Mpox outbreak control indicators used in Ontario, Canada: May 21-December 10, 2022.

Since May 2022, over 91 000 cases of mpox have been reported globally with the majority of cases occurring among adult males who identify as gay, bisexual, or men who have sex with men (gbMSM). Given the rapid emergence of the global mpox outbreak, many public health authorities did not have established mpox outbreak control indicators or criteria for declaring an mpox outbreak over. Expert consensus in Ontario, Canada, set thresholds for five key indicators of mpox outbreak control as follows: estimated number of currently infectious cases < 5; effective reproductive number < 1.0; doubling time > 42 days; weekly test positivity < 5%; and sporadic non-gbMSM cases (i.e., female and pediatric cases). Once all indicators were achieved, a 52-day period based on two incubation periods for mpox and a 10-day reporting delay was employed to monitor for indicator stability. After all five indicators remained at expected levels, the mpox outbreak in Ontario was declared over on December 10, 2022. Despite current low levels of mpox activity globally, some jurisdictions may benefit from utilizing or modifying these outbreak control indicators during a future localized mpox outbreak.

Exploring the Molecular Basis of Vesicular Stomatitis Virus Pathogenesis in Swine: Insights from Expression Profiling of Primary Macrophages Infected with M51R Mutant Virus.

Vesicular stomatitis virus (VSV) is an emergent virus affecting livestock in the US. Previously, using a recombinant VSV carrying the M51R mutation in the matrix protein (rNJ0612NME6-M51R), we evaluated the pathogenesis of this virus in pigs. Our results indicated that rNJ0612NME6-M51R represented an attenuated phenotype in in-vivo and in ex-vivo in pig macrophages, resembling certain clinical features observed in field VSV isolates. In order to gain more insight into the molecular basis leading to the attenuation of rNJ0612NME6-M51R in pigs, we conducted a microarray analysis to assess the gene expression profiles of primary porcine macrophages infected with rNJ0612NME6-M51R compared to its parental virus (rNJ0612NME6). Our results showed an overall higher gene expression in macrophages infected with rNJ0612NME6-M51R. Specifically, we observed that the pathways related with immune cytokine signaling and interferon (IFN)-related responses (including activation, signaling, induction, and antiviral mechanisms) were the ones comprising most of the relevant genes identified during this study. Collectively, the results presented herein highlight the relevance of type I interferon during the pathogenesis of VSV in pigs. The information generated from this study may represent a framework for future studies intended to understand the molecular bases of the pathogenesis of field strains in livestock.

Dopamine D2 receptor gene variants and response to rasagiline in early Parkinson's disease: a pharmacogenetic study.

The treatment of early Parkinson's disease with dopaminergic agents remains the mainstay of symptomatic therapy for this incurable neurodegenerative disorder. However, clinical responses to dopaminergic drugs vary substantially from person to person due to individual-, drug- and disease-related factors that may in part be genetically determined. Using clinical data and DNA samples ascertained through the largest placebo-controlled clinical trial of the monoamine oxidase B inhibitor, rasagiline (ClinicalTrials.gov number, NCT00256204), we examined how polymorphisms in candidate genes associate with the clinical response to rasagiline in early Parkinson's disease. Variants in genes that express proteins involved in the pharmacokinetics and pharmacodynamics of rasagiline, and genes previously associated with the risk to develop Parkinson's disease were genotyped. The LifeTechnologies OpenArray NT genotyping platform and polymerase chain reaction-based methods were used to analyse 204 single nucleotide polymorphisms and five variable number tandem repeats from 30 candidate genes in 692 available DNA samples from this clinical trial. The peak symptomatic response to rasagiline, the rate of symptom progression, and their relation to genetic variation were examined controlling for placebo effects using general linear and mixed effects models, respectively. Single nucleotide polymorphisms, rs2283265 and rs1076560, in the dopamine D2 receptor gene (DRD2) were found to be significantly associated with a favourable peak response to rasagiline at 12 weeks in early Parkinson's disease after controlling for multiple testing. From a linear regression, the betas were 2.5 and 2.38, respectively, with false discovery rate-corrected P-values of 0.032. These polymorphisms were in high linkage disequilibrium with each other (r(2) = 0.96) meaning that the same clinical response signal was identified by each of them. No polymorphisms were associated with slowing the rate of worsening in Parkinson symptoms from Weeks 12 to 36 after correction for multiple testing. This is the largest and most comprehensive pharmacogenetics study to date examining clinical response to an anti-parkinsonian drug and the first to be conducted in patients with early stage Parkinson's disease receiving monotherapy. The results indicate a clinically meaningful benefit to rasagiline in terms of the magnitude of improvement in parkinsonian symptoms for those with the favourable response genotypes. Future work is needed to elucidate the specific mechanisms through which these DRD2 variants operate in modulating the function of the nigrostriatal dopaminergic system.media-1vid110.1093/brain/aww109_video_abstractaww109_video_abstract.

