Overview

Did you know that parainfluenza viruses can cause much more complications than just respiratory illnesses? While parainfluenza is commonly associated with a variety of upper and lower respiratory diseases, it can also result in neurological complications that can be dangerous to patients if overlooked. 

Introduction to parainfluenza

Parainfluenza is caused by a group of viruses, called the human parainfluenza viruses (HPIVs). They are responsible for causing various upper and lower respiratory infections. There are 4 serotypes of viruses within the group, including types 1 to 4, each responsible for different illnesses.¹ Despite HPIVs sharing similarities in the symptoms that they present to the other common viruses we know of, such as SARS-CoV-2 or influenza, they each come from different viral families and result in different illnesses.¹ Parainfluenza is very contagious and is prevalent among children and infants,² with 90% of adults experiencing at least one HPIV infection in their lifetimes.³ Other symptoms that HPIV displays include ear pain, hoarseness, barking cough, decreased appetite and such.⁴ Furthermore, immunocompromised patients or those with chronic lung diseases are more likely to be severely affected by parainfluenza.

Types of neurological complications

Febrile seizures

Febrile seizures are one of the neurological complications that are caused by an infection by human parainfluenza viruses, as a result of fever. During the infection, the virus triggers the body's immune system, which induces an inflammatory response, releasing cytokines and chemokines. These inflammatory mediators can travel through the bloodstream and interact with the hypothalamus, which leads to the release of prostaglandin E2 in response to the cytokines.⁵ As prostaglandin E2 binds to its complementary EP3 receptor, it signals the hypothalamus to initiate thermogenesis, the process by which heat is produced, resulting in fever.⁶ Parainfluenza infections have shown to possess a higher rate of incidence of febrile seizures in comparison to other viruses⁷ and it is common in the younger age groups. 

Posterior reversible encephalopathy syndrome

Another neurological condition that parainfluenza can cause is posterior reversible encephalopathy syndrome (PRES), a neurological condition where a person experiences altered mentation, visual impairments and headaches.⁸ Similar to febrile seizures, the viral infection of HPIVs results in an inflammatory response, and through its various mechanisms leads to endothelial dysfunction, causing the blood vessels to be unable to relax and contract properly.⁹ These large fluctuations in blood pressure can result in high blood pressure,¹⁰ commonly known as hypertension, which is a major risk factor for PRES as it can result in subsequent vasogenic oedema in the brain and neurotrophic effects.

Encephalitis and ventriculitis 

Other neurological disorders that parainfluenza can cause are encephalitis and ventriculitis, in which both conditions are primarily caused by direct infection. Encephalitis is the inflammation of the brain tissue, which can be caused by an infection in these tissues, resulting in damage and leading to tissue dysfunction and damage.¹¹ In contrast, ventriculitis, the inflammation of the ventricles within the brain, is the result of the virus infecting the ventricular system of the brain by entering the cerebrospinal fluid.¹² Moreover, immune-mediated inflammatory response also contributes to both encephalitis and ventriculitis. 

Other complications 

Secondary bacteria infection

Patients with HPIV infections can become more susceptible to secondary bacterial infections. During the body's defence against the virus, the virus can induce oxidative stress and infect the epithelial cells spread across the airway epithelium, causing damage to these cells and impairing the body's ability to achieve mucociliary clearance.¹³ This can significantly impact the patient, as the mucociliary movement allows the movement of the mucous that has trapped the pathogens in it and propels them out towards the throat to be removed, playing a crucial role in preventing airway infections.¹⁵ With the impairment of the regular respiratory defences during a parainfluenza infection,¹⁴ the increased mucus production has provided an environment suited for the growth of bacteria, along with the weakened immune response from the body due to the existing viral infection, allowing them to colonise and infect the patient without the risk of being cleared away by immune cells.¹⁶ A common type of bacteria that coexists with parainfluenza is Streptococcus pneumonia, which is often found in the respiratory tract and causes pneumonia.¹⁷ 

