Introduction

Human parainfluenza virus (HPIV) is a group of viruses that causes respiratory disease in young children, the elderly, and individuals with a compromised immune system.¹ HPIV can infect both the upper and lower respiratory tract and is one of the leading causes of morbidity (illness) and infant mortality worldwide.²

Adenovirus is a group of viruses that causes cold or flu-like symptoms.³ It circulates all year round and infects people regardless of their age.³ Adenovirus virus can cause mild to severe infection in the body but it commonly colonises and affects the respiratory tract.⁴

Etiology and virology

Parainfluenza virus

HPIV is an enveloped, single-stranded RNA virus that belongs to the Paramyxoviridae family.² HPIV varies in size, ranging from 150 to 200 micrometres, and its RNA genome codes for 6 proteins:²

• Phosphoprotein is involved in signalling pathways, responsible for cellular processes
• Matrix protein is an important protein in viral assembly
• Nucleocapsid protein is a structural protein involved in the packaging of RNA genome 
• Fusion glycoprotein is involved in viral attachment by fusing the membrane between the virus envelope and the host cell
• Hemagglutinin-neuraminidase glycoprotein is responsible for the virus to attach and interact with the host cell
• RNA polymerase protein that is responsible for copying viruses' genomes

There are four serotypes of HIPV that are genetically and antigenically (antigens present on the virus, that the immune system recognises and targets) different from each other:²

• HPIV-1
• HPIV-2
• HPIV-3
• HPIV-4. HPI-4 can be further split into separate subtypes HPIV-4a and HPIV-4b

HPIV-1 and HPIV-3 belong to the Respirovirus genus whilst HPIV-2 and HPIV-4 belong to the Rubulavirus genus.² HPIV-1 and HPIV-3 are responsible for lower respiratory infection in young children, infants, adults and the elderly population.²

Adenovirus

Adenovirus is a DNA virus that infects both humans and animals.⁵ Adenovirus is a non-enveloped, icosahedral capsid, double-stranded DNA virus ranging from 70 to 100 nm in size.⁶ The capsid (virus’s head) of adenovirus contains structural proteins such as fibre proteins and hexon that are responsible for binding the virus to attach to the host cell by interacting with the Coxsackie-adenovirus receptor (CAR) which allows for successful infection.⁶

There are over 100 different types of adenovirus and 49 subtypes have been identified which can infect humans. Adenovirus belongs to the Adenoviridae family and can be further separated into two genera depending on the species they infect:⁵

• Avian adenovirus (avi-adenoviruses)
• Mammalian adenovirus (mast adenovirus)

Adenovirus can be further classified into seven species (A-G) depending on hemagglutinin properties, genetic information, and where the infection occurs.⁶ Species A, D, F, and G infect via the GI tract, species B, C, and E infect via the respiratory tract, species C through the eye, and species B through the urinary system.⁶

Adenovirus infection is commonly found in places where there are lots of children, such as day centres, nurseries, and households with young children.⁵ It is also commonly found in crowded and closed places such as military dormitories, medical facilities, and public swimming pools.⁵

Epidemiology

Parainfluenza virus

HPIV season of infection differs for each serotype.² HPIV-1 seasonality occurs once every two years, with a peak between September and December, whilst HPIV-3 occurs every year from April to June.² When there is no HPIV-1 circulating, HPIV-3 lasts longer and can extend into the winter months from November to December.² HPIV-2 and HPIV-4 outbreaks are smaller compared to the other serotypes with HPIV-2 occurring every two years, alternating with HPIV-1 whilst HPIV-4 follows similar seasonality like HPIV-3.²  

HPIV causes up to 17% of hospitalisations in children younger than 5 years due to respiratory tract infections.² Serotype HPIV-3 is responsible for 60% of HPIV infection in children under the age of 2, and can infect up to 80% of HPIV patients under 4 years old.²

HPIV is a community-acquired pathogen and is spread via direct contact from person to person or by inhaling viral droplets.² There are some risk factors that can cause an individual to develop HPIV infection and these include:²

• Overcrowding
• Vitamin A deficiency
• Malnutrition 
• Environmental toxins or smoke

Adenovirus

Adenovirus is present throughout the year, but peak outbreak season occurs in the winter months and early spring. Adenovirus infection can affect everyone of all ages but is more common in children, especially from 6 months to 2 years old, and between 5 to 9 years old.⁵ Adenovirus is spread amongst children in nurseries and schools as children are often in close contact with each other and their hands are not frequently washed.³ Adenovirus is spread amongst adults in crowded environments such as dorms or military rooms and in hospitals and nursing homes.³ 

Adenovirus infection is more severe in immunocompromised individuals, in whom it can be fatal without medical treatment. This may include individuals who have a weakened immune system and cannot fight off the viral infection, such as:⁵

• HIV/AIDS patients
• Cancer patients with recent chemotherapy
• People who have had an organ or bone marrow transplant
• People with an autoimmune disease such as lupus or rheumatoid arthritis
• People with a chronic disease such as diabetes or chronic kidney disease (CKD)

Clinical manifestations

Parainfluenza virus

Symptoms of HPIV are similar to those of the common cold and flu as HPIV causes infection in the upper and lower respiratory tract in patients.¹ Anyone is able to get infected with HPIV, but infection is more common in:

