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Background. Vaccines and antivirals against respiratory syncytial virus (RSV) are being developed, but there are scarce data on the full impact of RSV infection on outpatient children. Methods. We analyzed the burden of RSV illness in a prospective cohort study of children aged ≤13 years during 2 consecutive respiratory seasons in Turku, Finland (2231 child-seasons of follow-up). We examined the children and obtained nasal swabs for the detection of RSV during each respiratory illness. The parents filled out daily symptom diaries throughout the study. Results. Of 6001 medically attended respiratory infections, 302 (5%) were caused by RSV. Per 1000 children, the average annual RSV infection incidence rates among children aged <3, 3–6, and 7–13 years were 275, 117, and 46 cases, respectively. In children aged <3 years, acute otitis media developed in 58%, and 66% of children in this age group received antibiotics. The mean duration of RSV illness was longest (13.0 days) and the rate of parental work absenteeism was highest (136 days per 100 children with RSV illness) in children aged <3 years. Conclusions. The burden of RSV is particularly great among outpatient children aged <3 years. Young children are an important target group for the development of RSV vaccines and antivirals.

Abstract Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children. By the age of 1 year, 60%–70% of children have been infected by RSV. In addition, early-life RSV infection is associated with the development of recurrent wheezing and asthma in infancy and childhood. The need for precise epidemiologic data regarding RSV as a worldwide pathogen has been growing steadily as novel RSV therapeutics are reaching the final stages of development. To optimize the prevention, diagnosis, and treatment of RSV infection in a timely manner, knowledge about the differences in the timing of the RSV epidemics worldwide is needed. Previous analyses, based on literature reviews of individual reports obtained from medical databases, have failed to provide global country seasonality patterns. Until recently, only certain countries have been recording RSV incidence through their own surveillance systems. This analysis was based on national RSV surveillance reports and medical databases from 27 countries worldwide. This is the first study to use original-source, high-quality surveillance data to establish a global, robust, and homogeneous report on global country-specific RSV seasonality. Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children. This is the first study to use original-source, high-quality surveillance data to establish a global, robust, and homogeneous report on global country-specific RSV seasonality.

Oseltamivir has been used to treat children with influenza for nearly two decades, with treatment currently approved for infants 2 weeks of age or older, but efficacy and safety remain controversial. Newer randomized placebo controlled trials (RCT), not included in previous meta-analyses, can add to the evidence base. We conducted a systematic review to identify RCTs of oseltamivir therapy in children. We obtained individual patient data and examined protocol-defined outcomes. We then conducted a two-stage, random effects meta-analysis to determine the efficacy of treatment in reducing the duration of illness, estimated using differences in restricted mean survival time (RSMT) by treatment group. We also examined complications and safety. We identified 5 trials including 2561 patients in the intent to treat (ITT) and 1598 in the intent to treat infected (ITTI) population. Overall, oseltamivir treatment significantly reduced the duration of illness in the ITTI population (RMST difference -17.6 hours 95% CI: -34.7 to -0.62 hours). In trials that enrolled patients without asthma, the difference was larger (-29.9 hours 95% CI -53.9 to -5.8 hours). Risk of otitis media was 34% lower in the ITTI population. Vomiting was the only adverse event with a significantly higher risk in the treatment group. Despite substantial heterogeneity in pediatric trials, we found that treatment with oseltamivir significantly reduced the duration of illness in those with influenza and lowered the risk of developing otitis media. Alternative endpoints may be required to evaluate the efficacy of oseltamivir in pediatric patients with asthma.

The COVID-19 pandemic and relevant non-pharmaceutical interventions (NPIs) interrupted the circulation of common respiratory viruses. These viruses demonstrated an unprecedented asynchronous resurgence as NPIs were relaxed. We compiled a global dataset from a systematic review, online surveillance reports and unpublished data from Respiratory Virus Global Epidemiology Network, encompassing 92 sites. We compared the resurgence timings of respiratory viruses within each site and synthesised differences in timings across sites, using a generalised linear mixed-effects model. We revealed a distinct sequential timing in the first post-pandemic resurgence: rhinovirus resurged the earliest, followed by seasonal coronavirus, parainfluenza virus, respiratory syncytial virus, adenovirus, metapneumovirus and influenza A virus, with influenza B virus exhibiting the latest resurgence. Similar sequential timing was observed in the second resurgence except influenza A virus caught up with metapneumovirus. The consistent asynchrony across geographical regions suggests that virus-specific characteristics, rather than location-specific factors, determining the relative timing of resurgence. COVID-19-related non-pharmaceutical interventions impacted the circulation of other pathogens. Here, the authors compile a global viral activity dataset and compare the timing of resurgence of seven common respiratory viruses following the relaxation of interventions across different geographical regions.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread. This study on respiratory syncytial virus (RSV) reveals global genomic gaps. Using INFORM-RSV data, it uncovers selection’s impact on RSVA and RSVB diversity. Analysing full genomes, it highlights non-neutral epidemic processes. The research emphasises air travel’s influence on global spread, underscoring the need for comprehensive RSV genomic surveillance.

