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–associated acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in older adults aged ≥65 years. We aimed to identify all studies ...worldwide investigating the disease burden of RSV-ARI in this population. We estimated the community incidence, hospitalization rate, and in-hospital case-fatality ratio (hCFR) of RSV-ARI in older adults, stratified by industrialized and developing regions, using data from a systematic review of studies published between January 1996 and April 2018 and 8 unpublished population-based studies. We applied these rate estimates to population estimates for 2015 to calculate the global and regional burdens in older adults with RSV-ARI in the community and in hospitals for that year. We estimated the number of in-hospital deaths due to RSV-ARI by combining hCFR data with hospital admission estimates from hospital-based studies. In 2015, there were about 1.5 million episodes (95% confidence interval CI, .3 million–6.9 million) of RSV-ARI in older adults in industrialized countries (data for developing countries were missing), and of these, approximately 14.5% (214 000 episodes; 95% CI, 100 000–459 000) were admitted to hospitals. The global number of hospital admissions for RSV-ARI in older adults was estimated at 336 000 hospitalizations (uncertainty range UR, 186 000–614 000). We further estimated about 14 000 in-hospital deaths (UR, 5000–50 000) related to RSV-ARI globally. The hospital admission rate and hCFR were higher for those aged ≥65 years than for those aged 50–64 years. The disease burden of RSV-ARI among older adults is substantial, with limited data from developing countries. Appropriate prevention and management strategies are needed to reduce this burden.
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.
Respiratory syncytial virus (RSV) is a major worldwide cause of morbidity and mortality in children under five years of age. Evidence-based management guidelines suggest that there is no effective ...treatment for RSV lower respiratory tract infection (LRTI) and that supportive care, ie, hydration and oxygenation, remains the cornerstone of clinical management. However, RSV treatments in development in the past decade include 10 vaccines and 11 therapeutic agents in active clinical trials. Maternal vaccination is particularly relevant because the most severe disease occurs within the first 6 months of life, when children are unlikely to benefit from active immunisation. We must optimise the implementation of novel RSV therapeutics by understanding the target populations, showing safety, and striving for acceptable pricing in the context of this worldwide health problem. In this Review, we outline the limitations of RSV LRTI management, the drugs in development, and the remaining challenges related to study design, regulatory approval, and implementation.
Oseltamivir has been used to treat children with influenza for nearly 2 decades, with treatment currently approved for infants aged ≥2 weeks. However, efficacy and safety remain controversial. Newer ...randomized, placebo-controlled trials (RCTs), 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 2-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 (RMST) by treatment group. We also examined complications and safety.
We identified 5 trials that included 2561 patients in the intention-to-treat (ITT) and 1598 in the intention-to-treat infected (ITTI) populations. Overall, oseltamivir treatment significantly reduced the duration of illness in the ITTI population (RMST difference, -17.6 hours; 95% confidence interval 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.
Abstract
Acute respiratory tract infections (ARI) constitute a substantial disease burden in adults and elderly individuals. We aimed to identify all case-control studies investigating the potential ...role of respiratory viruses in the etiology of ARI in older adults aged ≥65 years. We conducted a systematic literature review (across 7 databases) of case-control studies published from 1996 to 2017 that investigated the viral profile of older adults with and those without ARI. We then computed a pooled odds ratio (OR) with a 95% confidence interval and virus-specific attributable fraction among the exposed (AFE) for 8 common viruses: respiratory syncytial virus (RSV), influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). From the 16 studies included, there was strong evidence of possible causal attribution for RSV (OR, 8.5 95% CI, 3.9–18.5; AFE, 88%), Flu (OR, 8.3 95% CI, 4.4–15.9; AFE, 88%), PIV (OR, not available; AFE, approximately 100%), HMPV (OR, 9.8 95% CI, 2.3–41.0; AFE, 90%), AdV (OR, not available; AFE, approximately 100%), RV (OR, 7.1 95% CI, 3.7–13.6; AFE, 86%) and CoV (OR, 2.8 95% CI, 2.0–4.1; AFE, 65%) in older adults presenting with ARI, compared with those without respiratory symptoms (ie, asymptomatic individuals) or healthy older adults. However, there was no significant difference in the detection of BoV in cases and controls. This review supports RSV, Flu, PIV, HMPV, AdV, RV, and CoV as important causes of ARI in older adults and provides quantitative estimates of the absolute proportion of virus-associated ARI cases to which a viral cause can be attributed. Disease burden estimates should take into account the appropriate AFE estimates (for older adults) that we report.
Abstract
Pneumonia constitutes a substantial disease burden among adults overall and those who are elderly. We aimed to identify all studies investigating the disease burden among older adults (age, ...≥65 years) admitted to the hospital with pneumonia. We estimated the hospital admission rate and in-hospital case-fatality ratio (CFR) of pneumonia in older adults, stratified by age and economic status (industrialized vs developing), with data from a systematic review of studies published from 1996 through 2017 and from 8 unpublished population-based studies. We applied these rate estimates to population estimates for 2015 to calculate the global and regional burden in older adults who would have been admitted to the hospital with pneumonia that year. We estimated the number of in-hospital pneumonia deaths by combining in-hospital CFRs with hospital admission estimates from hospital-based studies. We identified 109 eligible studies; 73 used clinical pneumonia as the case definition, and 36 used radiologically confirmed pneumonia as the case definition. We estimated that, in 2015, 6.8 million episodes (uncertainty range UR, 5.8–8.0 episodes) of clinical pneumonia resulted in hospital admissions of older adults worldwide. The hospital admission rate increased with advancing age and was higher in men. The total disease burden was likely underestimated when using the definition of radiologically confirmed pneumonia. Based on data from 52 hospital studies reporting data on pneumonia mortality, we estimated that about 1.1 million in-hospital deaths (UR, 0.9–1.4 in-hospital deaths) occurred among older adults. The burden of pneumonia requiring hospitalization among older adults is substantial. Appropriate prevention and management strategies should be developed to reduce its impact.
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.
Few studies have directly compared the clinical impact of different types and subtypes of influenza viruses in children.
In a prospective study of respiratory infections in preenrolled cohorts of ...children ≤13 years of age, we compared the clinical features and the overall burden of illness between outpatient children with A/H1N1, A/H3N2 and B infections. The data were derived from structured medical records filled out by study physicians and from daily symptom diaries filled out by the parents throughout the follow-up period.
Of 358 children included in the analyses, 203 (57%) had influenza A/H1N1, 96 (27%) had A/H3N2, and 59 (16%) had influenza B infection. Children with influenza A/H3N2 were significantly younger (median, 3.2 years) than those with A/H1N1 (median, 4.8 years) or B (median, 5.1 years) infections (P < 0.0001). When adjusted for age, children 3-6 years of age with A/H3N2 infection had a higher frequency of fever ≥39.0°C (67% vs. 38%; P = 0.002), longer duration of fever (median, 4 vs. 3 days; P = 0.02) and more antibiotic treatments (43% vs. 20%; P = 0.004) than did children with A/H1N1 infections. Overall, the clinical presentation, duration of illness, frequency of complications, children's absenteeism from day care or school and parental work absenteeism were comparable between children with A/H1N1, A/H3N2 and B infections.
Adjusted for age, the clinical manifestations and the burden of illness are largely comparable between children with influenza A/H1N1, A/H3N2 and B infections.
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.
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