Version July 2025
INTRODUCTION —
The family Filoviridae includes the genera Orthoebolavirus and Orthomarburgvirus, which are among the most virulent pathogens of humans [1-5]. The genus Orthoebolavirus consists of six species: Zairense, Sudanense, Bundibugyoense, Taiense, Restonense, and Bombaliense [6]. Of these, only the first four have caused recognized Ebola disease in humans. All but the restonense species are indigenous to Africa. Several other genera of filoviruses have recently been identified in animals, but there is no evidence that they cause disease in humans.
The Zairense species, now termed Ebola virus, was the first to be discovered [4,5,7]. From 1976 through 2013, it caused multiple outbreaks in the Democratic Republic of the Congo (DRC) and neighboring countries in Central Africa, with case fatality rates often approaching 90 percent. Those outbreaks usually involved fewer than 100 cases and were contained within a period of weeks to a few months. In 2014, Ebola virus appeared in West Africa, producing an epidemic in Liberia, Guinea, and Sierra Leone that took more than two years to bring under control [8]. There were nearly 29,000 total cases (suspected, probable, or confirmed), of which more than 15,000 were laboratory confirmed, and the overall case fatality rate was approximately 40 percent. Since then, Ebola virus has been responsible for additional epidemics, including several outbreaks in the DRC [9,10]. A subsequent outbreak in Guinea in early 2021 appears to have resulted from persistent human infection since the 2014 West African epidemic, though the manner of persistence could not be determined [11,12].
The Sudanense species, termed Sudan virus, was also discovered in 1976 [13]. In five outbreaks in Uganda and Sudan, including one that ended in January 2023, case fatality rates have averaged approximately 50 percent. The bundibugyoense species, termed Bundibugyo virus, has been responsible for small outbreaks in Uganda and the adjacent DRC [14], while the Ivory Coast virus has caused one nonfatal case [15]. The restonense species, termed Reston virus, which has been found in pigs in the Philippines, and the Bombaliense species, termed Bombali virus, identified as viral RNA in African bats, are not known to cause disease in humans.
Epidemics typically begin when a human comes into contact with an infected animal or its body fluids [1,3]. However, the persistence of virus in persons who have recovered from Ebola virus disease may also be a source of infection for new outbreaks [12,16-18]. Person-to-person transmission is based upon direct physical contact with the body fluids of a living or deceased patient. Patients typically present with a nonspecific febrile syndrome that may include headache, muscle aches, and fatigue [1,3,19]. Vomiting and diarrhea frequently develop during the first few days of illness and may lead to significant volume losses. A maculopapular rash is sometimes observed. Despite the traditional name of "Ebola hemorrhagic fever," major bleeding is not found in most patients, and severe hemorrhage tends to be observed only in the late stages of disease. Some patients develop progressive hypotension and shock with multiorgan failure, which typically results in death during the second week of illness. By comparison, patients who survive infection commonly begin to show signs of clinical improvement during the second week of illness.
The experience of the 2014 to 2016 West African epidemic demonstrated that the mortality associated with Ebola virus disease may be reduced through adequate supportive care [8]. It also accelerated the investigation of therapies and vaccines for treatment and prevention of Ebola virus disease [17,18]. As an example, two different monoclonal antibody therapies were found to be beneficial in the "PALM" clinical trial conducted in the North Kivu epidemic in the DRC [19]. In addition, the rVSV-ZEBOV vaccine, first found to provide significant protection in West Africa, was given to more than 300,000 people during the course of the North Kivu epidemic and to more than 30,000 people during the 2020 outbreak in the Équateur Province [10].
The epidemiology and pathogenesis of Ebola disease will be presented here. The clinical manifestations, diagnosis, treatment, and prevention of Ebola disease are discussed elsewhere. (See "Clinical manifestations and diagnosis of Ebola disease" and "Treatment and prevention of Ebola and Sudan virus disease".)
CLASSIFICATION —
Orthoebolaviruses are 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, Orthoebolaviruses and Orthomarburgviruses were classified as "hemorrhagic fever viruses," based upon their clinical manifestations, which include coagulation defects, bleeding, and shock. However, the term "hemorrhagic fever" is no longer used to refer to Ebola disease because only a small percentage of Ebola disease patients 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 disease", section on 'Clinical manifestations'.)
There are six Orthoebolaviruses: Ebola virus (species orthoebolavirus zairense), Sudan virus (species orthoebolavirus sudanense), Tai Forest virus (species orthoebolavirus taiense), Bundibugyo virus (species orthoebolavirus bundibugyoense), Reston virus (species orthoebolavirus restonense), and Bombali virus (species orthoebolavirus bombaliense) [4,6,20].
