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Human Metapneumo Virus (HMPV)- A Comprehensive Overview

M3 India Newsdesk Jan 09, 2025

This article provides a detailed understanding of human metapneumovirus (HMPV), a significant yet under-recognised cause of respiratory infections, especially in high-risk groups like children, the elderly, and immunocompromised patients.


Human metapneumovirus (HMPV) is a common respiratory virus that is a significant cause of acute respiratory infections, particularly in young children, the elderly, and individuals with compromised immune systems. Discovered relatively recently in 2001, HMPV has quickly been recognised as a crucial respiratory pathogen, rivalling respiratory syncytial virus (RSV) in terms of impact, especially in pediatric populations. 

Virology

HMPV is a single-stranded, negative-sense RNA virus belonging to the Pneumoviridae family, within the order Mononegavirales. Its classification places it alongside RSV, reflecting some overlapping features and clinical manifestations. HMPV is a pleomorphic enveloped virus containing a helical nucleocapsid. It possesses several key proteins, including:

  1. Fusion (F) protein: Essential for viral entry and fusion with host cells. A primary target for neutralising antibodies. [1]
  2. Attachment (G) protein: Facilitates initial binding to host cells, although its primary receptor is not yet fully understood. [2]
  3. Matrix (M) protein: Plays a role in viral assembly and structure. [3]
  4. Nucleocapsid (N) protein: Encapsulates the viral RNA genome. [4]
  5. Phosphoprotein (P): Involved in RNA replication and transcription. [5]
  6. Large (L) protein: Functions as the RNA-dependent RNA polymerase. [6]

HMPV exhibits genetic diversity, with two main lineages, A and B, further subdivided into sublineages. This genetic variability can influence the severity of infection and vaccine development. [7]


Epidemiology

HMPV has a global distribution, with seasonal patterns typically aligning with other respiratory viruses - outbreaks commonly occurring in late winter and early spring. [8] The virus spreads through respiratory droplets and direct contact with contaminated surfaces. [9]

  1. Prevalence: HMPV is estimated to cause a substantial percentage of respiratory illnesses in both children and adults. Studies have shown that most children will experience at least one HMPV infection by the age of five. [10]
  2. Age groups: While HMPV can infect all age groups, young children under the age of five and the elderly over the age of 65, are most vulnerable to severe infections. [11]
  3. Geographic distribution: HMPV is found worldwide. Incidence rates tend to vary by region because of differing population densities, weather, and diagnostic testing practices. [12]
  4. Seasonality: In temperate climates, HMPV infections peak during the late fall, winter, and early spring. In tropical regions, seasonality can be less pronounced. [13]
  5. Coinfections: HMPV can often occur with other respiratory viruses like RSV or influenza. These coinfections may increase disease severity, particularly in young children. [14]

Pathogenesis

HMPV infection begins when the virus enters the respiratory tract, attaching to host cells via its attachment (G) protein. The fusion (F) protein mediates the fusion of the viral envelope with the host cell membrane, facilitating the release of viral genetic material. The virus replicates within the respiratory epithelial cells, inducing inflammatory responses and cellular damage. [15]

  1. Replication: The virus primarily targets cells within the upper and lower respiratory tracts, causing inflammatory responses. [16]
  2. Immune response: The body's immune response to HMPV includes both innate and adaptive responses. The inflammatory reaction can sometimes lead to disease manifestations, especially in susceptible groups. However, reinfections are common, indicating that immunity is not long-lasting. [17]
  3. Cellular damage: HMPV infection can cause damage to respiratory epithelial cells, leading to the release of inflammatory mediators and causing symptoms like coughing and wheezing. [18]
  4. Pathological findings: Necrosis and sloughing off of the respiratory epithelium, along with infiltration of inflammatory cells, have been observed in pathological studies of HMPV-infected lungs. [19]
  5. Viral load: High viral loads have been associated with more severe disease outcomes. [20]

Clinical manifestations

The clinical presentation of HMPV infection is varied, ranging from mild upper respiratory tract illnesses to severe lower respiratory tract infections.

