Ebola virus disease

Ebola virus disease
Classification and external resources

1976 photograph of two nurses standing in front of Mayinga N., a patient with Ebola virus disease; she died only a few days later because of severe internal bleeding and hemorrhaging.
ICD-10 A98.4
ICD-9 065.8
DiseasesDB 18043
MedlinePlus 001339
eMedicine med/626
MeSH D019142

Ebola virus disease (EVD) (or more commonly, Ebola hemorrhagic fever (EHF)) is the name for the human disease which may be caused by any of the five known ebolaviruses. These five viruses are: Bundibugyo Ebolavirus (BEBOV or BDBV), Zaire Ebolavirus (ZEBOV or ambiguously, EBOV), Sudan Ebolavirus (SEBOV or SUDV), Reston Ebolavirus (REBOV) and Taï Forest virus (TAFV, formerly and more commonly Cote d'Ivoire Ebolavirus (Ivory Coast Ebolavirus, CIEBOV)). EVD is a viral hemorrhagic fever (VHF), and is clinically nearly indistinguishable from Marburg virus disease (MVD).

Contents

Classification

The genera Ebolavirus and Marburgvirus were originally classified as the species of the now-obsolete 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.[1]

Rates of genetic change are one hundred times slower than influenza A in humans, but on the same magnitude as those of hepatitis B. Extrapolating backwards using these rates indicates that Ebolavirus and Marburgvirus diverged several thousand years ago.[2] However, paleoviruses (genomic fossils) of filoviruses (Filoviridae) found in mammals indicate that the family itself is at least tens of millions of years old.[3]Viral fossils that are closely related to ebolaviruses have been found in the genome of the Chinese hamster.[4]

The five characterised Ebola species are:

Zaire ebolavirus (ZEBOV) 
Also known simply as the Zaire virus, ZEBOV 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 of any other species. The first outbreak took place on 26 August, 1976 in Yambuku.[5] Mabalo Lokela, a 44‑year-old schoolteacher, became the first recorded case. The symptoms resembled malaria, and subsequent patients received quinine. Transmission has been attributed to reuse of unsterilized needles and close personal contact.
Sudan ebolavirus (SEBOV) 
Like the Zaire virus, SEBOV emerged in 1976; it was at first assumed to be identical with the Zaire species.[6] SEBOV is believed to have broken out first amongst cotton factory workers in Nzara, Sudan, with the first case reported as a worker exposed to a potential natural reservoir. Scientists tested local animals and insects in response to this; however, none tested positive for the virus. The carrier is still unknown. The lack of barrier nursing (or "bedside isolation") 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 SEBOV 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, Virginia, it has since been found in non-human primates in Pennsylvania, Texas and Siena, Italy. In each case, the affected animals had been imported from a facility in the Philippines,[7] where the virus has also infected pigs.[8] Despite its status as a Level‑4 organism and its apparent pathogenicity in monkeys, REBOV did not cause disease in exposed human laboratory workers.[9]
Côte d'Ivoire ebolavirus (CIEBOV)
Also referred to as Taï Forest ebolavirus and by the English place name, "Ivory Coast", it was first discovered among chimpanzees from the Taï Forest in Côte d'Ivoire, Africa, in 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, many tested positive for Ebola using molecular techniques. The source of the virus 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.[10]
Bundibugyo ebolavirus
On November 24, 2007, the Uganda Ministry of Health confirmed an outbreak of Ebolavirus 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.[11] An epidemiological study conducted by WHO and Uganda Ministry of Health scientists determined there were 116 confirmed and probable cases the new Ebola species, and that the outbreak had a mortality rate of 34% (39 deaths).[12]

