title: Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta-analysis.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV-associated ALRI. We aimed to identify risk factors for RSV-associated ALRI in young children.
  
  
  METHODS
  We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN) collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta-analyses to estimate odds ratios with 95% confidence intervals (CI) for individual risk factors.
  
  
  RESULTS
  We identified 20 studies (3 were unpublished data) with "good quality" that investigated 18 risk factors for RSV-associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV-associated ALRI. The meta-estimates of their odds ratio (ORs) with corresponding 95% confidence intervals (CI) are prematurity 1.96 (95% CI 1.44-2.67), low birth weight 1.91 (95% CI 1.45-2.53), being male 1.23 (95% CI 1.13-1.33), having siblings 1.60 (95% CI 1.32-1.95), maternal smoking 1.36 (95% CI 1.24-1.50), history of atopy 1.47 (95% CI 1.16-1.87), no breastfeeding 2.24 (95% CI 1.56-3.20) and crowding 1.94 (95% CI 1.29-2.93). Although there were insufficient studies available to generate a meta-estimate for HIV, all articles (irrespective of quality scores) reported significant associations between HIV and RSV-associated ALRI.
  
  
  CONCLUSIONS
  This study presents a comprehensive report of the strength of association between various socio-demographic risk factors and RSV-associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause) ALRI and thus, in addition to the future impact of novel RSV vaccines, national action against ALRI risk factors as part of national control programmes can be expected to reduce burden of disease from RSV. Further research which identifies, accesses and analyses additional unpublished RSV data sets could further improve the precision of these estimates.
authors.affiliation: Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Ting
authors.initials: T
authors.lastname: Shi
authors.affiliation: Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Balsells
authors.affiliation: Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wastnedge
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infectious, National Centre for Emerging and Zoonotic Infectious Diseases (NCEZID), Centres for Disease Control and Prevention (CDC), Anchorage, AK, USA ; Alaska Native Tribal Health Consortium, Anchorage, AK, USA.
authors.forename: Rosalyn
authors.initials: R
authors.lastname: Singleton
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda MD, USA.
authors.forename: Zeba A
authors.initials: ZA
authors.lastname: Rasmussen
authors.affiliation: Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and MRC Unit on Child & Adolescent Health, University of Cape Town, South Africa.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Zar
authors.affiliation: Department of Pediatrics, Charité University Medical Center, Berlin, Germany.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Rath
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa ; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa ; Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.affiliation: Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Campbell
authors.affiliation: Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Linda Cheyenne
authors.initials: LC
authors.lastname: Vaccari
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infectious, National Centre for Emerging and Zoonotic Infectious Diseases (NCEZID), Centres for Disease Control and Prevention (CDC), Anchorage, AK, USA.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Bulkow
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda MD, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Thomas
authors.affiliation: Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and MRC Unit on Child & Adolescent Health, University of Cape Town, South Africa.
authors.forename: Whitney
authors.initials: W
authors.lastname: Barnett
authors.affiliation: Department of Pediatrics, Charité University Medical Center, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hoppe
authors.affiliation: Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom ; Centre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom ; Joint last authorship.
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.affiliation: Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom ; Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom ; Public Health Foundation of India, New Delhi, India ; Joint last authorship.
authors.forename: Harish
authors.initials: H
authors.lastname: Nair
mesh_terms: D000208:Acute Disease; D002675:Child, Preschool; D003906:Developing Countries; D005260:Female; D014943:Global Health; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D007223:Infant; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D018357:Respiratory Syncytial Virus Infections / Q000453:epidemiology* / Q000401:mortality; D012136:Respiratory Syncytial Viruses / Q000302:isolation & purification*; D012141:Respiratory Tract Infections / Q000453:epidemiology* / Q000401:mortality / Q000821:virology; D012307:Risk Factors