Introduction

Hantavirus Pulmonary Syndrome (HPS) is a rare infectious disease that affects the lungs caused by Hantaviruses.¹ HPS is a disease that begins with flu-like symptoms before progressing to a severe, life-threatening lung and heart infection.² Hantavirus is present all over the world, and transmission is caused by interaction with rodents such as mice or rats and when exposed to their droppings, urine and saliva.¹

HPS is a dangerous viral disease that infects and causes damage to the lungs, heart and other organs.³ HPS progresses quickly from flu-like symptoms to life-threatening, and it can be fatal. Unfortunately, there are limited treatment options available, and the best way to prevent HPS is to avoid contact with rodents and their habitats.²

HPS presents itself differently in children and adults in terms of symptoms and the immune response in adults and children. It is important to understand age-related differences in clinical presentations of HPS, as it can lead to an accurate diagnosis, which can allow for tailored treatments that offer quicker recovery time with minimal complications. This article will be discussing how HPS presents itself in children versus in adults and will be covering the epidemiology and pathophysiology of HPS, the clinical presentations in children and adults and the diagnostic differences between adults and children with HPS. 

Aetiology and epidemiology of HPS

Hantavirus was discovered in the 1950s in Korea, where the disease was named after the Hantaan River.³ The dominant virus strain in Northern America is the Sin Nombre virus, which is transmitted by the deer mouse, and in South America, the most common viral strain is the Andes virus, which is very virulent.³ 

Hantavirus belongs to the Orthohantavirus genus, and the virus is an enveloped, single-stranded RNA virus. They can affect a wide range of cells in the body by attaching itself to the cell surface receptors.³ Hantavirus is present in rodents’ urine, saliva and faeces, and transmission can occur by:¹

• Inhaling the virus when it becomes airborne, once the rodent’s droppings and nest are disturbed
• Digesting food that has been contaminated by rodent’s droppings or saliva,
• Being bitten or scratched by an infected rodent
• Touching contaminated environments such as a nest and then touching one's face, especially around the mouth, ears and eyes
• Person-to-person transmission is found in South America in the Andes viral strain¹ 

Hantavirus causes two main syndromes:

1. Hantavirus pulmonary syndrome
2. Hemorrhagic fever with renal syndrome 

HPS is the main form of hantavirus syndrome in the Western Hemisphere², and from most studies, HPS occurs due to exposure to rodent droppings around the home and in the workplace.

Risk factors for hantavirus infection can increase the likelihood of developing HPS. These include:

• High exposure to a rodent’s nest where droppings, urine and saliva are common:¹
• Farm buildings
• Storage sheds
• Construction sites
• Camp sites
• Attics and basements

Activities where there is increased exposure to hantavirus:¹

• Cleaning abandoned buildings,
• Cleaning a rodent’s nest without protective precautions
• Working in jobs where there is exposure to rodents, such as construction, pest control and farming

Pathophysiology of HPS

Once hantavirus is transmitted, usually through inhalation, it takes hold in the alveoli (air sacs) inside the lungs and causes a widespread infection of the blood vessels’ endothelial cells as it replicates.⁴ The virus causes the blood vessels to become weak and causes leaks to occur in the lungs, leading to blood filling in the alveoli, that makes breathing difficult.⁴

Hantavirus can also affect the heart by damaging the walls of the heart muscle, and this causes the blood vessels to become weak and leaky. This will affect the heart's ability to pump blood around the body and this can cause shock to the body.

The immune system detects the virus as a foreign object in the body and initiates an immune response, releasing inflammatory products like cytokines and macrophages, which initiate inflammation. An increase in viral RNA (due to the virus replicating) results in an increase in cytokines being produced, and more inflammation causes tissue damage. With the immune response causing tissue damage and the virus's impact on the pulmonary and cardiovascular systems, the cells and organs inside the body cannot get enough blood and cannot carry out their function, leading to HPS syndrome, where the body can go into shock, and this can be fatal.^3,4 

There are differences in immune response to hantavirus infection in children and adults. As children are still growing, their immune system has not had much exposure to pathogens (foreign microorganisms) This means that the immune system is less efficient at recognising and responding to the virus, meaning that the symptoms are more milder in children. On the other hand, an adult's immune system is well-equipped to respond to pathogens due to immunological memory from other infections, but this means that the immune system will trigger a stronger inflammatory response, leading to HPS syndrome.⁴

Clinical presentations

HPS is a rare but dangerous disease that affects the lungs^, and symptoms usually begin 2 to 3 weeks after infection with the hantavirus.^1,2 The common symptoms experienced by everyone, regardless of their age is:¹

• Fever and chills
• Headache
• Muscle pain or aches
• Difficulty in breathing

Some people may also experience:

• Vomiting and nausea
• Diarrhoea
• Stomach aches and pain

Symptoms in children

Children with HPS suffer from the following symptoms:⁵

• Shortness of breath 
• Chest pain
• Coughing
• High fever
• Headaches
• Vomiting

It is important to note that Hantavirus does not affect children as much as it does in adults and this could be due to the fact that the incidence rate for HPS in children is very low.⁶ There is an equal distribution of HPS between boys and girls.⁶ 

Symptoms in adults

Adults experience the following common symptoms:²

• Headaches
• Dizziness
• Chills
• Vomiting, diarrhoea and nausea
• Fatigue
• High fever
• Muscle aches

