Overview

Parainfluenzas, formally known as Human Parainfluenza Viruses (HPIVs), are viruses that cause respiratory infections. HPIVs usually infect children, but those who are suffering from weakened immune systems are also at risk of getting infected (Nationwide Children’s). HPIVs are one of the leading causes of mortality in children, and, consequently, it is important to recognise the signs of parainfluenza. HPIVs are different from the common cold, and they are also not the same as the flu (influenza). Depending on the location of the infection, other comorbidities (more than one illness/condition) can occur. These include pneumonia and bronchiolitis. This article aims to explain what parainfluenza is, the causes of the infection, the symptoms, the potential comorbidities that may occur, as well as its prevention and treatment. 

What are parainfluenzas?

HPIVs is a term used to classify a group of viruses caused by the Paramyxoviridae virus family.¹ They can be further subdivided into types based on antigens present in the virus. These subclasses are HPIV-1, HPIV-2, HPIV-3, and HPIV-4. HPIV-4 can further be classified into HPIV-4A and HPIV-4B (GOV UK).¹ The types of HPIV also have different periods of time that they are ‘in season,’ or more present in frequency. According to the CDC, the following seasons for each HPIV type are:

• HPIV-1:
  • Every other year during autumn.
• HPIV-2:
  • Every other year during autumn when HPIV-1 is lower in number.
• HPIV-3:
  • Usually in Spring or Summer, but is also present throughout the year, especially if HPIV-1 and HPIV-2 are low in frequency.
• HPIV-4A/B:
  • No particular pattern characterised as of yet, but there are some general trends towards autumn and winter.

Subtypes HPIV-1 to HPIV-3 have shown to be major causes of lower respiratory tract infections, but all subtypes can also cause upper respiratory infections.² Those who have lower respiratory tract infections from HPIV tend to have more severe symptoms and comorbidities, while those with upper respiratory infections generally have milder symptoms.²   

Biology of parainfluenzas

Parainfluenzas are single-stranded RNA (ribonucleic acid) viruses, and like other viruses, require the host's (in this case, humans’) cellular proteins/machinery in order to replicate and circulate within the body.^1,3 There are six main proteins that HPIVs encode (produce) to help them survive and evade the host’s immune system. These proteins are:¹

• Nucleocapsid protein (NP)
• Phosphoprotein (P)
• Fusion glycoprotein (F)
• Matrix protein (M)
• Haemagglutinin-neuraminidase (HN) glycoprotein
• RNA polymerase (L)

The most common proteins that are present in influenza viruses (viruses that cause the flu) are haemagglutinin-neuraminidase (HN), matrix protein (M), phosphoprotein (P), and nucleocapsid protein (NP).⁴ However, the influenza viruses have more proteins involved and are distinct in that influenza viruses are caused by a different family, known as Orthomyxoviruses.⁵

HPIVs use their HN proteins and F proteins to attach to host cells, particularly to substances called sialic acid residues.¹ The neuraminidase from HN is also able to cleave (or cut off) the sialic acid residues and cause further spread of the virus.¹ The matrix protein helps in providing the virus structure by enveloping its inner surface.⁶ 

NPs are responsible for packing the RNA in organised ways using proteins P and L and therefore aid in the replication of the virus.¹ The gene responsible for encoding P proteins also produces other proteins that are different among the subtypes. In HPIV-2, this is the V protein. In HPIV-1 and HPIV-3, a C protein is made. HPIV-3 also makes a D protein, but it has yet to be characterised.¹ Both V and C proteins have been shown to decrease immune system activity, particularly decreasing the activity of interferons (a type of signalling protein known as cytokines).⁷ These interferons are responsible for sending signals out to the rest of the body to make proteins or cells that can engulf or break down the viruses.¹ Therefore decreasing the activity of these proteins leads to infection, and particularly infections from other pathogens if the host’s immune system is weak.

