Introduction to Metapneumovirus Infection in Children

Human Metapneumovirus (hMPV) is a relatively recently discovered respiratory pathogen that primarily affects children, the elderly, and immunocompromised individuals. First identified in 2001 in the Netherlands, hMPV has since been recognized as a significant cause of upper and lower respiratory tract infections worldwide.

Key points about hMPV infection:

• It belongs to the Pneumoviridae family, closely related to respiratory syncytial virus (RSV)
• Causes a spectrum of illnesses ranging from mild upper respiratory infections to severe bronchiolitis and pneumonia
• Most children have been infected by hMPV by age 5
• Seasonality similar to other respiratory viruses, peaking in late winter and early spring

Etiology of Metapneumovirus Infection

Human Metapneumovirus (hMPV) is the causative agent of this infection. Key characteristics include:

• Single-stranded, negative-sense RNA virus
• Member of the Pneumoviridae family, genus Metapneumovirus
• Two main genetic lineages: A and B, each with two sublineages (A1, A2, B1, B2)
• Enveloped virus with surface glycoproteins F (fusion) and G (attachment)
• Size ranges from 150-600 nm in diameter

The virus spreads through respiratory droplets and close contact with infected individuals. It can survive on surfaces for several hours, facilitating transmission in households and healthcare settings.

Epidemiology of Metapneumovirus Infection

hMPV infections occur worldwide and affect all age groups, but are most common and severe in young children:

• Annual incidence in children <5 years: 5-15% of respiratory tract infections
• Peak incidence in children 6-12 months of age
• By age 5, nearly all children have serological evidence of infection
• Seasonality: Late winter to early spring in temperate climates
• Outbreaks have been reported in long-term care facilities and hospitals

Risk factors for severe disease:

• Young age (<2 years)
• Prematurity
• Underlying cardiopulmonary disease
• Immunocompromised status

Reinfection can occur throughout life, but subsequent infections are generally milder.

Pathophysiology of Metapneumovirus Infection

The pathophysiology of hMPV infection involves several stages:

1. Viral Entry and Replication:
   • hMPV enters respiratory epithelial cells via fusion, mediated by F protein
   • Replication occurs in the cytoplasm of infected cells
2. Local Spread and Inflammation:
   • Virus spreads cell-to-cell, causing local inflammation
   • Infected cells release inflammatory mediators, attracting immune cells
3. Immune Response:
   • Innate immune response: Type I interferons, natural killer cells
   • Adaptive immune response: T cells and neutralizing antibodies
4. Airway Obstruction:
   • Inflammation leads to increased mucus production
   • Cellular debris and edema contribute to airway obstruction
5. Recovery or Progression:
   • Most infections resolve with clearance of the virus
   • In severe cases, persistent inflammation can lead to lower respiratory tract involvement

The balance between viral replication and host immune response determines the severity and duration of illness.

Clinical Presentation of Metapneumovirus Infection

hMPV infections can cause a spectrum of respiratory illnesses, ranging from mild to severe:

1. Upper Respiratory Tract Infections:
   • Common cold-like symptoms: rhinorrhea, cough, sore throat
   • Fever (usually low-grade)
   • Duration: typically 3-7 days
2. Lower Respiratory Tract Infections:
   • Bronchiolitis: wheezing, tachypnea, chest retractions
   • Pneumonia: cough, fever, dyspnea, crackles on auscultation
   • Can be severe, especially in young infants and those with underlying conditions
3. Asthma Exacerbations:
   • hMPV can trigger asthma exacerbations in children with asthma
4. Extrapulmonary Manifestations (rare):
   • Febrile seizures
   • Rash
   • Diarrhea

The clinical presentation can be indistinguishable from other viral respiratory infections, such as RSV or influenza. Severity tends to be highest in young infants, the elderly, and immunocompromised individuals.

Diagnosis of Metapneumovirus Infection

Diagnosis of hMPV infection relies on clinical presentation and laboratory confirmation:

1. Clinical Diagnosis:
   • Based on symptoms and physical examination
   • Cannot definitively distinguish from other viral respiratory infections
2. Laboratory Tests:
   • RT-PCR: Most sensitive and specific method, detects viral RNA
   • Rapid antigen tests: Less sensitive but provide quick results
   • Viral culture: Not routinely used due to slow growth of hMPV
3. Specimen Collection:
   • Nasopharyngeal swabs or aspirates are preferred
   • Lower respiratory tract samples in severe cases (e.g., bronchoalveolar lavage)
4. Multiplex PCR Panels:
   • Often include hMPV along with other respiratory pathogens
   • Useful for differential diagnosis
5. Imaging Studies:
   • Chest X-ray: May show hyperinflation or infiltrates in severe cases
   • Not routinely needed for mild infections

Diagnosis is important for epidemiological purposes and can guide management, especially in severe cases or outbreaks.

Treatment of Metapneumovirus Infection

Treatment for hMPV infection is primarily supportive, as there are no specific antiviral therapies approved:

1. Supportive Care:
   • Adequate hydration
   • Fever control with acetaminophen or ibuprofen
   • Nasal suctioning for infants
2. Oxygen Therapy:
   • For patients with hypoxemia
   • May require high-flow nasal cannula or mechanical ventilation in severe cases
3. Bronchodilators:
   • May be used for wheezing, but efficacy is not well-established
4. Corticosteroids:
   • Not routinely recommended
   • May be considered in severe cases or for underlying conditions (e.g., asthma)
5. Antiviral Agents:
   • Ribavirin has shown in vitro activity but clinical efficacy is unproven
   • Investigational therapies are under study
6. Management of Complications:
   • Treatment of secondary bacterial infections if present
   • Intensive care support for respiratory failure

Most children with hMPV infection recover without complications. Hospitalization may be necessary for severe cases or in high-risk patients.

Prevention of Metapneumovirus Infection

Prevention strategies for hMPV infection focus on infection control measures, as there is currently no vaccine available:

1. Hand Hygiene:
   • Regular handwashing with soap and water
   • Use of alcohol-based hand sanitizers
2. Respiratory Etiquette:
   • Covering mouth and nose when coughing or sneezing
   • Proper disposal of tissues
3. Isolation Precautions:
   • Infected individuals should avoid close contact with others, especially high-risk groups
   • In healthcare settings, contact and droplet precautions are recommended
4. Environmental Cleaning:
   • Regular cleaning and disinfection of frequently touched surfaces
5. Avoiding Exposure:
   • Limiting exposure of high-risk individuals during peak seasons
6. Vaccine Development:
   • Several vaccine candidates are in preclinical and early clinical stages
   • No licensed vaccine is currently available

Education of families and healthcare providers about preventive measures is crucial in reducing the spread of hMPV.

Complications of Metapneumovirus Infection

While most hMPV infections are self-limiting, complications can occur, especially in high-risk groups:

1. Respiratory Complications:
   • Acute respiratory distress syndrome (ARDS)
   • Respiratory failure requiring mechanical ventilation
   • Secondary bacterial pneumonia
2. Exacerbation of Chronic Conditions:
   • Asthma exacerbations
   • COPD exacerbations (in adults)
3. Neurological Complications (rare):
   • Febrile seizures
   • Encephalitis
4. Cardiovascular Complications (rare):
   • Myocarditis
   • Pericarditis
5. Long-term Sequelae:
   • Possible association with recurrent wheezing
   • Potential impact on lung function development (under investigation)

The risk of complications is highest in young infants, elderly individuals, and those with underlying medical conditions. Close monitoring of high-risk patients is essential for early detection and management of complications.