PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Synonyms: Korean haemorrhagic fever, epidemic haemorrhagic syndrome, nephropathia epidemica
The preferred names are haemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS).
Hantavirus is named after the Hantaan River in Korea. It is a Bunyavirus usually classified with the viral haemorrhagic fevers.
- Over a dozen variations of hantavirus have been discovered from all over the world, each associated with a specific rodent reservoir.
- They cause two distinct clinical pictures: hantaviruses cause HCPS in the Americas and HFRS in Asia and Europe. In Scandinavia and Northern Europe, a milder form of HFRS is prevalent, termed nephropathica epidemica.
- Hantaviruses infect endothelial cells and in HFRS the cells of the kidney are infected.
- In HCPS the pulmonary microvasculature and the cells of the spleen and lymph nodes are infected causing a massive, pulmonary-specific immune response. The damage to pulmonary endothelium increases capillary permeability and leads to fulminant pulmonary oedema.
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- It occurs worldwide. Hantaviruses are carried by various species of rodents. Specific viruses have particular rodent hosts. Infection occurs through direct contact with the faeces, saliva or urine of infected rodents or by inhalation of the virus in rodent excreta.
- It does occur at times in Northern Europe. Worldwide there are thought to be over 200,000 cases a year - most in Eastern Europe, central and east Asia. In the Americas most cases are in Argentina and Chile. It is not uncommon in southern states of the USA and is also found in Canada.
- Several different hantaviruses known to infect humans circulate in Europe. The most common is Puumala virus (PUUV) carried by the bank vole. Another two important, genetically closely related ones are Dobrava-Belgrade virus (DOBV) and Saaremaa virus (SAAV) carried by certain mice of the Apodemus species.
- The European viruses cause only HFRS: DOBV with often severe symptoms and a high case fatality rate, and PUUV and SAAV more often mild disease.
- Human infection usually occurs from inhalation of virus in aerosol from the urine, faeces or saliva of infected rodents.
- Other means include direct transmission via the fingers to mucous membranes, eating contaminated food or bites (rare).
- The Andes variation can be spread by human-to-human contact.
- Dry sweeping or vacuum cleaning areas of infected rodent droppings is a high risk, as particles are put into the air.
- Construction, utility and pest control workers entering dirty vacant buildings are at particular risk.
When transmitted to humans, hantaviruses can cause two clinical syndromes - HCPS or HFRS.
Hantavirus cardiopulmonary syndrome (HCPS)
- There is an incubation period of two or three weeks.
- There is a prodromal phase of fever, chills and myalgia that lasts 3-10 days, followed by rapid deterioration over 24 hours.
- There is cardiopulmonary failure with pulmonary oedema.
- Those who recover may do so as rapidly as they became unwell. There is a marked diuresis.
- Early diagnosis is difficult, as symptoms are not much different from many other viral infections.
Haemorrhagic fever with renal syndrome (HFRS)
- This also has an incubation period of two or three weeks with relatively nonspecific symptoms.
- The febrile phase is 3-7 days. This is associated with head, abdominal and back pain, with eventual heavy proteinuria.
- In the severest cases there is a period of several hours to two days, with first appearance of haemorrhages associated with lethal shock syndrome.
- The oliguric phase lasts 3-7 days with associated nausea, vomiting, and acute renal failure, often combined with hypertension due to simultaneous hypervolaemia.
- The diuretic phase lasts days to weeks. There may be further problems with electrolytes and secondary infection.
- Convalescence lasts two or three months, usually with full recovery of renal function.
Hantavirus cardiopulmonary syndrome (HCPS)
- In the early stages there may be a normal FBC or slight thrombocytopenia. WCC does not rise until later in the disease. An elevated haematocrit means haemoconcentration and is an ominous sign.
- A falling platelet count is highly indicative of the cardiopulmonary phase beginning.
- LFTs: AST and LDH are often raised.
- There are three available serological tests for the virus:
- Enzyme-linked immunosorbent assay detects circulating IgM and IgG antibodies.
- Western blot assay indicates acute infection.
- There is also a rapid immunoblot strip assay (RIBA) with 100% sensitivity during the illness.
- CXR may show evidence of pulmonary oedema from the outset, but it usually develops over the next few days. Kerley B lines are common. Pleural effusion is seen in the late phase. The heart size is normal.
- ECG helps rule out myocardial infarction. Sinus tachycardia is common. Death usually occurs with pulseless electrical activity (electro-mechanical dissociation).
Haemorrhagic fever with renal syndrome (HFRS)
This variety shows abnormalities of the renal rather than pulmonary system.
- Albuminuria can be heavy.
- The rise in creatinine will depend upon the severity of the disease.
