What type of pathogen is Ebola?

The Ebolavirus genus is a member of the Filoviridae family.

It includes four distinct species that are pathogenic to humans: Zaire ebolavirus (ZEBOV), Bundibugyo ebolavirus (BDBV), Tai Forest ebolavirus (TAFV) and Sudan ebolavirus (SUDV). All four species are found in Africa and cause serious illness in humans. In addition, Reston ebolavirus (RESTV) can cause epizootics, but only causes asymptomatic infection in humans. Reston ebolavirus outbreaks have only been reported in Asia so far.

The Ebolavirus is classified as a biosafety level 4 (BSL-4) pathogen and requires special containment and barrier protection measures for laboratory personnel, as well as for any people taking care of potentially infected patients or dead bodies.

Clinical features and sequelae

In most cases, an infected patient experiences a sudden onset of flu-like illness, with fever, general malaise and weakness, muscle and joint pains and headache, followed by progressive weakness, anorexia, 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. Case fatality rates (CFR) vary depending on the specific species of the Ebola virus, with ZEBOV exhibiting the highest fatality rate. Based on one literature review, the weighted CFR for Ebola virus disease was assessed to be 65.0% [95% CI (54.0–76.0%)] [1].

Transmission 

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 for the Ebola virus ranges from 2 to 21 days. For previous outbreaks, the mean incubation period of Ebola virus disease has been estimated at 6.3 days [2]. Short incubation periods are likely due to exposure to highly contaminated materials (e.g. occupational exposure through needle-stick injuries).

Transmission modes

The Ebola virus is highly transmissible by direct contact with blood (e.g. through mucous membranes or broken skin), or other bodily fluids (e.g. saliva, urine or vomit) of living or dead infected people or any surfaces and materials soiled by infectious fluids [3].

Transmission can also occur by contact with dead or living infected animals, including the consumption and/or handling of bushmeat (e.g. monkeys, chimpanzees, forest antelopes and bats) or by visiting caves or mines colonised by bats [4].

Healthcare workers can be infected by nosocomial transmissions which can occur through improperly protected contact with infected patients. Healthcare settings can play a substantial role in the amplification of the disease, particularly at the beginning of an outbreak of Ebola virus disease before a definitive diagnosis is available and infection prevention and control (IPC) measures are implemented [5]. 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.

The Ebola virus can persist in immune-privileged sites (e.g.  testicles, central nervous system and aqueous humour) of certain survivors from which new transmissions can potentially arise, notably through sexual transmission [4, 6, 7].

In the large West Africa outbreak (2014–2016), it was recognised that there is a spectrum of Ebola virus disease presentations that also include asymptomatic or paucisymptomatic patients, especially in the contacts of confirmed cases of Ebola virus disease [1, 8]. Asymptomatic infections are considered a limited phenomenon and likely do not contribute significantly to human-to-human transmission [6, 7, 9­­­­­–12].

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 Ebola virus via transfusion and transplantation is possible, but has not been reported so far.

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 Ebola virus

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 little collared fruit bat (Myonycteris torquata) are considered natural reservoirs of Ebola virus [13].

In Africa, human Ebola virus infections have been linked to direct contact with wild gorillas, chimpanzees, monkeys, forest antelopes and porcupines found dead in the rainforest. Two Ebola virus species (ZEBOV and TAFV) have been detected in the wild in 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 caused major outbreaks in macaque monkeys in the Philippines, while asymptomatic infections have been reported in pigs.

Epidemiology

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 (ZEBOV) and the virus isolated in Sudan (SUDV). Multiple outbreaks of Ebola virus disease have been identified since its initial discovery [14].

Large autochthonous outbreaks of Ebola virus disease due to ZEBOV 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 2014 through 2016, with over 28 000 cases and 11 000 deaths [14].

Outbreaks of Ebola virus disease due to SUDV have been reported in Sudan and Uganda; outbreaks due to BDBV have been reported in the Democratic Republic of the Congo and Uganda; and outbreaks due to TAFV have been reported in Côte d’Ivoire. Lastly, epizootics due to RESTV have been documented in the Philippines [14].

Sporadic imported cases of Ebola virus disease due to ZEBOV were reported in several African and non-African countries as well. 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 [14].

Diagnostics

Laboratory tests on blood specimens detect viral material (viral genome or antigen) or specific antibodies. Ebola virus disease is diagnosed by the detection of Ebola virus 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 and urine [15, 16]. 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 for sexual or mother-to-child transmission. Identification of acute infections based on serology is uncommon.

