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Case-based population-level surveillance and cross-sectional serologic surveys to estimate incidence and patterns of influenza infection are limited by the lack of accurate denominator data, inability to account for subclinical infections, [...]

The role of T cells in mediating heterosubtypic protection against natural influenza illness in humans is uncertain. The 2009 H1N1 pandemic (pH1N1) provided a unique natural experiment to determine whether [...]

In April 2009, an influenza A subtype H1N1 virus was isolated from persons in Mexico and the United States (1). This virus was responsible for the first influenza pandemic of [...]

The first reported case-patient infected with Middle East respiratory syndrome coronavirus (MERS-CoV) died in June 2012 in the Kingdom of Saudi Arabia and was reported on September 20 (1). The [...]

Summary: Background: Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden. Methods: Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006–11; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable. Findings: Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16–22) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13–34), suggesting most influenza infections are asymptomatic. 25% (18–35) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10–26) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2. Interpretation: Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2. Funding: Medical Research Council and the Wellcome Trust. [Copyright &y& Elsevier]

We conducted a longitudinal community cohort study of healthy adults in the UK. We found significantly higher incidence of influenza A(H1N1)pdm09 infection in 2010-11 than in 2009-10, a substantial proportion of subclinical infection, and higher risk for infection during 2010-11 among persons with lower preinfection antibody titers. [ABSTRACT FROM AUTHOR]

The 2009/10 pandemic (p H1 N1) highlighted the need for vaccines conferring heterosubtypic immunity against antigenically shifted influenza strains. Although cross-reactive T cells are strong candidates for mediating heterosubtypic immunity, little is known about the population-level prevalence, frequency, and cytokine-secretion profile of heterosubtypic T cells to p H1 N1. To assess this, p H1 N1 sero-negative adults were recruited. Single-cell IFN-γ and IL-2 cytokine-secretion profiles to internal proteins of p H1 N1 or live virus were enumerated and characterised. Heterosubtypic T cells recognising p H1 N1 core proteins were widely prevalent, being detected in 90% (30 of 33) of p H1 N1-naïve individuals. Although the last exposure to influenza was greater than 6 months ago, the frequency and proportion of the IFN-γ-only-secreting T-cell subset was significantly higher than the IL-2-only-secreting subset. CD8+ IFN-γ-only-secreting heterosubtypic T cells were predominantly CCR7− CD45 RA− effector-memory phenotype, expressing the tissue-homing receptor CXCR3 and degranulation marker CD107. Receipt of the 2008-09 influenza vaccine did not alter the frequency of these heterosubtypic T cells, highlighting the inability of current vaccines to maintain this heterosubtypic T-cell pool. The surprisingly high prevalence of pre-existing circulating p H1 N1-specific CD8+ IFN-γ-only-secreting effector memory T cells with cytotoxic and lung-homing potential in p H1 N1-seronegative adults may partly explain the low case fatality rate despite high rates of infection of the pandemic in young adults. [ABSTRACT FROM AUTHOR]

Presents information on a study which investigated recombinant respiratory syncytial virus (rRSV) in which M2 second translational reading frame (ORF2) was disrupted by a frame shift or by ablation of translational start sites and the introduction of stop codons. Mutagenesis of M2 ORF2; Effect of M2-2 mutations on minireplicon transcription and replications; Recovery and growth in vitro of rRSV containing the M2-2 mutations.

The article discusses a study which investigated the emergence of community transmission of influenza A/H1N1 in England based on results from self sampling of NHS Direct callers with influenza-like illness. People in six Strategic Health Authorities with cold of flu symptoms or both were involved in the study, who called the NHS Direct multi-channel health advice and information service. It was found that a reliable indication of local community transmission was provided by Testing in Health Protection Agency regional laboratories.

