Public health responses to influenza in care homes: a questionnaire-based study of local Health Protection Units.

BACKGROUND: Influenza virus infection poses a major threat to the elderly people in residential care. We sought to describe the extent to which local public health services in England were positioned to detect and respond effectively to influenza-like illness (ILI) in nursing homes. METHODS: A questionnaire-based survey was conducted in all 34 Health Protection Units (HPUs) regarding the 2004-05 influenza season. RESULTS: Of the 20 responses, half reported 24 outbreaks of ILI in care homes. The mean resident population attack rate was 41% (range 15-79) with 31 deaths. Staff ILI occurred in 23 of 24 outbreaks. Seven of 20 HPUs stated that a local policy for the management of ILI in nursing homes was in place, with only four specifying the use of neuraminidase inhibitors (NI) for treatment of cases and prophylaxis of residents. In the outbreaks reported, NIs were used for treatment and prophylaxis, respectively, in only 46 and 54% of instances. CONCLUSIONS: Given the availability of effective interventions for treatment and prophylaxis, there is potential to prevent substantial morbidity and mortality from influenza in at-risk populations. This study suggests that challenges remain in the effective response to influenza outbreaks in care homes and that there are wide variations in practice at local level

Effects of seasonal and pandemic influenza on health-related quality of life, work and school absence in England: results from the Flu Watch cohort study

BACKGROUND: Estimates of health-related quality of life (HRQoL) and work/school absences for influenza are typically based on medically-attended cases or those meeting influenza-like-illness (ILI) case definitions, and thus biased towards severe disease. Although community influenza cases are more common, estimates of their effects on HRQoL and absences are limited. OBJECTIVES: To measure Quality-Adjusted Life Days and Years (QALDs and QALYs) lost and work/school absences among community cases of acute respiratory infections (ARI), ILI and influenza A and B and to estimate community burden of QALY loss and absences from influenza. PATIENTS/ METHODS: Flu Watch was a community cohort in England from 2006-2011. Participants were followed-up weekly. During respiratory illness they prospectively recorded daily symptoms, work/school absences and EQ-5D-3L data and submitted nasal swabs for RT-PCR influenza testing. RESULTS: Average QALD lost was 0.26, 0.93, 1.61 and 1.84 for ARI, ILI, H1N1pdm09 and influenza B cases respectively. 40% of influenza A cases and 24% of influenza B cases took time off work/school with an average duration of 3.6 days and 2.4 days respectively. In England, community influenza cases lost 24,300 QALYs in 2010/11 and had an estimated 2.9 million absences per season based on data from 2006/07 - 2009/10. CONCLUSIONS: Our QALDs and QALYs lost and work and school absence estimates are lower than previous estimates because we focus on community cases, most of which are mild, may not meet ILI definitions and do not result in healthcare consultations. Nevertheless, they contribute a substantial loss of HRQoL on a population level. This article is protected by copyright. All rights reserved

A Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence

The proapoptotic PB1-F2 protein of influenza A viruses has been shown to contribute to pathogenesis in the mouse model. Expression of full-length PB1-F2 increases the pathogenesis of the influenza A virus, causing weight loss, slower viral clearance, and increased viral titers in the lungs. After comparing viruses from the Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found in the PB1-F2 sequence at position 66 that correlated with pathogenicity. This same amino acid change (N66S) was also found in the PB1-F2 protein of the 1918 pandemic A/Brevig Mission/18 virus. Two isogenic recombinant chimeric viruses were created with an influenza A/WSN/33 virus background containing the PB1 segment from the HK/156/97: WH and WH N66S. In mice infected with WH N66S virus there was increased pathogenicity as measured by weight loss and decreased survival, and a 100-fold increase in virus replication when compared to mice infected with the WH virus. The 1918 pandemic strain A/Brevig Mission/18 was reconstructed with a pathogenicity-reducing mutation in PB1-F2 (S66N). The resultant 1918 S66N virus was attenuated in mice having a 3-log lower 50% lethal dose and caused less morbidity and mortality in mice than the wild-type virus. Viral lung titers were also decreased in 1918 S66N–infected mice compared with wild-type 1918 virus–infected mice. In addition, both viruses with an S at position 66 (WH N66S and wt 1918) induced elevated levels of cytokines in the lungs of infected mice. Together, these data show that a single amino acid substitution in PB1-F2 can result in increased viral pathogenicity and could be one of the factors contributing to the high lethality seen with the 1918 pandemic virus

Increased risk of A(H1N1)pdm09 influenza infection in UK pig industry workers compared to a general population cohort.

