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      Respiratory Viral Detection in Children and Adults: Comparing Asymptomatic Controls and Patients With Community-Acquired Pneumonia

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          Abstract

          Background.  The clinical significance of viruses detected in patients with community-acquired pneumonia (CAP) is often unclear.

          Methods.  We conducted a prospective study to identify the prevalence of 13 viruses in the upper respiratory tract of patients with CAP and concurrently enrolled asymptomatic controls with real-time reverse-transcriptase polymerase chain reaction. We compared age-stratified prevalence of each virus between patients with CAP and controls and used multivariable logistic regression to calculate attributable fractions (AFs).

          Results.  We enrolled 1024 patients with CAP and 759 controls. Detections of influenza, respiratory syncytial virus, and human metapneumovirus were substantially more common in patients with CAP of all ages than in controls (AFs near 1.0). Parainfluenza and coronaviruses were also more common among patients with CAP (AF, 0.5–0.75). Rhinovirus was associated with CAP among adults (AF, 0.93) but not children (AF, 0.02). Adenovirus was associated with CAP only among children <2 years old (AF, 0.77).

          Conclusions.  The probability that a virus detected with real-time reverse-transcriptase polymerase chain reaction in patients with CAP contributed to symptomatic disease varied by age group and specific virus. Detections of influenza, respiratory syncytial virus, and human metapneumovirus among patients with CAP of all ages probably indicate an etiologic role, whereas detections of parainfluenza, coronaviruses, rhinovirus, and adenovirus, especially in children, require further scrutiny.

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          Most cited references32

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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.
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              Gene quantification using real-time quantitative PCR: an emerging technology hits the mainstream.

              The recent flood of reports using real-time Q-PCR testifies to the transformation of this technology from an experimental tool into the scientific mainstream. Many of the applications of real-time Q-PCR include measuring mRNA expression levels, DNA copy number, transgene copy number and expression analysis, allelic discrimination, and measuring viral titers. The range of applications of real-time Q-PCR is immense and has been fueled in part by the proliferation of lower-cost instrumentation and reagents. Successful application of real-time Q-PCR is not trivial. However, this review will help guide the reader through the variables that can limit the usefulness of this technology. Careful consideration of the assay design, template preparation, and analytical methods are essential for accurate gene quantification.
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                Author and article information

                Journal
                J Infect Dis
                J. Infect. Dis
                jid
                jinfdis
                The Journal of Infectious Diseases
                Oxford University Press
                0022-1899
                1537-6613
                15 February 2016
                14 July 2015
                : 213
                : 4
                : 584-591
                Affiliations
                [1 ] Department of Emergency Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
                [2 ] Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
                [3 ] Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee
                [4 ] Department of Pathology, Microbiology & Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee
                [5 ] Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
                [6 ] Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee
                [7 ] Department of Pediatrics
                [8 ] Departments of Pediatrics and Internal Medicine
                [9 ] ARUP Institute for Clinical and Experimental Pathology
                [10 ] Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City
                [11 ] Centers for Disease Control and Prevention , Atlanta, Georgia
                Author notes

                Presented in part: Society for Academic Emergency Medicine Annual Meeting, Atlanta, Georgia, May 2013. Abstract 665.

                Correspondence: W. H. Self, 1313 21st Ave S, 703 Oxford House, Nashville, TN 37232 ( wesley.self@ 123456vanderbilt.edu ).
                Article
                jiv323
                10.1093/infdis/jiv323
                4721902
                26180044
                f064cc37-b974-42bc-93e3-fa74e1e6d6f6
                © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@ 123456oup.com .

                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.

                History
                : 11 March 2015
                : 22 May 2015
                Funding
                Funded by: the CDC
                Award ID: U18 IP000299
                Funded by: the Vanderbilt Institute for Clinical and Translational Research
                Award ID: UL1TR000445)
                Funded by: the National Institute for Advancing Translational Sciences
                Funded by: the National Institute of General Medical Sciences
                Award ID: 1K23GM110469
                Funded by: National Institute for Advancing Translational Sciences
                Award ID: KL2TR000446
                Funded by: National Institute of Allergy and Infectious Diseases http://dx.doi.org/10.13039/100000060
                Award ID: K23AI104779)
                Funded by: the Agency for HealthCare Research and Quality
                Award ID: 1R03HS022342)
                Funded by: National Institutes of Health http://dx.doi.org/10.13039/100000002
                Categories
                Major Articles and Brief Reports
                Viruses
                Editor's Choice

                Infectious disease & Microbiology
                pneumonia,etiology,virus,asymptomatic infection,attributable fraction

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