Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.

BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.

A Systematic Review of European Clinical Practice Guidelines for Respiratory Syncytial Virus Prophylaxis.

BACKGROUND: Since the widespread adoption of palivizumab prophylaxis in Europe, there have been a number of clinical practice guidelines (CPGs) published for the prevention of respiratory syncytial virus (RSV) infection in children. The aim of this systematic review was to identify CPGs for the prevention of RSV infection across Europe. METHODS: We performed a systematic literature search and contacted European influenza and respiratory virus networks and public health institutions, to identify national CPGs for the prevention of RSV infection. The Reporting Items for practice Guidelines in Healthcare (RIGHT) Statement checklist was applied to extract data and review the quality of reporting. RESULTS: A total of 20 national CPGs were identified, all published between 2000 and 2018. The greatest discrepancy between guidelines was the recommendations for palivizumab prophylaxis for premature infants, with recommendations varying by gestational age. All guidelines recommended or considered the use of palivizumab in infants with bronchopulmonary dysplasia, 85% (n = 17) in children with congenital heart disease (CHD), and 60% (n = 12) in children with severe combined immunodeficiency. CONCLUSIONS: We recommend that agencies publishing RSV prevention guidelines adopt the RIGHT reporting requirements when updating these guidelines to improve the presentation of the evidence-base for decisions.

Panel 4: Report of the Microbiology Panel.

Objective To perform a comprehensive review of the literature from July 2011 until June 2015 on the virology and bacteriology of otitis media in children. Data Sources PubMed database of the National Library of Medicine. Review Methods Two subpanels comprising experts in the virology and bacteriology of otitis media were created. Each panel reviewed the relevant literature in the fields of virology and bacteriology and generated draft reviews. These initial reviews were distributed to all panel members prior to meeting together at the Post-symposium Research Conference of the 18th International Symposium on Recent Advances in Otitis Media, National Harbor, Maryland, in June 2015. A final draft was created, circulated, and approved by all panel members. Conclusions Excellent progress has been made in the past 4 years in advancing our understanding of the microbiology of otitis media. Numerous advances were made in basic laboratory studies, in animal models of otitis media, in better understanding the epidemiology of disease, and in clinical practice. Implications for Practice (1) Many viruses cause acute otitis media without bacterial coinfection, and such cases do not require antibiotic treatment. (2) When respiratory syncytial virus, metapneumovirus, and influenza virus peak in the community, practitioners can expect to see an increase in clinical otitis media cases. (3) Biomarkers that predict which children with upper respiratory tract infections will develop otitis media may be available in the future. (4) Compounds that target newly identified bacterial virulence determinants may be available as future treatment options for children with otitis media.

Identification of respiratory viruses with a novel point-of-care multianalyte antigen detection test in children with acute respiratory tract infection.

BACKGROUND: Rapid etiological diagnosis of a respiratory virus infection may have impact on antiviral and antibiotic therapy, patient cohorting, and prediction of the clinical course. Most point-of-care tests for detection of respiratory viruses have limitations in diagnostic performance and clinical usability. A novel, multianalyte point-of-care antigen detection test system (mariPOC(®); ArcDia International Oy Ltd., Turku, Finland) detects eight respiratory viruses (influenza A and B viruses, respiratory syncytial virus (RSV), adenovirus, human metapneumovirus, and parainfluenza type 1, 2, and 3 viruses) from a single nasopharyngeal swab specimen by a fully automated, random-access immunoassay method. OBJECTIVES: To evaluate mariPOC(®) point-of-care test system in comparison with reverse transcription polymerase chain reaction (RT-PCR) in a pediatric emergency department setting. STUDY DESIGN: Prospectively collected samples from 158 children (mean age, 1.8 years) with respiratory symptoms and/or fever were analyzed both by mariPOC(®) and by multiplex RT-PCR. RESULTS: The sensitivities and specificities (95% confidence intervals) of the mariPOC(®) test were for influenza A (n = 7), 71% (38-100) and 100%; influenza B (n = 22), 86% (72-100) and 98% (95-100); RSV (n = 35), 89% (78-99) and 100%; adenovirus (n = 12), 25% (1-50) and 97% (95-99); and for human metapneumovirus (n = 8), 50% (15-85) and 100%, respectively. Parainfluenzaviruses were detected only in five patients. CONCLUSIONS: This novel point-of-care test system is a rapid, practical, and specific method for simultaneous detection of eight respiratory viruses. Compared with RT-PCR, its sensitivity is moderately high for detection of RSV and influenza viruses, and low for adenovirus.

Panel 5: Microbiology and immunology panel.

OBJECTIVE: The objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media. DATA SOURCES: PubMed database of the National Library of Medicine. REVIEW METHODS: Three subpanels with co-chairs comprising experts in the virology, bacteriology, and immunology of otitis media were formed. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a second draft was created. The entire panel met at the 10th International Symposium on Recent Advances in Otitis Media in June 2011 and discussed the review and refined the content further. A final draft was created, circulated, and approved by the panel. CONCLUSION: Excellent progress has been made in the past 4 years in advancing an understanding of the microbiology and immunology of otitis media. Advances include laboratory-based basic studies, cell-based assays, work in animal models, and clinical studies. IMPLICATIONS FOR PRACTICE: The advances of the past 4 years formed the basis of a series of short-term and long-term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media.