Signs and symptoms

EVD/EHF is clinically indistinguishable from Marburg virus disease (MVD), and it can also easily be confused with many other diseases prevalent in Equatorial Africa, such as other viral hemorrhagic fevers, falciparum malaria, typhoid fever, shigellosis, rickettsial diseases, cholera, gram-negative septicemia or EHEC enteritis. The most detailed studies on the frequency, onset, and duration of EVD clinical signs and symptoms were performed during the 1995 outbreak in Kikwit, Zaire (EBOV)[13][14][15] and the 2007-2008 outbreak in Bundibugyo, Uganda (BDBV).[16][17] The mean incubation period, best calculated currently for EVD outbreaks due to EBOV infection, is 12.7 days (standard deviation = 4.3 days), but can be as long as 25 days.[18] EVD begins with a sudden onset of an influenza-like stage characterized by general malaise, fever with chills, arthralgia and myalgia, and chest pain. Nausea is accompanied by abdominal pain, anorexia, diarrhea, and vomiting. Respiratory tract involvement is characterized by pharyngitis with sore throat, cough, dyspnea, and hiccups.

The central nervous system is affected as judged by the development of severe headaches, agitation, confusion, fatigue, depression, seizures, and sometimes coma. The circulatory system is also frequently involved, with the most prominent signs being edema and conjunctivitis. Hemorrhagic symptoms are infrequent (fewer than 10% of cases for most serotypes), (the reason why Ebola hemorrhagic fever (EHF) is a misnomer) and include hematemesis, hemoptysis, melena, and bleeding from mucous membranes (gastroinestinal tract, nose, vagina and gingiva).

Cutaneous presentation may include: maculopapular rash, petechiae, purpura, ecchymoses, and hematomas (especially around needle injection sites). Development of hemorrhagic symptoms is generally indicative of a negative prognosis. However, contrary to popular belief, hemorrhage does not lead to hypovolemia and is not the cause of death (total blood loss is low except during labor). Instead, death occurs due to multiple organ dysfunction syndrome (MODS) due to fluid redistribution, hypotension, disseminated intravascular coagulation, and focal tissue necroses.[19][20][21][22][23][13][14][15][24][16][17][25][26][27][28]

Causes

Main article: Ebolavirus

EVD is caused by four of five viruses classified in the genus Ebolavirus, family Filoviridae, order Mononegavirales: Bundibugyo virus (BDBV), Ebola virus (EBOV), Sudan virus (SUDV), and Taï Forest virus (TAFV). The fifth virus, Reston virus (RESTV), is thought to be apathogenic for humans and therefore not discussed here.

Genus Ebolavirus: species and their EVD-causing viruses
Species name Virus name (Abbreviation)
Bundibugyo ebolavirus (accepted)[29] Bundibugyo virus (BDBV; previously BEBOV)
Sudan ebolavirus Sudan virus (SUDV; previously SEBOV)
Taï Forest ebolavirus Taï Forest virus (TAFV; previously CIEBOV)
Zaire ebolavirus* Ebola virus (EBOV; previously ZEBOV)

Table legend: "*" denotes the type species and "accepted" refers to a taxon that has been accepted by the Executive Committee of the ICTV but that has yet to be ratified.

Risk factors

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 traces found in six rodents (Mus setulosus and Praomys) and one shrew (Sylvisorex ollula) collected from the Central African Republic.[30][31] Traces of EBOV were detected in the carcasses of gorillas and chimpanzees during outbreaks in 2001 and 2003, which later became the source of human infections. However, the high lethality from infection in these species makes them unlikely as a natural reservoir.[30]

Plants, arthropods, and birds have also been considered as possible reservoirs; however, bats are considered the most likely candidate.[32] 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 virus infections in 1975 and 1980.[30]Of 24 plant species and 19 vertebrate species experimentally inoculated with EBOV, only bats became infected.[33]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 EBOV RNA fragments.[34] As of 2005, three types of fruit bats (Hypsignathus monstrosus, Epomops franqueti, and Myonycteris torquata) have been identified as being in contact with EBOV. They are now suspected to represent the EBOV reservoir hosts.[35]

The existence of integrated genes of filoviruses in some genomes of small rodents, insectivorous bats, shrews, tenrecs, and marsupials indicates a history of infection with filoviruses in these groups as well.[3]However, it has to be stressed that infectious ebolaviruses have not yet been isolated from any nonhuman animal.

