Human Para-influenza Viruses (HPIV)

• Human para-influenza viruses (HPIV) are a group of viruses that commonly cause respiratory tract infections.
• HPIV is the second most common cause of acute respiratory infections in children under five years of age.
• HPIV belongs to the Paramyxoviridae family.
• Four types of HPIV infect humans: types 1, 2, 3, and 4.

Structure

• Para-influenza viruses are enveloped viruses, covered by a lipid membrane.
• Inside the lipid membrane is a nucleocapsid, containing a single-stranded, negative-sense RNA genome and an RNA polymerase enzyme.
• The lipid membrane contains two important glycoproteins: H/N (Hemagglutinin-Neuraminidase) and F (Fusion protein).

Transmission

• Para-influenza viruses spread through virus-containing droplets when an infected person sneezes or coughs, reaching up to 2 meters (6 feet) away, landing in the mouths or noses of people nearby or inhaled into their lungs.
• The virus can survive on surfaces for a few hours, spreading via contaminated surfaces such as doorknobs.
• The virus enters the body and uses hemagglutinin to bind to sialic acid sugars on the surface of epithelial cells in the respiratory tract.
• The F protein helps the virus fuse with the epithelial cell membrane and release the nucleocapsid into the cytoplasm.
• RNA polymerase transcribes the negative-sense viral RNA into positive-sense mRNA strands.
• Host cell ribosomes translate mRNA strands into viral proteins, which are assembled into new viruses.
• Neuraminidase cleaves sialic acid sugars from the host cell membrane, allowing the newly created viruses to bud out of the cell and infect neighboring cells.
• The virus destroys epithelial cells, triggering an immune response.
• Immune cells release chemokines, causing inflammation and increased mucus secretion.
• Blood vessels in the airway walls become more permeable, allowing fluid and immune cells to enter, leading to airway swelling.

Diseases Caused by HPIV

• HPIV-1 and HPIV-2 commonly cause croup (acute laryngotracheobronchitis), an inflammation of the larynx, trachea, and bronchi.
• HPIV-3 commonly affects the lower airways, causing pneumonia or bronchiolitis.
• HPIV-4 affects both upper and lower respiratory tracts, but infections are rare and mild.
• Narrower airways in children, when compounded by inflammation and swelling, lead to increased airway restriction.
• Hypoxemia (low oxygen levels in the blood) and Hypercarbia (high carbon dioxide levels in the blood) are potential consequences of restricted airways.

Epidemiology and Risk Factors

• Para-influenza virus outbreaks occur more frequently in late autumn.
• Higher risk individuals include children between 6 months and 3 years old, people with congenital airway narrowing, people with hyperactive airways (e.g. asthma patients), and individuals with a history of intubation.

Symptoms

• The incubation period lasts 2 to 6 days.
• Early, non-specific symptoms include abdominal pain, myalgia (muscle pain), fatigue, and headaches.
• Croup (HPIV-1, HPIV-2) symptoms include fever, inspiratory stridor (high-pitched breathing noise), laryngeal obstruction (breathing difficulty), barking cough, and hoarse voice.
• Severe croup can lead to agitation due to hypoxia.
• Bronchiolitis (HPIV-3) symptoms include chest congestion, sore throat, cough, and wheezing.
• Pneumonia (HPIV-3, HPIV-4) symptoms include shortness of breath, chest pain, and productive cough (may include pus or blood in sputum).

Diagnosis

• Nasopharyngeal secretions are taken via nasal/throat swabs or nasal aspiration to confirm para-influenza infection.
• Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) detects tiny amounts of viral RNA.
• Immunofluorescence or ELISA detects viral antigens.
• Viral culture grows the virus in a culture medium.
• Imaging of the neck via X-ray in croup shows tracheal narrowing, forming a "steeple sign".
• Imaging of the chest via X-ray in pneumonia may show pulmonary consolidation.

Treatment

• Most para-influenza infections are self-limiting and require only antipyretics to reduce fever.
• Moderate to severe croup treatment includes corticosteroids (dexamethasone) to reduce airway inflammation.
• Racemic epinephrine nebulization is given if corticosteroids are ineffective.
• Bronchiolitis treatment includes supplemental oxygen and IV fluids to prevent dehydration.