Ebola hemorrhagic fever (EHF)


by Rebecca Benson


Etiologic agent:  Ebola hemorrhagic fever (EHF) is caused by the Ebolavirus, which is in the viral family Filoviridae.  Five distinct species have been identified within the Ebolavirus genus.  These species include Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast, Ebola-Bundibugyo, and Ebola-Reston.  The Zaire, Sudan, and Bundibugyo species have been associated with large outbreaks and high mortality rates.  The Reston species infects humans, non-human primates, and pigs but has never been shown to cause illness or death in humans.  (8)


Means of transmission:   Ebola is spread by contact transmission, either directly or indirectly.  The disease is readily transmitted to family members and care providers by direct contact with blood or body fluids of infected individuals and corpses.   Infection is also spread by contaminated needles and other objects used in the care of Ebola patients.   Nosocomial transmission commonly spreads the virus quickly in hospital settings before the early signs of infection are correctly identified as Ebola Hemorrhagic Fever.  (5)


Reservoirs:  The precise natural reservoir for the Ebola virus is not known.  Evidence suggests that the natural reservoir is endemic to the rainforests of central Africa and the Phillipines.  Several species of animals are known to be affected by Ebola in Africa—humans, chimpanzees, gorillas, porcupines, and forest antelope-- but none of these are carriers (8).  In the Phillipines, infection by Ebola-Reston and subsequent death has been documented in pigs and cynomolgous monkeys (5).  Recent research  has identified three species of fruit bats in central Africa that are carry Ebola-Zaire subtype, but do not die from the infection.  These three bat species are found in the same areas where several outbreaks of Ebola-Zaire have occurred concurrently in human, chimpanzee, and gorilla populations.  Research suggests that outbreaks occur during dry months when sources of food are scarce.  The infected carrier bats are eaten by humans and other animals, which then become infected and pass the virus to other members of the population.  An outbreak results (4).


General Characteristics:  The Ebolavirus is an encapsulated, helical virion belonging to the family Filoviridae, named for the filamentous shape of its' members.  It's characteristic appearance is a long tube, looped at one end.   However the virus can also be branched, circular or U-shaped.  The virion diameter measures 80 nm, while the length varies widely.  The inner nucleocapsid consists of negative-sense, single-stranded RNA wrapped around several structural proteins (NP, VP35, VP30 and L) in a helical arrangement.  Just inside the viral envelope are two membrane-associated proteins, VP24 and VP40, which have several roles as structural proteins, mediators of host immune response, and viral replication and assembly.  The outer envelope has 7nm glycoprotein (GP) spikes, spaced about 10 nm apart,  which help the virus attach to and enter the host cell. The outer envelope membrane itself is composed of plasma membrane components acquired from the host cell (3).


Diagnostic tests: Several laboratory tests are used to identify Ebolavirus.  Within a few days of the onset of symptoms, antigen-capture ELISA can detect the presence of antigens.  Antibodies are found using IgM ELISA testing.  Viral RNA can also be detected using PCR techniques.  Because Ebola progresses rapidly and is very often fatal, post-mortem diagnosis is often necessary.  Tissue from deceased patients can be used in immunohistochemistry tests, virus isolation, and PCR. (5)


Signs and symptoms:  Ebolavirus causes severe hemorrhagic fever with a very high mortality rate. Unfortunately, the early signs and symptoms of Ebola infection resemble several other diseases.  This often slows diagnosis of the virus until nosocomial transmission results in an outbreak.  The incubation period for Ebolavirus is from 2 to 21 days.  Initial flu-like symptoms develop quickly, and include fever, headache, myalgia, sore throat, and lethargy.  Soon gastrointestinal symptoms arise—abdominal pain, nausea, vomiting, and diarrhea.   Later stages show vascular involvement:  a maculopapular rash, bleeding from the nose and mouth, hemorrhaging in the eyes, intestinal bleeding with blood in the stool,  and internal bleeding.  Disseminated intravascular coagulation, hypovolemic shock, and liver and kidney failure can result in death.  Because the virus attacks cells of the liver and blood vessel endothelium, lab values relating to these systems are associated with Ebola diagnosis.  Liver enzyme tests show elevated AST and ALT.  Urine tests show proteinuria.   Blood  tests often indicate leukopenia, thrombocytopenia, and hyperproteinemia.  (3)


