eMedicine Specialties > Infectious Diseases > Lower Respiratory Tract Infections

Human Metapneumovirus

Author: Ashley Maranich, MD, Pediatric Infectious Disease Fellow, National Capital Consortium, Walter Reed Army Medical Center
Coauthor(s): Michael Rajnik, MD, Assistant Professor, Department of Pediatrics, Acting Program Director, Pediatric Infectious Disease Fellowship Program, Uniformed Services University of the Health Sciences; Michael D Nissen, MBBS, BMedSc, FRACP, FRCPA, Associate Professor in Biomolecular, Biomedical Science & Health, Griffith University; Director of Infectious Diseases and Unit Head of Queensland Paediatric Infectious Laboratory, Sir Albert Sakzewski Viral Research Centre, Royal Children's Hospital; Theodorus P Sloots, PhD, Director, Sir Albert Sakzewski Virus Research Center, Queensland Pediatric Infectious Diseases Laboratory, Royal Children's Hospital and Health Service District
Contributor Information and Disclosures

Updated: May 1, 2009

Introduction

Background

Human metapneumovirus (hMPV), like human respiratory syncytial virus (RSV), is classified in the Pneumovirinae subfamily of the Paramyxoviridae family. However, hMPV is most closely genetically related to avian metapneumovirus (formerly called turkey rhinotracheitis virus). These two viruses are classified in the genus Metapneumovirus, with hMPV the first in this genus to cause disease in humans. Although it is hypothesized that the human virus originated from birds, the serological evidence that hMPV has been widespread in humans since at least 1958 suggests a zoonotic divergence before this time.1

hMPV was first described in 2001 by researchers in the Netherlands. Using polymerase chain reaction (PCR) amplification techniques, the virus was isolated from stored nasopharyngeal samples.1 Since this initial report, hMPV has been identified in countries on all continents except Antarctica.

hMPV is a single negative-stranded RNA-enveloped virus. Two major groups (A and B) and 4 subgroups of hMPV have been identified to date.2

Pathophysiology

Scarce data on hMPV pathophysiology based on human studies have been reported. Two prospective studies out of Argentina have quantified cytokine levels in nasal washes taken from subjects with hMPV infection and compared these with cytokine levels in RSV and influenza. They found that hMPV infection produces a low level of innate and adaptive cytokine response, although with a greater bias toward a Th2 response than the comparator viruses.3,4

Multiple animal models have been used to study the pathophysiology of hMPV. Chimpanzees have been the only animal to demonstrate symptomatology consistent with human disease.5 However, respiratory tract viral replication of hMPV has been demonstrated in cynomolgus macaques, cotton rats, and BALB/c mice, in addition to other small rodents.6,7,8,9

Studies of cytokine response in BALB/c mice have shown findings that are consistent with those of the human studies cited above, showing a weak innate cytokine response that corresponds with lower levels of pulmonary inflammation than with RSV infection.10

Studies on viral time course in these models demonstrates a peak of viral load at 4-5 days after infection. While most models show clearance of the virus by postinfection day 10-14, viable hMPV virus has been recovered in BALB/c mice up to 2 months following infection. The significance of this viral persistence in relation to human disease is unknown.9,11

Two recent studies have examined the significance of hMPV viral load, as assessed by real-time PCR, on illness parameters. One study showed that increased viral loads correlated with lower respiratory tract illness and hospitalization.12 The second found that an increasing viral load was associated with increased fever, increased bronchodilator use, and increased length of hospitalizations, independent of age and underlying chronic illness. This study also evaluated viral loads in RSV illness and did not find this same correlation with disease severity, again suggesting a different pathology mechanism between these two related viruses.13

Frequency

United States

Epidemiology

hMPV is considered ubiquitous worldwide. This belief is based on the widespread detection of infection and the high prevalence of antibodies against the virus in all age groups. In their initial 2001 report, van den Hoogen et al demonstrated 100% seropositivity by age 10 years in 28 young children in the Netherlands. Similar studies worldwide have confirmed this high rate of seroprevalence in early childhood.1,14,15

