Viral hemorrhagic fever

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Viral hemorrhagic fever (Trojon)
Classification and external resources
7042 lores-Ebola-Zaire-CDC Photo.jpg
ICD-10 A96-A99
eMedicine article/830594
MeSH D006482

The viral hemorrhagic (or haemorrhagic) fevers (VHFs) are a diverse group of animal and human illnesses that may be caused by five distinct families of RNA viruses: the families Arenaviridae, Filoviridae, Bunyaviridae, Flaviviridae, and Rhabdoviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in many cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica, while others, such as the African Ebola virus, can cause severe, life-threatening disease.

Etiologic agents[edit]

Five families of RNA viruses have been recognised as being able to cause this syndrome.

Clinical and treatment aspects[edit]

Signs and symptoms of VHFs include (by definition) fever and bleeding diathesis. Manifestations of VHF often also include flushing of the face and chest, petechiae, frank bleeding, edema, hypotension, and shock. Malaise, myalgias, headache, vomiting, and diarrhea occur frequently. Definitive diagnosis is usually made at a reference laboratory with advanced biocontainment capabilities.

The findings of laboratory investigation vary somewhat between the viruses but in general there is a decrease in the total white cell count particularly the lymphocytes, a decrease in the platelet count, an increase in the serum liver enzymes as well as increase in both the prothrombin (PT) and activated partial thromboplastin times (PTT). The hematocrit may be elevated. The serum urea and creatine may be raised but this is dependent on the hydration status of the patient. The bleeding time tends to be prolonged.

Medical management of VHF patients may require intensive supportive care. Antiviral therapy with intravenous ribavirin may be useful in Bunyaviridae and Arenaviridae infections (specifically Lassa fever, RVF, CCHF, and HFRS due to Old World Hantavirus infection) and can be used only under an experimental protocol as investigational new drug (IND) approved by the U.S. Food and Drug Administration (FDA). Interferon may be effective in Argentine or Bolivian hemorrhagic fevers (also available only as IND). Experimental vaccines for other VHFs are not readily available.

Prophylactic (preventive) ribavirin may be effective for some bunyavirus and arenavirus infections (again, available only as IND).

VHF isolation guidelines dictate that all VHF patients (with the exception of dengue patients) should be cared for using strict contact precautions, including hand hygiene, double gloves, gowns, shoe and leg coverings, and faceshield or goggles. Lassa, CCHF, Ebola, and Marburg viruses may be particularly prone to nosocomial (hospital-based) spread. Airborne precautions should be utilized including, at a minimum, a fit-tested, HEPA filter-equipped respirator (such as an N-95 mask), a battery-powered, air-purifying respirator, or a positive pressure supplied air respirator to be worn by personnel coming within six feet of a VHF patient. Multiple patients should be cohorted (sequestered) to a separate building or a ward with an isolated air-handling system. Environmental decontamination is typically accomplished with hypochlorite or phenolic disinfectants.[2]


The diversity of clinical features seen among the VHF infections probably originates from varying mechanisms of pathogenesis. An immunopathogenic mechanism, for example, has been identified for dengue hemorrhagic fever, which usually occurs among patients previously infected with a heterologous dengue serotype. An influential theory explaining this phenomenon is called “antibody-dependent enhancement.” In contrast, disseminated intravascular coagulation (DIC) is thought to underlie the hemorrhagic features of Rift Valley, Marburg and Ebola fevers. In most VHFs, however, the etiology of the coagulopathy is most likely multifactorial (e.g., hepatic damage, consumptive coagulopathy, primary marrow dysfunction, etc.).

The reasons for variation among patients infected with the same virus are unknown but stem from a complex system of virus-host interactions. Moreover, why some infected persons develop full-blown VHF while others do not also remains an unresolved issue. Virulence of the infecting agent clearly plays an important role. The “VHF syndrome” (capillary leak, bleeding diathesis and hemodynamic compromise leading to shock) occurs in a majority of patients manifesting disease from filoviruses, CCHF, and the South American hemorrhagic fever viruses, while it occurs in a small minority of patients with dengue, RVF and Lassa fever.

Biowarfare/bioterrorism potential[edit]

The VHF viruses are spread in a variety of ways. Some may be transmitted to humans through a respiratory route. Although evidence for a history of “weaponization” (development into a biological weapon) does not exist for many of these viruses, all are considered by military medical planners to have a potential for aerosol dissemination, weaponization, or likelihood for confusion with similar agents that might be weaponized.[3][4]

Notable VHF outbreaks[edit]

See also[edit]


  1. ^ Grard G, Fair JN, Lee D, et al. (September). "A novel rhabdovirus associated with acute hemorrhagic fever in central Africa". PLoS Pathog. 8 (9): e1002924. doi:10.1371/journal.ppat.1002924. PMC 3460624. PMID 23028323. 
  2. ^ Woods, Lt Col Jon B., ed. (2005). USAMRIID’s Medical Management of Biological Casualties Handbook (PDF) (6th ed.). Fort Detrick MA: U.S. Army Medical Institute of Infectious Diseases. pp. 143–4. 
  3. ^ Woods 2005, p. 145
  4. ^ Peters, C. (2000). "Are Hemorrhagic Fever Viruses Practical Agents for Biological Terrorism?". In Scheld, W. M.; Craig, W. A.; Hughes, J. M. Emerging Infections 4. Washington, DC: ASM Press. pp. 201–209. ISBN 1555811973. 
  5. ^ Was the Huey Cocoliztli a Haemorrhagic Fever?
  6. ^ Indigenous Hemorrhagic Fever and The Spanish Conquest
  7. ^ Acuna-Soto R, Romero LC, Maguire JH (June 2000). "Large Epidemics of Hemorrhagic Fevers in Mexico 1545–1815" (PDF). Am J Trop Med Hyg 62 (6): 733–9. PMID 11304065. 
  8. ^ Acuna-Soto R, Stahle DW, Cleaveland MK, Therrell MD (April). "Megadrought and megadeath in 16th century Mexico". Emerging Infect. Dis. 8 (4): 360–2. doi:10.3201/eid0804.010175. PMC 2730237. PMID 11971767. 
  9. ^ Epidemics in New Spain
  10. ^ Olson PE, Hames CS, Benenson AS, Genovese EN (1996). "The Thucydides syndrome: Ebola déjà vu? (or Ebola reemergent?)". Emerging Infect. Dis. 2 (2): 155–6. doi:10.3201/eid0202.960220. PMC 2639821. PMID 8964060. 
  11. ^ Briese, T.; Paweska, J.T.; McMullan, L.K.; Hutchison, S.K.; Street, C.; Palacios, G.; Khristova, M.L.; Weyer, J.; Swanepoel, R.; Engholm, M.; Nichol, S.T.; Lipkin, W.I. (2009). "Genetic Detection and Characterization of Lujo Virus, a New Hemorrhagic Fever–Associated Arenavirus from Southern Africa". PLoS Pathog 5 (5): e1000455. doi:10.1371/journal.ppat.1000455. PMC 2680969. PMID 19478873. 
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