Everything about Ebola totally explained
Ebola is the common term for a group of
viruses belonging to genus
Ebola, family
Filoviridae, and for the disease which they cause,
Ebola hemorrhagic fever. The viruses are characterised by a long, filamentous morphology surrounded by a protein/lipid
viral envelope. Ebola viruses are morphologically similar to the
Marburg virus, also in the family
Filoviridae, and share similar disease symptoms. Ebola has caused a number of serious and highly publicized outbreaks since its discovery.
Overview
The Ebola virus first came to notice in 1976 in outbreaks of Ebola
hemorrhagic fever in
Zaire and
Sudan. The strain of Ebola which broke out in Zaire has one of the highest
case fatality rates of any human pathogenic virus, roughly 90%. The strain which broke out later in Sudan has a mortality of approximately 50%. The virus is believed to be initially transmitted to a human via contact with an infected animal host. From the first human infected, the virus is then transmitted by human contact with infected blood and bodily fluids of a diseased person, and by human contact with contaminated medical equipment, such as needles. Both of these infectious mechanisms will occur in clinical (
nosocomial) and non-clinical situations. Due to the high fatality rate, the rapidity of demise, and the often remote areas where infections occur, the potential for widespread epidemic outbreaks is considered low.
Ebola is believed to be a
zoonotic virus as it's currently devastating the populations of lowland
gorillas in Central Africa. As of late 2005, three species of fruit bat were identified as carrying the virus, and didn't exhibit symptoms, and are now believed to be the natural host species, or reservoir, of the virus.
Ebola hemorrhagic fever is potentially lethal and encompasses a range of symptoms including
fever,
vomiting,
diarrhea, generalized pain or malaise, and sometimes
internal and
external bleeding.
Mortality rates are extremely high, with the human case-fatality rate ranging from 50% - 89%, according to viral subtype. The cause of death is usually due to
hypovolemic shock or
organ failure.
Because Ebola is potentially 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 by the
Centers for Disease Control and Prevention. It has the potential to be weaponized for use in
biological warfare and was investigated for that use by both the
Soviet Union and the
United States during the
Cold War. Its effectiveness as a biological-warfare agent is compromised by its extreme deadliness and its level of contagion: a typical outbreak spreads through a small village or hospital, affects the entire population, and then runs out of potential hosts, burning out before it reaches a larger community. Also important is that none of the strains of Ebola known to cause disease in humans have been found to be airborne; only the strain known as Ebola Reston (after the city of Reston, Virginia where it was first identified in Green Monkeys) is believed to be airborne.
Etymology
The virus is named after the
Ebola River Valley in the
Democratic Republic of the Congo (formerly
Zaïre), near the site of the first recognized outbreak in
1976, in a mission run by Flemish nuns.
Structure
Size and shape
Electron micrographs of members of
Ebola virus show them to have the characteristic thread-like structure of a
filovirus. EBOV VP30 is around 288 amino acids long.
Zaïre ebola virus
The
Zaïre Ebola virus 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 Ebola virus than any other strain.
The first outbreak took place on
August 26 1976 in
Yambuku, a town in the north of
Zaïre. The first recorded case was 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 diarrhea,
headache,
dizziness, and trouble breathing. Later, he began bleeding from his nose, mouth, and anus. 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 diarrhea, severe vomiting, and bleeding from the nose, mouth, and anus. 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.
Two nuns working in Yambuku as nurses also died in the same outbreak.
Sudan ebolavirus
Sudan Ebolavirus was the second strand of Ebola reported in 1976. It apparently originated amongst cotton factory workers in Nzara, Sudan. The first case reported was a worker exposed to a potential natural reservoir at the cotton factory. Scientists tested all animals and insects in response to this, however none tested positive for the virus. The carrier is still unknown.
A second case involved a nightclub owner in Nzara,
Sudan. The local hospital, Maridi, tested and attempted to treat the patient; however, nothing was successful, and he died. The hospital didn't advocate safe and practical procedures in sterilizing and disinfecting the medical tools used on the nightclub owner, likely facilitating the spread of the virus in the hospital.
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 neighbouring 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 54% in 1976, 68% in 1979, and 53% in 2000/2001. The average case-fatality rate is 54%.
Reston ebolavirus
First discovered in
November 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 didn't cause any fatalities in humans. Six of the Reston primate handlers tested positive for the virus, two due to previous exposure. The bio-thriller
The Hot Zone was based on this incident.
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 hemorragic fever (SHF) was present in all infected monkeys. No human illness has resulted from these two outbreaks.