Four of these Orthoebolaviruses cause disease in humans [21]:
●Ebola virus has caused multiple large outbreaks in Central Africa since it was first recognized in 1976, with mortality rates ranging from 55 to 88 percent [22-25]. Ebola virus was the causative agent of the 2014 to 2016 West African epidemic, and it has caused multiple outbreaks in the Democratic Republic of the Congo (DRC) since 2018. An outbreak caused by Ebola virus was recognized in the Équateur province of the DRC in April 2022, representing the third outbreak in this province and the sixth in the country since 2018 [26]. (See 'Democratic Republic of the Congo' below.)
●Sudan virus has been associated with a case fatality rate of approximately 50 percent in seven epidemics: three in Sudan in 1976, 1979, and 2004; one in the DRC in 2014; and three in Uganda in 2000, 2011, and 2022 [13,27-34].
●Tai Forest virus has only been identified as the cause of illness in one person in the Ivory Coast, and that individual survived [35]. 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.
●Bundibugyo virus emerged in Uganda in 2007, causing an outbreak of disease with a lower case fatality rate (approximately 30 percent) than is typical for Ebola and Sudan viruses [36]. Another epidemic with a case fatality rate of 34 percent among confirmed cases occurred in the northeastern DRC in 2012 [36,37]. Sequencing has shown that the agent is most closely related to the Tai Forest species [14].
An analysis of the pooled case fatality rates (CFR) of outbreaks of Ebola disease from 1976 to 2022 found a CFR of 66.6, 48.5, and 32.8 for infections due to Ebola virus, Sudan virus, and Bundibugyo virus, respectively [38]. Cases treated in sub-Saharan Africa had an overall fatality rate of 61.3 percent, while those treated elsewhere had a fatality rate of 24.5 percent.
The fifth 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 [39,40] (see 'Viral reservoirs' below). The 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 [41]. 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 animal caretakers who were exposed to sick animals without protective equipment became ill, but several showed evidence of seroconversion consistent with asymptomatic infection.
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 Reston virus [42]. 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 Reston virus is able to cause mild or asymptomatic infection in humans.
Similar to the Reston virus, the Bombali virus, which was identified as viral RNA in African bats, is not known to cause disease in humans [6,43].
EPIDEMIOLOGY
Overview — Filoviral disease of humans is a zoonosis, with bats in Sub-Saharan Africa as the apparent reservoir hosts. (See 'Viral reservoirs' below.)
Single infections or small clusters of cases may occur frequently within the enzootic region, but since human-to-human transmission requires direct physical contact with virus-containing body fluids of a sick person, these introductions may "burn out" without being diagnosed. Epidemics are typically recognized only after several generations of transmission have occurred, weeks after the initial infection, when a severely ill patient is treated in a medical facility. The initial case usually cannot be retrospectively identified. (See 'West Africa' below and 'Democratic Republic of the Congo' below and 'Uganda' below.)
The filoviruses were first recognized in 1967, when the inadvertent importation of infected monkeys from Uganda resulted in an explosive outbreak 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 [44]. The causative agent, designated Marburg virus, has caused several outbreaks in Africa, which are discussed in detail in a separate topic review. (See "Marburg virus".)
The genus, Orthoeblavirus, has caused outbreaks in Central, Northeast, and West Africa:
●Central Africa – Orthoeblaviruses were first recognized when two outbreaks occurred almost simultaneously in Zaire and in Sudan in 1976 [7,13]. An epidemic caused by Ebola virus subsequently caused several hundred cases in 1995 in Kikwit, Democratic Republic of the Congo (DRC) [24]. Additional outbreaks have subsequently occurred in the DRC, as described below. (See 'Democratic Republic of the Congo' below.)
●Northeast Africa – The Sudan virus caused an epidemic in the Sudan in 1976 and has been responsible for several outbreaks in East Africa since that time, including an epidemic of some 400 cases in Gulu, Uganda in 2000 [28,29]. The most recent outbreak occurred in late 2022 [31]. (See 'Uganda' below.)
●West Africa – The 2014 to 2016 Ebola epidemic, caused by Ebola virus, was not only the first to occur in West Africa, but was far larger than all previous outbreaks combined [25]. A small outbreak apparently caused by persistence of the same virus in humans occurred in Guinea in 2021 [11,12]. (See 'West Africa' below.)