Microbial virulence mechanisms:  The Ebola virus targets endothelial cells of the vascular system; neutrophils, monocytes and macrophages of the immune system; and liver cells.  Viral particles attach to and enter host cells via binding of envelope glycoprotein (GP) to receptors on the host cell surface.  This glycoprotein is produced in two forms, a secreted glycoprotein (sGP) found in serum and the spike-forming, rigid, transmembrane form (GP).  The secreted glycoprotein is thought to interfere with neutrophil activity, slowing the initial immune response to viral infection. (7)

The virus attacks the vascular system directly.  Infection of endothelial cells damages them causing cytopathic effects.   Presence of viral GP is thought to cause a reduction in the specific integrin proteins responsible for adhesion of endothelial cells to the basement membrane.  Damaged cells detach from the lining of the blood vessel, resulting in increased permeability of the vessel.  Damaged endothelial cells also release cytokines, resulting in migration of macrophages to infected tissues. 

Envelope GP enables viral binding and entry into host macrophages and dendritic cells.  The infected macrophage is no longer able to phagocytize invading virus particles, but instead serves as a viral production factory.  As macrophages travel throughout the body, the virus spreads far and wide.  Furthermore, the macrophage also releases cytokines in response to viral invasion.  Excessive endothelial permeability is further exacerbated by the circulating cytokines.  resulting ultimately in hemorrhage and hypovolemic shock.  Initially, cytokines cause the abrupt fever and inflammatory myalgia of Ebola Hemorrhagic Fever.  However, as serum levels of pro-inflammatory cytokines rise, a “cytokine storm” ravages the body and damages the liver.  Eventually liver and kidney failure may develop. (6)


Treatment and Control:  There is no treatment that eliminates the virus.  All treatment efforts are aimed at alleviating symptoms.  Maintaining blood volume and electrolyte balance is crucial in cases of hemorrhage. (8)  Because there is no cure, and the virus is severely pathogenic, quarantine is absolutely necessary when Ebola infection is suspected.  Clinical staff in Ebola-affected areas should be informed of the initial signs and symptoms so that infected patients can be isolated as quickly as possible.  Barrier nursing protocols should be strictly enforced.  All staff who come in contact with the infected patient should have disposable gowns, gloves, masks, and goggles.  Likewise, laboratory staff involved in diagnostic testing or research of the virus should observe all possible caution in handling infected samples.  All equipment, linens, and clothing used with an infected patient must be sterilized.  If sterilization is not appropriate, materials should be incinerated.  Likewise, infected corpses should not be handled directly.  Relatives and community members must be  informed of proper burial practices and of the importance of preventing contact with the deceased. (5)

A comprehensive manual detailing all aspects of Ebola containment has been developed by a collaboration of the Democratic Republic of Congo Ministty of Health, the Centers for Disease Control and Prevention, and the World Health Organization.  Details from specific materials required for barrier nursing and instructions for constructing a sharps container, to the appropriate dilution of bleach needed to disinfect a cadaver are given.  This collaborative and serious approach has been effective for reducing the potential lethality of Ebola outbreaks in affected regions. (2)

Prevention:  There is no vaccine currently approved to prevent Ebola infection in humans.  Because the natural reservoir for the virus is not yet definitively known, development of a vaccine is greatly hampered.  So far no signs of immunity to the virus have been observed following natural infection.  Recent research has shown some success in vaccinating cynomolgus monkeys with a DNA plasmid coding for the Ebola-Zaire glycoprotein.  The naked DNA plasmid was administered in 3 rounds, with a booster several months later.  All animals in the study survived when infected with the virus.  This approach would be useful for prevention in hospital workers, clinical staff, etc.  However the prolonged, multiple vaccination schedule would not work for an acute outbreak.  Single administration of an adenoviral vaccine in this study did confer protection against the virus, but with lower antibody titers.  This single vaccine administration would be appropriate for an acute outbreak.  Further research into natural reservoirs of the virus and viral pathogenic mechanisms will aid development of effective vaccines. (1)


