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      The Burden of Human Metapneumovirus and Respiratory Syncytial Virus Infections in Hospitalized Norwegian Children

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          Summary.

          In a population-based Norwegian hospital study in children, HMPV appeared in epidemics and with five times lower hospitalization rate than RSV. Median HMPV shedding time was 13 days. Low levels of HMPV were rarely detected in healthy children.

          Abstract

          Background.

          The burden of severe human metapneumovirus (HMPV) respiratory tract infections (RTIs) in European children has not been clarified. We assessed HMPV in Norwegian children and compared hospitalization rates for HMPV and respiratory syncytial virus (RSV).

          Methods.

          We prospectively enrolled children (<16 years old) hospitalized with RTI and asymptomatic controls (2006–2015). Nasopharyngeal aspirate samples were analyzed with polymerase chain reaction (PCR) tests for HMPV, RSV, and 17 other pathogens. We genotyped HMPV-positive samples and assessed shedding time in 32 HMPV-infected children.

          Results.

          In children with RTI, HMPV was detected in 7.3% (267 of 3650) and RSV in 28.7% (1048 of 3650). Among controls, 2.1% (7 of 339) had low HMPV levels detected by PCR, but all were culture negative. HMPV primarily occurred from January to April and in regular epidemics. At least 2 HMPV subtypes occurred each season. The average annual hospitalization rates in children <5 years old with lower RTI were 1.9/1000 (HMPV) and 10.4/1000 (RSV). Among children with RTI, the median HMPV shedding time by PCR was 13 days (range, 6–28 days), but all were culture negative (noninfectious) after 13 days.

          Conclusions.

          HMPV appears in epidemics in Norwegian children, with a hospitalization rate 5 times lower than RSV. Low levels of HMPV are rarely detected in healthy children.

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          Most cited references46

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          A newly discovered human pneumovirus isolated from young children with respiratory tract disease

          From 28 young children in the Netherlands, we isolated a paramyxovirus that was identified as a tentative new member of the Metapneumovirus genus based on virological data, sequence homology and gene constellation. Previously, avian pneumovirus was the sole member of this recently assigned genus, hence the provisional name for the newly discovered virus: human metapneumovirus. The clinical symptoms of the children from whom the virus was isolated were similar to those caused by human respiratory syncytial virus infection, ranging from upper respiratory tract disease to severe bronchiolitis and pneumonia. Serological studies showed that by the age of five years, virtually all children in the Netherlands have been exposed to human metapneumovirus and that the virus has been circulating in humans for at least 50 years.
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            Burden of human metapneumovirus infection in young children.

            The inpatient and outpatient burden of human metapneumovirus (HMPV) infection among young children has not been well established. We conducted prospective, population-based surveillance for acute respiratory illness or fever among inpatient and outpatient children less than 5 years of age in three U.S. counties from 2003 through 2009. Clinical and demographic data were obtained from parents and medical records, HMPV was detected by means of a reverse-transcriptase polymerase-chain-reaction assay, and population-based rates of hospitalization and estimated rates of outpatient visits associated with HMPV infection were determined. HMPV was detected in 200 of 3490 hospitalized children (6%), 222 of 3257 children in outpatient clinics (7%), 224 of 3001 children in the emergency department (7%), and 10 of 770 asymptomatic controls (1%). Overall annual rates of hospitalization associated with HMPV infection were 1 per 1000 children less than 5 years of age, 3 per 1000 infants less than 6 months of age, and 2 per 1000 children 6 to 11 months of age. Children hospitalized with HMPV infection, as compared with those hospitalized without HMPV infection, were older and more likely to receive a diagnosis of pneumonia or asthma, to require supplemental oxygen, and to have a longer stay in the intensive care unit. The estimated annual burden of outpatient visits associated with HMPV infection was 55 clinic visits and 13 emergency department visits per 1000 children. The majority of HMPV-positive inpatient and outpatient children had no underlying medical conditions, although premature birth and asthma were more frequent among hospitalized children with HMPV infection than among those without HMPV infection. HMPV infection is associated with a substantial burden of hospitalizations and outpatient visits among children throughout the first 5 years of life, especially during the first year. Most children with HMPV infection were previously healthy. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health.).
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              Antigenic and Genetic Variability of Human Metapneumoviruses

              Human metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxoviridae. Other members of this subfamily, respiratory syncytial virus and avian pneumovirus, can be divided into subgroups based on genetic or antigenic differences or both. For HMPV, the existence of different genetic lineages has been described on the basis of variation in a limited set of available sequences. We address the antigenic relationship between genetic lineages in virus neutralization assays. In addition, we analyzed the genetic diversity of HMPV by phylogenetic analysis of sequences obtained for part of the fusion protein (n = 84) and the complete attachment protein open reading frames (n = 35). On the basis of sequence diversity between attachment protein genes and the differences in virus neutralization titers, two HMPV serotypes were defined. Each serotype could be divided into two genetic lineages, but these did not reflect major antigenic differences.
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                Author and article information

                Journal
                J Infect Dis
                J. Infect. Dis
                jid
                The Journal of Infectious Diseases
                Oxford University Press (US )
                0022-1899
                1537-6613
                01 July 2017
                30 May 2017
                : 216
                : 1
                : 110-116
                Affiliations
                [1 ] Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology , and Departments of
                [2 ] Pediatrics and
                [3 ] Medical Microbiology, St Olavs Hospital, Trondheim University Hospital , Trondheim, Norway
                Author notes

                Correspondence: H. Døllner, MD, PhD, Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Health, 7006 Trondheim, Norway ( henrik.dollner@ 123456ntnu.no ).

                Article
                jix262
                10.1093/infdis/jix262
                7107394
                28838133
                76f7a4f2-2d5e-4898-8eb3-63eeec05348f
                © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.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
                : 13 February 2017
                : 26 May 2017
                Page count
                Pages: 7
                Categories
                Major Article

                Infectious disease & Microbiology
                burden of respiratory tract infections,hospitalization rate,human metapneumovirus,respiratory syncytial virus,virus shedding time

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