A plague on five of your houses - statistical re-assessment of three pneumonic plague outbreaks that occurred in Suffolk, England, between 1906 and 1918

<p>Abstract</p> <p>Background</p> <p>Plague is a re-emerging disease and its pneumonic form is a high priority bio-terrorist threat. Epidemiologists have previously analysed historical outbreaks of pneumonic plague to better understand the dynamics of infection, transmission and control. This study examines 3 relatively unknown outbreaks of pneumonic plague that occurred in Suffolk, England, during the first 2 decades of the twentieth century.</p> <p>Methods</p> <p>The Kolmogorov-Smirnov statistical test is used to compare the symptomatic period and the length of time between successive cases (i.e. the serial interval) with previously reported values. Consideration is also given to the case fatality ratio, the average number of secondary cases resulting from each primary case in the observed minor outbreaks (termed <it>R</it>_{<it>minor</it>}), and the proportion of individuals living within an affected household that succumb to pneumonic plague via the index case (i.e. the household secondary attack rate (SAR)).</p> <p>Results</p> <p>2 of the 14 cases survived giving a case fatality ratio of 86% (95% confidence interval (CI) = {57%, 98%}). For the 12 fatal cases, the average symptomatic period was 3.3 days (standard deviation (SD) = 1.2 days) and, for the 11 non index cases, the average serial interval was 5.8 days (SD = 2.0 days). <it>R</it>_{<it>minor </it>}was calculated to be 0.9 (SD = 1.0) and, in 2 households, the SAR was approximately 14% (95% CI = {0%, 58%}) and 20% (95% CI = {1%, 72%}), respectively.</p> <p>Conclusions</p> <p>The symptomatic period was approximately 1 day longer on average than in an earlier study but the serial interval was in close agreement with 2 previously reported values. 2 of the 3 outbreaks ended without explicit public health interventions; however, non-professional caregivers were particularly vulnerable - an important public health consideration for any future outbreak of pneumonic plague.</p

Using Ontario's "Telehealth" health telephone helpline as an early-warning system: a study protocol

BACKGROUND: The science of syndromic surveillance is still very much in its infancy. While a number of syndromic surveillance systems are being evaluated in the US, very few have had success thus far in predicting an infectious disease event. Furthermore, to date, the majority of syndromic surveillance systems have been based primarily in emergency department settings, with varying levels of enhancement from other data sources. While research has been done on the value of telephone helplines on health care use and patient satisfaction, very few projects have looked at using a telephone helpline as a source of data for syndromic surveillance, and none have been attempted in Canada. The notable exception to this statement has been in the UK where research using the national NHS Direct system as a syndromic surveillance tool has been conducted. METHODS/DESIGN: The purpose of our proposed study is to evaluate the effectiveness of Ontario's telephone nursing helpline system as a real-time syndromic surveillance system, and how its implementation, if successful, would have an impact on outbreak event detection in Ontario. Using data collected retrospectively, all "reasons for call" and assigned algorithms will be linked to a syndrome category. Using different analytic methods, normal thresholds for the different syndromes will be ascertained. This will allow for the evaluation of the system's sensitivity, specificity and positive predictive value. The next step will include the prospective monitoring of syndromic activity, both temporally and spatially. DISCUSSION: As this is a study protocol, there are currently no results to report. However, this study has been granted ethical approval, and is now being implemented. It is our hope that this syndromic surveillance system will display high sensitivity and specificity in detecting true outbreaks within Ontario, before they are detected by conventional surveillance systems. Future results will be published in peer-reviewed journals so as to contribute to the growing body of evidence on syndromic surveillance, while also providing an non US-centric perspective

Host Immune Transcriptional Profiles Reflect the Variability in Clinical Disease Manifestations in Patients with Staphylococcus aureus Infections

Staphylococcus aureus infections are associated with diverse clinical manifestations leading to significant morbidity and mortality. To define the role of the host response in the clinical manifestations of the disease, we characterized whole blood transcriptional profiles of children hospitalized with community-acquired S. aureus infection and phenotyped the bacterial strains isolated. The overall transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis related genes and under-expression of genes related to adaptive immunity. We assessed individual profiles using modular fingerprints combined with the molecular distance to health (MDTH), a numerical score of transcriptional perturbation as compared to healthy controls. We observed significant heterogeneity in the host signatures and MDTH, as they were influenced by the type of clinical presentation, the extent of bacterial dissemination, and time of blood sampling in the course of the infection, but not by the bacterial isolate. System analysis approaches provide a new understanding of disease pathogenesis and the relation/interaction between host response and clinical disease manifestations

Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response

<p>Abstract</p> <p>Background</p> <p>Ciguatoxins (CTXs) are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO) and molecular pathway enrichment of the gene expression data.</p> <p>Results</p> <p>A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p < 0.0001) with microarray results.</p> <p>Conclusions</p> <p>Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against neuroinflammation. Pathologic activity of the complement/coagulation cascade has been shown in patients suffering from a chronic form of ciguatera poisoning and is of particular interest in this model. Anti-inflammatory processes were at work not only in the brain but were also seen in whole blood and liver of these animals, creating a systemic anti-inflammatory environment to protect against the initial cellular damage caused by the toxin.</p

Human plague: An old scourge that needs new answers

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague’s resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a “One Health” approach