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Viral Hemorrhagic Fevers


Primary Distribution: Hemorrhagic fevers (HFs) are found in numerous areas of the world, with variants noted below under vectors and agents.

Agents and Vectors: Viruses are transmitted by:

The viral HFs are are considered by the CDC to be Category A biological warfare (BW) agents (CDC, 2000). See bioterror box below.

Incubation: Because the index of suspicion is increased with travel in an endemic area + hemorrhagic manifestations occurring within the incubation period, endemic areas and incubation periods are given in discussions of specific HFs. The range of incubation for HFs is 3-28 days.

Clinical Findings and Treatment

Note: The most important HFs are discussed separately in this site and summarized in this file. These include dengue fever, yellow fever, Lassa fever, and the Ebola and Marburg fevers). Those of lesser importance, i.e., lower incidence or virulence are summarized in this file. These include hemorrhagic fever with renal syndrome caused by hantavirus, hantavirus pulmonary syndrome, South American HFs, Kyasanur Forest HF, Omsk HF, Crimean-Congo HF, Chikungunya HF, and Rift Valley HF. The U.S. Centers for Disease Control groups Crimean-Congo, Lassa, Ebola, and Marburg hemorrhagic fevers together as causing viral hemorrhagic fevers (VHFs) and in some cases, presents management as of VHF as a unified concept (CDC, 1995). The Marburg and Ebola hemorrhagic fevers (both from Filoviruses) are characterized by easy transmissability, high mortality, lack of effective vaccine, and lack of effective treatment.

General Signs and Symptoms: The viral hemorrhagic syndrome (VHS) results from widespread increased permeability of microvasculature. Depending on the severity of vascular instability and decrease in platelet function, presentation may range from mild to severe illness; and hemorrhagic manifestations are not always apparent. A common course of illness begins with an abrupt onset of fever, myalgia, cutaneous flushing, and conjunctival suffusion. Within several days, the patient's condition worsens to include syncope, photophobia, headache, hyperesthesia, abdominal pain, nausea/vomiting, anorexia, and prostration.

Bioterror Considerations

The viral HFs (Lassa, Junin and related) are considered by the CDC to be Category A biological warfare agents as they pose a risk to national security because they "can be easily disseminated or transmitted from person to person; cause high mortality, with potential for major public health impact; might cause public panic and social disruption; and require special action for public health preparedness" (CDC, 2000, p. 5). Though Iraq is not known to have produced weaponized viral HFs (Shoham, 2000), "all are potentially infectious by the aerosol route and most are stable as respirable aerosols (Cieslak & Eitzen, 2000, p. 28). Treatment is supportive, hence very challenging in a mass casualty situation.

Specific Signs and Symptoms

Complications: Shock, multifocal hemorrhage, encephalopathy, seizures, convulsions, and/or coma may occur in more serious infections. Renal failure is a complication of HF with renal syndrome. Case mortality rates vary with the causative virus and level of care. For example, the mortality rate for patients with dengue HF who receive supportive care is less than 1%, while the mortality rate for patients with hantavirus pulmonary syndrome is 30-50%. The mortality rate for patients with Ebola HF ranges from 50-90%.

Laboratory Findings: Increased AST, leukopenia, proteinuria, hemoconcentration, thromboctopenia, and at least in the case of Crimean-Congo HF, also increased creatinine phosphokinase, bilirubin, leukocytosis, and signs of disseminated intravascular coagulation.

Diagnosis: Hemorrhagic manifestations + travel to an endemic area. Except for the presence of the rash, dengue fever is difficult to distinguish from other febrile illnesses (e.g., malaria, yellow fever, influenza) or arboviral disease with dengue-like courses (Colorado tick fever, Rift Valley fever, Ross River fever, sandfly fever). For this reason, an initial diagnosis may be "dengue-like disease." Serologic diagnosis is on the basis of a fourfold or greater increase in antibody titer in paired sera by hemagglutination inhibition, complement fixation, enzyme immunoassay, or neutralization test. Standardized immunoglobulin (Ig) M- and IgG-capture enzyme immunoassay are used to identify acute-phase antibodies. Samples are collected no earlier than five days, nor later than six weeks after onset. Viral RNA can be detected by specific complementary DNA probes or amplified first by polymerase chain reaction.

Differential Diagnosis: Rickettsial diseases (typhus, Q fever, trench fever, spotted fevers such as Rocky Mountain or Boutonneuse), meningococcemia, malaria, shigellosis, leptospirosis.

Treatment: Treatment is supportive with acetaminophen rather than aspirin for fever and pain relief, bed rest, fluid replacement, and gradual convalescence. Increased capillary permeability limits the extent of fluid replacement. Pressors may be required to maintain blood pressure. Renal failure requires dialysis. Lassa fever, South American HFs, and possibly Crimean-Congo HF and Rift Valley HF may be treated with a slow infusion of IV ribavirin 32 mg/kg; followed by 16 mg/kg qid for 4 days; and this by 8 mg/kg tid for 6 days. Dengue hemorrhagic fever and shock syndrome are medical emergencies treated in intensive care settings.

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References

Carlini, M.E. & Shandera, W.X. (1999). Infectious diseases: Viral and rickettsial. In L.M. Tierney, S.J. McPhee, & M.A. Papadakis (Eds.), Current Medical Diagnosis & Treatment (14th ed.) (pp.1255-1290). Stamford Connecticut: Appleton & Lange.

Centers for Disease Control (1999). Lassa fever. Available online at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/lassaf.htm Accessed 12/29/99.

Centers for Disease Control (1998). Rift Valley fever. Available online at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/rvf.htm Accessed 12/29/99.

Centers for Disease Control and Prevention. (2000). Biological and chemical terrorism: Strategic plan for preparedness and response. MMWR: Morbidity and Mortality Weekly Report, 49(RR-4), 1-14.

Chin, J. (Ed.) (2000). Control of communicable diseases manual (17th ed.). Washington, DC: American Public Health Association.

Cieslak, T.J. & Eitzen, E.M. (2000). Bioterrorism: Agents of concern. Journal of Public Health Management Practice. 6(4), 19-29.

Halstead, S. (1996). Arboviruses. In W.E. Nelson, R.E. Behrman, R.M. Kliegman, A.M. Arvin (Eds.), Nelson Textbook of Pediatrics (15th ed.) (pp. 920-929). Philadelphia: W.B. Saunders Company.

Levin, M.J. (1999). Infections: Viral and rickettsial. In W.W. Hay, A.R. Hatward, M.J. Levin & J.M. Sondheimer (Eds.). Current Pediatric Diagnosis & Treatment (14th ed.) (pp. 960-994). Stamford Connecticut: Appleton & Lange.

Peters, C.J. (1998). Infections caused by arthropod- and rodent-borne viruses. In A.S. Fauci, E. Braunwald, K.J. Isselbacher, J.D. Wilson, J.B. Martin, D.L Kasper, S.L. Hauser, & D.L. Longo, (Eds.) Harrison's Principles of Internal Medicine (14th ed.) (pp. 1132-1146). New York: McGraw-Hill.