In addition to causing human infections, these viruses have also spread to wild nonhuman primates, apparently as a result of their contact with an unidentified reservoir host (possibly bats) [45-48]. This has contributed to a reduction in chimpanzee and gorilla populations in Central Africa, and has also triggered some human epidemics due to handling and/or consumption of sick or dead animals by local villagers [45,49]. (See 'Viral reservoirs' below and 'Transmission from animals' below and 'Democratic Republic of the Congo' below.)
West Africa — An Ebola virus disease epidemic began in the West African nation of Guinea in late 2013 and was confirmed by the World Health Organization (WHO) in March 2014 [25]. Prior to that, all previous Ebola virus disease outbreaks occurred in Central Africa. (See 'Democratic Republic of the Congo' below and 'Overview' above.)
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 [25]. The epidemic subsequently spread to Liberia, Sierra Leone, Nigeria, Senegal, and Mali. Sequence analysis of viruses isolated from patients indicated that the epidemic resulted entirely from sustained person-to-person transmission, without additional introductions from animal reservoirs [50,51].
Nearly 29,000 probable, suspected, and laboratory-confirmed cases of Ebola virus disease were identified, with more than 11,000 deaths. These cases included 881 infected health care workers, of whom approximately 60 percent died. The magnitude of the epidemic, especially in Liberia and Sierra Leone, was probably underestimated, due in part to individuals with Ebola virus disease being cared for outside the hospital setting early in the epidemic.
In Guinea, Liberia, and Sierra Leone, there was widespread Ebola virus transmission, and the rate of new infections did not slow significantly until the spring of 2015. Extended periods of disease-free transmission were subsequently reported. In certain nearby countries (Senegal, Nigeria, Mali), introductions of Ebola virus resulted in short chains of person-to-person transmission, which were quickly terminated.
The end of the epidemic was officially recognized in early 2016. However, sporadic cases continued to be detected, which were attributed to sexual transmission from survivors with persistent virus [52]. (See 'Convalescent period' below.)
During the epidemic, cases of Ebola virus disease occurred in residents and health care workers who were exposed to the virus in West Africa and were then treated in hospitals in the United States and Europe [53-55]. As an example, on September 30, 2014, the first travel-associated case of Ebola virus disease was reported in the United States. 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.
Measures that appear to have contributed to the control of the epidemic include the introduction of infection control precautions in hospitals, instructions to the population regarding safe funeral practices, and the use of Ebola treatment units and community care centers to help isolate patients with suspected or confirmed infection [56-58]. (See "Treatment and prevention of Ebola and Sudan virus disease", section on 'Infection control precautions during acute illness'.)
In February 2021, a new outbreak of Ebola virus disease was detected in a region of Guinea affected by the 2014 to 2016 epidemic [11,12]. There were 16 confirmed and seven probable cases, of whom 12 died. The index case was a female nurse, whose family remained healthy. Virus isolates were closely related in sequence to those that circulated in the area in 2014 to 2016, suggesting that the outbreak resulted from persistent human infection, but the manner could not be determined.
Democratic Republic of the Congo — Since 1976, there have been multiple recognized outbreaks of Ebola virus disease in the DRC. These have usually involved fewer than 100 cases and have been contained within a period of weeks to a few months. All but one were caused by Ebola virus.
Several Ebola virus disease outbreaks have been reported since early 2018. These include:
●An outbreak in the Équateur Province was detected in early May 2018, leading to an intensive response by the DRC Ministry of Health, the WHO, Médecins Sans Frontières, and other international organizations to rapidly establish treatment facilities, case finding, and contact tracing to prevent further transmission. The end of the outbreak was announced on July 24, 2018 [59]. Of the 38 confirmed and 16 probable cases, there were 33 deaths (a case fatality rate of 61 percent). Notably, ring vaccination with the vesicular stomatitis virus-Ebola virus (VSV-Ebola) vaccine was begun less than two weeks after the outbreak was confirmed; nearly 4000 health care workers, contacts of patients, and their contacts received the vaccine.
●A subsequent outbreak was reported on August 1, 2018 in the North Kivu Province, which is located in the northeastern region of the country, bordering Rwanda and Uganda, where long-term armed conflicts have produced large numbers of refugees [9,60]. On June 11, 2019, the WHO reported that the outbreak spread to the Kasese District of Uganda, which borders the DRC; however, all the cases were imported from the DRC, and there were no transmission or secondary cases in Uganda. During this outbreak, mobile field laboratories and Ebola treatment centers were rapidly established, and vaccination of health care workers and close contacts of patients using the VSV-ZEBOV vaccine (sold as Ervebo) was initiated. When the epidemic was declared over on June 25, 2020, there had been 3470 confirmed cases with 2287 deaths, a fatality rate of 66 percent [61]. Of those cases, approximately 57 percent were female, 29 percent were younger than 18 years of age, and 5 percent were health care workers. During the North Kivu epidemic, medical workers investigated some 250,000 case contacts, tested 220,000 blood samples, and vaccinated more than 300,000 people.
