Change in Age profile of Respiratory Syncytial Virus disease over the course of annual epidemics: a multi-national study.

OBJECTIVES: We aimed to study whether the percentwise age distribution of RSV cases changes over time during annual epidemics. METHODS: We used surveillance data (2008-2019) from the Netherlands, Lyon (France), Portugal, Singapore, Ecuador, South Africa, and New Zealand. In each country, every season was divided into "epidemic quarters", i.e. periods corresponding to each quartile of RSV cases. Multinomial logistic regression models were fitted to evaluate whether the likelihood of RSV cases being aged <1 or ≥5 years (vs. 1 to <5) changed over time within a season. RESULTS: In all countries, RSV cases were significantly more likely to be aged <1 year in the 4th vs. 1st epidemic quarter; the relative risk ratio [RRR] ranged between 1.35 and 2.56. Likewise, RSV cases were significantly more likely to be aged ≥5 years in the 4th vs. 1st epidemic quarter (except in Singapore); the RRR ranged from 1.75 to 6.70. The results did not change when stratifying by level of care or moving the lower cut-off to 6 months. CONCLUSIONS: The age profile of RSV cases shifts within a season, with infants and adolescents, adults, and the elderly constituting a higher proportion of cases in the later phases of annual epidemics. These findings may have implications for RSV prevention policies with newly approved vaccines.

Pre-COVID-19-pandemic RSV epidemiology and clinical burden in pediatric primary care in Italy: a comparative analysis across two regions for the 2019/2020 season.

BACKGROUND: Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the epidemiology and burden of RSV in Italian children during the 2019/20 pre-pandemic winter season. METHODS: A prospective cohort study was conducted in two Italian regions. Children with Acute Respiratory Infection (ARI) visiting pediatricians were eligible. Nasopharyngeal swabs were collected and analyzed via multiplex PCR for RSV detection. A follow-up questionnaire after 14 days assessed disease burden, encompassing healthcare utilization and illness duration. Statistical analyses, including regression models, explored associations between variables such as RSV subtype and regional variations. RESULTS: Of 293 children with ARI, 41% (119) tested positive for RSV. Median illness duration for RSV-positive cases was 7 days; 6% required hospitalization (median stay: 7 days). Medication was prescribed to 95% (110/116) of RSV cases, with 31% (34/116) receiving antibiotics. RSV subtype B and regional factors predicted increased healthcare utilization. Children with shortness of breath experienced a 36% longer illness duration. CONCLUSIONS: This study highlights a significant clinical burden and healthcare utilization associated with RSV in pre-pandemic Italian primary care settings. Identified predictors, including RSV subtype and symptomatology, indicate the need for targeted interventions and resource allocation strategies. RSV epidemiology can guide public health strategies for the implementation of preventive measures.

Global analysis of respiratory viral circulation and timing of epidemics in the pre-COVID-19 and COVID-19 pandemic eras, based on data from the Global Influenza Surveillance and Response System (GISRS).

INTRODUCTION: The COVID-19 pandemic significantly changed respiratory viruses' epidemiology due to non-pharmaceutical interventions and possible viral interactions. This study investigates whether the circulation patterns of respiratory viruses have returned to pre-pandemic norms by comparing their peak timing and duration during the first three SARS-CoV-2 seasons to pre-pandemic times. METHODS: GISRS data from 194 countries (2014-2023) was analyzed for epidemic peak timing and duration, focusing on pre-pandemic and pandemic periods across both hemispheres and the intertropical belt. Analysis was restricted to countries meeting specific data thresholds to ensure robustness. RESULTS: In 2022/23, the Northern hemisphere experienced earlier influenza and RSV peaks by 1.9 months (p<0.001). The duration of influenza epidemics increased by 2.2 weeks (p<0.001), with RSV showing a similar trend. The Southern hemisphere's influenza peak shift was not significant (p=0.437). Intertropical regions presented no substantial change in peak timing but experienced a significant reduction in duration for hMPV and adenovirus (7.2 and 6.5 weeks shorter, p<0.001). CONCLUSIONS: The pandemic altered the typical patterns of influenza and RSV, with earlier peaks in 2022 in temperate areas. These findings highlight the importance of robust surveillance data to inform public health strategies on evolving viral dynamics in the years to come.

