Hand sanitisers for reducing illness absences in primary school children in New Zealand: a cluster randomised controlled trial study protocol

<p>Abstract</p> <p>Background</p> <p>New Zealand has relatively high rates of morbidity and mortality from infectious disease compared with other OECD countries, with infectious disease being more prevalent in children compared with others in the population. Consequences of infectious disease in children may have significant economic and social impact beyond the direct effects of the disease on the health of the child; including absence from school, transmission of infectious disease to other pupils, staff, and family members, and time off work for parents/guardians. Reduction of the transmission of infectious disease between children at schools could be an effective way of reducing the community incidence of infectious disease. Alcohol based no-rinse hand sanitisers provide an alternative hand cleaning technology, for which there is some evidence that they may be effective in achieving this. However, very few studies have investigated the effectiveness of hand sanitisers, and importantly, the potential wider economic implications of this intervention have not been established.</p> <p>Aims</p> <p>The primary objective of this trial is to establish if the provision of hand sanitisers in primary schools in the South Island of New Zealand, in addition to an education session on hand hygiene, reduces the incidence rate of absence episodes due to illness in children. In addition, the trial will establish the cost-effectiveness and conduct a cost-benefit analysis of the intervention in this setting.</p> <p>Methods/Design</p> <p>A cluster randomised controlled trial will be undertaken to establish the effectiveness and cost-effectiveness of hand sanitisers. Sixty-eight primary schools will be recruited from three regions in the South Island of New Zealand. The schools will be randomised, within region, to receive hand sanitisers and an education session on hand hygiene, or an education session on hand hygiene alone. Fifty pupils from each school in years 1 to 6 (generally aged from 5 to 11 years) will be randomly selected for detailed follow-up about their illness absences, providing a total of 3400 pupils. In addition, absence information will be collected on all children from the school rolls. Investigators not involved in the running of the trial, outcome assessors, and the statistician will be blinded to the group allocation until the analysis is completed.</p> <p>Trial registration</p> <p>ACTRN12609000478213</p

Identification of a human neonatal immune-metabolic network associated with bacterial infection

Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis

Transcriptomic profile of host response in Japanese encephalitis virus infection

<p>Abstract</p> <p>Background</p> <p>Japanese encephalitis (JE) is one of the leading causes of acute encephalopathy with the highest mortality rate of 30-50%. The purpose of this study was to understand complex biological processes of host response during the progression of the disease. Virus was subcutaneously administered in mice and brain was used for whole genome expression profiling by cDNA microarray.</p> <p>Results</p> <p>The comparison between viral replication efficiency and disease progression confirms the active role of host response in immunopathology and disease severity. The histopathological analysis confirms the severe damage in the brain in a time dependent manner. Interestingly, the transcription profile reveals significant and differential expression of various pattern recognition receptors, chemotactic genes and the activation of inflammasome. The increased leukocyte infiltration and aggravated CNS inflammation may be the cause of disease severity.</p> <p>Conclusion</p> <p>This is the first report that provides a detailed picture of the host transcriptional response in a natural route of exposure and opens up new avenues for potential therapeutic and prophylactic strategies against Japanese encephalitis virus.</p

Genomic Data Reveal Toxoplasma gondii Differentiation Mutants Are Also Impaired with Respect to Switching into a Novel Extracellular Tachyzoite State

Toxoplasma gondii pathogenesis includes the invasion of host cells by extracellular parasites, replication of intracellular tachyzoites, and differentiation to a latent bradyzoite stage. We present the analysis of seven novel T. gondii insertional mutants that do not undergo normal differentiation to bradyzoites. Microarray quantification of the variation in genome-wide RNA levels for each parasite line and times after induction allowed us to describe states in the normal differentiation process, to analyze mutant lines in the context of these states, and to identify genes that may have roles in initiating the transition from tachyzoite to bradyzoite. Gene expression patterns in wild-type parasites undergoing differentiation suggest a novel extracellular state within the tachyzoite stage. All mutant lines exhibit aberrant regulation of bradyzoite gene expression and notably some of the mutant lines appear to exhibit high proportions of the intracellular tachyzoite state regardless of whether they are intracellular or extracellular. In addition to the genes identified by the insertional mutagenesis screen, mixture model analysis allowed us to identify a small number of genes, in mutants, for which expression patterns could not be accounted for using the three parasite states – genes that may play a mechanistic role in switching from the tachyzoite to bradyzoite stage

