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{{ infobox disease
| Name = Ebola
| Image =7042 lores-Ebola-Zaire-CDC Photo.jpg
| Caption =1976 photograph of two nurses standing in front of Kinshasa case No. 3 (]), who was treated and later died in Ngaliema Hospital in ], ]
| DiseasesDB = 18043
| ICD10 = {{ICD10|A|98|4|a|90}}
| ICD9 = {{ICD9|065.8}}
| MedlinePlus = 001339
| eMedicineSubj = med
| eMedicineTopic = 626
| MeshID = D019142}}

{{ taxobox
| name = Ebola
| image = Ebola virus em.jpg
| image_width = frameless
| image_caption = Ebola virus ]
| virus_group = V
| ordo = ]
| familia = ]
| genus = Ebolavirus
| type_species = Zaire ebolavirus
| subdivision_ranks = Species
| subdivision =
Ivory Coast ebolavirus<br />
]<br />
Sudan ebolavirus
}}

'''Ebola''' is the ] '''Ebolavirus''' (EBOV), a viral ], and the disease '''Ebola hemorrhagic fever''' (EHF), a ] (VHF). The virus is named after the ] Valley in the ] (formerly ]), which is near the site of the first recognized outbreak in 1976 at a mission hospital run by ] ]s.<ref>{{ cite journal | last = Bardi | first = Jason Socrates | year = 2002 | title = Death Called a River | journal = Scripps Research Institute | volume = 2 | issue = 1 | url = http://www.scripps.edu/newsandviews/e_20020114/ebola1.html | accessdate = 2006-12-08 | ref = harv }}</ref> It remained largely obscure until 1989 when several widely publicized outbreaks occurred among monkeys in the United States.

The virus interferes with the ] lining the interior surface of blood vessels and with coagulation. As the blood vessel walls become damaged and destroyed, the platelets are unable to coagulate, patients succumb to ]. Ebola is transmitted through bodily fluids, while ] exposure may also lead to transmission.

There are five recognized species within the ebolavirus genus, which have a number of specific ].<ref>{{ cite web | url = http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/fs_filov.htm | title = Filoviridae | accessdate = 2009-10-04 | last1 = Netesov | first1 = SV | last2 = Feldmann | first2 = H | last3 = Jahrling | first3 = PB | last4 = Kiley | first4 = MP | last5 = Klenk | first5 = H-D | last6 = Sanchez | first6 = A | date = 2004-04-24 | publisher = International Committee on Taxonomy of Viruses }}</ref> The ''Zaire virus'' is the ], which is also the first discovered and the most lethal. Electron micrographs show long filaments, characteristic of the ] viral family.

==Classification==
The genera ''Ebolavirus'' and '']'' were originally classified as the species of the now-obsolete ''Filovirus'' genus. In March 1998, the Vertebrate Virus Subcommittee proposed in the ] (ICTV) to change the ''Filovirus'' genus to the '']'' 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''.<ref>{{Cite web|url=http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/01.025.0.02.htm|title=ICTVdB Virus Description – 01.025.0.02. Ebolavirus|accessdate=2009-06-02|last=Büchen-Osmond|first=Cornelia|date=2006-04-25|publisher=International Committee on Taxonomy of Viruses}}</ref>

] comparing the Ebolavirus and Marburgvirus. Numbers indicate percent confidence of branches.]]

Rates of genetic change are one hundred times slower than ] in humans, but on the same magnitude of that of ]. Using these rates, the Ebolavirus and Marburgvirus are estimated to have diverged several thousand years ago.<ref>{{Cite pmid|9254917}}</ref>However, ]es (genomic fossils) of ]es (Filoviridae) found in mammals indicate that the family itself is at least tens of millions of years old.<ref>{{Cite pmid| 20569424}}</ref>

