National Agricultural Biosecurity Center

Synopsis of Viral Hemorrhagic Fever

Viral hemorrhagic fevers (VHFs), a group of clinical febrile illnesses, are caused by a group of RNA viruses which belong to four distinct viral families. The viruses are zoonotic and totally dependent on an animal (rodents) or insect host (ticks, mosquitoes) for survival. They are found worldwide; however, because each virus is associated with one or more particular host species, they are usually only seen where the host species live(s). For example, the multimammate mouse (indigenous to West Africa) is the natural reservoir for the virus that causes Lassa fever, which is seen only in Nigeria, Liberia, Gunea, and Sierra Leone. Human cases or outbreaks of hemorrhagic fevers occur periodically; and, although humans are incidental hosts, they can transmit the virus to one another. These viruses are of major concern with respect to biological terrorism due to their high mortality and morbidity as well as their stability and ease of production. Since VHFs are not native to the United States, an outbreak of these diseases should arouse suspicion of a bioterrorist event if the outbreak cannot be linked to travel to a disease-endemic region.

• Transmission:
  • Transmission to humans initially occurs when the activities of infected reservoir hosts or vectors and humans overlap.
    • Contact with urine, fecal matter, saliva, or other body excretions of infected reservoir hosts
    • Vector mosquito or tick bites, or when a human crushed a tick
    • Mosquito or tick vectors may also infect livestock
      1. Humans can become infected when they care for or slaughter infected animals
  • Person-to-person (secondary transmission)
    • Examples: Ebola, Marburg, Lassa, and Crimean-Congo hemorrhagic fever viruses
    • Can occur directly, through close contact with infected people, or their body fluids
    • Can also occur indirectly, through contact with objects contaminated with infected body fluids
• Four distinct viral families:
  • Filoviridae
    • Ebola
    • Marburg
  • Arenaviridae
    • Lassa fever
    • New world hemorrhagic fever
    • Bolivian hemorrhagic fever (Machupo)
    • Argentine hemorrhagic fever (Junin virus)
    • Venezuelan hemorrhagic fever (Guanarito virus)
    • Brazilian hemorrhagic fever (Sabia virus)
  • Bunyaviridae
    • Crimean-Congo hemorrhagic fever
    • Rift Valley fever
    • Hantavirus
  • Flaviviridae
    • Dengue
    • Yellow fever
    • Omsk hemorrhagic fever
    • Kyasanur Forest disease

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Clinical Signs and Symptoms

Animals:

• Numerous wild and domestic animals, such as cattle, goats, sheep, and hares, serve as amplifying hosts
• Filoviridae:
  • Same clinical course as that of humans
  • High primate mortality rate: ~ 82%
• Bunyaviridae:
  • CCHF- unapparent infection in livestock
  • RVF- 100% abortion rate and mortality rate of > 90% in young animals and 5-60% in older animals
  • Hantavirus – unapparent infection in rodents
• Flaviviridae:
  • Non-human primates – varying clinical signs (Yellow fever); no clinical signs (Dengue)
  • Livestock – no symptoms (Kyasanur Forest Disease)
  • Rodents – no symptoms

Humans:

• Clinical signs and symptoms vary by the type of VHF
• Patients usually present with the following clinical signs and symptoms:
  • Fever ³ 38.3°C of < 3 week duration
  • Fatigue
  • Dizziness
  • Muscle aches
  • Loss of strength
  • Exhaustion
  • At least two of the following:
    • Hemorrhagic or purple rash
    • Epistaxis
    • Hemoptysis
    • Blood in stools
    • Petechiae in nondependent areas
  • No predisposing factors for hemorrhage and no established alternative diagnosis
• Signs and symptoms (severe cases):
  • Bleeding under the skin, in internal organs, or from body orifices (mouth, eyes, ears)
  • Shock
  • Nervous system malfunction
  • Coma
  • Delirium
  • Seizures
  • Renal failure (some types of VHF)
• Filoviridae:
  • Most severe hemorrhagic fevers with abrupt onset and death around day 7 to 11; painful recovery
  • Incubation: 4 to 10 days
  • Case fatality: 23-33% (Marburg) and 53-88% (Ebola)
• Arenaviridae:
  • Incubation: 10 to 14 days
  • Case fatality: 5-35%
• Bunyaviridae:
  • Incubation: 3 to 7 days (CCHF); 2 to 5 days (RVF); 7 to 21 days (Hantavirus)
  • Case fatality: 30% (CCHF); 1% (RVF); 1-50% (Hantavirus)
• Flaviviridae
  • Incubation: 2 to 6 days
  • Case fatality: 1-10% (Dengue); 3-5% (Kyasanur Forest virus); 0.5-3% (Omsk hemorrhagic fever); varies (Yellow fever)

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Diagnosis and Treatment

Diagnostic Samples:

• Blood
• Urine

Differential Diagnosis:

• In humans, the differential diagnoses include viral hepatitis, Gram-negative sepsis, toxic shock syndrome, meningococcemia, other bacterial sepsis, rickettsial diseases, leptospirosis, borreliosis, malaria, septicemic plague, or hemorrhagic smallpox.