4 to (missing numerical value) days after the initial common symptoms, more severe symptoms appear:^2,4

• Coughing
• Shortness of breath
• Tightness in the chest
• Lungs filling up with fluid
• Internal bleedings
• Difficulty in breathing
• Rapid heartbeat 

HPS is a fatal disease where up to 38% of patients who develop severe respiratory symptoms can die from it.²

Diagnosis

Blood samples are used to detect HPS in both children and adults, and this includes detecting antibodies for the hantavirus that the immune system would produce in response to the infection.1 Diagnosis is also accompanied by a physical examination, where a healthcare professional would ask questions to determine any exposure to rodents and their nests.⁴ The questions could be something like:

1. Have you been in contact with wild rodents such as rats or mice?
2. Are there any mouse droppings around the house or at your work site?
3. Have you cleaned any abandoned or rarely used buildings or rooms?
4. Have you been camping recently or working in wooded areas?

These questions are important to make sure that the healthcare professionals know that you have been in contact with rodent droppings, saliva or urine and could potentially have HPS.

However, it is difficult to diagnose hantavirus and HPS as the symptoms for HPS are very similar to other respiratory infections, such as influenza or pneumonia,² especially in children, as their symptoms are not as severe as in adults. 

Treatment and management approaches

There is no specific treatment available for HPS, and treatment is required immediately and is highly intensive. Treatments for both children and adults will need:^2,4

• Antiviral medications such as ribavirin are used to get rid of the hantavirus
• Oxygen treatment, such as mechanical ventilation, to increase oxygen saturation
• Fluids to replace fluid lost during diarrhoea and vomiting
• In some severe cases, ECMO (extracorporeal membrane oxygenation)² is also used where the blood is pumped through a machine that removes the carbon dioxide waste and adds oxygen to the blood, bringing oxygenated blood into the body

Medical treatment is needed against HPS to improve the outcome of the disease, otherwise, it can become fatal.

Prognosis and long-term outcomes

The prognosis for HPS is unfortunately poor, as 30% of patients who are in the intensive care unit will die within 48 hours after hospital admission.³ Unfortunately, studies have shown that children with HPS die more quickly compared to adults.⁷ However, it is important to remember that HPS does not affect children as severely as adults, and less children are developing severe symptoms that require medical treatment. As long as patients improve within the first few days of hospital admission, there is a higher likelihood of survival.⁴ The quicker the diagnosis and treatment, the increased likelihood of an improved prognosis of HPS.

Summary

HPS is a rare infectious disease that affects the lungs caused by Hantaviruses.¹ HPS is a disease that first begins with flu-like symptoms before progressing to a severe life-threatening lung and heart infection. Hantavirus is present in rodents’ urine, saliva and faeces and is transmitted by interacting with them. Once hantavirus is transmitted, usually through inhalation, it takes hold in the alveoli inside the lungs and causes a widespread infection of the blood vessel cells as it replicates.⁴ The virus causes the blood vessels to become weak and causes leaks to occur in the lungs, leading to blood filling in the alveoli, which makes breathing difficult. Children usually experience milder symptoms of HPS compared to adults, but they unfortunately have an increased morbidity if the condition worsens. HPS is a very rare disease, with a low incidence rate, but more studies are needed to explore the differences in HPS in children and adults, as there is limited information available between adults and children. 

References

1. Mayo Clinic. ‘Hantavirus Pulmonary Syndrome-Hantavirus Pulmonary Syndrome - Symptoms & Causes’. Accessed 18 October 2024. https://www.mayoclinic.org/diseases-conditions/hantavirus-pulmonary-syndrome/symptoms-causes/syc-20351838.
2. CDC. ‘About Hantavirus’. Hantavirus, 4 June 2024. https://www.cdc.gov/hantavirus/about/index.html.
3. Moore, Ross A., and David Griffen. ‘Hantavirus Pulmonary Syndrome’. In StatPearls. Treasure Island (FL): StatPearls Publishing, 2024. http://www.ncbi.nlm.nih.gov/books/NBK513243/.
4. Cleveland Clinic. ‘Hantavirus Pulmonary Syndrome: Symptoms & Treatment’. Accessed 18 October 2024. https://my.clevelandclinic.org/health/diseases/17897-hantavirus-pulmonary-syndrome.
5. ‘Hantavirus Pulmonary Syndrome in Five Pediatric Patients --- Four States, 2009’. Accessed 18 October 2024. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5850a3.htm.
6. Terças-Trettel, Ana Cláudia Pereira, Alba Valéria Gomes de Melo, Sandra Mara Fernandes Bonilha, Josdemar Muniz de Moraes, Renata Carvalho de Oliveira, Alexandro Guterres, Jorlan Fernandes, et al. ‘Hantavirus Pulmonary Syndrome in Children: Case Report and Case Series from an Endemic Area of Brazil’. Revista Do Instituto de Medicina Tropical de São Paulo 61 (20 December 2019): e65. https://doi.org/10.1590/S1678-9946201961065.
7. Thorp, Lauren, Lynne Fullerton, Amy Whitesell, and Walter Dehority. ‘Hantavirus Pulmonary Syndrome: 1993-2018’. Pediatrics 151, no. 4 (1 April 2023): e2022059352. https://doi.org/10.1542/peds.2022-059352.