The viral hemorrhagic fevers 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 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, the Crimean-Congo hemorrhagic fever virus from the Nairovirus
genus, Garissa virus and Ilesha virus from the Orthobunyavirus and the Rift Valley fever
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 fever and
increased susceptibility to bleeding.
Manifestations of VHF often also include flushing of the face and chest, small red or purple
spots, frank bleeding, swelling caused by edema, low blood pressure, and shock.
Malaise, muscle pain, headache, vomiting, and diarrhea occur frequently.
The severity of symptoms varies with the type of virus, with the “VHF syndrome” appearing
in a majority of patients with filovirus hemorhhagic fevers, CCHF, and the South American hemorrhagic
fevers, but in a small minority of patients with dengue, RVF, and Lassa fever.
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, a decrease in the platelet count, an
increase in the blood serum liver enzymes, and reduced blood clotting ability measured
as an increase in both the prothrombin and activated partial thromboplastin times.
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 and can be used only under an experimental protocol as investigational new drug approved
by the U.S. Food and Drug Administration.
Interferon may be effective in Argentine or Bolivian hemorrhagic fevers.
Experimental vaccines for other VHFs are not readily available.
Prophylactic ribavirin may be effective for some bunyavirus and arenavirus infections.
VHF isolation guidelines dictate that all VHF 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 spread.
Airborne precautions should be utilized including, at a minimum, a fit-tested, HEPA filter-equipped
respirator, 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 to a separate building or a ward with an isolated
air-handling system.
Environmental decontamination is typically accomplished with hypochlorite or phenolic
disinfectants.
Pathophysiology Different hemorrhagic fever viruses act on
the body in different ways, resulting in different symptoms.
In most VHFs, it is likely that several mechanisms contribute to symptoms, including liver damage,
disseminated intravascular coagulation, and bone marrow dysfunction.
In DIC, small blood clots form in blood vessels throughout the body, removing platelets necessary
for clotting from the bloodstream and reducing clotting ability.
DIC is thought to cause bleeding in Rift Valley, Marburg, and Ebola fevers.
The reasons for variation among patients infected with the same virus are unknown but stem from
a complex system of virus-host interactions.
Dengue fever becomes more virulent during a second infection by means of antibody dependent
enhancement.
After the first infection, macrophages display antibodies on their cell membranes specific
to the dengue virus.
By attaching to these antibodies, dengue viruses from a second infection are better able to
infect the macrophages, thus reducing the immune system’s ability to fight off infection.
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” 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 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 was 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 that started in August
2007, and that has killed 103 people, has been shown to be caused by Ebola virus.
A viral hemorrhagic fever is a possible cause of the Plague of Athens during the Peloponnesian
War.
A viral hemorrhagic fever is an alternate theory of the cause of the Black Death and
the Plague of Justinian The initial, and currently only, outbreak
of Lujo virus in September–October 2008 left 4/5 patients dead.
The ongoing 2014 West Africa Ebola outbreak, with record numbers already reached.
See also
References
Health Protection Agency This article includes information that originally
came from US Government publications and websites and is in the public domain.