Human metapneumovirus infections
- James E Crowe, Jr, MD
James E Crowe, Jr, MD
- Vanderbilt Vaccine Center
- Vanderbilt University Medical Center
- Section Editors
- Martin S Hirsch, MD
Martin S Hirsch, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Viral Infections
- Professor of Medicine
- Harvard Medical School
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
Respiratory tract infections commonly are caused by viral pathogens, especially in young children. Respiratory syncytial virus (RSV) is the most common pathogen identified in these infections, followed historically by parainfluenza virus (PIV); both of these viruses are in the Paramyxoviridae family. Other important viruses that cause respiratory tract infection include influenza and adenoviruses. However, despite improved methods for identifying viral pathogens in these infections, the etiology remains undetermined in a significant number of patients.
In 2001, investigators from the Netherlands discovered a new member of the Paramyxoviridae family in the genus Metapneumovirus . The first representative of this genus to cause infection in humans has been called the human metapneumovirus (hMPV). Data suggest this virus has been responsible for respiratory tract infections for at least 60 years with a worldwide distribution [1-4].
The virology, pathogenesis, epidemiology, clinical manifestations, diagnosis, and treatment of hMPV will be discussed here. Other common respiratory viruses are reviewed separately. (See "Respiratory syncytial virus infection: Clinical features and diagnosis" and "Seasonal influenza in children: Clinical features and diagnosis" and "Clinical manifestations of seasonal influenza in adults" and "Parainfluenza viruses in children" and "Parainfluenza viruses in adults" and "Epidemiology and clinical manifestations of adenovirus infection".)
Within the Paramyxoviridae family, there are two subfamilies, Pneumovirinae and Paramyxovirinae. Genetic analysis determined that human metapneumovirus (hMPV) is most similar to the Pneumovirinae family, of which respiratory syncytial virus is a prominent member.
HMPV is an enveloped virus with a nonsegmented negative-sense RNA genome. HMPV is most closely related phylogenetically to avian metapneumovirus (APV) . The complete genome sequence reveals a high level of homology with APV . Phylogenetic analysis has identified two subgroups of hMPV, subgroups A and B, and two clades within each of these subgroups (designated A1, A2, B1, and B2), which often circulate concurrently [6,7]. A study of 727 Australian hMPV isolates was undertaken from 2001 to 2004 to determine the epidemiologic profile of genetic subtypes associated with acute respiratory tract infections . Concurrent annual circulation of all four hMPV subtypes was common, although a single, and usually different, hMPV subtype predominated each year.
- van den Hoogen BG, de Jong JC, Groen J, et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med 2001; 7:719.
- Boivin G, Abed Y, Pelletier G, et al. Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups. J Infect Dis 2002; 186:1330.
- Nissen MD, Siebert DJ, Mackay IM, et al. Evidence of human metapneumovirus in Australian children. Med J Aust 2002; 176:188.
- Peret TC, Boivin G, Li Y, et al. Characterization of human metapneumoviruses isolated from patients in North America. J Infect Dis 2002; 185:1660.
- van den Hoogen BG, Bestebroer TM, Osterhaus AD, Fouchier RA. Analysis of the genomic sequence of a human metapneumovirus. Virology 2002; 295:119.
- Boivin G, Mackay I, Sloots TP, et al. Global genetic diversity of human metapneumovirus fusion gene. Emerg Infect Dis 2004; 10:1154.
- Mackay IM, Bialasiewicz S, Jacob KC, et al. Genetic diversity of human metapneumovirus over 4 consecutive years in Australia. J Infect Dis 2006; 193:1630.
- Kuiken T, van den Hoogen BG, van Riel DA, et al. Experimental human metapneumovirus infection of cynomolgus macaques (Macaca fascicularis) results in virus replication in ciliated epithelial cells and pneumocytes with associated lesions throughout the respiratory tract. Am J Pathol 2004; 164:1893.
- Cseke G, Maginnis MS, Cox RG, et al. Integrin alphavbeta1 promotes infection by human metapneumovirus. Proc Natl Acad Sci U S A 2009; 106:1566.
- Hamelin ME, Prince GA, Gomez AM, et al. Human metapneumovirus infection induces long-term pulmonary inflammation associated with airway obstruction and hyperresponsiveness in mice. J Infect Dis 2006; 193:1634.
- Openshaw PJ, Dean GS, Culley FJ. Links between respiratory syncytial virus bronchiolitis and childhood asthma: clinical and research approaches. Pediatr Infect Dis J 2003; 22:S58.
- Peiris JS, Tang WH, Chan KH, et al. Children with respiratory disease associated with metapneumovirus in Hong Kong. Emerg Infect Dis 2003; 9:628.
- Kim S, Sung H, Im HJ, et al. Molecular epidemiological investigation of a nosocomial outbreak of human metapneumovirus infection in a pediatric hemato-oncology patient population. J Clin Microbiol 2009; 47:1221.
- Tu CC, Chen LK, Lee YS, et al. An outbreak of human metapneumovirus infection in hospitalized psychiatric adult patients in Taiwan. Scand J Infect Dis 2009; 41:363.