Determining the timing of respiratory syncytial virus (RSV) epidemics: a systematic review, 2016 to 2021; method categorisation and identification of influencing factors.

BackgroundThere is currently no standardised approach to estimate respiratory syncytial virus (RSV) epidemics' timing (or seasonality), a critical information for their effective prevention and control.AimWe aimed to provide an overview of methods to define RSV seasonality and identify factors supporting method choice or interpretation/comparison of seasonal estimates.MethodsWe systematically searched PubMed and Embase (2016-2021) for studies using quantitative approaches to determine the start and end of RSV epidemics. Studies' features (data-collection purpose, location, regional/(sub)national scope), methods, and assessment characteristics (case definitions, sampled population's age, in/outpatient status, setting, diagnostics) were extracted. Methods were categorised by their need of a denominator (i.e. numbers of specimens tested) and their retrospective vs real-time application. Factors worth considering when choosing methods and assessing seasonal estimates were sought by analysing studies.ResultsWe included 32 articles presenting 49 seasonality estimates (18 thereof through the 10% positivity threshold method). Methods were classified into eight categories, two requiring a denominator (1 retrospective; 1 real-time) and six not (3 retrospective; 3 real-time). A wide range of assessment characteristics was observed. Several studies showed that seasonality estimates varied when methods differed, or data with dissimilar assessment characteristics were employed. Five factors (comprising study purpose, application time, assessment characteristics, healthcare system and policies, and context) were identified that could support method choice and result interpretation.ConclusionMethods and assessment characteristics used to define RSV seasonality are heterogeneous. Our categorisation of methods and proposed framework of factors may assist in choosing RSV seasonality methods and interpretating results.

Contribution of Infant Rhinovirus Bronchiolitis to Hospital Bed and Ventilation Use.

This cohort study compares the use of hospital resources related to human rhinovirus and respiratory syncytial virus infections among infants during 3 consecutive seasons before nirsevimab implementation.

Impact of Subgroup Distribution on Seasonality of Human Respiratory Syncytial Virus: A Global Systematic Analysis.

BACKGROUND: Previous studies reported inconsistent findings regarding the association between respiratory syncytial virus (RSV) subgroup distribution and timing of RSV season. We aimed to further understand the association by conducting a global-level systematic analysis. METHODS: We compiled published data on RSV seasonality through a systematic literature review, and unpublished data shared by international collaborators. Using annual cumulative proportion (ACP) of RSV-positive cases, we defined RSV season onset and offset as ACP reaching 10% and 90%, respectively. Linear regression models accounting for meteorological factors were constructed to analyze the association of proportion of RSV-A with the corresponding RSV season onset and offset. RESULTS: We included 36 study sites from 20 countries, providing data for 179 study-years in 1995-2019. Globally, RSV subgroup distribution was not significantly associated with RSV season onset or offset globally, except for RSV season offset in the tropics in 1 model, possibly by chance. Models that included RSV subgroup distribution and meteorological factors explained only 2%-4% of the variations in timing of RSV season. CONCLUSIONS: Year-on-year variations in RSV season onset and offset are not well explained by RSV subgroup distribution or meteorological factors. Factors including population susceptibility, mobility, and viral interference should be examined in future studies.

Respiratory Syncytial Virus-Associated Hospitalization in Adults With Comorbidities in 2 European Countries: A Modeling Study.

BACKGROUND: Individuals with comorbidities are at increased risk of severe respiratory syncytial virus (RSV) infection. We estimated RSV-associated respiratory hospitalization among adults aged ≥45 years with comorbidities in Denmark and Scotland. METHODS: By analyzing national hospital and virologic data, we estimated annual RSV-associated hospitalizations by 7 selected comorbidities and ages between 2010 and 2018. We estimated rate ratios of RSV-associated hospitalization for adults with comorbidity than the overall population. RESULTS: In Denmark, annual RSV-associated hospitalization rates per 1000 adults ranged from 3.1 for asthma to 19.4 for chronic kidney disease (CKD). In Scotland, rates ranged from 2.4 for chronic liver disease to 9.0 for chronic obstructive pulmonary disease (COPD). In both countries, we found a 2- to 4-fold increased risk of RSV hospitalization for adults with COPD, ischemic heart disease, stroke, and diabetes; a 1.5- to 3-fold increased risk for asthma; and a 3- to 7-fold increased risk for CKD. RSV hospitalization rates among adults aged 45 to 64 years with COPD, asthma, ischemic heart disease, or CKD were higher than the overall population. CONCLUSIONS: This study provides important evidence for identifying risk groups and assisting health authorities in RSV vaccination policy making.