Bats drop partially eaten fruits and pulp, then 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 led 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.[36] 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.[37] The virus then spreads person-to-person, especially within families, hospitals, and during some mortuary rituals where contact among individuals becomes more likely.[38]

The virus has been confirmed to be transmitted through body fluids. Transmission through oral exposure and through conjunctiva exposure is likely[39] and has been confirmed in non-human primates.[40] Filoviruses are not naturally transmitted by aerosol. They are, however, highly infectious as breathable 0.8–1.2 micrometre droplets in laboratory conditions;[41] because of this potential route of infection, these viruses have been classified as Category A biological weapons.[42]

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.[43]

Virology

Main article: Ebola virus

Genome

Like all mononegaviruses, ebolavirions contain linear nonsegmented, single-stranded, non-infectious RNA genomes of negative polarity that possesses inverse-complementary 3' and 5' termini, do not possess a 5' cap, are not polyadenylated, and are not covalently linked to a protein.[44] Ebolavirus genomes are approximately 19 kilobase pairs long and contain seven genes in the order 3'-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR.[45] The genomes of the five different ebolaviruses (BDBV, EBOV, RESTV, SUDV, and TAFV) differ in sequence and the number and location of gene overlaps.

Structure

Like all filoviruses, ebolavirions are filamentous particles that may appear in the shape of a shepherd's crook or in the shape of a "U" or a "6", and they may be coiled, toroid, or branched.[45] Ebolavirions are generally 80 nm in width, but vary somewhat in length. In general, the median particle length of ebolaviruses ranges from 974–1,086 nm (in contrast to marburgvirions, whose median particle length was measured to be 795–828 nm), but particles as long as 14,000 nm have been detected in tissue culture.[46]. Ebolavirions consist of seven structural proteins. At the center is the helical ribonucleocapsid, which consists of the genomic RNA wrapped around a polymer of nucleoproteins (NP). Associated with the ribonucleoprotein is the RNA-dependent RNA polymerase (L) with the polymerase cofactor (VP35) and a transcription activator (VP30). The ribonucleoprotein is embedded in a matrix, formed by the major (VP40) and minor (VP24) matrix proteins. These particles are surrounded by a lipid membrane derived from the host cell membrane. The membrane anchors a glycoprotein (GP1,2) that projects 7 to 10 nm spikes away from its surface. While nearly identical to marburgvirions in structure, ebolavirions are antigenically distinct.

Replication

The ebolavirus life cycle begins with virion attachment to specific cell-surface receptors, followed by fusion of the virion envelope with cellular membranes and the concomitant release of the virus nucleocapsid into the cytosol. The virus RdRp partially uncoats the nucleocapsid and transcribes the genes into positive-stranded mRNAs, which are then translated into structural and nonstructural proteins. Ebolavirus L binds to a single promoter located at the 3' end of the genome. Transcription either terminates after a gene or continues to the next gene downstream. This means that genes close to the 3' end of the genome are transcribed in the greatest abundance, whereas those toward the 5' end are least likely to be transcribed. The gene order is therefore a simple but effective form of transcriptional regulation. The most abundant protein produced is the nucleoprotein, whose concentration in the cell determines when L switches from gene transcription to genome replication. Replication results in full-length, positive-stranded antigenomes that are in turn transcribed into negative-stranded virus progeny genome copies. Newly synthesized structural proteins and genomes self-assemble and accumulate near the inside of the cell membrane. Virions bud off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles then infect other cells to repeat the cycle.[47]

