Human Metapneumovirus 

Updated: Jan 18, 2017
Author: Aliyah Baluch, MD, MSc, FACP; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD 

Overview

Practice Essentials

Human metapneumovirus (hMPV) is a single negative-stranded RNA-enveloped virus classified in the Pneumovirinae subfamily of the Paramyxoviridae family. hMPV infection has clinical features that range from mild upper respiratory tract infections (URTIs) to lower respiratory tract infections (LRTIs) complicated by significant wheezing, leading to life-threatening bronchiolitis and pneumonia, in all age groups. This virus is second only to respiratory syncytial virus (RSV) as the most commonly identified cause of pediatric LRTI. See the image below.

Phylogenetic tree showing sequence analysis of hum Phylogenetic tree showing sequence analysis of human metapneumovirus (hMPV).

Signs and symptoms

Infection with 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 the following:

  • Fever

  • Myalgia

  • Rhinorrhea

  • Dyspnea, tachypnea, and wheezing

Bronchiolitis, with or without pneumonia, is the most common presentation of hMPV illness. Other reported syndromes have included the following[1, 2, 3, 4, 5, 6, 7] :

  • Asthma exacerbation

  • Otitis media

  • Pneumonitis

  • Flulike illness

  • Community-acquired pneumonia

  • COPD (chronic obstructive pulmonary disease) exacerbation

See Clinical Presentation for more detail.

Diagnosis

Laboratory testing

  • Polymerase chain reaction of respiratory secretions: This is the most sensitive method for hMPV diagnosis; also useful to quantify viral load in research settings

  • Enzyme-linked immunoassay (ELISA): Note that seropositivity is nearly universal after early childhood, making definitive serologic diagnosis reliant on seroconversion or a 4-fold titer increase on serial samples

  • Immunofluorescence testing

It is difficult to grow hMPV in cell culture; therefore, this is method is no longer a timely mode of diagnosis. Isolation is possible in a limited number of cell lines and requires trypsin supplementation.

Imaging studies

Chest radiography is generally not helpful. Findings in patients with significant lower respiratory tract disease are indistinguishable between hMPV and other causes of viral pneumonia or bronchiolitis. Immunosuppressed persons, such as stem cell transplant or organ transplant recipients, may require CT scanning to clarify upper respiratory versus lower respiratory infection.

See Workup for more detail.

Management

There is no specific antiviral therapy available for hMPV infection; therefore, most treatment is supportive. Hospitalization, supplemental oxygen, and mechanical ventilation may be necessary in severe hMPV infections. In severely immunosuppressed persons, oral or inhaled ribavirin can be considered.[8, 9, 50]

See Treatment and Medication for more detail.

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.[8, 10]

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.[8] 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 on whole-genome analysis.[11, 51]

See the figure below.

Phylogenetic tree showing sequence analysis of hum Phylogenetic tree showing sequence analysis of human metapneumovirus (hMPV).

Pathophysiology

Scarce data on hMPV pathophysiology based on human studies have been reported. Two prospective studies from 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.[12, 13]

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.[14] 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.[15, 16, 17, 18]

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.[19]

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.[18, 20]

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.[21] 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.[22]

Epidemiology

hMPV is considered ubiquitous. This belief is based on the widespread detection of infection, as well as 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.[8, 23, 24]

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. In the northern hemisphere, the hMPV peak tends to be from January to March; in the southern hemisphere, the peak is from June to July.[51] Over a 20-year period, hMPV was detected in 1%-5% of pediatric upper respiratory infections, with variation from year to year.[25] 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.[26] The incubation period may vary but averages between 3 and 5 days from exposure.[51]

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.[1, 2, 3] Multiple outbreaks in healthcare facilities have been detailed in the literature, not only from infected residents but also from asymptomatic shedding of the virus in nonresidents.[54]

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.[27, 28] 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.[29] 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.[30] Peak viral activity in tropical regions occurs during the spring and summer months, as demonstrated in studies from Hong Kong.[31] Strains have also circulated in Latin America,[32] Italy,[33] and India.[34]