Tai (Ivory Coast) ebolavirus
This subtype of Ebola was first discovered amongst
chimpanzees of the Tai Forest in
Côte 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 Zaïre 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, upon which the chimpanzees preyed.
One of the scientists performing the necropsies on the infected chimpanzees contracted Ebola. She developed symptoms similar to
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.
Bundibugyo ebolavirus
On
November 24 2007, the Uganda Ministry of Health confirmed an outbreak of Ebola in the
Bundibugyo District. After confirmation of samples tested by the United States National Reference Laboratories and the
Centers for Disease Control, the World Health Organization has confirmed the presence of a new species of the Ebola virus. On
February 20 2008, the Uganda Ministry officially announced the end of the epidemic in Bundibugyo with the last infected person discharged on
January 8 2008. Ugandan officials confirmed a total of 149 cases of this new Ebola species, with 37 deaths attributed to the strain.
Ebola hemorrhagic fever
Symptoms
Symptoms are varied and often appear suddenly. Initial symptoms include high
fever (at least 38.8°C; 101.8°F),
severe headache,
muscle,
joint, or
abdominal pain,
severe weakness and
exhaustion,
sore throat,
nausea, and
dizziness. Before an
outbreak is suspected, these early symptoms are easily mistaken for
malaria,
typhoid fever,
dysentery,
influenza, or various
bacterial infections, which are all far more common and reliably less fatal.
Ebola may progress to cause more serious symptoms, such as
diarrhea, dark or bloody
feces,
vomiting blood, red eyes due to
Distension and hemorrhage of
sclerotic arterioles,
petechia,
maculopapular rash, and
purpura. Other secondary symptoms include
hypotension (less than 90 mm Hg systolic /60 mm Hg diastolic),
hypovolemia,
tachycardia, organ damage (especially the
kidneys,
spleen, and
liver) as a result of disseminated systemic
necrosis, and
proteinuria. The interior bleeding is caused by a chemical reaction between the virus and the platelets which creates a chemical that will cut cell sized holes into the capillary walls. After 5-7 days the person will die of "a million cuts."
Occasionally,
internal and external hemorrhage from
orifices, such as the nose and mouth may also occur, as well as from incompletely healed injuries such as needle-puncture sites. Ebola virus can affect the levels of
white blood cells and
platelets, disrupting
clotting. Fewer than 50 percent of patients won't develop any hemorrhaging.
Methods of diagnosis of Ebola include testing saliva and urine samples. 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 (the fever will lessen) or undergo systemic multi-organ failure. Mortality rates are generally high, ranging from 50% - 90%.
Filoviruses replicate well in a wide range of organs and cell types such as hepatocytes, epithelial cells, fibroblasts, fibroblastic reticular cells and adrenal cortical cells.
Treatments
Treatment is primarily supportive and includes minimizing invasive procedures, balancing electrolytes since patients are frequently dehydrated, replacing lost
coagulation factors to help stop bleeding, maintaining oxygen and blood levels, and treating any complicating infections. Convalescent Plasma (factors from those who have survived Ebola infection) shows promise as a treatment for the disease . Ribavirin is ineffective.
Interferon is also thought to be ineffective. In monkeys, administration of an inhibitor of coagulation (rNAPc2) has shown some benefit, protecting 33% of infected animals from a usually 100% (for monkeys) lethal infection (unfortunately this inoculation doesn't work on humans). 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 99% 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. The biggest problem with the vaccine is that unless the patient is given it near the onset of the virus (1-4 days after the symptoms begin) then there will be too much damage to the human body to repair, ie: ruptured arteries and capillaries, vomiting, and other symptoms which may still cause enough harm to kill or seriously traumatize the patient.
Viral reservoirs
Despite numerous studies, the wildlife reservoir of
Ebolavirus hasn't been identified. Between 1976 and 1998, from 30,000 mammals, birds, reptiles, amphibians, and arthropods sampled from outbreak regions, no
Ebolavirus was detected apart from some genetic material found in six rodents (
Mus setulosus and
Praomys species) and a
shrew (
Sylvisorex ollula) collected from the
Central African Republic in 1998.
Ebolavirus was detected in the carcasses of
gorillas, chimpanzees and
duikers during outbreaks in 2001 and 2003 (the carcasses were the source of the initial human infections) but the high mortality from infection in these species precludes them from acting as reservoirs.. Bats were known to reside in the cotton factory in which the index cases for the 1976 and 1979 outbreaks were employed and have also been implicated in Marburg infections in 1975 and 1980. The absence of clinical signs in these bats is characteristic of a reservoir species. In 2002-03, a survey of 1,030 animals from
Gabon and the
Republic of the Congo including 679 bats found
Ebolavirus RNA in 13
fruit bats (
Hyspignathus monstrosus, Epomops franquetti and Myonycteris torquata). Bats are also known to be the reservoirs for a number of related viruses including
Nipah virus,
Hendra virus and
lyssaviruses.