Only a few tests to detect Ebola virus disease are commercially available. The Ebola virus is a group 4 biological agent, according to Directive 2000/54/EC of the European Parliament and of the Council [17]. 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 for viral replication should be handled in biosafety level 4 laboratories [18, 19]. 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 [20]. The study showed that both the drugs drastically reduce death rates and can be used for both adults and children [21].

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 [22].

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 [23].

Public health control measures

The goal of Ebola virus 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 under appropriate infection prevention and control (IPC) measures, timely and comprehensive contact tracing, disinfection of infectious materials and the appropriate use of personal protective equipment. Isolation of infected patients with appropriate IPC measures has been shown to effectively stop the spread of disease in previous outbreaks.

Early and culturally relevant community engagement and social mobilisation is essential to support outbreak response activities. This is also useful in enhancing the knowledge of affected populations on the risk factors of viral infection and 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 Ebola virus disease is reported. Manipulation or consumption of any type of bushmeat should be avoided, along with any form of close contact with wild animals (such as, monkeys, forest antelopes, rodents and bats, both alive or dead).

Infection control, personal protection and prevention

Healthcare workers have been frequently infected while treating patients with cases of suspected or confirmed Ebola virus disease. This occurs through close contact with patients when IPC measures are not strictly implemented or viral aetiology not yet recognised.

The appropriate use of infection control precautions and strict barrier nursing procedures are critical to prevent nosocomial transmission. Implementation of appropriate infection control measures in healthcare settings, including use of personal protective equipment, is effective in minimising the risk for transmission of filoviruses.

Transmission by sexual contact has been documented and male survivors are recommended to practise safe sex for at least 12 months after clinical recovery according to WHO, unless their semen has tested negative on two separate occasions [4, 24, 25]. Sexual transmission events from male survivors with documented ZEBOV RNA persistence in semen beyond 12 months have also been reported [6, 7], indicating the necessity to document the absence of the virus in semen through repeat testing after clinical recovery.

Individuals with evidence of Ebola virus 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 virus disease-affected area) should defer from the 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 virus disease. Organ donation from deceased individuals or live donors who have recovered from Ebola virus disease should be evaluated individually by assessing the urgency of the recipients’ need, obtaining donor laboratory tests to flag the presence of filovirus, recipient informed consent, and specific post-transplant monitoring. The risk to healthcare workers should also be considered.

Significant developments have been made for the prevention of Ebola virus disease, with two vaccines now licensed for use in several countries [26].

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 the Zaire ebolavirus in recombinant vesicular stomatitis virus construct [27]. 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 on quality, safety, and efficacy, and therefore allows its procurement for at-risk countries [28].

The EU has authorised the use of the vaccine [29], as has the United States [30], Burundi, Central African Republic, the Democratic Republic of the Congo, Ghana, Guinea, Rwanda, Uganda and Zambia [31]. Over 40 000 individuals in the Democratic Republic of the Congo were vaccinated with Ervebo during the 10th and 11th Ebola outbreaks, which occurred respectively between August 2018 and June 2020, and between June and November 2020 [32].

The second of these vaccines is a two-component vaccine manufactured by Janssen: the prime component is Zabdeno (Ad26.ZEBOV) and the booster component is Mvabea (MVA-BN-Filo) [33, 34]. These first and second components are vector vaccines using primate adenovirus and modified vaccinia Ankara (MVA) viruses as backbones, respectively [35]. This two-dose vaccine regimen was licensed for use in the EU on 1 July 2020.

Further reading

Articles (in alphabetical order)

Brainard J, Pond K, Hooper L, Edmunds K, Hunter P. Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review. PLoS Negl Trop Dis. 2016 Feb 29;10(2):e0004475.

Brainard J, Hooper L, Pond K, Edmunds K, Hunter PR. Risk factors for transmission of Ebola or Marburg virus disease: a systematic review and meta-analysis. Int J Epidemiol. 2016 Feb;45(1):102–16.

Den Boon S, Marston BJ, Nyenswah TG, Jambai A, Barry M, Keita S, et al. Ebola Virus Infection Associated with Transmission from Survivors. Emerg Infect Dis. 2019 Feb;25(2):249–55.

Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011 Mar5;377(9768):849–62.

Fischer WA, Vetter P, Bausch DG, Burgess T, Davey RT, Fowler R, et al. Ebola virus disease: an update on post-exposure prophylaxis. Lancet Infect Dis. 2018 Jun;18(6):e183–e192.

Malvy D, McElroy AK, de Clerck H, Günther S, van Griensven J. Ebola virus disease. Lancet. 2019 Mar 2;393(10174):936–48.