BACKGROUND: Pigs are mixing vessels for influenza viral reassortment but the extent of influenza transmission between swine and humans is not well understood. OBJECTIVES: To assess whether occupational exposure to pigs is a risk factor for human infection with human and swine-adapted influenza viruses. METHODS: UK pig industry workers were frequency-matched on age, region, sampling month, and gender with a community-based comparison group from the Flu Watch study. HI assays quantified antibodies for swine and human A(H1) and A(H3) influenza viruses (titres≥40 considered seropositive and indicative of infection). Virus-specific associations between seropositivity and occupational pig exposure were examined using multivariable regression models adjusted for vaccination. Pigs on the same farms were also tested for seropositivity. RESULTS: 42% of pigs were seropositive to A(H1N1)pdm09. Pig industry workers showed evidence of increased odds of A(H1N1)pdm09 seropositivity compared to the comparison group, albeit with wide confidence intervals (CI), Adjusted Odds Ratio after accounting for possible cross reactivity with other swine A(H1) viruses (aOR) 25.3, 95% CI [1.4-536.3], p=0.028. CONCLUSION: The results indicate that A(H1N1)pdm09 virus was common in UK pigs during the pandemic and subsequent period of human A(H1N1)pdm09 circulation, and occupational exposure to pigs was a risk factor for human infection. Influenza immunization of pig industry workers may reduce transmission and the potential for virus reassortment. This article is protected by copyright. All rights reserved

Association between inactivated influenza vaccine and primary care consultations for autoimmune rheumatic disease flares: a self-controlled case series study using data from the Clinical Practice Research Datalink.

Objectives: To examine the association between inactivated influenza vaccine (IIV) administration and primary care consultation for joint pain, rheumatoid arthritis (RA) flare, corticosteroid prescription, vasculitis and unexplained fever in people with autoimmune rheumatic diseases (AIRDs). METHODS: We undertook within-person comparisons using self-controlled case-series methodology. AIRD cases who received the IIV and had an outcome of interest in the same influenza cycle were ascertained in Clinical Practice Research Datalink. The influenza cycle was partitioned into exposure periods (1-14 days prevaccination and 0-14, 15-30, 31-60 and 61-90 days postvaccination), with the remaining time-period classified as non-exposed. Incidence rate ratios (IRR) and 95% CI for different outcomes were calculated. RESULTS: Data for 14 928 AIRD cases (69% women, 80% with RA) were included. There was no evidence for association between vaccination and primary care consultation for RA flare, corticosteroid prescription, fever or vasculitis. On the contrary, vaccination associated with reduced primary care consultation for joint pain in the subsequent 90 days (IRR 0.91 (95% CI 0.87 to 0.94)). CONCLUSION: This study found no evidence for a significant association between vaccination and primary care consultation for most surrogates of increased disease activity or vaccine adverse-effects in people with AIRDs. It adds to the accumulating evidence to support influenza vaccination in AIRDs

Acute kidney injury in patients hospitalized with COVID-19 from the ISARIC WHO CCP-UK Study: a prospective, multicentre cohort study.