The impact of influenza and pneumococcal vaccination on antibiotic use: an updated systematic review and meta-analysis.

BACKGROUND: Vaccination can prevent bacterial and viral infections that could otherwise increase the chances of receiving (unnecessary) antibiotic treatment(s). As a result, vaccination may provide an important public health intervention to control antimicrobial resistance (AMR). OBJECTIVES: Perform a systematic literature review to better understand the impact of influenza, pneumococcal and COVID-19 vaccination on antibiotic use, and to identify differences in effect between world regions and study designs. METHODS: We performed a systematic literature review and meta-analysis which updated previous literature reviews with new data from 1 October 2018 to 1 December 2021. The study focuses on randomised controlled trials (RCTs) and observational studies. Results from the meta-analysis of RCTs were stratified by WHO region and age group. Vote counting based on the direction of effect was applied to synthesize the results of the observational studies. RESULTS: Most studies are performed in the WHO European Region and the Region of the Americas in high-income countries. RCTs show that the effect of influenza vaccination on the number of antibiotic prescriptions or days of antibiotic use (Ratio of Means (RoM) 0.71, 95% CI 0.62-0.83) is stronger compared to the effect of pneumococcal vaccination (RoM 0.92, 95% CI 0.85-1.00). These studies also confirm a reduction in the proportion of people receiving antibiotics after influenza vaccination (Risk Ratio (RR) 0.63, 95% CI 0.51-0.79). The effect of influenza vaccination in the European and American regions ranged from RoM 0.63 and 0.87 to RR 0.70 and 0.66, respectively. The evidence from observational studies supports these findings but presents a less consistent picture. No COVID-19 studies were identified. CONCLUSION: We find that both RCTs and observational studies show that influenza vaccination significantly reduces antibiotic use, while the effect of pneumococcal vaccination is less pronounced. We were unable to study the effect of COVID-19 vaccination and no clear regional patterns were found due to the high heterogeneity between studies. Overall, our data supports the use of influenza vaccination as an important public health intervention to reduce antibiotic use and possibly control AMR.

Age Differences in Comorbidities, Presenting Symptoms, and Outcomes of Influenza Illness Requiring Hospitalization: A Worldwide Perspective From the Global Influenza Hospital Surveillance Network.

Background: The Global Influenza Hospital Surveillance Network (GIHSN) was established in 2012 to conduct coordinated worldwide influenza surveillance. In this study, we describe underlying comorbidities, symptoms, and outcomes in patients hospitalized with influenza. Methods: Between November 2018 and October 2019, GIHSN included 19 sites in 18 countries using a standardized surveillance protocol. Influenza infection was laboratory-confirmed with reverse-transcription polymerase chain reaction. A multivariate logistic regression model was utilized to analyze the extent to which various risk factors predict severe outcomes. Results: Of 16 022 enrolled patients, 21.9% had laboratory-confirmed influenza; 49.2% of influenza cases were A/H1N1pdm09. Fever and cough were the most common symptoms, although they decreased with age (P < .001). Shortness of breath was uncommon among those <50 years but increased with age (P < .001). Middle and older age and history of underlying diabetes or chronic obstructive pulmonary disease were associated with increased odds of death and intensive care unit (ICU) admission, and male sex and influenza vaccination were associated with lower odds. The ICU admissions and mortality occurred across the age spectrum. Conclusions: Both virus and host factors contributed to influenza burden. We identified age differences in comorbidities, presenting symptoms, and adverse clinical outcomes among those hospitalized with influenza and benefit from influenza vaccination in protecting against adverse clinical outcomes. The GIHSN provides an ongoing platform for global understanding of hospitalized influenza illness.

The impact of the SARS-CoV-2 pandemic on global influenza surveillance: Insights from 18 National Influenza Centers based on a survey conducted between November 2021 and March 2022.