●On June 1, 2020, an outbreak of Ebola virus disease was identified in Mbandaka, Équateur Province of the DRC, the same region in which an epidemic was reported in May 2018, as described above. In contrast to the earlier outbreak, cases were widely distributed within the province, occurring in 13 of the 18 health zones. By the time it was declared over on November 18, 2020, there had been 119 confirmed and 11 probable cases, with 55 deaths. More than 40,000 people at high risk of infection were given the VSV-Ebola vaccine. A retrospective genomic study of 87 patients found that 97 percent had been infected by a newly introduced virus, while the virus recovered from the others resembled the agent responsible for the 2018 outbreak [62].
●On February 7, 2021, an outbreak of Ebola virus disease was identified in the North Kivu region. After the occurrence of 11 confirmed cases and six deaths, and the administration of 2000 doses of vaccine to persons at risk, the outbreak was declared over on May 3, 2021. Virus sequencing suggests that it had resulted from transmission of virus from a survivor of the 2014 to 2016 epidemic and not through the introduction from an animal reservoir [63]. In October 2021, a cluster of Ebola virus disease cases in the same area was recognized and quickly contained; these cases originated from persistent virus in a survivor of an earlier epidemic in North Kivu [26]. As discussed below, numerous instances of persist infectious virus in the semen of male survivors have been recognized. (See 'Convalescent period' below.)
●On April 23, 2022, the Ministry of Health of the DRC declared an outbreak of Ebola virus disease in the northwestern Equateur province. Full genome sequencing of the virus performed at the INRB (Institut National de Recherche Biomédicale) in Kinshasa has shown that this outbreak is due to a new spillover event from an animal source and not from viral persistence in a survivor. This outbreak was declared over in July 2022.
●A single case that occurred in North Kivu in August 2022 was determined by sequencing to be linked to earlier outbreaks in the region [64].
Updated information on outbreaks of Ebola virus disease can be found on the WHO website. Discussions of vaccines and therapies are presented in a separate topic review. (See "Treatment and prevention of Ebola and Sudan virus disease", section on 'Vaccination to prevent Ebola virus disease' and "Treatment and prevention of Ebola and Sudan virus disease", section on 'Ebola virus-specific therapies'.)
Uganda — Sudan virus has been responsible for several outbreaks in East Africa, including an epidemic of some 400 cases in Gulu, Uganda, in 2000 [28,29].
On September 20, 2022, an outbreak of Sudan virus disease was detected in Uganda [32]. The first recognized patient became ill on the 11th of September, with high fever, vomiting, diarrhea, and other signs consistent with Ebola disease [33]. A positive RT-PCR test for Sudan virus was obtained on September 19th, the day of his death. The patient was diagnosed in Mubende district, where similar cases appear to have been occurring as early as the beginning of September.
The 2022 outbreak was of particular concern since it is likely that there were undetected chains of transmission over several weeks and because of the potential wide mobility of infected individuals who were asymptomatic, including men working in local gold mines. In addition, available countermeasures, such as vaccination, were more limited than those employed in recent Ebola virus disease epidemics in the Democratic Republic of the Congo. As an example, the single-dose recombinant vesicular stomatitis virus vaccine, which elicits a rapid immune response against Ebola virus, was not expected to protect against the Sudan virus. Although a two-dose vaccine approved by the European Medicines Agency expresses the Sudan virus surface glycoprotein among other antigens, it requires a 56-day interval between doses and would thus offer less protection in a rapidly spreading outbreak.
On January 11, 2023, the Ministry of Health of Uganda declared the end of the epidemic [34]. By the end there were a total of 164 cases (142 confirmed, 22 probable) with 77 deaths. A retrospective study found that one individual was the source of infection for 18 secondary cases and another individual for 33 secondary cases [65]. The modes of transmission from these two individuals included extended time in the community while ill, cross-district travel for treatment, and certain religious practices.
Analyses of blood samples from a majority of confirmed cases found that the causative agent, designated the Mubende variant, exhibited 96 percent amino acid similarity with Sudan viruses isolated in the 1970s and that it underwent little sequence change over the course of the outbreak [66].
