Introduction

Parainfluenza is a respiratory infection that occurs in infants and young children with weakened immune systems. It is caused by Human Parainfluenza Viruses (HPIVs) which are responsible for nearly 40% of respiratory infections diagnosed in infants and children.¹ Patients suffering from this usually recover on their own while in some it can cause other severe illnesses, such as croup or pneumonia, otitis media, pharyngitis, conjunctivitis, tracheobronchitis.

Anyone can be infected due to HPIV and in some instances people may have multiple HPIV infections in their lifetime. The reinfections in such cases usually develop mild illness in the upper respiratory tract with cold-like symptoms. However, reinfections in some cases may lead to serious illness in the lower respiratory tract, such as bronchitis, bronchiolitis and pneumonia. People with weak immune systems and older adults are prone to severe infections. 

Parainfluenza is one of the prominent reasons for mortality and morbidity in infants worldwide. The terminal airways of an infant is small, therefore, bronchiolitis is commonly found in infants and young children. While in the patients above 15 years of age, pneumonia was most common (10.5%) amongst the hospitalized patients suffering with HPIV infection. Bronchitis and upper respiratory infections are the prevalent illnesses that occur due to HPIVs in adults.¹ In older adults and people with weak immune systems, pneumonia is the most common.⁶

Bronchitis is an inflammation caused by infection in the airways of the lungs (bronchial tubes). Often it causes coughing with mucus and can be for short duration or long duration. Acute bronchitis (short-term) is very common and contagious caused by infection. In chronic bronchitis (long-term) breathing can become difficult due to inflamed airway leading to swelling and more mucus production. Usually, recovery in acute bronchitis takes a few days or weeks, however chronic bronchitis can take three months and may return at least two years in a row.³

Parainfluenza and types 

Human parainfluenza viruses (HPIVs) are single-stranded, RNA-enveloped viruses belonging to the Paramyoviridaie family of viruses. HPIVs bind and replicate in the ciliated epithelial cells of the upper and lower respiratory tract and the extent of the infection correlates with the location involved. The incubation period (the duration of getting infected by HPIV to onset of symptoms), generally requires 2 to 6 days. Here, four serotypes (HPIV-1, HPIV-2, HPIV-3, HPIV-4) are responsible for respiratory illnesses in children as well as adults.⁴

• HPIV-1 is often identified as the major cause in children. HPIV-1 and HPIV-2 are most commonly associated with croup and both can be considered for cold-like symptoms as well as upper and lower respiratory illness
• HPIV-3 is commonly considered to cause bronchiolitis, bronchitis, and pneumonia
• HPIV-4 is less associated with this but can be responsible for mild to severe respiratory tract illnesses

Transmission and common symptoms

Human parainfluenza viruses (HPIVs) generally transmitted from an infected person to others by different modes:

• Air droplets due to coughing and sneezing
• Close person to person contacts through touching or hand shaking
• Contact with objects or surfaces infected with HPIVs and then touch the mouth, nose, or eyes

People can get infected by HPIV throughout the year, but often it occurs in the spring, summer and fall. Symptoms associated with parainfluenza usually appear 2 to 6 days after infection.¹ The signs and symptoms are identical to common cold and can be listed as:

• Sore throat 
• Sneezing
• Runny nose
• Cough
• Fever

Other symptoms of HPIV infection are:

• Irritation
• Ear pain
• Less appetite

Critical infection or more serious infection reflect symptoms which include:

• Hoarseness
• Barking cough
• Wheezing
• Stridor (noisy breathing or high-pitched sound with breathing)

HPIVs may leads to serious infection in children which include:

• Croup (infection in the vocal cords/larynx, windpipe/trachea and can reach up to the bronchial tubes/bronchi)
• Bronchitis (infection in the central air passages which connect the windpipe with the lungs)
• Bronchiolitis (infection of the smallest air passages in the lungs)
• Pneumonia (lungs infection)

