1,721,021 research outputs found
The burden of respiratory syncytial virus in healthy term-born infants in Europe:a prospective birth cohort study
Full text linkBackgroundRespiratory syncytial virus (RSV) is a major cause of hospitalization in infants. The burden of RSV infection in healthy term infants has not yet been established. Accurate healthcare burden data in healthy infants are necessary to determine RSV immunization policy when RSV immunization becomes available. MethodsWe performed a multicenter prospective, observational birth cohort study in healthy term-born infants (≥37 weeks of gestation) in five sites located in different European countries to determine the healthcare burden of RSV. The incidence of RSV-associated hospitalizations in the first year of life was determined by parental questionnaires and hospital chart reviews. We performed active RSV surveillance in a nested cohort to determine the incidence of medically-attended RSV infection. FindingsIn total, 9154 infants born between July 2017 and April 2020 were followed during the first year of life and 993 participated in the nested active surveillance cohort. The incidence of RSV hospitalization in the total cohort was 1·8% (95% CI 1·6-2·1). There were eight pediatric intensive care unit admissions, corresponding to 5·5% of RSV hospitalizations and 0·09% of the total cohort. Incidences of RSV infection confirmed by any diagnostic assay and medically-attended RSV infection in the active surveillance cohort were 26·2% (95% CI 24·0-28·6) and 14·1% (95% CI 12·3-16·0), respectively. InterpretationRSV-associated acute respiratory infection causes substantial morbidity, leading to the hospitalization of one in every 56 healthy term-born infants in high-income settings. Immunization of pregnant women or healthy term-born infants during their first winter season could have a significant impact on the healthcare burden caused by RSV infections.<br/
Publisher Correction:: Distinct patterns of within-host virus populations between two subgroups of human respiratory syncytial virus
Full text linkCorrection to: Nature Communications https://doi.org/10.1038/s41467-021-25265-4, published online 26 August 2021. The original HTML version of this Article contained errors in the author affiliations, which were correct in the PDF version. Specifically, affiliations after number 14 in the PDF version were displaying incorrectly in the online version of the paper. This has been updated so that all affiliations are accurate in the HTML version of the Article
Low Sensitivity of BinaxNOW RSV in Infants.
Full text linkBACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants. Early detection of RSV can optimize clinical management and minimize use of antibiotics. BinaxNOW RSV (BN) is a rapid antigen detection test that is widely used. We aimed to validate the sensitivity of BN in hospitalized and nonhospitalized infants against the gold standard of molecular diagnosis. METHODS: We evaluated the performance of BN in infants with acute respiratory tract infections with different degrees of disease severity. Diagnostic accuracy of BN test results were compared with molecular diagnosis as reference standard. RESULTS: One hundred sixty-two respiratory samples from 148 children from October 2017 to February 2019 were studied. Sixty-six (40.7%) samples tested positive for RSV (30 hospitalizations, 31 medically attended episodes not requiring hospitalization, and 5 nonmedically attended episodes). Five of these samples tested positive with BN, leading to an overall sensitivity of BN of 7.6% (95% confidence interval [CI], 3.3%-16.5%) and a specificity of 100% (95% CI, 96.2%-100%). Sensitivity was low in all subgroups. CONCLUSIONS: We found a low sensitivity of BN for point-of-care detection of RSV infection. BinaxNOW RSV should be used and interpreted with caution
A Retrospective Cohort Study on Infant Respiratory Tract Infection Hospitalizations and Recurrent Wheeze and Asthma Risk: Impact of Respiratory Syncytial Virus
No full textBackground Infant respiratory syncytial virus infection (RSV) has been associated with asthma later in life. We explored the risk of recurrent wheeze or asthma in children with infant RSV-associated hospitalization compared to other respiratory infections. Methods We performed a retrospective cohort study using Danish national hospital discharge registers. Infants younger than 6 months, born between January 1995 and October 2018, and with a RSV hospital admission were compared to infants hospitalized for injuries, non-RSV acute upper respiratory tract infection (AURTI), pneumonia and other respiratory pathogens, nonpathogen-coded lower respiratory tract infections (LRTI), pertussis, or nonspecific respiratory infections. Infants were followed until recurrent wheeze or asthma diagnosis, death, migration, age 10 years, or study end. We estimated cumulative incidence rate ratios (CIRR) and hazard ratios (HR) adjusted for sex, age at inclusion, hospital length of stay (LOS), maternal smoking, 5-minute APGAR score (APGAR5), prematurity, and congenital risk factors (CRF). Results We included 68 130 infants, of whom 20 920 (30.7%) had RSV hospitalization. The cumulative incidence rate of recurrent wheeze or asthma was 16.6 per 1000 person-years after RSV hospitalization, higher than after injury (CIRR, 2.69; 95% confidence