Hantaviruses: Fatal Viral Diseases With No Cure

History

Hantavirus disease was first described in Chinese literature some 900 years ago. But, the condition gained global attention during the Korean war (1950-1953) when over 3,000 United Nations armed forces were diagnosed with HFRS. At the time, the disease was called ‘Korean Hemorrhagic Fever’ (KHF) [1]. 

However, it took over 20 years before the virus was isolated. In 1976, Ho Wang Lee and his colleagues discovered an antigen in mice’s lung and kidney tissues. A couple of years later, a similar antigen was isolated from patients with hemorrhagic fever. In 1980, this novel virus was named the Hantaan virus after the Hantan river in South Korea, where it was originally discovered. 

In 1982, the World Health Organization (WHO) termed diseases similar to KHF as HFRS. Shortly after, in 1984, all viruses that cause HFRS were grouped under a new genus named Hantavirus [7]. 

During the early-1990s, a second group of hantaviruses, known as ‘New World’ hantaviruses, were described in the Americas. These hantaviruses cause Hantavirus Cardiopulmonary Syndrome (HCPS) or Hantavirus Pulmonary Syndrome (HPS) [1]. 

In the United States, HCPS was first identified in the southwestern region (known as ‘Four Corners’) in 1993. The disease was identified by Dr. Bruce Tempest and initially called “Four Corners Disease.” Later, the pathogen was renamed ‘Sin Nombre’ (without name) because residents in the ‘Four Corners’ objected to the stigma of having a disease associated with their location [8].

Epidemiology

Around 28 hantaviruses are known to cause human diseases worldwide. Old World hantaviruses that cause HFRS are predominantly found in Europe and Asia, including China, Korea, and Russia. China, in particular, accounts for almost 90% of cases reported worldwide [7,9]. New World hantaviruses causing HCPS are found only in the North and South American continents [1].

HFRS – Hemorrhagic Fever with Renal Syndrome

HFRS infections mainly occur during the dry seasons – late spring, fall, and sometimes early winter [7]. Soldiers, farmers, construction and forest workers are at greater risk of contracting the infection because they are prone to high rodent exposure at their workplace [1].

Worldwide, there are about 100,000 HFRS cases reported annually. The actual number may be higher because HFRS infections are either undetected or unreported in many countries [1].

China

Among all the 70 countries with reported cases of HFRS, China stands out as the most affected. China is hyper-endemic to HFRS, reporting 10,000 to 30,000 cases annually in the last few years. It accounts for a whopping 70% – 90% of HFRS cases yearly reported worldwide [10]. 

Of all the hantaviruses, the Hantan (HTNV) and Seoul (SEOV) viruses cause the majority of HFRS cases. HTNV, in particular, accounts for around 70% of all reported cases [10]. HTNV-inflicted HFRS is potentially life-threatening, with a case-fatality rate as high as 15% [1].

Russia

Between 2000 and 2017, the Russian Ministry of Public Health reported around 131,500 HFRS cases caused by the DOBV (Dobrava) and PUUV (Puumala) hantaviruses. Most of these cases were in Western Russia. 

In Eastern Russia, HFRS cases reported were mainly caused by the HTNV (Hantan) and the SEOV (Seoul). The eastern city of Vladivostok was an epicenter of HFRS infections in the country. Between 1997 and 2019, the total number of laboratory-confirmed cases in the town was 750. About 12.9% of cases turned out to be severe, 62.7% of patients had a moderate illness, and 24.4% had mild symptoms [11].    

Europe

In Europe, over 10,000 HFRS cases are reported each year, mainly caused by PUUV, whose primary vector is the back vole, a small, furry mammal. PUUV-inflicted HFRS is usually mild, with a case fatality rate between 0.1% and 0.4%. Finland tops the list of European countries with the highest incidence of HFRS cases, with between 1,000 and 3,000 serological diagnoses occurring annually [12].   

European countries with a moderate incidence of PUUV-inflicted HFRS include Germany and Belgium. These are followed by Norway, France, Hungary, Austria, and Slovenia, to name a few. Other mild forms of the disease caused by SAAV (Saaremaa) are reported in Germany and Slovakia. There are no reported fatalities from SAAV-inflicted HFRS [1].  

HCPS – Hantavirus Cardiopulmonary Syndrome 

Around 15 hantaviruses are known to cause HCPS in humans. SNV (Sin Nombre) and ANDV (Andes) cause the majority of infections in the Americas. SNV-inflicted HCPS infections are predominant in the US, whereas ANDV-inflicted HCPS infections are common in South American countries.

Globally, over 1,000 cases of HCPS have been reported, with an average of 200 cases annually in North and South America [1]. Approximately 728 HCPS cases were reported in the US between 1993 and 2017 [13]. Though the incidence of HCPS is very low compared to HFRS, it has a case-fatality rate as high as 40% [1].

How is it spread?

