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Hantavirus Hemorrhagic Fever with Renal Syndrome

Hantavirus hemorrhagic fever with renal syndrome (HFRS) is a group of clinically similar illnesses caused by different species of hantaviruses. Known also as Korean hemorrhagic fever and epidemic hemorrhagic fever, HFRS is prevalent in Europe, Asia, and Africa. The primary causative agents include Hantaan orthohantavirus, Dobrava-Belgrade orthohantavirus, Saaremaa virus, Seoul orthohantavirus, and Puumala orthohantavirus.

The most severe cases are attributed to Hantaan River virus and Dobrava-Belgrade virus. When caused by the Puumala virus, the condition is referred to as nephropathia epidemica. This infection is also known locally as sorkfeber in Swedish, myyräkuume in Finnish, and musepest in Norwegian.

Transmission electron micrograph of Sin Nombre virus, a hantavirus.
Transmission electron micrograph of Sin Nombre virus, a hantavirus.

Both HFRS and hantavirus pulmonary syndrome (HPS) result from humans inhaling aerosolized excreta from infected rodents. These diseases are immunopathologic, with inflammatory mediators playing a very important role in the clinical manifestations.

Signs and Symptoms

Symptoms of HFRS typically appear within one to two weeks after exposure, but may take up to eight weeks in rare cases. In nephropathia epidemica, the incubation period is around three weeks. Early symptoms include intense headaches, back and abdominal pain, fever, chills, nausea, and blurred vision. Flushing of the face, eye inflammation, or a rash may also occur. Later symptoms can progress to low blood pressure, acute shock, vascular leakage, and acute kidney failure, which can lead to severe fluid overload.

The severity of the disease varies with the causative virus. Hantaan and Dobrava virus infections usually result in severe symptoms, while Seoul, Saaremaa, and Puumala virus infections tend to be milder. Recovery can take weeks or months.

The illness progresses through five phases:

Febrile Phase

Redness of the cheeks and nose, fever, chills, sweaty palms, diarrhoea, malaise, headaches, nausea, abdominal and back pain, respiratory issues, and gastrointestinal problems. This phase lasts three to seven days, occurring about two to three weeks after exposure.

Hypotensive Phase

Characterised by a drop in blood platelet levels, leading to tachycardia and hypoxaemia. This phase can last two days.

Oliguric Phase

Lasting three to seven days, this phase is marked by the onset of renal failure and proteinuria.

Diuretic Phase

Characterised by diuresis of three to six litres per day, lasting from a few days to weeks.

Convalescent Phase

Recovery occurs and symptoms begin to improve during this phase.

HFRS can be fatal and in some cases, it may lead to permanent renal failure.


Hantaviruses infect various rodents without causing disease in them. Humans contract the virus through inhalation of aerosolized rodent excreta. For nephropathia epidemica, the bank vole is the reservoir, and humans contract the virus through inhalation of aerosolized vole droppings.


Diagnosing HFRS on clinical grounds alone is challenging, and serological evidence is often necessary. A fourfold rise in IgG antibody titer within a week and the presence of IgM antibodies against hantaviruses indicate an acute infection. HFRS should be considered in patients with acute febrile flu-like illness, kidney failure of unknown origin, and sometimes liver dysfunction.


Primary prevention includes rodent control in and around the home, workplace, and campsites. Airing out closed storage sheds and cabins before use is recommended. Avoid direct contact with rodent droppings and wear a mask to prevent inhalation of aerosolized rodent secretions.


There is no cure for HFRS. Treatment involves supportive therapy, including renal dialysis. Ribavirin treatment in China and Korea, if administered within seven days of fever onset, has been found to reduce mortality and shorten illness duration.


HFRS primarily affects Eurasia, whereas HPS is confined to the Americas. The distribution is linked to the indigenous rodent hosts and the viruses coevolved with them. Though nephropathia epidemica is milder and less fatal compared to HFRS caused by other hantaviruses, it still demands medical attention.

Self-assessment MCQs (single best answer)

What is the primary method through which humans contract hantavirus hemorrhagic fever with renal syndrome (HFRS)?

Which virus is associated with the mildest form of HFRS, known as nephropathia epidemica?

What phase of HFRS is characterised by the onset of renal failure and proteinuria?

Which of the following is NOT a typical early symptom of HFRS?

What is the incubation period for nephropathia epidemica?

Which virus is NOT a primary causative agent of HFRS?

What is the best method to prevent HFRS?

Which phase of HFRS involves diuresis of three to six litres per day?

What type of therapy is primarily used to treat HFRS?

Which statement is true regarding the epidemiology of HFRS and hantavirus pulmonary syndrome (HPS)?


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