; 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 ]<ref>{{Cite journal|author=Isaacson, M; Sureau, P; Courteille, G; Pattyn, SR;|title=Clinical Aspects of Ebola Virus Disease at the Ngaliema Hospital, Kinshasa, Zaire, 1976|url=http://www.itg.be/ebola/ebola-12.htm|accessdate=2009-07-08|ref=harv}}</ref>. Mabalo Lokela, a 44-year-old schoolteacher, became the first recorded case. The symptoms resembled ], and subsequent patients received ]. 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 ] and the traditional burial preparation method, which involves washing and ] cleansing.{{Citation needed|date=May 2010}}
; 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, ], 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 SEBOV were 54% in 1976, 68% in 1979, and 53% in 2000 and 2001.
; ] (REBOV) : Discovered during an outbreak of ] (SHFV) in ] from ] (now Covance) in 1989. Since the initial outbreak in ], it has emerged in Siena Italy, Texas,<ref name="KnownCasesCDC">{{Cite web|url=http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/ebolatable.htm|title=Known Cases and Outbreaks of Ebola Hemorrhagic Fever|accessdate=2008-08-02|author=Special Pathogens Branch CDC|date=2008-01-14|publisher=Center for Disease Control and Prevention}}</ref> and among pigs in the Philippines.<ref>{{cite news|url=http://www.nytimes.com/2009/01/24/health/24ebola.html|title=Pig-to-Human Ebola Case Suspected in Philippines|accessdate=2009-01-26|date=2009-01-24|publisher=New York Times | first=Donald G. | last=McNeil Jr}}</ref> Despite its status as a ] organism, it is non-]ic to humans however hazardous in monkeys.<ref>{{harvnb|McCormick|Fisher-Hoch|1999|p=300}}</ref>
; Côte d'Ivoire ebolavirus (CIEBOV): Also referred to as ''Ivory Coast ebolavirus'' and ''Tai ebolavirus'', it was first discovered among ]s from the Tai Forest in ], Africa, on 1 November 1994. ] 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 contamination was believed to be the meat of infected ] 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 ] 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.<ref>{{Cite book|last=Waterman|first=Tara|title=Ebola Cote D'Ivoire Outbreaks|url=http://virus.stanford.edu/filo/eboci.html|accessdate=2009-05-30|year=1999|publisher=Stanford University}}</ref>
; Bundibugyo ebolavirus: On November 24, 2007, the Uganda Ministry of Health confirmed an outbreak of Ebola in the ]. After confirmation of samples tested by the United States National Reference Laboratories and the ], the ] 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.<ref>{{Cite press release|title=End of Ebola outbreak in Uganda|publisher=World Health Organization|date=2008-02-20|url=http://www.who.int/csr/don/2007_02_20b/en/index.html}}</ref> 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) <ref>{{Cite journal|author=Wamala, J; Lukwago, L; Malimbo, M; Nguku, P; Yoti, Z; Musenero, M; Amone, J; Mbabazi, W; Nanyunja, M; Zaramba, S; Opio, A; Lutwama, J; Talisuna, A; Okware, I;|title=Ebola Hemorrhagic Fever Associated with Novel Virus Strain, Uganda, 2007–2008 | year = 2010 | journal = Emerging Infectious Disease | volume = 16 | issue = 7 | url = http://www.cdc.gov/eid/content/16/7/1087.htm | accessdate = 2010-06-24|ref=harv }}</ref>.

==Signs and symptoms==
Although the ] is generally 5–18&nbsp;days, it ranges from 2 to 21&nbsp;days<ref>{{Cite pmid|14718087}}</ref> Illness is characterized by the rapid onset of fever, malaise, muscle pain, headache, and the inflammation of the ]. Six days following vomiting and bloody diarrhea, individuals may develop ] with bleeding at needle sites and bodily orifices.<ref name="10.1371/journal.pmed.0010059" />

''Reston ebolavirus'' is non-pathogenic to humans and individuals often do not show any symptoms, although it is fatal in monkeys. There is only one known case of ''Ivory Coast ebolavirus'', and one outbreak of ''Bundibugyo ebolavirus''. ''Zaire ebolavirus'' and ''Sudan ebolavirus'' (SEBOV) are the most common and whose symptoms include: ] (60–80%), ] (90–100%), ] (40–90%), ] (10–40%), ] (5–20%), ] (75–85%), ] and ] pain (40–80%), ] (20–40%),<ref>{{Cite pmid|9893380}}</ref> ] (71–78%), ] (SEBOV only 83%), ] involvement (rare), dry and ] (63%), ] (71–78%), ] (15%), non-bloody ] (81%), ] (59%).<ref>{{Cite book|last1=Zaki|first1=S. R.|last2=Kilmarx|first2=P.|title=Pathology of Emerging Infections|year=1997|publisher=American Society for Microbiology|location=Washington, DC|chapter=Ebola Virus Hemorrhagic Fever}}</ref> ], ], ], and low ] are characteristic as the disease progresses.