BACKGROUND: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). This study investigated adults hospitalized with COVID-19 and hypothesized that risk factors for AKI would include comorbidities and non-White race. METHODS: A prospective multicentre cohort study was performed using patients admitted to 254 UK hospitals with COVID-19 between 17 January 2020 and 5 December 2020. RESULTS: Of 85 687 patients, 2198 (2.6%) received acute kidney replacement therapy (KRT). Of 41 294 patients with biochemistry data, 13 000 (31.5%) had biochemical AKI: 8562 stage 1 (65.9%), 2609 stage 2 (20.1%) and 1829 stage 3 (14.1%). The main risk factors for KRT were chronic kidney disease (CKD) [adjusted odds ratio (aOR) 3.41: 95% confidence interval 3.06-3.81], male sex (aOR 2.43: 2.18-2.71) and Black race (aOR 2.17: 1.79-2.63). The main risk factors for biochemical AKI were admission respiratory rate >30 breaths per minute (aOR 1.68: 1.56-1.81), CKD (aOR 1.66: 1.57-1.76) and Black race (aOR 1.44: 1.28-1.61). There was a gradated rise in the risk of 28-day mortality by increasing severity of AKI: stage 1 aOR 1.58 (1.49-1.67), stage 2 aOR 2.41 (2.20-2.64), stage 3 aOR 3.50 (3.14-3.91) and KRT aOR 3.06 (2.75-3.39). AKI rates peaked in April 2020 and the subsequent fall in rates could not be explained by the use of dexamethasone or remdesivir. CONCLUSIONS: AKI is common in adults hospitalized with COVID-19 and it is associated with a heightened risk of mortality. Although the rates of AKI have fallen from the early months of the pandemic, high-risk patients should have their kidney function and fluid status monitored closely

The Effect of Influenza Virus on the Human Oropharyngeal Microbiome

BACKGROUND: Secondary bacterial infections are an important cause of morbidity and mortality associated with influenza infections. As bacterial disease can be caused by a disturbance of the host microbiome, we examined the impact of influenza on the upper respiratory tract microbiome in a human challenge study. METHODS: The dynamics and ecology of the throat microbiome were examined following an experimental influenza challenge of 52 previously-healthy adult volunteers with influenza A/Wisconsin/67/2005 (H3N2) by intranasal inoculation; 35 healthy control subjects were not subjected to the viral challenge. Serial oropharyngeal samples were taken over a 30-day period, and the V1-V3 region of the bacterial 16S ribosomal RNA sequences were amplified and sequenced to determine the composition of the microbiome. The carriage of pathogens was also detected. RESULTS: Of the 52 challenged individuals, 43 developed proven influenza infections, 33 of whom became symptomatic. None of the controls developed influenza, although 22% reported symptoms. The diversity of bacterial communities remained remarkably stable following the acquisition of influenza, with no significant differences over time between individuals with influenza and those in the control group. Influenza infection was not associated with perturbation of the microbiome at the level of phylum or genus. There was no change in colonization rates with Streptococcus pneumoniae or Neisseria meningitidis. CONCLUSIONS: The throat microbiota is resilient to influenza infection, indicating the robustness of the upper-airway microbiome

Effects of seasonal and pandemic influenza on health‐related quality of life, work and school absence in England: Results from the Flu Watch cohort study

BACKGROUND: Estimates of health-related quality of life (HRQoL) and work/school absences for influenza are typically based on medically-attended cases or those meeting influenza-like-illness (ILI) case definitions, and thus biased towards severe disease. Although community influenza cases are more common, estimates of their effects on HRQoL and absences are limited. OBJECTIVES: To measure Quality-Adjusted Life Days and Years (QALDs and QALYs) lost and work/school absences among community cases of acute respiratory infections (ARI), ILI and influenza A and B and to estimate community burden of QALY loss and absences from influenza. PATIENTS/ METHODS: Flu Watch was a community cohort in England from 2006-2011. Participants were followed-up weekly. During respiratory illness they prospectively recorded daily symptoms, work/school absences and EQ-5D-3L data and submitted nasal swabs for RT-PCR influenza testing. RESULTS: Average QALD lost was 0.26, 0.93, 1.61 and 1.84 for ARI, ILI, H1N1pdm09 and influenza B cases respectively. 40% of influenza A cases and 24% of influenza B cases took time off work/school with an average duration of 3.6 days and 2.4 days respectively. In England, community influenza cases lost 24,300 QALYs in 2010/11 and had an estimated 2.9 million absences per season based on data from 2006/07 - 2009/10. CONCLUSIONS: Our QALDs and QALYs lost and work and school absence estimates are lower than previous estimates because we focus on community cases, most of which are mild, may not meet ILI definitions and do not result in healthcare consultations. Nevertheless, they contribute a substantial loss of HRQoL on a population level. This article is protected by copyright. All rights reserved