Populations at risk 

In the children under 5 years of age suffering from acute respiratory tract infection, 17% of hospitalization is majorly caused due to HPIVs. According to Serological surveys 60% of children (around 2 years of age) are infected with HPIV-3, whereas HPIV-3 infection rate rises up to 80% in children around 4 years of age. The prominent cause of lower respiratory infections in infants, young children, adults, elderly and the immunocompromised is HPIV-1, HPIV-2 and HPIV-3. Infection caused by HPIV in the elderly and immunocompromised patients accompanying various diseases such as mild upper respiratory tract illness or more severe illness in the lower respiratory tract. This may require mechanical ventilation and can become a reason for death. However, HPIV-4 rarely leads to serious illness. People with weak immune systems and older adults are more prone to severe infections caused by HPIV. Antibodies against HPIV-3 are present in children 5 years of age and above while, approximately 75% have antibodies against HPIV-1 and HPIV-2.⁵

Bronchitis

Bronchitis is an inflammation of the airways connecting with the lungs. Bronchitis is an inflammation of the airways leading into your lungs. It is stimulated due to irritation in the airways (trachea and bronchi), leading to swelling up and cough caused by mucus. This cough is the main symptom of bronchitis and may last for days or a couple of weeks. Smoke and other irritants can trigger acute and chronic bronchitis.⁶

Generally, Acute bronchitis is induced by airway inflammation caused by viral infections such as influenza (flu), respiratory syncytial virus RSV, cold or COVID-19 viruses. In some instances, it can be caused by bacterial infection. In the patients suffering with chronic obstructive pulmonary disease (COPD), chronic bronchitis is a frequent symptom, accompanied with emphysema and asthma. The risk factors associated with chronic bronchitis include:

• Older age 
• Exposure to cigarette smoke, fumes or dust 
• A family history of COPD (chronic obstructive pulmonary disease) and respiratory diseases such as asthma, cystic fibrosis, or bronchiecstasis
• Gastroesophageal reflux disease (GERD)

Chronic bronchitis is not related to increasing the risk of COVID-19 but it increases the risk of complications after being infected by COVID-19. The symptoms associated with acute and chronic bronchitis are the same such as:

• Cough with mucus
• Tiredness
• Shortness of breath
• Chest pain
• Wheezing
• Fever below 100.4 degrees Fahrenheit

In acute bronchitis symptoms appear clearly after 2 − 3 weeks, but in chronic cases a productive cough can persist up to three months or more.

Mechanism of Infection

The infection caused by parainfluenza virus initiates at the mucociliary airway epithelium of the nose and pharynx. Later advances to the large and small airways. In the ciliated epithelial cells of the upper and lower respiratory tract, attachment and replication of the virus takes place. The peak replication occurs after 2 to 5 days of initiation of infection. However, the severity and the extent of infection is related to location, that is, upper respiratory tract infection correlates with mild infection and infection in the lower respiratory tract increases illness such as pneumonia, croup and bronchiolitis.⁵

The inception of infection in the epithelial cells of small airways causes development of inflammatory infiltrate and the host-immune response assists in disease pathogenesis. When a cell gets infected with the HPIV, the first morphological change is noticed in the cytoplasm and nucleus with increase in size and focal rounding. While after 24 hours of inoculation of the HPIV, mitotic activity of the host cell decreases. The formation of multinucleated (2-7 nucleus) giant cells are generally observed in the later phase of infection. Paramyxoviruses causing parainfluenza are one of the family of pathogens that can be responsible for apoptosis (a type of cell death) in tissue culture cells. HPIV is responsible for mild destruction of rapidly repaired focal tissue which remains unnoticed in major cases. If the infection approaches beyond respiratory epithelium it can also be a rare cause of death, which is particularly found in immunocompromised patients.

Diagnosis

Human parainfluenza virus 1 (HPIV-1) is generally related to croup and can be diagnosed based on only clinical presentations. While, other serotypes of HPIV do not contain clinical features which aids in clinical diagnosis, hence require laboratory testing for diagnosis. Samples of various types are used for testing, such as sputum, nasopharyngeal swabs, nose and throat swabs, nasal aspiration and bronchoalveolar lavage. The diagnostic tests associated with parainfluenza are:

• Viral culture: This is a time consuming method of diagnosis and accessibility of results takes time, therefore rarely used in HPIV infection. While it was considered the gold standard for diagnosis for year
• Fluorescent antibody assays: It has been utilized as a rapid method of diagnosis since the 1970s. This method depends upon the identification of viral antigens directly on clinical samples. Specified immunofluorescent-labeled antibodies are used for the direct detection of HPIV 1–3 with sensitivities of 63 to 95%. But antibodies to HPIV-4 are not feasible which narrow down the clinical features of the HPIV infection
• Serologic diagnosis: It is predominantly used for research purposes and rarely used for diagnostic purposes