==Virology==
===Structure===

] of members of genus ''Ebolavirus'' show them to have the characteristic thread-like structure of a ].<ref>{{harvnb|Klenk|Feldmann|2004|p=2}}</ref> EBOV VP30 is around 288 amino acids long.<ref>{{harvnb|Klenk|Feldmann|2004|p=13}}</ref> 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; laboratory techniques, such as ], may be the origin of some of these formations.<ref>{{harvnb|Klenk|Feldmann|2004|pp=33–35}}</ref> Virions are generally 80&nbsp;] in diameter with a lipid bilayer anchoring the glycoprotein which projects 7 to 10&nbsp;nm long spikes from its surface.<ref>{{harvnb|Klenk|Feldmann|2004|p=28}}</ref> They are of variable length, typically around 800&nbsp;nm, but may be up to 1000&nbsp;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.<ref name="BiomarkerDatabase">{{Cite book|last=Biomarker Database|title=Ebola virus|url=http://biomarker.cdc.go.kr:8080/pathogen/pathogen_view_en.jsp?pclass=2&id=44|accessdate=2009-05-31|publisher=Korea National Institute of Health}}</ref> It has a diameter of 80&nbsp;nm and contains a central channel of 20–30&nbsp;nm in diameter. Virally encoded ] (GP) spikes 10&nbsp;nm long and 10&nbsp;nm apart are present on the outer ] 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.<ref name="pmid8219816">{{Cite pmid|8219816}}</ref>

===Genome===
Each virion contains one molecule of linear, single-stranded, ] 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.<ref>{{harvnb|Klenk|Feldmann|2004|p=9}}</ref> 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. Sections of the NP and the L genes from filoviruses have been identified as endogenous in the genomes of several groups of small mammals. <ref>{{Cite pmid| 20569424}}</ref>

===Replication===

Being acellular, viruses do not grow through cell division; instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble in the cell.<ref name="BiomarkerDatabase" />

* The virus attaches to host receptors through the ] (GP) surface ] and is ] into vesicles in the host cell
* Viral membrane fuses with ] membrane, ] is released into the ]
* Encapsidated, negative-sense genomic ssRNA is used as a template for the synthesis (3' – 5') of polyadenylated, monocistronic mRNAs
* Using the host cell's machinery translation of the mRNA into viral proteins occurs
* Viral proteins are processed, glycoprotein precursor (GP0) 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. Secreted glycoprotein (sGP) 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; ] occurs, destroying the cell.

==Pathogenesis==

]

], mononuclear ], and ] 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 ], which binds the virus to the endothelial cells lining the interior surface of blood vessels. The sGP forms a ] which interferes with the signaling of ], a type of ], which allows the virus to evade the immune system by inhibiting early steps of neutrophil activation. The presence of viral particles and cell damage resulting from ] causes the release of ] (specifically ], ], ], etc.), which are the signaling molecules for fever and inflammation. The ], 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 ]. Without vascular integrity and effective ], blood quickly leaks through the blood vessel leading to ].<ref name="doi10.1128/JVI.77.18.9733-9737.2003">{{Cite doi|10.1128/JVI.77.18.9733-9737.2003}}</ref>

==Diagnosis==

Before outbreaks are confirmed in areas of weak surveillance on the local or regional levels ebola is often mistaken for ], ], ], ], or various ] which may be endemic to the region. Learning from the failure response such as the 2000 Uganda outbreak, public health measures such as the WHO's Global Outbreak and Response Network were instituted in areas at high risk. Field laboratories were established in order to confirm cases as to shipping samples to South Africa.<ref name="10.1371/journal.pmed.0010059">{{Cite doi|10.1371/journal.pmed.0010059}}</ref>

Methods of diagnosis of Ebola include testing saliva and urine samples. Ebola is diagnosed with an ] (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 ], which was later improved with ] (IFA). It was however not used during the serosurvey following Reston.<ref name="L4VH302-303">{{harvnb|McCormick|Fisher-Hoch|1999|pp=302–303}}</ref> These tests are not commercially available.<ref name="WHO_EPR">{{Cite book|title=Ebola and Marburg haemorrhagic fever – Factsheet|url=http://ecdc.europa.eu/en/Health_topics/ebola_marburg_fevers/factsheet.aspx|accessdate=2009-05-31|date=2008-07-10|year=2009|publisher=European Centre for Disease Prevention and Control}}</ref> Polymerase Chain Reaction (PCR) technique has been successfully used for detection of Ebola virus

