Systematic review of respiratory viral pathogens identified in adults with community-acquired pneumonia in Europe.

Community-acquired pneumonia (CAP) is an important respiratory disease and the fifth leading cause of mortality in Europe. The development of molecular diagnostic tests has highlighted the contributions of respiratory viruses to the aetiology of CAP, suggesting the incidence of viral pneumonia may have been previously underestimated. We performed a systematic review and meta-analysis to describe the overall identification of respiratory viruses in adult patients with CAP in Europe, following PRISMA guidelines (PROSPERO; CRD42016037233). We searched EMBASE, MEDLINE, CINAHL, WHOLIS, COCHRANE library and grey literature sources for relevant studies, and screened these against protocol eligibility criteria. Two researchers performed data extraction and risk of bias assessments, independently, using a piloted form. Results were synthesised narratively, and random effects meta-analyses performed to calculate pooled estimates of effect; heterogeneity was quantified using I2. Twenty-eight studies met inclusion criteria of which 21 were included in the primary meta-analysis. The pooled proportion of patients with identified respiratory viruses was 22.0% (95% CI: 18.0%-27.0%), rising to 29.0% (25.0%-34.0%) in studies where polymerase chain reaction (PCR) diagnostics were performed. Influenza virus was the most frequently detected virus in 9% (7%-12%) of adults with CAP. Respiratory viruses make a substantial contribution to the aetiology of CAP in adult patients in Europe; one or more respiratory viruses are detected in about one quarter of all cases.

Impact of infection control interventions on rates of Staphylococcus aureus bacteraemia in National Health Service acute hospitals, East Midlands, UK, using interrupted time-series analysis.

BACKGROUND: Reducing healthcare-associated infection (HCAI) is a UK national priority. Multiple national and regional interventions aimed at reduction have been implemented in National Health Service acute hospitals, but assessment of their effectiveness is methodologically challenging. AIM: To assess the effectiveness of national and regional interventions undertaken between 2004 and 2008 on rates of meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-sensitive Staphylococcus aureus (MSSA) bacteraemia within acute hospitals in the East Midlands, using interrupted time-series analysis. METHODS: We used segmented regression to compare rates of MRSA and MSSA bacteraemia in the pre-intervention, implementation, and post-intervention phases for combined intervention packages in eight acute hospitals. FINDINGS: Most of the change in MSSA and MRSA rates occurred during the implementation phase. During this phase, there were significant downward trends in MRSA rates for seven of eight acute hospital groups; in four, this was a steeper quarter-on-quarter decline compared with the pre-intervention phase, and, in one, an upward trend in the pre-intervention phase was reversed. Regarding MSSA, there was a significant positive effect in four hospital groups: one upward trend during the pre-intervention phase was reversed, two upward trends plateaued, and in one hospital group an indeterminate trend decreased significantly. However, there were significant increasing trends in quarterly MSSA rates in four hospital groups during the implementation or post-intervention periods. CONCLUSION: The impact of interventions varied by hospital group but the overall results suggest that national and regional campaigns had a beneficial impact on MRSA and MSSA bacteraemia within the East Midlands.

Neuraminidase inhibitors: who, when, where?

Although the neuraminidase inhibitors (NIs), oseltamivir and zanamivir were first licensed in 1999, their clinical effectiveness is still hotly debated. Two rigorous systematic reviews and meta-analyses of the data from clinical trials conducted in community settings against relatively benign influenza, both suggest that reductions in symptom duration are extremely modest, under one day. Whilst one of these reviews could find no evidence of reductions in complications, the most recent review reported clinically meaningful and statistically significant reductions in the likelihood of requiring antibiotics (44%) and hospitalizations (63%) in adult patients with confirmed influenza, treated with oseltamivir. A further meta-analysis of observational data from the 2009 influenza A(H1N1) pandemic suggested that, in hospitalised patients, NIs significantly reduced mortality in adults by 25% overall, and by 62% if started within 48 hours of symptom onset, compared with no treatment. But, the effectiveness of NIs in children is far less clear. Taken together, these data suggest that NIs should be reserved for patients with influenza who are at high-risk of complications, or when clinically assessed found to be markedly unwell, or rapidly deteriorating. In such patients, treatment should be initiated empirically, as soon as possible, preferably with follow-on virological confirmation.

