Ebola is the virus Ebolavirus (EBOV), a viral genus, and the disease Ebola hemorrhagic fever (EHF), a viral hemorrhagic fever (VHF). There are four recognised species within the ebolavirus genus, which have a number specific strains. The ''Zaire virus'' is the type species, which is also the first discovered and the most lethal. Electron micrographs show long filaments, characteristic of the Filoviridae viral family. The virus interferes with the endothelial cells lining the interior surface of blood vessels and coagulation. As the blood vessel walls become damaged and the platelets are unable to coagulate, patients succumb to hypovolemic shock. Ebola is transmitted through bodily fluids. Skin and conjunctiva exposure may also lead to transmission, but to a lesser extent. Ebola first emerged in 1976 in Zaire. It, however, remained largely obscure until 1989 with a widely publicized outbreak in Reston.
The virus is named after the Ebola River Valley in the Democratic Republic of the Congo (formerly Zaire), which is near the site of the first recognized outbreak in 1976, in a mission hospital run by Flemish nuns.
The genera ''Ebolavirus'' and ''Marburgvirus'' was originally classified as the species of the now nonexistent ''Filovirus'' genus. In March 1998, the Vertebrate Virus Subcommittee proposed in the International Committee on Taxonomy of Viruses (ICTV) to change the ''Filovirus'' genus to the ''Filoviridae'' family with two specific genera: ''Ebola-like viruses'' and ''Marburg-like viruses''. This proposal was implemented in Washington, D.C. as of April 2001 and in Paris as of July 2002. In 2000, another proposal was made in Washington, D.C. to change the "-like viruses" to "-virus" resulting in today's ''Ebolavirus'' and ''Marburgvirus''.
Rates of genetic change are one hundred times slower than Influenza A in humans, but on the same magnitude of that of Hepatitis B. Using these rates, the Ebolavirus and Marburgvirus are estimated to have diverged several thousand years ago.
- Zaire virus (ZEBOV) : The ''Zaire virus'', formerly named ''Zaire Ebola Virus'', has the highest case-fatality rate, up to 90% in some epidemics, with an average case fatality rate of approximately 83% over 27 years. There have been more outbreaks of ''Zaire ebolavirus'' than any other species. The first outbreak took place on 26 August 1976 in Yambuku. Mabalo Lokela, a 44-year-old schoolteacher, became the first recorded case. The symptoms resembled malaria, and subsequent patients received quinine. 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 lack of barrier nursing and the traditional burial preparation method, which involves washing and gastrointestinal tract cleansing.
- Sudan ebolavirus (SEBOV) : The virus was the second species of Ebola emerging simultaneous with the ''Zaire virus''. It was believed to have originated amongst cotton factory workers in Nzara, Sudan, with the first case reported as a worker exposed to a potential natural reservoir. Scientists tested all animals and insects in response to this; however, none tested positive for the virus. The carrier is still unknown. The lack of barrier nursing facilitated the spread of the disease. The most recent outbreak occurred in May 2004. 20 confirmed cases were reported in Yambio County, Sudan, with five deaths resulting. The average fatality rates for were 54% in 1976, 68% in 1979, and 53% in 2000 and 2001.
- Reston ebolavirus (REBOV) : Discovered during an outbreak of Simian hemorrhagic fever virus (SHFV) in crab-eating macaques from Hazleton Laboratories (now Covance) in 1989. Since the initial outbreak in Reston, it has emerged in the Philippines, Siena Italy, Texas, and among pigs in the Philippines. Despite its status as a Level-4 organism, it is non-pathogenic to humans however hazardous in monkeys.
- Cote d'Ivoire ebolavirus (CIEBOV) : Also referred to as ''Ivory Coast ebolavirus'' and ''Tai ebolavirus'', it was first discovered among chimpanzees from the Tai Forest in Côte d'Ivoire, Africa on 1 November 1994. Necropsies showed blood within the heart to be brown, no obvious marks were seen on the organs, and one necropsy displayed lungs filled with blood. Studies of tissues taken from the chimpanzees showed results similar to human cases during the 1976 Ebola outbreaks in Zaire and Sudan. As 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 those of dengue fever approximately a week after the necropsy, and was transported to Switzerland for treatment. She was discharged from hospital after two weeks and had 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 CDC, the World Health Organization confirmed the presence of the new species. On 20 February 2008, the Uganda Ministry officially announced the end of the epidemic in Bundibugyo with the last infected person discharged on 8 January 2008. Ugandan officials confirmed a total of 149 cases of this new Ebola species, with 37 deaths attributed to the strain (24.83%).
Electron micrographs of members of genus ''Ebolavirus'' show them to have the characteristic thread-like structure of a filovirus. EBOV VP30 is around 288 amino acids long. The virions are tubular in general form but variable in overall shape and may appear as the classic shepherd's crook or eyebolt, as a ''U'' or a ''6'', or coiled, circular, or branched. However, laboratory purification techniques, such as centrifugation, may contribute to some of these. Virions are generally 80 nm in diameter with a lipid bilayer anchoring the glycoprotein which projects 7 to 10 nm long spikes from its surface. They are of variable length, typically around 800 nm, but may be up to 1000 nm long. 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 80 nm and contains a central channel of 20–30 nm in diameter. Virally-encoded glycoprotein (GP) 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.
