Age-Specific Estimates of Respiratory Syncytial Virus-Associated Hospitalizations in 6 European Countries: A Time Series Analysis.

BACKGROUND: Knowledge on age-specific hospitalizations associated with RSV infection is limited due to limited testing, especially in older children and adults in whom RSV infections are not expected to be severe. Burden estimates based on RSV coding of hospital admissions are known to underestimate the burden of RSV. We aimed to provide robust and reliable age-specific burden estimates of RSV-associated hospital admissions based on data on respiratory infections from national health registers and laboratory-confirmed cases of RSV. METHODS: We conducted multiseason regression analysis of weekly hospitalizations with respiratory infection and weekly laboratory-confirmed cases of RSV and influenza as covariates, based on national health registers and laboratory databases across 6 European countries. The burden of RSV-associated hospitalizations was estimated by age group, clinical diagnosis, and presence of underlying medical conditions. RESULTS: Across the 6 European countries, hospitalizations of children with respiratory infections were clearly associated with RSV, with associated proportions ranging from 28% to 60% in children younger than 3 months and we found substantial proportions of admissions to hospital with respiratory infections associated with RSV in children younger than 3 years. Associated proportions were highest among hospitalizations with ICD-10 codes of "bronchitis and bronchiolitis." In all 6 countries, annual incidence of RSV-associated hospitalizations was >40 per 1000 persons in the age group 0-2 months. In age group 1-2 years the incidence rate ranged from 1.3 to 10.5 hospitalizations per 1000. Adults older than 85 years had hospitalizations with respiratory infection associated to RSV in all 6 countries although incidence rates were low. CONCLUSIONS: Our findings highlight the substantial proportion of RSV infections among hospital admissions across different ages and may help public health professionals and policy makers when planning prevention and control strategies. In addition, our findings provide valuable insights for health care professionals attending to both children and adults presenting with symptoms of viral respiratory infections.

A Systematic Review of European Clinical Practice Guidelines for Respiratory Syncytial Virus Prophylaxis.

BACKGROUND: Since the widespread adoption of palivizumab prophylaxis in Europe, there have been a number of clinical practice guidelines (CPGs) published for the prevention of respiratory syncytial virus (RSV) infection in children. The aim of this systematic review was to identify CPGs for the prevention of RSV infection across Europe. METHODS: We performed a systematic literature search and contacted European influenza and respiratory virus networks and public health institutions, to identify national CPGs for the prevention of RSV infection. The Reporting Items for practice Guidelines in Healthcare (RIGHT) Statement checklist was applied to extract data and review the quality of reporting. RESULTS: A total of 20 national CPGs were identified, all published between 2000 and 2018. The greatest discrepancy between guidelines was the recommendations for palivizumab prophylaxis for premature infants, with recommendations varying by gestational age. All guidelines recommended or considered the use of palivizumab in infants with bronchopulmonary dysplasia, 85% (n = 17) in children with congenital heart disease (CHD), and 60% (n = 12) in children with severe combined immunodeficiency. CONCLUSIONS: We recommend that agencies publishing RSV prevention guidelines adopt the RIGHT reporting requirements when updating these guidelines to improve the presentation of the evidence-base for decisions.

Respiratory Syncytial Virus-Associated Hospital Admissions and Bed Days in Children <5 Years of Age in 7 European Countries.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections (RTIs) in young children. High-quality country-specific estimates of bed days and length of stay (LOS) show the population burden of RSV-RTI on secondary care services and the burden among patients, and can be used to inform RSV immunization implementation decisions. METHODS: We estimated the hospital burden of RSV-associated RTI (RSV-RTI) in children under 5 years in 7 European countries (Finland, Denmark, Norway, Scotland, England, the Netherlands, and Italy) using routinely collected hospital databases during 2001-2018. We described RSV-RTI admission rates during the first year of life by birth month and assessed their correlation with RSV seasonality in 5 of the countries (except for England and Italy). We estimated average annual numbers and rates of bed days for RSV-RTI and other-pathogen RTI, as well as the hospital LOS. RESULTS: We found that infants born 2 months before the peak month of RSV epidemics more frequently had the highest RSV-RTI hospital admission rate. RSV-RTI hospital episodes accounted for 9.9-21.2 bed days per 1000 children aged <5 years annually, with the median (interquartile range) LOS ranging from 2 days (0.5-4 days) to 4 days (2-6 days) between countries. Between 70% and 89% of these bed days were in infants aged <1 year, representing 40.3 (95% confidence interval [CI], 40.1-40.4) to 91.2 (95% CI, 90.6-91.8) bed days per 1000 infants annually. The number of bed days for RSV-RTI was higher than that for RTIs associated with other pathogens in infants aged <1 year, especially in those <6 months. CONCLUSIONS: RSV disease prevention therapies (monoclonal antibodies and maternal vaccines) for infants could help prevent a substantial number of bed days due to RSV-RTI. "High-risk" birth months should be considered when developing RSV immunization schedules. Variation in LOS between countries might reflect differences in hospital care practices.

Increasing burden of viral bronchiolitis in the pediatric intensive care unit; an observational study.

PURPOSE: Viral bronchiolitis is a major cause of pediatric intensive care unit (PICU) admission. Insight in the trends of bronchiolitis-associated PICU admissions is limited, but imperative for future PICU resource and capacity planning. MATERIALS AND METHODS: We retrospectively studied trends in PICU admissions for bronchiolitis in six European sites, including three full national registries, between 2000 and 2019 and calculated population-based estimates per 100,000 children where appropriate. Information concerning risk factors for severe disease and use of invasive mechanical ventilation was also collected when available. RESULTS: In total, there were 15,606 PICU admissions for bronchiolitis. We observed an increase in the annual number, rate and estimates per 100,000 children of PICU admissions for bronchiolitis at all sites over the last two decades, while the proportion of patients at high risk for severe disease remained relatively stable. CONCLUSIONS: The international increased burden of bronchiolitis for the PICU is concerning, and warrants further international attention and investigation.

Respiratory Syncytial Virus-Associated Hospital Admissions in Children Younger Than 5 Years in 7 European Countries Using Routinely Collected Datasets.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infection (RTI) in young children. Registries provide opportunities to explore RSV epidemiology and burden. METHODS: We explored routinely collected hospital data on RSV in children aged < 5 years in 7 European countries. We compare RSV-associated admission rates, age, seasonality, and time trends between countries. RESULTS: We found similar age distributions of RSV-associated hospital admissions in each country, with the highest burden in children < 1 years old and peak at age 1 month. Average annual rates of RTI admission were 41.3-112.0 per 1000 children aged < 1 year and 8.6-22.3 per 1000 children aged < 1 year. In children aged < 5 years, 57%-72% of RTI admissions with specified causal pathogen were coded as RSV, with 62%-87% of pathogen-coded admissions in children < 1 year coded as RSV. CONCLUSIONS: Our results demonstrate the benefits and limitations of using linked routinely collected data to explore epidemiology and burden of RSV. Our future work will use these data to generate estimates of RSV burden using time-series modelling methodology, to inform policymaking and regulatory decisions regarding RSV immunization strategy and monitor the impact of future vaccines.