hemorrhagic fever

The viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses that are caused by five distinct families of RNA viruses: the Arenaviridae, Filoviridae, Bunyaviridae, Togaviridae, and Flaviviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in extreme 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

• The Arenaviridae include the viruses responsible for Lassa fever and Argentine, Bolivian, Brazilian and Venezuelan hemorrhagic fevers.
• The 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, and the Rift Valley fever (RVF) virus from the Phlebovirus genus.
• The Filoviridae include Ebola and Marburg viruses.
• Finally, the 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.

The most recently recognised virus capable of causing haemorrhagic fever is Lujo virus, a new member of the arenaviruses described in 2009 and found in South Africa.

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 and an increase in both the prothrombin and active partial prothrombin times. The haemocrit 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 Bunyaviridae and Arenaviridae 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. ^[1]

Pathophysiology

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. ^[2]

Notable VHF outbreaks

• Mékambo in Gabon is the site of several outbreaks of Ebola hemorrhagic fever.
• Orientale, Congo villages of Durba and Watsa were the epicenter of the 1998–2000 outbreak of Marburg hemorrhagic fever.
• Uige Province in Angola is the site of world's worst haemorrhagic fever epidemic, which occurred in 2005.
• The ongoing 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 the Ebola virus.
• Some experts believe that the Black Death of the Middle Ages may have been caused by a VHF and not by the bubonic plague.^[3]

See also

• Agent Fact Sheet: Viral Hemorrhagic Fevers,Center for Biosecurity
• Biological agent
• Biopreparat
• Bioterrorism
• Fever
• List of viruses
• Dr. Matthew Lukwiya (1957-2000)
• C.J. Peters

Sources

• Health Protection Agency
• This article includes information that originally came from US Government publications and websites and is in the public domain.