Influenza A (H3) illness and viral aerosol shedding from symptomatic naturally infected and experimentally infected cases.

BACKGROUND: It has long been known that nasal inoculation with influenza A virus produces asymptomatic to febrile infections. Uncertainty persists about whether these infections are sufficiently similar to natural infections for studying human-to-human transmission. METHODS: We compared influenza A viral aerosol shedding from volunteers nasally inoculated with A/Wisconsin/2005 (H3N2) and college community adults naturally infected with influenza A/H3N2 (2012-2013), selected for influenza-like illness with objectively measured fever or a positive Quidel QuickVue A&B test. Propensity scores were used to control for differences in symptom presentation observed between experimentally and naturally infected groups. RESULTS: Eleven (28%) experimental and 71 (86%) natural cases shed into fine particle aerosols (P < .001). The geometric mean (geometric standard deviation) for viral positive fine aerosol samples from experimental and natural cases was 5.1E + 3 (4.72) and 3.9E + 4 (15.12) RNA copies/half hour, respectively. The 95th percentile shedding rate was 2.4 log10 greater for naturally infected cases (1.4E + 07 vs 7.4E + 04). Certain influenza-like illness-related symptoms were associated with viral aerosol shedding. The almost complete lack of symptom severity distributional overlap between groups did not support propensity score-adjusted shedding comparisons. CONCLUSIONS: Due to selection bias, the natural and experimental infections had limited symptom severity distributional overlap precluding valid, propensity score-adjusted comparison. Relative to the symptomatic naturally infected cases, where high aerosol shedders were found, experimental cases did not produce high aerosol shedders. Studying the frequency of aerosol shedding at the highest observed levels in natural infections without selection on symptoms or fever would support helpful comparisons.

Minimal transmission in an influenza A (H3N2) human challenge-transmission model within a controlled exposure environment.

Uncertainty about the importance of influenza transmission by airborne droplet nuclei generates controversy for infection control. Human challenge-transmission studies have been supported as the most promising approach to fill this knowledge gap. Healthy, seronegative volunteer 'Donors' (n = 52) were randomly selected for intranasal challenge with influenza A/Wisconsin/67/2005 (H3N2). 'Recipients' randomized to Intervention (IR, n = 40) or Control (CR, n = 35) groups were exposed to Donors for four days. IRs wore face shields and hand sanitized frequently to limit large droplet and contact transmission. One transmitted infection was confirmed by serology in a CR, yielding a secondary attack rate of 2.9% among CR, 0% in IR (p = 0.47 for group difference), and 1.3% overall, significantly less than 16% (p<0.001) expected based on a proof-of-concept study secondary attack rate and considering that there were twice as many Donors and days of exposure. The main difference between these studies was mechanical building ventilation in the follow-on study, suggesting a possible role for aerosols.

The importance of local epidemic conditions in monitoring progress towards HIV epidemic control in Kenya: a modelling study.

INTRODUCTION: Setting and monitoring progress towards targets for HIV control is critical in ensuring responsive programmes. Here, we explore how to apply targets for reduction in HIV incidence to local settings and which indicators give the strongest signal of a change in incidence in the population and are therefore most important to monitor. METHODS: We use location-specific HIV transmission models, tailored to the epidemics in the counties and major cities in Kenya, to project a wide range of plausible future epidemic trajectories through varying behaviours, treatment coverage and prevention interventions. We look at the change in incidence across modelled scenarios in each location between 2015 and 2030 to inform local target setting. We also simulate the measurement of a library of potential indicators and assess which are most strongly associated with a change in incidence. RESULTS: Considerable variation was observed in the trajectory of the local epidemics under the plausible scenarios defined (only 10 of 48 locations saw a median reduction in incidence of greater than or equal to an 80% target by 2030). Indicators that provide strong signals in certain epidemic types may not perform consistently well in settings with different epidemiological features. Predicting changes in incidence is more challenging in advanced generalized epidemics compared to concentrated epidemics where changes in high-risk sub-populations track more closely to the population as a whole. Many indicators demonstrate only limited association with incidence (such as "condom use" or "pre-exposure prophylaxis coverage"). This is because many other factors (low effectiveness, impact of other interventions, countervailing changes in risk behaviours, etc.) can confound the relationship between interventions and their ultimate long-term impact, especially for an intervention with low expected coverage. The population prevalence of viral suppression shows the most consistent associations with long-term changes in incidence even in the largest generalized epidemics. CONCLUSIONS: Target setting should be appropriate for the local epidemic and what can feasibly be achieved. There is no one universally reliable indicator to predict future HIV incidence across settings. Thus, the signature of epidemic control must contain indications of success across a wide range of interventions and outcomes.