- Matsuzaki Y, Itagaki T, Ikeda T, et al. Human metapneumovirus infection among family members. Epidemiol Infect 2013; 141:827.
- Stockton J, Stephenson I, Fleming D, Zambon M. Human metapneumovirus as a cause of community-acquired respiratory illness. Emerg Infect Dis 2002; 8:897.
- Jartti T, van den Hoogen B, Garofalo RP, et al. Metapneumovirus and acute wheezing in children. Lancet 2002; 360:1393.
- Feikin DR, Njenga MK, Bigogo G, et al. Etiology and Incidence of viral and bacterial acute respiratory illness among older children and adults in rural western Kenya, 2007-2010. PLoS One 2012; 7:e43656.
- Wang Y, Chen Z, Yan YD, et al. Seasonal distribution and epidemiological characteristics of human metapneumovirus infections in pediatric inpatients in Southeast China. Arch Virol 2013; 158:417.
- Osterhaus A, Fouchier R. Human metapneumovirus in the community. Lancet 2003; 361:890.
- Williams JV, Harris PA, Tollefson SJ, et al. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med 2004; 350:443.
- Esper F, Martinello RA, Boucher D, et al. A 1-year experience with human metapneumovirus in children aged <5 years. J Infect Dis 2004; 189:1388.
- Edwards KM, Zhu Y, Griffin MR, et al. Burden of human metapneumovirus infection in young children. N Engl J Med 2013; 368:633.
- Døllner H, Risnes K, Radtke A, Nordbø SA. Outbreak of human metapneumovirus infection in norwegian children. Pediatr Infect Dis J 2004; 23:436.
- Louie JK, Schnurr DP, Pan CY, et al. A summer outbreak of human metapneumovirus infection in a long-term-care facility. J Infect Dis 2007; 196:705.
- Bhattacharyya S, Gesteland PH, Korgenski K, et al. Cross-immunity between strains explains the dynamical pattern of paramyxoviruses. Proc Natl Acad Sci U S A 2015; 112:13396.
- Schuster JE, Cox RG, Hastings AK, et al. A broadly neutralizing human monoclonal antibody exhibits in vivo efficacy against both human metapneumovirus and respiratory syncytial virus. J Infect Dis 2015; 211:216.
- Corti D, Bianchi S, Vanzetta F, et al. Cross-neutralization of four paramyxoviruses by a human monoclonal antibody. Nature 2013; 501:439.
- Williams JV, Wang CK, Yang CF, et al. The role of human metapneumovirus in upper respiratory tract infections in children: a 20-year experience. J Infect Dis 2006; 193:387.
- Boivin G, De Serres G, Côté S, et al. Human metapneumovirus infections in hospitalized children. Emerg Infect Dis 2003; 9:634.
- Mullins JA, Erdman DD, Weinberg GA, et al. Human metapneumovirus infection among children hospitalized with acute respiratory illness. Emerg Infect Dis 2004; 10:700.
- Papenburg J, Hamelin MÈ, Ouhoummane N, et al. Comparison of risk factors for human metapneumovirus and respiratory syncytial virus disease severity in young children. J Infect Dis 2012; 206:178.
- Falsey AR, Erdman D, Anderson LJ, Walsh EE. Human metapneumovirus infections in young and elderly adults. J Infect Dis 2003; 187:785.
- Walsh EE, Peterson DR, Falsey AR. Human metapneumovirus infections in adults: another piece of the puzzle. Arch Intern Med 2008; 168:2489.
- Widmer K, Zhu Y, Williams JV, et al. Rates of hospitalizations for respiratory syncytial virus, human metapneumovirus, and influenza virus in older adults. J Infect Dis 2012; 206:56.
- Centers for Disease Control and Prevention (CDC). Outbreaks of human metapneumovirus in two skilled nursing facilities -West Virginia and Idaho, 2011-2012. MMWR Morb Mortal Wkly Rep 2013; 62:909.
- Xepapadaki P, Psarras S, Bossios A, et al. Human Metapneumovirus as a causative agent of acute bronchiolitis in infants. J Clin Virol 2004; 30:267.
- Schlapbach LJ, Agyeman P, Hutter D, et al. Human metapneumovirus infection as an emerging pathogen causing acute respiratory distress syndrome. J Infect Dis 2011; 203:294.
- Esper F, Boucher D, Weibel C, et al. Human metapneumovirus infection in the United States: clinical manifestations associated with a newly emerging respiratory infection in children. Pediatrics 2003; 111:1407.
- Wolf DG, Greenberg D, Shemer-Avni Y, et al. Association of human metapneumovirus with radiologically diagnosed community-acquired alveolar pneumonia in young children. J Pediatr 2010; 156:115.
- Williams JV, Tollefson SJ, Heymann PW, et al. Human metapneumovirus infection in children hospitalized for wheezing. J Allergy Clin Immunol 2005; 115:1311.
- Pancham K, Sami I, Perez GF, et al. Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity. Pediatr Neonatol 2016; 57:27.
- Greensill J, McNamara PS, Dove W, et al. Human metapneumovirus in severe respiratory syncytial virus bronchiolitis. Emerg Infect Dis 2003; 9:372.
