Encyclopedia
Ebola is the common term for a group of
viruses belonging to genus
Ebolavirus, family
Filoviridae, which cause Ebola haemorrhagic fever. The disease can be deadly and encompasses a range of symptoms, usually including vomiting, diarrhoea, general body pain, internal and external bleeding, and fever . Mortality rates are generally high, ranging from 50% - 90%, with the cause of death usually due to
shock or multiple organ failure.
The virus is named after the Ebola River in the
African state of the
Democratic Republic of the Congo , near the site of the first outbreaks.The Democratic Republic of Congo has been the site of four recent outbreaks, including one in May 2005.
Ebola is believed to be a zoonotic virus, although despite considerable effort by the
World Health Organization, no animal reservoir capable of sustaining the virus between outbreaks has been identified. One possible candidate reservoir is the
fruit bat.
Because ebola is lethal and since no approved vaccine or treatment is available, Ebola is classified as a biosafety level 4 agent; as well as a category A bioterrorism agent and a select agent by the
CDC.
Structure
Size and shape
Electron micrographs of members of
Ebolavirus show them to have the characteristic thread-like structure of a
filovirus. The virions are variable in shape and may appear as a "U", "6", coiled, circular, or branched shape, however, laboratory purification techniques, such as centrifugation, may contribute to the various shapes seen. Virions are generally 80
nm in diameter. They are variable in length, and can be up to 1400 nm long. On average however, the length of a typical ebolavirus is closer to 1000 nm. In the center of the virion is a structure called nucleocapsid, which is formed by the helically wound viral genomic RNA complexed with the proteins NP, VP35, VP30 and L. It has a diameter of 40 – 50 nm and contains a central channel of 20 – 30 nm in diameter. Virally encoded glycoprotein spikes 10 nm long and 10 nm apart are present on the outer
viral envelope of the virion, which is derived from the host cell membrane. Between envelope and nucleocapsid, in the so called matrix space, the viral proteins VP40 and VP24 are located.
Genome
Each virion contains one molecule of linear, single-stranded, negative-sense
RNA, totalling 18900
nucleotides in length. The 3’ terminus is not
polyadenylated and the 5’ end is not
capped. It codes for seven structural proteins and one non-structural protein. The gene order is 3' - leader - NP - VP35 - VP40 - GP/sGP - VP30 - VP24 - L - trailer - 5'; with the leader and trailer being non-transcribed regions which carry important signals to control transcription, replication and packaging of the viral genome into new virions. The genomic material by itself is not infectious, because viral proteins, among them the RNA-dependent
RNA polymerase, are necessary to transcribe the viral genome into
mRNAs, as well as for replication of the viral genome.
Proteins
Nucleocapsid proteins
The Ebola virus synthesises seven viral-associated proteins. The nucleocapsid proteins NP, VP35, VP30 and L are involved in transcription and replication of the viral genome. NP encapsidates the genomic RNA and is a major structural component of the nucleocapsid. L, the , produces mRNAs and copies the negative-sense genome first into a positive-sense antigenome and then this antigenome back into negative-sense genomes, thus replicating the genomic information. VP35 serves as a cofactor for L, and VP30 is a viral transcription factor. Also, VP35 impairs the function of the
immune system by blocking the production of
Interferon.
Matrix proteins
The major matrix protein VP40 is crucial for assembly and budding of new virions. VP24, the minor matrix protein, has been shown to be involved in assembly of nucleocapsids, although VP24 itself is not part of them. VP24 also blocks the effects of
Interferon.
Glycoproteins
The envelope glycoprotein at the viral membrane surface, GP, is a trimer of dimers. Individual GP molecules passing through the cell are proteolytically cleaved into two disulphide-linked polypeptides: GP1 and GP2. GP2 anchors the glycoprotein to the membrane through an hydrophobic stretch of amino acids and is covalently attached to GP1 via disulphide bonds. These GP1-GP2 dimers associate at the viral surface as a trimer, and have been shown to mediate attachment of virions to target cells as well as fusion of the
virus membrane with the
target cell membrane. The mRNA for GP is produced after
transcriptional editing, which involves the addition of an
adenosine base into the mRNA, which is not encoded in the viral genome. The additional
adenosine is inserted at the end of a stretch of six adenosine residues coded for in the genome; it is thought this editing event occurs as a result of slippage of the RNA polymerase against the template. In the absence of this editing event, the non-structural protein sGP is produced, which is the major product of the glycoprotein gene; its function is currently unknown. However, laboratory strains of the virus that are unable to synthesise sGP are extremely toxic to the host cell and cause the infected cell to die. Therefore, it has been suggested that the synthesis of sGP limits the extreme toxicity of the virus associated with full length GP to provide a balance between virus infectivity and toxicity, so as to permit continued cycles of infection.
Species
Zaïre ebolavirus
The
Zaïre ebolavirus has the highest mortality rate, up to 90% in some epidemics, with an average of approximately 83% mortality over 27 years. The case-fatality rates were 88% in 1976, 100% in 1977, 59% in 1994, 81% in 1995, 73% in 1996, 80% in 2001-2002 and 90% in 2003. There have been more outbreaks of
Zaïre ebolavirus than any other strain.