Weaponization
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.
Ebola shows potential as a biological weapon because of its lethality but due to its relatively short incubation period it may be more difficult to spread since it may kill its victim before it has a chance to be transmitted, meaning that it would be hard to spread amongst small populations. However, if an outbreak occurred in a city the effects would likely be devastating.
As a terrorist weapon, Ebola has been considered by members of
Japan's
Aum Shinrikyo cult, whose leader,
Shoko Asahara led about 40 members to Zaire in 1992 under the guise of offering medical aid to Ebola victims in what was presumably an attempt to acquire a sample of the virus.
Recent outbreaks
As of
August 30,
2007, 103 people (100 adults and three children) were infected by a suspected hemorrhagic fever outbreak in the village of
Mweka, Democratic Republic of the Congo (DRC). The outbreak started after the funerals of two village chiefs, and 217 people in four villages fell ill. The
World Health Organization sent a team to take blood samples for analysis and confirmed that many of the cases are the result of the Ebola virus . The Congo's last major Ebola epidemic killed 245 people in 1995 in
Kikwit, about 200
miles from the source of the Aug. 2007 outbreak.
On
November 30,
2007, the
Uganda Ministry of Health confirmed an outbreak of Ebola in the
Bundibugyo District. After confirmation of samples tested by the United States National Reference Laboratories and the Centers for Disease Control, the World Health Organization confirmed the presence of a new species of the Ebola virus. The epidemic came to an official end on February 20, 2008. 149 cases of this new strain were reported and 37 of those led to deaths.
Life Cycle
- Virus attaches to host receptors through the GP (glycoprotein) surface peplomer and is endocytosed into vesicles in the host cell.
- Fusion of virus membrane with the vesicle membrane occurs; nucleocapsid is released into the cytoplasm.
- The encapsidated, negative-sense genomic ssRNA is used as a template for the synthesis (3' - 5') of polyadenylated, monocistronic mRNAs.
- Translation of the mRNA into viral proteins occurs using the host cell's machinery.
- Post-translational processing of viral proteins occurs. GP0 (glycoprotein precursor) is cleaved to GP1 and GP2, which are heavily glycosylated. These two molecules assemble, first into heterodimers, and then into trimers to give the surface peplomers. SGP (secreted glycoprotein) precursor is cleaved to SGP and delta peptide, both of which are released from the cell.
- As viral protein levels rise, a switch occurs from translation to replication. Using the negative-sense genomic RNA as a template, a complementary +ssRNA is synthesized; this is then used as a template for the synthesis of new genomic (-)ssRNA, which is rapidly encapsidated.
- The newly-formed nucleocapsides and envelope proteins associate at the host cell's plasma membrane; budding occurs, and the virions are released.
Cultural impact
Ebola and Marburg have 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 bodily orifices.
In the movie
Outbreak, the virus looks the same as the Ebola virus. In fact, the entire movie's made up virus "Motaba" is based very closely on Ebola. The symptoms and area of infection had relevance.
The Rage Virus from the movies
28 Days Later and
28 Weeks Later is a modified version of the Ebola virus.
In the book
Outbreak, by
Robin Cook, the Ebola virus is used in name as a possible weapon, with criminal intent. This book is different from the movie
Outbreak of the same name
Biological warfare using airborne modifications of the Ebola virus was a main theme in
Tom Clancy's novels
Executive Orders and
Rainbow Six.
In
Resident Evil, the T-Virus is a modified version of the Progenitor Virus, created by inserting it with Ebola genes.
features a biological weapon consisting of a greatly accelerated form of Ebola, capable of causing death within minutes.
Much of the representation of the Ebola virus in fiction and the media is considered
exaggerated or myth. 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. Although this would prevent the transmission of the virus to many people, it's still enough time for some people to catch the disease.
Another myth states that the virus causes patients to melt, liquefy, or bleed profusely. In depictions of this type, victims of Ebola suffer from squirting blood, liquefying flesh,
zombie-like faces and dramatic projectile bloody vomiting, at times, from even recently deceased. In actual fact, only a fraction of Ebola victims have severe bleeding, and most accounts of the course of the disease describe patients as dull and lethargic. 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, diarrhea, 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 1996:
Further Information
Get more info on 'Ebola'.
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