- Semple MG, Cowell A, Dove W, et al. Dual infection of infants by human metapneumovirus and human respiratory syncytial virus is strongly associated with severe bronchiolitis. J Infect Dis 2005; 191:382.
- König B, König W, Arnold R, et al. Prospective study of human metapneumovirus infection in children less than 3 years of age. J Clin Microbiol 2004; 42:4632.
- Madhi SA, Ludewick H, Kuwanda L, et al. Pneumococcal coinfection with human metapneumovirus. J Infect Dis 2006; 193:1236.
- Schildgen O, Glatzel T, Geikowski T, et al. Human metapneumovirus RNA in encephalitis patient. Emerg Infect Dis 2005; 11:467.
- Sánchez Fernández I, Rebollo Polo M, Muñoz-Almagro C, et al. Human Metapneumovirus in the Cerebrospinal Fluid of a Patient With Acute Encephalitis. Arch Neurol 2012; 69:649.
- Williams JV, Crowe JE Jr, Enriquez R, et al. Human metapneumovirus infection plays an etiologic role in acute asthma exacerbations requiring hospitalization in adults. J Infect Dis 2005; 192:1149.
- Boivin G, De Serres G, Hamelin ME, et al. An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility. Clin Infect Dis 2007; 44:1152.
- Vicente D, Montes M, Cilla G, Pérez-Trallero E. Human metapneumovirus and chronic obstructive pulmonary disease. Emerg Infect Dis 2004; 10:1338.
- Beckham JD, Cadena A, Lin J, et al. Respiratory viral infections in patients with chronic, obstructive pulmonary disease. J Infect 2005; 50:322.
- Pelletier G, Déry P, Abed Y, Boivin G. Respiratory tract reinfections by the new human Metapneumovirus in an immunocompromised child. Emerg Infect Dis 2002; 8:976.
- Sumino KC, Agapov E, Pierce RA, et al. Detection of severe human metapneumovirus infection by real-time polymerase chain reaction and histopathological assessment. J Infect Dis 2005; 192:1052.
- Williams JV, Martino R, Rabella N, et al. A prospective study comparing human metapneumovirus with other respiratory viruses in adults with hematologic malignancies and respiratory tract infections. J Infect Dis 2005; 192:1061.
- Englund JA, Boeckh M, Kuypers J, et al. Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients. Ann Intern Med 2006; 144:344.
- Debiaggi M, Canducci F, Sampaolo M, et al. Persistent symptomless human metapneumovirus infection in hematopoietic stem cell transplant recipients. J Infect Dis 2006; 194:474.
- Larcher C, Geltner C, Fischer H, et al. Human metapneumovirus infection in lung transplant recipients: clinical presentation and epidemiology. J Heart Lung Transplant 2005; 24:1891.
- Hoellein A, Hecker J, Hoffmann D, et al. Serious outbreak of human metapneumovirus in patients with hematologic malignancies. Leuk Lymphoma 2016; 57:623.
- Groome MJ, Moyes J, Cohen C, et al. Human metapneumovirus-associated severe acute respiratory illness hospitalisation in HIV-infected and HIV-uninfected South African children and adults. J Clin Virol 2015; 69:125.
- Poritz MA, Blaschke AJ, Byington CL, et al. FilmArray, an automated nested multiplex PCR system for multi-pathogen detection: development and application to respiratory tract infection. PLoS One 2011; 6:e26047.
- BioFire Diagnostics. FilmArray Respiratory Panel. http://www.biofiredx.com/pdfs/FilmArray/InfoSheet,%20FilmArray%20Respiratory%20Panel-0229.pdf (Accessed on October 21, 2014).
- Hamelin ME, Boivin G. Development and validation of an enzyme-linked immunosorbent assay for human metapneumovirus serology based on a recombinant viral protein. Clin Diagn Lab Immunol 2005; 12:249.
- Landry ML, Ferguson D, Cohen S, et al. Detection of human metapneumovirus in clinical samples by immunofluorescence staining of shell vial centrifugation cultures prepared from three different cell lines. J Clin Microbiol 2005; 43:1950.
- Wyde PR, Chetty SN, Jewell AM, et al. Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune serum globulin in vitro. Antiviral Res 2003; 60:51.
- Hamelin ME, Prince GA, Boivin G. Effect of ribavirin and glucocorticoid treatment in a mouse model of human metapneumovirus infection. Antimicrob Agents Chemother 2006; 50:774.
- Buchholz UJ, Nagashima K, Murphy BR, Collins PL. Live vaccines for human metapneumovirus designed by reverse genetics. Expert Rev Vaccines 2006; 5:695.
- Cseke G, Wright DW, Tollefson SJ, et al. Human metapneumovirus fusion protein vaccines that are immunogenic and protective in cotton rats. J Virol 2007; 81:698.
- CLINICAL MANIFESTATIONS
- - Possible role in COPD exacerbations
- Recurrent infection
- Immunocompromised hosts
- Reverse transcriptase PCR
- Direct fluorescent antibody
- Viral culture
- Shell vial cultures
- Infection control
- Vaccine development
- SUMMARY AND RECOMMENDATIONS