Background: National Influenza Centers (NICs) have played a crucial role in the surveillance of SARS-CoV-2. The FluCov project, covering 22 countries, was initiated to monitor the impact of the SARS-CoV-2 pandemic on influenza activity. Methods: This project consisted of an epidemiological bulletin and NIC survey. The survey, designed to assess the impact of the pandemic on the influenza surveillance system, was shared with 36 NICs located across 22 countries. NICs were invited to reply between November 2021 and March 2022. Results: We received 18 responses from NICs in 14 countries. Most NICs (76%) indicated that the number of samples tested for influenza decreased. Yet, many NICs (60%) were able to increase their laboratory testing capacity and the "robustness" (e.g., number of sentinel sites) (59%) of their surveillance systems. In addition, sample sources (e.g., hospital or outpatient setting) shifted. All NICs reported a higher burden of work following the onset of the pandemic, with some NICs hiring additional staff or partial outsourcing to other institutes or departments. Many NICs anticipate the future integration of SARS-CoV-2 surveillance into the existing respiratory surveillance system. Discussion: The survey shows the profound impact of SARS-CoV-2 on national influenza surveillance in the first 27 months of the pandemic. Surveillance activities were temporarily disrupted, whilst priority was given to SARS-CoV-2. However, most NICs have shown rapid adaptive capacity underlining the importance of strong national influenza surveillance systems. These developments have the potential to benefit global respiratory surveillance in the years to come; however, questions about sustainability remain.

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.

Estimation of the Number of Respiratory Syncytial Virus-Associated Hospitalizations in Adults in the European Union.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in adults that can result in hospitalizations. Estimating RSV-associated hospitalization is critical for planning RSV-related healthcare across Europe. METHODS: We gathered RSV-associated hospitalization estimates from the RSV Consortium in Europe (RESCEU) for adults in Denmark, England, Finland, Norway, Netherlands, and Scotland from 2006 to 2017. We extrapolated these estimates to 28 European Union (EU) countries using nearest-neighbor matching, multiple imputations, and 2 sets of 10 indicators. RESULTS: On average, 158 229 (95% confidence interval [CI], 140 865-175 592) RSV-associated hospitalizations occur annually among adults in the EU (≥18 years); 92% of these hospitalizations occur in adults ≥65 years. Among 75-84 years, the annual average is estimated at 74 519 (95% CI, 69 923-79 115) at a rate of 2.24 (95% CI, 2.10-2.38) per 1000. Among ≥85 years, the annual average is estimated at 37 904 (95% CI, 32 444-43 363) at a rate of 2.99 (95% CI, 2.56-3.42). CONCLUSIONS: Our estimates of RSV-associated hospitalizations in adults are the first analysis integrating available data to provide the disease burden across the EU. Importantly, for a condition considered in the past to be primarily a disease of young children, the average annual hospitalization estimate in adults was lower but of a similar magnitude to the estimate in young children (0-4 years): 158 229 (95% CI, 140 865-175 592) versus 245 244 (95% CI, 224 688-265 799).

Application of a forecasting model to mitigate the consequences of unexpected RSV surge: Experience from the post-COVID-19 2021/22 winter season in a major metropolitan centre, Lyon, France.

Background: The emergence of COVID-19 triggered the massive implementation of non-pharmaceutical interventions (NPI) which impacted the circulation of respiratory syncytial virus (RSV) during the 2020/2021 season. Methods: A time-series susceptible-infected-recovered (TSIR) model was used early September 2021 to forecast the implications of this disruption on the future 2021/2022 RSV epidemic in Lyon urban population. Results: When compared to observed hospital-confirmed cases, the model successfully captured the early start, peak timing, and end of the 2021/2022 RSV epidemic. These simulations, added to other streams of surveillance data, shared and discussed among the local field experts were of great value to mitigate the consequences of this atypical RSV outbreak on our hospital paediatric department. Conclusions: TSIR model, fitted to local hospital data covering large urban areas, can produce plausible post-COVID-19 RSV simulations. Collaborations between modellers and hospital management (who are both model users and data providers) should be encouraged in order to validate the use of dynamical models to timely allocate hospital resources to the future RSV epidemics.

Global and national influenza-associated hospitalisation rates: Estimates for 40 countries and administrative regions.

