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For further information, see CMDT Part 32-04: Viral Hemorrhagic Fevers

Key Features

Essentials of Diagnosis

  • Transmitted by rodents and cause two clinical syndromes

  • Hemorrhagic fever with renal syndrome (HFRS): mild to severe illness

  • Hantavirus pulmonary syndrome (HPS): 40% mortality rate

General Considerations

  • Hantaviruses are enveloped RNA bunyaviruses; hosts are rodents, moles, and shrews

  • Hantavirus infection in humans can cause several disease syndromes

  • HFRS caused by Old World hantaviruses

    • Dobrava-Belgrade virus

    • Puumala virus

    • Seoul virus and Hantaan virus in Asia and Europe; these viruses are called Old World hantaviruses

  • Nephropathia epidemica (NE) is a milder form of HFRS. Puumala virus is the most prevalent pathogen and is present throughout Europe.

  • HPS, also known as hantavirus cardiopulmonary syndrome, is caused mainly by Sin Nombre virus and Andes virus, the New World Hantaviruses in Americas

  • A specific strain is not associated with a specific syndrome and overlap is seen between the syndromes

  • Aerosols of virus-contaminated rodent urine and feces are thought to be the main vehicle for transmission to humans

  • Person-to-person transmission is observed only with the Andes virus

  • Occupation at highest risk for transmission of all hantaviruses include

    • Animal trappers

    • Forestry workers

    • Laboratory personnel

    • Farmers

    • Military personnel


  • A total of 728 cases of hantavirus infection have been reported in the United States since 1993

  • Average case fatality rate of 36%

  • Most of the cases were reported from states west of the Mississippi River

  • Outbreaks of HPS associated with other hantavirus types are also reported in Central and South America as well as the Caribbean

Clinical Findings

Symptoms and Signs

  • Vascular leakage is the hallmark of the disease for both syndromes

    • Kidneys are main target with variants associated with HFRS

    • Lungs are the main target with variants associated with HPS

  • HFRS manifests as mild, moderate, or severe illness depending on the causative strain

    • A 2- to 3-week incubation period is followed by a protracted clinical course, typically consisting of five distinct phases

      • Febrile period

      • Hypotension

      • Oliguria

      • Diuresis

      • Convalescence phase

    • Various degrees of renal involvement are usually seen, occasionally with frank hemorrhage

    • Disseminated intravascular coagulation (DIC) and thromboembolic phenomena are recognized complications

    • Pulmonary edema is not typically seen but when present usually occurs in the final stages of disease (oliguric and diuretic phase)

    • Encephalitis and pituitary involvement are rare, although a few cases are reported with Puumala virus

    • Patients may have persistent hematuria, proteinuria, or hypertension up to 35 months after infection

    • Smoking appears to exacerbate the viremia with the Puumula variant of HFRS

  • Clinical course of HPS is divided into a febrile prodrome, a cardiopulmonary stage, oliguric and diuretic phase followed by convalescence

    • A 14- to 17-day incubation period is followed by a prodromal phase

      • Typically lasts 3–6 days

      • Associated with myalgia, malaise, abdominal pain ...

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