shedding, and enhanced transmission opportunity in child-care and educational institutions. 1 Consistent with this experience, initial reports of the introduction and indigenous transmission of 2009 influenza A(H1N1) infection in many countries have largely involved children, 2 often attending day or boarding schools. [3][4][5] Serosurveys have demonstrated little or no cross-reactivity of the pediatric sera sample to the new virus strain, under-Context In the ongoing influenza pandemic, a safe and effective vaccine against 2009 influenza A(H1N1) is needed for infants and children.Objective To assess the immunogenicity and safety of a 2009 influenza A(H1N1) vaccine in children.Design, Setting, and Participants Randomized, observer-blind, age-stratified, parallel group study assessing 2 doses of an inactivated, split-virus 2009 influenza A(H1N1) vaccine in 370 healthy infants and children aged 6 months to less than 9 years living in Australia.Intervention Intramuscular injection of 15 µg or 30 µg of hemagglutinin antigen dose of monovalent, unadjuvanted 2009 influenza A(H1N1) vaccine in a 2-dose regimen, administered 21 days apart.Main Outcome Measures Hemagglutination inhibition assay to estimate the proportion of participants with antibody titers of 1:40 or greater, seroconversion, or a significant antibody titer increase, and factor increase in geometric mean titer. Assessments of solicited adverse events during 7 days and unsolicited adverse events for 21 days after each vaccination. ResultsFollowing the first dose of vaccine, antibody titers of 1:40 or greater were observed in 161 of 174 infants and children in the 15-µg group (92.5%; 95% confidence interval [CI], 87.6%-95.6%) and in 168 of 172 infants and children in the 30-µg group (97.7%; 95% CI, 94.2%-99.1%). Corresponding seroconversion rates were 86.8% (95% CI, 80.9%-91.0%) and 94.2% (95% CI, 89.6%-96.8%), and factor increases in geometric mean titer were 13.6 (95% CI,). All participants demonstrated antibody titers of 1:40 or greater after the second vaccine dose. Immune responses were robust regardless of age, baseline serostatus, or seasonal influenza vaccination status. The majority of adverse events were mild to moderate in severity. ConclusionOne 15-µg dose of vaccine was immunogenic in infants and children starting at 6 months of age and vaccine-associated reactions were mild to moderate in severity. Trial Registration clinicaltrials.gov Identifier: NCT00940108

RSV bronchiolitis causes significant infant mortality. Bronchiolitis is characterised by airway epithelial cell (AEC) death, however the mode of death remains unknown. Objectives:To determine whether necroptosis contributes to RSV bronchiolitis pathogenesis via high mobility group box 1 (HMGB1) release. Methods:Nasopharyngeal samples were collected from children presenting to hospital with acute respiratory infection. Primary human AECs and neonatal mice were inoculated with RSV and murine pneumovirus respectively. Necroptosis was determined via viability assays and immunohistochemistry for receptor-interacting protein kinase-1 (RIPK1), mixed lineage kinase domain-like protein (MLKL) and caspase-3. Necroptosis was blocked using pharmacological inhibitors, and RIPK1 kinase-dead knock-in mice. Measurements and Main Results:HMGB1 levels were elevated in nasopharyngeal samples of children with acute RSV infection. RSV-induced epithelial cell death was associated with increased pRIPK1 and pMLKL, but not active caspase-3 expression. Inhibition of RIPK1 or MLKL attenuated RSVinduced HMGB1 translocation and release, and lowered viral load. MLKL inhibition increased active caspase-3 expression in a caspase-8/9-dependent manner. In susceptible mice, Pneumovirus infection up-regulated RIPK1 and MLKL expression in the airway epithelium at 8-10 days post infection; coinciding with AEC sloughing, HMGB1 release, and

The clinical utility of EEG in cases of NMDA encephalitis is broad with many findings indicating not just epileptiform activity but also encephalopathy and potentially providing insights into pathophysiologic mechanisms of disease. We aimed to determine the frequency of different abnormalities described on EEG and their association with outcome in patients affected by NMDARE through a systematic review of all cases published. Method: A systematic literature review of PubMed and Embase of all published cases of anti-NMDA receptor encephalitis with EEG results, was performed from inception to January 2018. Results: A total of 446 cases of anti-NMDA receptor encephalitis with reported EEG findings were identified. 373 EEGs were abnormal, and this strongly correlated with ICU admission and time to recovery (p = 0.014 and 0.04 respectively). ICU admission and recovery were also correlated with delta range abnormalities including extreme delta brush (p = 0.007 and 0.03). Electrographic seizures correlated strongly with clinical seizures (p < 0.0001), however only 39 cases had EEG seizures captured, while there were 294 cases with clinical seizures. Conclusions: EEG is useful in the clinical management and prognostication of cases on NMDA encephalitis. This is particularly true of certain findings which portend a higher likelihood of ICU admission or poorer outcome and this may assist in the decision to pursue more aggressive treatment options.

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