Peptide receptor radionuclide therapy for metastatic paragangliomas

There is little evidence to direct the management of malignant paragangliomas (mPGL) beyond initial surgical treatment. Peptide receptor radionuclide therapy (PRRT), using somatostatin analogues, is effective in other neuroendocrine tumours, but data on its efficacy in treating mPGL are scarce. We report safety and efficacy outcomes from a case series of five patients with advanced mPGLs treated with 177Lu-DOTATATE PRRT. The mean age of our cohort was 34 years (range 16-47); 4 patients were male with bone disease being the most prevalent metastatic site. PRRT scheme varied between 1 and 4 cycles, with premature cessation due to suspected pneumonitis in one case and disease progression in another. Three patients with previously documented progressive disease achieved stabilization following treatment; one had partial response and one was treatment refractory. Median progression-free survival was 17 months (range 0-78 months). 177-Lu-DOTATATE is an effective therapy in mPGLs in this molecularly defined patient cohort, warranting further investigation in larger studies including hereditary and sporadic mPGL

A meta‐analysis on allergen‐specific immunotherapy using MCT ®

BACKGROUND: The World Allergy Organization and the European Academy of Allergy and Clinical Immunology recommend to perform product‐specific meta‐analyses for allergen‐specific immunotherapies because of the high degree of heterogeneity between individual products. This meta‐analysis evaluates the efficacy and safety of Glutaraldehyde‐modified and MCT(®) (MicroCrystalline Tyrosine)‐adsorbed allergoids (MATA). METHODS: The databases MEDLINE, LILACS, embase, LIVIVO, Web of Science and Google (Scholar) were searched for publications on MATA up to June 2019. Primary endpoint was the combined symptom and medication score (CSMS). Secondary endpoints were single scores, immunogenicity and improvement of allergic condition. Secondary safety endpoints were the occurrence of side effects. A random effects model was applied with (standardized) mean differences ([S]MDs) including confidence intervals (CI). Heterogeneity was analyzed using the I(2) index and publication bias using Egger's test and Funnel plots. Subgroups were analyzed regarding age and asthma status. RESULTS: Eight randomized double‐blind placebo‐controlled trials were selected for efficacy and 43 publications for safety analysis. In total, 4531 patients were included in this analysis including eight studies containing data on children and adolescents. AIT with MATA significantly reduced allergic symptoms and medication use with a SMD for CSMS of −0.8 (CI: −1.24, −0.36) in comparison to placebo. Heterogeneity was moderate between the studies. The total symptom score (−1.2 [CI: −2.11, −0.29]) and the total medication score (−2.2 [CI: −3.65, −0.74]) were also significantly reduced after MATA treatment. Patient's condition improved significantly after treatment with MATA, with an odds ratio of 3.05 (CI: 1.90, 4.90) when compared to placebo. The proportion of patients, who developed side effects was 38% (CI: 19%, 57%). No serious side effects occurred. Safety in the subgroups of asthmatic patients, children and adolescents did not differ from the overall patient population. CONCLUSIONS: This meta‐analysis reveals a large body of evidence from publications investigating MATA. MATA significantly improved allergic symptoms and reduced the use of anti‐allergic medication in comparison to placebo, with an excellent safety profile. Especially for children and asthmatic patients, the use of MATAs can be considered as safe, because the safety profiles in these groups did not differ from the total patient population