- There are also various methods of detecting antibody. Direct immunofluoresence is often used but quality control is essential and not always good.
- Treatment is mainly cardiovascular, respiratory and renal function support, with fluid and electrolyte homeostasis. Inotropic support may be required to maintain mean arterial pressure above 70 mm Hg.
- The antiviral ribavarin is of no value, although antibiotics may be required for secondary infection.
- In HCPR, intubation and respiratory support may be required.
- In HCPS, the use of extracorporeal membrane oxygenation (ECMO) in decompensated patients has also been shown to be beneficial. ECMO supports the failing heart and lungs long enough to allow recovery.
- HCPS has a mortality of about 35%. HFRS may cause less severe infections. However, Dobrova and Hantaan viruses cause a more severe HFRS with a mortality rate of up to 15%.
- Most deaths occur within 24 hours of hospital admission. Those who recover tend to do so completely, so that several weeks after being in pulmonary oedema a young person may have no significant impairment of exercise tolerance.
Hantavirus is a zoonosis. Contact with infected rodents or their excreta is the means of spread.
- The virus is fragile and can easily be killed by fat solvents (alcohol), household detergents, disinfectants and bleach. Thus, thorough wetting before cleaning (using gloves) is effective.
- Based on current human population growth and development trends, hantavirus diseases will become more common in the near future unless public health measures are taken to curtail or eliminate rodents from human communities.
- A vaccine is being developed but its efficacy is not entirely satisfactory, and it is not ready for commercial exploitation.
- Passive immunity with immunoglobulin may possibly be of value.
- Identification of the aetiological agent took from the Korean War in 1951 to 1976. 3,000 soldiers had developed a disease characterised by fever and renal failure, with a fatality rate of 10%.
- In 1993 the unknown hantavirus (named Muerto Canyon virus - later changed to Sin Nombre - that is, Spanish for 'no name') and the rodent reservoir (deer mouse Paromyscus maniculatus) were identified. This was six months after an outbreak of unexplained pulmonary illness in 'The Four Corners area' of the USA - ie Arizona, New Mexico, Colorado, and Utah.
- Retrospective serological investigations on unexplained pulmonary deaths, put the earliest proven case in 1959, though it is recognised in Navajo Indian medical traditions (associated with mice).
Further reading & references
- Hantavirus; Centers for Disease Control and Prevention
- Mir MA; Hantaviruses. Clin Lab Med. 2010 Mar;30(1):67-91. doi: 10.1016/j.cll.2010.01.004.
- Sargianou M, Watson DC, Chra P, et al; Hantavirus infections for the clinician: from case presentation to diagnosis and treatment. Crit Rev Microbiol. 2012 Nov;38(4):317-29. doi: 10.3109/1040841X.2012.673553. Epub 2012 May 3.
- Hantavirus diseases; World Health Organization
- Vaheri A, Henttonen H, Voutilainen L, et al; Hantavirus infections in Europe and their impact on public health. Rev Med Virol. 2013 Jan;23(1):35-49. doi: 10.1002/rmv.1722. Epub 2012 Jul 3.
- Kruger DH, Schonrich G, Klempa B; Human pathogenic hantaviruses and prevention of infection. Hum Vaccin. 2011 Jun;7(6):685-93. Epub 2011 Jun 1.
- Biel SS, Donoso Mantke O, Lemmer K, et al; Quality control measures for the serological diagnosis of hantavirus infections. J Clin Virol. 2003 Dec;28(3):248-56.
- Mertz GJ, Miedzinski L, Goade D, et al; Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America. Clin Infect Dis. 2004 Nov 1;39(9):1307-13. Epub 2004 Oct 11.
- Dietl CA, Wernly JA, Pett SB, et al; Extracorporeal membrane oxygenation support improves survival of patients with severe Hantavirus cardiopulmonary syndrome. J Thorac Cardiovasc Surg. 2008 Mar;135(3):579-84. Epub 2008 Jan 18.
- Hantavirus; Health Protection Agency
- Lednicky JA; Hantaviruses. a short review. Arch Pathol Lab Med. 2003 Jan;127(1):30-5.
- Maes P, Clement J, Gavrilovskaya I, et al; Hantaviruses: immunology, treatment, and prevention. Viral Immunol. 2004;17(4):481-97.
- Ferres M, Vial P; Hantavirus infection in children. Curr Opin Pediatr. 2004 Feb;16(1):70-5.
- Klein SL, Calisher CH; Emergence and persistence of hantaviruses. Curr Top Microbiol Immunol. 2007;315:217-52.
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Dr Hayley Willacy
Dr Colin Tidy
Dr Adrian Bonsall