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.[27, 28, 4, 35] hMPV infection in lung transplant recipients can lead to permanent lung graft dysfunction and increased morbidity.[52]

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.[36]

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.[8, 23, 24] However, reinfection is possible, and hMPV disease has been documented in adult patients.[1]

 

Presentation

History

Infection with human metapneumovirus (hMPV) causes a broad spectrum of respiratory illness, from mild symptoms to severe cough, bronchiolitis, and pneumonia. hMPV is believed to be transmitted via contaminated secretions such as saliva, droplets, or large-particle aerosols. The clinical symptoms are similar to those seen with RSV infection and may also include fever, myalgia, rhinorrhea, dyspnea, tachypnea, and wheezing. The average duration of fever during hMPV infection is 10 days.[51] Hospitalization, supplemental oxygen, and mechanical ventilation may be necessary in severe hMPV infections.[8, 9]

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.[1, 2, 3, 4, 5, 6, 7]

 

DDx

Diagnostic Considerations

Coinfection with human metapneumovirus (hMPV) and other viral respiratory pathogens has been documented in several studies, with the clinical significance in these situations unclear.[37, 38, 39, 40] RSV and hMPV coinfection was found in 70% of children with RSV infection who required intensive care in Liverpool, United Kingdom.[37] 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.[39] However, other studies have not shown that coinfection plays a significant role in disease severity.[38, 41] Thus, further research is needed to definitively elucidate the clinical impact of coinfection.

Differential Diagnoses

 

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. Multiplex PCRs are being used with increasing frequency to diagnose hMPV infection and to rule out concomitant viral infections.

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 infection (LRTI), no findings distinguish hMPV from other causes of viral pneumonia or bronchiolitis. Chest CT scanning without contrast is the image of choice to evaluate for LRTI in combination with viral testing such as multiplex PCR. The most common findings of hMPV infection on CT scanning are patchy ground-glass opacities, centrilobular nodules, bronchial wall thickening, and multifocal areas of consolidation.[53] Nonetheless, these findings can be found in nearly all presentations of viral pneumonia.

 

Treatment

Medical Care

No specific FDA approved antiviral therapy is currently available for human metapneumovirus (hMPV) infection. Routine treatment includes symptomatic care, with respiratory support when required.

Ribavirin, which has broad antiviral activity, has been shown to have activity against hMPV in vitro.[42] Additionally, treatment with ribavirin in hMPV-infected cotton rats demonstrated decreased viral replication in the lungs and decreased pulmonary inflammation.[43] However, the use of ribavirin in any viral infection remains controversial, and no human studies in hMPV infection have been performed. Case reports have supported ribavirin therapy with concomitant intravenous immunoglobulins (IVIG) for improving symptoms in immunosuppressed persons.[50]

 

Follow-up

Deterrence/Prevention

Currently, no vaccine is available for human metapneumovirus (hMPV) infection. This is an active area of research, with several groups investigating different vaccination strategies in animal models.[44] A vaccine using the F (fusion) protein seems to be promising in cotton rat studies.[45] Inactivated, epitope, chimeric, subunit, and liver-attenuated vaccines are just a few of the different vaccines being assessed for validity against hMPV infection.[51]

Development of prophylactic antiviral preparations is also underway, with hMPV effectively inhibited in vivo using specific viral fusion inhibitors.[46]

Because hMPV transmission is likely to occur by contact with respiratory secretions, adherence to strict infection control methods is recommended in clinic and hospital settings. Droplet isolation is often put in place once testing is ordered for the workup of respiratory infections to prevent further transmission during the initial part of a patient's inpatient stay. If the respiratory workup results are negative, the empiric isolation is discontinued.

Patient Education

For patient education resources, see the Bacterial and Viral Infections Center, Pneumonia Center, Cold and Flu Center, and Lung and Airway Center, as well as Measles, Mumps, Viral Pneumonia, Flu in Adults, Flu in Children,Croup, and Bronchitis.