Airway obstruction and bronchiolitis

During a parainfluenza infection, the trachea can become inflamed due to the immune response and this causes the trachea to swell, which narrows the airway. The inflammation of the trachea can also alter the ion transport, such as the inhibition of sodium absorption and activation of chloride secretion, which can result in the formation of oedemas.¹⁸ As mentioned previously, the patient can experience the loss of ciliary function as a result of the viral infection, which would also contribute to the obstruction of the airways as mucus cannot be cleared properly. All these different factors contribute to bronchitis, and can also develop into apnea, the condition in which the person does not have enough oxygen due to inability to breathe. This is a particular result of an HPIV type 3 infection,¹ which commonly infects the lower respiratory tract and this is a larger risk for children as they have a much smaller airway diameter.¹⁹

Transmission and diagnosis

The primary mode of transmission for human parainfluenza viruses is airborne, where respiratory aerosols and droplets, containing the virus, are released from a parainfluenza patient sneezing or coughing,²⁰ which could be then inhaled by a healthy person. HPIVs can also be transmitted through contact with contaminated surfaces and objects or being in close proximity to infected individuals for a prolonged period. HPIVs type 1 and 2 are more commonly found during fall, whereas type 3 is more prevalent in the spring and the peak timings for type 4 remain unknown.²¹ The virus is easily transmitted within crowded areas where there is not much ventilation and open spaces and children and infants are more likely to contract parainfluenza due to their underdeveloped immune systems, making them more susceptible to the virus. Moreover, transmission of the parainfluenza virus can still occur before the presentation of clinical manifestation,⁴ so it is crucial to take a test if uncertain or suspicious. 

Diagnosing parainfluenza can be done through clinical assessments of the patient, looking out for symptoms and signs that could indicate an HPIV infection. However, since the symptoms of parainfluenza are similar to many other viruses, laboratory testing needs to be carried out to differentiate between the viruses, such as RSV and SARS-CoV-2. The most common test done is the polymerase chain reaction (PCR) test, which is used to detect the genetic material belonging to the virus within the sample.²² The samples taken often involve nasopharyngeal aspirates, a swab at the back of the throat or nose and a sputum sample. Rapid antigen tests are also widely used due to their speed and ease of use, although they are less sensitive, easily resulting in false negative results. 

Prevention and treatment 

As of now, there are no vaccines available to protect against HPIVs. However, safety precautions can be taken to prevent being infected by HPIVs. This includes maintaining good hygiene practices and minimising contact with those who are infected or at risk. People should regularly wash their hands or use alcohol-based hand sanitisers if water is not accessible. Surfaces that are potentially contaminated, such as shared spaces, should also be disinfected frequently. Furthermore, avoid touching the mouth or eyes after being near infected patients and masks should be worn as much as possible if close contact cannot be avoided. In addition, parents should educate their children about parainfluenza, making them aware of the modes of transmission and prevention methods of the virus as they have the biggest risk against HPIVs and the places they visit, like schools or playgrounds, are locations where HPIVs are most likely to be contracted from.  

If a patient has parainfluenza, they would not require antiviral medications since most patients are able to recover on their own. If needed, there are medications available to alleviate symptoms, such as ibuprofen or acetaminophen, that can help with pain management and reduce fever. Patients should also constantly hydrate themselves by drinking water or using humidifiers, which can both help ease sore throats and relieve any congestion in the airways. Patients can consider taking hot showers or staying in steamy rooms to help with their breathing difficulties and taking rests and enough sleep will help support the immune system defending from the viral infection. If the condition does not get better over time, it is crucial to contact a healthcare professional and seek medical advice from them.

Conclusion 

Not only can parainfluenza viruses cause respiratory illnesses, but they can also result in various neurological conditions, such as seizures, encephalitis, ventriculitis and posterior reversible encephalopathy syndrome. Thankfully, most HPIV infections are not fatal and can be treated by themselves, but it is important to be wary of any symptoms and raise awareness.