The Effects of Media Reports on Disease Spread and Important Public Health Measurements.

Controlling the spread of influenza to reduce the effects of infection on a population is an important mandate of public health. Mass media reports on an epidemic or pandemic can provide important information to the public, and in turn, can induce positive healthy behaviour practices (i.e., handwashing, social distancing) in the individuals, that will reduce the probability of contracting the disease. Mass media fatigue, however, can dampen these effects. Mathematical models can be used to study the effects of mass media reports on epidemic/pandemic outcomes. In this study we employ a stochastic agent based model to provide a quantification of mass media reports on the variability in important public health measurements. We also include mass media report data compiled by the Global Public Health Intelligence Network, to study the effects of mass media reports in the 2009 H1N1 pandemic. We find that the report rate and the rate at which individuals relax their healthy behaviours (media fatigue) greatly affect the variability in important public health measurements. When the mass media reporting data is included in the model, two peaks of infection result.

Modelling the effects of media during an influenza epidemic.

BACKGROUND: Mass media is used to inform individuals regarding diseases within a population. The effects of mass media during disease outbreaks have been studied in the mathematical modelling literature, by including 'media functions' that affect transmission rates in mathematical epidemiological models. The choice of function to employ, however, varies, and thus, epidemic outcomes that are important to inform public health may be affected. METHODS: We present a survey of the disease modelling literature with the effects of mass media. We present a comparison of the functions employed and compare epidemic results parameterized for an influenza outbreak. An agent-based Monte Carlo simulation is created to access variability around key epidemic measurements, and a sensitivity analysis is completed in order to gain insight into which model parameters have the largest influence on epidemic outcomes. RESULTS: Epidemic outcome depends on the media function chosen. Parameters that most influence key epidemic outcomes are different for each media function. CONCLUSION: Different functions used to represent the effects of media during an epidemic will affect the outcomes of a disease model, including the variability in key epidemic measurements. Thus, media functions may not best represent the effects of media during an epidemic. A new method for modelling the effects of media needs to be considered.

A modeling and simulation study of siderophore mediated antagonism in dual-species biofilms.

BACKGROUND: Several bacterial species possess chelation mechanisms that allow them to scavenge iron from the environment under conditions of limitation. To this end they produce siderophores that bind the iron and make it available to the cells later on, while rendering it unavailable to other organisms. The phenomenon of siderophore mediated antagonism has been studied to some extent for suspended populations where it was found that the chelation ability provides a growth advantage over species that do not have this possibility. However, most bacteria live in biofilm communities. In particular Pseudomonas fluorescens and Pseudomonas putida, the species that have been used in most experimental studies of the phenomenon, are known to be prolific biofilm formers, but only very few experimental studies of iron chelation have been published to date for the biofilm setting. We address this question in the present study. METHODS: Based on a previously introduced model of iron chelation and an existing model of biofilm growth we formulate a model for iron chelation and competition in dual species biofilms. This leads to a highly nonlinear system of partial differential equations which is studied in computer simulation experiments. CONCLUSIONS: (i) Siderophore production can give a growth advantage also in the biofilm setting, (ii) diffusion facilitates and emphasizes this growth advantage, (iii) the magnitude of the growth advantage can also depend on the initial inoculation of the substratum, (iv) a new mass transfer boundary condition was derived that allows to a priori control the expect the expected average thickness of the biofilm in terms of the model parameters.