Factsheet about Ebola disease
Ebola disease is caused by a group of viruses within the genus Ebolavirus. This is a rare disease, but can cause outbreaks with high case fatality rates. So far, most outbreaks have occurred in sub-Saharan countries; the largest outbreak having occurred in three West African countries (Guinea, Liberia, and Sierra Leone) between 2013 and 2016, with over 28 000 cases and 11 000 deaths.
Ebola disease is not an airborne disease and is generally not considered to be contagious before the onset of symptoms. Transmission requires direct contact with the organs, blood, secretions or other bodily fluids of infected people/animals or their dead bodies. Therefore, the risk of infection is considered to be very low if strict infection prevention and control precautions are followed.
Clinical illness starts as a flu-like syndrome, often rapidly evolving to severe disease with haemorrhagic symptoms. Two vaccines against Ebola disease due to Zaire ebolavirus have been granted market authorisations by the EU. There are no licensed vaccines against Ebola disease due to the other ebolavirus species.
The Ebolavirus genus is a member of the Filoviridae family.
It includes four distinct species that are pathogenic to humans: Zaire ebolavirus, Bundibugyo ebolavirus, Taï Forest ebolavirus and Sudan ebolavirus. All four species are found in Africa and cause serious illness in humans. In addition, Reston ebolavirus can cause epizootics, but only causes asymptomatic infection in humans. So far, Reston ebolavirus outbreaks have only been reported in Asia.
Ebolaviruses are classified as a biosafety level 4 (BSL-4) pathogen and require special containment and barrier protection measures for laboratory personnel and anyone taking care of potentially infected patients or handling dead bodies .
Clinical features and sequelae
In most cases, an infected patient experiences a sudden onset of flu-like illness, with
- general malaise and weakness
- muscle and joint pains
This is followed by
- progressive weakness
- diarrhoea (watery stools that sometimes contain blood and mucus)
- nausea and vomiting.
This first set of symptoms corresponds to the prodromal phase (duration up to 10 days).
The next stage of the disease is characterised by symptoms and clinical manifestations from several organ systems. Symptoms can be
- gastrointestinal (vomiting, diarrhoea, anorexia and abdominal pain)
- neurological (headaches and confusion)
- vascular (conjunctival/pharyngeal injections)
- cutaneous (maculopapular rash)
- respiratory (cough, chest pain and shortness of breath) and can include complete exhaustion (prostration).
Haemorrhagic manifestations can also appear (e.g. bloody diarrhoea, nosebleeds, haematemesis, petechiae, ecchymoses and prolonged bleeding from needle-puncture sites). Certain patients develop profuse internal and external haemorrhages and disseminated intravascular coagulation.
Patients in the final stage of the disease die from a combination of multi-organ failure and hypovolemic shock due to severe fluid losses. Based on one systematic review, the weighted case fatality rate (CFR) for Ebola disease (all species included but Reston ebolavirus) was assessed to be 65.0% [95% CI (54.0–76.0%)] . The CFR varies depending on the virus species, with Zaire ebolavirus exhibiting the highest fatality rate (75%), followed by Sudan ebolavirus (53%) .
In rare instances, infected individuals may remain asymptomatic or paucisymptomatic [2,3].
A spill-over from animal to human is a rare event, but subsequent human-to-human transmission can sustain large outbreaks. The typical incubation period ranges from 2 to 21 days and the mean incubation period has been estimated at 6.3 days . Short incubation periods are likely due to exposure to highly contaminated materials (e.g. occupational exposure through needle-stick injuries).
Ebolaviruses are highly transmissible by direct contact with the blood (e.g. through mucous membranes or broken skin), or other bodily fluids (e.g. saliva, urine or vomit) of infected people, their dead bodies, or any surfaces and materials soiled by infectious fluids .
Transmission can also occur through contact with infected animals (living or dead), including the consumption and/or handling of bushmeat (e.g. monkeys, apes, forest antelopes and bats) or by visiting caves or mines colonised by bats .
Healthcare workers can be infected by nosocomial transmissions which can occur as a result of contact with infected patients without wearing the proper protection. Healthcare settings can play a substantial role in the amplification of the disease, particularly at the beginning of an outbreak of Ebola disease before a definitive diagnosis is available and infection prevention and control (IPC) measures have been implemented . The risk of infection can be significantly reduced through the appropriate use of infection control precautions and adequate barrier protection. This is especially important when performing invasive procedures.
Ebolaviruses can persist in immune-privileged sites (e.g. testicles, central nervous system and aqueous humour) of some survivors and, as a result, new transmissions can potentially arise, notably through sexual transmission [6,8,9].
Asymptomatic infections are a limited phenomenon and probably do not contribute significantly to human-to-human transmission [8-13].
The presence of the virus in the blood and, consequently, the organs and tissues of asymptomatic, infected or recovered individuals indicates that transmission of the virus via transfusion and transplantation is possible, although this has not been reported to date.