On January 30, 2025, the Ministry of Health of Uganda declared a new outbreak of Sudan virus disease; the index case was an adult male nurse [67,68]. As of February 20, 2025, there were nine confirmed cases with one death [69,70]. After an interval with no new cases, a new cluster caused by the same virus strain was identified in early March, indicating continuing undetected transmission. Nearly 500 contacts are being followed; a clinical trial of a recombinant vesicular stomatitis virus vaccine encoding the Sudan virus surface glycoprotein is being performed among contacts [71]. On March 20th, 2025 following the discharge of the last two patients from hospital, the Ugandan Ministry of Health began a 42-day countdown to be able to declare the outbreak over.
More detailed information on vaccination to prevent Sudan virus disease is presented in a separate topic review. (See "Treatment and prevention of Ebola and Sudan virus disease", section on 'Vaccination to prevent Sudan virus disease'.)
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 [20,47]. While Marburg virus has been isolated directly from bats captured in Uganda [72], only Orthoebolavirus RNA sequences, not infectious virus, have been detected in samples collected from bats in Central Africa, and none has been isolated in West Africa [73,74]. Nevertheless, data suggest that bats are at least one of the reservoir hosts of Orthoebolavirus in Africa [75].
Research employing captive bats is beginning to elucidate their ability to tolerate filovirus infection without evident disease [76]. An experimental study in captive Angolan free-tailed bats, a known reservoir of the Bombali virus, found that Bombali virus caused disseminated viral replication and shedding without evident disease, while other filoviruses pathogenic for humans did not cause productive infection [77]. The transmission pathway from bats to humans and the possible role of bats in the initiation of Ebola disease outbreaks have not been defined.
TRANSMISSION —
Epidemics of Ebola disease are generally thought to begin when an individual becomes infected through contact with the tissues 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 orthoebolaviruses through droplet inoculation of virus into the mouth or eyes [78-81], suggesting that human infection can result from the inadvertent transfer of virus to these sites from contaminated hands. More recent studies in macaques have shown that most animals survive the introduction of a low dose of 100 plaque-forming unit of virus into the mouth or onto the conjunctiva, while larger doses cause lethal disease [80,81]One report found that oral exposure of cynomolgus macaques to 100 plaque-forming units of Ebola virus (Makona variant), the agent of the 2013 to 2016 West African epidemic, was lethal for most animals [82]. Persistence of virus in semen can also transmit infection. (See 'Convalescent period' below.)
Prior to the epidemic in West Africa, outbreaks of Ebola disease were typically controlled within a period of a few 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 West African epidemic showed that Ebola virus disease can spread rapidly and widely because of the extensive movement of infected individuals (including undetected travel across national borders), the spread of the disease to densely populated urban areas, the avoidance and/or lack of adequate personal protective equipment (PPE), and the absence of dedicated medical isolation centers. (See "Treatment and prevention of Ebola and Sudan virus disease", section on 'Infection control precautions during acute illness'.)
Person-to-person — Person-to-person transmission is principally associated with direct contact with the body fluids of individuals with Ebola disease or have died from the infection, in the absence of PPE [83,84]. 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 compared with 2.1 percent for those household members who had direct physical contact but did not provide nursing care [85].
●The ritual washing of Ebola disease victims at funerals has played a significant role in the spread of infection in past outbreaks and contributed to the epidemic in West Africa. As an example, a single funeral ceremony in late 2014 in Guinea was linked to 85 subsequent cases of Ebola virus disease [86].
●During the early phase of the West African epidemic, several hundred African doctors and nurses who performed patient care without appropriate personal protection acquired Ebola virus disease. (See 'West Africa' above and 'Nosocomial transmission' below.)
●A retrospective study of intra-household transmission in the West African epidemic found that the spread of infection was more likely in larger households [87]. In addition, more transmissions resulted from older patients and those with severe disease. The estimated secondary attack rate was 18 percent.
●A retrospective study evaluating the 2022 epidemic of Sudan virus disease in Uganda found that mistaken beliefs about the cause of disease and reliance on traditional healers likely contributed to the spread of infection [88].
Men who have recovered from Ebola disease can also be a source of virus transmission through semen. (See 'Convalescent period' below.)
Risk of transmission through different body fluids — 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. 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.
Acute infection — According to the World Health Organization, the most infectious body fluids are blood, feces, and vomitus. Infectious virus has also been detected in urine, semen, saliva, aqueous humor, vaginal fluid, and breast milk [53,89-92]. Reverse-transcription polymerase chain reaction (RT-PCR) testing has also identified viral RNA in tears and sweat, suggesting that infectious virus may be present.