Background. Oseltamivir provides modest clinical benefits to children with influenza when started within 48 hours of symptom onset. The effectiveness of oseltamivir could be substantially greater if the treatment were started earlier during the course of the illness. Methods. We carried out a randomized, double-blind, placebo-controlled trial of the efficacy of oseltamivir started within 24 hours of symptom onset in children 1–3 years of age with laboratory-confirmed influenza during the seasons of 2007–2008 and 2008–2009. Eligible children received either orally administered oseltamivir suspension or a matching placebo twice daily for 5 days. The children received clinical examinations, and the parents filled out detailed symptom diaries for 21 days. Results. Of 408 randomized children who received the study drug (oseltamivir, 203, and placebo, 205), 98 had laboratory-confirmed influenza (influenza A, 79, and influenza B, 19). When started within 12 hours of the onset of symptoms, oseltamivir decreased the incidence of acute otitis media by 85% (95% confidence interval, 25%–97%), but no significant reduction was observed with treatment started within 24 hours. Among children with influenza A, oseltamivir treatment started within 24 hours shortened the median time to resolution of illness by 3.5 days (3.0 vs 6.5 days; P = .002) in all children and by 4.0 days (3.4 vs 7.3; P = .006) in unvaccinated children and reduced parental work absenteeism by 3.0 days. No efficacy was demonstrated against influenza B infections. Conclusions. Oseltamivir treatment started within 24 hours of symptom onset provides substantial benefits to children with influenza A infection. Clinical trials registration. ClinicalTrials.gov identifier: NCT00593502.

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017–2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups. Respiratory syncytial virus (RSV) is a common infection in children and older adults but little is known about within-host viral population diversity. Here, the authors perform deep sequencing and find that RSV subgroup B exhibited more diversity than subgroup A, with implications for development of therapeutics and vaccines.

Background Trivalent influenza vaccines encompass one influenza B lineage; however, predictions have been unreliable on which of two antigenically distinct circulating lineages will dominate. Quadrivalent seasonal influenza vaccines contain strains from both lineages. This analysis assesses the cost effectiveness of switching from trivalent inactivated influenza vaccination (TIV) in Finland to quadrivalent vaccination, using inactivated (QIV) or live-attenuated (Q-LAIV) vaccines. Methods A transmission model simulated the dynamics of influenza infection while accounting for indirect (herd) protection. Prior distributions for key transmission parameters were repeatedly sampled and simulations that fitted the available information on influenza in Finland were recorded. The resulting posterior parameter distributions were used in a probabilistic sensitivity analysis in which economic parameters were sampled, simultaneously encompassing uncertainty in the transmission and economic parameters. The cost effectiveness of a range of trivalent and quadrivalent vaccine policies over a 20-year time horizon was assessed from both a societal and payer perspective in 2014 Euros. Results The simulated temporal incidence pattern of symptomatic infections corresponded well with case surveillance data. A switch from the current TIV to Q-LAIV in children (2 to <18 years) and to QIV in other ages was estimated to annually avert approximately 76,100 symptomatic infections (95 % range 36,700–146,700), 11,500 primary care consultations (6100–20,000), 540 hospitalisations (240–1180), and 72 deaths (32–160), and was cost-saving relative to TIV (€374 million averted [€161–€752], in 2014 Euros, discounted at 3 %). This scenario had the highest probability of being the most cost-effective scenario considered. Conclusions This analysis demonstrates that quadrivalent vaccination is expected to be highly cost effective, reducing the burden of influenza-related disease.

Understanding the distribution of respiratory syncytial virus (RSV) disease burden by more granular age bands in infants is necessary for optimising infant RSV immunisation strategies. Using a Bayesian model, we synthesised published data from a systematic literature review and unpublished data shared by international collaborators for estimating the distribution of infant RSV hospitalisations by month of age. Based on local RSV seasonality data, we further developed and validated a web-based prediction tool for estimating infant RSV hospitalisation distribution by birth month. Although RSV hospitalisation burden mostly peaked at the second month of life and was concentrated in infants under six months globally, substantial variations were noted in the age distribution of RSV hospitalisation among infants born in different months. Passive immunisation strategies should ideally be tailored to the local RSV disease burden distribution by age and birth month to maximise their per-dose effectiveness before a universal immunisation can be achieved. Passive immunisation for respiratory syncytial virus for infants is recommended by the World Health Organization but products currently available have limited duration of protection. Here, the authors investigate the age distribution of infant hospitalisation for respiratory syncytial virus to inform optimal timing of immunisation.

Background Influenza illness in children causes significant clinical and economic burden. Although some European countries have adopted influenza immunisation policies for healthy children, the debate about paediatric influenza vaccination in most countries of the European Union is ongoing. Our aim was to summarise influenza burden (in terms of health outcomes and economic burden) in children in Western Europe via a systematic literature review. Methods We conducted a systematic literature search of PubMed, EMBASE, and the Cochrane Library (1970-April 2011) and extracted data on influenza burden in children (defined as aged ≤ 18 years) from 50 publications (13 reporting laboratory-confirmed influenza; 37 reporting influenza-like illness). Results Children with laboratory-confirmed influenza experienced hospitalisations (0.3%-20%), medical visits (1.7-2.8 visits per case), antibiotic prescriptions (7%-55%), and antipyretic or other medications for symptomatic relief (76%-99%); young children and those with severe illness had the highest rates of health care use. Influenza in children also led to absenteeism from day care, school, or work for the children, their siblings, and their parents. Average (mean or median) length of absence from school or day care associated with confirmed influenza ranged from 2.8 to 12.0 days for the children, from 1.3 to 6.0 days for their siblings, and from 1.3 to 6.3 days for their parents. Influenza negatively affected health-related quality of life in children with asthma, including symptoms and activities; this negative effect was smaller in vaccinated children than in non-vaccinated children. Conclusions Influenza burden in children is substantial and has a significant direct impact on the ill children and an indirect impact on their siblings and parents. The identified evidence regarding the burden of influenza may help inform both influenza antiviral use in children and paediatric immunisation policies in European countries.