Hantavirus hemorrhagic fever with renal syndrome (HFRS) is a group of clinically similar illnesses caused by species of

hantavirus ''Orthohantavirus'' is a genus of single-stranded, enveloped, negative-sense RNA viruses in the family ''Hantaviridae'' within the order ''Bunyavirales''. Members of this genus may be called orthohantaviruses or simply hantaviruses. Orthohantav ...

es. It is also known as Korean hemorrhagic fever and epidemic hemorrhagic fever. It is found in Europe, Asia, and Africa. The species that cause HFRS include ''

Hantaan orthohantavirus ''Hantaan orthohantavirus'' (HTNV) is an enveloped, single-stranded, negative-sense RNA virus species of Old World ''Orthohantavirus''. It is the causative agent of Korean hemorrhagic fever in humans. It is named for the Hantan River in South ...

'', ''

Dobrava-Belgrade orthohantavirus ''Dobrava-Belgrade orthohantavirus'' (DOBV), also known as Dobrava virus, is an enveloped, single-stranded, negative-sense RNA virus species of Old World ''Orthohantavirus''. It is one of several species of Hantavirus that is the causative agent ...

'',

Saaremaa virus Saaremaa virus is a single-stranded, negative-sense, RNA virus ''Orthohantavirus'' that causes a milder form of Hantavirus hemorrhagic fever with renal syndrome. It is a member virus of ''Dobrava-Belgrade orthohantavirus''. It was first isolated ...

, '' Seoul orthohantavirus'', '' Puumala orthohantavirus'' and other orthohantaviruses. Of these species, Hantaan River virus and Dobrava-Belgrade virus cause the most severe form of the syndrome and have the highest morbidity rates. When caused by the Puumala virus, it is also called nephropathia epidemica. This infection is known as ''sorkfeber'' in Swedish, ''myyräkuume'' (vole fever) in Finnish, and ''musepest'' (mouse plague) in Norwegian. Both HFRS and

hantavirus pulmonary syndrome Hantavirus pulmonary syndrome (HPS) is one of two potentially fatal syndromes of zoonotic origin caused by species of hantavirus. These include Black Creek Canal virus (BCCV), New York orthohantavirus (NYV), Monongahela virus (MGLV), ''Sin Nomb ...

(HPS) are caused by hantaviruses, specifically when humans inhale aerosolized excrements of infected rodents. Both diseases appear to be immunopathologic, and inflammatory mediators are important in causing the clinical manifestations.

Signs and symptoms

Symptoms of HFRS usually develop within one to two weeks after exposure to infectious material, but in rare cases, they may take up to eight weeks to develop. In Nephropathia epidemica, the incubation period is three weeks. Initial symptoms begin suddenly and include intense headaches, back and abdominal pain, fever, chills, nausea, and blurred vision. Individuals may have flushing of the face, inflammation or redness of the eyes, or a rash. Later symptoms can include low blood pressure, acute shock, vascular leakage, and acute kidney failure, which can cause severe fluid overload. The severity of the disease varies depending upon the virus causing the infection. Hantaan and Dobrava virus infections usually cause severe symptoms, while Seoul, Saaremaa, and Puumala virus infections are usually more moderate. Complete recovery can take weeks or months. The course of the illness can be split into five phases: ;Febrile phase:Symptoms include redness of cheeks and nose,

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

, chills, sweaty palms, diarrhea,

malaise As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

abdominal The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the torso. ...

and

back pain Back pain is pain felt in the back. It may be classified as neck pain (cervical), middle back pain (thoracic), lower back pain (lumbar) or coccydynia (tailbone or sacral pain) based on the segment affected. The lumbar area is the most common area ...

respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies grea ...

problems such as the ones common in the

influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

, as well as gastro-intestinal problems. These symptoms normally occur for three to seven days and arise about two to three weeks after exposure. ;Hypotensive phase: This occurs when the blood platelet levels drop and symptoms can lead to

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

and

hypoxemia Hypoxemia is an abnormally low level of oxygen in the blood. More specifically, it is oxygen deficiency in arterial blood. Hypoxemia has many causes, and often causes hypoxia as the blood is not supplying enough oxygen to the tissues of the body ...

. This phase can last for two days. ;Oliguric phase: This phase lasts for three to seven days and is characterised by the onset of

renal failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

and

proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...

. ;Diuretic phase: This is characterized by

diuresis Diuresis () is increased urination (polyuria) or, in the related word senses more often intended, the physiological process that produces such an increase or the administration of medications to encourage that process. It involves extra urine pro ...

of three to six litres per day, which can last for a couple of days up to weeks. ;Convalescent phase: This is normally when recovery occurs and symptoms begin to improve. This syndrome can also be fatal. In some cases, it has been known to cause permanent renal failure.

Transmission

Hantaviruses infect various rodents, generally without causing disease. Transmission by aerosolized rodent excreta still remains the only known way the virus is transmitted to humans. In general, droplet and/or

fomite A fomite () or fomes () is any inanimate object that, when contaminated with or exposed to infectious agents (such as pathogenic bacteria, viruses or fungi), can transfer disease to a new host. Transfer of pathogens by fomites A fomite is any ina ...

transfer has not been shown in the hantaviruses in either the pulmonary or hemorrhagic forms. For Nephropathia epidemica, the

bank vole The bank vole (''Myodes glareolus'') is a small vole with red-brown fur and some grey patches, with a tail about half as long as its body. A rodent, it lives in woodland areas and is around in length. The bank vole is found in much of Europe an ...

is the reservoir for the virus, which humans contract through inhalation of aerosolised vole droppings.

Diagnosis

HFRS is difficult to diagnose on clinical grounds alone and

serological Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...

evidence is often needed. A fourfold rise in

IgG antibody Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG a ...

titer Titer (American English) or titre (British English) is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positiv ...

in a one-week interval and the presence of the

IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...

type of antibodies against hantaviruses are good evidence for an acute hantavirus infection. HFRS should be suspected in patients with acute febrile flu-like illness, kidney failure of unknown origin and sometimes liver dysfunction.

Treatment

There is no cure for HFRS. Treatment involves supportive therapy including renal dialysis. Treatment with

ribavirin Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, pegin ...

in China and Korea, administered within seven days of onset of fever, resulted in a reduced mortality as well as shortened course of illness.

Prevention

Rodent control in and around the home remains the primary prevention strategy, as well as eliminating contact with rodents in the workplace and campsite. Closed storage sheds and cabins are often ideal sites for rodent infestations. Airing out of such spaces prior to use is recommended. Avoid direct contact with rodent droppings and wear a mask to avoid inhalation of aerosolized rodent secretions.

Epidemiology

HFRS is primarily a Eurasian disease, whereas HPS appears to be confined to the Americas. The geography is directly related to the indigenous rodent hosts and the viruses that coevolved with them. Although fatal in a small percentage of cases, nephropathia epidemica is generally milder than the HFRS that is caused by hantaviruses in other parts of the world.

References

External links

Sloan Science and Film / Short Films / Muerto Canyon
by Jen Peel 29 minutes

by Brian Hjelle, M.D., Department of Pathology, School of Medicine, University of New Mexico
Virus Pathogen Database and Analysis Resource (ViPR): BunyaviridaeSignificant rise in number of Puumala virus cases in Southern Finland.
Helsinki Sanomat Sep 29 2008. {{Authority control Hantavirus infections Rodent-carried diseases Biological weapons Hemorrhagic fevers