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Epidemiology and pathogenesis of Ebola virus disease
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Epidemiology and pathogenesis of Ebola virus disease
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2016. | This topic last updated: Apr 12, 2016.

INTRODUCTION — The family Filoviridae consists of two genera, the Ebola and Marburg viruses, which are among the most virulent pathogens in humans [1]. The Zaire species of Ebola virus is the causative agent of the 2014-2015 epidemic in West Africa, in which the case fatality rate has been reported to be as high as 70 percent [2]; rates in earlier outbreaks have reached 80 to 90 percent [3]. Marburg virus has caused a similar disease in a smaller number of outbreaks in Central Africa [4].

The epidemiology and pathogenesis of Ebola virus disease will be presented here, including new knowledge emerging from the 2014-2015 epidemic of Ebola virus disease in West Africa. The clinical manifestations, diagnosis, treatment, and prevention of Ebola virus disease are discussed elsewhere. (See "Clinical manifestations and diagnosis of Ebola virus disease" and "Treatment and prevention of Ebola virus disease".)

CLASSIFICATION — Ebola virus is a nonsegmented, negative-sense, single-stranded RNA virus that resembles rhabdoviruses (eg, rabies) and paramyxoviruses (eg, measles, mumps) in its genome organization and replication mechanisms. It is a member of the family Filoviridae, taken from the Latin "filum," meaning thread-like, based upon their filamentous structure.

In the past, Ebola and Marburg viruses were classified as "hemorrhagic fever viruses", based upon their clinical manifestations, which include coagulation defects, bleeding, and shock [5,6]. However, the term "hemorrhagic fever" is no longer used to refer to Ebola virus disease since only a small percentage of Ebola patients actually develop significant hemorrhage, and it usually occurs in the terminal phase of fatal illness, when the individual is already in shock. (See "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Clinical manifestations'.)

The genus Ebola virus is divided into five species (Zaire, Sudan, Ivory Coast, Bundibugyo, and Reston) [7]. The following four species cause disease in humans:

The Zaire virus, since it was first recognized in 1976, has caused multiple large outbreaks in Central Africa, with mortality rates ranging from 55 to 88 percent [2,8-13]. It is the causative agent of the 2014-2015 West African epidemic.

The Sudan virus has been associated with a case-fatality rate of approximately 50 percent in four epidemics: two in Sudan in the 1970s, one in Uganda in 2000, and another in Sudan in 2004 [14-18].

The Ivory Coast virus has only been identified as the cause of illness in one person, and that individual survived [19]. The exposure occurred when an ethologist performed a necropsy on a chimpanzee found dead in the Tai Forest, where marked reductions in the great ape population had been observed.

The Bundibugyo virus emerged in Uganda in 2007, causing an outbreak of Ebola virus disease with a lower case-fatality rate (approximately 30 percent) than is typical for the Zaire and Sudan viruses. Sequencing has shown that the agent is most closely related to the Ivory Coast species [20].

The fifth Ebola species, the Reston virus, differs markedly from the others, because it is apparently maintained in an animal reservoir in the Philippines and has not been found in Africa [21,22] (see 'Viral reservoirs' below). The Ebola Reston virus was discovered when it caused an outbreak of lethal infection in macaques imported into the United States in 1989. This episode brought the filoviruses to worldwide attention through the publication of Richard Preston's book, The Hot Zone [23]. Three more outbreaks occurred among nonhuman primates in quarantine facilities in the United States and Europe before the Philippine animal supplier ceased operations. None of the personnel who were exposed to sick animals without protective equipment became ill, but several animal caretakers showed evidence of seroconversion.

Nothing further was heard of the Reston virus until 2008, when the investigation of an outbreak of disease in pigs in the Philippines unexpectedly revealed that some of the sick animals were infected both by an arterivirus (porcine reproductive and respiratory disease virus) and by Ebola Reston virus [24]. Serologic studies have shown that a small percentage of Philippine pig farmers have IgG antibodies against the agent without ever developing severe symptoms, providing additional evidence that Ebola Reston virus is able to cause mild or asymptomatic infection in humans.

