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      Viral Pathogen Detection by Metagenomics and Pan-Viral Group Polymerase Chain Reaction in Children With Pneumonia Lacking Identifiable Etiology

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          Two broad-spectrum pathogen detection methods, next-generation sequencing and pan-viral group polymerase chain reaction, detected previously missed, putative pathogens in 34% of children hospitalized with community-acquired pneumonia with no identified etiology.



          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.

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            Community-acquired pneumonia requiring hospitalization among U.S. children.

            Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed.
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              Viral pneumonia.

              About 200 million cases of viral community-acquired pneumonia occur every year-100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries. Copyright © 2011 Elsevier Ltd. All rights reserved.

                Author and article information

                J Infect Dis
                J. Infect. Dis
                The Journal of Infectious Diseases
                Oxford University Press (US )
                01 May 2017
                31 May 2017
                01 May 2018
                : 215
                : 9
                : 1407-1415
                [1 ] Department of Pathology ,
                [2 ] Department of Biomedical Informatics ,
                [3 ] Department of Pediatrics , and
                [4 ] Department of Human Genetics, University of Utah , and
                [5 ] ARUP Institute for Clinical and Experimental Pathology , Salt Lake City, Utah; and
                [6 ] Centers for Disease Control and Prevention , Atlanta, Georgia
                Author notes

                R. S. and K. Q. contributed equally to the study. S. T. and K. A. contributed equally to the study.

                Correspondence: R. Schlaberg, MD, MPH, 500 Chipeta Way, Salt Lake City, UT 84108 ( robert.schlaberg@ ).

                © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail:

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                Page count
                Pages: 9
                Funded by: National Institutes of Health 10.13039/100000002
                Funded by: National Center for Advancing Translational Sciences 10.13039/100006108
                Award ID: 1KL2TR001065
                Award ID: UL1TR001067
                Funded by: Primary Children’s Hospital Foundation
                Funded by: ARUP Institute for Clinical and Experimental Pathology
                Award ID: U181P00030
                Funded by: Centers for Disease Control and Prevention
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