interval [CI], 2.48-2.92), AURTI (CIRR, 1.48; 95% CI, 1.34-1.58), or pertussis (CIRR, 2.32; 95% CI, 1.85-2.91), similar to pneumonia and other respiratory pathogens (CIRR, 1.15; 95% CI, .99-1.34) and LRTI (CIRR, 0.79; 95% CI, .60-1.04), but lower than nonspecific respiratory infections (CIRR, 0.79; 95% CI, .73-.87). Adjusted HRs for recurrent wheeze or asthma after RSV hospitalization compared to injuries decreased from 2.37 (95% CI, 2.08-2.70) for 0 to <1 year to 1.23 (95% CI, .88-1.73) for 6 to <10 years for term-born children, and from 1.48 (95% CI, 1.09-2.00) to 0.60 (95% CI, .25-1.43) for preterm-born children. Sex, maternal smoking, LOS, CRF, and APGAR5 were independent risk factors. Conclusions Infant RSV hospitalization is associated with recurrent wheeze and asthma hospitalization, predominantly at preschool age. If causal, RSV prophylaxis, including vaccines, may significantly reduce disease burden of wheeze and asthma
T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults
No full textAbstract: IntroductionThe immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older adults, symptoms are typically mild but can be serious in patients with comorbidities when the infection extends to the lower respiratory tract.MethodsThis study formed part of the RESCEU older-adults prospective-cohort study in Northern Europe (2017-2019; NCT03621930) in which a thousand participants were followed over an RSV season. Peripheral-blood samples (taken pre-season, post-season, during illness and convalescence) were analyzed from participants who (i) had a symptomatic acute respiratory tract infection by RSV (RSV-ARTI; N=35) or (ii) asymptomatic RSV infection (RSV-Asymptomatic; N=16). These analyses included evaluations of antibody (Fc-mediated-) functional features and cell-mediated immunity, in which univariate and machine-learning (ML) models were used to explore differences between groups.ResultsPre-RSV-season peripheral-blood biomarkers were predictive of symptomatic RSV infection. T-cell data were more predictive than functional antibody data (area under receiver operating characteristic curve [AUROC] for the models were 99% and 76%, respectively). The pre-RSV season T-cell phenotypes which were selected by the ML modelling and which were more frequent in RSV-Asymptomatic group than in the RSV-ARTI group, coincided with prominent phenotypes identified during convalescence from RSV-ARTI (e.g., IFN-gamma+, TNF-alpha+ and CD40L+ for CD4+, and IFN-gamma+ and 4-1BB+ for CD8+).ConclusionThe evaluation and statistical modelling of numerous immunological parameters over the RSV season suggests a primary role of cellular immunity in preventing symptomatic RSV infections in older adults
The age profile of respiratory syncytial virus burden in preschool children of low- and middle-income countries : a semi-parametric, meta-regression approach
No full textAbstract: Author summary Why was this study done? Respiratory syncytial virus (RSV) is the most common cause of acute pulmonary infections in children. The RSV disease burden is high, especially in the nearly 600 million children under 5 living in 121 low-income (LIC) and middle-income countries (MICs) on which this study focuses.Evidence on the age distribution of RSV infections in these countries is based on sparse data using age breakdowns that are not always comparable.Different pharmaceutical products are becoming available that can reduce the RSV burden. Given that the immunity these products confer differs and wanes over time, it is essential to understand well at which months of age RSV infections drive the RSV disease burden.This study uses improved statistical models to estimate in depth the age profile of RSV cases, hospitalizations, and in-hospital deaths in young children. What did the researchers do and find? We calculated the distributions of the age of infection, hospitalization, and in-hospital deaths. Depending on whether we use hospital-based or community-based incidence studies to inform our methods, we estimate the peak age of infection at 2.6 to 4.8 months, the mean age at 15.8 to 18.9, and the median age at 11.6 to 14.7 months.We estimate that on an average year, there are 28.23 to 31.34 million cases of RSV, 2.95 to 3.35 million hospitalizations, and 34,114 to 46,485 deaths in children under 5 in LICs and MICs. About half the deaths occur in the community, outside of hospital settings.More severe outcomes, such as hospitalizations and in-hospital deaths have a younger age profile. Children under 6 months of age constitute 10% of the population under 5 years of age but bear 20% to 29% of cases, 28% to 39% of hospitalizations, and 38% to 50% of deaths. What do these findings mean? Our results support strategies using passive immunity products, such as maternal vaccines and monoclonal antibodies, to protect infants and active vaccination strategies for children over one, who also bear a large proportion of the burden.These results improve the choice of strategies offering the best value for money from a given budget.This study may enable modelers to make improved estimates thus allowing policymakers to gain a better understanding of the potential impact that new pharmaceutical products could have. BackgroundRespiratory syncytial virus (RSV) infections are among the primary causes of death for children under 5 years of age