Effect of ethnicity on care pathway and outcomes in patients hospitalized with influenza A(H1N1)pdm09 in the UK.

Data were extracted from the case records of UK patients admitted with laboratory-confirmed influenza A(H1N1)pdm09. White and non-White patients were characterized by age, sex, socioeconomic status, pandemic wave and indicators of pre-morbid health status. Logistic regression examined differences by ethnicity in patient characteristics, care pathway and clinical outcomes; multivariable models controlled for potential confounders. Whites (n = 630) and non-Whites (n = 510) differed by age, socioeconomic status, pandemic wave of admission, pregnancy, recorded obesity, previous and current smoking, and presence of chronic obstructive pulmonary disease. After adjustment for a priori confounders non-Whites were less likely to have received pre-admission antibiotics [adjusted odds ratio (aOR) 0·43, 95% confidence interval (CI) 0·28-0·68, P < 0·001) but more likely to receive antiviral drugs as in-patients (aOR 1·53, 95% CI 1·08-2·18, P = 0·018). However, there were no significant differences by ethnicity in delayed admission, severity at presentation for admission, or likelihood of severe outcome.

Guidance on the use of respiratory and facial protection equipment.

Infectious micro-organisms may be transmitted by a variety of routes, and some may be spread by more than one route. Respiratory and facial protection is required for those organisms that are usually transmitted via the droplet/airborne route, or when airborne particles have been artificially created, such as during 'aerosol-generating procedures'. A range of personal protective equipment that provides different degrees of facial and respiratory protection is available. It is apparent from the recent experiences with severe acute respiratory syndrome and pandemic (H1N1) 2009 influenza that healthcare workers may have difficulty in choosing the correct type of facial and respiratory protection in any given clinical situation. To address this issue, the Scientific Development Committee of the Healthcare Infection Society established a short-life working group to develop guidance. The guidance is based upon a review of the literature, which is published separately, and expert consensus.

Virus shedding and environmental deposition of novel A (H1N1) pandemic influenza virus: interim findings.

BACKGROUND: The relative importance of different routes of influenza transmission, including the role of bioaerosols, and ability of masks and/or hand hygiene to prevent transmission, remains poorly understood. Current evidence suggests that infectious virus is not typically released from adults after 5 days of illness, however, little is known about the extent to which virus is deposited by infected individuals into the environment and whether deposited virus has the ability to infect new hosts. Further information about the deposition of viable influenza virus in the immediate vicinity of patients with pandemic influenza is fundamental to our understanding of the routes and mechanisms of transmission. OBJECTIVES: To collect data on patients infected with pandemic H1N1 2009 (swine flu). Primary objectives were to correlate the amount of virus detected in a patient's nose with that recovered from his/her immediate environment, and with symptom duration and severity. Secondary objectives were to describe virus shedding and duration according to major patient characteristics: adults versus children, and those with mild illness (community patients) versus those with more severe disease (hospitalised patients). METHODS: Adults and children, both in hospital and from the community, who had symptoms of pandemic H1N1 infection, were enrolled and visited every day during follow-up for a maximum of 12 days. Symptom data was collected and samples were taken, including nose swabs and swabs from surfaces and objects around patients. Samples of air were obtained using validated sampling equipment. The samples were tested for the presence of pandemic H1N1 virus, using polymerase chain reaction (PCR) to detect virus genome and an immunofluorescence technique to detect viable virus. RESULTS: Forty-three subjects were followed up, and 19 of them were subsequently proven to be infected with pandemic H1N1 virus. The median duration of virus shedding from the 19 infected cases was 6 days when detection was performed by PCR, and 3 days when detection was performed by a culture technique. Over 30% of cases remained potentially infectious for at least 5 days. Only 0.5% of all community and none of the hospital swabs taken revealed virus on surfaces. Five subjects had samples of the air around them collected and virus was detected by PCR from four; some of the air particles in which virus was detected were small enough to be inhaled and deposited deep in the lungs. LIMITATION: Small number of subjects recruited. CONCLUSIONS: The finding that over 30% of infected individuals have infectious virus in their noses for 5 days or more has infection control implications. The data suggest that contact transmission of pandemic influenza via fomites may be less important than previously thought, but transmission via bioaerosols at short range may be possible, meaning that high-level personal protective equipment may be needed by health-care workers when attending patients with pandemic influenza. Further work is being undertaken to consolidate these findings, as they have important potential implications for the protection of health-care workers and the formulation of advice to households, nationally and internationally.

Risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza: United Kingdom first wave (May-September 2009).

BACKGROUND: During the first wave of pandemic H1N1 influenza in 2009, most cases outside North America occurred in the UK. The clinical characteristics of UK patients hospitalised with pandemic H1N1 infection and risk factors for severe outcome are described. METHODS: A case note-based investigation was performed of patients admitted with confirmed pandemic H1N1 infection. RESULTS: From 27 April to 30 September 2009, 631 cases from 55 hospitals were investigated. 13% were admitted to a high dependency or intensive care unit and 5% died; 36% were aged <16 years and 5% were aged > or = 65 years. Non-white and pregnant patients were over-represented. 45% of patients had at least one underlying condition, mainly asthma, and 13% received antiviral drugs before admission. Of 349 with documented chest x-rays on admission, 29% had evidence of pneumonia, but bacterial co-infection was uncommon. Multivariate analyses showed that physician-recorded obesity on admission and pulmonary conditions other than asthma or chronic obstructive pulmonary disease (COPD) were associated with a severe outcome, as were radiologically-confirmed pneumonia and a raised C-reactive protein (CRP) level (> or = 100 mg/l). 59% of all in-hospital deaths occurred in previously healthy people. CONCLUSIONS: Pandemic H1N1 infection causes disease requiring hospitalisation of previously fit individuals as well as those with underlying conditions. An abnormal chest x-ray or a raised CRP level, especially in patients who are recorded as obese or who have pulmonary conditions other than asthma or COPD, indicate a potentially serious outcome. These findings support the use of pandemic vaccine in pregnant women, children <5 years of age and those with chronic lung disease.

Pandemic (H1N1) 2009 influenza in the UK: clinical and epidemiological findings from the first few hundred (FF100) cases.

The UK was one of few European countries to document a substantial wave of pandemic (H1N1) 2009 influenza in summer 2009. The First Few Hundred (FF100) project ran from April-June 2009 gathering information on early laboratory-confirmed cases across the UK. In total, 392 confirmed cases were followed up. Children were predominantly affected (median age 15 years, IQR 10-27). Symptoms were mild and similar to seasonal influenza, with the exception of diarrhoea, which was reported by 27%. Eleven per cent of all cases had an underlying medical condition, similar to the general population. The majority (92%) were treated with antiviral drugs with 12% reporting adverse effects, mainly nausea and other gastrointestinal complaints. Duration of illness was significantly shorter when antivirals were given within 48 h of onset (median 5 vs. 9 days, P=0.01). No patients died, although 14 were hospitalized, of whom three required mechanical ventilation. The FF100 identified key clinical and epidemiological characteristics of infection with this novel virus in near real-time.

An assessment of the effect of statin use on the incidence of acute respiratory infections in England during winters 1998-1999 to 2005-2006.

