Burden of Respiratory Syncytial Virus in the European Union:estimation of RSV-associated hospitalizations in children under 5 years

Background No overall estimate of respiratory syncytial virus (RSV)-associated hospitalizations in children aged under 5 years has been published for the European Union (EU). We aimed to estimate the RSV hospitalization burden in children aged under 5 years in EU countries and Norway, by age group. Methods We collated national RSV-associated hospitalization estimates calculated using linear regression models via the RESCEU project for Denmark, England, Finland, Norway, the Netherlands, and Scotland, 2006-2018. Additional estimates were obtained from a systematic review. Using multiple imputation and nearest neighbor matching methods, we estimated overall RSV-associated hospitalizations and rates in the EU. Results Additional estimates for 2 countries (France and Spain) were found in the literature. In the EU, an average of 245 244 (95% confidence interval [CI], 224 688-265 799) yearly hospital admissions with a respiratory infection per year were associated with RSV in children aged under 5 years, with most cases occurring among children aged under 1 year (75%). Infants aged under 2 months represented the most affected group (71.6 per 1000 children; 95% CI, 66.6-76.6). Conclusions Our findings will help support decisions regarding prevention efforts and represent an important benchmark to understand changes in the RSV burden following the introduction of RSV immunization programs in Europe.The study estimated that an average of 245 244 children aged under 5 years are hospitalized annually due to RSV in the EU, with the highest hospitalization rates in children aged less than 2 months (71.6 per 1000 children)

Current practices for respiratory syncytial virus surveillance across the EU/EEA Member States, 2017

Background: Respiratory syncytial virus (RSV) is a major contributor to lower respiratory tract infections worldwide and several vaccine candidates are currently in development. Following vaccine introduction, reliable RSV surveillance should enable monitoring of vaccination impact. Data on the RSV disease burden in the European Union and European Economic Area (EU/EEA) are sparse. Aim: The aim of this study was to gather knowledge on current practices of national RSV surveillance in the EU/EEA. Methods: National Coordinators and National Focal Points for Influenza (epidemiologists and virologists) from the EU/EEA countries (n = 31) were invited to participate in an online survey in August and September 2017. The questionnaire covered questions on epidemiological and laboratory aspects of RSV surveillance. Results: All EU/EEA countries except Liechtenstein replied to the survey. Eighteen countries reported to have a sentinel surveillance system, 26 countries a non-sentinel surveillance system and three countries to have neither. RSV data collection was mostly done within the context of influenza surveillance. A wide range of diagnostic and characterisation assays was used for the detection of RSV. Discussion: The majority of EU/EEA countries have some surveillance for RSV in place. The prevailing integration of RSV surveillance into the existing influenza sentinel surveillance system may lead to under-reporting of RSV. The documented variations in existing RSV surveillance systems and their outputs indicate that there is scope for developing guidelines on establishing comparable methods and outcomes for RSV surveillance across the EU/EEA, to ensure the availability of a consistent evidence base for assessing future vaccination programmes.S

Recommendations for respiratory syncytial virus surveillance at national level

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections and hospitalisations among young children and is globally responsible for many deaths in young children, especially in infants aged <6 months. Furthermore, RSV is a common cause of severe respiratory disease and hospitalisation among older adults. The development of new candidate vaccines and monoclonal antibodies highlights the need for reliable surveillance of RSV. In the European Union (EU), no up-to-date general recommendations on RSV surveillance are currently available. Based on outcomes of a workshop with 29 European experts in the field of RSV virology, epidemiology and public health, we provide recommendations for developing a feasible and sustainable national surveillance strategy for RSV that will enable harmonisation and data comparison at the European level. We discuss three surveillance components: active sentinel community surveillance, active sentinel hospital surveillance and passive laboratory surveillance, using the EU acute respiratory infection and World Health Organization (WHO) extended severe acute respiratory infection case definitions. Furthermore, we recommend the use of quantitative reverse transcriptase PCR-based assays as the standard detection method for RSV and virus genetic characterisation, if possible, to monitor genetic evolution. These guidelines provide a basis for good quality, feasible and affordable surveillance of RSV. Harmonisation of surveillance standards at the European and global level will contribute to the wider availability of national level RSV surveillance data for regional and global analysis, and for estimation of RSV burden and the impact of future immunisation programmes

New perspectives on respiratory syncytial virus surveillance at the national level:lessons from the COVID-19 pandemic

