Program Schedule

779
Viral Pathogen Detection by Metagenomics and Panviral PCR in Children with Pneumonia with no Identifiable Etiology: Preliminary Results from the CDC Etiology of Pneumonia in the Community (EPIC) Study

Session: Poster Abstract Session: Clinical Respiratory Infections
Friday, October 10, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Posters
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  • Background: Community-acquired pneumonia (CAP) is a leading cause of pediatric hospitalization. Consistent with previous studies, no pathogen was identified in 19% of children hospitalized with clinical and radiographic CAP in the CDC EPIC study despite comprehensive viral and bacterial diagnostic testing. Pathogen identification is a critical step for appropriate antimicrobial use. Here we applied two broad pathogen detection approaches, RNA-Seq-based metagenomics and a panviral family/genus PCR panel, to identify unrecognized pathogens in children with CAP of no identifiable etiology. Age and season-matched children served as controls.

    Methods: We obtained nasopharyngeal/oropharyngeal (NP/OP) swabs from hospitalized children <5 years with CAP and controls enrolled at the Utah site of the EPIC study.  Patients included in this analysis had negative results by blood culture, whole blood PCR, pleural fluid culture and PCR, NP/OP PCR for viruses and atypical bacteria, and paired serologies for selected viruses. Total RNA was subjected to metagenomics (mean 12 million sequencing reads/sample) and viral sequences identified with a custom data analysis pipeline. Total nucleic acid was also tested by panviral family/genus conventional PCR for detection of 19 viral genera and family with known and potentially novel viral pathogens.

    Results: We studied 14 hospitalized children <5 years with CAP (median age 1.8 years; interquartile range [IQR] 1.1-2.7) and 53 controls (median age 1.7 years; IQR 0.8-3.4).  Viruses were identified in 9/14 (53%) children with CAP and in 21/53 (40%) controls (Figure).  Human bocavirus (HBoV) was detected significantly more frequently in children with CAP (odds ratio 21; 95% CI 2-206).

    Conclusion: Two broad pathogen detection approaches identified human viruses in >50% of children with CAP of previously unrecognized etiology. However, most viruses, including anellovirus and herpes viruses were also prevalent among controls making their role uncertain. HBoV detection was associated with CAP. In addition to pathogen detection, metagenomics allows for genome sequencing, phylogenetic analyses, and identification of entirely unexpected viruses. Further analysis on a larger sample is underway.

     

    Robert Schlaberg, MD, MPH1,2, Krista Queen, PhD3, Keith Simmon, MS4, Keith Tardif, PhD2, Chris Stockmann, MSc5, Steven Flygare, MS6, Brett Kennedy, PhD6, Karl Voelkerding, MD1,2, Anna M. Bramley, MPH3, Karen Eilbeck, PhD4, Mark Yandell, PhD6, Seema Jain, MD, MPH7, Andrew Pavia, MD, FIDSA, FSHEA5, Suxiang Tong, PhD3 and Krow Ampofo, MD5, (1)Department of Pathology, University of Utah, Salt Lake City, UT, (2)ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, (3)Centers for Disease Control and Prevention (CDC), Atlanta, GA, (4)Department of Biomedical Informatics, University of Utah, Salt Lake City, UT, (5)Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Utah School of Medicine, Salt Lake City, UT, (6)Department of Human Genetics, University of Utah, Salt Lake City, UT, (7)Centers for Disease Control and Prevention, Atlanta, GA

    Disclosures:

    R. Schlaberg, None

    K. Queen, None

    K. Simmon, None

    K. Tardif, None

    C. Stockmann, None

    S. Flygare, None

    B. Kennedy, None

    K. Voelkerding, None

    A. M. Bramley, None

    K. Eilbeck, None

    M. Yandell, None

    S. Jain, None

    A. Pavia, None

    S. Tong, None

    K. Ampofo, None

    Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

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