Journal of Clinical Virology 46 (2009) 318–324 Contents lists available at ScienceDirect Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv Incidence, molecular epidemiology and clinical presentations of human metapneumovirus; assessment of its importance as a diagnostic screening target Eleanor Gaunt a,∗ , E. Carol McWilliam-Leitch a , Kate Templeton b , Peter Simmonds a a Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, United Kingdom b Department of Virology, Royal Infirmary of Edinburgh, 51 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SA, United Kingdom article info Article history: Received 22 May 2009 Received in revised form 8 September 2009 Accepted 11 September 2009 Keywords: Human metapneumovirus Molecular epidemiology Genotype Respiratory syncytial virus Molecular diagnostics abstract Background: Human metapneumovirus (HMPV) is a recently discovered human paramyxovirus associated with a spectrum of respiratory symptoms from the common cold to pneumonia and bronchiolitis. Objectives: To assess the clinical significance and epidemiology of HMPV, standardized comparison of frequencies of infection, age profiles and disease associations were made with other respiratory viruses in Scotland. Study design: 7091 respiratory samples collected in Scotland between 1 July 2006 and 30 June 2008 from 4282 individuals were screened by multiplex RT-PCR for respiratory syncytial virus (HRSV), adenovirus (AdV), parainfluenzaviruses 1–3 (PIV-1, -2 and -3), influenza A and B and by nested RT-PCR for HMPV. Results: HMPV was the fifth most prevalent virus (2.0% of samples), found predominantly in young chil- dren in winter months. In the 2006–2007 respiratory season, 70% of HMPV isolates were genotype A, but a switch to predominantly type B infections occurred next winter. For samples with information on clinical presentations, 26% of HMPV infections were from subjects with lower respiratory tract presen- tations, lower than recorded for HRSV, but similar to adenovirus, parainfluenza viruses and influenza viruses A and B. Around 13% of HMPV infections were associated with upper respiratory tract symptoms or disease, comparable with other respiratory virus infections. Conclusions: Numerically and through its association with respiratory disease, HMPV represents a diag- nostically significant target that should be included in PCR-based routine screening of respiratory samples. Understanding the biological basis of observed rapid turnover of HMPV variants, including the observed HMPV genotype change between respiratory seasons requires further longitudinal studies. © 2009 Elsevier B.V. All rights reserved. 1. Background The Paramyxoviridae family comprises enveloped viruses with single-stranded non-segmented negative sense RNA genomes. Respiratory syncytial virus (HRSV) was the only known human pathogen belonging to the Pneumovirus subfamily until the discov- ery of HMPV in 2001. 1 Though newly discovered, this virus was demonstrated by serology to have been circulating in the human population for at least 50 years. 1 HMPV and HRSV share several epidemiologic and clinical characteristics, both being detectable throughout the year with a winter peak in prevalence in temperate regions. 2,3 Both viruses cause a range of respiratory outcomes from the common cold 4 to pneumonia and bronchiolitis. 2 HMPV infec- tion frequencies ranging from 2% to 13% have been observed among hospital patients with respiratory disease, 5–16 whereas HRSV has been detected at frequencies of up to 50% in similar groups. 17 ∗ Corresponding author. Tel.: +44 131 650 7945; fax: +44 131 650 6511. E-mail address: E.Gaunt@sms.ed.ac.uk (E. Gaunt). There are two HMPV genotypes, A and B, which differ by 15% at the nucleotide level. 18 HMPV genotypes are further divided into 4 subgroups A1, A2, B1 and B2. Some report no clinical dif- ferences between HMPV genotypes, 19 while others find different symptoms 20 and a greater disease severity associated with geno- type A. 21 Temporal changes in the circulation of different HMPV genotypes have been reported. 10,19,22 There are also two HRSV genotypes, A and B, differing by 16% at the nucleotide level, each comprising an undefined number of strains, with predominant cir- culating strain replacement occurring between seasons. 23,24 Some report no clinical differences between HRSV genotypes, 25 while others report higher morbidity associated with genotype A. 26–28 No consistent pattern of genotype switching between respiratory seasons has been identified. 29–31 2. Objectives We have investigated the incidence, epidemiology and dis- ease association of HMPV in Scotland to assess its importance as a component of PCR-based respiratory virus screening. Through 1386-6532/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jcv.2009.09.016