Learning from the COVID-19 pandemic and considering the effects of this pandemic, we provide recommendations that can guide towards sustainable RSV surveillance with the potential to be integrated into the broader perspective of respiratory surveillance. https://bit.ly/40TsO0

Longevity and Composition of Cellular Immune Responses Following Experimental Plasmodium falciparum Malaria Infection in Humans

Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFNγ) production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation to exposure are difficult to study and data about the persistence of such responses are controversial. Here we assess the longevity and composition of cellular immune responses following experimental malaria infection in human volunteers. We conducted a longitudinal study of cellular immunological responses to sporozoites (PfSpz) and asexual blood-stage (PfRBC) malaria parasites in naïve human volunteers undergoing single (n = 5) or multiple (n = 10) experimental P. falciparum infections under highly controlled conditions. IFNγ and interleukin-2 (IL-2) responses following in vitro re-stimulation were measured by flow-cytometry prior to, during and more than one year post infection. We show that cellular responses to both PfSpz and PfRBC are induced and remain almost undiminished up to 14 months after even a single malaria episode. Remarkably, not only ‘adaptive’ but also ‘innate’ lymphocyte subsets contribute to the increased IFNγ response, including αβT cells, γδT cells and NK cells. Furthermore, results from depletion and autologous recombination experiments of lymphocyte subsets suggest that immunological memory for PfRBC is carried within both the αβT cells and γδT compartments. Indeed, the majority of cytokine producing T lymphocytes express an CD45RO+ CD62L- effector memory (EM) phenotype both early and late post infection. Finally, we demonstrate that malaria infection induces and maintains polyfunctional (IFNγ+IL-2+) EM responses against both PfRBC and PfSpz, previously found to be associated with protection. These data demonstrate that cellular responses can be readily induced and are long-lived following infection with P. falciparum, with a persisting contribution by not only adaptive but also (semi-)innate lymphocyte subsets. The implications hereof are positive for malaria vaccine development, but focus attention on those factors potentially inhibiting such responses in the field

Sex differences in COVID-19 mortality in the Netherlands.

INTRODUCTION: Since the first reports of COVID-19 cases, sex-discrepancies have been reported in COVID-19 mortality. We provide a detailed description of these sex differences in relation to age and comorbidities among notified cases as well as in relation to age and sex-specific mortality in the general Dutch population. METHODS: Data on COVID-19 cases and mortality until May 31st 2020 was extracted from the national surveillance database with exclusion of healthcare workers. Association between sex and case fatality was analyzed with multivariable logistic regression. Subsequently, male–female ratio in standardized mortality ratios and population mortality rates relative to all-cause and infectious disease-specific mortality were computed stratified by age. RESULTS: Male–female odds ratio for case fatality was 1.33 [95% CI 1.26–1.41] and among hospitalized cases 1.27 [95% CI 1.16–1.40]. This remained significant after adjustment for age and comorbidities. The male–female ratio of the standardized mortality ratio was 1.70 [95%CI 1.62–1.78]. The population mortality rate for COVID-19 was 35.1 per 100.000, with a male–female rate ratio of 1.25 (95% CI 1.18–1.31) which was higher than in all-cause population mortality and infectious disease mortality. CONCLUSION: Our study confirms male sex is a predisposing factor for severe outcomes of COVID-19, independent of age and comorbidities. In addition to general male–female-differences, COVID-19 specific mechanisms likely contribute to this mortality discrepancy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s15010-021-01744-0

Estimating Transmission Parameters for Respiratory Syncytial Virus and Predicting the Impact of Maternal and Pediatric Vaccination.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illness in young children and a major cause of hospital admissions globally. METHODS: Here we fit age-structured transmission models with immunity propagation to data from the Netherlands (2012–2017). Data included nationwide hospitalizations with confirmed RSV, general practitioner (GP) data on attendance for care from acute respiratory infection, and virological testing of acute respiratory infections at the GP. The transmission models, equipped with key parameter estimates, were used to predict the impact of maternal and pediatric vaccination. RESULTS: Estimates of the basic reproduction number were generally high (R(0) > 10 in scenarios with high statistical support), while susceptibility was estimated to be low in nonelderly adults (<10% in persons 20–64 years) and was higher in older adults (≥65 years). Scenario analyses predicted that maternal vaccination reduces the incidence of infection in vulnerable infants (<1 year) and shifts the age of first infection from infants to young children. CONCLUSIONS: Pediatric vaccination is expected to reduce the incidence of infection in infants and young children (0–5 years), slightly increase incidence in 5 to 9-year-old children, and have minor indirect benefits