Introduction 

Parainfluenza is a respiratory illness that occurs in infants, young children, the elderly population, and people with weakened immune systems. The parainfluenza virus can infect anyone and, in some cases, multiple infections may occur. Human Parainfluenza Viruses (HPIVs) are responsible for the infection. Affected patients may recover on their own, but in other circumstances, it can cause other severe illnesses, such as pharyngitis, croup, otitis media, conjunctivitis, and tracheobronchitis. When an individual is infected with the same virus, they often show cold-like symptoms with mild illness in the upper respiratory tract. However, they can also show serious illness in the lower respiratory tract including pneumonia, bronchitis, and bronchiolitis. Severe illness and fatal pneumonia can occur in immunocompromised adults and the elderly.

Human parainfluenza viruses (HPIVs) are an important cause of respiratory infection in children and adults. Immunocompromised and elderly people may become affected by the lower respiratory tract illness, potentially resulting in life-threatening pneumonia. Respiratory viral infections play an essential role in death and disability among older adults. The HPIV usually causes self-limited illness in healthy adults but the specific reason for enhanced disease in the elderly population is not identified. The difficulty in separating the effects of age from chronic diseases such as parainfluenza leads to complications in the analysis of this issue.¹ Parainfluenza viruses are implicated as possible causes of critical illness in some elderly people.

Parainfluenza Virus (HPIV)

Parainfluenza is caused by the human parainfluenza virus (HPIV) of the Paramyoviridaie family which is a single-stranded, enveloped RNA virus. The HPIV has four major serotypes: HPIV1, HPIV2, HPIV3, and HPIV4. HPVI4 is further categorised into HPIV4a and HPIV4b. Parainfluenza virions are pleomorphic, with diameters ranging from 150-200 µm. In parainfluenza viruses, binding and replication processes occur in the upper and lower respiratory tract on the ciliated epithelial cells. The beginning of infection occurs in the nose and oropharynx. It then spreads to the lower respiratory airways and the highest replication occurs 2-5 days after the start of infection. The host immune response starts once epithelial cells of the small airways get infected with HPIV. The illness associated with infection depends on the location. For example, cold symptoms are related to upper airway infection, croup, and bronchiolitis are linked to larynx and trachea infections and pneumonia is caused by an infection of the lower respiratory airways.

Transmission and symptoms

Parainfluenza infections occur throughout the world and have a seasonal pattern with increased frequency during the spring, fall, and winter. The infection seasonal patterns observed in the northern hemisphere are rare in tropical and subtropical regions and have fewer alterations in the infection rates throughout the year.

Transmission of HPIV can occur due to: 

• Person-to-person contact
• Transmission of large droplets  
• Contact with objects or surfaces interacted with HPIVs infected persons 
• Household outbreaks include outbreaks in daycare facilities and nursing homes 

The symptoms associated with parainfluenza are similar to the symptoms of the common cold such as:

• Runny nose
• Sore throat 
• Cough
• Sneezing
• Fever
• Difficulty in breathing

Other symptoms include ear pain, irritation, and reduced appetite. When the infection becomes critical or more serious, symptoms like barking cough, hoarseness, wheezing, and stridor (noisy breathing or high-pitched sound with breathing) are observed. Pneumonia and severe forms of croup are the most common complications caused by HPIV in children younger than 5, elderly population (older than 65) and immunocompromised people. This may cause breathing difficulties and the need to be hospitalised. In the elderly population, affected immune systems with age and the presence of comorbidities like chronic diseases aggravate the illness caused by HPIV infection.  This causes difficulty in finding the actual reason for the issues related to the illness.

Diagnosis of parainfluenza

Generally, a viral infection is not initially recognised as a parainfluenza infection due to the similarity in symptoms with other infections. People infected with HPIV are tested using a swab where mucus is collected and tested for bacterial or viral infectious diseases. Here, various types of samples are accepted for laboratory tests such as sputum, nasopharyngeal swabs (NPS), nose and throat swabs (NTS), bronchoalveolar lavage (BAL), and nasal washes. The sample collection type depends on the age and immunity status of a patient along with the stage and criticalness of the illness. The illness caused by HPIV is diagnosed by: 

• Measuring oxygen in the blood using a pulse oximeter or pulse ox
• Listening to the sound of the heart and lungs
• Measuring blood pressure

