• Clinical science

Viral hemorrhagic fevers

Summary

Viral hemorrhagic fevers (VHFs) are a group of viral infections caused by viruses from five different families: Arenaviridae, Bunyaviridae, Filoviridae, Flaviviridae, and Paramyxoviridae. The most well-known VHFs are Lassa fever, Hantavirus syndromes, Ebola virus disease, Dengue hemorrhagic fever, and yellow fever. Transmission of VHFs occurs via contact with their animal or insect reservoirs or vectors (e.g., rodents, mosquitoes, ticks). Human-to-human transmission is also possible, e.g., via bodily fluids. VHFs predominantly occur in tropical and subtropical regions. Clinical features of VHFs vary but often include an initial nonspecific flu-like illness that progresses to multisystem hemorrhage. VHFs are diagnosed via antibody detection (e.g., IgG, IgM), PCR, or immunohistochemistry. Treatment is typically supportive, but antivirals may be used in some cases (e.g., ribavirin in Lassa fever). Case fatality rates vary greatly between VHFs but can be up to 90%. Vaccines are licensed internationally for yellow fever only, so prevention primarily consists of infection control measures.

Etiology

Overview

Overview of common viral hemorrhagic fevers
Family Virus Disease(s) Geography Transmission

Incubation period

Case fatality rate

Vaccine

Arenaviridae

Lassa virus

Lassa fever

  • West Africa (e.g., Liberia, Sierra Leone, Guinea)
  • Ingestion/inhalation of rodent urine or droppings from reservoir hosts of the virus: the multimammate rat
  • Contact with bodily fluids of other infected animals or humans
  • 1–21 days
  • Only ∼ 1% of infections are fatal
  • Mortality rate in those requiring hospitalization: 15–20%
  • None internationally licensed

Hantaviridae

Hantaviruses (especially Sin Nombre virus for HCPS)

Hantavirus cardiopulmonary syndrome (HCPS)

  • North and South America
  • Contact with infected rodent reservoir hosts or ingestion/inhalation of their blood, urine, droppings, or saliva
  • 1 –8 weeks
  • 35–45% in severe cases (bilateral infiltrates on chest x-ray)
  • Mild cases are not fatal.
  • None internationally licensed
Hemorrhagic fever with renal syndrome (HFRS)
  • Asia, Korea, Russia, Europe
  • Highest annual incidence in China
  • Contact with infected rodent reservoir hosts or ingestion/inhalation of their urine, droppings, or saliva
  • Up to 15%
Nairoviridae Crimean Congo hemorrhagic fever virus Crimean-Congo hemorrhagic fever
  • Southeastern Europe, Africa, Middle East, Asia
  • Tick bites from Ixodid tick reservoir hosts
  • Contact with infected animal or human bodily fluids
  • 1–13 days
  • Up to 80%
  • None internationally licensed
Phenuiviridae Rift valley fever virus Rift valley fever
  • Eastern and Southern Africa (e.g., Kenya, Tanzania, Somalia)
  • Sporadic cases also reported throughout Africa and the Middle East
  • Contact with infected livestock (i.e., bodily fluids)
  • Mosquito bites
  • 2–6 days
  • None internationally licensed
Filoviridae

Ebola virus

Ebola virus disease

  • Sub-Saharan Africa
  • Contact with bodily fluids of infected people, nonhuman primates (e.g., gorillas, chimpanzees, monkeys), or fruit bats
  • Direct contact with fomites increases the likelihood of nosocomial spread.
  • 2–21 days
  • Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV) vaccine (approved in the US in December 2019)
Marburg virus Marburg hemorrhagic fever
  • Africa (e.g., Uganda, Zimbabwe, the Democratic Republic of the Congo)
  • Contact with the reservoir host of the virus, the African fruit bat
  • Contact with bodily fluids of infected individuals or animals
  • 5–10 days
  • 25–90%
  • None internationally licensed
Flaviviridae Dengue virus Dengue hemorrhagic fever
  • Worldwide in tropical regions of Central and South America, the Caribbean, Africa, and Asia
  • Mosquito bites
  • 4–10 days
  • 2–5%
Yellow fever virus Yellow fever
  • Tropical regions of South America and sub-Saharan Africa
  • Mosquito bites
  • 3–6 days
  • 30–60% of those who develop severe infection (The vast majority of infections are asymptomatic or very mild.)

Clinical features

Clinical features of VHFs vary depending on which virus is involved. Onset may be acute (e.g., Ebola virus disease) or insidious (e.g., Lassa fever) and often includes the following:

Diagnostics

  • Approach
    • Diagnosis of VHF during the early stages is difficult because the symptoms are nonspecific.
    • If clinical and laboratory features are consistent with the condition, further studies should be conducted to confirm the diagnosis.
  • Medical history
    • A detailed travel history to endemic regions is essential!
    • History of exposure to a potential source of infection (e.g., rodents, mosquitoes, ticks)
  • General laboratory studies
  • Confirmatory tests
    • Generally performed by specialized reference laboratories; presumptive positive results must be confirmed by the CDC.
    • Serology: IgM and/or rising levels of IgG antibodies detected using enzyme-linked immunosorbent assay (ELISA) or other diagnostic assays
    • Reverse transcription-polymerase chain reaction (RT-PCR)
    • Immunohistochemistry

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

Aspirin and NSAIDs should be avoided in VHFs because they are associated with an increased risk of bleeding!

Prevention

Immunization

See “Vaccine” in “Overview of viral hemorrhagic fevers” above.

Prevention

  • Avoid contact with blood, body fluids, or tissue from infected reservoirs or humans
  • Avoid travel to endemic areas
  • In suspected cases
    • Immediate notification of local health authorities and the CDC of any suspected cases of VHF
    • Strict isolation of infected patients and their contacts with disinfection and sterilization measures
    • Wear appropriate personal protective equipment (e.g., impermeable gown, gloves, respiratory protection, rubber boots).

Reportable disease

  • Probable, suspected, or confirmed cases of VHFs are notifiable conditions to local and state health authorities, as well as the CDC National Notifiable Disease Surveillance System.

Hantavirus infection

There are two notable syndromes that can develop from a hantavirus infection: hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS)

last updated 07/27/2020
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