History:   The Ebolavirus is named for the Ebola River Valley, near the area of the initial outbreak.  Ebola virus was first recognized in 1976, following two separate outbreaks in central Africa, one in Sudan and one in Zaire (now Democratic Republic of Congo). Nosocomial transmission led to rapid spread of the virus in both cases.  The Sudan outbreak involved 284 infected patients, with 151 deaths (53% mortality rate).  The Zaire outbreak involved 318 infected patients, with 280 deaths (88% mortality rate).   Another outbreak occurred in the same area in Sudan in 1979, resulting in 22 deaths.  In a severe 1995 outbreak of Ebola-Zaire, 250 out of 315 infected individuals died.  Outbreaks of Ebola-Sudan and Ebola-Zaire have occurred sporadically every couple of years since the mid-1990's.  Ebola-Zaire remains the most deadly form, with the highest mortality rate of the 5 subtypes.  The most recent documented outbreak of Ebola-Zaire occurred in the Democratic Republic of Congo in December of 2008. By the time the outbreak was declared over, 32 people had been infected, and 15 died. (5)

From 1989 to 1992, a new subtype was characterized that killed only non-human primates.  The Ebola-Reston species caused an outbreak among cynomolgus monkeys in a quarantine facility in Reston, Virginia.  Humans who were infected with the virus did show antibodies, but did not get sick.

 In 1994, a new subtype was identified as Ebola-Ivory Coast.  One researcher became ill after examining a dead chimpanzee, but he recovered.   The latest distinct subtype to be discovered is Ebola-Bundibugyo.  This species caused an outbreak in Uganda in late 2007, and resulted in 37 deaths (25% mortality rate).  (5)


Current Local and World Incidence:  Luckily, no known cases of Ebola virus pathogenic to humans have ever been documented in the United States.  At this time, the World Health Organization reports  no cases of human-pathogenic Ebola infection worldwide. 




1.      Armandola, E.  “Conference Report – I.  Investigating New Vaccines:  Ebola and HIV.” Medscape Today News.  3 Dec. 2003.  http://www.medscape.com/viewarticle/464592  6 May 2011. 


2.      Centers for Disease Control and Prevention and World Health Organization.  “Infection Control for Viral Haemorrhagic Fevers in the African Health Care Setting.” Atlanta, Centers for Disease Control and Prevention, 1998:  1-198.    http://www.cdc.gov/ncidod/dvrd/spb/mnpages/vhfmanual.htm#content  6 May 2011.


3.      Feldman, H., and Kjenk, H.-D.  Filoviruses.  In:  Baron, S., ed.  Medical Microbiology. 4th ed.  Galveston, TX:  University of Texas Medical Branch at Galveston:  1996.

http://www.ncbi.nlm.nih.gov/books/NBK8129/#A3866   5 May 2011.


4.      Hassanin, A. (2005).  “Fruit Bats as Reservoirs of Ebola Virus.”  Nature 438 (7068) 575-76. http://mnhn.academia.edu/AlexandreHassanin/Papers/445852/Fruit_Bats_As_Reservoirs_of_Ebola_Virus  7 May 2011.


5.      Special Pathogens Branch.  Division of High-Consequence Pathogens and Pathology.  “Ebola Hemorrhagic Fever Information Packet.”  Centers for Disease Control and Prevention.  9 April 2010. http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Fact_Sheets/Ebola_Fact_Booklet.pdf   5 May 2011.


6.      Sullivan, N., Yang, Z.-Y., and Nabel, G.  (2003).  “Ebola Virus Pathogenesis:  Implications  for Vaccines and Therapies.”  Journal of Virology 77(18) 9733-9737.   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC224575/   6 May 2011.


7.      Wahl-Jensen, V., et al.  (2005).  “Role of Ebola Virus Secreted Glycoproteins and Virus-Like Particles in Activation of Human Macrophages.”  Journal of Virology 79 (4) 2413-2419.  http://jvi.asm.org/cgi/reprint/79/4/2413  6 May 2011.


8.      WHO Media Centre.  “Fact Sheet No. 103:  Ebola Haemorrhagic Fever.”  World Health Organization.  Dec. 2008 http://www.who.int/mediacentre/factsheets/fs103/en/  5 May 2011.