==Prevention==
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 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 ] procedures, isolate patients, and observe strict ] 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.<ref>{{Cite book|last=Centers for Disease Control and Prevention and World Health Organization|title=Infection Control for Viral Haemorrhagic Fevers in the African Health Care Setting|url=http://www.cdc.gov/ncidod/dvrd/spb/mnpages/vhfmanual/entire.pdf|format=PDF|accessdate=2009-05-31|year=1998|publisher=Centers for Disease Control and Prevention|location=Atlanta, Georgia, USA|ref=CITEREFCDCWHO1998}}</ref>

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 ] (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.<ref name="Sullivan2003">{{Cite doi|10.1038/nature01876}}</ref> In 2005 a vaccine based on attenuated recombinant ] (VSV) vector carrying either the Ebola glycoprotein or Marburg glycoprotein successfully protected non-human primates,<ref name="Jones2005">{{Cite doi|10.1038/nm1258}}</ref> opening clinical trials in humans.<ref>{{Cite book|last=Oplinger|first=Anne A.|date=2003-11-18|title=NIAID Ebola vaccine enters human trial|url=http://news.bio-medicine.org/medicine-news-2/NIAID-Ebola-vaccine-enters-human-trial-4881-1/|publisher=Bio-Medicine}}</ref> 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.<ref name="NIAIDVaccineDevelopment">{{Cite press release|title=Ebola/Marburg Vaccine Development|publisher=National Institute of Allergy and Infectious Diseases|date=2008-09-15|url=http://www3.niaid.nih.gov/topics/ebolaMarburg/default.htm}}</ref>

==Treatment==
There is no standard treatment for Ebola hemorrhagic fever. Treatment is primarily supportive and includes minimizing invasive procedures, balancing electrolytes (since patients are frequently dehydrated), replacing lost ]s 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. ] is ineffective. ] 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 ]s with ''Ebolavirus'' and administering ] ].<ref>{{Cite book|last=Linden|first=Caree Vander|title=Gene-Specific Ebola Therapies Protect Nonhuman Primates from Lethal Disease|url=http://www.usamriid.army.mil/press%20releases/warfield_press_release.pdf|format=New Release|accessdate=2009-05-31|date=2006-01-13|publisher=U.S. Army Medical Research Institute of Infectious Diseases}}</ref> Development of improved Morpholino antisense conjugated with ]s is ongoing.<ref name="USAMRIID">{{Cite doi|10.1128/AAC.00936-08}}</ref>

], ], during the October 2000 outbreak]]

In May 2010, a group of scientists from the ] at ] announced they had developed a drug containing ]s packaged into ]s (SNALPs) that prevented reproduction of the virus in monkeys.<ref>{{Cite journal |last=Geisbert |first=Thomas W. |last2=''et al.'' |year=2010 |first2=Amy CH |last3=Robbins |first3=Marjorie |last4=Geisbert |first4=Joan B |last5=Honko |first5=Anna N |last6=Sood |first6=Vandana |last7=Johnson |first7=Joshua C |last8=De Jong |first8=Susan |last9=Tavakoli |first9=Iran |title=Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study |journal=] |volume=375 |issue=9729 |pages=1896–1905 |doi=10.1016/S0140-6736(10)60357-1 |ref=harv |postscript=<!--None--> }}.</ref><ref name="AFP">{{cite news|url=http://www.google.com/hostednews/afp/article/ALeqM5hJLE2DbCy31Uqu4UOvkxXlfZ4ucQ|title=Drug shields lab monkeys from deadly Ebola virus|date=29 May 2010|work=AFP|accessdate=30 May 2010}}</ref> The group's leader Thomas Geisbert claimed the results of the group's study showed their experimental treatment resulted in "complete protection" of monkeys from the virus. Virologist Heinz Feldmann hailed the findings of the study as a "milestone" that could be used to combat similar viruses.<ref>{{cite news|url=http://www.npr.org/templates/story/story.php?storyId=127226355|title=New Ebola Drug 100 Percent Effective In Monkeys|last=Knox|first=Richard|date=28 May 2010|work=]|accessdate=30 May 2010}}</ref> Geisbert claimed a lack of market interest could impair the development of the treatment for humans, given the comparatively low number of Ebola cases worldwide.<ref>{{cite news|url=http://www.vancouversun.com/health/Potential+Ebola+cure+uses+made+technology/3087071/story.html|title=Potential Ebola cure uses made-in-B. C. technology|last=Skelton|first=Chad|date=29 May 2010|work=]|accessdate=30 May 2010}}</ref> The trial on monkeys had been funded by the ].<ref name="AFP"/>