Deposition of respiratory virus pathogens on frequently touched surfaces at airports.

BACKGROUND: International and national travelling has made the rapid spread of infectious diseases possible. Little information is available on the role of major traffic hubs, such as airports, in the transmission of respiratory infections, including seasonal influenza and a pandemic threat. We investigated the presence of respiratory viruses in the passenger environment of a major airport in order to identify risk points and guide measures to minimize transmission. METHODS: Surface and air samples were collected weekly at three different time points during the peak period of seasonal influenza in 2015-16 in Finland. Swabs from surface samples, and air samples were tested by real-time PCR for influenza A and B viruses, respiratory syncytial virus, adenovirus, rhinovirus and coronaviruses (229E, HKU1, NL63 and OC43). RESULTS: Nucleic acid of at least one respiratory virus was detected in 9 out of 90 (10%) surface samples, including: a plastic toy dog in the children's playground (2/3 swabs, 67%); hand-carried luggage trays at the security check area (4/8, 50%); the buttons of the payment terminal at the pharmacy (1/2, 50%); the handrails of stairs (1/7, 14%); and the passenger side desk and divider glass at a passport control point (1/3, 33%). Among the 10 respiratory virus findings at various sites, the viruses identified were: rhinovirus (4/10, 40%, from surfaces); coronavirus (3/10, 30%, from surfaces); adenovirus (2/10, 20%, 1 air sample, 1 surface sample); influenza A (1/10, 10%, surface sample). CONCLUSIONS: Detection of pathogen viral nucleic acids indicates respiratory viral surface contamination at multiple sites associated with high touch rates, and suggests a potential risk in the identified airport sites. Of the surfaces tested, plastic security screening trays appeared to pose the highest potential risk, and handling these is almost inevitable for all embarking passengers.

Interventions to strengthen the HIV prevention cascade: a systematic review of reviews.

BACKGROUND: Much progress has been made in interventions to prevent HIV infection. However, development of evidence-informed prevention programmes that translate the efficacy of these strategies into population effect remain a challenge. In this systematic review, we map current evidence for HIV prevention against a new classification system, the HIV prevention cascade. METHODS: We searched for systematic reviews on the effectiveness of HIV prevention interventions published in English from Jan 1, 1995, to July, 2015. From eligible reviews, we identified primary studies that assessed at least one of: HIV incidence, HIV prevalence, condom use, and uptake of HIV testing. We categorised interventions as those seeking to increase demand for HIV prevention, improve supply of HIV prevention methods, support adherence to prevention behaviours, or directly prevent HIV. For each specific intervention, we assigned a rating based on the number of randomised trials and the strength of evidence. FINDINGS: From 88 eligible reviews, we identified 1964 primary studies, of which 292 were eligible for inclusion. Primary studies of direct prevention mechanisms showed strong evidence for the efficacy of pre-exposure prophylaxis (PrEP) and voluntary medical male circumcision. Evidence suggests that interventions to increase supply of prevention methods such as condoms or clean needles can be effective. Evidence arising from demand-side interventions and interventions to promote use of or adherence to prevention tools was less clear, with some strategies likely to be effective and others showing no effect. The quality of the evidence varied across categories. INTERPRETATION: There is growing evidence to support a number of efficacious HIV prevention behaviours, products, and procedures. Translating this evidence into population impact will require interventions that strengthen demand for HIV prevention, supply of HIV prevention technologies, and use of and adherence to HIV prevention methods. FUNDING: Bill & Melinda Gates Foundation.

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: Forty-two percent 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 (CIs), 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 immunisation of pig industry workers may reduce transmission and the potential for virus reassortment.

The environmental deposition of influenza virus from patients infected with influenza A(H1N1)pdm09: Implications for infection prevention and control.