Statins reduce cardiovascular mortality and related risks associated with pneumonia suggesting potentially beneficial use in influenza pandemics. We investigated the effect of current statin use on acute respiratory infections in primary care. Data from anonymized electronic medical records of persons aged 45 years were examined for statin use, chronic morbidity, respiratory diagnoses, vaccination procedures, and immune suppression. Logistic regression models were used to calculate odds ratios (ORs) for statin users vs. non-users in respiratory infection outcomes. A total of 329 881 person-year observations included 18% statin users and 46% influenza vaccinees. Adjusted ORs for statin users vs. non-users were: influenza-like illness, 1.05 (95% CI 0.92-1.20); acute bronchitis, 1.08 (95% CI 1.01-1.15); pneumonia, 0.91 (95% CI 0.73-1.13); all acute respiratory infections, 1.03 (95% CI 0.98-1.07); and urinary tract infections, 0.91 (95% CI 0.85-0.98). We found no benefit in respiratory infection outcomes attributable to statin use, although uniformly higher ORs in non-vaccinated statin users might suggest synergism between statins and influenza vaccination.

Observational study to investigate vertically acquired passive immunity in babies of mothers vaccinated against H1N1v during pregnancy.

OBJECTIVE: The primary objective was to determine the proportion of babies who acquired passive immunity to A/H1N1v, born to mothers who accepted vaccination as part of the national vaccination programme while pregnant (during the second and/or third trimesters) against the novel A/H1N1v influenza virus (exposed group) compared with unvaccinated (unexposed) mothers. DESIGN: An observational study at three sites in the UK. The purpose was to determine if mothers immunised against A/H1N1v during the pandemic vaccination period transferred that immunity to their child in utero. SETTING: Three sites in the UK [Queen's Medical Centre, Nottingham; City Hospital, Nottingham (both forming University Hospitals Nottingham), and Leicester Royal Infirmary (part of University Hospitals Leicester)]. PARTICIPANTS: All pregnant women in the second and third trimester presenting at the NHS hospitals above to deliver were eligible to participate in the study. Women were included regardless of age, social class, ethnicity, gravida and parity status, past and current medical history (including current medications), ethnicity, mode of delivery and pregnancy outcome (live/stillbirth). INTERVENTIONS: At enrolment, participants provided written consent and completed a questionnaire. At parturition, venous cord blood was obtained for serological antibody analysis. Serological analysis was undertaken by the Respiratory Virus Unit (RVU), Health Protection Agency (HPA) Centre for Infections, London. MAIN OUTCOME MEASURES: The primary end point in the study was the serological results of the cord blood samples for immunity to A/H1N1v. Regarding a suitable threshold for the determination of a serological response consistent with clinical protection, this issue is somewhat complex for pandemic influenza. The European Medicines Agency (EMEA) Committee for Human Medicinal Products (CHMP) judges that a haemagglutination inhibition (HI) titre of 1 : 40 is an acceptable threshold. However, this level was set in the context of licensing plain trivalent seasonal vaccine, where a titre of 1 : 40 is but one of several related immunogenicity criteria, and supported by paired sera capable of demonstrating a fourfold rise in antibody titre in response to vaccination. The current study mainly investigated the effects of an AS03-adjuvanted monovalent vaccine, and it was not possible to obtain paired sera where the initial sample was taken before vaccination (in vaccinated subjects). Of possibly greater relevance is the fact that it has been established from the study of early outbreaks of pandemic influenza in secondary schools in the UK (HPA, unpublished observations) that an HI antibody titre of 1 : 32 seems to be the threshold for a humoral response to 'wild-type' A/H1N1v infection. On that basis, a threshold of 1 : 32 is at least as appropriate as one of 1 : 40, especially in unvaccinated individuals. Given the difficulties that would accrue by applying thresholds of 1 : 32 in unvaccinated patients and 1 : 40 in vaccinated patients, we have therefore applied a threshold of 1 : 32 and 1 : 40, to increase the robustness of our findings. Differences arising are described. A microneutralisation (MN) titre of 1 : 40 may be also used, although it is not part of the CHMP criteria for vaccine licensure. Nonetheless, we utilised this analysis as a secondary end point, based on a conservative threshold of 1 : 60. RESULTS: Reverse cumulative distribution percentage curves for haemagglutinin dilution and MN titres demonstrate background immunity in babies of unvaccinated mothers of 25%-30%. Humoral immunity in babies of vaccinated mothers was present in 80% of the group. The difference in positive immunity between the babies of unvaccinated and vaccinated mothers was statistically significant (chi-squared test, p < 0.001). CONCLUSIONS: Our findings reveal a highly significant difference in HI titres between babies born to mothers vaccinated with pandemic-specific vaccine against A/H1N1v during the 2009-10 pandemic period. The subjects recruited were comparable from a baseline perspective and thus do not represent different groups that otherwise could have introduced bias into the study. Continued circulation of 2009 A/H1N1-like viruses is uncertain, but is possible as seasonal influenza in years to come. It is possible that future seasonal waves may display increased virulence. Given the adverse outcomes experienced for a small proportion of pregnant women during the influenza pandemic of 2009-10, this study provides useful evidence to support vaccination in pregnancy to protect both the mother and baby. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A randomised, partially observer blind, multicentre, head-to-head comparison of a two-dose regimen of Baxter and GlaxoSmithKline H1N1 pandemic vaccines, administered 21 days apart.