• Infants and young children
• Elderly patients
• Immunocompromised individuals

Symptoms of HPIV occur from 2 to 6 days of infection and include:¹

• Runny nose
• Coughing and sneezing
• Sore throat
• Fever
• Ear pain 
• Decreased appetite
• Wheezing

HPIV can cause the following respiratory inflammations:¹

• Bronchitis (inflammation of the airways)
• Bronchiolitis (inflammation of the airways)
• Pneumonia (inflammation of the lungs)
• Croup (inflammation of the upper airways)

Adenovirus

Most adenovirus infections are asymptomatic⁵ and symptoms of adenovirus infection depend on the site of infection.³ Adenovirus usually infects the respiratory system and has similar symptoms to the flu.³ These can include:

• High fever
• Cough
• Runny nose 
• Sore throat 
• Pink eye
• Ear infection
• Pneumonia

When the virus infects the gastrointestinal tract, symptoms include:⁴

• Diarrhoea
• Stomach aches
• Nausea
• Vomiting

If the virus infects the urinary tract, it can cause urinary tract infections.⁴ 

Diagnosis

Parainfluenza virus

HPIV infection is diagnosed by using laboratory tests, including:

• Viral cultures detect the presence of viruses using monoclonal antibodies specific to the virus.² However, viral cultures are not commonly used as they are time-consuming
• Immunofluorescent assays that detect the presence of viral antigens in samples
• Molecular assays, such as PCR, are used to detect HPIV infection
• Serological diagnosis

The timing of collecting samples is an important factor when diagnosing HPIV infection.² During the early stage of infection, samples are taken from the upper respiratory tract; towards the later stage of infection, samples are taken from the lower respiratory tract.² Samples can include nasopharyngeal swabs, sputum, or bronchoalveolar fluid.²

Adenovirus

Adenovirus is usually detected by examining clinical symptoms, however, sometimes lab techniques are used and these can include:³

• PCR
• Viral antigen assay
• Serology
• Viral culture swab

Clinical examination is also used to detect adenovirus infection. Examination techniques used may include:⁴

• Listening to your lungs and heart
• Taking blood pressure
• Measuring oxygen levels
• Looking at your mouth and nose

Treatment and management

Parainfluenza virus

HPIV infection does not need antiviral medication to treat the infection and most people with the infection do not need any medical intervention as they can recover on their own. Treatment options are available for providing symptomatic relief, and these include:¹

• Taking over-the-counter pain relief and fever medicine such as ibuprofen
• Taking a hot shower or using a room humidifier to aid with coughing and sore throat
• Drinking water and fluids
• Resting at home

Adenovirus

Most adenovirus infections are asymptomatic and mild, and treatments are focused on providing symptomatic relief.³ This includes:

• Taking over-the-counter medicines to reduce fevers and pain relievers
• Drinking water and fluids
• Resting at home

Antiviral medications are not effective against adenovirus and are not used to treat the infection.

Prevention

Parainfluenza Virus

There is no vaccination program against HPIV infection, however, there are steps available that can help to prevent one from developing HPIV infection. These include:¹

• Washing your hands frequently with soap and water
• Avoiding contact with individuals who are sick
• Avoiding touching your face, including eyes, mouth and nose

If you have HPIV infection, you can prevent transmission of the virus and prevent others from getting the infection by:¹

• Avoiding close contact with others
• Covering your mouth and nose when you cough or sneeze
• Staying home and recovering when you are sick
• Keeping surfaces disinfected and clean 

Adenovirus

The steps recommended to prevent adenovirus infection and prevent the spreading of the virus include:³

• Frequent hand washing
• Resting at home to recover
• Covering your mouth and nose when sneezing
• Keeping good hygiene practice

Prognosis

Parainfluenza virus

HPIV is a virus that is commonly responsible for respiratory viral infection. In healthy children and adults the prognosis for HPIV is good, with most individuals recovering with treatment,² however the prognosis is worse in immunocompromised individuals.² HPIV can cause severe complications in immunocompromised patients and can be fatal. Hence, early diagnosis and treatment are important to improve outcomes in immunocompromised patients. 

Adenovirus

Adenovirus has an excellent prognosis, with the majority of people infected with the virus clearing the infection without experiencing any severe symptoms.⁵ However, for immunocompromised patients, the prognosis is poor, with a mortality rate of 70% for immunocompromised individuals.⁵ Complications associated with adenovirus include:⁵

• Bronchiolitis obliterans
• Disseminated adenovirus infection
• Bronchiectasis

Summary

Both HPIV and adenovirus are viral infections that infect both adults and children. HPIV is an RNA virus that infects infants, young children, the elderly, and immunocompromised individuals and causes respiratory infections. Adenovirus, on the other hand, is a DNA virus that infects all ages and circulates all year round. Adenovirus can cause mild to severe infection all over the body but it most commonly affects the respiratory system.

Both adenovirus and HPIV have similar symptoms such as fever, coughing, and sore throat, and are diagnosed through laboratory testing and clinical examination. Antiviral medication is not given against HPIV as it is not effective against adenovirus, and treatment against both infections mostly focuses on symptomatic relief. However, it is important to differentiate between these infections in order to diagnose the correct infection and provide early treatment, as both infections in immunocompromised individuals can be fatal. Despite their differences and similarities, for the best outcome for immunocompromised patients, early diagnosis and correct treatment are needed.