The effect of patient characteristics upon uptake of the influenza vaccination: a study comparing community based older adults in two healthcare systems

Background: Uptake of influenza vaccination represents a simple marker of proactive care of older people. However, many still do not receive the vaccine. To understand this challenge better, we investigated the relationship between patient characteristics (demographic, physical and psychological health, and health service use) and vaccination uptake in a sample of community-dwelling older people in two adjacent but differently structured healthcare systems (Northern Ireland (NI) and the Republic of Ireland (RoI)). Methods: 2,033 randomly selected community-dwelling older adults (65 years and older) were interviewed in their homes. Results: Rates of uptake were 78% in NI and 72% in RoI. Uptake was greater with older age (odds ratio (OR) 1.6, 95% confidence interval (CI) = 1.3-2.1, p

Referral to an Extracorporeal Membrane Oxygenation Center and Mortality Among Patients With Severe 2009 Influenza A(H1N1)

Context Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat patients with ARDS during the 2009 influenza A(H1N1) pandemic.

False-positive PCR results linked to administration of seasonal influenza vaccine

False-positive PCR results usually occur as a consequence of specimen-to-specimen or amplicon-to-specimen contamination within the laboratory. Evidence of contamination at time of specimen collection linked to influenza vaccine administration in the same location as influenza sampling is described. Clinical, circumstantial and laboratory evidence was gathered for each of five cases of influenza-like illness (ILI) with unusual patterns of PCR reactivity for seasonal H1N1, H3N2, H1N1 (2009) and influenza B viruses. Two 2010 trivalent influenza vaccines and environmental swabs of a hospital influenza vaccination room were also tested for influenza RNA. Sequencing of influenza A matrix (M) gene amplicons from the five cases and vaccines was undertaken. Four 2009 general practitioner (GP) specimens were seasonal H1N1, H3N2 and influenza B PCR positive. One 2010 GP specimen was H1N1 (2009), H3N2 and influenza B positive. PCR of 2010 trivalent vaccines showed high loads of detectable influenza A and B RNA. Sequencing of the five specimens and vaccines showed greatest homology with the M gene sequence of Influenza A/Puerto Rico/8/1934 H1N1 virus (used in generation of influenza vaccine strains). Environmental swabs had detectable influenza A and B RNA. RNA detection studies demonstrated vaccine RNA still detectable for at least 66 days. Administration of influenza vaccines and clinical sampling in the same room resulted in the contamination with vaccine strains of surveillance swabs collected from patients with ILI. Vaccine contamination should therefore be considered, particularly where multiple influenza virus RNA PCR positive signals (e.g. H1N1, H3N2 and influenza B) are detected in the same specimen.

A comparison of self-report and health care provider data to assess surveillance definitions of influenza-like illness in outpatients

Objective: Several surveillance definitions of influenza-like illness (ILI) have been proposed, based on the presence of symptoms. Symptom data can be obtained from patients, medical records, or both. Past research has found that agreements between health record data and self-report are variable depending on the specific symptom. Therefore, we aimed to explore the implications of using data on influenza symptoms extracted from medical records, similar data collected prospectively from outpatients, and the combined data from both sources as predictors of laboratory-confirmed influenza. Methods: Using data from the Hutterite Influenza Prevention Study, we calculated: 1) the sensitivity, specificity and predictive values of individual symptoms within surveillance definitions; 2) how frequently surveillance definitions correlated to laboratory-confirmed influenza; and 3) the predictive value of surveillance definitions. Results: Of the 176 participants with reports from participants and medical records, 142 (81%) were tested for influenza and 37 (26%) were PCR positive for influenza. Fever (alone) and fever combined with cough and/or sore throat were highly correlated with being PCR positive for influenza for all data sources. ILI surveillance definitions, based on symptom data from medical records only or from both medical records and self-report, were better predictors of laboratory-confirmed influenza with higher odds ratios and positive predictive values. Discussion: The choice of data source to determine ILI will depend on the patient population, outcome of interest, availability of data source, and use for clinical decision making, research, or surveillance. © Canadian Public Health Association, 2012.

Detection of avian influenza virus by fluorescent DNA barcode-based immunoassay with sensitivity comparable to PCR

In this paper, a coupling of fluorophore-DNA barcode and bead-based immunoassay for detecting avian influenza virus (AIV) with PCR-like sensitivity is reported. The assay is based on the use of sandwich immunoassay and fluorophore-tagged oligonucleotides as representative barcodes. The detection involves the sandwiching of the target AIV between magnetic immunoprobes and barcode-carrying immunoprobes. Because each barcode-carrying immunoprobe is functionalized with a multitude of fluorophore-DNA barcode strands, many DNA barcodes are released for each positive binding event resulting in amplification of the signal. Using an inactivated H16N3 AIV as a model, a linear response over five orders of magnitude was obtained, and the sensitivity of the detection was comparable to conventional RT-PCR. Moreover, the entire detection required less than 2 hr. The results indicate that the method has great potential as an alternative for surveillance of epidemic outbreaks caused by AIV, other viruses and microorganisms.

Detection of Avian Influenza Virus with PCR-Like Sensitivity by Fluorescent DNA Barcode-Based Immunoassay

In this paper, we report a coupling of fluorophore-DNA barcode and bead-based
immunoassay for the detection of Avian Influenza Virus (AIV), a potential pandemic threat for human health and enormous economic losses. The detection strategy is based on the use of sandwich immunoassay and fluorophore-tagged oligonucleotides as representatively fluorescent barcodes. Despite its simplicity the assay has sensitivity comparable to RT-PCR amplification, and possesses a great potential as a rapid and sensitive on-chip detection format.