worldwide. A notable challenge with many of the upcoming prophylactic interventions against RSV is their short duration of protection, making the age profile of key interest to the design of prevention strategies. Methods and findingsWe leverage the RSV data collected on cases, hospitalizations, and deaths in a systematic review in combination with flexible generalized additive mixed models (GAMMs) to characterize the age burden of RSV incidence, hospitalization, and hospital-based case fatality rate (hCFR). Due to the flexible nature of GAMMs, we estimate the peak, median, and mean incidence of infection to inform discussions on the ideal "window of protection" of prophylactic interventions. In a secondary analysis, we reestimate the burden of RSV in all low- and middle-income countries. The peak age of community-based incidence is 4.8 months, and the mean and median age of infection is 18.9 and 14.7 months, respectively. Estimating the age profile using the incidence coming from hospital-based studies yields a slightly younger age profile, in which the peak age of infection is 2.6 months and the mean and median age of infection are 15.8 and 11.6 months, respectively. More severe outcomes, such as hospitalization and in-hospital death have a younger age profile. Children under 6 months of age constitute 10% of the population under 5 years of age but bear 20% to 29% of cases, 28% to 39% of hospitalizations, and 38% to 50% of deaths.On an average year, we estimate 28.23 to 31.34 million cases of RSV, between 2.95 to 3.35 million hospitalizations, and 16,835 to 19,909 in-hospital deaths in low, lower- and upper middle-income countries. In addition, we estimate 17,254 to 23,875 deaths in the community, for a total of 34,114 to 46,485 deaths. Globally, evidence shows that community-based incidence may differ by World Bank Income Group, but not hospital-based incidence, probability of hospitalization, or the probability of in-hospital death (p & LE; 0.01, p = 1, p = 0.86, 0.63, respectively). Our study is limited mainly due to the sparsity of the data, especially for low-income countries (LICs). The lack of information for some populations makes detecting heterogeneity between income groups difficult, and differences in access to care may impact the reported burden. ConclusionsWe have demonstrated an approach to synthesize information on RSV outcomes in a statistically principled manner, and we estimate that the age profile of RSV burden depends on whether information on incidence is collected in hospitals or in the community. Our results suggest that the ideal prophylactic strategy may require multiple products to avert the risk among preschool children
Patient involvement in RSV research: towards patients setting the research agenda
Full text linkRespiratory syncytial virus (RSV) causes a substantial disease burden among children, elderly and immunocompromised adults. Recognition of patient involvement in research is gradually increasing. Most research is being carried out without active patient involvement other than patients participating as study subjects, and most knowledge gained through research only partially reaches the general public. Since 2016, the RSV Patient Advisory Board has officially been involved as an advisory group in the Respiratory Syncytial Virus Consortium in Europe (RESCEU). What started as a small single-center initiative, is now growing towards an international organization providing patient perspectives as inputs to scientists, and improving awareness of RSV. This article summarizes the history, current role, and future aims of the RSV Patient Advisory Board as an advocate to improve patient involvement in research. RSV patients and their representatives are important stakeholders in setting the global research agenda, and educating patients, professionals, and the general public
A systematic review of clinical practice guidelines for the diagnosis and management of bronchiolitis
No full textBackground. Bronchiolitis is the leading cause of hospital admission for respiratory disease among infants aged <1 year. Clinical practice guidelines can benefit patients by reducing the performance of unnecessary tests, hospital admissions, and treatment with lack of a supportive evidence base. This review aimed to identify current clinical practice guidelines worldwide, appraise their methodological quality, and discuss variability across guidelines for the diagnosis and management of bronchiolitis. Methods. A systematic literature review of electronic databases EMBASE, Global Health, and Medline was performed. Manual searches of the gray literature, national pediatric society websites, and guideline-focused databases were performed, and select international experts were contacted to identify additional guidelines. The Appraisal of Guidelines for Research and Evaluation assessment tool was used by 2 independent reviewers to appraise each guideline. Results. Thirty-two clinical practice guidelines met the selection criteria. Quality assessment revealed significant shortcomings in a number of guidelines, including lack of systematic processes in formulating guidelines, failure to state conflicts of interest, and lack of consultation with families of affected children. There was widespread agreement about a number of aspects, such as avoidance of the use of unnecessary diagnostic