==Prognosis==

Ebola hemorrhagic fever is potentially lethal and encompasses a range of symptoms including ], ], ], generalized pain or ], and sometimes ] and ]. The span of time from onset of symptoms to death is usually between 2 and 21&nbsp;days. By the second week of infection, patients will either ] (the fever will lessen) or undergo ]. ]s are typically high, with the human case-fatality rate ranging from 50 to 89%, depending on the species or viral strain.<ref name="Cite pmid|15752448">{{Cite pmid|15752448}}</ref> The cause of death is usually due to ] or organ failure.<ref>{{Cite doi|10.1016/j.biocel.2005.02.018}}</ref>

==Epidemiology==
{{Multiple image|direction=vertical|align=right|image1=Ecologic and Geographic Distribution of Filovirus Disease in Africa.jpg|image2=Ecologic and Geographic Distribution of Filovirus Disease in Asia and the Philippines.jpg|width=180|caption2=Distribution of Ebola and ] in Africa (note that integrated genes from filoviruses have been detected in mammals from the New World as well<ref>{{Cite pmid| 20569424}}</ref>). (A) Known points of filovirus hemorrhagic fevers. Projected distribution of ecological niche of: (B) all filoviruses, (C) Ebola, (D) Marburg.|Distribution of ecological niche of Reston ebolavirus in southeastern Asia and the Philippines. (A) Areas of research determining whether similar ecological conditions exist. (B) Projected distribution. Insert, detailed view of ], Philippines}}
===Natural reservoirs===

Between 1976 and 1998, from 30,000 mammals, birds, reptiles, amphibians, and ]s sampled from outbreak regions, no ''Ebolavirus'' was detected apart from some genetic material found in six rodents ('']'' and '']'') and one ] ('']'') collected from the ].<ref name="Pourrut2005">{{Cite doi|10.1016/j.micinf.2005.04.006}}</ref><ref name="Morvan1999">{{Cite doi|10.1016/S1286-4579(99)00242-7}}</ref> The virus was detected in the carcasses of ]s, ]s, and ]s 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.<ref name="Pourrut2005" />

]s, ], and birds have also been considered as possible reservoirs; however, ]s are considered the most likely candidate.<ref>{{Cite news|title=Fruit bats may carry Ebola virus |url=http://news.bbc.co.uk/2/hi/health/4484494.stm|work=BBC News|date=2005-12-11|accessdate=2008-02-25}}</ref> 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.<ref name="Pourrut2005" /> Of 24 plant species and 19 vertebrate species experimentally inoculated with ''Ebolavirus'', only bats became infected.<ref>{{Cite pmid|8969248}}</ref> 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 ] and the ], 13 fruit bats were found to contain ''Ebolavirus'' RNA.<ref>{{Cite doi|10.1038/438575a}}</ref> As of 2005, three ] species ('']'', '']'', and '']'') have been identified as carrying the virus while remaining asymptomatic. They are believed to be a natural host species, or reservoir, of the virus.<ref>{{Cite pmid|17940947}}</ref>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.<ref>{{Cite pmid| 20569424}}</ref>

''Reston ebolavirus''—unlike its African counterparts—is non-pathogenic in humans. The high mortality among monkeys and its recent emergence in swine, makes them unlikely natural reservoirs.<ref>{{Cite web|first=Juan|last=Lubroth|title=Ebola-Reston Virus in Pigs: Disease situation in swine in the Philippines|url=http://www.fao.org/Ag/againfo/programmes/en/empres/ebola_111208.html|publisher=Food and Agriculture Organization of the United Nations|accessdate=2009-09-27}}</ref>

===Transmission===

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.<ref>{{Cite pmid|17848072}}</ref> 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.<ref>{{Cite pmid|15078595}}</ref> The virus then spreads person-to-person, especially within families, hospitals, and during some ] rituals where contact among individuals becomes more likely.<ref>{{Cite book|title=Questions and Answers about Ebola Hemorrhagic Fever|url=http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/qa.htm|accessdate=2009-05-31|date=2009-03-25|publisher=Centers for Disease Control and Prevention}}</ref>