Pathophysiology

Endothelial cells, mononuclear phagocytes, and hepatocytes are the main targets of infection. After infection, in a secreted glycoprotein (sGP) the Ebola virus glycoprotein (GP) is synthesized. Ebola replication overwhelms protein synthesis of infected cells and host immune defenses. The GP forms a trimeric complex, which binds the virus to the endothelial cells lining the interior surface of blood vessels. The sGP forms a dimeric protein which interferes with the signaling of neutrophils, a type of white blood cell, which allows the virus to evade the immune system by inhibiting early steps of neutrophil activation. These white blood cells also serve as carriers to transport the virus throughout the entire body to places such as the lymph nodes, liver, lungs, and spleen.[48] The presence of viral particles and cell damage resulting from budding causes the release of cytokines (specifically TNF-α, IL-6, IL-8, etc.), which are the signaling molecules for fever and inflammation. The cytopathic effect, from infection in the endothelial cells, results in a loss of vascular integrity. This loss in vascular integrity is furthered with synthesis of GP, which reduces specific integrins responsible for cell adhesion to the inter-cellular structure, and damage to the liver, which leads to coagulopathy.[49]

Diagnosis

EVD is clinically indistinguishable from Marburg virus disease (MVD), and it can also easily be confused with many other diseases prevalent in Equatorial Africa, such as other viral hemorrhagic fevers, falciparum malaria, typhoid fever, shigellosis, rickettsial diseases such as typhus, cholera, gram-negative septicemia, borreliosis such as relapsing fever or EHEC enteritis. Other infectious diseases that ought to be included in the differential diagnosis include leptospirosis, scrub typhus, plague, Q fever, candidiasis, histoplasmosis, trypanosomiasis, visceral leishmaniasis, hemorrhagic smallpox, measles, and fulminant viral hepatitis. Non-infectious diseases that can be confused with EVD are acute promyelocytic leukemia, hemolytic uremic syndrome, snake envenomation, clotting factor deficiencies/platelet disorders, thrombotic thrombocytopenic purpura, hereditary hemorrhagic telangiectasia, Kawasaki disease, and even warfarin intoxication.[50][51][52][53]

The most important indicator that may lead to the suspicion of EVD at clinical examination is the medical history of the patient, in particular the travel and occupational history (which countries were visited?) and the patient's exposure to wildlife (exposure to bats, bat excrement, nonhuman primates?). EVD can be confirmed by isolation of ebolaviruses from or by detection of ebolavirus antigen or genomic or subgenomic RNAs in patient blood or serum samples during the acute phase of EVD. Ebolavirus isolation is usually performed by inoculation of grivet kidney epithelial Vero E6 or MA-104 cell cultures or by inoculation of human adrenal carcinoma SW-13 cells, all of which react to infection with characteristic cytopathic effects.[54][55] Filovirions can easily be visualized and identified in cell culture by electron microscopy due to their unique filamentous shapes, but electron microscopy cannot differentiate the various filoviruses alone despite some overall length differences.[46] Immunofluorescence assays are used to confirm ebolavirus presence in cell cultures. During an outbreak, virus isolation and electron microscopy are most often not feasible options. The most common diagnostic methods are therefore RT-PCR[56][57][58][59][60][61][62] in conjunction with antigen-capture ELISA[63][64][65][66][67] which can be performed in field or mobile hospitals and laboratories. Indirect immunofluorescence assays (IFAs) are not used for diagnosis of EVD in the field anymore.

Prevention

Ebolaviruses are highly infectious, but not very contagious.

As an outbreak of ebola progresses, bodily fluids from diarrhea, vomiting, and bleeding represent a hazard. Due to lack of proper equipment and hygienic practices, large-scale epidemics occur mostly in poor, isolated areas without modern hospitals 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, isolate patients, and observe strict barrier nursing procedures with the use of a medical-rated disposable face mask, gloves, goggles, and a gown at all times, strictly enforced for all medical personnel and visitors.[68]The aim of all of these techniques is to avoid any person’s contact with the blood or secretions of any patient, including those who are deceased.[69]

Vaccines have successfully protected nonhuman 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 28 days later, and remained resistant.[70] In 2005, a vaccine based on attenuated recombinant vesicular stomatitis virus (VSV) vector carrying either the Ebola glycoprotein or Marburg glycoprotein successfully protected nonhuman primates,[71] opening clinical trials in humans.[72] 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.[73]

