Hemorrhagic Fever with Renal Syndrome (HFRS)

Hemorrhagic Fever with Renal Syndrome encompasses a spectrum of diseases caused by Old World hantaviruses. Hantaan virus (carried by the striped field mouse, Apodemus agrarius) causes the most severe form in Asia with fatality rates of 5–15%. Puumala virus (carried by the bank vole, Myodes glareolus) causes a milder variant known as nephropathia epidemica in Europe, with fatality rates below 1%. Seoul virus (carried by the Norway rat, Rattus norvegicus) causes moderate disease worldwide, and Dobrava-Belgrade virus (carried by the yellow-necked mouse, Apodemus flavicollis) causes severe HFRS in the Balkans. The pathogenesis centers on infection of vascular endothelial cells, particularly in the renal medulla, leading to increased capillary permeability, complement activation, and immune complex deposition that damages the renal microvasculature. HFRS is highly endemic in China, which reports over 90% of global cases — approximately 20,000–50,000 annually. Russia, particularly the Ural and Far East regions, reports thousands of cases each year. In Europe, Puumala virus infections peak in Scandinavia (Finland, Sweden, Norway) and Central Europe (Germany, France, Belgium) during years of high bank vole density, which cycle every 3–4 years in response to mast seeding of beech and oak trees. Seoul virus infections occur globally in port cities due to the cosmopolitan distribution of Rattus norvegicus and have been linked to pet rat ownership in recent years. The clinical course of HFRS classically progresses through five phases. The febrile phase (days 1–7) presents with abrupt onset of high fever, headache, myalgia, facial flushing, conjunctival injection, and petechiae. The hypotensive phase (days 5–7) features falling blood pressure, tachycardia, and may progress to frank shock — this is the period of highest mortality. The oliguric phase (days 8–13) is characterized by acute kidney injury with rising serum creatinine, decreased urine output, electrolyte disturbances (hyperkalemia), and hemorrhagic complications including petechiae, ecchymoses, and gastrointestinal bleeding. The diuretic phase (days 14–28) marks the onset of renal recovery with polyuria of 3–6 liters per day, but patients remain at risk for dehydration and electrolyte imbalance. The convalescent phase extends weeks to months as renal function gradually normalizes, though some patients retain mild tubular defects long-term. Treatment for HFRS is primarily supportive. During the hypotensive phase, careful intravenous fluid resuscitation and vasopressors are critical. The oliguric phase may require hemodialysis for severe renal failure or life-threatening hyperkalemia. Electrolyte monitoring is essential throughout. Intravenous ribavirin has shown benefit in controlled trials from China when administered early in Hantaan virus infections, reducing mortality and shortening the duration of renal failure, and is recommended by WHO for severe HFRS. A bivalent inactivated vaccine against Hantaan and Seoul viruses is licensed and widely used in China and South Korea for high-risk populations, though it requires periodic boosters. In Europe, no vaccine is currently approved. Prevention relies on reducing contact with rodent excreta, using personal protective equipment in high-risk occupations (forestry, agriculture, military), and public awareness campaigns during predicted high-incidence years.