The virus has been confirmed to be transmitted through ]s. Transmission through oral exposure and through ] exposure is likely,<ref>{{Cite pmid|8551825}}</ref> which have been confirmed in non-human primates.<ref>{{Cite pmid|8712894}}</ref> Filoviruses are not naturally transmitted by aerosol. They are, however, highly infectious as breathable 0.8–1.2 micron droplets in laboratory conditions;<ref>{{Cite pmid|7547435}}</ref> because of this potential route of infection, these viruses have been classified as Category A biological weapons.<ref>{{Cite pmid|15588056}}</ref>

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 ]s are unavailable or too expensive. In modern hospitals with disposable needles and knowledge of basic hygiene and ] 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.<ref name="nyt">{{Cite news|first=Blaine|last=Harden|title=Dr. Matthew's Passion|url=http://www.nytimes.com/library/magazine/home/20010218mag%2debola.html|work=] Magazine|date=2001-02-18|accessdate=2008-02-25}}</ref>

===Prevalence===

{{For|more about specific outbreaks and their descriptions|List of Ebola outbreaks}}

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 while the lack of roads and transportation helps to contain the outbreak.<ref name="KnownCasesCDC" />

* '''''Zaire ebolavirus''''' first emerged in an outbreak among human populations in 1976 in ] (now Democratic Republic of the Congo) with no further recognized cases until 1994. Since then it has occurred again in the ], ], and ]. There have been two contained cases in ].
* '''Sudan ebolavirus''' emerged in a simultaneous outbreak with the Zaire virus in 1976 in ]. It appeared again in another outbreak in 1979. No further cases were recognized until a 2000 outbreak in ] and 2004 outbreak in Sudan. There has been one confirmed accidental incidence in 1976 in England.
* '''''Reston ebolavirus''''' was first recognized among monkeys in 1989 in the ], and again in ], in the United States; both were traced to the ]. In 1994 it was recognized in cases among monkeys in an import facility in Italy. In 2008 cases of infection among pigs were recognized in the Philippines.
* '''''Ivory Coast ebolavirus''''' was first recognized in 1994 after a scientist became ill after conducting an autopsy on a wild chimpanzee in the ], ].
* '''''Bundibugyo ebolavirus''''' was first recognized in 2007 in an outbreak in ], ].

==History==
===Emergence===

{{For|more about the outbreak in Virginia|Reston ebolavirus}}

Ebolavirus first emerged in 1976 in outbreaks of Ebola hemorrhagic fever in ] and ].<ref>{{Cite pmid|7787519}}</ref> The strain of Ebola that broke out in Zaire has one of the highest ]s of any human pathogenic virus, roughly 90%,<ref name="emedicine.com">{{Cite web|url=http://www.emedicine.com/MED/topic626.htm|accessdate=2008-10-06|author=King, John W|title=Ebola Virus|date=April 2, 2008|work=eMedicine|publisher=WebMd}}</ref> 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%.<ref name="emedicine.com"/> The virus is believed to be transmitted to humans via contact with an infected animal ]. 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 (]) 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 ] 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.<ref>{{harvnb|Pattyn|1978|p=3}}</ref>

While investigating an outbreak of ] (SHFV) in November 1989, an ] from USAMRIID discovered filoviruses similar in appearance to Ebola in tissue samples taken from ] imported from the ] to ] ].<ref>{{harvnb|McCormick|Fisher-Hoch|1999|pp=277–279}}</ref> Due to the lethality of the suspected and previously obscure virus, the investigation quickly attracted attention.{{Citation needed|date=January 2009}}

Blood samples were taken from 178 animal handlers during the incident.<ref>{{Cite book|last=Waterman|first=Tara|url=http://www.stanford.edu/group/virus/filo/ebor.html|title=Ebola Reston Outbreaks|accessdate=2008-08-02|year=1999|publisher=Stanford University}}</ref> Of those, six animal handlers eventually ]. When the handlers failed to become ill, the CDC concluded that the virus had a very low ]icity to humans.<ref>{{harvnb|McCormick|Fisher-Hoch|1999|pp=298–299}}</ref>

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.