There are currently no Food and Drug Administration-approved vaccines for the prevention of EVD. Many candidate vaccines have been developed and tested in various animal models.[74][75][76]Of those, the most promising ones are DNA vaccines[77] or are based on adenoviruses,[70] vesicular stomatitis Indiana virus (VSIV)[78][79][80] or filovirus-like particles (VLPs)[81] as all of these candidates could protect nonhuman primates from ebolavirus-induced disease. DNA vaccines, adenovirus-based vaccines, and VSIV-based vaccines have entered clinical trials.[82][83][73][84]

Contrary to popular belief, ebolaviruses are not transmitted by aerosol during natural EVD outbreaks. Due to the absence of an approved vaccine, prevention of EVD therefore relies predominantly on behavior modification, proper personal protective equipment, and sterilization/disinfection.

In 6 December 2011 the development of a successful vaccine against Ebola for mice were reported. Unlike the predecessors it can be freeze-dried and thus stored for long periods in wait for an outbreak. The research will be presented in Proceedings of National Academy of Spieces. [85]

In endemic zones

The natural maintenance hosts of ebolaviruses remain to be identified. This means that primary infection cannot necessarily be prevented in nature. The avoidance of EVD risk factors, such as contact with nonhuman primates or bats, is highly recommended, but may not be possible for inhabitants of tropical forests or people dependent on nonhuman primates as a food source.

During outbreaks

Since ebolaviruses do not spread via aerosol, the most straightforward prevention method during EVD outbreaks is to avoid direct (skin-to-skin) contact with patients, their excretions and body fluids, or possibly contaminated materials and utensils. Patients ought to be isolated but still have the right to be visited by family members. Medical staff should be trained and apply strict barrier nursing techniques (disposable face mask, gloves, goggles, and a gown at all times). Traditional burial rituals, especially those requiring embalming of bodies, ought to be discouraged or modified, ideally with the help of local traditional healers.[86]

In the laboratory

Ebolaviruses are World Health Organization Risk Group 4 Pathogens, requiring Biosafety Level 4-equivalent containment. Laboratory researchers have to be properly trained in BSL-4 practices and wear proper personal protective equipment.

Treatment

There is currently no Food and Drug Administration-approved ebolavirus-specific therapy for EVD. Treatment is primarily supportive in nature and includes minimizing invasive procedures, balancing fluids and electrolytes to counter dehydration, administration of anticoagulants early in infection to prevent or control disseminated intravascular coagulation, administration of procoagulants late in infection to control hemorrhaging, maintaining oxygen levels, pain management, and administration of antibiotics or antimycotics to treat secondary infections.[87][88][89] Hyperimmune equine immunoglobulin raised against EBOV has been used in Russia to treat a laboratory worker who accidentally infected herself with EBOV—but the patient died anyway.[28] Experimentally, recombinant vesicular stomatitis Indiana virus (VSIV) expressing the glycoprotein of EBOV or SUDV has been used successfully in nonhuman primate models as post-exposure prophylaxis.[90][91] Such a recombinant post-exposure vaccine was also used to treat a German researcher who accidentally pricked herself with a possibly EBOV-contaminated needle. Treatment might have been successful as she survived. However, actual EBOV infection could never be demonstrated without a doubt.[92] Novel, very promising, experimental therapeutic regimens rely on antisense technology. Both small interfering RNAs (siRNAs) and phosphorodiamidate morpholino oligomers (PMOs) targeting the EBOV genome could prevent disease in nonhuman primates.[93][94]

Prognosis

Prognosis is generally poor (average case-fatality rate of all EVD outbreaks to date = 68%). If a patient survives, recovery may be prompt and complete, or protracted with sequelae, such as orchitis, arthralgia, myalgia, desquamation or alopecia. Ocular manifestations, such as photophobia, hyperlacrimation, iritis, iridocyclitis, choroiditis and blindness have also been described. Importantly, EBOV and SUDV are known to be able to persist in the sperm of some survivors, which could give rise to secondary infections and disease via sexual intercourse.[95][96][97][98][99]

Epidemiology

Distribution of Ebola and Marburg virus in Africa (note that integrated genes from filoviruses have been detected in mammals from the New World as well[3]). (A) Known points of filovirus disease. Projected distribution of ecological niche of: (B) all filoviruses, (C) ebolaviruses, (D) marburgviruses.
For more about specific outbreaks and their descriptions, see List of Ebola outbreaks.

