Aetiology of acute respiratory infection in preschool children requiring hospitalisation in Europe—results from the PED-MERMAIDS multicentre case–control study

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Abstract

Background

Both pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation.

Methods

349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019. Admission day NP swabs were analysed by multiplex PCR for 25 targets.

Results

RSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly associated with ARI hospitalisation (OR adjusted for age and season: 20.6, 95% CI: 9.4 to 45.3). Detection of three other viral pathogens showed strong associations with ARI hospitalisation: influenza viruses had an adjusted OR of 6.1 (95% CI: 2.5 to 14.9), parainfluenza viruses (PIVs) an adjusted OR of 4.6 (95% CI: 1.8 to 11.3) and metapneumoviruses an adjusted OR of 4.5 (95% CI: 1.3 to 16.1). Influenza viruses had a PAF of 7.9%, PIVs of 6.5% and metapneumoviruses of 3.0%. In contrast, most other pathogens were found in similar proportions in cases and controls, including Streptococcus pneumoniae, which was weakly associated with case status, and endemic coronaviruses.

Conclusion

RSV is the predominant cause of ARI hospitalisations in young children in Europe and its detection, as well as detection of influenza virus, PIV or metapneumovirus, on NP swabs can establish aetiology with high probability. PAFs for RSV and influenza virus are highly seasonal and age dependent.

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Most cited references 39

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Community-acquired pneumonia requiring hospitalization among U.S. children.

Seema Jain, Derek Williams, Sandra Arnold … (2015)

Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed.

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Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation

Chris Feudtner, James Feinstein, Wenjun Zhong … (2014)

Background The pediatric complex chronic conditions (CCC) classification system, developed in 2000, requires revision to accommodate the International Classification of Disease 10th Revision (ICD-10). To update the CCC classification system, we incorporated ICD-9 diagnostic codes that had been either omitted or incorrectly specified in the original system, and then translated between ICD-9 and ICD-10 using General Equivalence Mappings (GEMs). We further reviewed all codes in the ICD-9 and ICD-10 systems to include both diagnostic and procedural codes indicative of technology dependence or organ transplantation. We applied the provisional CCC version 2 (v2) system to death certificate information and 2 databases of health utilization, reviewed the resulting CCC classifications, and corrected any misclassifications. Finally, we evaluated performance of the CCC v2 system by assessing: 1) the stability of the system between ICD-9 and ICD-10 codes using data which included both ICD-9 codes and ICD-10 codes; 2) the year-to-year stability before and after ICD-10 implementation; and 3) the proportions of patients classified as having a CCC in both the v1 and v2 systems. Results The CCC v2 classification system consists of diagnostic and procedural codes that incorporate a new neonatal CCC category as well as domains of complexity arising from technology dependence or organ transplantation. CCC v2 demonstrated close comparability between ICD-9 and ICD-10 and did not detect significant discontinuity in temporal trends of death in the United States. Compared to the original system, CCC v2 resulted in a 1.0% absolute (10% relative) increase in the number of patients identified as having a CCC in national hospitalization dataset, and a 0.4% absolute (24% relative) increase in a national emergency department dataset. Conclusions The updated CCC v2 system is comprehensive and multidimensional, and provides a necessary update to accommodate widespread implementation of ICD-10.

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Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis

Harish Nair, Eric AF Simões, Igor Rudan … (2013)

Summary Background The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. Methods We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. Findings We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3–13·9 million) episodes of severe and 3·0 million (2·1–4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265 000 (95% CI 160 000–450 000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. Interpretation Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. Funding WHO.

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Journal

Journal ID (nlm-ta): BMJ Open Respir Res

Journal ID (iso-abbrev): BMJ Open Respir Res

Journal ID (hwp): bmjresp

Journal ID (publisher-id): bmjopenrespres

Title: BMJ Open Respiratory Research

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2052-4439

Publication date Collection: 2021

Publication date (Electronic): 29 July 2021

Volume: 8

Issue: 1

Electronic Location Identifier: e000887

Affiliations

[1 ]departmentPaediatric Infectious Diseases Research Group, Institute for Infection and Immunity , St. George’s, University of London , London, UK

[2 ]departmentInstitute for Medical Microbiology and Hospital Hygiene , Heinrich Heine University Düsseldorf , Düsseldorf, Germany

[3 ]departmentLaboratory of Clinical Microbiology , Antwerp University Hospital , Edegem, Belgium

[4 ]departmentLaboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO) , University of Antwerp , Antwerp, Belgium

[5 ]departmentCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine , University of Oxford , Oxford, UK

