title: Rapid Metagenomic Next-Generation Sequencing during an Investigation of Hospital-Acquired Human Parainfluenza Virus 3 Infections.
abstract: Metagenomic next-generation sequencing (mNGS) is increasingly used for the unbiased detection of viruses, bacteria, fungi, and eukaryotic parasites in clinical samples. Whole-genome sequencing (WGS) of clinical bacterial isolates has been shown to inform hospital infection prevention practices, but this technology has not been utilized during potential respiratory virus outbreaks. Here, we report on the use of mNGS to inform the real-time infection prevention response to a cluster of hospital-acquired human parainfluenza 3 virus (HPIV3) infections at a children's hospital. Samples from 3 patients with hospital-acquired HPIV3 identified over a 12-day period on a general medical unit and 10 temporally associated samples from patients with community-acquired HPIV3 were analyzed. Our sample-to-sequencer time was <24 h, while our sample-to-answer turnaround time was <60 h with a hands-on time of approximately 6 h. Eight (2 cases and 6 controls) of 13 samples had sufficient sequencing coverage to yield the whole genome for HPIV3, while 10 (2 cases and 8 controls) of 13 samples gave partial genomes and all 13 samples had >1 read for HPIV3. Phylogenetic clustering revealed the presence of identical HPIV3 genomic sequence in the two of the cases with hospital-acquired infection, consistent with the concern for recent transmission within the medical unit. Adequate sequence coverage was not recovered for the third case. This work demonstrates the promise of mNGS for providing rapid information for infection prevention in addition to microbial detection.
authors: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA agrening@uw.edu.
authors: Alexander L
authors: AL
authors: Greninger
authors: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors: Danielle M
authors: DM
authors: Zerr
authors: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors: Xuan
authors: X
authors: Qin
authors: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors: Amanda L
authors: AL
authors: Adler
authors: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors: Reigran
authors: R
authors: Sampoleo
authors: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors: Jane M
authors: JM
authors: Kuypers
authors: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors: Janet A
authors: JA
authors: Englund
authors: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.|Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors: Keith R
authors: KR
authors: Jerome
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D003428:Cross Infection / Q000453:epidemiology* / Q000821:virology; D004196:Disease Outbreaks; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D056186:Metagenomics; D017720:Molecular Epidemiology; D010224:Parainfluenza Virus 3, Human / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D010802:Phylogeny; D010253:Respirovirus Infections / Q000453:epidemiology* / Q000821:virology; D017385:Sequence Homology; D013997:Time Factors; D055815:Young Adult
keywords: HPIV3; hospital-acquired infections; human parainfluenza 3 virus; infection prevention; mNGS; metagenomics; next-generation sequencing; parainfluenza; rapid sequencing; viral sequencing