Everything about Viral Hemorrhagic Fever totally explained
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, whilst 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, 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.
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.
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 a
US FDA approved
investigational new drug (IND).
Convalescent plasma may be effective in Argentine or Bolivian hemorrhagic fevers (also available only as IND). The only licensed vaccine for a VHF is the 17D
yellow fever vaccine. 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.
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 (for example, 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 don't 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) doesn't 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
Further Information
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