[6 ]departmentInfectious Diseases Unit, 3rd Department of Paediatrics , Aristotle University School of Health Sciences, Hippokration General Hospital , Thessaloniki, Greece

[7 ]departmentPaediatric Infectious Diseases Unit, Department of Paediatrics, Hospital Universitario 12 de Octubre and Red de Investigación Traslacional en Infectología Pediátrica (RITIP) , Instituto de Investigación 12 de Octubre (imas12) , Madrid, Spain

[8 ]departmentDivision of Paediatric Infectious Diseases, Department of Women’s and Children’s Health , University Hospital of Padua , Padova, Italy

[9 ]departmentPaediatric Emergency Department, Department of Women’s and Children’s Health , University Hospital of Padua , Padova, Italy

[10 ]departmentNIHR Southampton Biomedical Research Centre , University of Southampton and University Hospital Southampton NHS Foundation Trust , Southampton, UK

[11 ]department2nd Department of Paediatrics , National and Kapodistrian University of Athens (NKUA) School of Medicine, P. and A. Kyriakou Children’s Hospital , Athens, Greece

[12 ]departmentPaediatric Department, University Hospital Lewisham , Lewisham and Greenwich NHS Trust , London, UK

[13 ]departmentDepartment of Paediatric Cardiology, Pulmonology and Intensive Care Medicine , University Children’s Hospital Tübingen , Tübingen, Germany

[14 ]departmentClinical Pathways and Epidemiology Unit , IRCCS Bambino Gesù Children’s Hospital , Rome, Italy

[15 ]departmentTranslational Paediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago , Servizo Galego de Saude , Santiago de Compostela, Spain

[16 ]departmentGenetics, Vaccines and Infectious Diseases Research Group, Instituto de Investigación Sanitaria de Santiago , Universidade de Santiago de Compostela , Santiago de Compostela, Spain

[17 ]departmentClinic of Children’s Diseases, Institute of Clinical Medicine , Vilnius University , Vilnius, Lithuania

[18 ]departmentDepartment of Paediatrics , St-Pierre Hospital Brussels , Brussels, Belgium

[19 ]department1st Department of Paediatrics , National and Kapodistrian University of Athens (NKUA) School of Medicine, Agia Sophia Children’s Hospital of Athens , Athens, Greece

[20 ]departmentDepartment of Paediatric Infectious Diseases , Alder Hey Children's Hospital , Liverpool, UK

[21 ]departmentPaediatrics and Infectious Diseases Department , La Paz University Hospital , Madrid, Spain

[22 ]departmentDepartment of Paediatrics , University General Hospital of Patras, Patras Medical School , Patras, Greece

[23 ]departmentDivision of Paediatric Infectious Diseases and Rheumatology, Department of Paediatrics and Adolescent Medicine , University Medical Centre, Medical Faculty, University of Freiburg , Freiburg, Germany

[24 ]departmentNational Heart and Lung Division, Faculty of Medicine , Imperial College London , London, UK

[25 ]departmentDepartment of Medical Microbiology , Amsterdam UMC , Amsterdam, The Netherlands

[26 ]departmentDepartment of Viroscience , ErasmusMC , Rotterdam, The Netherlands

[27 ]departmentSophia Children’s Hospital , ErasmusMC , Rotterdam, The Netherlands

[28 ]departmentDepartment of Infectious Diseases and Vaccinology , University of Basel Children’s Hospital (UKBB) , Basel, Switzerland

Author notes

[Correspondence to ] Dr Malte Kohns Vasconcelos; mkohns@ 123456sgul.ac.uk

Author information

Malte Kohns Vasconcelos http://orcid.org/0000-0002-6207-9442

Jessica Jarvis http://orcid.org/0000-0002-8591-5378

Article

Publisher ID: bmjresp-2021-000887

DOI: 10.1136/bmjresp-2021-000887

PMC ID: 8323363

PubMed ID: 34326154

SO-VID: e6219dd7-f822-4bdc-9ed8-c0c98f959c9b

License:

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 29 January 2021

Date accepted : 05 July 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100011272, FP7 Health;

Award ID: HEALTH-F3-2013-602525

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Keywords: clinical epidemiology,paediatric lung disaese,pneumonia,respiratory infection,viral infection

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Keywords: clinical epidemiology, paediatric lung disaese, pneumonia, respiratory infection, viral infection

Aetiology of acute respiratory infection in preschool children requiring hospitalisation in Europe—results from the PED-MERMAIDS multicentre case–control study

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Abstract

Background

Methods

Results

Conclusion

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Novel Coronavirus Disease COVID-19

Most cited references 39

Community-acquired pneumonia requiring hospitalization among U.S. children.

Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation

Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis

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