EPIDEMIOLOGY — The filoviruses were first recognized in 1967, when the inadvertent importation of infected monkeys from Uganda resulted in explosive outbreaks of severe illness among vaccine plant workers in Marburg, Germany who came into direct contact with the animals by killing them, removing their kidneys, or preparing primary cell cultures for polio vaccine production [25]. The causative agent, designated Marburg virus, has caused a number of outbreaks in Africa, including one in Uganda that was recognized in the beginning of October 2014, and was declared over in November 2014.

The other genus, Ebola virus, was first recognized when two outbreaks occurred in Zaire and in Sudan in 1976 [1]. Outbreaks of Ebola virus disease have been confined to Sub-Saharan Africa. An epidemic caused by the Zaire species caused several hundred cases in 1995 in Kikwit, Democratic Republic of the Congo, and the Sudan virus infected more than 400 people in Gulu, Uganda in 2000. The 2014-2015 Ebola epidemic, caused by the Zaire species of virus, is not only the first to occur in West Africa, but is far larger than all previous outbreaks combined [11,12,26-31].

In addition to causing human infections, Ebola virus has also spread to wild nonhuman primates, apparently as a result of their contact with an unidentified reservoir host (possibly bats) [32-35]. This has contributed to a marked reduction in chimpanzee and gorilla populations in Central Africa, and has also triggered some human epidemics due to handling of and/or consumption of sick or dead animals by local villagers as a source of food [32,36]. (See 'Viral reservoirs' below and 'Transmission from animals' below and '2014 outbreak in the Democratic Republic of the Congo' below.)

2014-2015 outbreak in West Africa — Although all previous Ebola outbreaks occurred in Central Africa, an epidemic began in the West African nation of Guinea in late 2013 and was confirmed by the World Health Organization (WHO) in March 2014 [12,13]. The initial case is believed to have been a two-year-old child who developed fever, vomiting, and black stools, without other evidence of hemorrhage [12]. The outbreak subsequently spread to Liberia, Sierra Leone, Nigeria, Senegal, and Mali [37-39]. Sequence analysis of viruses isolated from patients in Sierra Leone indicated that the epidemic resulted from sustained person-to-person transmission, without additional introductions from animal reservoirs [40].

Approximately 28,500 probable, suspected, and laboratory-confirmed cases attributed to Ebola have been identified, with more than 11,000 deaths [41]. These cases included 881 infected healthcare workers, of whom approximately 60 percent have died [41]. The magnitude of the outbreak, especially in Liberia and Sierra Leone, has probably been underestimated, due in part to individuals with Ebola virus disease being cared for outside the hospital setting early in the epidemic [42].

In certain areas of West Africa (Senegal, Nigeria, Mali), introductions of Ebola virus resulted in short chains of person-to-person transmission, but the outbreaks were quickly terminated [43-48]. In other areas (Guinea, Liberia, Sierra Leone), there was widespread transmission, and the rate of new infections did not slow significantly until the spring of 2015. Extended periods of disease free transmission have subsequently been reported [41,49-51]. However, sporadic cases have since occurred, which may be due in part to sexual transmission from survivors with persistent virus [52-55]. Thus, surveillance measures continue in these areas [49]. (See 'Risk of transmission through different body fluids' below and 'Transmission from animals' below.)

Cases of Ebola virus disease have also occurred in residents and healthcare workers who were exposed to the virus in West Africa, and were then treated in hospitals in the United States and Europe [56]. As an example, on September 30, 2014, the first travel-associated case of Ebola was reported in the United States [57]. An individual who was asymptomatic while traveling from Liberia to Dallas, Texas developed clinical findings consistent with Ebola virus disease approximately five days after arriving in the United States, and subsequently died. Two nurses involved in his care developed Ebola virus disease, but recovered [58].

