title: Viral Etiology and the Impact of Codetection in Young Children Presenting With Influenza-Like Illness.
abstract: BACKGROUND
  Children with acute respiratory tract infection (ARTI) frequently exhibit virus-virus codetection, yet the clinical significance of ARTI remains contentious. Using data from a prospective cohort of children with influenza-like illness, we examined the virology of ARTI and determined the clinical impact of virus-virus codetection.
  
  
  METHODS
  Children aged 6 to 59 months who presented to a tertiary pediatric hospital between influenza seasons 2008 and 2012 with fever and acute respiratory symptoms were enrolled, and nasal samples were collected. Respiratory viruses were identified by culture and polymerase chain reaction. We compared demographics, presenting symptoms, and clinical outcomes of children with a single-virus infection and those in whom 2 or more viruses were detected (virus-virus codetection). We used logistic regression models and estimated marginal means to calculate the adjusted odds ratios and probabilities of symptom presentation, prescription of antibiotics, and hospitalization.
  
  
  RESULTS
  Of 2356 children, a virus was detected in 1630 (69.2%) of them; rhinovirus (40.8%), influenza (29.5%), and respiratory syncytial virus (26.4%) were detected most commonly. Two or more viruses were detected in 25% of these children. After we adjusted for demographic factors, children with virus-virus codetection had greater odds of presenting with cough (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.2-3.1) and rhinorrhea (aOR, 1.8; 95% CI, 1.1-2.9) than those with a single-virus infection, although both symptoms were common. Children with influenza and respiratory syncytial virus combined had the highest probability of hospitalization (55%; 95% CI, 35%-73%), which was significantly greater than for those with influenza infection alone (22%; 95% CI, 16%-29%).
  
  
  CONCLUSIONS
  Overall, virus-virus codetection has limited impact on clinical severity among children with influenza-like illness. However, infection with specific pathogen pairs might be associated with more severe outcomes. Routine diagnostics to identify specific viruses should be restricted to common pathogens.
authors.affiliation: Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, West Perth.
authors.forename: Faye J
authors.initials: FJ
authors.lastname: Lim
authors.affiliation: Department of General Paediatrics.|Department of Infectious Diseases.
authors.forename: Zoe V
authors.initials: ZV
authors.lastname: Wake
authors.affiliation: PathWest Laboratory Medicine WA, QEII Medical Centre, Nedlands.|School of Pathology and Laboratory Medicine, Crawley.
authors.forename: Avram
authors.initials: A
authors.lastname: Levy
authors.affiliation: PathWest Laboratory Medicine WA, QEII Medical Centre, Nedlands.
authors.forename: Simone
authors.initials: S
authors.lastname: Tempone
authors.affiliation: Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, West Perth.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Moore
authors.affiliation: Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, West Perth.|Department of General Paediatrics.|School of Paediatrics and Child Health, University of Western Australia.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Richmond
authors.affiliation: Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, West Perth.
authors.forename: Nicholas
authors.initials: N
authors.lastname: de Klerk
authors.affiliation: Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, West Perth.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Conway
authors.affiliation: Department of Microbiology, PathWest Laboratory Medicine WA, Princess Margaret Hospital for Children, Perth.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Keil
authors.affiliation: Communicable Disease Control Directorate, Department of Health, Grace Vaughan House, Shenton Park, Australia.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Effler
authors.affiliation: PathWest Laboratory Medicine WA, QEII Medical Centre, Nedlands.|School of Pathology and Laboratory Medicine, Crawley.
authors.forename: David W
authors.initials: DW
authors.lastname: Smith
authors.affiliation: Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, West Perth.|Department of Infectious Diseases.|School of Paediatrics and Child Health, University of Western Australia.|Department of Microbiology, PathWest Laboratory Medicine WA, Princess Margaret Hospital for Children, Perth.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Blyth
mesh_terms: D002675:Child, Preschool; D060085:Coinfection / Q000175:diagnosis / Q000821:virology*; D005260:Female; D006801:Humans; D007223:Infant; D007251:Influenza, Human / Q000821:virology*; D008297:Male; D010850:Picornaviridae Infections / Q000175:diagnosis / Q000821:virology; D011446:Prospective Studies; D018357:Respiratory Syncytial Virus Infections / Q000175:diagnosis / Q000821:virology; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000821:virology*; D012229:Rhinovirus; D014904:Western Australia / Q000453:epidemiology
keywords: child; codetection; respiratory infection; viral infection