The first outbreak took place on August 26, 1976 in Yambuku, a town in the north of the
Democratic Republic of the Congo. The first recorded case is Mabalo Lokela, a 44-year-old schoolteacher returning from a trip around the north of the state. His high fever was diagnosed as possible
malaria and he was subsequently given a
quinine shot. Lokela returned to the hospital every day. A week later, his symptoms included uncontrolled vomiting, bloody diarrhoea, headache, dizziness, and trouble breathing. Later, he began bleeding from his nose, mouth, and rectum. Mabalo Lokela died on September 8, 1976, roughly 14 days after the onset of symptoms.
Soon after, more patients arrived with varying but similar symptoms including fever, headache, muscle and joint aches, fatigue, nausea and dizziness. These often progressed to bloody diarrhoea, severe vomiting, and bleeding from the nose, mouth, and rectum. The initial transmission was believed to be due to reuse of the needle for Lokela’s injection without sterilization. Subsequent transmission was also due to care of the sick patients without barrier nursing and the traditional burial preparation method, which involved washing and
gastrointestinal tract cleansing.
Sudan ebolavirus
The most recent outbreak of
Sudan ebolavirus occurred in May 2004. As of May 2004, 20 cases of
Sudan ebolavirus were reported in Yambio County, Sudan, with 5 deaths resulting. The
Centers for Disease Control and Prevention confirmed the virus a few days later. The neighboring countries of
Uganda and the
Democratic Republic of Congo have increased surveillance in bordering areas, and other similar measures have been taken to control the outbreak. The average fatality rates for
Sudan ebolavirus were 53% in 1976, 68% in 1979, and 53% in 2000/2001. The average case-fatality rate is 53.76%.
Reston ebolavirus
First discovered in November of 1989 in a group of 100 Crab-eating Macaques imported from the
Philippines to
Reston,
Virginia. A parallel infected shipment was also sent to
Philadelphia. This strain was highly lethal in monkeys, but did not cause any fatalities in humans. Six of the Reston primate handlers tested positive for the virus, two due to previous exposure.
Further
Reston ebolavirus infected monkeys were shipped again to Reston, and
Alice,
Texas in February of 1990. More
Reston ebolavirus infected monkeys were discovered in 1992 in
Siena,
Italy and in Texas again in March 1996. A high rate of co-infection with Simian Hemorrhagic Fever was present in all infected monkeys. No human illness has resulted from these two outbreaks.
Ivory Coast ebolavirus
This species of Ebola was first discovered amongst
chimpanzees of the Tai Forest in
Cote d'Ivoire,
Africa. On November 1, 1994, the corpses of two chimpanzees were found in the forest. Necropsies showed blood within the heart to be liquid and brown, no obvious marks seen on the organs, and one presented lungs filled with liquid blood. Studies of tissues taken from the chimps showed results similar to human cases during the 1976 Ebola outbreaks in Zaire and Sudan. Later in 1994, more dead chimpanzees were discovered, with many testing positive to Ebola using molecular techniques. The source of contamination was believed to be the meat of infected Western Red Colobus monkeys, which the chimpanzees preyed upon.
One of the scientists performing the necropsies on the infected chimpanzees contracted Ebola. She developed syndromes similar to a
dengue fever approximately a week after the necropsy and was transported to Switzerland for treatment. After two weeks she was discharged from hospital, and was fully recovered six weeks after the infection.
Replication
The viral attachment protein recognizes specific receptors, which may be protein, carbohydrate or lipid, on the outside of the cell. The mechanism of virus entry into host cells is unknown, but it is reasonable to assume that the glycoprotein spikes on the surface of the virion would mediate the process, as they are the only transmembrane protein present on the surface.
The virus next activates and releases its own genetic material, causing the host to begin manufacturing the proteins necessary for virus reproduction using its own resources. This replication continues until the cell ruptures and bursts. The virus is then spread to neighbouring cells, and continues this chain of reproduction until masses of host cells are damaged. The host dies soon after. The spread of the virus through the population can be halted if the proper sterilization and quarantine measures are taken, as the only method by which the virus may continue to propagate is via direct contact with body fluids.
Ebola haemorrhagic fever
Symptoms
Symptoms are varied and often appear suddenly. Initial symptoms include: high
fever , severe headache, muscle, joint or abdominal pain, severe weakness and exhaustion, sore throat, nausea, and dizziness. Before an epidemic is suspected, these early symptoms are easily mistaken for
malaria, typhoid fever, dysentery,
influenza, or various
bacterial infections, which are all far more common.
Ebola goes on to cause diarrhoea, dark or bloody
stools, vomiting blood, red eyes from swollen blood vessels, red spots on the skin from subcutaneous bleeding, maculopapular rash,
purpura, and bleeding internally and externally from any orifice, including from the nose, mouth, rectum, genitals or needle puncture sites.