Measures that appear to have contributed to the control of the epidemic include the introduction of infection control precautions in hospitals and funerals, as well as the use of Ebola treatment units and community care centers to help isolate patients with suspected or confirmed Ebola virus disease [59-61]. More detailed discussions of how to prevent transmission of Ebola virus are found elsewhere. (See "Treatment and prevention of Ebola virus disease", section on 'Preventing transmission'.)

2014 outbreak in the Democratic Republic of the Congo — In August of 2014, an outbreak of Ebola virus disease was reported in the Democratic Republic of the Congo [62,63]. The index case was a pregnant woman who butchered an animal that had been killed by her husband. As of November 11, 2014, a total of 66 cases of Ebola virus disease (confirmed and probable), including 49 deaths, had been connected to this outbreak [64]. Sequence analysis has shown that the Zaire strain of Ebola virus causing this outbreak is most closely related to one that caused the 1995 outbreak in Kikwit; there is no connection with the current epidemic in West Africa [65].

VIRAL RESERVOIRS — Perhaps the greatest mysteries regarding the filoviruses are the identity of their natural reservoir(s) and the mode of transmission to wild apes and humans [7,34]. While Marburg virus has been isolated directly from bats captured in Uganda [66], only Ebola virus sequences, not infectious virus, have been detected in samples collected from bats in Central Africa [67,68]. However, data suggest that bats are at least one of the reservoir hosts of Ebola viruses in Africa [69]. The transmission pathway from bats to humans, and the possible role of bats in the initiation of the 2014-2015 West African outbreak have not been defined.

TRANSMISSION — Epidemics of Ebola virus disease are generally thought to begin when an individual becomes infected through contact with the meat or body fluids of an infected animal. Once the patient becomes ill or dies, the virus then spreads to others who come into direct contact with the infected individual’s blood, skin, or other body fluids. Studies in laboratory primates have found that animals can be infected with Ebola virus through droplet inoculation of virus into the mouth or eyes [70,71], suggesting that human infection can result from the inadvertent transfer of virus to these sites from contaminated hands.

Prior to the 2014-2015 epidemic in West Africa, outbreaks of Ebola virus disease were typically controlled within a period of weeks to a few months. This outcome was generally attributed to the fact that most outbreaks occurred in remote regions with low population density, where residents rarely traveled far from home. However, the 2014-2015 West African epidemic has shown that Ebola virus disease can spread rapidly and widely as a result of the extensive movement of infected individuals (including undetected travel across national borders), the spread of the disease to densely populated urban areas, and the avoidance and/or lack of adequate personal protective equipment and medical isolation centers [72,73]. (See "Treatment and prevention of Ebola virus disease", section on 'Preventing transmission'.)

Person-to-person — Person-to-person transmission is associated with direct contact with the body fluids of individuals who are ill with Ebola virus disease, or have died from the infection, in the absence of personal protective equipment [28,74,75]. Those who provide hands-on medical care or prepare a cadaver for burial are at greatest risk. As examples:

In a meta-analysis of Ebola virus transmission among household contacts that included nine studies, the secondary attack rates for those providing nursing care was 47.9 percent (95% CI 23.3%-72.6%) compared with 2.1 percent (95% CI 0% -6.3%) for those household members who had direct physical contact, but did not provide nursing care [76].

The ritual washing of Ebola victims at funerals has played a significant role in the spread of infection in past outbreaks, and has contributed to the epidemic in West Africa.

During the early phase of the 2014-2015 West African epidemic, several hundred African doctors and nurses became infected while caring for patients with Ebola virus disease, showing that healthcare workers are at high risk of infection if they do not use appropriate protective measures. (See '2014-2015 outbreak in West Africa' above and 'Nosocomial transmission' below.)

The likelihood of infection depends, in part, upon the type of body fluid to which an individual is exposed and the amount of virus it contains.

Risk of transmission through different body fluids — Transmission is most likely to occur through direct contact of broken skin or unprotected mucous membranes with virus-containing body fluids from a person who has developed signs and symptoms of illness [75,77].