Reynolds P, Marzi A. Ebola and Marburg virus vaccines. Virus Genes. 2017 Aug;53(4):501–515.

Schindell BG, Webb AL, Kindrachuk J. Persistence and Sexual Transmission of Filoviruses. Viruses. 2018 Dec 2;10(12):E683. 

Selvaraj SA, Lee KE, Harrell M, Ivanov I, Allegranzi B. Infection Rates and Risk Factors for Infection Among Health Workers During Ebola and Marburg Virus Outbreaks: A Systematic Review. J Infect Dis. 2018 Nov 22;218(suppl_5):S679–S689.

Institutional resources (in alphabetical order)

European Centre for Disease Prevention and Control. Technical guidance on risk assessment guidelines for diseases transmitted on aircraft (RAGIDA). Part 2: Operational guidelines – Second edition. Stockholm: ECDC; 2010. Available from: http://ecdc.europa.eu/publications-data/technical-guidance-risk-assessment-guidelines-diseases-transmitted-aircraft  

World Health Organization. Ebola virus disease. Geneva: WHO; 2018 [cited 15 May 2019]. Available from: http://www.who.int/news-room/fact-sheets/detail/ebola-virus-disease

World Health Organization. Ebola and Marburg virus disease epidemics: preparedness, alert, control, and evaluation. Geneva: WHO; August 2014. Available from: https://apps.who.int/iris/handle/10665/130160

World Health Organization. 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. Geneva: WHO; December 2014. Available from: https://apps.who.int/iris/handle/10665/130596

References

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2.   Van Kerkhove MD, Bento AI, Mills HL, Ferguson NM, Donnelly CA. A review of epidemiological parameters from Ebola outbreaks to inform early public health decision-making. Sci Data. 2015 May 26;2:150019.

3.   Brainard J, Hooper L, Pond K, Edmunds K, Hunter PR. Risk factors for transmission of Ebola or Marburg virus disease: a systematic review and meta-analysis. Int J Epidemiol. 2016 Feb;45(1):102–16. 

4.   World Health Organization. Ebola virus disease. Geneva: WHO; 2018 [cited 15 May 2019]. Available from: http://www.who.int/en/news-room/fact-sheets/detail/ebola-virus-disease

5.   Selvaraj SA, Lee KE, Harrell M, Ivanov I, Allegranzi B. Infection Rates and Risk Factors for Infection Among Health Workers During Ebola and Marburg Virus Outbreaks: A Systematic Review. J Infect Dis. 2018 Nov 22;218(suppl_5):S679–S689.

6.   Diallo B, Sissoko D, Loman NJ, Bah HA, Bah H, Worrell MC, et al. Resurgence of Ebola Virus Disease in Guinea Linked to a Survivor With Virus Persistence in Seminal Fluid for More Than 500 Days. Clin Infect Dis. 2016 Nov 15;63(10):1353–6.

7.   Den Boon S, Marston BJ, Nyenswah TG, Jambai A, Barry M, Keita S, et al. Ebola Virus Infection Associated with Transmission from Survivors. Emerg Infect Dis. 2019 Feb;25(2):249–55.

8.   Diallo MSK, Rabilloud M, Ayouba A, Touré A, Thaurignac G, Keita AK, et al. Prevalence of infection among asymptomatic and paucisymptomatic contact persons exposed to Ebola virus in Guinea: a retrospective, cross-sectional observational study. Lancet Infect Dis. 2019 Mar;19(3):308–16.

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17.  The European Parliament and the Council of the European Union. Directive 2000/54/EC of the European Parliament and of the Council of 18 September 2000 on the protection of workers from risks related to exposure to biological agents at work (seventh individual directive within the meaning of Article 16(1) of Directive 89/391/EEC). Brussels: The European Parliament and the Council of the European Union; 2000; current consolidated version June 2020. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A02000L0054-…

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33.  European Medicines Agency. Zabdeno. Amsterdam: EMA; July 2020; last update Jan 2022. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/zabdeno

34.  European Medicines Agency. Mvabea. Amsterdam: EMA; July 2020; last update Jan 2022. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/mvabea

35.  Johnson & Johnson. Johnson & Johnson Receives Positive CHMP Opinion for Janssen’s Investigational Preventive Ebola Vaccine Regimen. New Brunswick: J&J; 29 May 2020. Available from: Johnson & Johnson Receives Positive CHMP Opinion for Janssen’s Investigational Preventive Ebola Vaccine Regimen | Johnson & Johnson (jnj.com)