Outbreaks of EVD have mainly been restricted to Africa. The virus often consumes the population. Governments and individuals quickly respond to quarantine the area while the lack of roads and transportation helps to contain the outbreak.[7] EVD was first described after almost simultaneous viral hemorrhagic fever outbreaks occurred in Zaire and Sudan in 1976.[100][101] EVD is believed to occur after an ebolavirus is transmitted to a human index case via contact with an infected animal host. Human-to-human transmission occurs via direct contact with blood or bodily fluids from an infected person (including embalming of a deceased victim) or by contact with contaminated medical equipment such as needles. In the past, explosive nosocomial transmission has occurred in underequipped African hospitals due to the reuse of needles and/or absence of proper barrier nursing. Aerosol transmission has not been observed during natural EVD outbreaks. The potential for widespread EVD epidemics is considered low due to the high case-fatality rate, the rapidity of demise of patients, and the often remote areas where infections occur.

Ebola virus disease (EVD) outbreaks
Year Virus Geographic location Human cases/deaths (case-fatality rate)
1976 SUDV Juba, Maridi, Nzara, and Tembura, Sudan 284/151 (53%)
1976 EBOV Yambuku, Zaire 318/280 (88%)
1977 EBOV Bonduni, Zaire 1/1 (100%)
1979 SUDV Nzara, Sudan 34/22 (65%)
1988 EBOV Porton Down, United Kingdom 1/0 (0%) [laboratory accident]
1994 TAFV Taï National Park, Côte d'Ivoire; Switzerland 1/0 (0%)
1994–1995 EBOV Woleu-Ntem and Ogooué-Ivindo Provinces, Gabon 52/32 (62%)
1995 EBOV Kikwit, Zaire 317/245 (77%)
1996 EBOV Mayibout 2, Gabon 31/21 (68%)
1996 EBOV Sergiyev Posad, Russia 1/1 (100%) [laboratory accident]
1996–1997 EBOV Ogooué-Ivindo Province, Gabon; Cuvette-Ouest Department, Republic of the Congo 62/46 (74%)
2000–2001 SUDV Gulu, Mbarara, and Masindi Districts, Uganda 425/224 (53%)
2001–2002 EBOV Ogooué-Ivindo Province, Gabon; Cuvette-Ouest Department, Republic of the Congo 124/97 (78%)
2002 EBOV Ogooué-Ivindo Province, Gabon; Cuvette-Ouest Department, Republic of the Congo 11/10 (91%)
2002–2003 EBOV Cuvette-Ouest Department, Republic of the Congo; Ogooué-Ivindo Province, Gabon 143/128 (90%)
2003–2004 EBOV Cuvette-Ouest Department, Republic of the Congo 35/29 (83%)
2004 EBOV Koltsovo, Russia 1/1 (100%) [laboratory accident]
2004 SUDV Yambio County, Sudan 17/7 (41%)
2005 EBOV Cuvette-Ouest Department, Republic of the Congo 11/9 (82%)
2007 EBOV Kasai Occidental Province, Democratic Republic of the Congo 264/186 (71%)
2007–2008 BDBV Bundibugyo District, Uganda 116/39 (34%)
2008–2009 EBOV Kasai Occidental Province, Democratic Republic of the Congo 32/15 (47%)
2011 SUDV Luweero District, Uganda 1/1 (100%)