Discussions of how to prevent transmission of Ebola virus from these body fluids are found elsewhere. (See "Treatment and prevention of Ebola virus disease", section on 'Infection control precautions' and "Treatment and prevention of Ebola virus disease", section on 'Breastfeeding and infant care' and "Treatment and prevention of Ebola virus disease", section on 'Sexual transmission'.)

Acute infection — According to the World Health Organization, the most infectious body fluids are blood, feces, and vomit [78]. Infectious virus has also been detected in urine, semen, saliva, aqueous humor, vaginal fluid, and breast milk [79-83]. Reverse-transcription polymerase chain reaction (RT-PCR) testing has also identified viral RNA in tears and sweat, suggesting that infectious virus may be present.

Ebola virus can also be spread through direct contact with the skin of a patient, but the risk of developing infection from this type of exposure is lower than from exposure to blood or body fluids [75]. Virus present on the skin surface might result either from viral replication in dermal and epidermal structures, contamination with blood or other body fluids, or both.

The risk of Ebola transmission also depends upon the quantity of virus in the fluid. During the early phase of illness, the amount of virus in the blood may be quite low, but levels then increase rapidly and may exceed 108 RNA copies/mL of serum in severely ill patients [75,84]. As an example, an epidemiologic study found that family members were at greatest risk of infection if they had physical contact with sick relatives (or their body fluids) during the later stages of illness, or helped to prepare a corpse for burial [74].

Convalescent period — Infectious virus or viral RNA can persist in some fluids even after it is no longer detected in blood. As examples:

Follow-up studies of approximately 40 survivors in the 1995 Kikwit, Democratic Republic of Congo outbreak found that viral RNA sequences could be detected by RT-PCR in the semen of male patients for up to three months, and infectious virus was recovered from the semen of one individual 82 days after disease onset [79].

In a study of patient samples collected during the outbreak of Ebola Sudan virus disease in Gulu, Uganda in 2000 detected virus in the breast milk of a patient, even after virus was no longer detectable in the bloodstream [80]. Two children who were breastfed by infected mothers died of the disease.

During the 2014-2015 outbreak in West Africa, infectious virus or viral RNA has been detected from several sites. These include:

Urine — Ebola virus was cultured from a patient’s urine 26 days after the onset of symptoms, which was 9 days after the plasma RNA level became negative [81].

Semen — In a sample of 93 men who were discharged from an Ebola treatment center, virus was detected in semen up to nine months after discharge [85]; however, the percentage of patients with persistent virus, and the level of virus detected in semen, decreased over time. (See "Treatment and prevention of Ebola virus disease", section on 'Sexual transmission'.)

Aqueous humor — Ebola virus RNA was detected and infectious virus isolated from the aqueous humor of a patient with uveitis 14 weeks after the onset Ebola symptoms and 9 weeks after viremia had resolved [82].

Cerebrospinal fluid — A patient who had recovered from Ebola virus disease developed meningitis approximately 10 months after her initial diagnosis, and infectious virus was recovered in the cerebrospinal fluid [86,87].

Although transmission from persistent virus at these sites is possible; the risk of transmission is not well established [87]. As an example, a patient in West Africa who had viral RNA in his semen at least 199 days after symptom onset transmitted Ebola virus to one, but not another, of his sexual contacts [88,89]. The transmission occurred approximately 5 months after his blood tested negative for Ebola virus.

Risk of transmission through contact with contaminated surfaces — Ebola virus may be transmitted though contact with contaminated surfaces and objects. The Centers for Disease Control and Prevention (CDC) indicates that virus on surfaces may remain infectious from hours to days [90,91]. There are no high-quality data to confirm transmission through exposure to contaminated surfaces [90], but it is clear that the potential risk can be greatly reduced or eliminated by proper environmental cleaning [78]. (See "Treatment and prevention of Ebola virus disease", section on 'Environmental infection control'.)

