title: Rule-Out Outbreak: 24-Hour Metagenomic Next-Generation Sequencing for Characterizing Respiratory Virus Source for Infection Prevention.
abstract: Metagenomic next-generation sequencing (mNGS) has been used to uncover unusual causes of infectious diseases but has not been used routinely for the investigation of putative nosocomial outbreaks. Here, we describe the use of mNGS during investigation of a cluster of human rhinovirus (HRV)-positive infections on a high-risk pulmonary ward.
  We performed mNGS on 6 midnasal turbinate swabs from 4 case-patients and 10 swabs from 9 control outpatients that tested positive for enterovirus/rhinovirus by the FilmArray system.
  HRV reads were recovered in 15 (94%) of the 16 samples sequenced. Phylogenetic analysis of HRV whole genomes from the 4 case-patients and 5 outpatient controls along with partial genomes from additional outpatient controls revealed that isolates from the case-patients were not directly related and that the 2 closest case HRV genomes had an estimated time to most recent common ancestor of 172 years. Our turnaround time from receipt of the sample to phylogenetic analysis was 24 hours.
  We found the use of mNGS downstream of a rapid polymerase chain reaction respiratory panel during an investigation of 4 hospital-acquired rhinovirus infections to rapidly dispel concern of a single-source transmission event.
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle.|Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington ; and.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Greninger
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington ; and.|Seattle Children's Research Institute, Washington.
authors.forename: Alpana
authors.initials: A
authors.lastname: Waghmare
authors.affiliation: Seattle Children's Research Institute, Washington.
authors.forename: Amanda
authors.initials: A
authors.lastname: Adler
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle.
authors.forename: Xuan
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Crowley
authors.affiliation: Seattle Children's Research Institute, Washington.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Englund
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Kuypers
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle.|Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington ; and.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Jerome
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington ; and.|Seattle Children's Research Institute, Washington.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Zerr
mesh_terms: D002648:Child; D002675:Child, Preschool; D003428:Cross Infection / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D004196:Disease Outbreaks / Q000517:prevention & control*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007223:Infant; D056186:Metagenomics / Q000379:methods*; D010802:Phylogeny; D010850:Picornaviridae Infections / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012229:Rhinovirus / Q000235:genetics*; D014861:Washington / Q000453:epidemiology
keywords: HPIV3; human parainfluenza 3 virus; mNGS; next-generation sequencing; respiratory virus; rule out outbreak.