Generation of replication-proficient influenza virus NS1 point mutants with interferon-hyperinducer phenotype

The NS1 protein of influenza A viruses is the dedicated viral interferon (IFN)-antagonist. Viruses lacking NS1 protein expression cannot multiply in normal cells but are viable in cells deficient in their ability to produce or respond to IFN. Here we report an unbiased mutagenesis approach to identify positions in the influenza A NS1 protein that modulate the IFN response upon infection. A random library of virus ribonucleoproteins containing circa 40 000 point mutants in NS1 were transferred to infectious virus and amplified in MDCK cells unable to respond to interferon. Viruses that activated the interferon (IFN) response were subsequently selected by their ability to induce expression of green-fluorescent protein (GFP) following infection of A549 cells bearing an IFN promoter-dependent GFP gene. Using this approach we isolated individual mutant viruses that replicate to high titers in IFN-compromised cells but, compared to wild type viruses, induced higher levels of IFN in IFN-competent cells and had a reduced capacity to counteract exogenous IFN. Most of these viruses contained not previously reported NS1 mutations within either the RNA-binding domain, the effector domain or the linker region between them. These results indicate that subtle alterations in NS1 can reduce its effectiveness as an IFN antagonist without affecting the intrinsic capacity of the virus to multiply. The general approach reported here may facilitate the generation of replication-proficient, IFN-inducing virus mutants, that potentially could be developed as attenuated vaccines against a variety of viruses.

An unbiased genetic screen reveals the polygenic nature of the influenza virus anti-interferon response

UNLABELLED: Influenza A viruses counteract the cellular innate immune response at several steps, including blocking RIG I-dependent activation of interferon (IFN) transcription, interferon (IFN)-dependent upregulation of IFN-stimulated genes (ISGs), and the activity of various ISG products; the multifunctional NS1 protein is responsible for most of these activities. To determine the importance of other viral genes in the interplay between the virus and the host IFN response, we characterized populations and selected mutants of wild-type viruses selected by passage through non-IFN-responsive cells. We reasoned that, by allowing replication to occur in the absence of the selection pressure exerted by IFN, the virus could mutate at positions that would normally be restricted and could thus find new optimal sequence solutions. Deep sequencing of selected virus populations and individual virus mutants indicated that nonsynonymous mutations occurred at many phylogenetically conserved positions in nearly all virus genes. Most individual mutants selected for further characterization induced IFN and ISGs and were unable to counteract the effects of exogenous IFN, yet only one contained a mutation in NS1. The relevance of these mutations for the virus phenotype was verified by reverse genetics. Of note, several virus mutants expressing intact NS1 proteins exhibited alterations in the M1/M2 proteins and accumulated large amounts of deleted genomic RNAs but nonetheless replicated to high titers. This suggests that the overproduction of IFN inducers by these viruses can override NS1-mediated IFN modulation. Altogether, the results suggest that influenza viruses replicating in IFN-competent cells have tuned their complete genomes to evade the cellular innate immune system and that serial replication in non-IFN-responsive cells allows the virus to relax from these constraints and find a new genome consensus within its sequence space.

IMPORTANCE: In natural virus infections, the production of interferons leads to an antiviral state in cells that effectively limits virus replication. The interferon response places considerable selection pressure on viruses, and they have evolved a variety of ways to evade it. Although the influenza virus NS1 protein is a powerful interferon antagonist, the contributions of other viral genes to interferon evasion have not been well characterized. Here, we examined the effects of alleviating the selection pressure exerted by interferon by serially passaging influenza viruses in cells unable to respond to interferon. Viruses that grew to high titers had mutations at many normally conserved positions in nearly all genes and were not restricted to the NS1 gene. Our results demonstrate that influenza viruses have fine-tuned their entire genomes to evade the interferon response, and by removing interferon-mediated constraints, viruses can mutate at genome positions normally restricted by the interferon response.

Belief, Knowledge and Expertise. The emergence of the lay expert in medical sociology

The paper has three main aims. First, to trace – through the pages of the Journal – the changing ways in which lay understandings of health and illness have been represented during the 1979-2002 period. Second, to say something about the limits of lay knowledge (and particularly lay expertise) in matters of health and medicine. Third, to call for a re-assessment of what lay people can offer to a democratised and customer sensitive system of health care and to attempt to draw a boundary around the domain of expertise. In following through on those aims, the author calls upon data derived from three current projects. These latter concern the diagnosis of Alzheimer’s disease in people with Down’s syndrome; the development of an outcome measure for people who have suffered a traumatic brain injury; and a study of why older people might reject annual influenza vaccinations. Key words: Lay health beliefs, lay expertise, Alzheimer’s, Traumatic Brain Injury, Vaccinations

Future novel threats and opportunities facing UK biodiversity identified by horizon scanning

1. Horizon scanning is an essential tool for environmental scientists if they are to contribute to the evidence base for Government, its agencies and other decision makers to devise and implement environmental policies. The implication of not foreseeing issues that are foreseeable is illustrated by the contentious responses to genetically modified herbicide-tolerant crops in the UK, and by challenges surrounding biofuels, foot and mouth disease, avian influenza and climate change.