Ebola virus disease: For health professionals and humanitarian aid workers

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What health professionals and humanitarian aid workers need to know about Ebola virus disease

Health professionals in Canada are advised to be vigilant in the recognition, reporting and prompt investigation of patients with a history of potential exposure to a source of Ebola viruses (e.g., travel to an outbreak affected area) and symptoms of:

  • Ebola virus disease (EVD)
  • similar diseases that can cause viral hemorrhagic fevers (VHFs)

Consult the EVD outbreak case definition for further information on symptoms, risk factors and testing.

For details on preventive measures and the monitoring and surveillance of returning travellers, review the Committee to Advise on Tropical Medicine and Travel's (CATMAT) statement on Ebola Virus Disease Prevention, Monitoring and Surveillance Recommendations. Also refer to the related information section for links to additional documents.

History and context

Ebola virus disease (EVD) (formerly known as Ebola Hemorrhagic Fever) is a rare, severe, acute viral illness first identified over 30 years ago. It is caused by viruses from the genus Ebolavirus. These viruses can cause disease in human and non-human primates (e.g., monkeys, gorillas, chimpanzees) and can infect other animals (e.g., fruit bats, forest antelope, pigs).

EVD is generally limited geographically, occurring primarily in outbreak-prone areas of sub-Saharan Africa. Historically, between 1976 and 2012, sporadic cases and outbreaks of EVD were reported in several African countries (Cote d'Ivoire, DRC, Gabon, Republic of Congo, South Africa, South Sudan and Uganda), averaging fewer than 150 cases per outbreak, and having case fatality rates around 50% (range: 25 to 90%) (1, 2).

The largest recorded outbreak of EVD to date began in late 2013, with initial cases reported in Guinea, followed by spread to other countries in West Africa - mainly Liberia, Sierra Leone, and Nigeria. The Makona strain of Zaire Ebolavirus species was identified as the causative agent of the outbreak (3). Overall, the 2014-16 West Africa outbreak resulted in over 28,500 cases and 11,300 deaths (4).

During the 2014-16 West Africa EVD outbreak, imported cases were identified in other countries in Africa, as well as locations in Europe and North America (5-9). The occurrence of secondary transmission outside of the affected areas in Africa was also documented, although it was very limited (8).

To date, no cases of EVD have ever been identified in Canada.

Causative agents

EVD is caused by ribonucleic acid (RNA) viruses that are members of the genus Ebolavirus, a member of the Filoviridae family. To date, there are 5 recognized species of ebolaviruses (10-12) (see below).

  • Zaire ebolavirus (EBOV)
  • Sudan ebolavirus (SUDV)
  • Taï Forest ebolavirus (TAFV, formerly Côte d'Ivoire)
  • Bundibugyo ebolavirus (BDBV)
  • Reston ebolavirus (RESTV)

Among the 5 well-described species to date, only 4 are known to cause illness in people: EBOV, SUDV, TAFV, and BDBV. While these species are all pathogenic to humans, EBOV and SUDV are considered especially virulent, and are associated with higher case fatality rates (13). In contrast, RESTV is known to cause illness in non-human primates and pigs, but appears to be non-pathogenic in humans.

In July 2018 a potential new species, tentatively named Bombali ebolavirus (BOMV), was identified in insectivorous bats roosting inside people's homes in Sierra Leone. Very little is known about BOMV at this time; investigations are ongoing.

Ebola viruses are believed to persist within forest-dwelling fruit bats in Africa (14, 15). Other animals, in particular non-human primates, have been identified as incidental hosts (not reservoirs).

Additional information is available from the Pathogen Safety Data Sheet for EBOV.

Transmission

Outbreaks in humans can occur through initial exposure to either the reservoir population or an intermediate infected host (generally, non-human primates such as monkeys or gorillas), with subsequent person-to-person transmission.

Person-to-person transmission can occur though:

  • direct contact with blood and/or other body fluids (e.g., feces, urine, emesis, saliva, sweat, breast milk, semen) from an infected symptomatic person or dead body and/or
  • indirect contact with surfaces and fomites (e.g., needles) that are contaminated with these fluids

Infected persons are not considered to be infectious before the onset of symptoms. The risk of transmission is highest when the viral load is greatest, usually when a person is acutely unwell. Cases remain communicable as long as blood and body fluids contain the virus (16), including the post-mortem period (2, 17).

During clinical recovery, EBOV can also persist for weeks to months in some body fluids (e.g., semen, urine, and breast milk) (16, 18-22). For example, the virus has been detected in semen for as long as 18 months later (23, 24). The virus can also persist in certain areas of the body (e.g., the eyes, central nervous system), even after the patient recovers from illness (19). With the exception of the potential for sexual transmission of the virus during recovery, Ebola viruses cannot be spread to others by an asymptomatic person.

Ebola viruses are not transmitted between humans through airborne transmission or casual interactions. Examples of casual interactions include sharing a seating area on public transportation or sitting in the same waiting room, but with no direct or indirect contact (25).