Each virion contains one molecule of linear, single-stranded, negative-sense RNA, 18,959 to 18,961 nucleotides in length. The 3′ terminus is not polyadenylated and the 5′ end is not capped. It was found that 472 nucleotides from the 3' end and 731 nucleotides from the 5' end are sufficient for replication. 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 genomes 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.
Viruses do not grow through cell division, because they are not cells (acellular); instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble in the cell.
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'') and one shrew (''Sylvisorex ollula'') collected from the Central African Republic. The virus was detected in the carcasses of gorillas, chimpanzees, and duikers during outbreaks in 2001 and 2003, which later became the source of human infections. However, the high mortality from infection in these species makes them unlikely as a natural reservoir. Bats were known to reside in the cotton factory in which the index cases for the 1976 and 1979 outbreaks were employed, and they 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 a 2002–2003 survey of 1,030 animals which included 679 bats from Gabon and the Republic of the Congo, 13 fruit bats were found to contain ''Ebolavirus'' RNA. As of 2005, three fruit bat species (''Hypsignathus monstrosus'', ''Epomops franqueti'', and ''Myonycteris torquata'') have been identified as carrying the virus while remaining asymptomatic. They are believed to be a natural host species, or reservoir, of the virus.
Reston ebolavirus—unlike its African counterparts—is non-pathogenic, non-lethal in humans. It has been documented in chimpanzees and swine; although the high mortality among monkeys, and its recent emergence in swine, makes them unlikely natural reservoirs.
Bats drop partially eaten fruits and pulp, terrestrial mammals such as gorillas and duikers feed on these fallen fruits. This chain of events forms a possible indirect means of transmission from the natural host to animal populations, which have lead to research towards viral shedding in the saliva of bats. Fruit production, animal behavior, and other factors vary at different times and places which may trigger outbreaks among animal populations. Transmission between natural reservoirs and humans are rare, and outbreaks are usually traceable to a single index case where an individual has handled the carcass of gorilla, chimpanzee, or duiker. The virus then spreads person-to-person, especially within families, hospitals, and during some mortuary rituals where contact among individuals becomes more likely.
The virus has been confirmed to be transmitted through body fluids. Transmission through oral exposure and through conjunctiva exposure is likely, which have been confirmed in non-human primates. Filoviruses are not naturally transmitted by aerosol. They are, however, highly infectious as breathable 0.8-1.2 micron droplets in laboratory conditions; because of this potential route of infection, these viruses have been classified as Category A biological weapons.
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 has never spread on a large scale. In isolated settings such as a quarantined hospital or a remote village, most victims are infected shortly after the first case of infection is present. The quick onset of symptoms from the time the disease becomes contagious in an individual makes it easy to identify sick individuals and limits an individual's ability to spread the disease by traveling. Because bodies of the deceased are still infectious, some doctors had to take measures to properly dispose dead bodies in a safe manner despite local traditional burial rituals.
Outbreaks of Ebola, with the exception of Reston ebolavirus, have mainly been restricted to Africa. The virus often consumes the population, governments and individuals quickly respond to quarantine the area, and the lack of roads and transportation—helps to contain the outbreak.
Vaccines have successfully protected non-human primates, however the six months needed to complete immunization made it impractical in an epidemic. To resolve this, in 2003 a vaccine using an adenoviral (ADV) vector carrying the Ebola spike protein was tested on crab-eating macaques. The monkeys were challenged with the virus twenty-eight days later, and remained resistant. In 2005 a vaccine based on attenuated recombinant vesicular stomatitis virus (VSV) vector carrying either the Ebola glycoprotein or Marburg glycoprotein successfully protected non-human primates, opening clinical trials in humans. By October the study completed the first human trial giving three vaccinations over three months showing capability of safely inducing an immune response. Individuals were followed for a year, and in 2006 a study testing a faster-acting, single shot vaccine began. This study was completed in 2008.
The incubation period can range from 2 to 21 days but is generally 5–10 days. 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, exhaustion, sore throat, nausea, dizziness, internal and external bleeding. 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 (low blood pressure), hypovolemia, and tachycardia. The interior bleeding is caused by a reaction between the virus and the platelets that produces a chemical that will cut cell-size holes into the capillary walls.
On occasion, 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. More than 50% of patients will develop some degree of hemorrhaging.
Methods of diagnosis of Ebola include testing saliva and urine samples. Ebola is diagnosed with an Enzyme-Linked ImmunoSorbent Assay (ELISA) test. This diagnosis method has produced potentially ambiguous results during non-outbreak situations. Following Reston, and in an effort to evaluate the original test, Dr. Karl Johnson of the CDC tested San Blas Indians from Central America, who have no history of Ebola infection, and observed a 2% positive result. Other researchers later tested sera from Native Americans in Alaska and found a similar percentage of positive results. To combat the false positives, a more complex test based on the ELISA system was developed by Tom Kzaisek at USAMRIID, which was later improved with Immunofluorescent antibody analysis (IFA). It was however not used during the serosurvey following Reston. These tests are not commercially available.