HFRS – Hemorrhagic Fever with Renal Syndrome

Rodents are the primary hosts of HFRS-causing hantaviruses. Human-to-human transmission of these infectious diseases is rare. 

HFRS Infections can occur due to:

• Exposure to air contaminated with virus particles – aerosolized urine, saliva, or other droppings of infected rodents
• Touching eyes, mouth, or nose with hands that have touched contaminated surfaces
• Bites from infected rodents [2].

HCPS – Hantavirus Cardiopulmonary Syndrome

HCPS cannot spread from one person to another — with one exception. Although rare, the Andes virus can be transmitted from person to person. 

HCPS infections can occur due to:

• Exposure to air contaminated with virus particles – aerosolized urine, saliva, or other droppings of infected rodents
• Touching eyes, mouth, or nose with hands that have touched contaminated surfaces.
• Eating food contaminated by urine, saliva, or other droppings of infected rodents
• Bites of infected rodents (relatively rare) [3].

Biology of the disease

Hantavirus infections start when a person inhales air contaminated with viral particles. Once the virus enters the respiratory tract, it settles in the lungs and multiplies. Eventually, the virus spreads to other organs through the lymphatic system. 

As the virus continues to replicate in the lungs and circulatory system, it can damage blood vessels, the lungs, and other organs. As a response, the body’s immune system shifts into high gear. This can result in inflammation and fluid accumulation, which causes difficulty in breathing. If the infection is severe, the lungs may fail, leading to death [14].

Symptoms

HFRS

Since several hantaviruses can cause HFRS, the severity of the disease depends on the virus that causes the disease. 

Disease inflicted by Hantaan and Dobrava viruses causes severe symptoms. In contrast, Seoul, Saaremaa, and Puumala viruses cause moderate or mild illness. The incubation period of hantaviruses that cause HFRS is between 1-2 weeks. Sometimes, the incubation period can be as long as 8 weeks. 

Generally, HFRS symptoms occur all of a sudden. They begin with:

• Severe headaches
• Body pains
• Fever
• Chills
• Blurred vision
• Nausea
• Flushing of the face (less common)
• Inflammation or redness of the eyes (less common)
• Rashes (less common).

As the disease progresses, people may have:

• Low blood pressure
• Acute shock
• Vascular leakage
• Acute kidney failure – causing severe fluid overload [2]. 

HCPS

It takes 1-8 weeks for HCPS symptoms to appear following exposure to the infection. Hantavirus Pulmonary Syndrome symptoms begin with:

• Tiredness
• Fever
• Muscle pains. 

Around 50% of patients may also have:

• Headaches
• Dizziness
• Chills
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain.

After four to ten days following the disease onset, the following symptoms appear:

• Cough
• Chest congestion or suffocation – due to fluid accumulation in the lungs [4].

Diagnosis

There are several diagnostic methods to detect the presence of hantavirus infections in humans. 

Some commonly used tests include:

• Serological tests such as indirect IgM and IgG ELISA, and IgM-capture ELISAs detect the presence of hantaviruses in the blood serum
• Indirect immunofluorescence assays. While commonly used, these tests are less accurate than serological tests
• Immunochromatographic IgM-antibody tests are one of the fastest ways to diagnose the illness. Results can be obtained in five minutes
• RT-PCR detects the viral genome in blood or serum samples [1].

Treatment

Currently, there is no treatment for HFRS and HCPS. But, supportive care is given to reduce the severity of the illness. 

It includes:

• Having patients moved to the ICU for close monitoring
• Maintaining proper fluid and electrolyte balance
• Performing platelet transfusions in the case of low platelet count and bleeding
• In the case of HCPS, patients are put under ventilator support
• In the case of HFRS, patients with poor renal function may require dialysis [1]
• Antiviral drugs such as ribavirin are administered intravenously to reduce the severity of illness and deaths due to HFRS. But, for the drug to be effective, it has to be administered during the early stages of the disease [2].

Prevention

Currently, no vaccines are available to protect against illnesses caused by hantaviruses. But, preventive measures like controlling the local rodent population can be helpful. These include:

• Sealing gaps or holes at home, garage, or workplace
• Placing rodent traps to decrease rodent infestation
• Cleaning up food that could be easily accessed by rodents
• Frequently cleaning rodent-infested areas
• Avoiding contact with surfaces that could be contaminated with urine, saliva, or other rodent droppings [1,15].

Viral hemorrhagic fevers (VHFs) like hantaviruses, dengue, Ebola, Crimean-Congo hemorrhagic fever (CCHF), Chapare, Lassa fever, Alkhurma, Lujo, and more have many things in common. They are all caused by RNA viruses. The CDC notes that these viruses are the most common cause of emerging diseases because they can quickly modify themselves over time. These viruses usually have animal or insect hosts and can spread to humans who come in contact with infected animals. 

VHF outbreaks can be difficult to predict since they are sporadic. As a result, constant vigilance and improved reporting from frontline clinicians can help detect outbreaks early and help prevent their spread. 

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