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 thought to be lower than from exposure to blood or body fluids. 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 viral 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 and moribund patients [93]. Epidemiologic studies have 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 [83,87].
Discussions of how to prevent transmission of virus during acute infection are found elsewhere. (See "Treatment and prevention of Ebola and Sudan virus disease", section on 'Infection control precautions during acute illness'.)
Convalescent period — Infectious virus or viral RNA can persist in some body fluids of patients recovering from Ebola disease even after it is no longer detected in blood. As examples:
●Follow-up studies of approximately 40 survivors in the 1995 outbreak in Kikwit, Democratic Republic of the Congo found that Ebola virus RNA 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 [89].
●A study of patient samples collected during the outbreak of Sudan virus disease in Gulu, Uganda in 2000 detected virus in the breast milk of a patient after virus was no longer detectable in the bloodstream [90]. Two children who were breastfed by infected mothers died of the disease. Similarly, during the West Africa epidemic, a nine-month-old infant died of Ebola virus disease, while its mother remained healthy; Ebola virus RNA was subsequently detected in her breast milk, but urine and blood were negative [94].
●During the 2014 to 2016 outbreak in West Africa, infectious virus or viral RNA was detected in several body fluids. These include:
•Semen – The persistence of Ebola virus in the semen of survivors has been evaluated in several studies. 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; however, the percentage of patients with persistent virus and the level of virus detected in semen decreased over time [95]. In another study that evaluated a cohort of 267 male survivors, Ebola virus RNA was detected in the semen of 30 percent of survivors an average of 19 months following acute Ebola virus disease illness [96]. Many of these men (44 percent) had two negative tests followed by a positive test, and one man had Ebola virus RNA detected in semen 40 months after acute illness. In one report, the concentration of Ebola virus RNA in semen during early recovery was 4 logs higher than in blood during peak infection [97]. A study of male survivors from the West African epidemic found that the persistence of Ebola virus RNA in semen more than a year after recovery was more common in older patients who had experienced milder disease [98].
•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 of Ebola virus disease symptoms and 9 weeks after viremia had resolved [91].
•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 from the cerebrospinal fluid [99].
•Urine – Ebola virus was cultured from a patient's urine 26 days after the onset of symptoms, which was nine days after the plasma RNA level became negative [53].
Transmission from persistent virus in semen has been shown to occur. A review of all known Ebola disease epidemics from 1976 through 2022 suggests that as many as one-fourth may have resulted from exposure to a persistently infected survivor of an earlier outbreak [100]. As one example, a patient in the 2014 to 2016 West African epidemic who had Ebola virus RNA in his semen at least 199 days after symptom onset transmitted Ebola virus to one, but not another, of his sexual contacts [101,102]. The transmission occurred approximately five months after his blood tested negative for Ebola virus RNA.
Similarly, a retrospective study of the 2018 to 2020 outbreak in the North Kivu region of the Democratic Republic of the Congo (DRC) has supported the potential epidemiologic importance of persistent virus [16]. One man who developed Ebola virus disease despite prior vaccination, and who recovered following treatment with the monoclonal antibody mAb114, relapsed six months later and died from the disease. Sequence analysis showed that the same virus strain persisted in the patient throughout his illness, and during his convalescence, he was the source of a transmission chain that resulted in 91 additional cases.
The outbreak declared in Guinea on February 14, 2021 also appears to have been initiated by the persistence of virus in an individual who developed Ebola virus disease during the 2014 to 2016 epidemic, but the manner of persistence could not be determined [11,12]. (See 'West Africa' above.)
Discussions of how to prevent transmission of virus during the convalescent period are found elsewhere. (See "Treatment and prevention of Ebola and Sudan virus disease", section on 'Infection Prevention'.)
Risk of transmission through contact with contaminated surfaces — Orthoebolaviruses may be transmitted though contact with contaminated surfaces and objects. The US Centers for Disease Control and Prevention (CDC) indicates that virus on surfaces may remain infectious from hours to days. There are no high-quality data to confirm transmission through exposure to contaminated surfaces, but it is clear that the potential risk can be greatly reduced or eliminated by proper environmental cleaning. (See "Treatment and prevention of Ebola and Sudan virus disease", section on 'Environmental infection control'.)
