Quarantine for pandemic influenza control at the borders of small island nations

Background: Although border quarantine is included in many influenza pandemic plans, detailed guidelines have yet to be formulated, including considerations for the optimal quarantine length. Motivated by the situation of small island nations, which will probably experience the introduction of pandemic influenza via just one airport, we examined the potential effectiveness of quarantine as a border control measure. Methods: Analysing the detailed epidemiologic characteristics of influenza, the effectiveness of quarantine at the borders of islands was modelled as the relative reduction of the risk of releasing infectious individuals into the community, explicitly accounting for the presence of asymptomatic infected individuals. The potential benefit of adding the use of rapid diagnostic testing to the quarantine process was also considered. Results: We predict that 95% and 99% effectiveness in preventing the release of infectious individuals into the community could be achieved with quarantine periods of longer than 4.7 and 8.6 days, respectively. If rapid diagnostic testing is combined with quarantine, the lengths of quarantine to achieve 95% and 99% effectiveness could be shortened to 2.6 and 5.7 days, respectively. Sensitivity analysis revealed that quarantine alone for 8.7 days or quarantine for 5.7 days combined with using rapid diagnostic testing could prevent secondary transmissions caused by the released infectious individuals for a plausible range of prevalence at the source country (up to 10%) and for a modest number of incoming travellers (up to 8000 individuals). Conclusion: Quarantine atthe borders of island nations could contribute substantially to preventing the arrival of pandemic influenza (or at least delaying the arrival date). For small island nations we recommend consideration of quarantine alone for 9 days or quarantine for 6 days combined with using rapid diagnostic testing (if available). © 2009 Nishiura et al; licensee BioMed Central Ltd.published_or_final_versio

The RNA Chaperone Hfq Is Important for Growth and Stress Tolerance in Francisella novicida

The RNA-binding protein Hfq is recognized as an important regulatory factor in a variety of cellular processes, including stress resistance and pathogenesis. Hfq has been shown in several bacteria to interact with small regulatory RNAs and act as a post-transcriptional regulator of mRNA stability and translation. Here we examined the impact of Hfq on growth, stress tolerance, and gene expression in the intracellular pathogen Francisella novicida. We present evidence of Hfq involvement in the ability of F. novicida to tolerate several cellular stresses, including heat-shock and oxidative stresses, and alterations in hfq gene expression under these conditions. Furthermore, expression of numerous genes, including several associated with virulence, is altered in a hfq mutant strain suggesting they are regulated directly or indirectly by Hfq. Strikingly, we observed a delayed entry into stationary phase and increased biofilm formation in the hfq mutant. Together, these data demonstrate a critical role for Hfq in F. novicida growth and survival

Early efforts in modeling the incubation period of infectious diseases with an acute course of illness

The incubation period of infectious diseases, the time from infection with a microorganism to onset of disease, is directly relevant to prevention and control. Since explicit models of the incubation period enhance our understanding of the spread of disease, previous classic studies were revisited, focusing on the modeling methods employed and paying particular attention to relatively unknown historical efforts. The earliest study on the incubation period of pandemic influenza was published in 1919, providing estimates of the incubation period of Spanish flu using the daily incidence on ships departing from several ports in Australia. Although the study explicitly dealt with an unknown time of exposure, the assumed periods of exposure, which had an equal probability of infection, were too long, and thus, likely resulted in slight underestimates of the incubation period

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

Aims/hypothesis Islet-specific autoantibodies can predict the development of type 1 diabetes. However, it remains unclear if B cells, per se, contribute to the causal pancreatic immunopathology. We aimed to identify phenotypic signatures of disease progression among naive and memory B cell subsets in the peripheral blood of individuals with type 1 diabetes. Methods A total of 69 participants were recruited across two separate cohorts, one for discovery purposes and the other for validation purposes. Each cohort comprised two groups of individuals with type 1 diabetes (one with newly diagnosed type 1 diabetes and the other with long-standing type 1 diabetes) and one group of age- and sex-matched healthy donors. The phenotypic characteristics of circulating naive and memory B cells were investigated using polychromatic flow cytometry, and serum concentrations of various chemokines and cytokines were measured using immunoassays. Results A disease-linked phenotype was detected in individuals with long-standing type 1 diabetes, characterised by reduced C-X-C motif chemokine receptor 3 (CXCR3) expression on switched (CD27+IgD−) and unswitched (CD27intermediateIgD+) memory B cells. These changes were associated with raised serum concentrations of B cell activating factor and of the CXCR3 ligands, chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11. A concomitant reduction in CXCR3 expression was also identified on T cells. Conclusions/interpretation Our data reveal a statistically robust set of abnormalities that indicate an association between type 1 diabetes and long-term dysregulation of a chemokine ligand/receptor system that controls B cell migration

The protocol of the Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID:a randomised placebo-controlled trial

Background Delirium affects 15% of hospitalised patients and is linked with poor outcomes, yet few pharmacological treatment options exist. One hypothesis is that delirium may in part result from exaggerated and/or prolonged stress responses. Dexmedetomidine, a parenterally-administered alpha2-adrenergic receptor agonist which attenuates sympathetic nervous system activity, shows promise as treatment in ICU delirium. Clonidine exhibits similar pharmacodynamic properties and can be administered orally. We therefore wish to explore possible effects of clonidine upon the duration and severity of delirium in general medical inpatients. Methods/Design The Oslo Study of Clonidine in Elderly Patients with Delirium (LUCID) is a randomised, placebo-controlled, double-blinded, parallel group study with 4-month prospective follow-up. We will recruit 100 older medical inpatients with delirium or subsyndromal delirium in the acute geriatric ward. Participants will be randomised to oral clonidine or placebo until delirium free for 2 days (Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria), or after a maximum of 7 days treatment. Assessment of haemodynamics (blood pressure, heart rate and electrocardiogram) and delirium will be performed daily until discharge or a maximum of 7 days after end of treatment. The primary endpoint is the trajectory of delirium over time (measured by Memorial Delirium Assessment Scale). Secondary endpoints include the duration of delirium, use of rescue medication for delirium, pharmacokinetics and pharmacodynamics of clonidine, cognitive function after 4 months, length of hospital stay and need for institutionalisation. Discussion LUCID will explore the efficacy and safety of clonidine for delirium in older medical inpatients. Trial registration ClinicalTrials.gov NCT01956604 . EudraCT Number: 2013-000815-2