In a multi-center, prospective, observational study over two influenza seasons, we sought to quantify and correlate the amount of virus recovered from the nares of infected subjects with that recovered from their immediate environment in community and hospital settings. We recorded the symptoms of adults and children with A(H1N1)pdm09 infection, took nasal swabs, and sampled touched surfaces and room air. Forty-two infected subjects were followed up. The mean duration of virus shedding was 6.2 days by PCR (Polymerase Chain Reaction) and 4.2 days by culture. Surface swabs were collected from 39 settings; 16 (41%) subject locations were contaminated with virus. Overall, 33 of the 671 (4.9%) surface swabs were PCR positive for influenza, of which two (0.3%) yielded viable virus. On illness Day 3, subjects yielding positive surface samples had significantly higher nasal viral loads (geometric mean ratio 25.7; 95% CI 1.75, 376.0, p=0.021) and a positive correlation (r=0.47, p=0.006) was observed between subject nasal viral loads and viral loads recovered from the surfaces around them. Room air was sampled in the vicinity of 12 subjects, and PCR positive samples were obtained for five (42%) samples. Influenza virus shed by infected subjects did not detectably contaminate the vast majority of surfaces sampled. We question the relative importance of the indirect contact transmission of influenza via surfaces, though our data support the existence of super-spreaders via this route. The air sampling results add to the accumulating evidence that supports the potential for droplet nuclei (aerosol) transmission of influenza.

Influenza vaccination for immunocompromised patients: summary of a systematic review and meta-analysis.

Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta-analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta-analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta-analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.

An evaluation of community assessment tools (CATs) in predicting use of clinical interventions and severe outcomes during the A(H1N1)pdm09 pandemic.

During severe influenza pandemics healthcare demand can exceed clinical capacity to provide normal standards of care. Community Assessment Tools (CATs) could provide a framework for triage decisions for hospital referral and admission. CATs have been developed based on evidence that supports the recognition of severe influenza and pneumonia in the community (including resource limited settings) for adults, children and infants, and serious feverish illness in children. CATs use six objective criteria and one subjective criterion, any one or more of which should prompt urgent referral and admission to hospital. A retrospective evaluation of the ability of CATs to predict use of hospital-based interventions and patient outcomes in a pandemic was made using the first recorded routine clinical assessment on or shortly after admission from 1520 unselected patients (800 female, 480 children <16 years) admitted with PCR confirmed A(H1N1)pdm09 infection (the FLU-CIN cohort). Outcome measures included: any use of supplemental oxygen; mechanical ventilation; intravenous antibiotics; length of stay; intensive or high dependency care; death; and "severe outcome" (combined: use of intensive or high dependency care or death during admission). Unadjusted and multivariable analyses were conducted for children (age <16 years) and adults. Each CATs criterion independently identified both use of clinical interventions that would in normal circumstances only be provided in hospital and patient outcome measures. "Peripheral oxygen saturation ≤ 92% breathing air, or being on oxygen" performed well in predicting use of resources and outcomes for both adults and children; supporting routine measurement of peripheral oxygen saturation when assessing severity of disease. In multivariable analyses the single subjective criterion in CATs "other cause for clinical concern" independently predicted death in children and in adults predicted length of stay, mechanical ventilation and "severe outcome"; supporting the role of clinical acumen as an important independent predictor of serious illness.

Multi-centre observational study of transplacental transmission of influenza antibodies following vaccination with AS03(A)-adjuvanted H1N1 2009 vaccine.

INTRODUCTION: Illness and death from influenza increase during pregnancy. In the United Kingdom pregnant women were targeted in a national programme for vaccination during the H1N1 2009-10 pandemic. METHODS: In this study, pregnant women were recruited in labour from November 9, 2009 to March 10, 2010. Pandemic vaccination status was determined. Venous cord blood collected at delivery was evaluated for transplacental transfer of antibodies by measurement of haemagglutination inhibition and microneutralization titres. RESULTS: Samples were collected from 77 vaccinated and 27 unvaccinated women. Seroprotection (HI titre ≥1:40) was detected in 58 (75.3%, 95% CI 64.2-84.4) cord blood samples from vaccinated women and 5 (18.5%, 95% CI 6.3-38.1) from unvaccinated women (P<0.0001). There was evidence of transplacental seroprotection 8 days after maternal immunization (77.9%, 95 CI 66.2-87.1), maintained in most cases for at least 16 weeks. DISCUSSION: Immunization of pregnant women with AS03(A)-adjuvanted vaccine is followed by transplacental transfer of passive immunity at titres consistent with clinical protection in three-quarters of new-born infants. The findings support national and international pandemic H1N1 2009 recommendations for immunization during pregnancy.

Differences between asthmatics and nonasthmatics hospitalised with influenza A infection.

