title: Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children.
abstract: Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort.
  
  
  
  Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged <5 years within 24 hours of hospital admission during sentinel surveillance for severe acute respiratory illness (SARI) hospitalization conducted in South Africa during February 2009-December 2013. The primary outcome was life-threatening disease, defined as mechanical ventilation, intensive care unit admission, or death.
  
  
  
  Of 2322 HIV-uninfected children with respiratory syncytial virus (RSV)-associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease, ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6-7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0-4.5; P = .05) compared with RSV monoinfection.
  
  
  
  RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study.
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa.|Wilhelmina Children's Hospital, Utrecht, The Netherlands.|Julius Global Health Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
authors.forename: Natalie I
authors.initials: NI
authors.lastname: Mazur
authors.affiliation: Wilhelmina Children's Hospital, Utrecht, The Netherlands.|Respiratory Syncytial Virus Network (ReSViNET) Ultrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Bont
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia,  USA.|Influenza Program, Centers for Disease Control and Prevention-South Africa, Pretoria, South Africa.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Cohen
authors.affiliation: Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, 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: Cheryl
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.|School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Anne
authors.initials: A
authors.lastname: von Gottberg
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.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Groome
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.|School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Orienka
authors.initials: O
authors.lastname: Hellferscee
authors.affiliation: Julius Global Health Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.|Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Klipstein-Grobusch
authors.affiliation: Klerksdorp Hospital, Klerksdorp, North West Province, South Africa.
authors.forename: Omphile
authors.initials: O
authors.lastname: Mekgoe
authors.affiliation: Department of Pediatrics, Pietermaritzburg Metropolitan Hospital, University of KwaZulu-Natal, KwaZulu-Natal South Africa.
authors.forename: Fathima
authors.initials: F
authors.lastname: Naby
authors.affiliation: Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, 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: Jocelyn
authors.initials: J
authors.lastname: Moyes
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia,  USA.|Influenza Program, Centers for Disease Control and Prevention-South Africa, Pretoria, South Africa.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tempia
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Florette K
authors.initials: FK
authors.lastname: Treurnicht
authors.affiliation: Global Disease Detection Center South Africa, Division of Global Health Protection, Centers for Disease Control and Prevention, Pretoria, South Africa.|Department of Medical Virology, University of Pretoria, South Africa.
authors.forename: Marietje
authors.initials: M
authors.lastname: Venter
authors.affiliation: Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, 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: Sibongile
authors.initials: S
authors.lastname: Walaza
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.|School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wolter
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.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
mesh_terms: D002675:Child, Preschool; D060085:Coinfection / Q000401:mortality / Q000473:pathology* / Q000821:virology; D003422:Critical Care / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D025202:Molecular Diagnostic Techniques; D009305:Nasopharynx / Q000821:virology; D011446:Prospective Studies; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D012141:Respiratory Tract Infections / Q000401:mortality / Q000473:pathology* / Q000821:virology; D013019:South Africa; D016019:Survival Analysis; D014777:Virus Diseases / Q000401:mortality / Q000473:pathology* / Q000821:virology; D014780:Viruses / Q000145:classification / Q000302:isolation & purification*
keywords: lower respiratory tract infection disease severity; respiratory syncytial virus; viral coinfection