Risk of airborne transmission — There are no reported cases of Ebola virus being spread from person to person by the respiratory route [75,92]. However, laboratory experiments have shown that Ebola virus released as a small-particle aerosol is highly infectious for rodents and nonhuman primates [93,94]. Healthcare workers may therefore be at risk of Ebola virus disease if exposed to aerosols generated during medical procedures.

Nosocomial transmission — Transmission to healthcare workers may occur when appropriate personal protective equipment is not available or is not properly used, especially when caring for a severely ill patient who is not recognized as having Ebola virus disease.

During the 2014-2015 outbreak in West Africa, a large number of doctors and nurses have become infected with Ebola virus (see '2014-2015 outbreak in West Africa' above). In Sierra Leone, the incidence of confirmed cases over a seven month period was approximately 100-fold higher in healthcare workers than in the general population [95]. Several factors have accounted for these infections, including incorrect triage and/or failure to recognize patients and corpses with Ebola virus disease; delayed laboratory diagnosis; limited availability of appropriate personal protective equipment and hand washing facilities; and inadequate training about safe management of contaminated waste and burial of corpses.

Medical procedures played a major role in some past Ebola epidemics by amplifying the spread of infection.

A tragic example of an iatrogenic point-source outbreak occurred in 1976, when an individual infected with Ebola virus was among the patients treated in a small missionary hospital in Yambuku, Zaire [96]. At this hospital, the medical staff routinely injected all febrile patients with antimalarial medications, employing syringes that were rinsed in the same pan of water, then re-used. Virus from the index case was transmitted simultaneously to nearly 100 people, all of whom developed fulminant Ebola virus disease and died [97]. Infection then spread to family caregivers, hospital staff, and those who prepared bodies for burial.

A different type of iatrogenic amplification occurred in 1995 in Kikwit, Democratic Republic of the Congo when a patient was hospitalized with abdominal pain and underwent exploratory laparotomy [10]. The entire surgical team became infected, probably through unprotected respiratory exposure to aerosolized blood. Once those persons were hospitalized, the disease spread to hospital staff, patients, and family members through direct physical contact.

Despite these dramatic episodes of nosocomial transmission, other hospital-based experiences have demonstrated a much lower incidence of secondary spread. As an example, when a patient with unrecognized Ebola virus disease was treated in a South African hospital in 1998, only one person became infected among 300 potentially exposed healthcare workers [98,99]. A similar observation was made when a patient with an unrecognized infection with Marburg virus, a closely related filovirus, was treated in a South African hospital in 1975, resulting in the spread of infection to only two people with close physical contact [100].

Assistance from the international medical community has played an important role in controlling large epidemics in Africa. In the past, intervention strategies focused largely on helping local healthcare workers to identify Ebola patients, transfer them to isolation facilities, provide basic supportive care, monitor all persons who had been in direct contact with cases, and rigorously enforce infection control practices [28,101-103]. During the 2014-2015 West African epidemic, the massive international response is making it possible to supplement isolation procedures with more effective supportive care [104]. (See "Treatment and prevention of Ebola virus disease", section on 'Infection control precautions' and "Treatment and prevention of Ebola virus disease", section on 'Public health response'.)

Transmission from animals

Contact with infected animals — Human infection with Ebola virus can occur through contact with wild animals (eg, hunting, butchering, and preparing meat from infected animals) [105,106]. In Mayibou, Gabon in 1996, for example, a dead chimpanzee found in the forest was butchered and eaten by 19 people, all of whom became severely ill over a short interval [36]. Since that time, several similar episodes have resulted from human contact with infected gorillas or chimpanzees through hunting [107]. To help prevent infection, food products should be properly cooked since the Ebola virus is inactivated through cooking [108]. In addition, basic hygiene measures (eg, hand washing, and changing clothes and boots after touching the animals) should be followed.

Exposure to bats — Direct transmission of Ebola virus infection from bats to wild primates or humans has not been proven. However, Ebola RNA sequences and antibodies to Ebola virus have been detected in bats captured in Central Africa [67,68,109]. Bats have been identified as a direct source of human infection with Marburg virus. (See 'Viral reservoirs' above.)