Asthmatics hospitalised because of influenza A infection are less likely to require intensive care or die compared with nonasthmatics. The reasons for this are unknown. We performed a retrospective analysis of data on 1520 patients admitted to 75 UK hospitals with confirmed influenza A/H1N1 2009 infection. A multivariable model was used to investigate reasons for the association between asthma and severe outcomes (intensive care unit support or death). Asthmatics were less likely than nonasthmatics to have severe outcome (11.2% versus 19.8%, unadjusted OR 0.51, 95% CI 0.36-0.72) despite a greater proportion requiring oxygen on admission (36.4% versus 26%, unadjusted OR 1.63) and similar rates of pneumonia (17.1% versus 16.6%, unadjusted OR 1.04). The results of multivariable logistic regression suggest the association of asthma with outcome (adjusted OR 0.62, 95% CI 0.36-1.05; p=0.075) are explained by pre-admission inhaled corticosteroid use (adjusted OR 0.34, 95% CI 0.18-0.66) and earlier admission (≤ 4 days from symptom onset) (adjusted OR 0.60, 95% CI 0.38-0.94). In asthmatics, systemic corticosteroids were associated with a decreased likelihood of severe outcomes (adjusted OR 0.36, 95% CI 0.18-0.72). Corticosteroid use and earlier hospital admission explained the association of asthma with less severe outcomes in hospitalised patients.

The comparative clinical course of pregnant and non-pregnant women hospitalised with influenza A(H1N1)pdm09 infection.

INTRODUCTION: The Influenza Clinical Information Network (FLU-CIN) was established to gather detailed clinical and epidemiological information about patients with laboratory confirmed A(H1N1)pdm09 infection in UK hospitals. This report focuses on the clinical course and outcomes of infection in pregnancy. METHODS: A standardised data extraction form was used to obtain detailed clinical information from hospital case notes and electronic records, for patients with PCR-confirmed A(H1N1)pdm09 infection admitted to 13 sentinel hospitals in five clinical 'hubs' and a further 62 non-sentinel hospitals, between 11th May 2009 and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women aged 15-44 years, using univariate and multivariable techniques. RESULTS: Of the 395 women aged 15-44 years, 82 (21%) were pregnant; 73 (89%) in the second or third trimester. Pregnant women were significantly less likely to exhibit severe respiratory distress at initial assessment (OR = 0.49 (95% CI: 0.30-0.82)), require supplemental oxygen on admission (OR = 0.40 (95% CI: 0.20-0.80)), or have underlying co-morbidities (p-trend <0.001). However, they were equally likely to be admitted to high dependency (Level 2) or intensive care (Level 3) and/or to die, after adjustment for potential confounders (adj. OR = 0.93 (95% CI: 0.46-1.92). Of 11 pregnant women needing Level 2/3 care, 10 required mechanical ventilation and three died. CONCLUSIONS: Since the expected prevalence of pregnancy in the source population was 6%, our data suggest that pregnancy greatly increased the likelihood of hospital admission with A(H1N1)pdm09. Pregnant women were less likely than non-pregnant women to have respiratory distress on admission, but severe outcomes were equally likely in both groups.

Comparison of CATs, CURB-65 and PMEWS as triage tools in pandemic influenza admissions to UK hospitals: case control analysis using retrospective data.

Triage tools have an important role in pandemics to identify those most likely to benefit from higher levels of care. We compared Community Assessment Tools (CATs), the CURB-65 score, and the Pandemic Medical Early Warning Score (PMEWS); to predict higher levels of care (high dependency--Level 2 or intensive care--Level 3) and/or death in patients at or shortly after admission to hospital with A/H1N1 2009 pandemic influenza. This was a case-control analysis using retrospectively collected data from the FLU-CIN cohort (1040 adults, 480 children) with PCR-confirmed A/H1N1 2009 influenza. Area under receiver operator curves (AUROC), sensitivity, specificity, positive predictive values and negative predictive values were calculated. CATs best predicted Level 2/3 admissions in both adults [AUROC (95% CI): CATs 0.77 (0.73, 0.80); CURB-65 0.68 (0.64, 0.72); PMEWS 0.68 (0.64, 0.73), p<0.001] and children [AUROC: CATs 0.74 (0.68, 0.80); CURB-65 0.52 (0.46, 0.59); PMEWS 0.69 (0.62, 0.75), p<0.001]. CURB-65 and CATs were similar in predicting death in adults with both performing better than PMEWS; and CATs best predicted death in children. CATs were the best predictor of Level 2/3 care and/or death for both adults and children. CATs are potentially useful triage tools for predicting need for higher levels of care and/or mortality in patients of all ages.