===Recent cases===

Because of the virus's high mortality, it is a potential agent for biological warfare.<ref>{{Cite pmid|15207310}}</ref> In 1992, members of Japan's ] ] considered using Ebola as a terror weapon. Their leader, ], 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.<ref>{{Cite book|last=Monterey Institute for International Studies|title=Chronology of Aum Shinrikyo's CBW Activities|publisher=James Martin Center for Nonproliferation Studies|url=http://cns.miis.edu/pubs/reports/pdfs/aum_chrn.pdf|year=2001|format=PDF}}</ref>

Given the lethal nature of Ebola, and since no approved ] or treatment is available, it is classified as a ] agent, as well as a ] agent by the ]. It has the potential to be weaponized for use in ].<ref>{{Cite doi|10.1001/jama.287.18.2391}}</ref> 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.{{Citation needed|date=January 2009}}

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 in a study that frequent outbreaks of ebola may have resulted in the deaths of 5,000 gorillas.<ref>{{Cite book|title=Ebola 'kills over 5,000 gorillas'|url=http://news.bbc.co.uk/2/hi/science/nature/6220122.stm|accessdate=2009-05-31|date=2006-12-08|publisher=BBC}}</ref>

As of August 30, 2007, 103 people (100 adults and three children) were infected by a suspected hemorrhagic fever outbreak in the village of ], Democratic Republic of the Congo. The outbreak started after the funerals of two village chiefs, and 217 people in four villages fell ill. The ] sent a team to take blood samples for analysis and confirmed that many of the cases are the result of ''Ebolavirus''.<ref>{{Cite news|title=Ebola Outbreak Confirmed in Congo|url=http://www.newscientist.com/article/dn12624-ebola-outbreak-confirmed-in-congo.html|work=NewScientist.com|date=2007-09-11|accessdate=2008-02-25}}</ref><ref>{{Cite book|title=Ebola outbreak in Congo|url=http://www.cbc.ca/health/story/2007/09/12/ebola-outbreak.html|accessdate=2009-05-31|date=2007-09-12|publisher=CDC news}}</ref> The Congo's last major Ebola epidemic killed 245 people in 1995 in ], about 200 miles from the source of the August 2007 outbreak.<ref>{{Cite news|title=Mystery DR Congo fever kills 100|url=http://news.bbc.co.uk/2/hi/africa/6973013.stm|work=BBC News|date=2007-08-31|accessdate=2008-02-25}}</ref>

On November 30, 2007, the ] Ministry of Health confirmed an outbreak of Ebola in the ]. 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.<ref>{{Cite news|title=Uganda: Deadly Ebola Outbreak Confirmed – UN|url=http://allafrica.com/stories/200711301070.html|work=UN News Service|date=2007-11-30|accessdate=2008-02-25}}</ref> 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, ], ], during March 2008.<ref>{{Cite book|title=The IV International Symposium on Filoviruses|url=http://www.ird.fr/filomeeting2008/venue.php|accessdate=2009-0-31|publisher=l'Institut de recherche pour le développement (IRD)}}</ref> The virus appeared in southern Western ] on November 27, 2008,<ref>{{Cite book|last=World Health Organization|title=RD Congo: Fièvre hémorragique à virus Ebola au Kasaï Occidental, Rapport de situation No 1 des 26 & 27 décembre 2008|url=http://www.reliefweb.int/rw/rwb.nsf/db900sid/ASAZ-7MSCBQ?OpenDocument|accessdate=2009-06-02|date=2008-12-27|publisher=Relief Web|language=French}}</ref> 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 eleven and infected twenty-one people in southern Democratic Republic of Congo was identified as the Ebola virus.<ref>{{Cite book|title=Ebola epidemic kills nine in central DR Congo: report|url=http://www.google.com/hostednews/afp/article/ALeqM5hGhlK2pjCd0SJVrJKYNFTAP5I6Fg|accessdate=2009-05-30|date=2008-12-25|publisher=Agence France-Presse}}</ref> 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 their border with DRC to prevent the spread of the outbreak.<ref>{{Cite book|title=Ebola alert shuts Angolan border|url=http://news.bbc.co.uk/2/hi/africa/7812868.stm|accessdate=2009-05-31|date=2009-01-06|publisher=BBC}}</ref>