tests, risk factors for severe disease, indicators for hospital admission, discharge criteria, and nosocomial infection control. However, there was variability, even within areas of consensus, over specific recommendations, such as variable thresholds for oxygen therapy. Guidelines showed significant variability in recommendations for the pharmacological management of bronchiolitis, with conflicting recommendations over whether use of nebulized epinephrine, hypertonic saline, or bronchodilators should be routinely trialled. Conclusions. Future guidelines should aim to be compliant with international standards for clinical guidelines to improve their quality and clarity and to promote their adoption into practice. Variable recommendations between guidelines may reflect the evolving evidence base for bronchiolitis management, and platforms should be created to understand this variability and promote evidence-based recommendations
Cost of respiratory syncytial virus-associated acute lower respiratory infection management in young children at the regional and global level : a systematic review and meta-analysis
No full textAbstract: Background. Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection (ALRI) in young children aged <5 years. Methods. We aimed to identify the global inpatient and outpatient cost of management of RSV-ALRI in young children to assist health policy makers in making decisions related to resource allocation for interventions to reduce severe morbidity and mortality from RSV in this age group. We searched 3 electronic databases including Global Health, Medline, and EMBASE for studies reporting cost data on RSV management in children under 60 months from 2000 to 2017. Unpublished data on the management cost of RSV episodes were collected through collaboration with an international working group (RSV GEN) and claim databases. Results. We identified 41 studies reporting data from year 1987 to 2017, mainly from Europe, North America, and Australia, covering the management of a total of 365 828 RSV disease episodes. The average cost per episode was _3452 (95% confidence interval [CI], 3265-3639) and is an element of 299 (95% CI, 295-303) for inpatient and outpatient management without follow-up, and it increased to _8591(95% CI, 8489-8692) and is an element of 2191 (95% CI, 2190-2192), respectively, with follow-up to 2 years after the initial event. Conclusions. Known risk factors (early and late preterm birth, congenital heart disease, chronic lung disease, intensive care unit admission, and ventilator use) were associated with is an element of 4160 (95% CI, 3237-5082) increased cost of hospitalization. The global cost of inpatient and outpatient RSV ALRI management in young children in 2017 was estimated to be approximately is an element of 4.82 billion (95% CI, 3.47-7.93), 65% of these in developing countries and 55% of global costs accounted for by hospitalization. We have demonstrated that RSV imposed a substantial economic burden on health systems, governments, and the society
Economic burden and health-related quality-of-life among infants with respiratory syncytial virus infection : a multi-country prospective cohort study in Europe
No full textAbstract: Background: Respiratory syncytial virus (RSV) causes a considerable disease burden in young children globally, but reliable estimates of RSV-related costs and health-related quality-of-life (HRQoL) are scarce. This study aimed to evaluate the RSV-associated costs and HRQoL effects in infants and their caregivers in four European countries.Methods: Healthy term-born infants were recruited at birth and actively followed up in four European countries. Symptomatic infants were systematically tested for RSV. Caregivers recorded the daily HRQoL of their child and themselves, measured by a modified EQ-5D with Visual Analogue Scale, for 14 consecutive days or until symptoms resolved. At the end of each RSV episode, caregivers reported healthcare resource use and work absenteeism. Direct medical costs per RSV episode were estimated from a healthcare payer's perspective and indirect costs were estimated from a societal perspective. Means and 95% confidence intervals (CI) of direct medical costs, total costs (direct costs + productivity loss) and quality-adjusted life-day (QALD) loss per RSV episode were estimated per RSV episode, as well as per subgroup (medical attendance, country).Results: Our cohort of 1041 infants experienced 265 RSV episodes with a mean symptom duration of 12.5 days. The mean (95% CI) cost per RSV episode was 6399.5 (242.3, 584.2) and 6494.3 (317.7, 696.1) from the healthcare payer's and societal perspective, respectively. The mean QALD loss per RSV episode of 1.9 (1.7, 2.1) was independent of medical attendance (in contrast to costs, which also differed by country). Caregiver and infant HRQoL evolved similarly.Conclusion: This study fills essential gaps for future economic evaluations by prospectively estimating direct and indirect costs and HRQoL effects on healthy term infants and caregivers separately, for both medically attended (MA) and non-MA laboratory-confirmed RSV episodes. We generally observed greater HRQoL losses than in previous studies which used non-community and/or non-prospective designs.(c) 2023 Elsevier Ltd. All rights reserved
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