Other routes — Other potential routes of transmission include the following:

Accidental infection of workers in any Biosafety-Level-4 (BSL-4) facility where filoviruses are being studied.

Use of filoviruses as biological weapons [110,111]. (See "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Bioterrorism'.)

To date, there is no evidence that Ebola virus is carried from person to person by mosquitoes or other biting arthropods. Past epidemics of Ebola virus disease in Central Africa would certainly have been larger and more difficult to control if the virus were transmitted by these mechanisms.

PATHOGENESIS — Because of the difficulty of performing clinical studies under outbreak conditions, almost all data on the pathogenesis of Ebola virus disease have been obtained from laboratory experiments employing mice, guinea pigs, and nonhuman primates. However, case reports and large-scale observational studies of patients in the 2014-2015 West African outbreak are providing urgently needed data on the pathogenesis of the disease in humans [81,104,112].

Cell entry and tissue damage — After entering the body through mucous membranes, breaks in the skin, or parenterally, Ebola virus infects many different cell types. Macrophages and dendritic cells are probably the first to be infected; filoviruses replicate readily within these ubiquitous "sentinel" cells, causing their necrosis and releasing large numbers of new viral particles into extracellular fluid (figure 1) [6,113].

Rapid systemic spread is aided by virus-induced suppression of type I interferon responses [114]. Dissemination to regional lymph nodes results in further rounds of replication, followed by spread through the bloodstream to dendritic cells and fixed and mobile macrophages in the liver, spleen, thymus, and other lymphoid tissues. Necropsies of infected animals have shown that many cell types (except for lymphocytes and neurons) may be infected, including endothelial cells, fibroblasts, hepatocytes, adrenal cortical cells, and epithelial cells. Fatal infection is characterized by multifocal necrosis in tissues such as the liver and spleen.

Gastrointestinal dysfunction — Patients with Ebola virus disease commonly suffer from vomiting and diarrhea, which can result in acute volume depletion, hypotension, and shock [1,4,115]. It is not clear if such dysfunction in Ebola virus disease is the result of viral infection of the gastrointestinal tract, or if it is induced by circulating cytokines, or both. Discussions on the gastrointestinal manifestations of Ebola virus disease, as well as their impact on treatment and prognosis are found elsewhere. (See "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Signs and symptoms' and "Treatment and prevention of Ebola virus disease", section on 'Supportive care' and "Treatment and prevention of Ebola virus disease", section on 'Prognostic factors'.)

Systemic inflammatory response — In addition to causing extensive tissue damage, Ebola virus also induces a systemic inflammatory syndrome by inducing the release of cytokines, chemokines, and other proinflammatory mediators from macrophages and other cells [6,113].

Infected macrophages produce tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, macrophage chemotactic protein (MCP)-1, and nitric oxide (NO) [116]. These and other substances have also been identified in blood samples from Ebola-infected macaques and from acutely ill patients in Africa [17,117,118]. Breakdown products of necrotic cells also stimulate the release of the same mediators [119].

This systemic inflammatory response may play a role in inducing gastrointestinal dysfunction, as well as diffuse vascular leak and multiorgan failure that is seen later in the disease course [120]. (See 'Gastrointestinal dysfunction' above and "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Clinical manifestations'.)

Coagulation defects — The coagulation defects seen in Ebola virus disease appear to be induced indirectly, through the host inflammatory response. Virus-infected macrophages synthesize cell-surface tissue factor (TF), triggering the extrinsic coagulation pathway; proinflammatory cytokines also induce macrophages to produce TF [121]. The simultaneous occurrence of these two stimuli helps to explain the rapid development and severity of the coagulopathy in Ebola virus infection.

Additional factors may also play a role in the coagulation defects that are seen with Ebola virus disease. As examples, blood samples from Ebola-infected monkeys contain D-dimers within 24 hours after virus challenge, and D-dimers are also present in the plasma of humans with Ebola virus disease [121,122]. In Ebola virus-infected macaques, activated protein C is decreased on day two, but the platelet count does not begin to fall until days three or four after virus challenge, suggesting that activated platelets are adhering to endothelial cells. As the disease progresses, hepatic injury may also cause a decline in plasma levels of certain coagulation factors. (See "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Laboratory findings'.)

