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      Clinical Burden of Respiratory Syncytial Virus in Hospitalized Children Aged ≤5 Years (INSPIRE Study) 

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          Abstract

          Background

          Respiratory syncytial virus (RSV) is a leading cause of hospitalizations in children (≤5 years of age); limited data compare burden by age.

          Methods

          This single-center retrospective study included children (≤5 years of age) hospitalized for >24 hours with reverse-transcription polymerase chain reaction (RT-PCR)–confirmed RSV infection (2015–2018). Hospital length of stay (LOS), intensive care unit (ICU) admissions, ICU LOS, supplemental oxygen, and medication use were assessed. Multivariate logistic regression analyses identified predictors of hospital LOS >5 days.

          Results

          Three hundred twelve patients had RSV infection (ages 0 to <6 months [35%], 6 to <12 months [15%], 1 to <2 years [25%], and 2–5 years [25%]); 16.3% had predefined comorbidities (excludes preterm infants). Median hospital LOS was 5.0 days and similar across age; 5.1% (16/312) were admitted to ICU (ICU LOS, 5.0 days), with those aged 0 to <6 months admitted most frequently (10/108 [9.3%]). Supplemental oxygen was administered in 57.7% of patients, with similar need across ages. Antibiotics were administered frequently during hospitalization (43.6%). Predictors of prolonged LOS included pneumonia (odds ratio [OR], 2.33), supplemental oxygen need (OR, 5.09), and preterm births (OR, 3.37). High viral load (RT-PCR RSV cycle threshold value <25) was associated with greater need for supplemental oxygen.

          Conclusions

          RSV causes substantial burden in hospitalized children (≤5 years), particularly preterm infants and those aged <6 months.

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          Most cited references45

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          Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study

          Summary Background We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. Methods We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. Findings We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6–50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7–3·8) hospital admissions, and 59 600 (48 000–74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2–1·7) hospital admissions, and 27 300 (UR 20 700–36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600–149 400). Incidence and mortality varied substantially from year to year in any given population. Interpretation Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. Funding The Bill & Melinda Gates Foundation.
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            Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

            Summary Background Lower respiratory infections are a leading cause of morbidity and mortality around the world. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, provides an up-to-date analysis of the burden of lower respiratory infections in 195 countries. This study assesses cases, deaths, and aetiologies spanning the past 26 years and shows how the burden of lower respiratory infection has changed in people of all ages. Methods We used three separate modelling strategies for lower respiratory infections in GBD 2016: a Bayesian hierarchical ensemble modelling platform (Cause of Death Ensemble model), which uses vital registration, verbal autopsy data, and surveillance system data to predict mortality due to lower respiratory infections; a compartmental meta-regression tool (DisMod-MR), which uses scientific literature, population representative surveys, and health-care data to predict incidence, prevalence, and mortality; and modelling of counterfactual estimates of the population attributable fraction of lower respiratory infection episodes due to Streptococcus pneumoniae, Haemophilus influenzae type b, influenza, and respiratory syncytial virus. We calculated each modelled estimate for each age, sex, year, and location. We modelled the exposure level in a population for a given risk factor using DisMod-MR and a spatio-temporal Gaussian process regression, and assessed the effectiveness of targeted interventions for each risk factor in children younger than 5 years. We also did a decomposition analysis of the change in LRI deaths from 2000–16 using the risk factors associated with LRI in GBD 2016. Findings In 2016, lower respiratory infections caused 652 572 deaths (95% uncertainty interval [UI] 586 475–720 612) in children younger than 5 years (under-5s), 1 080 958 deaths (943 749–1 170 638) in adults older than 70 years, and 2 377 697 deaths (2 145 584–2 512 809) in people of all ages, worldwide. Streptococcus pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more deaths than all other aetiologies combined in 2016 (1 189 937 deaths, 95% UI 690 445–1 770 660). Childhood wasting remains the leading risk factor for lower respiratory infection mortality among children younger than 5 years, responsible for 61·4% of lower respiratory infection deaths in 2016 (95% UI 45·7–69·6). Interventions to improve wasting, household air pollution, ambient particulate matter pollution, and expanded antibiotic use could avert one under-5 death due to lower respiratory infection for every 4000 children treated in the countries with the highest lower respiratory infection burden. Interpretation Our findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults. By highlighting regions and populations with the highest burden, and the risk factors that could have the greatest effect, funders, policy makers, and programme implementers can more effectively reduce lower respiratory infections among the world's most susceptible populations. Funding Bill & Melinda Gates Foundation.
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              The burden of respiratory syncytial virus infection in young children.