Predictors of clinical outcome in a national hospitalised cohort across both waves of the influenza A/H1N1 pandemic 2009-2010 in the UK.

BACKGROUND: Although generally mild, the 2009-2010 influenza A/H1N1 pandemic caused two major surges in hospital admissions in the UK. The characteristics of patients admitted during successive waves are described. METHODS: Data were systematically obtained on 1520 patients admitted to 75 UK hospitals between May 2009 and January 2010. Multivariable analyses identified factors predictive of severe outcome. RESULTS: Patients aged 5-54 years were over-represented compared with winter seasonal admissions for acute respiratory infection, as were non-white ethnic groups (first wave only). In the second wave patients were less likely to be school age than in the first wave, but their condition was more likely to be severe on presentation to hospital and they were more likely to have delayed admission. Overall, 45% had comorbid conditions, 16.5% required high dependency (level 2) or critical (level 3) care and 5.3% died. As in 1918-1919, the likelihood of severe outcome by age followed a W-shaped distribution. Pre-admission antiviral drug use decreased from 13.3% to 10% between the first and second waves (p=0.048), while antibiotic prescribing increased from 13.6% to 21.6% (p<0.001). Independent predictors of severe outcome were age 55-64 years, chronic lung disease (non-asthma, non-chronic obstructive pulmonary disease), neurological disease, recorded obesity, delayed admission (≥5 days after illness onset), pneumonia, C-reactive protein ≥100 mg/litre, and the need for supplemental oxygen or intravenous fluid replacement on admission. CONCLUSIONS: There were demographic, ethnic and clinical differences between patients admitted with pandemic H1N1 infection and those hospitalised during seasonal influenza activity. Despite national policies favouring use of antiviral drugs, few patients received these before admission and many were given antibiotics.

Use of a human influenza challenge model to assess person-to-person transmission: proof-of-concept study.

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.

Survival of influenza A(H1N1) on materials found in households: implications for infection control.

BACKGROUND: The majority of influenza transmission occurs in homes, schools and workplaces, where many frequently touched communal items are situated. However the importance of transmission via fomites is unclear since few data exist on the survival of virus on commonly touched surfaces. We therefore measured the viability over time of two H1N1 influenza strains applied to a variety of materials commonly found in households and workplaces. METHODOLOGY AND PRINCIPAL FINDINGS: Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity. Virus genome was measured by RT-PCR; plaque assay (for PR8) or fluorescent focus formation (for pandemic H1N1) was used to assess the survival of viable virus. CONCLUSIONS/SIGNIFICANCE: The genome of either virus could be detected on most surfaces 24 h after application with relatively little drop in copy number, with the exception of unsealed wood surfaces. In contrast, virus viability dropped much more rapidly. Live virus was recovered from most surfaces tested four hours after application and from some non-porous materials after nine hours, but had fallen below the level of detection from all surfaces at 24 h. We conclude that influenza A transmission via fomites is possible but unlikely to occur for long periods after surface contamination (unless re-inoculation occurs). In situations involving a high probability of influenza transmission, our data suggest a hierarchy of priorities for surface decontamination in the multi-surface environments of home and hospitals.

Potential role of human challenge studies for investigation of influenza transmission.

The importance of different routes of influenza transmission (including the role of bioaerosols) and the ability of masks and hand hygiene to prevent transmission remain poorly understood. Interest in transmission of influenza has grown as the effectiveness of prevention measures implemented during the 2009 H1N1 pandemic are questioned and as plans to better prepare for the next pandemic are debated. Recent studies of naturally infected patients have encountered difficulties and have fallen short of providing definitive answers. Human challenge studies with influenza virus date back to the 1918 pandemic. In more recent decades they have been undertaken to investigate the efficacy of antiviral agents and vaccines. Could experimental challenge studies, in which volunteers are deliberately infected with influenza virus, provide an alternative approach to the study of transmission? Here, we review the latest intervention studies and discuss the potential of challenge studies to address the remaining gaps in our knowledge.

Pre-admission statin use and in-hospital severity of 2009 pandemic influenza A(H1N1) disease.