Impairment of adaptive immunity — Failure of adaptive immunity through impaired dendritic cell function and lymphocyte apoptosis helps to explain how filoviruses are able to cause a severe, frequently fatal illness [5].

Ebola virus acts both directly and indirectly to disable antigen-specific immune responses. Dendritic cells, which have primary responsibility for the initiation of adaptive immune responses, are a major site of filoviral replication. In vitro studies have shown that infected cells fail to undergo maturation and are unable to present antigens to naive lymphocytes, potentially explaining why patients dying from Ebola virus disease may not develop antibodies to the virus [17,123-126].

Adaptive immunity is also impaired by the loss of lymphocytes that accompanies lethal Ebola virus infection [123,127-129]. Although these cells appear to remain uninfected, they undergo "bystander" apoptosis, presumably induced by inflammatory mediators and/or the loss of support signals from dendritic cells. A similar phenomenon is observed in septic shock [119,130,131]. However, one study has shown that at least in Ebola-infected mice, virus-specific lymphocyte proliferation still occurs despite the surrounding massive apoptosis, but it arrives too late to prevent a fatal outcome [132]. Discovering ways to accelerate and strengthen such responses may prove to be a fruitful area of research.

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SUMMARY AND RECOMMENDATIONS

The family Filoviridae contains two genera, the Ebola viruses and Marburg virus. (See 'Introduction' above.)

The Zaire species of Ebola virus, the causative agent of the 2014-2015 West African epidemic, is among the most virulent human pathogens known. The case-fatality rate in past outbreaks in Central Africa reached 80 to 90 percent, and has been reported to be as high as 70 percent in West Africa. (See 'Introduction' above.)

In the past, Ebola virus was classified as a "hemorrhagic fever virus." However, that term is no longer used since only a small percentage of patients actually develop significant bleeding, and it usually occurs in the terminal phase of illness. (See 'Classification' above.)

Until the 2014-2015 epidemic in West Africa, all outbreaks of Ebola virus disease had occurred in Central Africa or the Sudan. (See 'Epidemiology' above.)

The 2014-2015 West African epidemic is the largest filovirus outbreak on record. It started in the nation of Guinea in late 2013 and was confirmed by the World Health Organization in March 2014. The countries with widespread transmission included Guinea, Liberia, and Sierra Leone. Cases of Ebola virus disease have occurred in hundreds of healthcare workers who were infected while caring for patients. (See '2014-2015 outbreak in West Africa' above.)

A number of patients with Ebola virus disease (eg, doctors and nurses infected in West Africa, returning travelers from the region) have been treated in hospitals in the United States and Europe. (See '2014-2015 outbreak in West Africa' above.)

The reservoir host of Ebola virus is not known. Evidence is accumulating that various bat species may serve as a source of infection for both humans and wild primates. (See 'Viral reservoirs' above.)

Person-to-person transmission is associated with direct contact with symptomatic individuals with Ebola virus disease (or the bodies of people who have died from Ebola) and direct contact with body fluids from patients with Ebola virus disease. Transmission to healthcare workers may occur when appropriate personal protective equipment is not available or is not properly used, especially when caring for a severely ill patient. (See 'Transmission' above.)

Infectious virus and/or viral RNA can persist for weeks to months in certain bodily fluids of convalescent patients; such fluids include semen, urine, and breast milk. However, the risk of transmission from persistent virus at these sites is not well established. (See 'Convalescent period' above.)

Patients with Ebola virus disease commonly suffer from severe vomiting and diarrhea. It is not clear if such dysfunction in Ebola virus disease is the result of viral infection of the gastrointestinal tract, or if it is induced by circulating cytokines, or both. (See 'Gastrointestinal dysfunction' above.)

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