OPHEPR; Viral Hemorrhagic Fevers - Profile for Healthcare Workers

Arenaviridae – Junin virus (Argentine hemorrhagic fever), Machupo virus (Bolivian hemorrhagic fever), Guanarito virus (Venezuelan hemorrhagic fever), Sabia virus (Brazillian hemorrhagic fever), Lassa virus (Lassa fever)

Bunyaviridae – Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, Hantaan and related viruses of the hantavirus genus (hemorrhagic fever with renal syndrome)

Filoviviridae – Ebola virus, Marburg virus

Flaviviridae – Dengue virus, Yellow fever virus, Omsk hemorrhagic fever virus, Kyasanur Forest disease virus

Routes of Transmission: Dependent on the specific virus. Routes transmission include the bite of an infected tick or mosquito, inhalation of aerosol generated from infected rodent excreta, contact with infected animal carcasses, or person-to-person transmission by close contact with infectious body fluids.

In the laboratory all the viral hemorrhagic fever agents, except dengue virus, are infectious by aerosol.

Incubation Period: The overall incubation period ranges from 2 to 21 days.

Clinical Effects: There is great diversity in the symptoms of these illnesses and infection by these viruses does not necessarily lead to viral hemorrhagic fever disease. Common presenting symptoms and complaints include high fever, headache, malaise, arthralgias, myalgias, nausea, abdominal pain, and nonbloody diarrhea. Clinical examination may reveal fever, hypotension, relative bradycardia, tachypnea, conjunctivitis, and pharyngitis. Rash and cutaneous flushing are typical manifestations, though the specific characteristics of the rash differ by disease. Full blown viral hemorrhagic fevers can evolve to progressive hemorrhagic diathesis, such as petechiae, mucous membrane and conjunctival hemorrhage; hematuria; hematemesis; and melena, disseminated intravascular coagulation, and circulatory shock.

Arenaviruses progress to illness gradually, while filoviruses are characterized by an abrupt onset of disease.

Lethality: The mortality rate varies greatly among these diseases, from 0.5% for Omsk hemorrhagic fever to 90% for Ebola (subtype Zaire).

Transmissibility: Some viral hemorrhagic fevers can be spread person to person. These are: Argentine hemorrhagic fever, Bolivian hemorrhagic fever, Venezuelan hemorrhagic fever, Brazillian hemorrhagic fever, Lassa fever, Crimean-Congo hemorrhagic fever, hemorrhagic fever with renal syndrome, Ebola hemorrhagic fever, and Marburg hemorrhagic fever.

Primary Contamination & Methods of Dissemination: A likely method of dissemination as a biological weapon would be through aerosolization.

Secondary Contamination & Persistence of Organism: Some of the viral hemorrhagic fever viruses can remain present in bodily fluids for long periods after clinical recovery. Because of this continued risk of contagion patients convalescing from an arenaviral or a filoviral infection should abstain from sexual activity for three months following clinical recovery.

Decontamination & Isolation:

Patients – Strict hand hygiene plus use of double gloves, impermeable gowns, face shields, eye protection, leg and shoe coverings, and N95 respirators are recommended. The majority of person-to-person transmission of filoviruses and arenaviruses has been due to direct contact with infected blood and bodily fluids.

Equipment, clothing & other objects – Environmental surfaces in patients’ rooms and contaminated medical equipment should be disinfected with 0.5% hypochlorite solution (1 part household bleach + 9 parts water = 0.5% solution). Contaminated linens and clothes can be placed in double bags and washed without sorting in a normal hot water cycle with bleach. Alternatively, they may be autoclaved or incinerated.

Outbreak Control: All individuals who have been potentially exposed to a hemorrhagic fever virus should be placed under medical surveillance for 21 days and instructed to record their temperatures twice daily and report any symptoms they are experiencing, including any temperature 101º F or higher.

Laboratory testing: Laboratory detection consists of antigen-capture enzyme-linked immunosorbent assay (ELISA), IgM antibody detection by antibody-capture ELISA, RT-PCR, and viral isolation. The most useful of these for the clinical setting are antigen detection (by ELISA) and RT-PCR. If viral hemorrhagic fever is suspected, the laboratory should be notified so that they can avoid procedures that could aerosolize the virus.

Therapeutic Treatment: Treatment is mainly supportive and should include maintenance of fluid and electrolyte balance, circulatory volume, and blood pressure. Early vasopressor support with hemodynamic monitoring should be considered since some viral hemorrhagic fevers have a propensity for pulmonary capillary leaks and vigorous fluid resuscitation of hypotensive patients can contribute to pulmonary endema without reversing hypotension. Mechanical ventilation, renal dialysis, and antiseizure therapy may be required. Intramuscular injections, aspirin, nonsteroidal anti-inflammatory drugs, and other anticoagulant therapies that would aggravate a bleeding disorder should be avoided.

There are no antiviral drugs approved by the US Food and Drug Administration for treatment of viral hemorrhagic fevers. Ribavirin, a nucleoside analog, has some in vitro and in vivo activity against Arenaviridae and Bunyaviridae but no utility against Filoviridae or Flaviviridae. Ribavirin is available via compassionate use protocols.

Prophylactic Treatment: The prophylactic use of oral ribavirin has been suggested for high-risk contacts (those who have had direct exposure to body fluids) of patients with either Congo-Crimean hemorrhagic fever or Lassa fever.

Yellow fever is the only licensed vaccine for any of the viral hemorrhagic fevers, but it is not efficacious for post exposure disease prevention. Under an investigational new drug application vaccines are available for Argentine hemorrhagic fever and Rift Valley fever. A vaccine for Kyasanur Forest disease is also in existence.

Differential Diagnosis: Differential diagnoses should include illnesses that cause severe sepsis and hemorrhage, including influenza, viral hepatitis, staphylococcal or gram negative sepsis, toxic shock syndrome, meningococcemia, salmonellosis and shigellosis, rickettsial diseases (such as Rocky Mountain spotted fever), leptospirosis, borreliosis, psittacosis, dengue, hantavirus pulmonary syndrome, malaria, trypanosomiasis, septicemic plague, rubella, measles, hemorrhagic smallpox, idiopathic or thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, acute leukemia, and collagen-vascular diseases.

References:

Chin J. Control of Communicable Diseases Manual, Seventeenth Edition, American Public Health Association; 2000.
Borio L, Inglesby T, Peters CJ, et al. Hemorrhagic Fever Viruses as Biological Weapons: Medical and Public Health Management, JAMA. 2002; 287: 2391-2405.
Kortepeter M, Christopher G, Cieslak T, et al. Medical Management of Biological Casualties Handbook, U.S. Army Medical Research Institute of Infectious Diseases, U.S. Department of Defense; 2001:54-61.
Jahrling PB. Viral Hemorrhagic Fevers. In: Zajtchuk R, Bellamy RF, eds. Medical Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General, U.S. Department of the Army; 1997:591-602.

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