Abstract: In order to comply with national and international clinical laboratory accreditation standards (e.g. the ISO 15189, Clinical Pathology Accreditation standards) and with the joint code of practice for research, there must be a method of assessing that test methods are “fit for purpose”. This document gives guidance on development and describes how a validation file is produced. A test method may be a commercial kit, an in-house assay or reagent or a set of reagents bought separately and used to prepare an in house assay. A validation file is needed for both current and new test procedures. The file may refer to data recorded in workbooks, papers and reports. Modifications to assays (including commercially available assays) necessitate either an update to the validation file or creation of a new file. This paper is intended to provide a generic framework for in-house assay development and validation of new nucleic acid amplification assays including real-time polymerase chain reaction (PCR). [Copyright &y& Elsevier]

Background: Western industrialised nations face a large increase in the number of older people. People over the age of 60 years account for almost half of the 16.8 million hospital admissions in England from 2009 to 2010. During 2009-10, respiratory infections accounted for approximately 1 in 30 hospital admissions and 1 in 20 of the 51.5 million bed-days., Objective: To determine the diagnostic accuracy and clinical effectiveness and cost-effectiveness of rapid molecular and near-patient diagnostic tests for influenza, respiratory syncytial virus (RSV) and Streptococcus pneumoniae infections in comparison with traditional laboratory culture., Methods: We carried out a randomised controlled trial (RCT) to evaluate impact on prescribing and clinical outcomes of point-of-care tests (POCTs) for influenza A and B and pneumococcal infection, reverse transcriptase-polymerase chain reaction (RT-PCR) tests for influenza A and B and RSV A and B, and conventional culture for these pathogens. We evaluated diagnostic accuracy of POCTs for influenza and pneumococcal infection, RT-PCR for influenza and sputum culture for S. pneumoniae using samples collected during the RCT. We did a systematic review and meta-analysis of POCTs for influenza A and B. We evaluated ease and speed of use of each test, process outcomes and cost-effectiveness., Results: There was no evidence of association between diagnostic group and prescribing or clinical outcomes. Using PCR as 'gold standard', Quidel Influenza A + B POCT detected 24.4% [95% confidence interval (CI) 16.0% to 34.6%] of influenza infections (specificity 99.7%, 95% CI 99.2% to 99.9%); viral culture detected 21.6% (95% CI 13.5% to 31.6%; specificity 99.8%, 95% CI 99.4% to 100%). Using blood culture as 'gold standard', BinaxNOW pneumococcal POCT detected 57.1% (95% CI 18.4% to 90.1%) of pneumococcal infections (specificity 92.5%; 95% CI 90.6% to 94.1%); sputum culture detected 100% (95% CI 2.5% to 100%; specificity 97.2%, 95% CI 94.3% to 98.9%). Overall, pooled estimates of sensitivity and specificity of POCTs for influenza from the literature were 74% (95% CI 67% to 80%) and 99% (95% CI 98% to 99%), respectively. Median intervals from specimen collection to test result were 15 minutes [interquartile range (IQR) 10-23 minutes) for Quidel Influenza A + B POCT, 20 minutes (IQR 15-30 minutes) for BinaxNOW pneumococcal POCT, 50.8 hours (IQR 44.3-92.6 hours) for semi-nested conventional PCR, 29.2 hours (IQR 26-46.9 hours) for real-time PCR, 629.6 hours (IQR 262.5-846.7 hours) for culture of influenza and 84.4 hours (IQR 70.7-137.8 hours) and 71.4 hours (IQR 69.15-84.0 hours) for culture of S. pneumoniae in blood and sputum, respectively. Both POCTs were rated straightforward and undemanding; blood culture was moderately complex and all other tests were complex. Costs and quality-adjusted life-years (QALYs) of each diagnostic strategy were similar. Incrementally, PCR was most cost-effective (78.3% probability at a willingness to pay of £20,000/QALY). Few patients were admitted within a timescale conducive to treatment with a neuraminidase inhibitor according to National Institute for Health and Care Excellence guidance., Limitations: The accuracy study was limited by inadequate gold standards., Conclusions: All tests had limitations. We found no evidence that POCTs for influenza or S. pneumoniae, or PCR for influenza or RSV influenced antimicrobial prescribing or clinical outcomes. The total costs and QALYs of each diagnostic strategy were similar, although, incrementally, PCR was the most cost-effective strategy. The analysis does not support routine use of POCTs for either influenza or pneumococcal antigen for adults presenting with acute cardiopulmonary conditions, but suggests that conventional viral culture for clinical diagnosis should be replaced by PCR., Trial Registration: Current Controlled Trials ISRCTN21521552., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 36. See the NIHR Journals Library website for further project information.

