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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 [...]

The M2 mRNA of human respiratory syncytial virus (RSV) contains two overlapping ORFs, encoding the transcription antitermination protein (M2-1) and the 90-aa M2-2 protein of unknown function. Viable recombinant RSV was recovered in which expression of M2-2 was ablated, identifying it as an accessory factor dispensable for growth in vitro. Virus lacking M2-2 grew less efficiently than did the wild-type parent in vitro, with titers that were reduced 1,000-fold during the initial 2-5 days and 10-fold by days 7-8. Compared with wild-type virus, the intracellular accumulation of RNA by M2-2 knockout virus was reduced 3- to 4-fold or more for genomic RNA and increased 2- to 4-fold or more for mRNA. Synthesis of the F and G glycoproteins, the major RSV neutralization and protective antigens, was increased in proportion with that of mRNA. In cells infected with wild-type RSV, mRNA accumulation increased dramatically up to approximately 12-15 hr after infection and then leveled off, whereas accumulation continued to increase in cells infected with the M2-2 knockout viruses. These findings suggest that M2-2 mediates a regulatory 'switch' from transcription to RNA replication, one that provides an initial high level of mRNA synthesis followed by a shift in the RNA synthetic program in favor of genomic RNA for virion assembly. With regard to vaccine development, the M2-2 knockout has a highly desirable phenotype in which virus growth is attenuated while gene expression is concomitantly increased.

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]

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.

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.