Common symptoms: The infection often manifests with cold-like symptoms, including:

  • Fever
  • Cough
  • Runny nose (rhinorrhea)
  • Sore throat
  • Headache [21]

Lower respiratory tract involvement: In more severe cases, especially in young children and immunocompromised individuals, HMPV can lead to:

  • Bronchiolitis (inflammation of the small airways in the lungs)
  • Pneumonia (inflammation of the lung tissue)
  • Wheezing
  • Dyspnea (difficulty breathing)
  • Respiratory distress [22]

Disease severity: Severity depends on the patient's age, underlying health conditions, and immune status. Premature infants and individuals with chronic lung diseases are at a higher risk for serious complications with HMPV infections. [23]

Complications: Severe infections can lead to hospitalisation, the need for intensive care and, in rare cases, death. Complications may include secondary bacterial infections and exacerbation of pre-existing conditions. [24]


Diagnosis

Diagnosing HMPV infection typically relies on laboratory testing using respiratory specimens (e.g., nasopharyngeal swabs, and nasal washes).

  1. Molecular assays: Reverse transcription-polymerase chain reaction (RT-PCR) is the gold standard for HMPV detection due to its high sensitivity and specificity. It detects the viral RNA genome. [25]
  2. Antigen detection: Rapid antigen tests, although less sensitive than PCR, can offer quick results and are useful in clinical settings for rapid diagnosis. [26]
  3. Viral culture: Viral culture can be used to detect HMPV but it is not routinely used due to its lengthy turnaround time and difficulty. [27]
  4. Serology: Serological tests can be used in research settings to measure antibody responses to HMPV. However, they are not typically used for acute diagnosis. [28]
  5. Differential diagnosis: It's crucial to differentiate HMPV from other common respiratory viruses, such as RSV, influenza, and adenovirus, as clinical symptoms often overlap. [29]

Treatment

Currently, there is no specific antiviral treatment routinely approved for HMPV infections. Treatment focuses on supportive care to alleviate symptoms and prevent complications.

Supportive care:

  • Rest and adequate hydration
  • Over-the-counter fever reducers/pain relievers (e.g. acetaminophen or ibuprofen)
  • Nasal saline drops or spray, especially for young children
  • Oxygen therapy for patients with breathing difficulties [30]

Bronchodilators: In cases of severe wheezing or bronchiolitis, bronchodilators (e.g., albuterol) may be administered to open up airways. However, their effectiveness may be limited in HMPV infections and are not a routine measure. [31]

Antiviral agents: Ribavirin, a broad-spectrum antiviral drug, has been used in severe HMPV infections, particularly in immunocompromised patients, but it has limited efficacy and considerable side effects. [32] Research is ongoing to develop more effective antiviral against HMPV.

Corticosteroids: The routine use of corticosteroids is not recommended for HMPV infections unless indicated for specific reasons such as severe reactive airway disease. [33]

Hospitalisation: Patients with severe symptoms, such as respiratory distress, dehydration, or underlying conditions, may necessitate hospitalisation for closer monitoring and management. [34]


Prevention

Preventing HMPV infection involves the same basic hygiene measures used for other respiratory viruses.

Hygiene practices

  • Frequent handwashing with soap and water or using an alcohol-based hand sanitiser
  • Avoiding close contact with symptomatic individuals
  • Covering the mouth and nose when coughing or sneezing
  • Disinfecting regularly touched surfaces and objects [35]

Vaccine development: There is currently no licensed vaccine for HMPV. Research and development efforts are underway to develop a safe and effective vaccine, especially for high-risk populations. The development of a vaccine is complicated by the genetic diversity of HMPV as well as a lack of understanding of the correlates of protection. [36]

Passive immunisation: Monoclonal antibodies against the F-protein of HMPV are being evaluated as passive immunisation products for vulnerable populations. [37]


HMPV is a significant respiratory pathogen that affects a large number of people, especially young children, the elderly, and immunocompromised individuals. While the majority of infections are mild, HMPV can lead to severe lower respiratory tract diseases such as bronchiolitis and pneumonia. Diagnosis relies primarily on RT-PCR testing. Treatment is primarily supportive, as no specific antiviral therapy is currently available. The development of an effective vaccine represents the greatest hope for limiting morbidity and mortality associated with HMPV. Continued research into understanding all aspects of this virus, as well as continued public health measures, are essential to minimise the impact of HMPV infections.

 

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Partha Ghosh, BNYS, MD(YS), is a general physician and a medical writer from Siliguri, Darjeeling.

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