Filoviruses can survive in liquid or dried material for many days. They are inactivated by gamma irradiation, heating for 60 minutes at 60°C or boiling for five minutes, and are sensitive to lipid solvents, sodium hypochlorite, and other disinfectants. Freezing or refrigeration does not inactivate filoviruses.
Reservoirs of ebolaviruses
Several fruit bats of the Pteropodidae family in central and western Africa, particularly the hammer-headed bat species (Hypsignathus monstrosus), Franquet's epauletted fruit bat (Epomops franqueti) and the little collared fruit bat (Myonycteris torquata) are considered natural reservoirs for ebolaviruses .
In Africa, human infections have been linked to direct contact with wild gorillas, chimpanzees, monkeys, forest antelopes and porcupines found dead in the rainforest. Zaire ebolavirus and Sudan ebolavirus have been detected in the wild in the carcasses of chimpanzees in Côte d’Ivoire and the Republic of the Congo; gorillas in Gabon and the Republic of the Congo; and forest antelopes in the Republic of the Congo. Reston ebolavirus has caused major outbreaks in macaque monkeys in the Philippines, while asymptomatic infections have been reported in pigs.
In 1976, epidemics of severe haemorrhagic fever occurred simultaneously in southern Sudan and the northern part of the Democratic Republic of the Congo, where a new virus was identified and named after a small river called Ebola, in the Mongala province. Later studies showed some differences between the virus isolated in the Democratic Republic of the Congo (Zaire ebolavirus) and the virus isolated in Sudan (Sudan ebolavirus). Multiple outbreaks of Ebola disease have been identified since its initial discovery .
Ebola disease due to Zaire ebolavirus is referred as Ebola virus disease. Large autochthonous outbreaks of Ebola virus disease have so far been reported in the Democratic Republic of the Congo, Gabon, Guinea, Liberia, the Republic of the Congo and Sierra Leone.
To date, the largest reported outbreak of Ebola virus disease occurred in the three West African countries (Guinea, Liberia and Sierra Leone) from 2013 through 2016, with over 28 000 cases and 11 000 deaths [15,16].
Ebola disease due to Sudan ebolavirus is referred as Sudan virus disease. Outbreaks of Sudan virus disease have been reported in Sudan and Uganda .
Ebola disease due to Bundibugyo ebolavirus and Taï Forest ebolavirus is referred to as Bundibugyo virus disease and Taï Forest virus disease, respectively. Outbreaks of Bundibugyo virus disease have been reported in the Democratic Republic of the Congo and Uganda; and outbreaks of Taï Forest virus disease have been reported in Côte d’Ivoire .
Sporadic imported cases of Ebola virus disease have also been reported in several non-endemic African and non-African countries. In some instances, short chains of transmission have occurred in countries such as Mali, Nigeria, Senegal, Uganda, South Africa, Spain, Italy, the United Kingdom and the United States .
Laboratory tests on blood specimens detect viral material (viral genome or antigen) or specific antibodies. Ebola disease is diagnosed by the detection of ebolavirus ribonucleic acid (RNA) in whole blood, plasma or serum during the acute phase of illness, using reverse transcription polymerase chain reaction (RT-PCR) tests. Viral RNA can usually be detected up to a few days after the disappearance of symptoms.
Viral RNA may also be detected in other bodily fluids, such as semen, saliva or urine [17,18]. Throat swabs are suitable for virus detection in deceased patients. Viral RNA has been detected in seminal fluid and in the breast milk of survivors, months to years after acute illness. This poses a risk of sexual or mother-to-child transmission. Identification of acute infections based on serology is uncommon.
Only a few diagnostic tests are commercially available for Ebola disease and these are specific to Ebola virus disease. According to Directive 2000/54/EC of the European Parliament and of the Council, the ebolaviruses are group 4 biological agents . Therefore, samples from infected patients should be handled under strict biological containment conditions in biosafety level 3 (e.g. RT-PCR and enzyme-linked immunosorbent assay on non-inactivated samples) or level 4 laboratories (virus isolation). Any attempt at viral replication should be handled in biosafety level 4 laboratories  . For inactivated samples, RT-PCR and ELISA testing can be performed at a laboratory with BSL-2 facilities.
Case management and treatment
Advances have been made in the treatment of the Ebola virus disease. Two drugs were trialled in the PALM study (‘Pamoja Tulinde Maisha’, which in Kiswahili means ‘Together Save Lives’) during the 2018–20 Ebola outbreak in the Democratic Republic of the Congo . The study showed that both the drugs drastically reduce death rates of Ebola virus disease due to ZEBOV and can be used for both adults and children .
The first of the two treatments, Inmazeb (formerly REGN-EB3), is manufactured by Regeneron Pharmaceuticals. It is a mixture of three monoclonal antibodies (atoltivimab, maftivimab, and odesivimab-ebgn). The drug was approved for use in the US in October 2020 .
