Viral hemorrhagic fever
|Viral hemorrhagic fever (Trojon)|
|Classification and external resources|
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 
Five families of RNA viruses have been recognised as being able to cause this syndrome.
- The family Arenaviridae include the viruses responsible for Lassa fever, Lujo virus, Argentine, Bolivian, Brazilian and Venezuelan hemorrhagic fevers.
- The family Bunyaviridae include the members of the Hantavirus genus that cause hemorrhagic fever with renal syndrome (HFRS), the Crimean-Congo hemorrhagic fever (CCHF) virus from the Nairovirus genus, Garissa virus from the Orthobunyavirus and the Rift Valley fever (RVF) virus from the Phlebovirus genus.
- The family Filoviridae include Ebola virus and Marburg virus.
- The family Flaviviridae include dengue, yellow fever, and two viruses in the tick-borne encephalitis group that cause VHF: Omsk hemorrhagic fever virus and Kyasanur Forest disease virus.
- In September 2012 scientists writing in the journal PLOS Pathogens reported the isolation of a member of the Rhabdoviridae responsible for 2 fatal and 2 non-fatal cases of hemorrhagic fever in the Bas-Congo district of the Democratic Republic of Congo. The non-fatal cases occurred in healthcare workers involved in the treatment of the other two, suggesting the possibility of person-to-person transmission. This virus appears to be unrelated to previously known Rhabdoviruses.
Clinical and treatment aspects 
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.
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 
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.
Notable VHF outbreaks 
- Cocoliztli in New Mexico 1545.
- The Great Yellow Fever Epidemic of 1793 in Philadelphia, PA USA. Nearly 10% of the population of 50,000 succumbed to the disease.
- Mékambo in Gabon is the site of several outbreaks of Ebola virus disease.
- Orientale Province, Democratic Republic of the Congo villages of Durba and Watsa were the epicenter of the 1998–2000 outbreak of Marburg virus disease.
- Uíge Province in Angola is the site of world's worst hemorrhagic fever epidemic, which occurred in 2005.
- A VHF outbreak in the village of Mweka, Democratic Republic of the Congo (DRC) that started in August 2007, and that has killed 103 people (100 adults and three children), has been shown to be caused (at least partially) by Ebola virus.
- A viral hemorrhagic fever is a possible cause of the Plague of Athens during the Peloponnesian War.
- The initial, and currently only, outbreak of Lujo virus in September-October 2008 left 4/5 patients dead. 
See also 
- Grard G, Fair JN, Lee D, Slikas E, Steffen I, Muyembe JJ, Sittler T, Veeraraghavan N, Ruby JG, Wang C, Makuwa M, Mulembakani P, Tesh RB, Mazet J, Rimoin AW, Taylor T, Schneider BS, Simmons G, Delwart E, Wolfe ND, Chiu CY, Leroy EM (2012) A novel rhabdovirus associated with acute hemorrhagic Fever in central Africa. PLoS Pathog 8(9):e1002924. doi: 10.1371/journal.ppat.1002924
- 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.
- Woods, Op. cit., pg 145.
- 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.
- Was the Huey Cocoliztli a Haemorrhagic Fever?
- Indigenous Hemorrhagic Fever and The Spanish Conquest
- 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.
- Acuna-Soto R, Stahle DW, Cleaveland MK, Therrell MD (April 2002). "Megadrought and Megadeath in 16th Century Mexico". Emerg Infect Dis 8 (4).
- Epidemics in New Spain
- Olson, P. E.; Hames, C. S.; Benenson, A. S.; Genovese, E. N. (1996). "The Thucydides syndrome: ebola deja vu? (or ebola reemergent?)". Emerging Infectious Diseases 2: 155–156. ISSN 1080-6059.
- 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. PMID 19478873.
- Health Protection Agency
- This article includes information that originally came from US Government publications and websites and is in the public domain.