While not normally transmissible by the airborne route, certain medical procedures, such as intubation, may generate virus-carrying droplets.

Incubation period

EVD has an incubation period ranging between 2 and 21 days, with most cases experiencing onset of symptoms 4 to 10 days after exposure (26).

Risk groups

Activities associated with a higher risk of exposure to the virus include:

  • provision of care to EVD cases who are ill, without proper and consistent use of appropriate personal protective equipment
  • unprotected sexual contact with an EVD case who is acutely ill, or during their recovery
  • pregnancy (from mother to child)
  • breastfeeding
  • participation in unsafe burial practices, including the preparation of the deceased for burial, and
  • handling and/or consumption of wild animals hunted or gathered for food (i.e. bushmeat) in affected areas

Contacts

For the purposes of implementing public health measures contacts of EVD cases are classified according to their risk of exposure.

A high-risk of exposure includes any of the following:

  • Direct physical contact, without adhering to recommended infection, prevention and control (IPC) precautions or due to a breach in IPC precautions, with:
    • the body surface, mucous membranes or body fluids of a symptomatic EVD case, or their dead body
    • any other known source of Ebola virus (e.g., contaminated medical instruments, objects or environmental surfaces)
  • Unprotected sexual contact with an acute or convalescent EVD case.

A low-risk of exposure includes any of the following:

  • Physical contact, while adhering to recommended IPC precautions and no known breach in IPC precautions, with:
    • the body surface, mucous membranes or body fluids of a symptomatic EVD case, or their dead body
    • any other known source of Ebola virus (e.g., contaminated medical instruments or environmental surfaces)
  • Having only casual interactions AND no direct (unprotected body surface to body surface) physical contact with an EVD case or their body fluids. Examples of casual interactions include sharing a seating area on public transportation or sitting in the same waiting room.

Humanitarian aid workers

Humanitarian aid workers returning from an outbreak affected area should follow the advice for returning travellers and the guidance provided by their organization, including:

  • calling the appropriate public health authority during the first business day following arrival in Canada to self-identify, even if they have no exposures or a low risk of exposure
  • self-identifying to a Canada Border Services Agent on arrival in Canada, if they have a high risk of exposure or have Ebola compatible symptoms

Risk in Canada

The Public Health Agency of Canada (PHAC) works closely with its national and international partners to track and monitor EVD activity around the world, and assesses the risks of EVD to Canadians on an ongoing basis. Information on current outbreaks of EVD can be found on the World Health Organization (WHO) website.

Although the risk of exposure to an Ebola virus in Canada is considered to be very low, it is possible that the introduction of a case connected to an outbreak in an EVD-affected area could occur (27). If this were to occur, public health authorities at all levels of government would be involved in managing the response.

Clinical features

Symptoms usually begin with a sudden onset of flu-like symptoms, such as fever, myalgia, severe headache and malaise, typically followed by worsening gastrointestinal symptoms (e.g., anorexia, nausea, abdominal discomfort, vomiting, and diarrhea). Other symptoms include pharyngitis and conjunctival injection. A nonpruritic, erythematous, maculopapular rash that involves neck, trunk, and arms, may develop in 25% to 52% of patients by days 5 to 7 (28-30).

Diarrhea and vomiting can be profuse in later stages of the illness. The disease can progress to severe volume depletion, electrolyte abnormalities, wasting, and shock. In fewer than half of cases, hemorrhage may occur as a late manifestation, usually from venipuncture sites through the gastrointestinal tract or other mucosa (e.g., gums, nose). Secondary bacterial infections may also occur. Case fatality in humans can range from 25 to 90%.

Non-fatal cases have fever for several days and typically begin improving around day 6 to 11 (26). Full recovery occurs over a long period of time, and is may be associated with long-term sequelae such as myelitis, recurrent hepatitis, psychosis, or uveitis (18).

Diagnosis

Laboratory testing, clinical evaluation, and epidemiological investigation is recommended to properly diagnose EVD cases and ensure management of contacts and the immediate environment.

Laboratory testing

Laboratory methods for confirming a case of EVD are based on isolation of the virus, detection of its RNA or components, and/or demonstration of antibodies against it. While the gold standard for confirmatory testing is a PCR positive result by 2 molecular targets, all sufficient methods and specimens for confirming a case are defined in detail in the EVD outbreak case definition.

Laboratories receiving specimens from patients under Ebola investigation should know that mishandled specimens are a serious risk to laboratory personnel. Before testing occurs, consult the Biosafety Guidelines for Laboratories Handling Specimens from Patients Under Investigation for Ebola Virus Disease.

The decision for specimen collection and testing should be predicated on:

  • the clinical status of the patient
  • the risk of exposure to a source of Ebola viruses

Virus cultures for EBOV should not be attempted outside of the biosafety level 4 containment laboratories at the National Microbiology Laboratory (NML).

For diagnostic or confirmatory services for Ebola viruses, liaise with the provincial public health laboratory of your jurisdiction. The provincial public health laboratory should coordinate with the NML Operations Centre Director (OCD) at 1-866-262-8433. This number is staffed at all times.