Ebanga (Ansuvimab-zykl), the second drug used in the PALM study, is manufactured by Ridgeback Biotherapeutics. It is a human monoclonal antibody (mAb114). The drug was approved for use in the US on 21 December 2020 .
To date there are no treatments approved against Ebola virus disease due to species other than ZEBOV.
Public health control measures
The goal of Ebola disease outbreak control is to interrupt direct human-to-human transmission. Outbreak control activities are based on the early identification and systematic rapid isolation of cases, through
- appropriate infection prevention and control (IPC) measures
- timely and comprehensive contact tracing
- disinfection of infectious materials
- use of personal protective equipment.
In previous outbreaks, isolation of infected patients and the implementation of appropriate IPC measures has been shown to effectively stop the spread of disease.
Early and culturally-relevant community engagement and social mobilisation is essential for the support of outbreak response activities. This is also useful in enhancing the knowledge of affected populations on the risk factors of viral infection and the individual protective measures that they can adopt, especially regarding safe and dignified burial practices.
It is advisable to avoid habitats that may be populated by bats, such as caves or mines in areas/countries where ebolaviruses might be present. The handling or consumption of any type of bushmeat should be avoided, as should close contact with wild animals (such as monkeys, forest antelopes, rodents and bats - alive or dead).
Infection control, personal protection and prevention
Healthcare workers have frequently been infected while treating patients with cases of suspected or confirmed Ebola disease. This occurs through close contact with patients where IPC measures are not strictly implemented or viral aetiology has not yet been recognised.
The appropriate use of infection control precautions and the application of strict barrier nursing procedures are critical to preventing nosocomial transmission. Implementation of appropriate infection control measures in healthcare settings, including use of personal protective equipment, will minimise the risk of transmission of ebolaviruses.
For Zaire ebolavirus transmission by sexual contact has been documented and the World Health Organization (WHO) recommends that male survivors practise safe sex for at least 12 months after clinical recovery, unless their semen has tested negative on two separate occasions [6,25,26]. Sexual transmission events have also been reported in male survivors with documented Zaire ebolavirus RNA persistence in semen after 12 months [3,9], indicating the need to document the absence of the virus in semen through repeated testing after clinical recovery.
Substances of human origin
Individuals with evidence of Ebola disease should not donate blood and other substances of human origin (SoHO). Potentially exposed individuals (those being monitored, asymptomatic travellers or residents returning from an Ebola disease-affected area) should defer donation of SoHO for eight weeks after return or from the beginning of the monitoring period.
Due to the possibility of intermittent low-level viraemia after recovery from illness, permanent deferral of the donation of blood, cells and tissues is suggested for donors who have recovered from Ebola disease.
Organ donation from deceased individuals or live donors who have recovered from Ebola disease should be evaluated individually by assessing the urgency of the recipients’ need; obtaining donor laboratory tests to flag the presence of filovirus; acquiring informed consent from the recipient and performing specific post-transplant monitoring. The risk to healthcare workers should also be considered.
Significant developments have been made for the prevention of Ebola disease (Zaire ebolavirus), with two vaccines now licensed for use in several countries .
The first of these vaccines is the Ervebo vaccine, which is a recombinant rVSVΔG-ZEBOV-GP live vaccine manufactured by Merck. It is a vector vaccine, expressing the surface glycoprotein of Zaire ebolavirus in a recombinant vesicular stomatitis virus construct . It is administered as a single-dose vaccine by intramuscular injection, and was prequalified by WHO on 12 November 2019. This means that the vaccine meets the standards required by WHO in terms of quality, safety and efficacy, facilitating its procurement for at-risk countries.
The EU has authorised the use of the vaccine , as has the United States , Burundi, Central African Republic, the Democratic Republic of the Congo, Ghana, Guinea, Rwanda, Uganda and Zambia . Over 40 000 individuals in the Democratic Republic of the Congo were vaccinated with Ervebo during the tenth and eleventh Ebola disease outbreaks, which occurred August 2018 − June 2020 and June − November 2020 respectively .
The second vaccine is a two-component vaccine manufactured by Janssen: the prime component is Zabdeno (Ad26.ZEBOV) and the booster component is Mvabea (MVA-BN-Filo)  . These first and second components are vector vaccines using primate adenovirus and modified vaccinia Ankara (MVA) viruses as backbones, respectively. This two-dose vaccine regimen was licensed for use in the EU on 1 July 2020.
To date there are no vaccines approved against Ebola disease due to species other than Zaire ebolavirus.
Technical guidance on risk assessment guidelines for diseases transmitted on aircraft (RAGIDA) - ECDC.
Ebola and Marburg virus disease epidemics: preparedness, alert, control, and evaluation - WHO
Interim infection prevention and control guidance for care of patients with suspected or confirmed filovirus haemorrhagic fever in health-care settings, with Focus on Ebola - WHO
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