The largest study of hMPV epidemiology is an examination of nasal washes collected prospectively during acute respiratory illnesses in an outpatient cohort of children over a 20-year period. Consistent with other studies, hMPV was detected throughout the year, with a peak incidence from late winter to early spring, later than the seasonal peak of RSV and influenza during the entire period studied. Over the entire 20-year period, hMPV was detected in 1%-5% of pediatric upper respiratory infections, with variation from year to year.16 A similar study by the same group found a 12% incidence of hMPV in lower respiratory tract infections. Additionally, this study isolated hMPV from only 1% of asymptomatic children, further establishing disease causality.17

These studies and many others indicate that hMPV is the second most commonly identified cause of pediatric lower respiratory illness, behind only RSV. While there are geographical differences in seasonality and incidence of hMPV infection, this virus undoubtedly plays a significant role in respiratory illnesses in the pediatric population.

Little research has been done to determine the incidence of hMPV in adult populations, although hMPV infection has been well established in high-risk adult populations, including those with chronic obstructive pulmonary disease (COPD), elderly patients, and immunocompromised patients.18,19,20

hMPV has been documented as a significant cause of illness in transplant recipients. Studies have linked hMPV with idiopathic pneumonia, fulminant respiratory failure, and high mortality rates in stem cell transplant recipients.21,22 Additionally, in one study, hMPV was found in 10% of lung transplant recipients with acute respiratory tract infections, similar to the rate of RSV detection.23 Thus, transplant patients appear to be at significant risk for severe hMPV illness.

International

In temperate climates, the seasonality of hMPV infection mimics that in the United States, with most infections occurring in the winter and spring. Peak viral activity in tropical regions occurs during the spring and summer months, as demonstrated in studies from Hong Kong.24

Mortality/Morbidity

  • hMPV is the second-leading identifiable cause of lower respiratory tract disease in children and is known to cause disease in all age groups. hMPV infection likely accounts for up to 10% of hospitalizations for pediatric respiratory illnesses.
  • Risk factors for severe hMPV disease appear to be similar to those for severe RSV disease and include prematurity, heart disease, pulmonary disease, immunocompromise, and organ or stem cell transplantation.21,22,25,26
  • Little is known about the sequelae of hMPV illness. However, a small study of premature infants infected with hMPV did show increased airway resistance at follow-up.27

Sex

hMPV infection has no reported sexual predilection, with attack rates similar in males and females.

Age

Initial hMPV infection occurs early in childhood, with most individuals seroconverting by age 5 years. The seropositivity rate approaches 100% by age 10 years in multiple populations studied.1,14,15 However, reinfection is possible, and hMPV disease has been documented in adult patients.18

Clinical

History

Infection with human metapneumovirus (hMPV) causes a broad spectrum of respiratory illness, from mild symptoms to severe cough, bronchiolitis, and pneumonia. The clinical symptoms are similar to those seen with RSV infection and may also include high fever, myalgia, rhinorrhea, dyspnea, tachypnea, and wheezing. Hospitalization, supplemental oxygen, and mechanical ventilation may be necessary in severe hMPV infections.1,28

While bronchiolitis, with or without pneumonia, is the most common presentation of hMPV illness, other reported syndromes have included asthma exacerbation, otitis media, pneumonitis, flulike illness, community-acquired pneumonia, and COPD exacerbation.18,19,20,25,29,30,31

More on Human Metapneumovirus

Overview: Human Metapneumovirus
Differential Diagnoses & Workup: Human Metapneumovirus
Treatment & Medication: Human Metapneumovirus
Follow-up: Human Metapneumovirus
References
[ CLOSE WINDOW ]

References

  1. 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. Jun 2001;7(6):719-24. [Medline].

  2. Peret TC, Boivin G, Li Y, et al. Characterization of human metapneumoviruses isolated from patients in North America. J Infect Dis. Jun 1 2002;185(11):1660-3. [Medline].

