Hantavirus Infection

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 2 distinct clinical pictures:
  • HFRS is usually seen in Asia and Europe.
  • HCPS was first recognised in New Mexico in 1993 and that is the form that is found in America.
• 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.

• The virus tends to strike healthy young adults with a slight preponderance for men, because of occupational factors.
• The Andes variation often affects children, who seem to suffer a milder disease than adults, unless they are under 1 year.
• China has about 100,00 cases a year.
• 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 America most cases are in Argentina and Chile. It is not uncommon in southern states of the USA and is also found in Canada.

The table below gives numbers of cases and deaths reported in America between 1993 and 2004.¹ The total also includes figures from Panama, Paraguay and Uruguay.

Risk factors

• 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.

Hantavirus cardiopulmonary syndrome

• Incubation period of 2 or 3 weeks.
• There is a prodromal phase of fever, chills and myalgia that lasts 3 to 10 days, followed by rapid deterioration over 24 hours.
• There is cardio-pulmonary 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

• Also has an incubation period of 2 or 3 weeks with relatively nonspecific symptoms.
• The febrile phase is 3 to 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 2 days, with first appearance of haemorrhages associated with lethal shock syndrome.
• The oliguric phase lasts 3 to 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 2 or 3 months, usually with full recovery of renal function.

Hantavirus cardiopulmonary syndrome

• 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.
• AST and LDH are often raised.
• There are 3 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

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.²

• Largely supportive.
• The antiviral ribavarin is of no value, although antibiotics may be required for secondary infection.³ A third-generation cephalosporin and an aminoglycoside are good first-line treatment.⁴ Consider adding a fluoroquinolone for Legionella species and chloramphenicol if pneumonic plague is in the differential diagnosis.
• Management of fluids and electrolytes may be required. Inotropic support may be required to maintain MAP >70mmHg.
• In HCPR intubation and respiratory support may be required. If the hospital has adult extracorporeal membrane oxygenation (ECMO) facilities, consider this early on. ECMO supports the failing heart and lungs long enough to allow recovery.⁵

The renal haemorrhagic variety has a mortality rate around 10%.
The more virulent HCPS had a mortality rate of approximately 80% in the initial outbreak. Now, because of increased recognition of the disease and more aggressive intervention e.g. ECMO or early mechanical ventilation, the rate is approximately 38%.⁴ 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.⁶
• A vaccine is being developed but its efficacy is not entirely satisfactory, and it is not ready for commercial exploitation.^7,8
• Passive immunity with immunoglobulin may possibly be of value.⁹

• Identifying the aetiological agent took from the Korean War in 1951 to 1976.¹⁰ 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 6 months after an outbreak of unexplained pulmonary illness in "The Four Corners area" of the USA i.e. 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).