The diagnosis of bronchitis begins with a physical exam and is performed by a healthcare provider who will ask about medical history and symptoms of the patient. This may also require a blood test or a chest X-ray to check infection. These additional tests aids to distinguish it from other illnesses like pneumonia, COVID-19, asthma as cough is a symptom for many such conditions. Bronchitis has symptoms linked with pneumonia, but differs in symptoms like higher heart rate, high fever (100.4 degrees or above) and fast breathing. Wheezing and coughing also has a history linked to asthma, while two of three people suffering from bronchitis (twice in 5 years) also had asthma.⁵

Treatment and management

Treatment options for parainfluenza infection

HPIV infection does not have specific antiviral treatment. Antibiotics are not effective against HPIVs as they are active against bacteria not viruses. In most of the cases people suffering from HPIV infection recover on their own. While, the symptoms can be mitigated by: 

1. Medications to relieve pain and fever- ibuprofen, acetaminophen and other over-the-counter
2. Ease cough and sore throat by using a humidifier or take a hot shower
3. Consume plenty of liquids
4. Take rest

Treatment options for bronchitis

Acute bronchitis does not require treatment, often it goes away on its own. Healthcare providers prescribe antibiotics particularly if the patient has a bacterial infection, commonly found in young children. However, steps can be taken to feel better which include:

1. If prescribed, use inhaled medicines such as albuterol which may mitigate the symptoms
2. To mitigate cough symptoms or to loosen mucus, over-the-counter (OTC) medicines consisting of dextromethorphan or guaifenesin can be used
3. Use throat lozenges
4. Consume hot tea or water with honey
5. For supportive care use a humidifier

A healthcare provider can also ask about:

• Avoid smoking
• Oxygen therapy for better breathing
• Pulmonary rehabilitation for breathing techniques.

Prevention

Currently, there is no vaccine available to treat human parainfluenza viruses (HPIV) infection. However, researchers are working to develop vaccines. The risk associated with HPIV and other respiratory viral infections can be reduced by hampering the spread of germs through everyday actions which include:

• Wash your hands for a minimum 20 seconds with soap and water or use an alcohol-based hand rub/ sanitizer
• Avoid touching the eyes, nose, or mouth
• Avoid close contact with infected people

If a person is infected with a common cold or cough can be caused by HPIV, then take following steps to stop its further spreading by:

• Stay at home when infected or sick.
• Avoid close contact with others
• Cover mouth and nose when cough or sneeze
• Keep surfaces and objects disinfected
• Wear a well-fitted mask. Children ages 2 years and older can wear masks or respirators to protect themselves and others from HPIVs.

Summary

Parainfluenza viruses are associated as one of the prominent reasons for respiratory viral infection. Therefore in healthy children and adults, symptomatic treatment against HPIV infection is more acceptable for prognosis and outcome. However, once an immunocompromised population gets affected with the infection and viral replication prognosis becomes difficult and can become grave. Consequently, in immunocompromised patients infected with HPIV early diagnosis with treatment has major importance. The parainfluenza virus is predominantly transmitted through large-particle aerosols between people. Viruses emitted by young children can last for a duration 10 hours on porous surfaces, while small particle aerosols are rarely related to the mechanism for transmission.

If HPIV outbreaks are detected, stringent infection control measures should be adopted for immunocompromised patient health care.The measures include limited visitors with physical distance and avoid patient-to-patient contact, mandatory use of masks of people visiting HPIV patients, surface cleaning measures and maintenance of hygiene. The parainfluenza virus can not be managed without a team of healthcare professionals which includes nurses, clinicians, epidemiologists, infectious disease experts, pediatricians, pharmacists, and in severe cases, the ICU team. The prevention of HPIV infection from spreading is the primary measure to be taken after its diagnosis. The primary role is played by clinician and the nurse to educate the patient with family about the significance of preventive measures such as isolation and physical distancing.

However, the management of parainfluenza virus outbreak requires the participation of not only a team of healthcare professionals in the hospital settings managing the patient, but also needs local resources to spread education related to the disease as fast as possible. In this resources at the national level (centers for disease control/CDC) and global level (world health organization/WHO), must assist in the management of local cases, prevention of further spread, recognize the genesis of the outbreak and avail diagnostic assistance from high-level biosafety laboratories.⁵