Other secondary symptoms include hypotension , hypovolemia,
tachycardia, severe organ damage as a result of necrosis, and proteinuria. The span of time from onset of symptoms to death is usually between 7 and 14 days. By the second week of infection, patients will either defervesce or undergo systemic multiorgan failure.
Transmission
Among humans, the virus is transmitted by direct contact with infected body fluids, or to a lesser extent, skin or mucus membrane contact. The incubation period can be anywhere from 2 to 21 days, but is generally between 5 and 10 days.
Although airborne transmission between monkeys has been demonstrated in a laboratory, there is very limited evidence for human-to-human airborne transmission in any reported epidemics.
16,17,18 Nurse Mayinga
might represent the only possible case. The means by which she contracted the virus remain uncertain.
So far all epidemics of Ebola have occurred in sub-optimal hospital conditions, where practices of basic hygiene and sanitation are often either luxuries or unknown to caretakers and where disposable needles and
autoclaves are unavailable or too expensive. In modern hospitals with disposable needles and knowledge of basic hygiene and barrier nursing techniques, Ebola rarely spreads on such a large scale.
In the early stages, Ebola may not be highly contagious. Contact with someone in early stages may not even transmit the disease. As the illness progresses, bodily fluids from diarrhoea, vomiting, and bleeding represent an extreme biohazard. Due to lack of proper equipment and hygienic practices, large scale epidemics occur mostly in poor, isolated areas without modern hospitals and/or well-educated medical staff. Many areas where the infectious reservoir exists have just these characteristics. In such environments all that can be done is to immediately cease all needle sharing or use without adequate sterilization procedures, to isolate patients, and to observe strict barrier nursing procedures with the use of a medical rated disposable face mask, gloves, goggles, and a gown at all times. This should be strictly enforced for all medical personnel and visitors.
Treatments
Treatment is primarily supportive and includes minimizing invasive procedures, balancing electrolytes, replacing lost
coagulation factors to help stop bleeding, maintaining oxygen and blood levels, and treating any complicating infections. Despite some initial anecdotal evidence, blood serum from Ebola survivors has been shown to be ineffective in treating the virus.
Interferon is also thought to be ineffective. In monkeys, administration of an inhibitor of coagulation has shown some benefit, protecting 33% of infected animals from a usually 100% lethal infection. In early 2006, scientists at
USAMRIID announced a 75% recovery rate after infecting four
rhesus monkeys with Ebola virus and administering antisense drugs.
Vaccines
Vaccines have been produced for both Ebola and Marburg that were 100% effective in protecting a group of monkeys from the disease. These vaccines are based on either a recombinant Vesicular stomatitis virus or a recombinant
Adenovirus carrying the Ebola spikeprotein on its surface. Early human vaccine efforts, like the one at NIAID in 2003, have so far not reported any successes.
Cultural impact
Ebola has served as a rich source of ideas and plotlines for many forms of entertainment. The infatuation with the virus is likely due to the high mortality rate of its victims, its mysterious nature, and its tendency to cause gruesome bleeding from body orifices.
Much of the representation of the Ebola virus in fiction and the media is considered exaggerated or myth. Many of the stories about Ebola in Preston's book
The Hot Zone is a 1995 non-fiction [i] bio-thriller by Richard Preston [i] describing the origins of ...
are refuted in the book "Level 4: Virus Hunters of the CDC" by Joseph B. McCormick, an employee of the CDC at the time of the early outbreaks. One pervasive myth follows that the virus kills so fast that it has little time to spread. Victims die very soon after contact with the virus. In reality, the incubation time is usually about a week. The average time from onset of early symptoms to death varies in the range 3-21 days, with a mean of 10.1.
Another myth states that the symptoms of the virus are horrifying beyond belief. Victims of Ebola suffer from squirting blood, liquifying flesh, zombie-like faces and dramatic projectile bloody vomiting. In actual fact, only a fraction of Ebola victims have severe bleeding that would be even somewhat dramatic to witness. Approximately 10% of patients suffer some bleeding, but this is often internal or subtle, such as bleeding from the gums. Ebola symptoms are usually limited to extreme exhaustion, vomiting, diarrhoea, abdominal pain, a high fever, headaches and other body pains. The following is an excerpt from an interview with Philippe Calain, M.D. Chief Epidemiologist, CDC Special Pathogens Branch, Kikwit 1995:
- At the end of the disease the patient does not look, from the outside, as horrible as you can read in some books. They are not melting. They are not full of blood. They're in shock, muscular shock. They are not unconscious, but you would say 'obtunded', dull, quiet, very tired. Very few were hemorrhaging. Hemorrhage is not the main symptom. Less than half of the patients had some kind of hemorrhage. But the ones that bled, died.
Other resources
See also
Ebolavirus [i] ...
disease
External links
- – Centers for Disease Control and Prevention
- - a comprehensive overview of the disease
- - Jason Socrates Bardi, Scripps Research Institute
- Brett Russel, retrieved 10 July 2006
- - general information on the virus, retrieved 10 July 2006
Footnotes
References