OBJECTIVES: To evaluate the immunogenicity of a two-dose schedule of Baxter cell-cultured, non-adjuvanted, whole-virion H1N1 vaccine, and GlaxoSmithKline AS03(A)-adjuvanted split-virion H1N1 vaccine with respect to the EU Committee for Medicinal Products for Human Use (CHMP) and the US Food and Drug Administration (FDA) licensing criteria. DESIGN: An age-stratified, randomised, observer-blind, parallel-group, multicentre controlled trial was carried out in volunteers aged ≥ 18-44, ≥ 45-64 and ≥ 65 years. SETTING: Three teaching hospitals in the UK (Leicester Royal Infirmary, Leicester; Nottingham City Hospital, Nottingham; and Royal Hallamshire Hospital, Sheffield). PARTICIPANTS: Three hundred and forty-seven subjects were identified and randomised to AS03(A)-adjuvanted split-virion H1N1 vaccine or whole-virion (WV) vaccine in age groups [≥ 18-44 years (n = 140), ≥ 45-64 years (n = 136) and ≥ 65 years (n = 71)]. INTERVENTIONS: Vaccine was administered by intramuscular injection into the deltoid muscle of the non-dominant arm. One hundred and seventy-five randomised subjects were allocated AS03(A)-adjuvanted split H1N1 vaccine; one hundred and sixty-nine subjects had a second dose of the same vaccine 21 days later. One hundred and seventy-two subjects were allocated WV vaccine; one hundred and seventy-one subjects had a second dose of the same vaccine 21 days later. Serum samples for antibody measurements were collected on days 0 (before the first vaccination), 7, 14, 21 (before the second vaccination), 28, 35, 42 and 180. Subjects were observed for local and systemic reactions for 30 minutes after each injection, and for the next 7 days they recorded, in self-completed diaries, the severity of solicited local (pain, bruising, erythema and swelling) and systemic symptoms (chills, malaise, muscle aches, nausea and headache), oral temperature and use of analgesic medications. MAIN OUTCOME MEASURES: Vaccine immunogenicity using the CHMP and the FDA licensing criteria. Antibody titres were measured using haemagglutination inhibition (HI) and microneutralisation (MN) assays at baseline and 7, 14 and 21 days after each vaccination and at day 180. The three immunogenicity criteria end points were the seroprotection rate, the seroconversion rate and the mean-fold titre elevation. RESULTS: Both vaccine doses were given in 340 subjects (98%). Data from 680 (99%) of 687 issued diary cards were returned. Sera were obtained from 340 (98.0%), 333 (96.0%), 341 (98.3%), 331 (95.4%), 329 (94.8%) and 332 (95.7%) subjects on days 7, 14, 21, 28, 35 and 42, respectively. Three hundred and forty-six and 345 subjects were included in the safety and