Background: WHO estimates that seasonal influenza epidemics result in three to five million cases of severe illness (hospitalisations) every year. We aimed to improve the understanding of influenza-associated hospitalisation estimates at a national and global level. Methods: We performed a systematic literature review of English- and Chinese-language studies published between 1995 and 2020 estimating influenza-associated hospitalisation. We included a total of 127 studies (seven in Chinese) in the meta-analysis and analyzed their data using a logit-logistic regression model to understand the influence of five study factors and produce national and global estimates by age groups. The five study factors assessed were: 1) the method used to calculate the influenza-associated hospitalisation estimates (rate- or time series regression-based), 2) the outcome measure (divided into three envelopes: narrow, medium, or wide), 3) whether every case was laboratory-confirmed or not, 4) whether the estimates were national or sub-national, 5) whether the rates were based on a single year or multiple years. Results: The overall pooled influenza-associated hospitalisation rate was 40.5 (95% confidence interval (CI) = 24.3-67.4) per 100 000 persons, with rates varying substantially by age: 224.0 (95% CI = 118.8-420.0) in children aged 0-4 years and 96.8 (95% CI = 57.0-164.3) in the elderly aged >65 years. The overall pooled hospitalisation rates varied by calculation method; for all ages, the rates were significantly higher when they were based on rate-based methods or calculated on a single season and significantly lower when cases were laboratory-confirmed. The national hospitalisation rates (all ages) varied considerably, ranging from 11.7 (95% CI = 3.8-36.3) per 100 000 in New Zealand to 122.1 (95% CI = 41.5-358.4) per 100 000 in India (all age estimates). Conclusions: Using the pooled global influenza-associated hospitalisation rate, we estimate that seasonal influenza epidemics result in 3.2 million cases of severe illness (hospitalisations) per annum. More extensive analyses are required to assess the influence of other factors on the estimates (e.g. vaccination and dominant virus (sub)types) and efforts to harmonize the methods should be encouraged. Our study highlights the high rates of influenza-associated hospitalisations in children aged 0-4 years and the elderly aged 65+ years.

Preparing for the upcoming 2022/23 influenza season: A modelling study of the susceptible population in Australia, France, Germany, Italy, Spain and the United Kingdom.

We analysed the influenza epidemic that occurred in Australia during the 2022 winter using an age-structured dynamic transmission model, which accounts for past epidemics to estimate the population susceptibility to an influenza infection. We applied the same model to five European countries. Our analysis suggests Europe might experience an early and moderately large influenza epidemic. Also, differences may arise between countries, with Germany and Spain experiencing larger epidemics, than France, Italy and the United Kingdom, especially in children.

Assessment of the inclusion of vaccination as an intervention to reduce antimicrobial resistance in AMR national action plans: a global review.

BACKGROUND: Vaccination can reduce antibiotic use by decreasing bacterial and viral infections and vaccines are highlighted in the WHO Global Action Plan on Antimicrobial Resistance (AMR) as an infection prevention measure to reduce AMR. Our study aimed to analyze whether WHO Member States have developed AMR national action plans that are aligned with the Global Action Plan regarding objectives on vaccination. METHODS: We reviewed 77 out of 90 AMR national action plans available in the WHO library that were written after publication of the Global Action Plan in 2015. Each plan was analyzed using content analysis, with a focus on vaccination and key components as defined by WHO (I. Strategic plan (e.g. goals and objectives), II. Operational plan, III. Monitoring and Evaluation plan). RESULTS: Vaccination was included in 67 of 77 AMR plans (87%) across all WHO Regions (Africa: n = 13/13, the Eastern Mediterranean: n = 15/16, Europe: n = 10/14, the Americas: n = 8/8, South-East Asia: n = 8/11, and the Western Pacific: n = 13/15). Pneumococcal and influenza vaccination were most frequently highlighted (n = 12 and n = 11). We found indications that vaccination objectives are more often included in AMR plans from higher income countries, while lower income countries more often include specific vaccines. The key WHO components of national action plans were frequently not covered (I. 47% included, II. 57%, III. 40%). In total, 33 countries (43%) included indicators (e.g. strategic objectives) to capture the role of vaccines against AMR. CONCLUSIONS: While vaccination to reduce AMR is seen as an important global public health issue by WHO, there appears to be a gap in its adoption in national AMR plans. Country income levels seem to influence the progress, implementation and focus of national action plans, guided by a lack of funding and prioritization in developing countries. To better align the global response to AMR, our review suggests there is a need to update national action plans to include objectives on vaccination with more focus on specific vaccines that impact antibiotic use.