title: Viral Pathogen Detection by Metagenomics and Pan-Viral Group Polymerase Chain Reaction in Children With Pneumonia Lacking Identifiable Etiology.
abstract: Community-acquired pneumonia (CAP) is a leading cause of pediatric hospitalization. Pathogen identification fails in approximately 20% of children but is critical for optimal treatment and prevention of hospital-acquired infections. We used two broad-spectrum detection strategies to identify pathogens in test-negative children with CAP and asymptomatic controls.
  
  
  
  Nasopharyngeal/oropharyngeal (NP/OP) swabs from 70 children <5 years with CAP of unknown etiology and 90 asymptomatic controls were tested by next-generation sequencing (RNA-seq) and pan viral group (PVG) PCR for 19 viral families. Association of viruses with CAP was assessed by adjusted odds ratios (aOR) and 95% confidence intervals controlling for season and age group.
  
  
  
  RNA-seq/PVG PCR detected previously missed, putative pathogens in 34% of patients. Putative viral pathogens included human parainfluenza virus 4 (aOR 9.3, P = .12), human bocavirus (aOR 9.1, P < .01), Coxsackieviruses (aOR 5.1, P = .09), rhinovirus A (aOR 3.5, P = .34), and rhinovirus C (aOR 2.9, P = .57). RNA-seq was more sensitive for RNA viruses whereas PVG PCR detected more DNA viruses.
  
  
  
  RNA-seq and PVG PCR identified additional viruses, some known to be pathogenic, in NP/OP specimens from one-third of children hospitalized with CAP without a previously identified etiology. Both broad-range methods could be useful tools in future epidemiologic and diagnostic studies.
authors.affiliation: Department of Pathology.|ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah ; and.
authors.forename: Robert
authors.initials: R
authors.lastname: Schlaberg
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Krista
authors.initials: K
authors.lastname: Queen
authors.affiliation: Department of Biomedical Informatics.
authors.forename: Keith
authors.initials: K
authors.lastname: Simmon
authors.affiliation: ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah; and.
authors.forename: Keith
authors.initials: K
authors.lastname: Tardif
authors.affiliation: Department of Pediatrics, and.
authors.forename: Chris
authors.initials: C
authors.lastname: Stockmann
authors.affiliation: Department of Human Genetics, University of Utah, and.
authors.forename: Steven
authors.initials: S
authors.lastname: Flygare
authors.affiliation: Department of Human Genetics, University of Utah, and.
authors.forename: Brett
authors.initials: B
authors.lastname: Kennedy
authors.affiliation: Department of Pathology.|ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah ; and.
authors.forename: Karl
authors.initials: K
authors.lastname: Voelkerding
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Anna
authors.initials: A
authors.lastname: Bramley
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Informatics.
authors.forename: Karen
authors.initials: K
authors.lastname: Eilbeck
authors.affiliation: Department of Human Genetics, University of Utah, and.
authors.forename: Mark
authors.initials: M
authors.lastname: Yandell
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Seema
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Pediatrics, and.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Pavia
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Suxiang
authors.initials: S
authors.lastname: Tong
authors.affiliation: Department of Pediatrics, and.
authors.forename: Krow
authors.initials: K
authors.lastname: Ampofo
mesh_terms: D002675:Child, Preschool; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000175:diagnosis / Q000821:virology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D056186:Metagenomics / Q000379:methods*; D011024:Pneumonia, Viral / Q000175:diagnosis / Q000821:virology*; D016133:Polymerase Chain Reaction / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods; D014780:Viruses / Q000235:genetics*
keywords: RNA sequencing (RNA-seq); metagenomics; pan-viral group polymerase chain reaction (PVG PCR); pneumonia.