              The primary role of respiratory syncytial virus (RSV) in causing infant hospitalizations is well recognized, but the total burden of RSV infection among young children remains poorly defined. We conducted prospective, population-based surveillance of acute respiratory infections among children under 5 years of age in three U.S. counties. We enrolled hospitalized children from 2000 through 2004 and children presenting as outpatients in emergency departments and pediatric offices from 2002 through 2004. RSV was detected by culture and reverse-transcriptase polymerase chain reaction. Clinical information was obtained from parents and medical records. We calculated population-based rates of hospitalization associated with RSV infection and estimated the rates of RSV-associated outpatient visits. Among 5067 children enrolled in the study, 919 (18%) had RSV infections. Overall, RSV was associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of office visits for acute respiratory infections from November through April. Average annual hospitalization rates were 17 per 1000 children under 6 months of age and 3 per 1000 children under 5 years of age. Most of the children had no coexisting illnesses. Only prematurity and a young age were independent risk factors for hospitalization. Estimated rates of RSV-associated office visits among children under 5 years of age were three times those in emergency departments. Outpatients had moderately severe RSV-associated illness, but few of the illnesses (3%) were diagnosed as being caused by RSV. RSV infection is associated with substantial morbidity in U.S. children in both inpatient and outpatient settings. Most children with RSV infection were previously healthy, suggesting that control strategies targeting only high-risk children will have a limited effect on the total disease burden of RSV infection. 2009 Massachusetts Medical Society
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                Author and article information

                Contributors
                Journal
                J Infect Dis
                J Infect Dis
                jid
                The Journal of Infectious Diseases
                Oxford University Press (US )
                0022-1899
                1537-6613
                01 August 2022
                13 April 2022
                13 April 2022
                : 226
                : 3
                : 386-395
                Affiliations
                Department of Pediatrics, University Hospital Würzburg , Würzburg, Germany
                Department of Pediatrics, University Hospital Würzburg , Würzburg, Germany
                Department of Pediatrics, University Hospital Würzburg , Würzburg, Germany
                Institute of Virology and Immunobiology, University of Würzburg , Würzburg, Germany
                Institute of Virology and Immunobiology, University of Würzburg , Würzburg, Germany
                Janssen Pharmaceutica , Beerse, Belgium
                Janssen Pharmaceutica , Beerse, Belgium
                Global Medical Affairs, Infectious Diseases and Vaccines (IDV) , Janssen-Cilag, Vienna, Austria
                Department of Pediatrics, University Hospital Würzburg , Würzburg, Germany
                Author notes
                [a]

                K. W. and A. S. contributed equally to this work.

                Presented in part: Congress of the European Society for Paediatric Infectious Diseases, Virtual, 26–29 October 2020 (abstract P0764); International Society for Pharmacoeconomics and Outcomes Research Europe, 16–19 November 2020 (abstract 108199); Kongress für Infektionskrankheiten und Tropenmedizin, Virtual, June 2021 (abstract A-408).

                Correspondence: Andrea Streng, Ph.D., Department of Pediatrics, University Hospital Würzburg, Josef-Schneider-Str 2, 97080 Würzburg, Germany ( streng_a@ 123456ukw.de ).
                Article
                jiac137
                10.1093/infdis/jiac137
                9417125
                35417015
                03f22c1e-f32e-4f5f-b3c5-fa51173ed5f6
                © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 07 January 2022
                : 04 April 2022
                : 08 April 2022
                : 26 May 2022
                Page count
                Pages: 10
                Categories
                Major Article
                Viruses
                AcademicSubjects/MED00290

                Infectious disease & Microbiology
                infant,children,hospitalization,burden of disease,predictors
                Infectious disease & Microbiology
                infant, children, hospitalization, burden of disease, predictors

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