The 2009/10 pandemic (pH1N1) highlighted the need for vaccines conferring heterosubtypic immunity against antigenically shifted influenza strains. Although cross-reactive T cells are strong candidates for mediating heterosubtypic immunity, little is known about the population-level prevalence, frequency, and cytokine-secretion profile of heterosubtypic T cells to pH1N1. To assess this, pH1N1 sero-negative adults were recruited. Single-cell IFN-γ and IL-2 cytokine-secretion profiles to internal proteins of pH1N1 or live virus were enumerated and characterised. Heterosubtypic T cells recognising pH1N1 core proteins were widely prevalent, being detected in 90% (30 of 33) of pH1N1-naïve individuals. Although the last exposure to influenza was greater than 6 months ago, the frequency and proportion of the IFN-γ-only-secreting T-cell subset was significantly higher than the IL-2-only-secreting subset. CD8(+) IFN-γ-only-secreting heterosubtypic T cells were predominantly CCR7(-) CD45RA(-) effector-memory phenotype, expressing the tissue-homing receptor CXCR3 and degranulation marker CD107. Receipt of the 2008-09 influenza vaccine did not alter the frequency of these heterosubtypic T cells, highlighting the inability of current vaccines to maintain this heterosubtypic T-cell pool. The surprisingly high prevalence of pre-existing circulating pH1N1-specific CD8(+) IFN-γ-only-secreting effector memory T cells with cytotoxic and lung-homing potential in pH1N1-seronegative adults may partly explain the low case fatality rate despite high rates of infection of the pandemic in young adults., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We analyzed data on all laboratory-confirmed cases of H1N1pdm influenza in the UK to 10th June 2009 to estimate epidemiological characteristics. We estimated a mean incubation period of 2.05 days and serial interval of 2.5 days with infectivity peaking close to onset of symptoms. Transmission was initially sporadic but increased from mid-May in England and from early June in Scotland. We estimated 37% of transmission occurred in schools, 24% in households, 28% through travel abroad and the remainder in the wider community. Children under 16 were more susceptible to infection in the household (adjusted OR 5.80, 95% CI 2.99-11.82). Treatment with oseltamivir plus widespread use of prophylaxis significantly reduced transmission (estimated reduction 16%). Households not receiving oseltamivir within 3 days of symptom onset in the index case had significantly increased secondary attack rates (adjusted OR 3.42, 95% CI 1.51-8.55).

Objective: To evaluate ascertainment of the onset of community transmission of influenza A/H1N1 2009 (swine flu) in England during the earliest phase of the epidemic through comparing data from two surveillance systems., Design: Cross sectional opportunistic survey., Study Samples: Results from self samples by consenting patients who had called the NHS Direct telephone health line with cold or flu symptoms, or both, and results from Health Protection Agency (HPA) regional microbiology laboratories on patients tested according to the clinical algorithm for the management of suspected cases of swine flu., Setting: Six regions of England between 24 May and 30 June 2009., Main Outcome Measure: Proportion of specimens with laboratory evidence of influenza A/H1N1 2009., Results: Influenza A/H1N1 2009 infections were detected in 91 (7%) of the 1385 self sampled specimens tested. In addition, eight instances of influenza A/H3 infection and two cases of influenza B infection were detected. The weekly rate of change in the proportions of infected individuals according to self obtained samples closely matched the rate of increase in the proportions of infected people reported by HPA regional laboratories. Comparing the data from both systems showed that local community transmission was occurring in London and the West Midlands once HPA regional laboratories began detecting 100 or more influenza A/H1N1 2009 infections, or a proportion positive of over 20% of those tested, each week., Conclusions: Trends in the proportion of patients with influenza A/H1N1 2009 across regions detected through clinical management were mirrored by the proportion of NHS Direct callers with laboratory confirmed infection. The initial concern that information from HPA regional laboratory reports would be too limited because it was based on testing patients with either travel associated risk or who were contacts of other influenza cases was unfounded. Reports from HPA regional laboratories could be used to recognise the extent to which local community transmission was occurring.