BACKGROUND: Statins are drugs that are used to lower plasma cholesterol levels. Recently, contradictory claims have been made about possible additional effects of statins on progression of a variety of inflammatory disorders, including infections. We therefore examined the clinical course of patients admitted to hospital with 2009 pandemic influenza A(H1N1), who were or weren't taking statins at time of admission. METHODS: A retrospective case-control study was performed using the United Kingdom Influenza Clinical Information Network (FLU-CIN) database, containing detailed information on 1,520 patients admitted to participating hospitals with confirmed 2009 pandemic influenza A(H1N1) infection between April 2009 and January 2010. We confined our analysis to those aged over 34 years. Univariate analysis was used to calculate unadjusted odds ratios (OR) and 95 percent confidence intervals (95%CI) for factors affecting progression to severe outcome (high dependency or intensive care unit level support) or death (cases); two multivariable logistic regression models were then established for age and sex, and for age, sex, obesity and "indication for statin" (e.g., heart disease or hypercholesterolaemia). RESULTS: We found no statistically significant association between pre-admission statin use and severity of outcome after adjustment for age and sex [adjusted OR: 0.81 (95% CI: 0.46-1.38); n = 571]. After adjustment for age, sex, obesity and indication for statin, the association between pre-admission statin use and severe outcome was not statistically significant; point estimates are compatible with a small but clinically significant protective effect of statin use [adjusted OR: 0.72 (95% CI: 0.38-1.33)]. CONCLUSIONS: In this group of patients hospitalized with pandemic influenza, a significant beneficial effect of pre-admission statin use on the in-hospital course of illness was not identified. Although the database from which these observations are derived represents the largest available suitable UK hospital cohort, a larger study would be needed to confirm whether there is any benefit in this setting.

Nosocomial pandemic (H1N1) 2009, United Kingdom, 2009-2010.

To determine clinical characteristics of patients hospitalized in the United Kingdom with pandemic (H1N1) 2009, we studied 1,520 patients in 75 National Health Service hospitals. We characterized patients who acquired influenza nosocomially during the pandemic (H1N1) 2009 outbreak. Of 30 patients, 12 (80%) of 15 adults and 14 (93%) of 15 children had serious underlying illnesses. Only 12 (57%) of 21 patients who received antiviral therapy did so within 48 hours after symptom onset, but 53% needed escalated care or mechanical ventilation; 8 (27%) of 30 died. Despite national guidelines and standardized infection control procedures, nosocomial transmission remains a problem when influenza is prevalent. Health care workers should be routinely offered influenza vaccine, and vaccination should be prioritized for all patients at high risk. Staff should remain alert to the possibility of influenza in patients with complex clinical problems and be ready to institute antiviral therapy while awaiting diagnosis during influenza outbreaks.

Clinical and laboratory features distinguishing pandemic H1N1 influenza-related pneumonia from interpandemic community-acquired pneumonia in adults.

BACKGROUND: Early identification of patients with H1N1 influenza-related pneumonia is desirable for the early instigation of antiviral agents. A study was undertaken to investigate whether adults admitted to hospital with H1N1 influenza-related pneumonia could be distinguished clinically from patients with non-H1N1 community-acquired pneumonia (CAP). METHODS: Between May 2009 and January 2010, clinical and epidemiological data of patients with confirmed H1N1 influenza infection admitted to 75 hospitals in the UK were collected by the Influenza Clinical Information Network (FLU-CIN). Adults with H1N1 influenza-related pneumonia were identified and compared with a prospective study cohort of adults with CAP hospitalised between September 2008 and June 2010, excluding those admitted during the period of the pandemic. RESULTS: Of 1046 adults with confirmed H1N1 influenza infection in the FLU-CIN cohort, 254 (25%) had H1N1 influenza-related pneumonia on admission to hospital. In-hospital mortality of these patients was 11.4% compared with 14.0% in patients with inter-pandemic CAP (n=648). A multivariate logistic regression model was generated by assigning one point for each of five clinical criteria: age ≤ 65 years, mental orientation, temperature ≥ 38 °C, leucocyte count ≤ 12 × 10(9)/l and bilateral radiographic consolidation. A score of 4 or 5 predicted H1N1 influenza-related pneumonia with a positive likelihood ratio of 9.0. A score of 0 or 1 had a positive likelihood ratio of 75.7 for excluding it. CONCLUSION: There are substantial clinical differences between H1N1 influenza-related pneumonia and inter-pandemic CAP. A model based on five simple clinical criteria enables the early identification of adults admitted with H1N1 influenza-related pneumonia.