Clinical Diagnosis:

• Clinical manifestations of VHFs may overlap, making clinical diagnosis unlikely.

Laboratory Tests:

• Clinical diagnostic testing:
  • WBC with differential
  • Platelet count
  • PT/PTT and bleeding time
  • LFT’s
  • Fibrin split products
  • Fibrinogen
  • UA and BUN
  • Electrolytes
  • Glucose
  • pH and bicarbonate levels
• Specific (specimens must be sent to the CDC or USAMRIID—BSL-4 laboratories)
  • Antigen-capture ELISA
  • IgM by antibody-capture ELISA
  • RT-PCR (most useful clinically)
  • Immunohistochemistry
  • Viral isolation (requires BSL-4 laboratory)
  • Electron microscopy
  • Acute or convalescent IgG serologies in survivors (retrospective)

Treatment:

• In humans:
  • Supportive care
  • There is no established treatment or cure
  • Treatment with convalescent-phase plasma has shown some success in patients with Argentine hemorrhagic fever
  • Antiviral drugs:
    • Ribavirin has shown some success in patients with arenavirus or bunyavirus infection
  • Vaccines:
    • Vaccines have been developed for yellow fever and Argentine hemorrhagic fever
    • No vaccines exist for other VHFs

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Economic Consequences and Disease Eradication

Economic Consequences:

• Medical costs
• Costs associated with disease control and prevention

Disease Eradication:

• Immediate notification of state and federal health officials
• Prevention:
  • Rodent population control
  • Safe cleanup of rodent nests and droppings
  • Insect and arthropod vector control (e.g., mosquitoes and other biting insects)
  • Use of insect repellents
  • Proper protective clothing and equipment (i.e., long sleeves, long pants, bednets, window screens, etc)
  • Avoid close contact with infected individuals and their body fluids
• Control measures:
  • Airborne:
    • Place patients in a private room with negative air pressure (6 to 12 air changes per hour)
    • Restricted access of nonessential staff and visitors
  • Personal protective equipment
    • N-95 respirator or powered air-purifying respirator
    • Double gloves
    • Impermeable gowns
    • Face shields
    • Goggles for eye protection
    • Leg and shoe coverings
  • Hand hygiene:
    • Clean hands prior to patient contact
    • After patient care, remove gloves, gown, and leg/shoe coverings, immediately clean hands, then remove protective facial equipment, clean hands again after removing protective facial equipment
  • Medical equipment and environmental contamination:
    • All equipment, surfaces, and inanimate objects should be disinfected with an EPA-registered hospital disinfectant or a 1:100 dilution of household bleach
    • Contaminated linens should be incinerated, autoclaved, or placed in double, leak-proof bags at the site of use and washed without sorting in a normal hot water cycle with bleach
    • Hospital housekeeping staff and linen handlers should wear appropriate personal protective equipment
  • Initiate appropriate infection control practices
  • Barrier nursing or infection control techniques (e.g., isolation of infected patients, wearing protective clothing, cleaning and disinfecting of instruments and equipment used to treat or care for infected patients)
  • The World Health Organization Has developed practical, hospital-based guidelines for caring for patients infected with VHFs titled: Infection Control for Viral Haemorrhagic Fevers In the African Health Care System

VHFs and Bioterrorims:

• VHFs are a major concern with respect to biological terrorism for the following reasons:
  • The diseases caused by these viruses are associated with high morbidity and mortality
  • High infectivity
  • Environmentally stable
  • Ease of production

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Outbreaks

2005: 351 human cases and 312 deaths from Marburg hemorrhagic fever in Angola

2005: 12 human cases and 9 deaths from Ebola hemorrhagic fever in South Africa

2004: 17 human cases and 7 deaths from Ebola hemorrhagic fever in southern Sudan

2004: 1 human case of Lassa fever in New Jersey U.S.; the patient had acquired the disease while traveling to West Africa

2004: 58,301 human cases and 658 deaths from Dengue fever in Indonesia

2003: 2,185 human cases and 4 deaths from Crimean-Congo hemorrhagic fever in Mauritania