Statistics

HPIV in children has been shown to account for 17% of hospitalisations in children below five years old.8 Studies have shown that 60% of HPIV-3 infections are in children around two years of age, and increase up to 80% in children of four years of age.⁹ Outbreaks can happen, especially in particular facilities, such as nursing homes and daycares.¹⁰ 

Symptoms

Unfortunately, parainfluenza has symptoms that overlap with the common cold, flu, COVID-19 and RSV (Respiratory Syncytial Virus) (Mayo Clinic).¹ As such, your GP/doctor will likely take a swab test to rule out any other possible illnesses or infections. Due to the high percentage rate of HPIVs in children and patients with weakened immune systems, it may be worth seeing a doctor for the following symptoms (Mayo Clinic):

• Fever
• Cough
  • Mild or barky cough (known as Croup [inflammation of the larynx and trachea]) or cough with mucus
• Stuffy and/or runny nose
• Sore throat
• Wheezing and high-pitched sounds while breathing
• Hoarseness
• Sneezing

Comorbidities

• Bronchiolitis
  • More common in younger children and infants due to their underdeveloped airways.¹ 
• Pneumonia
  • Most commonly caused by HPIV-1 and HPIV-3
  • 2–12% of HPIV-3 causes pneumonia hospitalisations in children¹
  • 1–6% of HPIV-1 causes pneumonia hospitalisations in children¹
  • For adults, HPIV-related pneumonia hospitalisations range from 0.5–11.5%¹

HPIV spreads through human contact, through the air (coughing and sneezing), and through touching objects/surfaces that an infected person has touched (CDC). 

Diagnosis, treatment, management, & prevention

To diagnose parainfluenza, it is important to consider the timing of the infection. Since the infection can spread to the lower respiratory tract, your GP may need to swab the lower respiratory tract for symptoms that have presented for a while.¹ In comparison, infections caught earlier should be able to trace positive signs of parainfluenza in the upper respiratory tract. For HPIV-3, diagnosis of the virus has been as early as 36 days (six days before the six-week mark) after the first symptom.1 In both older and immunocompromised patients, HPIV-1, HPIV-2, and HPIV-3 have been shown to stay in the body for months at a time.² 

Methods to detect parainfluenza include:

• Viral culture
  • The sample is taken from a patient and put into a culture with cells that can be infected by parainfluenza. If the cells show any changes, that shows that parainfluenza is present (DermNet).
  • Not as common anymore due to the time needed to culture the virus.¹ 
• Fluorescent antibody assays
  • A blood sample is taken from the patient which contains antibodies. Antibodies are produced by the body to fight against infection. A specific antigen is then introduced (specific to the virus) and if the antibodies bind to the antigen, then the patient is positive for the virus. The antibodies are linked to another protein that emits light (fluorescence) when it binds to antigens, which lets scientists know for certain that the reaction has taken place.¹¹ 
  • Unfortunately, the accuracies of antibody assays for parainfluenza are varied, having accuracy ranges between 63–95% for HPIV-1, HPIV-2 and HPIV-3. Antibodies for HPIV-4 have not been characterised.¹ 
• Molecular assays (Polymerase Chain Reaction [PCR])
  • PCR is used to amplify a sample. If there are small amounts of the virus in the sample, it will be amplified and therefore show a positive result of the virus (Medline). 

Treatment of parainfluenza is limited to treating the symptoms as viral medications have not shown to be very effective in later stages of the infection.¹ Consequently the medicines used will consist of the following:

• Corticosteroids
  • More commonly known as steroids are used to treat inflammation (NHS). They are used to treat croup.¹
• Epinephrine
  • Commonly known as adrenaline, it is used in spray form to help reduce inflammatory symptoms.¹ 

For the most severe cases, treatment is generally focused on supporting the patient through palliative care.

Summary

Parainfluenza viruses or HPIVs are a group of viruses under the Paramyxoviridae family. The rate of infection is quite high among children and those who are immunocompromised. It is spread through the air from sneezing or coughing or from contact with someone who has been infected. There are four types of HPIV, which are HPIV-1, HPIV-2, HPIV-3, and HPIV-4A/B. Each subtype is correlated with different symptoms and different severity of symptoms. Due to the virus’ ability to decrease the effectiveness of the immune system, it is possible for the infection to cause comorbidities such as pneumonia and bronchiolitis. Multiple methods exist for diagnosing parainfluenza in patients, with PCR being the most accurate. Unfortunately, treatments are usually localised to treating symptoms as viral medication has not shown to be too effective in later stages of the infection. It is therefore important to recognise the symptoms of parainfluenza early and to get interventions as soon as possible.