Human parainfluenza viruses (HPIVs) are the second most common viral causes of severe respiratory tract infection in infants and children. Human parainfluenza viruses belong to the family Paramyxoviridae. -. HPIV has four serotypes— 1 to 4. HPIV 1, 2, and 3 are first isolated from children with lower respiratory tract infection and HPIV 4 was isolated from children with mild respiratory tract infection.

The name “Parainfluenza” was given because it produces influenza-like symptoms and the virus particle also resembles influenza virus as it possesses lipid envelop and hemagglutinin and neuraminidase surface glycoproteins.

VIRUS

HPIVs are spherical or pleomorphic, enveloped viruses with single stranded, non-segmented, negative sense RNA genome. The nucleocapsid is of helical symmetry. Hemagglutinin neuraminidase (HN) and fusion (F) protein are the two surface glycoproteins present on the envelop.

Classification: The virus has four serotypes— HPIV 1 to 4 which is based on the less than 50% antigenic similarities for F and HN proteins. According to the recent ICTV classification, HPIV 1 and 3 belong to the genus Respirovirus (renamed human respirovirus 1 and 3, respectively) and HPIV 2 and 4 belong to the genus Rubulavirus (renamed human rubulavirus 2 and 4, respectively). Both the genera presently classified under the family Paramyxoviridae.

VIRAL SURFACE PROTEINS

Hemagglutinin Neuraminidase (HN) Protein

These proteins are present on the virus envelop as surface projections.

Structure

It is a type II glycoprotein, present in the form of a tetramer. It consists of a stem and a globular head. Globular head bears the antigenic sites and HA and NA activities.

Function

• Possess the activities of both hemagglutinin and neuraminidase.

 • In the initial part of infection, it mediates the attachment to host cell surface receptor sialic acid by hemagglutination activity.

• In the later part of infection, it breaks the sialic acid residue by neuraminidase to release the progeny virions.

• Both hemagglutination and neuraminidase activities are modulated by pH.

Fusion (F) Protein

Structure

It is a type I glycoprotein. Present in the form of a trimmer. It is synthesized as inactive F0 form which is cleaved by endopeptidase to active form which consists of F1 and F2 that are linked by disulphide bond. The N terminal of F1 is responsible for fusion.

Function

• Responsible for fusion of viral envelop with the plasma membrane of the host cell. This in turn leads to entry of the virus and release of viral nucleic acid to host cell cytoplasm.

 • Responsible for fusion with the neighboring cell producing syncytia (cytopathic effect in in vitro).

EPIDEMIOLOGY

HPIVs are ubiquitous virus and are present worldwide. These viruses are responsible for causing acute respiratory tract infections in all age groups but more commonly in infants and children less than 5 years. The peak rate of infection of different HPIV types is:

• HPIV-1 and 2: Children between 1 and 3 years age.

• HPIV-3: Infants less than six months. •

 HPIV-4: No specific age group predilection.

Modes of Transmission

 • Through person-to-person contact.

• Infected large droplet.

Seasonality

HPIV-1: Biennial epidemics during fall months (September to December). Mostly associated with croup (laryngotracheobronchitis)

HPIV-2: Biennial fall epidemics along with HPIV-1 or biennially alternate with HPIV-1 or annual epidemic

HPIV-3: Summer and spring months.

CLINICAL FEATURES

HPIVs cause acute respiratory tract infections (ARTI) affecting either upper or lower respiratory tract or both. Primary infection by HPIV is usually symptomatic in nature which manifests with respiratory illness. The most common symptoms are pharyngitis, rhinitis, laryngitis leading to fever, cough, and hoarse ness. Cervical lymphadenopathy is uncommon, whereas otitis media occurs frequently.

 Croup (acute laryngotracheobronchitis): As the name suggests, croup is inflammation of larynx, trachea and bronchus, which leads to hoarse barking cough, inspiratory stridor, fever and laryngeal obstruction. It is most commonly seen in children between 1 and 2 years age.

Croup is most commonly associated with HPIV-1 (more than 50%) followed by HPIV-2 and HPIV-3.

Bronchiolitis and pneumonia: These are the main symptoms of LRTI in children. It manifests with fever, tachypnea, expiratory wheeze, rales, retraction and trapping of air. Young infants and children up to 2–3 years age are most commonly affected. HPIV is the second common viral cause of LRTI to respiratory syncytial virus (RSV). All four serotypes of HPIVs can cause bronchiolitis or pneumonia but HPIV-1 and HPIV-3 are most frequently associated. HPIV-3 is more frequently associated in hospitalized patients. Interstitial or perihilar infiltrates are the common radiologic findings of chest.

In immunocompromised patients, more commonly hematopoietic transplant and severe combined immunodeficiency syndrome (SCID) patients and elderly individuals are more prone to develop severe respiratory illness caused by HPIV. HPIV-3 is most frequently associated with infection in this patient group though all four HPIV can cause infection.

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