Type of diagnostic methods

• Laboratory diagnosis: Most symptoms associated with HPIV infection do not express unique features, except for croup whose clinical symptoms are usually related to HPIV1. The diagnosis of viral infections typically requires more than clinical assessment alone and often involves laboratory testing to detect either the body's antibody response to the infection or the presence of the virus itself. The timing of sample collection is critical to accuracy. In the early stages of illness, upper airway samples (such as nasal or throat swabs) tend to yield the most reliable results. However, as the infection progresses, samples from the lower respiratory tract (e.g., sputum or bronchoalveolar lavage (BAL) fluid) are more likely to detect the virus in the later stages of the disease
• Fluorescent antibody assays: Since the 1970s, the detection of viral antigens directly on clinical samples has been used as a rapid method for diagnosis of viral illness. Enzyme-linked immunoassays (EIAs) have been used as a simple commercial method for RSV and influenza in children suffering from primary infection. However, there is no rapid antigen test commercially available for HPIV detection. Immunofluorescent-labelled antibodies are used for the detection of HPIV1, HPIV2, and HPIV3. However, antibodies for HPIV4 detection are usually unavailable. Therefore, in case of limited clinical resources, immunofluorescent assay (IFA) becomes a reasonable method to test clinical samples
• Molecular assays: These are preferred to other diagnostic tests for HPIV infection due to their rapidity, sensitivity, and specificity. The molecular assays which include polymerase chain reaction (PCR) exhibit high sensitivity to viral culture. Earlier, high cost and technical expertise have limited the use of PCR for clinical utility or in tertiary-care facilities. However, the development of commercial assays has simplified its use and increased the accessibility of PCR in clinical microbiology laboratories. The currently available multiplex real-time PCR assays can test viral pathogens including HPIV 1–4. Some variation occurs in the sensitivity when testing different HPIV serotypes, but for individual targets the loss of sensitivity is minimal. Different types of samples are used for PCR testing and viral samples of low quantity can also be detected using PCR assays, which is crucial for early infection control in transplant and elderly populations
• Serologic diagnosis: This method of diagnosis is predominantly used as a research tool and rarely used in clinical practice. Serotype-specific testing of the infection using only antibody response becomes difficult due to cross-reactive immune responses to HPIV1 and 3 antigens. The diagnosis of HPIV-specific IgM has been reported in HPIV-infected children but is not commercially available

Treatment of parainfluenza

There is no antiviral treatment predominantly for HPIV infection. As antibiotics are effective against bacteria, they cannot be used to treat parainfluenza, which is a virus-causing illness. In most cases, people infected by HPIV recover on their own. Symptomatic treatments can be used, such as: 

• Medicine to relieve pain and fever including ibuprofen, acetaminophen, and other available over-the-counter (OTC) treatments.  Some OTC medicines containing dextromethorphan or guaifenesin can be used to loosen mucus or soothe cough symptoms
• Use a humidifier or take a hot shower to ease cough and sore throat
• Consume plenty of liquids, including hot tea with honey
• Use inhaled medicines such as albuterol if prescribed to mitigate the symptoms. It can be suggested for elderly patients to ease breathing
• Throat lozenges can be used
• A humidifier can be used for supportive care
• Pulmonary rehabilitation for breathing techniques
• Rest

Preventive measures

Nowadays, licensed vaccines to prevent parainfluenza infection are not available. The vaccine efforts are predominantly focused on HPIV3 which is a prime reason for severe disease and pneumonia in older adults as well as in infants. The immature immune system and maternal antibody hamper active immunisation in young children. Croup infections associated with HPIV1 and HPIV2 take place at an older age and consequently delay the timing of vaccination.² Transmission of HPIV occurs through large particle aerosols. HPIV transmission risk can be reduced by:

• Use alcohol-based hand rub/sanitiser to keep hands clean, and use soap with water to wash hands for a minimum of 20 seconds
• Abstain from touching the eyes, nose, or mouth
• Avoid close contact with infected people 
• Stay at home when infected or sick and abstain from close contact with others
• When coughing or sneezing, cover one’s mouth and nose
• Keep surfaces and objects disinfected
• Use a well-fitted mask

In an instance of a critical HPIV3 outbreak in an LTCF (long-term-care facility), 49 elderly residents were reported with a 50% attack rate, 11 radiographic pneumonia, and 4 deaths. However, HPIV epidemics are reported in LTCFs, there is finite evidence of its impact on the wider elderly community. The true impact of parainfluenza is underestimated due to non-screening or negligence for the patients affected with acute respiratory illness. An A3-year-long study study that examined respiratory viral infections reported that a diversity of respiratory viruses co-circulated in the LTCFs, rather than a single prominent pathogen.

Summary

Parainfluenza has been observed as a possible cause of critical illness in some elderly individuals. Sensitive molecular diagnostics are present for the rapid diagnosis of HPIV infection, but potent antiviral therapies are currently unavailable. In the treatment of parainfluenza or HPIV infection, only supportive care is present, except for croup which is cured through corticosteroids. Novel drugs such as DAS181 appear potent to treat severe illness in immunocompromised patients. Vaccines are in the development stage to reduce the burden of disease. The declining immune system and presence of comorbidities demand effective therapies to treat parainfluenza in the elderly population.

Preventive measures include limiting visitors' presence with physical distancing, reducing patient-to-patient contact, compulsory use of masks by people visiting HPIV patients, and maintenance of good hygiene. The management of the parainfluenza virus requires a team of healthcare professionals including nurses, clinicians, epidemiologists, infectious disease experts, paediatricians, pharmacists, and ICU teams in critical cases. Interventions have to be considered at the local, and national levels (Centres for Disease Control/CDC) and global level (World Health Organisation/ WHO).