There is no standard treatment for Ebola hemorrhagic fever. Treatment is primarily supportive and includes minimizing invasive procedures, balancing electrolytes, and, 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 that 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 (however, this inoculation does not work on humans). In early 2006, scientists at USAMRIID announced a 75% recovery rate after infecting four rhesus monkeys with ''Ebolavirus'' and administering Morpholino antisense drugs. Development of improved Morpholino antisense conjugated with cell penetrating peptides is ongoing.
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. The span of time from onset of symptoms to death is usually between 2 and 21 days. By the second week of infection, patients will either defervesce (the fever will lessen) or undergo systemic multi-organ failure. Mortality rates are typically high, with the human case-fatality rate ranging from 50–89%, depending on the species or viral strain. The cause of death is usually due to hypovolemic shock or organ failure.
Ebola In Other Animals
Outbreaks of Ebola among human populations generally result from handling infected wild animal carcasses. Declines in animal populations generally precede outbreaks among human populations. These have led to in 2003 surveillance of animal populations in order to predict and prevent Ebola outbreaks.
Outbreaks of Ebola have shown a 88% observed decline in chimpanzee populations in 2003.
Reston ebolavirus, which has not previous outbreak in Africa and is non-pathogenic in humans, have recently been recognized among swine populations in the Philippines; this discovery suggest that the virus has been circulating since and possibly before the initial discovery of Reston ebolavirus in 1989 among monkeys.
Ebolavirus first emerged in 1976 in outbreaks of Ebola hemorrhagic fever in Zaire and Sudan. The strain of Ebola that broke out in Zaire has one of the highest case fatality rates of any human pathogenic virus, roughly 90%, with case-fatality rates at 88% in 1976, 59% in 1994, 81% in 1995, 73% in 1996, 80% in 2001-2002, and 90% in 2003. The strain that broke out later in Sudan has a case fatality rate of around 50%.
While investigating an outbreak of Simian hemorrhagic fever (SHFV) in November 1989, an electron microscopist from USAMRIID discovered filoviruses similar in appearance to Ebola in tissue samples taken from Crab-eating Macaque imported from the Philippines to Hazleton Laboratories Reston. Due to the lethality of the suspected and previously obscure virus, the investigation quickly attracted attention.
Blood samples were taken from 178 animal handlers during the incident. Of those, six animal handlers eventually seroconverted. When the handlers failed to become ill, the CDC concluded that the virus had a very low pathogenicity to humans.
Both the Philippines and the United States had no previous cases of infection, and upon further isolation it was concluded to be another species of Ebola or a new filovirus of Asian origin, and named ''Reston ebolavirus'' (REBOV) after the location of the incident.
In 1992, members of Japan's Aum Shinrikyo cult considered using Ebola as a terror weapon. Their leader, Shoko Asahara, led about forty members to Zaire under the guise of offering medical aid to Ebola victims in a presumed attempt to acquire a virus sample. Because of the virus's high morbidity, it is a potential agent for biological warfare.
Given the lethal nature of Ebola, and, since no approved vaccine or treatment is available, it 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. The effectiveness as a biological weapon is compromised by its rapid lethality as patients quickly die off before they are capable of effectively spreading the contagion.
The attention gathered from the outbreak in Reston prompted an increase in public interest, leading to the publication of numerous fictional works.
The BBC reports that in a study that frequent outbreaks of ebola may have resulted in the deaths of 5,000 gorillas.
As of August 30, 2007, 103 people (100 adults and three children) were infected by a suspected hemorrhagic fever outbreak in the village of Kampungu, Democratic Republic of the Congo. 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 ''Ebolavirus''. The Congo's last major Ebola epidemic killed 245 people in 1995 in Kikwit, about 200 miles from the source of the August 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 ''Ebolavirus'' which is now tentatively named Bundibugyo. The epidemic came to an official end on February 20, 2008. While it lasted, 149 cases of this new strain were reported, and 37 of those led to deaths.
An International Symposium to explore the environment and filovirus, cell system and filovirus interaction, and filovirus treatment and prevention is to be held at Centre Culturel Français, Libreville, Gabon during March 2008. The virus appeared in southern Western Kasai Province on November 27, 2008, and blood and stool samples were sent to laboratories in Gabon and South Africa for identification.
A mysterious disease that has killed eleven and infected twenty-one people in southern Democratic Republic of Congo has been identified as the Ebola virus. Doctors Without Borders reports 11 deaths as of Monday 29 December 2008 in the Western Kasai province of the Democratic Republic of Congo. It is said that a further 24 cases are being treated. In January 2009, Angola closed down part their border with DRC to prevent the spread of ebola.
On March 12, 2009, an unidentified 45-year-old female scientist from Germany accidentally pricked her finger with a needle used to inject Ebola into lab mice. She was given an experimental vaccine never before used on humans. Since the peak period for an outbreak during the 21-day Ebola incubation period has passed as of April 2, 2009, she has been declared healthy and safe. It remains unclear whether or not she was ever actually infected with the virus.
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Last Updated: Feb 1, 2011