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Objective: The uptake and safety of pneumococcal vaccination in people with immune mediated inflammatory diseases (IMIDs) is poorly understood. We investigated the UK wide pneumococcal vaccine uptake in adults with IMIDs and explored the association between vaccination and IMID flare., Methods: Adults with IMIDs diagnosed on or before 01/09/2018, prescribed steroid-sparing drugs within the last 12 months and contributing data to the Clinical Practice Research Datalink Gold were included. Vaccine uptake was assessed using a cross-sectional study design. Self-controlled case series (SCCS) analysis investigated the association between pneumococcal vaccination and IMID flare. The SCCS observation period was up-to six-month before and after pneumococcal vaccination. This was partitioned into a 14-day pre-vaccination induction, 90-days post-vaccination exposed, and the remaining unexposed periods., Results: We included 32 277 patients, 14 151 with RA, 13 631 with IBD, 3,804 with axial spondyloarthritis and 691 with SLE. Overall, 57% were vaccinated against pneumococcus. Vaccine uptake was lower in those younger than 45 years (32%), with IBD (42%), and without additional indication(s) for vaccination (46%). In the vaccine-safety study, data for 1,067, 935, and 451vaccinated patients with primary-care consultations for joint pain, AIRD flare and IBD flare respectively were included. Vaccination against pneumococcal pneumonia was not associated with primary-care consultations for joint pain, AIRD flare and IBD flare in the exposed period with incidence rate ratios (95% Confidence Interval) 0.95 (0.83-1.09), 1.05 (0.92-1.19), and 0.83 (0.65-1.06) respectively., Conclusion: Uptake of pneumococcal vaccination in UK patients with IMIDs was suboptimal. Vaccination against pneumococcal disease was not associated with IMID flare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and autoimmune rheumatic disease (AIRD) flare., Material and Methods: Patients with AIRDs vaccinated against COVID-19 who consulted for disease flare between 1 December 2020 and 31 December 2021 were ascertained in Clinical Practice Research Datalink (Aurum). AIRD flare was defined as consultation for AIRD with CS prescription on the same day or the next day. Vaccination was defined using date of vaccination and product code. The observation period was partitioned into vaccine-exposed (21 days after vaccination), pre-vaccination (7 days before vaccination) and remaining vaccine-unexposed periods. Participants contributed data with multiple vaccinations and outcomes. Season adjusted incidence rate ratios (aIRR) and 95% CI were calculated using self-controlled case series analysis., Results: Data for 3554 AIRD cases, 72% female, mean age 65 years and 68.3% with RA, were included. COVID-19 vaccination was associated with significantly fewer AIRD flares in the 21-day vaccine-exposed period when all vaccinations were considered [aIRR (95% CI) 0.89 (0.80, 0.98)]. Using dose-stratified analyses there was a statistically significant negative association in the 21 days after first COVID-19 vaccination but no association after the second or third COVID-19 vaccinations [aIRR (95% CI) 0.76 (0.66, 0.89), 0.94 (0.79, 1.11) and 1.01 (0.85, 1.20), respectively]. On AIRD-type stratified analyses, vaccination was not associated with disease flares. Vaccination without or after severe acute respiratory syndrome coronavirus 2 infection, and with vectored DNA or mRNA vaccines, associated with comparable reduced risk of AIRD flares in the vaccine-exposed period after first COVID-19 vaccination., Conclusions: Vaccination against COVID-19 was not associated with increased AIRD flares regardless of prior COVID-19, AIRD type, and whether mRNA or DNA vaccination technology were used., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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 Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background: Few pediatric cases of coronavirus disease 2019 (COVID-19) have been reported and we know little about the epidemiology in children, although more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes, and transmission dynamics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to inform clinical and public health measures., Methods: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in pediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched 3 databases and the COVID-19 resource centers of 11 major journals and publishers. English abstracts of Chinese-language papers were included. Data were extracted and narrative syntheses conducted., Results: Twenty-four studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, although radiological abnormalities are noted. Severe cases are not reported in detail and there are few data relating to transmission., Conclusions: Children appear to have a low observed case rate of COVID-19 but may have rates similar to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention and be tested and counted in observed cases of COVID-19., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: The effectiveness of inactivated influenza vaccine in people with autoimmune rheumatic disease (AIRDs) is not known. We investigated whether the influenza vaccine is effective in preventing respiratory morbidity, mortality and all-cause mortality in AIRD patients., Methods: Adults with AIRDs treated with DMARDs prior to 1 September of each year between 2006 and 2009, and 2010 and 2015 were identified from the Clinical Practice Research Datalink. Exposure and outcome data were extracted. Data from multiple seasons were pooled. Propensity score (PS) for vaccination was calculated. Cox-proportional hazard ratios (HRs) and 95% CIs were calculated, and were (i) adjusted, (ii) matched for PS for vaccination., Results: Data for 30 788 AIRD patients (65.7% female, 75.5% with RA, 61.1% prescribed MTX) contributing 125 034 influenza cycles were included. Vaccination reduced risk of influenza-like illness [adjusted HR (aHR) 0.70], hospitalization for pneumonia (aHR 0.61) and chronic obstructive pulmonary disease exacerbations (aHR 0.67), and death due to pneumonia (aHR 0.56) on PS-adjusted analysis in the influenza active periods (IAPs). The associations were of similar magnitude and remained statistically significant on PS-matched analysis except for protection from influenza-like illness, which became non-significant. Sub-analysis restricted to pre-IAP, IAP and post-IAP did not yield evidence of residual confounding on influenza-like illness and death due to pneumonia. Vaccination reduced risk of all-cause mortality, although IAP-restricted analysis demonstrated residual confounding for this outcome., Conclusion: Influenza vaccine associates with reduced risk of respiratory morbidity and mortality in people with AIRDs. These findings call for active promotion of seasonal influenza vaccination in immunosuppressed people with AIRDs by healthcare professionals., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: We studied the effect of age, baseline viral load, vaccination status, antiviral therapy, and emergence of drug resistance on viral shedding in children infected with influenza A or B virus., Methods: Samples from children (aged ≤13 years) enrolled during the 7 years of the prospective Influenza Resistance Information Study were analyzed using polymerase chain reaction to determine the influenza virus (sub-)type, viral load, and resistance mutations. Disease severity was assessed; clinical symptoms were recorded. The association of age with viral load and viral clearance was examined by determining the area under the curve for viral RNA shedding using logistic regression and Kaplan-Meier analyses., Results: A total of 2131 children infected with influenza (683, A/H1N1pdm09; 825, A/H3N2; 623, influenza B) were investigated. Age did not affect the mean baseline viral load. Children aged 1-5 years had prolonged viral RNA shedding (±1-2 days) compared with older children and up to 1.2-fold higher total viral burden. Besides, in older age (odds ratio [OR], 1.08; confidence interval [CI], 1.05-1.12), prior vaccination status (OR, 1.72; CI, 1.22-2.43) and antiviral treatment (OR, 1.74; CI, 1.43-2.12) increased the rate of viral clearance. Resistance mutations were detected in 49 children infected with influenza A virus (34, A/H1N1pdm09; 15, A/H3N2) treated with oseltamivir, most of whom were aged <5 years (n = 39)., Conclusions: Children aged 1-5 years had a higher total viral burden with prolonged virus shedding and had an increased risk of acquiring resistance mutations following antiviral treatment., Clinical Trials Registration: NCT00884117., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear., Methods: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded., Results: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS., Conclusions: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Many countries have acquired antiviral stockpiles for pandemic influenza mitigation and a significant part of the stockpile may be focussed towards community-based treatment., Methods: We developed a spreadsheet-based, decision tree model to assess outcomes averted and cost-effectiveness of antiviral treatment for outpatient use from the perspective of the healthcare payer in the UK. We defined five pandemic scenarios-one based on the 2009 A(H1N1) pandemic and four hypothetical scenarios varying in measures of transmissibility and severity., Results: Community-based antiviral treatment was estimated to avert 14-23% of hospitalizations in an overall population of 62.28 million. Higher proportions of averted outcomes were seen in patients with high-risk conditions, when compared to non-high-risk patients. We found that antiviral treatment was cost-saving across pandemic scenarios for high-risk population groups, and cost-saving for the overall population in higher severity influenza pandemics. Antiviral effectiveness had the greatest influence on both the number of hospitalizations averted and on cost-effectiveness., Conclusions: This analysis shows that across pandemic scenarios, antiviral treatment can be cost-saving for population groups at high risk of influenza-related complications., (Published by Oxford University Press on behalf of Faculty of Public Health [2018]. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

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., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: To examine temporal trend in uptake of seasonal influenza vaccine (SIV) in the UK and explore disease and demographic factors associated with vaccination., Methods: From the Clinical Practice Research Datalink, 32 751 people with auto-immune rheumatic diseases prescribed DMARDs between 2006 and 2016 were identified. The proportion vaccinated between 1 September of one year and 31 March of the next year was calculated and stratified by age, other indications for vaccination, auto-immune rheumatic diseases type and number of DMARDs prescribed. Stata and Joinpoint regression programs were used., Results: SIV uptake was high in those aged ⩾65 years (82.3 and 80.7% in 2006-07 and 2015-16, respectively). It was significantly lower in other age groups, but improved over time with 51.9 and 61.9% in the 45-64 year age group, and 32.3 and 50.1% in the <45 year age group being vaccinated in 2006-07 and 2015-16, respectively. While 64.9% of the vaccinations in those ⩾65 years old occurred by 3 November, in time to mount a protective immune response before the influenza activity becomes substantial in the UK, only 38.9% in the 45-64 year and 26.2% in the <45 year age group without any other reason for vaccination received SIV by this date. Women, those with additional indications for vaccination, on multiple DMARDs and with SLE were more likely to be vaccinated., Conclusion: SIV uptake is low in the under 65s, and the majority of them are not vaccinated in time. Additional effort is required to promote timely uptake of SIV in this population.