Risk of airborne transmission — There are no reported cases of Orthoebolaviruses being spread from person to person by the respiratory route. However, laboratory experiments have shown that virus released as a small-particle aerosol is infectious for rodents and nonhuman primates [103,104]. A study employing Ebola virus (Makona variant) from the 2013 to 2016 West African epidemic found that very small amounts of aerosolized virus were lethal for cynomolgus macaques; time to death was dose dependent [105]. Health care workers may therefore be at risk of Ebola disease if exposed to aerosols generated during medical procedures.
Nosocomial transmission — Transmission to health care workers may occur when appropriate PPE is not available or is not properly used, especially when caring for a severely ill patient who is not recognized as having Ebola disease.
During the epidemic in West Africa, a large number of doctors and nurses became infected with Ebola virus (see 'West Africa' above). In Sierra Leone, the incidence of confirmed cases over a seven-month period was approximately 100-fold higher in health care workers than in the general population [106]. Several factors accounted for these infections, including errors in triage and/or failure to recognize patients and corpses with Ebola virus disease, delayed laboratory diagnosis, limited availability of appropriate PPE 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 disease epidemics by amplifying the spread of infection.
●An 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 [107]. 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 reused. Virus from the index case was transmitted simultaneously to nearly 100 people, all of whom developed Ebola virus disease and died [108]. 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 [24]. 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 disease was treated in a South African hospital in 1998, only one person became infected among 300 potentially exposed health care workers [109,110]. 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 [111].
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 health care workers to identify patients with Ebola disease, 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 [112-114]. During the West African epidemic, the massive international response made it possible to supplement isolation procedures with more effective supportive care [115].
The subsequent outbreaks in the DRC have also benefited from a response from international aid organizations. In the epidemic in the North Kivu region, patient care included enrollment in a randomized trial of four potential therapies, of which two (REGN-EB3 and mAb114, both monoclonal antibody preparations) provided a significant survival benefit [116,117]. These agents have been approved by the US Food and Drug Administration (FDA) for the treatment of Ebola virus infection. (See "Treatment and prevention of Ebola and Sudan virus disease".)
Transmission from animals
Contact with infected animals — Human infection with Orthoebolaviruses can occur through contact with wild animals (eg, hunting, butchering, and preparing meat from infected animals). 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 [49]. Since that time, several similar episodes have resulted from human contact with infected gorillas or chimpanzees through hunting [118]. To help prevent infection, food products should be properly cooked, since virus is inactivated through cooking. In addition, basic hygiene measures (eg, hand washing and changing clothes and boots after touching the animals) should be followed. Some public health messages in West Africa regarding the consumption of "bush meat" have contained incorrect information and may have been counterproductive [119].
Exposure to bats — Direct transmission of Orthoebolaviruses from bats to wild primates or humans has not been proven. However, Ebola virus RNA sequences and antibodies to the virus have been detected in bats captured in Central Africa [73,74,120]. 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 [121,122]. (See "Clinical manifestations and diagnosis of Ebola disease", section on 'Bioterrorism'.)
There is no evidence that Orthoebolaviruses can be transferred from person to person by mosquitoes or other biting arthropods. Epidemics of Ebola disease would certainly be much 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, most data on the pathogenesis of Ebola disease have been obtained from laboratory experiments employing mice, guinea pigs, and nonhuman primates. Case reports and large-scale observational studies of patients in the West African epidemic provided additional data on pathogenesis; observations of disease mechanisms from the epidemic were consistent with findings in animal studies [19,53,54,115,123].
Cell entry and tissue damage — After entering the body through mucous membranes, breaks in the skin, or parenterally, pathogenic Orthoebolaviruses infect many different cell types. Macrophages and dendritic cells are probably the first to be infected; viruses replicate readily within these ubiquitous "sentinel" cells, causing their necrosis and releasing large numbers of new viral particles into extracellular fluid (figure 1).
Rapid systemic spread is aided by virus-induced suppression of type I interferon responses [124]. 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 may be infected, including endothelial cells, fibroblasts, hepatocytes, adrenal cortical cells, and epithelial cells; lymphocytes and neurons are the only major cell types that remain uninfected. Laboratory studies in a human skin explant model have shown Orthoebolavirus infection of multiple cell types in the dermis and epidermis [125]. Fatal disease is characterized by multifocal necrosis in tissues such as the liver and spleen.