2003: 35 human cases and 29 deaths from Ebola hemorrhagic fever in South Africa

2002: 5,833 human cases of Dengue fever in Ecuador

2002: 2,249 human cases and 6 deaths from Dengue fever in El Salvador

2002: 3,993 human cases and 8 deaths from Dengue fever in Honduras

2002: 317,787 human cases and 57 deaths from Dengue fever in Brazil

2001: 69 suspected human cases and 6 deaths from Crimean-Congo hemorrhagic fever in Kosovo

2001: 30 human cases and 22 deaths from Ebola hemorrhagic fever in South Africa

2001: 423 human cases and 169 deaths from Ebola hemorrhagic fever in Uganda

2000: 16 human cases of Marburg hemorrhagic fever in South Africa

Click on the following hyperlink for the most recent outbreak information located at the Office International des Epizooties Website. http://www.oie.int/eng/info/hebdo/A_DSUM.htm.¹⁷

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Sources and Related Articles

Sources:

1. CDC. August 23, 2004. Viral Hemorrhagic Fevers Fact Sheet. Available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Fact_Sheets/ Viral_Hemorrhagic_Fevers_Fact_Sheet.pdf
2. CIDRAP, August 31, 2005. Viral Hemorrhagic Fever (VHF): Current, comprehensive information on pathogenesis, microbiology, epidemiology, diagnosis, treatment, and prophylaxis. Available at http://www.cidrap.umn.edu/cidrap/content/bt/vhf/biofacts/vhffactsheet.html.
3. UAB Bioterrorism and Emerging Infectious Education. Viral Hemorrhagic Fevers Summary. Available at http://www.bioterrorism.uab.edu/CategoryA/VHF/summary.asp.
4. University of Pittsburg Medical Center's Center for Biosecurity, 2005. Answers to frequently asked questions about VHF. Available at http://www.upmc-biosecurity.org/pages/agents/vhf.html.
5. WHO, April 30, 2006. Viral Haemorrhagic Fevers. Available at http://www.who.int/topics/haemorrhagic_fevers_viral/en/.

Related Articles:

6. Anonymous. Arenavirus Fact Sheet. Published on the CDC Website. Available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Fact_Sheets/Arenavirus_Fact_Sheet.pdf.
7. Anonymous. Lassa Fever Fact Sheet. Published on the CDC Website. Available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Fact_Sheets/Lassa_Fever_Fact_Sheet.pdf.
8. Anonymous. Marburg Hemorrhagic Fever Fact Sheet. Published on the CDC Website. Available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Fact_Sheets/Marburg_Hemmorhagic_Fever_Fact_Sheet.pdf.
9. Anonymous. Rift Valley Fever Fact Sheet. Published on the CDC Website. Available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Fact_Sheets/Rift_Valley_Fever_Fact_Sheet.pdf.
10. Anonymous, June 12, 2001. Fact Sheet: Crimean Congo Hemorrhagic Fever. Published by the U.S. Army Center for Health Promotion and Preventive Medicine – Europe. Available at http://chppm-www.apgea.army.mil/ento/FACTS/CCHF%20fact%20sheet.pdf.
11. Anonymous, 2002. Ebola Hemorrhagic Fever Information Packet. Published on the CDC Website. Available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/ebola.pdf.
12. Anonymous, January 2004. Viral Hemorrhagic Fevers—Machupo and Lassa Fever. Published on the OIE Website. Available at http://www.cfsph.iastate.edu/Factsheets/pdfs/viral_hemorrhagic_fever_arenavirus.pdf.
13. Anonymous, January 2005. Public Health Information Sheet: Hantavirus. Published by the U.S. Department of the Interior’s National Park Service. Available at http://www.nps.gov/public_health/inter/info/factsheets/fs_hvgen.pdf.
14. Anonymous, August 22, 2005. Dengue Fever. Published on the CDC Website. Available at http://www.cdc.gov/ncidod/dvbid/dengue/.
15. Anonymous, 2006. Infection control for viral haemorrhagic fevers in the African health care setting. Published on the World Health Organization Website. Available at http://www.who.int/csr/resources/publications/ebola/WHO_EMC_ESR_98_2_EN/en/index.html.
16. Jahrling P. B. Viral Hemorrhagic Fevers. Available at http://www.nbc-med.org/SiteContent/HomePage/WhatsNew/MedAspects/Ch-29electrv699.pdf.
17. Click on the following hyperlink for the most recent outbreak information located at the Office International des Epizooties Website. http://www.oie.int/eng/info/hebdo/A_DSUM.htm.←

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