Background: While evidence exists to support the effectiveness of neuraminidase inhibitors (NAIs) in reducing mortality when given to hospitalized patients with A(H1N1)pdm09 virus infection, the impact of outpatient treatment on hospitalization has not been clearly established. We investigated the impact of outpatient NAI treatment on subsequent hospitalization in patients with A(H1N1)pdm09 virus infection., Methods: We assembled general community and outpatient data from 9 clinical centers in different countries collected between January 2009 and December 2010. We standardized data from each study center to create a pooled dataset and then used mixed-effects logistic regression modeling to determine the effect of NAI treatment on hospitalization. We adjusted for NAI treatment propensity and preadmission antibiotic use, including "study center" as a random intercept to account for differences in baseline hospitalization rate between centers., Results: We included 3376 patients with influenza A(H1N1)pdm09, of whom 3085 (91.4%) had laboratory-confirmed infection. Eight hundred seventy-three patients (25.8%) received outpatient or community-based NAI treatment, 928 of 2395 (38.8%) with available data had dyspnea or respiratory distress, and hospitalizations occurred in 1705 (50.5%). After adjustment for preadmission antibiotics and NAI treatment propensity, preadmission NAI treatment was associated with decreased odds of hospital admission compared to no NAI treatment (adjusted odds ratio, 0.24; 95% confidence interval, 0.20-0.30)., Conclusions: In a population with confirmed or suspected A(H1N1)pdm09 and at high risk of hospitalization, outpatient or community-based NAI treatment significantly reduced the likelihood of requiring hospital admission. These data suggest that community patients with severe influenza should receive NAI treatment., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Respiratory viruses spread in humans across wide geographical areas in short periods of time, resulting in high levels of morbidity and mortality. We undertook a systematic review to assess the evidence that air, ground and sea mass transportation systems or hubs are associated with propagating influenza and coronaviruses., Methods: Healthcare databases and sources of grey literature were searched using pre-defined criteria between April and June 2014. Two reviewers screened all identified records against the protocol, undertook risk of bias assessments and extracted data using a piloted form. Results were analysed using a narrative synthesis., Results: Forty-one studies met the eligibility criteria. Risk of bias was high in the observational studies, moderate to high in the reviews and moderate to low in the modelling studies. In-flight influenza transmission was identified substantively on five flights with up to four confirmed and six suspected secondary cases per affected flight. Five studies highlighted the role of air travel in accelerating influenza spread to new areas. Influenza outbreaks aboard cruise ships affect 2-7% of passengers. Influenza transmission events have been observed aboard ground transport vehicles. High heterogeneity between studies and the inability to exclude other sources of infection means that the risk of influenza transmission from an index case to other passengers cannot be accurately quantified. A paucity of evidence was identified describing severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus transmission events associated with transportation systems or hubs., Conclusion: Air transportation appears important in accelerating and amplifying influenza propagation. Transmission occurs aboard aeroplanes, at the destination and possibly at airports. Control measures to prevent influenza transmission on cruise ships are needed to reduce morbidity and mortality. There is no recent evidence of sea transport accelerating influenza or coronavirus spread to new areas. Further investigation is required regarding the roles of ground transportation systems and transport hubs in pandemic situations., (© The Author 2016. Published by Oxford University Press on behalf of International society of travel medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Most studies have reported that corticosteroid therapy adversely influences influenza-related outcomes., Methods: Electronic databases were searched from inception to March 2013 for experimental and observational studies investigating systemic corticosteroid therapy for presumed influenza-associated complications. Meta-analysis of Observational Studies in Epidemiology guidelines were adopted. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects models, and heterogeneity was assessed using the I(2) statistic. Quality of evidence was assessed using the Grading Assessment, Development, and Evaluation system., Results: We identified 16 eligible studies (3039 individuals), all of which were observational; 10 (1497 individuals) were included in the meta-analysis of mortality, of which 9 studied patients with 2009 pandemic influenza A virus subtype H1N1. Risk of bias was greatest in the comparability domain of the Newcastle-Ottawa scale, consistent with potential confounding by indication, and data specific to mortality were of low quality. Meta-analysis found an increased odds of mortality (OR, 2.12; 95% CI, 1.36-3.29) associated with corticosteroid therapy. Subgroup analysis of adjusted estimates from 4 studies with very low statistical heterogeneity found a similar association (OR, 2.58; 95% CI, 1.39-4.79)., Conclusions: No completed clinical trials were identified. Evidence from observational studies, with important limitations, suggests that corticosteroid therapy for presumed influenza-associated complications is associated with increased mortality., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (SARIs) of viral etiology. We conducted a systematic review and exploratory meta-analysis to assess the overall evidence., Methods: Healthcare databases and sources of grey literature were searched in July 2013. All records were screened against the protocol eligibility criteria, using a 3-stage process. Data extraction and risk of bias assessments were undertaken., Results: We identified 32 studies of SARS coronavirus infection and severe influenza. Narrative analyses revealed consistent evidence for a reduction in mortality, especially when convalescent plasma is administered early after symptom onset. Exploratory post hoc meta-analysis showed a statistically significant reduction in the pooled odds of mortality following treatment, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, .14-.45; I(2) = 0%). Studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias. Sources of clinical and methodological heterogeneity were identified., Conclusions: Convalescent plasma may reduce mortality and appears safe. This therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including for treatment of Middle East respiratory syndrome coronavirus CoV infection., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: Following emergence of naturally occurring oseltamivir-resistant influenza A(H1N1) viruses, a global observational investigation, the Influenza Resistance Information Study (IRIS; NCT00884117), was initiated in 2008 to study neuraminidase inhibitor (NAI) resistance and clinical outcome., Methods: Patients with influenza-like illness and/or positive rapid test results agreed to swabs of the posterior nares that were assessed by semiquantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) for influenza type and subtype and NAI resistance. RT-qPCR-positive specimens were cultured, sequenced, and phenotypically tested for NAI resistance. Treatment was at the physician's discretion., Results: Of 1799 influenza-positive (RT-qPCR) patients, 1281 had influenza A (47 seasonal H1N1; 335 H3N2; 899 H1N1pdm2009) and 518 had influenza B. Antivirals were administered to 1041 (58%) patients (26, 245, 514, and 256, respectively). All seasonal H1N1 strains were genotypically (H275Y) and phenotypically resistant to oseltamivir. No genotypic resistance was detected in the day 1 samples of any other viral subtypes. Mutation-specific (MS) RT-PCR detected resistance to oseltamivir in 19 patients postbaseline (17 H1N1pdm2009 [H275Y]; 2 H3N2 [R292K]), 14 of whom were children aged ≤5 years. In 12 of 19 patients, viral loads were too low to permit cell culture and 14 of 19 were RT-qPCR negative by day 10. In 1 other H1N1pdm2009 patient, H275Y was detected by sequencing but not by MS RT-PCR. No emergent resistance was found in influenza B infections., Conclusions: In years 1-3 of IRIS, emergent resistance to oseltamivir in influenza viruses during treatment was uncommon (2.2%) and mostly found in patients aged 1-5 years. Viral loads were low in many cases and viral clearance rapid.

Background: The impact of neuraminidase inhibitor (NAI) treatment on clinical outcomes of public health importance during the 2009-2010 pandemic has not been firmly established., Methods: We conducted a systematic review and meta-analysis, searching 11 databases (2009 through April 2012) for relevant studies. We used standard methods conforming to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random effects models., Results: Regarding mortality we observed a nonsignificant reduction associated with NAI treatment (at any time) versus none (OR, 0.72 [95% CI, .51-1.01]). However we observed significant reductions for early treatment (≤48 hours after symptom onset) versus late (OR, 0.38 [95% CI, .27-.53]) and for early treatment versus none (OR, 0.35 [95% CI, .18-.71]). NAI treatment (at any time) versus none was associated with an elevated risk of severe outcome (OR, 1.76 [95% CI, 1.22-2.54]), but early versus late treatment reduced the likelihood (OR, 0.41 [95% CI, .30-.56])., Conclusions: During the 2009-2010 influenza A(H1N1) pandemic, early initiation of NAI treatment reduced the likelihood of severe outcomes compared with late or no treatment., Prospero Registration: CRD42011001273.