  3. Laham FR, Israele V, Casellas JM, Garcia AM, Lac Prugent CM, Hoffman SJ. Differential production of inflammatory cytokines in primary infection with human metapneumovirus and with other common respiratory viruses of infancy. J Infect Dis. Jun 1 2004;189(11):2047-56. [Medline].

  4. Melendi GA, Laham FR, Monsalvo AC, Casellas JM, Israele V, Polack NR, et al. Cytokine profiles in the respiratory tract during primary infection with human metapneumovirus, respiratory syncytial virus, or influenza virus in infants. Pediatrics. Aug 2007;120(2):e410-5. [Medline].

  5. Skiadopoulos MH, Biacchesi S, Buchholz UJ, Riggs JM, Surman SR, Amaro-Carambot E. The two major human metapneumovirus genetic lineages are highly related antigenically, and the fusion (F) protein is a major contributor to this antigenic relatedness. J Virol. Jul 2004;78(13):6927-37. [Medline].

  6. Kuiken T, van den Hoogen BG, van Riel DA, Laman JD, van Amerongen G, Sprong L. 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. Jun 2004;164(6):1893-900. [Medline].

  7. Williams JV, Tollefson SJ, Johnson JE, Crowe JE Jr. The cotton rat (Sigmodon hispidus) is a permissive small animal model of human metapneumovirus infection, pathogenesis, and protective immunity. J Virol. Sep 2005;79(17):10944-51. [Medline].

  8. Wyde PR, Chetty SN, Jewell AM, Schoonover SL, Piedra PA. Development of a cotton rat-human metapneumovirus (hMPV) model for identifying and evaluating potential hMPV antivirals and vaccines. Antiviral Res. Apr 2005;66(1):57-66. [Medline].

  9. Alvarez R, Harrod KS, Shieh WJ, Zaki S, Tripp RA. Human metapneumovirus persists in BALB/c mice despite the presence of neutralizing antibodies. J Virol. Dec 2004;78(24):14003-11. [Medline].

  10. Guerrero-Plata A, Baron S, Poast JS, Adegboyega PA, Casola A, Garofalo RP. Activity and regulation of alpha interferon in respiratory syncytial virus and human metapneumovirus experimental infections. J Virol. Aug 2005;79(16):10190-9. [Medline].

  11. Alvarez R, Tripp RA. The immune response to human metapneumovirus is associated with aberrant immunity and impaired virus clearance in BALB/c mice. J Virol. May 2005;79(10):5971-8. [Medline].

  12. Bosis S, Esposito S, Osterhaus AD, Tremolati E, Begliatti E, Tagliabue C. Association between high nasopharyngeal viral load and disease severity in children with human metapneumovirus infection. J Clin Virol. Jul 2008;42(3):286-90. [Medline].

  13. Martin ET, Kuypers J, Heugel J, Englund JA. Clinical disease and viral load in children infected with respiratory syncytial virus or human metapneumovirus. Diagn Microbiol Infect Dis. Dec 2008;62(4):382-8. [Medline].

  14. Leung J, Esper F, Weibel C, Kahn JS. Seroepidemiology of human metapneumovirus (hMPV) on the basis of a novel enzyme-linked immunosorbent assay utilizing hMPV fusion protein expressed in recombinant vesicular stomatitis virus. J Clin Microbiol. Mar 2005;43(3):1213-9. [Medline].

  15. Ebihara T, Endo R, Kikuta H, Ishiguro N, Yoshioka M, Ma X, et al. Seroprevalence of human metapneumovirus in Japan. J Med Virol. Jun 2003;70(2):281-3. [Medline].

  16. Williams JV, Wang CK, Yang CF, Tollefson SJ, House FS, Heck JM. The role of human metapneumovirus in upper respiratory tract infections in children: a 20-year experience. J Infect Dis. Feb 1 2006;193(3):387-95. [Medline].

  17. Williams JV, Harris PA, Tollefson SJ, Halburnt-Rush LL, Pingsterhaus JM, Edwards KM. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med. Jan 29 2004;350(5):443-50. [Medline].