immunogenicity analyses, respectively. Prevaccination antibody was detected by HI (titre ≥ 1 : 8) and MN (titre ≥ 1 : 10) in 14% and 31% of subjects, respectively. Among the 298 (85.9%) subjects without baseline antibody on HI assay, a titre of ≥ 1 : 40 (seroprotection) was achieved after a single dose of AS03(A)-adjuvanted vaccine and WV vaccine by day 21 in 93.0% and 65.5%, respectively, of subjects between 18 and 44 years, 76.4% and 36.1% of subjects between 45 and 64 years, and 53.1% and 30.0% of subjects ≥ 65 years. Among all 347 subjects, a titre of ≥ 1 : 40 was achieved after a single dose of AS03(A)-adjuvanted vaccine and WV vaccine by day 21 in 94.0% and 71.4%, respectively, of subjects between 18 and 44 years, 77.3% and 38.8% of subjects between 45 and 64 years, and 51.4% and 32.4% of subjects ≥ 65 years. The age-adjusted odds ratio (OR) for adjuvanted compared with WV vaccine, in terms of seroprotection, was 4.42 [95% confidence interval (CI) 2.63 to 7.44, p < 0.001]. On day 42, among subjects without baseline antibody on HI assay, a titre of ≥ 1 : 40 was achieved after the second dose of AS03(A)-adjuvanted vaccine and WV vaccine by 100% and 67.9%, respectively, of subjects between 18 and 44 years, 89.3% and 41% of subjects between 45 and 64 years, and 76.5% and 34.5% of subjects ≥ 65 years. Among all 347 subjects, a titre of ≥ 1 : 40 was achieved on day 42 after the second dose of AS03(A)-adjuvanted vaccine and WV vaccine in 100% and 73.1%, respectively, of subjects between 18 and 44 years, 90.8% and 43.9% of subjects between 45 and 64 years, and 75.7% and 36.4% of subjects ≥ 65 years. The age-adjusted OR for adjuvanted vaccine compared with WV vaccine, in terms of seroprotection, was 11.21 (95% CI 5.80 to 21.64, p < 0.001). Age-related decline in antibody response occurred after both doses of both vaccines. WV vaccine was associated with fewer local and systemic reactions and lower immune responses than was AS03(A)-adjuvanted vaccine. The most frequent solicited local event was pain, reported by 28% and 76% of subjects after either dose of WV or adjuvanted vaccine, respectively (OR 7.71, 95% CI 4.48 to 13.24, p < 0.0001). The most common systemic event was myalgia, reported by 24% and 49% of subjects after either dose of WV or adjuvanted vaccine (OR 2.99, 95% CI 1.86 to 4.80, p < 0.0001). CONCLUSIONS: AS03(A)-adjuvanted 2009 H1N1 vaccine is more immunogenic and provides greater antigen-sparing capacity than WV 2009 H1N1 vaccine. TRIAL REGISTRATION: Current Controlled Trials ISRCTN92328241. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 14, No. 55. See the HTA programme website for further project information.

