Hemorrhagic fever with renal syndrome

Hemorrhagic fever with renal syndrome begins as a flu-like illness and then hypotensive, oliguric, diuretic, and convalescent stages. Hantaviral diseases manifest: febrile prodrome, thrombocytopenia, leukocytosis, and capillary leakage. Primarily endemic in Asia, Europe, the Balkans, and Russia.

10 (US); 100,000 (Global)
HFRS; Epidemic hemorrhagic fever; Korean hemorrhagic fever; Nephropathia epidemica; Hemorrhagic nephrosonephritis; Hantaan, Dobrava, Puumala, or Seoul virus infections;
Few days to 2 months; usually 2-4 weeks; [CCDM]
Five phases beginning with flu-like illness and then hypotensive, oliguric, diuretic, and convalescent; The hantaviral diseases share the following: febrile prodrome, thrombocytopenia, leukocytosis, and capillary leakage. [CCDM]
No human-to-human transmission has been reported; [CCDM, p. 248]
In the severe disease caused by Hantaan and Dobrava viruses, five clinical phases have been described: febrile, hypotensive, oliguric, diuretic, and convalescent. Common symptoms during the febrile phase include flu-like symptoms, abdominal pain, low back pain, vomiting, facial and chest flushing, petechiae, conjunctival injection, and blurred vision. Pulmonary edema is recognized in about 10% to 20% of the cases. After appearance of the petechiae, capillary leaking and hemoconcentration are marked by elevation of the hematocrit. The ensuing shock is fatal in some cases. Renal failure for 3-7 days is followed by slow recovery. Fatal hemorrhages, usually of the CNS, occur rarely. Laboratory abnormalities after the initial phase include leukocytosis with left shift, thrombocytopenia, proteinuria, hematuria, and elevated BUN and creatinine. Case-fatality rates for this syndrome range from less than 1% for the Puumala virus to 5%-15% for the Hanta and Dobrava viruses. [CCDM, p. 245-9; ID, p. 2023-9, 2140-4] Bleeding and kidney effects can be severe (+++). Heart effects are common (++). Pulmonary and neurological effects are occasionally noted. Not typically noted are rash, jaundice, and eye effects. [Cecil, p. 2217t] Rashes include petechiae on the upper trunk and an erythematous flush that blanches on pressure on the torso and face. [PPID, p. 2172] Neurological disease dominates in some cases, suggesting viral encephalitis. [Guerrant, p. 475]

Field rodents are the reservoir, and the virus is present in feces, urine, and saliva of infected animals. Workers are infected by inhaling dust contaminated with rodent excreta. Person-to-person transmission occurs rarely. Two of the viruses cause severe HFRS: Hantaan in East Asia and Dobrava in the Balkans. Puumala virus causes mild disease in Europe and the Balkans, and Seoul virus causes mild to severe disease worldwide. HFRS is a rural disease except for Seoul virus that infects urban rats. Seoul virus also infects laboratory rats and the technicians and scientists who handle them. An estimated 100,000 Hantaan virus infections occur in China each year. Dobrava virus infects a few hundred people a year. Exposure usually occurs indoors where mice live or search for food. The highest infection rates are in workers who have contact with mice. [CCDM, p. 245-9; ID, p. 2023-9, 2140-4] This virus does not replicate to high concentrations in cell cultures, and, therefore, is not likely to be used as a biological weapon. [JAMA] Puumala virus causes asymptomatic infections in up to 90% of cases. The disease is called nephropathia epidemica, which is rarely hemorrhagic. Seoul virus causes mild to moderately severe HFRS in Eurasia, and hepatic involvement is prominent. [PPID, p. 2172]
Almost all patients have IgM antibodies at the time of hospitalization, and most have IgG detectable; PCR preferred over culture; [CCDM]
Primarily in Asia (China and South Korea) and in most of Europe, the Balkans and Russia west of the Ural Mountains; Seoul virus is found worldwide in captured urban rats, but has been reported regularly as a human disease only in Asia;; [CCDM]
  • >fever
  • >myalgia
  • >relative bradycardia
  • E epistaxis
  • G abdominal pain
  • G blood in stool
  • G hematemesis
  • G liver function test, abnormal
  • G nausea, vomiting
  • H leukocytosis
  • H thrombocytopenia
  • N headache
  • N seizure
  • O conjunctivitis, acute
  • R cough
  • R dyspnea
  • R hemoptysis
  • S petechiae and ecchymoses
  • S rash (exanthem)
  • U hematuria
  • U pyuria
  • X lung infiltrates
  • X pleural effusions
  • *acute renal failure
  • *bleeding tendency
  • *pneumonitis
  • *pulmonary edema
  • *shock




Inhalation, Skin or Mucous Membranes (Includes Conjunctiva)
Animal Excreta
  • Handle infected laboratory rats or mice
  • Handle infected rodents (not bite)
  • Raise dust of excreta from rodents
  • Travel to endemic area
  • Victim--air release of infectious agents
  • Work in a medical or research lab
1. (US) Guesstimate: 10 cases/year from exposure to infected laboratory rats;
2. (Global) 50,000 to 150,000 cases/year; [Cecil, p. 2214]