While investigating an outbreak of Simian hemorrhagic fever virus (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, Virginia.[102] 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.[103] 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.[104]

The Philippines and the United States had no previous cases of infection, and upon further isolation it was concluded to be another strain of Ebola or a new filovirus of Asian origin, and named Reston ebolavirus (REBOV) after the location of the incident. Because of the virus's high mortality, it is a potential agent for biological warfare.[105] In 1992, members of Japan's Aum Shinrikyo cult considered using Ebola as a terror weapon. Their leader, Shoko Asahara, led about 40 members to Zaire under the guise of offering medical aid to Ebola victims in a presumed attempt to acquire a virus sample.[106]

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.[107] 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 and a non-fiction work authored by Richard Preston known as The Hot Zone.

The BBC reports in a study that frequent outbreaks of Ebola may have resulted in the deaths of 5,000 gorillas.[108]

Recent cases

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.[109][110] The Congo's last major Ebola epidemic killed 245 people in 1995 in Kikwit, about 200 miles (320 km) from the source of the August 2007 outbreak.[111]

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.[112] 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 was held at Centre Culturel Français, Libreville, Gabon, during March 2008.[113] The virus appeared in southern Kasai Occidental on November 27, 2008,[114] and blood and stool samples were sent to laboratories in Gabon and South Africa for identification.

On December 25, 2008, a mysterious disease that had killed 11 and infected 21 people in southern Democratic Republic of Congo was identified as the Ebola virus.[115] Doctors Without Borders reported 11 deaths as of Monday 29 December 2008 in the Western Kasai province of the Democratic Republic of Congo, stating that a further 24 cases were being treated. In January 2009, Angola closed down part of its border with DRC to prevent the spread of the outbreak.[116]

On March 12, 2009, an unidentified 45-year-old 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.[117]

In May 2011, a 12-year-old girl in Uganda died from Ebola (Sudan subspecies). No further cases were recorded. [118]

In December 2011, an unidentified woman presented at a Nairobi hospital with "Ebola-like symptoms" and subsequently expired. The pathogen has yet to be identified. [119]

History

For more about the outbreak in Virginia, see Reston ebolavirus.

Ebolavirus first emerged in 1976 in outbreaks of Ebola hemorrhagic fever in Zaire and Sudan.[120] The strain of Ebola that broke out in Zaire has one of the highest case fatality rates of any human pathogenic virus, roughly 90%,[121] 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%.[121] The virus is believed to be transmitted to humans via contact with an infected animal host. The virus is then transmitted to other people that come into contact with blood and bodily fluids of the infected 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.

Proceedings of an International Colloquium on Ebola Virus Infection and Other Hemorrhagic Fevers were held in Antwerp, Belgium, on December 6 through December 8 in 1977.[122]

While investigating an outbreak of Simian hemorrhagic fever virus (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, Virginia.[123] 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.[124] 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.[125]

The Philippines and the United States had no previous cases of infection, and upon further isolation it was concluded to be another strain of Ebola or a new filovirus of Asian origin, and named Reston ebolavirus (REBOV) after the location of the incident.

In other animals

Outbreaks of EVD among human populations generally result from handling infected wild animal carcasses. Declines in animal populations generally precede outbreaks among human populations. Since 2003, such declines have been monitored through surveillance of animal populations with the aim of predicting and preventing EVD outbreaks in humans.[126] Recovered carcasses from gorillas contain multiple Ebola virus strains, which suggest multiple introductions of the virus. Bodies decompose quickly and carcasses are not infectious after three to four days. Contact between gorilla groups is rare, suggesting transmission among gorilla groups is unlikely, and that outbreaks result from transmission between viral reservoir and animal populations.[127]

Outbreaks of EVD have been responsible for an 88% decline in observed chimpanzee populations since 2003.[127] Transmission among chimpanzees through meat consumption constitutes a significant 5.2 (1.3–21.1 with 95% confidence) relative risk factor, while contact between individuals, such as touching dead bodies and grooming, do not.[128]

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Bibliography

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