eMedicine Specialties > Infectious Diseases > Lower Respiratory Tract Infections

Human Metapneumovirus: Differential Diagnoses & Workup

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

Differential Diagnoses

Adenoviruses
Picornavirus-Overview
Bocavirus
Pneumonia, Viral
Bronchiolitis
Respiratory Syncytial Virus (RSV) Infection
Influenza
Rhinoviruses
Parainfluenza Virus
Pharyngitis, Bacterial
Pharyngitis, Viral

Other Problems to Be Considered

Coinfection with human metapneumovirus (hMPV) and other viral respiratory pathogens has been documented in several studies, with the clinical significance in these situations unclear.32,33,34,35 RSV and hMPV coinfection was found in 70% of children with RSV infection who required intensive care in Liverpool, United Kingdom.32 In addition, Semple et al showed that the rate of intensive care admissions and mechanical ventilation in patients coinfected with RSV and hMPV was greater than in infection with either pathogen alone.34 However, other studies have not shown that coinfection plays a significant role in disease severity.33,36 Thus, further research is needed to definitively elucidate the clinical impact of coinfection.

Workup

Laboratory Studies

Human metapneumovirus (hMPV) is difficult to grow in cell culture, largely explaining the delay in recognizing this pathogen, which has been causing disease for 50 years. Isolation is possible in a limited number of cell lines and requires trypsin supplementation. This is not a clinically useful mode of diagnosis given these technical limitations and the prolonged time to effectively culture hMPV.

  • Serological diagnosis is possible using enzyme-linked immunoassays (ELISA). However, seropositivity is nearly universal after early childhood, making definitive serological diagnosis reliant on seroconversion or a 4-fold titer increase on serial samples.
  • Immunofluorescence testing has been developed for hMPV and is available through commercial laboratories but is not yet widely used in clinical settings.
  • The most sensitive means of hMPV infection diagnosis is by PCR of respiratory secretions, which is currently the most commonly used method. In research settings, this technique is also being used to quantify viral load.

Given the prevalence of hMPV, more widespread availability of rapid diagnostic tests would be clinically useful.

Imaging Studies

Although chest radiography is often obtained in patients with significant lower respiratory tract disease, no findings distinguish hMPV from other causes of viral pneumonia or bronchiolitis.

More on Human Metapneumovirus

Overview: Human Metapneumovirus
Differential Diagnoses & Workup: Human Metapneumovirus
Treatment & Medication: Human Metapneumovirus
Follow-up: Human Metapneumovirus
References
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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].

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Further Reading

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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

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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.

 
 
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