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.<ref>{{Cite news|last=Eddyn|first=Melissan|title=Scientist Injects Self With Ebola|url=http://www.gouverneurtimes.com/index.php?option=com_content&view=article&id=2202:scientist-injects-self-with-ebola&catid=54:worldnational-news&Itemid=153|accessdate=2009-05-02|date=2009-03-27|publisher=Associated Press}}</ref>

==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. Since 2003, such declines have been monitored through surveillance of animal populations with the aim of predicting and preventing Ebola outbreaks in humans.<ref name="Cite pmid|15752448"/>

Recovered carcasses from gorillas contain multiple Ebola 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. This suggests transmission among gorilla groups unlikely and that outbreaks result from transmission between viral reservoir and animal populations.<ref name="doi10.1126/science.1092528">{{Cite doi|10.1126/science.1092528}}</ref>

Outbreaks of Ebola have been responsible for an 88% decline in observed chimpanzee populations since 2003.<ref name="doi10.1126/science.1092528" /> Transmission among chimpanzees through meat consumption constitute a significant 5.2 (1.3–21.1 with 95% ]) ] factor, while contact between individuals such as touching dead bodies and grooming do not.<ref>{{Cite pmid|9988175}}</ref>

Reston ebolavirus, which has not had a previous outbreak in Africa and is non-pathogenic in humans, has recently been recognized among swine populations in the Philippines; this discovery suggests that the virus has been circulating since and possibly before the initial discovery of Reston ebolavirus in 1989 among monkeys.<ref>{{Cite pmid|19590002}}</ref>

==References==

{{Reflist|colwidth=30em}}

==Bibliography==

{{Refbegin}}
* {{Cite book|last=Klenk|first=Hans-Dieter|title=Marburg and Ebola Viruses (Current Topics in Microbiology and Immunology)|year=1999|month=January|publisher=Springer-Verlag Telos|location=Berlin, Germany|isbn=978-3540647294|ref=CITEREFKlenk1999}}
* {{Cite book|first1=Hans-Dieter|last1=Klenk|first2=Heinz|last2=Feldmann|title=Ebola and Marburg viruses: molecular and cellular biology|url=http://books.google.com/?id=EV_mFgnyPoMC&printsec=frontcover|format=Limited preview|year=2004|publisher=Horizon Bioscience|location=Wymondham, Norfolk, UK|isbn=978-0954523237|ref=CITEREFKlenkFeldmann2004}}
* {{Cite book|last=Kuhn|first=Jens H.|title=Filoviruses – A Compendium of 40 Years of Epidemiological, Clinical, and Laboratory Studies. Archives of Virology Supplement, vol. 20|url=http://books.google.com/?id=LaOue0F9Ns4C&printsec=frontcover|format=Limited preview|year=2008|publisher=SpringerWienNewYork|location=Vienna, Austria|isbn=978-3211206706|ref=CITEREFKuhn2008}}
* {{Cite book|last1=McCormick|first1=Joseph|last2=Fisher-Hoch|first2=Susan|others=Horvitz, Leslie Alan|title=Level 4: Virus Hunters of the CDC|url=http://books.google.com/?id=QEvR3aJX2m0C&printsec=frontcover|format=Limited preview|origyear=1996|edition="Updated edition" 3rd|year=1999|publisher=Barnes & Noble|isbn=9780760712085|ref=CITEREFMcCormickFisher-Hoch1999|month=June}}
* {{Cite book|last=Pattyn|first=S. R.|title=Ebola Virus Haemorrhagic Fever|year=1978|url=http://www.itg.be/ebola/|format=Full free text|edition=1st|publisher=Elsevier/North-Holland Biomedical Press|location=Amsterdam, Netherlands|isbn=0-444-80060-3|ref=CITEREFPattyn1978}}
* {{Cite book|last1=Ryabchikova|first1=Elena I.|last2=Price|first2=Barbara B.|title=Ebola and Marburg Viruses – A View of Infection Using Electron Microscopy|year=2004|publisher=Battelle Press|location=Columbus, Ohio, USA
|isbn=978-1574771312|ref=CITEREFRyabchikovaPrice2004}}
{{Refend}}

==External links==

{{Sisterlinks|Ebola}}

{{Refbegin}}
* —Virological repository from the Swiss Institute of Bioinformatics
* —Centers for Disease Control and Prevention, Special Pathogens Branch
* —World Health Organization, Global Alert and Response
*
{{Refend}}

{{Zoonotic viral diseases}}

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Revision as of 14:18, 12 October 2010

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