  18. Falsey AR, Erdman D, Anderson LJ, Walsh EE. Human metapneumovirus infections in young and elderly adults. J Infect Dis. Mar 1 2003;187(5):785-90. [Medline].

  19. Rohde G, Borg I, Arinir U, Kronsbein J, Rausse R, Bauer TT. Relevance of human metapneumovirus in exacerbations of COPD. Respir Res. 2005;6:150. [Medline].

  20. McManus TE, Marley AM, Baxter N, Christie SN, O'Neill HJ, Elborn JS. Respiratory viral infection in exacerbations of COPD. Respir Med. Nov 2008;102(11):1575-80. [Medline].

  21. Williams JV, Martino R, Rabella N, Otegui M, Parody R, Heck JM, et al. A prospective study comparing human metapneumovirus with other respiratory viruses in adults with hematologic malignancies and respiratory tract infections. J Infect Dis. Sep 15 2005;192(6):1061-5. [Medline].

  22. Englund JA, Boeckh M, Kuypers J, Nichols WG, Hackman RC, Morrow RA, et al. Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients. Ann Intern Med. Mar 7 2006;144(5):344-9. [Medline].

  23. Hopkins P, McNeil K, Kermeen F, Musk M, McQueen E, Mackay I, et al. Human metapneumovirus in lung transplant recipients and comparison to respiratory syncytial virus. Am J Respir Crit Care Med. Oct 15 2008;178(8):876-81. [Medline].

  24. Peiris JS, Tang WH, Chan KH, Khong PL, Guan Y, Lau YL, et al. Children with respiratory disease associated with metapneumovirus in Hong Kong. Emerg Infect Dis. Jun 2003;9(6):628-33. [Medline].

  25. 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. Nov 1 2002;186(9):1330-4. [Medline].

  26. Pelletier G, Déry P, Abed Y, Boivin G. Respiratory tract reinfections by the new human Metapneumovirus in an immunocompromised child. Emerg Infect Dis. Sep 2002;8(9):976-8. [Medline].

  27. Broughton S, Sylvester KP, Fox G, Zuckerman M, Smith M, Milner AD, et al. Lung function in prematurely born infants after viral lower respiratory tract infections. Pediatr Infect Dis J. Nov 2007;26(11):1019-24. [Medline].

  28. Wilkesmann A, Schildgen O, Eis-Hubinger AM, et al. Human metapneumovirus infections cause similar symptoms and clinical severity as respiratory syncytial virus infections. Eur J Pediatr. Mar 23 2006;[Medline].

  29. Schildgen O, Geikowski T, Glatzel T, Schuster J, Simon A. Frequency of human metapneumovirus in the upper respiratory tract of children with symptoms of an acute otitis media. Eur J Pediatr. Jun 2005;164(6):400-1. [Medline].

  30. Suzuki A, Watanabe O, Okamoto M, Endo H, Yano H, Suetake M. Detection of human metapneumovirus from children with acute otitis media. Pediatr Infect Dis J. Jul 2005;24(7):655-7. [Medline].

  31. Jartti T, van den Hoogen B, Garofalo RP, et al. Metapneumovirus and acute wheezing in children. Lancet. Nov 2 2002;360(9343):1393-4. [Medline].

  32. Greensill J, McNamara PS, Dove W, Flanagan B, Smyth RL, Hart CA. Human metapneumovirus in severe respiratory syncytial virus bronchiolitis. Emerg Infect Dis. Mar 2003;9(3):372-5. [Medline].

  33. McNamara PS, Flanagan BF, Smyth RL, Hart CA. Impact of human metapneumovirus and respiratory syncytial virus co-infection in severe bronchiolitis. Pediatr Pulmonol. Aug 2007;42(8):740-3. [Medline].

  34. Semple MG, Cowell A, Dove W, Greensill J, McNamara PS, Halfhide C, et al. Dual infection of infants by human metapneumovirus and human respiratory syncytial virus is strongly associated with severe bronchiolitis. J Infect Dis. Feb 1 2005;191(3):382-6. [Medline].