Personal protective equipment in an influenza pandemic: a UK simulation exercise.

There is limited experience of both operational and financial impacts that adoption of UK pandemic influenza infection control guidance will have on the use of personal protective equipment (PPE), patients and staff. We attempted to assess these issues from a live exercise in a hospital in north-west England. During this 24h exercise, all staff on an acute general medical ward wore PPE and adopted the procedures described in the UK pandemic influenza infection control guidance. Teams of infection control nurses observed and recorded staff behaviour and practice throughout the exercise, including staff attitudes towards the use of PPE. Although World Health Organization recommendations on the likely use of high-level PPE (FFP3 respirators) proved to be excessive, more gloves and surgical masks were used than expected. Despite pre-exercise training, many staff lacked confidence in using PPE and following infection control measures. They found PPE uncomfortable, with even basic tasks taking longer than usual. Large quantities of clinical waste were generated: an additional 12 bags (570 L) per day. The estimates of PPE usage within this exercise challenge assumptions that large amounts of high-level PPE are required, with significant implications for healthcare budgets. A programme of ongoing infection control education is needed. Healthcare in a pandemic situation is not simply a case of applying pandemic influenza infection control guidance to current practice; hospitals need to consider changing the way care and services are delivered.

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.

Timing of monoclonal antibody for seasonal RSV prophylaxis in the United Kingdom.

Respiratory syncytial virus (RSV) infection produces more severe disease and increased hospitalization rates in high-risk babies. The monoclonal antibody palivizumab offers protection against complications, and the first of five monthly doses should be administered before the onset of community RSV activity. However, the required real-time prediction of this onset is problematic. We attempted to identify seasonal RSV patterns by retrospectively examining 10 years of laboratory reports for RSV and clinical episode reports for certain respiratory presentations in both primary and secondary care. Analysis of hospital laboratory reports, incidence of acute bronchitis in primary care, and hospital admissions for acute bronchitis and bronchiolitis in young children revealed a consistent increase in RSV activity during week 43 each year. Promptly commencing prophylaxis during the second week of each October (week 42) would precede the onset of the RSV season in the United Kingdom, and provide coverage until its decline in mid-March.

Uptake and acceptability of influenza vaccination in day nursery children.

Preschoolers play an important role in the transmission of influenza, and suffer significant morbidity. Paediatric vaccination could prevent serious outcomes and offer broader societal benefits. This study explored parental views on influenza and paediatric vaccination and determined the uptake of a nursery-based vaccination programme for infants aged 6-23 months. Children were offered two doses of inactivated vaccine in 2004/05, and a single dose at the start of the 2005/06 season. An uptake rate of 11% (60/535) was achieved with 83% (50/60) of participants completing the programme. Semi-structured interviews were conducted with 10 parents. Thematic analysis of the data informed the development of a questionnaire. This was distributed to 650 parents, with children aged 6-30 months attending one of the 18 supporting nurseries. A response rate of 13% (83/650) was achieved. The low uptake rate achieved in the programme and findings from the interviews/questionnaire suggest parents were not convinced about the seriousness of paediatric influenza. Indeed, over two-thirds (55/81) questioned the necessity for an annual vaccination. Parents found it difficult to differentiate influenza from other respiratory illnesses, and expressed concerns about the need for annual injections and vaccine safety. Paediatric vaccination to increase herd immunity was held in balance with the notion that children should only be vaccinated if they are the main beneficiaries. Parental education on the burden of childhood influenza, on the direct benefits of influenza vaccination, and on indirect benefits to society is a necessity for a successful paediatric vaccination programme.

Costs of running a universal adolescent hepatitis B vaccination programme.

In the first UK study to examine feasibility and acceptability of universal adolescent hepatitis B vaccination, the costs associated with the administration and uptake (80.2 and 89.3% for three doses and at least two doses, respectively), of a three-dose regimen in pupils in Glasgow schools (2001/2002) were measured. These data were used to estimate the economic outlay for the delivery of a routine, ongoing three-dose and two-dose hepatitis B vaccine programme in schools. Vaccine, accounting for almost 70% of the overall costs, was the largest cost item for both the pilot and routine programmes, using either regimen. However, the ongoing, two-dose regimen was the cheapest option in this analysis, irrespective of vaccine price. Cost data from this study may be useful for other countries wishing to implement a similar programme.

Influenza burden of illness, diagnosis, treatment, and prevention: what is the evidence in children and where are the gaps?

Influenza is a disease of global public health significance. Traditionally the emphasis has been on adult disease because of the impact of influenza related mortality in the elderly and other high risk groups. However, it is becoming increasingly better recognised that young children suffer considerable morbidity from influenza. There are also potential consequences for siblings, parents, other carers, and extended family members in terms of secondary infections and carer leave. Influenza infection in childhood could be effectively prevented through vaccination. However, the United States is the only industrialised country currently recommending universal influenza vaccination for young children (between the ages of 6 and 23 months), as opposed to vaccinating only those with high risk conditions.