Human Metapneumovirus 

  • Author: Ashley Maranich, MD; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Jan 12, 2012
 

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, 2]

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.[3]

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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.[4, 5]

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.[6] 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.[7, 8, 9, 10]

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.[11]

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.[10, 12]

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.[13] 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.[14]

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Epidemiology

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, 15, 16]

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.[17] 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.[18]

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.[19, 20, 21]

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.[22, 23] 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.[24] 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.[25] Peak viral activity in tropical regions occurs during the spring and summer months, as demonstrated in studies from Hong Kong.[26] Strains have also circulated in Latin America,[27] Italy,[28] and India.[29]

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.[22, 23, 30, 31]
  • 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.[32]

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, 15, 16] However, reinfection is possible, and hMPV disease has been documented in adult patients.[19]

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Contributor Information and Disclosures
Author

Ashley Maranich, MD  Pediatric Infectious Disease Staff, San Antonio Military Medical Center, Wilford Hall Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Michael Rajnik, MD  Associate Professor, Department of Pediatrics, 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.

Specialty Editor Board

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.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

John W King, MD  Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University Health Sciences Center; Consultant in Infectious Diseases, Overton Brooks 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; MERCK None Other

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.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Michael D Nissen, MBBS, FRACP, FRCPA, Theodorus P Sloots, PhD, and David Siebert, MD, to the development and writing of this article.

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