Gastrointestinal dysfunction — Patients with Ebola disease commonly suffer from severe vomiting and diarrhea, which can result in acute volume depletion, hypotension, and shock [126]. It is not clear if such dysfunction in Ebola disease is the result of viral infection of the gastrointestinal tract, or if it is induced by circulating cytokines, or both. Discussions of the gastrointestinal manifestations of Ebola disease and their impact on treatment and prognosis are found elsewhere. (See "Clinical manifestations and diagnosis of Ebola disease", section on 'Signs and symptoms' and "Treatment and prevention of Ebola and Sudan virus disease", section on 'Supportive care' and "Treatment and prevention of Ebola and Sudan virus disease", section on 'Prognostic factors'.)
Systemic inflammatory response — In addition to causing extensive tissue damage, pathogenic Orthoebolaviruses also produces a systemic inflammatory syndrome by causing the release of cytokines, chemokines, and other proinflammatory mediators from macrophages and other cells [123].
Infected macrophages produce proinflammatory mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, macrophage chemotactic protein (MCP)-1, as well as the vasoactive molecule nitric oxide (NO). These and other substances have also been identified in blood samples from infected macaques and from acutely ill patients in Africa [29]. Breakdown products of necrotic cells also stimulate the release of these mediators.
This systemic inflammatory response may play a role in inducing gastrointestinal dysfunction, as well as the diffuse vascular leak and multiorgan failure that are seen later in the disease course. (See 'Gastrointestinal dysfunction' above and "Clinical manifestations and diagnosis of Ebola disease", section on 'Clinical manifestations'.)
Coagulation defects — The coagulation defects seen in Ebola 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 [123,127]. The simultaneous occurrence of these two stimuli helps to explain the rapid development and severity of the coagulopathy in Ebola disease.
Additional factors may also play a role in the coagulation defects that are seen with Ebola disease. As examples, blood samples from infected monkeys contain D-dimers within 24 hours after virus challenge, and D-dimers are also present in the plasma of humans with Ebola disease [127,128]. In 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 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 [123]. Pathogenic Orthoebolaviruses act 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 disease may not develop antibodies to the virus [29,129-131].
Adaptive immunity is also impaired by the loss of lymphocytes that accompanies lethal virus infection [129,132,133]. 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. However, one study has shown that, at least in Ebola virus-infected mice, virus-specific lymphocyte proliferation still occurs despite the surrounding massive apoptosis, but it arrives too late to prevent a fatal outcome [134]. Discovering ways to accelerate and strengthen such responses may prove to be a fruitful area of research.
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ebola virus".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Ebola (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Virology – The family Filoviridae includes the genera Orthoebolavirus and Orthomarburgvirus, which are among the most virulent pathogens of humans [1-5]. The genus Orthoebolavirus consists of six species: Zairense, Sudanense, Bundibugyoense, Taiense, Restonense, and Bombaliense. (See 'Introduction' above.)
Orthoebolaviruses are among the most virulent human pathogens known. The case-fatality rate in outbreaks has been reported to be as high as 80 to 90 percent. (See 'Classification' above.)
●Epidemiology – Most outbreaks of Ebola disease have occurred in Central Africa or the Sudan. However, the largest filovirus outbreak on record occurred in West Africa between 2014 and 2016. During the West African epidemic, there was widespread transmission of Ebola virus in Guinea, Liberia, and Sierra Leone, with nearly 29,000 cases of Ebola virus disease identified and more than 11,000 deaths. (See 'West Africa' above.)
Since then, there have been several outbreaks Ebola virus in the Democratic Republic of the Congo and outbreaks of Sudan virus in Uganda. (See 'Democratic Republic of the Congo' above and 'Uganda' above.)
●Viral reservoirs – The reservoir hosts of Orthoebolaviruses are 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.)
●Transmission
•Person to person – Person-to-person transmission is principally associated with direct contact with body fluids from patients with Ebola disease or from cadavers of deceased patients. Transmission to health care workers may occur when appropriate personal protective equipment (PPE) is not available or is not properly used, especially when caring for a severely ill patient. (See 'Person-to-person' above.)
Infectious virus and/or viral RNA can persist in certain bodily fluids of convalescent patients; such fluids include semen, urine, and breast milk. Several instances of sexual transmission of the virus from convalescent men have been identified. (See 'Convalescent period' above.)
•Animal to human – Human infection with Orthoebolaviruses can also occur through contact with wild animals (eg, hunting, butchering, and preparing meat from infected animals). (See 'Transmission from animals' above.)
●Pathogenesis – Almost all data on the pathogenesis of Ebola disease have been obtained from laboratory experiments employing mice, guinea pigs, and nonhuman primates. Case reports and large-scale observational studies of patients in the West African epidemic provided additional data on pathogenesis consistent with findings in laboratory animals. (See 'Pathogenesis' above.)