  35. Chan PK, Tam JS, Lam CW, Chan E, Wu A, Li CK. Human metapneumovirus detection in patients with severe acute respiratory syndrome. Emerg Infect Dis. Sep 2003;9(9):1058-63. [Medline].

  36. Lazar I, Weibel C, Dziura J, Ferguson D, Landry ML, Kahn JS. Human metapneumovirus and severity of respiratory syncytial virus disease. Emerg Infect Dis. Jul 2004;10(7):1318-20. [Medline].

  37. Wyde PR, Chetty SN, Jewell AM, Boivin G, Piedra PA. Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune serum globulin in vitro. Antiviral Res. Sep 2003;60(1):51-9. [Medline].

  38. Hamelin ME, Prince GA, Boivin G. Effect of ribavirin and glucocorticoid treatment in a mouse model of human metapneumovirus infection. Antimicrob Agents Chemother. Feb 2006;50(2):774-7. [Medline].

  39. Herfst S, Fouchier RA. Vaccination approaches to combat human metapneumovirus lower respiratory tract infections. J Clin Virol. Jan 2008;41(1):49-52. [Medline].

  40. Cseke G, Wright DW, Tollefson SJ, Johnson JE, Crowe JE Jr, Williams JV. Human metapneumovirus fusion protein vaccines that are immunogenic and protective in cotton rats. J Virol. Jan 2007;81(2):698-707. [Medline].

  41. Deffrasnes C, Hamelin ME, Prince GA, Boivin G. Identification and evaluation of a highly effective fusion inhibitor for human metapneumovirus. Antimicrob Agents Chemother. Jan 2008;52(1):279-87. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

human metapneumovirus, metapneumovirus, hMPV, human parainfluenza virus 1, HPIV-1, paramyxoviruses, Paramyxoviridae, human respiratory syncytial virus, hRSV, respiratory syncytial virus, RSV infection, avian pneumovirus, APV, turkey rhinotracheitis virus, TRTV

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Ashley Maranich, MD, Pediatric Infectious Disease Fellow, National Capital Consortium, Walter Reed Army Medical Center
Disclosure: Nothing to disclose.

Coauthor(s)

Michael Rajnik, MD, Assistant Professor, Department of Pediatrics, Acting Program Director, Pediatric Infectious Disease Fellowship Program, Uniformed Services University of the Health Sciences
Michael Rajnik, MD is a member of the following medical societies: American Academy of Pediatrics, Armed Forces Infectious Diseases Society, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Michael D Nissen, MBBS, BMedSc, FRACP, FRCPA, Associate Professor in Biomolecular, Biomedical Science & Health, Griffith University; Director of Infectious Diseases and Unit Head of Queensland Paediatric Infectious Laboratory, Sir Albert Sakzewski Viral Research Centre, Royal Children's Hospital
Michael D Nissen, MBBS, BMedSc, FRACP, FRCPA is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Pediatric Infectious Diseases Society, Royal Australasian College of Physicians, and Royal College of Pathologists of Australasia
Disclosure: Nothing to disclose.

Theodorus P Sloots, PhD, Director, Sir Albert Sakzewski Virus Research Center, Queensland Pediatric Infectious Diseases Laboratory, Royal Children's Hospital and Health Service District
Disclosure: Nothing to disclose.

Medical Editor

Douglas A Drevets, MD, Assistant Professor, Department of Medicine, Section of Infectious Disease, Oklahoma University Health Sciences Center
Douglas A Drevets, MD is a member of the following medical societies: American Association of Immunologists, American Society for Microbiology, Central Society for Clinical Research, and Christian Medical & Dental Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

John W King, MD, Professor of Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center; Director, Viral Therapeutics Clinics for Hepatitis; Consulting Staff, Department of Infectious Diseases, Overton Brook Veterans Affairs Medical Center
John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, and Sigma Xi
Disclosure: emedicine $50.00 author of chapter

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.