Human metapneumovirus: Clinical and virological aspects in Norwegian children

Background It is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV). Methods We prospectively enrolled hospitalized children aged 16 years with LRTI from 2006 to 2015. Children were clinically examined, and nasopharyngeal aspirates were analyzed using semi-quantitative, real-time polymerase chain reaction tests for HMPV, RSV and 17 other pathogens. HMPV-positive samples were genotyped. Results A total of 171 children had HMPV infection. HMPV-infected children with single virus (n = 106) and co-detections (n = 65) had similar clinical manifestations. No clinical differences were found between HMPV genotypes A (n = 67) and B (n = 80). The HMPV-infected children were older (median 17.2 months) than RSV-infected children (median 7.3 months, n = 859). Among single virus-infected children, no differences in age-adjusted LRTI diagnoses were found between HMPV and RSV. Age was an important factor for disease severity among single virus-infected children, where children 6 months old with HMPV had a milder disease than those with RSV, while in children 12–23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age 12 months (HMPV), and age 6 months (RSV), prematurity, 1 chronic disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease. PLOSONE | DOI:10.1371/journal.pone.0170200 January 17, 2017 1 / 19 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 Citation:Moe N, Krokstad S, Stenseng IH, Christensen A, Skanke LH, Risnes KR, et al. (2017) Comparing HumanMetapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease. PLoS ONE 12(1): e0170200. doi:10.1371/journal. pone.0170200 Editor: Oliver Schildgen, Kliniken der Stadt Köln gGmbH, GERMANY Received:November 16, 2016 Accepted:December 30, 2016 Published: January 17, 2017 Copyright: 2017 Moe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper, including 5 tables, and in the Supporting Information files (2 tables). Funding: This research was supported by the Central Norway Regional Health Authority, Department of Pediatrics at Trondheim University Hospital, Department of Medical Microbiology at Trondheim University Hospital and the Norwegian University of Science and Technology. The supporters had no role in the study design, data Conclusions Among hospitalized children with LRTI, HMPVmanifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPVand RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPVand RSV-infected children. Introduction Since the discovery of human metapneumovirus (HMPV) in 2001 [1], studies from all parts of the world have shown that HMPV causes respiratory tract infection (RTI) in children [2–7]. HMPV is usually detected in airway secretions from children with RTI by use of polymerase chain reaction (PCR) tests, and the virus seldom appears in healthy children [8]. HMPV has been classified into the Pneumoviridae family. Two main genotypes (A and B) and at least four genetic subtypes (A1, A2, B1 and B2) exist [9–12]. Whether these genotypes cause similar or different infections is largely unclarified because some studies have shown quite similar manifestations [13–15], whereas others found that either genotypes A [16,17] or B [18] may cause more severe disease. Using sensitive nucleic-acid based molecular tests to diagnose viral pathogens has revealed that many children with LRTI have more than one virus present in the respiratory tract [14,19,20]. Previous studies in HMPV-infected children found that such viral co-detections were associated with increased disease severity [21,22]. However, this was not confirmed in other studies [14,17,19,23]. HMPV is closely related to respiratory syncytial virus (RSV), by far the most important airway virus affecting children worldwide [6,14,20,24]. It has been reported that RSV and HMPV infections in children may be quite similar [23,25,26], but there is also some evidence that RSV causes more severe disease than HMPV [6,18]. Risk factors for severe RSV infection are young age, prematurity, chronic lung disease, chronic heart disease and severe neurological disabilities [18,24,27–30]. Although it has not been studied to the same extent, it seems that some of these factors may also increase the risk of severe HMPV infection [2,17,18,29,31–33]. With some exceptions [18,29], most studies have separately dealt with risk factors for severe HMPV and RSV infections. In the present study, we prospectively enrolled a large cohort of children<16 years old, who were admitted to hospital with acute RTI during a nearly 9-year long period from 2006 to 2015, and diagnosed a broad panel of respiratory viruses. Our primary aim was to study clinical manifestations in children with HMPV lower respiratory tract infection (LRTI), taking viral co-detections and HMPV genotypes into account. Our secondary aim was to compare HMPVand RSV-infected children with LRTI, with a special emphasis on clinical manifestations and risk factors for severe disease. Materials and Methods Study Design and Population During the period from November 2006 to August 2015, we prospectively enrolled children aged<16 years who were admitted with acute RTI at the Pediatric Emergency Department, at the Department of Pediatrics, St. Olav’s Hospital, University Hospital of Trondheim, Norway, and who were sampled on clinical indications with a nasopharyngeal aspirate (Fig 1). The Comparing HumanMetapneumovirus and Respiratory Syncytial Virus PLOSONE | DOI:10.1371/journal.pone.0170200 January 17, 2017 2 / 19 collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.