Many national guidelines recommend annual influenza vaccination of immunocompromised patients, although the decision to vaccinate is usually at clinical discretion. We conducted a systematic review and meta-analyses to assess the evidence for influenza vaccination in this group, and we report our results by etiology. Meta-analyses showed significantly lower odds of influenza-like illness after vaccination in patients with human immunodeficiency virus (HIV) infection, patients with cancer, and transplant recipients and of laboratory-confirmed influenza in HIV-positive patients, compared with patients receiving placebo or no vaccination. Pooled odds of seroconversion and seroprotection were typically lower in HIV-positive patients, patients with cancer, and transplant recipients, compared with immunocompetent controls. Vaccination was generally well tolerated, with variation in mild adverse events between etiological groups. Limited evidence of a transient increase in viremia and a decrease in the percentage of CD4(+) cells in HIV-positive patients was found although not accompanied by worsening of clinical symptoms. Clinical judgment remains important when discussing the benefits and safety profile with immunocompromised patients.

Background: Influenza transmission in humans remains poorly understood. In particular, the relative contribution of contact, large droplet, and aerosol transmission is unknown. The aims of this proof-of-concept study were to determine whether an experimentally induced influenza infection is transmissible between humans and whether this would form a viable platform for future studies., Methods: In a quarantine facility, healthy volunteers ("donors") were inoculated with A/Wisconsin/67/2005 (H3N2) influenza virus via intranasal drops. On study days 2 and 3 "recipient" volunteers were exposed to donors under close living conditions. Volunteers socialized for 30 hours during a 2-day period. Infection was confirmed by ≥1 positive results from polymerase chain reaction, virus culture, or serology., Results: After inoculation, 4 of 9 donors developed symptoms consistent an influenza-like illness (ILI) and 7 of 9 were proven to be influenza-infected. After exposure, 4 of 15 recipients developed symptoms of ILI and 3 of 15 were proven to be infected. Serum collected within 2 days of study initiation indicated that 1 donor and 3 recipients were seropositive at study initiation. After adjustment for preexposure immunity, the overall secondary attack rate was 25% (3 of 12)., Conclusions: Experimental human exposure studies offer an attractive potential method for answering outstanding questions related to influenza transmission and the evaluation of interventions to reduce it.

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.

Three recent outbreaks of influenza A in nursing and residential homes in Sheffield were characterized by high attack rates among both residents and staff, and a high mortality rate among residents. The epidemiology of the outbreaks was unusual in that all three occurred towards the end of a quiet influenza season, against a generally low level of community activity, and involved strains of influenza that were not included in the current season's vaccine. The outbreak investigation was aided by the use of a novel rapid diagnostic technique. In future the combination of vaccination, surveillance, rapid diagnosis and new antineuraminidase drugs should improve prospects for control of influenza within closed communities.

Background: The elderly residents of nursing and old people's homes are at substantially increased risk from influenza and its complications. Annual vaccination is therefore strongly recommended by the UK Departments of Health. However, few data exist on the uptake of influenza vaccine in this setting; this was last estimated to be 45 percent in 1988-1989. A major epidemic of influenza A occurred in 1989-1990 which may have changed vaccination behaviours., Methods: A structured interview survey was conducted in 49 old people's homes in Nottingham to determine practices and policies for influenza vaccine. The medical records of 151 randomly selected elderly residents were examined to determine vaccine uptake in the 1992-1993 season., Results: Twenty-five homes (52.1 percent) claimed to operate a policy for influenza immunization but only 3 (12.0 percent) were written down and none set targets. Methods of vaccine promotion were generally weak. Accordingly, vaccine uptake was only 39.6% percent (95 percent confidence interval 33.2-46.0)., Conclusions: In contrast to other high-risk groups living in the open community, no improvement in influenza vaccine uptake has occurred in nursing and old people's homes since the late 1980s. Future attempts to increase vaccine uptake in this setting should focus on developing joint policies between general practitioners and home staff to facilitate better co-ordinated programmes of vaccine promotion and administration.