The NML OCD will:

  • work with the requesting provincial or territorial jurisdiction to activate the Emergency Response Assistance Plan (ERAP)
  • connect you with the appropriate subject matter expert if you require assistance with:
    • the shipping process
    • sample requirements
    • sample shipping conditions

Alongside laboratory service requests for EVD or other VHFs, provinces and territories should report a patient's clinical history of illness to the Health Portfolio Operations Centre (HPOC). Contact the HPOC at 1-800-545-7661.

Clarification or further information may be requested from the patient's clinician to optimize delivery of requested laboratory services.

Diagnostic testing and possible impacts of vaccination

Diagnostic testing for Ebola virus using the molecular testing approaches of the NML would not be impacted by recent vaccination with the rVSV-ZEBOV vaccine. The molecular targets for this test (the Ebola virus NP and L genes) are not found in the rVSV-ZEBOV vaccine, which is based on the Ebola virus glycoprotein or GP gene. Testing in other countries may use the GeneXpert platform which uses the NP and GP genes as targets. As such, it is conceivable that a recent vaccine recipient would be NP negative but GP positive. If the history of vaccination was not readily available, this could cause uncertainty. The gold standard for diagnosis remains being positive by 2 molecular targets, but a diagnostic result positive only by the GP gene would warrant repeat testing and other investigations. This would include re-testing and confirmation at the NML. To note, serologic testing cannot currently distinguish between vaccinations and naturally acquired infections.

Reporting

Patients under investigation for EVD should be reported immediately to local public health authorities. This is a requirement as per jurisdictional protocols in the respective Canadian province or territory. The national EVD case report form is available online, including instructions for reporting.

A patient's clinical history of illness should be reported to the Public Health Agency of Canada Health Portfolio Operations Centre (HPOC). Provinces and territories can contact HPOC at 1-800-545-7661. They should also fill out the Ebola Virus Disease Case Report Form at the time of the initial report.

Canadian monitoring, surveillance and reporting

Canadian public health authorities monitor and respond, as appropriate, to all EVD-related events and adjust recommended practices in Canada as required.

Viral hemorrhagic fevers, including EVD, have been nationally notifiable in Canada since 2002 (in addition to a brief period from 1979 to 1982). A specific EVD outbreak case definition was developed during the 2014-16 West Africa outbreak and has been updated to facilitate reporting as part of public health response activities in Canada.  

PHAC, on behalf of the Government of Canada, would also report confirmed cases to the World Health Organization (WHO), as part of Canada's commitments under the International Health Regulations (2005).

Treatment

Cases should receive care in highly specialized centres, in order to ensure appropriate supportive care (maintaining blood pressure, electrolyte balance and organ systems function) under strict infection prevention control management. Provincial and territorial public health authorities can provide information regarding whether a treatment facility has been designated for this purpose in their jurisdiction. Consult the Ebola Clinical Care Guidelines: A Guide for Clinicians in Canada (PDF) for more information.

There is currently no Health Canada approved treatment for EVD. A number of investigational therapeutics, namely antivirals and monoclonal antibodies, are currently under development. Additionally, limited trials have assessed existing medications (e.g., amiodarone) for efficacy against Ebola viruses.

Although clinical trials for some of these investigational therapies have shown positive results, none have yet reached the point of application for approved use in Canada. These include the monoclonal antibody cocktails (e.g., ZMapp, REGN3470-3471-3479, mAb 114), as well as antiviral medications (e.g., Favipiravir, GS-5734).

If a confirmed case occurs in Canada the Public Health Agency of Canada (PHAC), in coordination with the province or territory, will provide guidance to the treating physician regarding access to investigational products, including monoclonal antibodies and vaccine, through the appropriate regulatory mechanism.

In outbreak situations, investigational monoclonal antibody preparations have been used under an ethical framework developed by World Health Organization called the Monitored Emergency Use of Unregistered and Investigational Interventions. The framework is not designed to evaluate the drugs but to provide treatment on compassionate grounds.

Clinical trials to test the effectiveness of some new, investigational monoclonal antibody preparations are occurring in outbreak settings. The results of clinical trials will inform future licensing and recommendations for use of these products.

Vaccine

There is currently no approved vaccine for EVD in Canada. An investigational vaccine (rVSV-ZEBOV-GP, Merck) for the Zaire ebolavirus species has completed early stage investigational trials, and has been available on compassionate grounds in recent outbreaks (West Africa 2014 to 2016, DRC 2018). The vaccine may also be offered to front-line health care and humanitarian workers in EVD-affected areas as part of an outbreak management strategy.

The vaccine is not approved or marketed in Canada. In the event of a Canadian case, the vaccine may be deemed helpful for outbreak control purposes. Under these circumstances, access to this unapproved product, will be facilitated by the Public Health Agency of Canada (PHAC) through the appropriate regulatory mechanism.

References

Footnote 1

40 Years of Ebola Virus Disease around the World [Internet]. [updated June 20, 2018; ]. Available from: https://www.cdc.gov/vhf/ebola/history/chronology.html.

Return to footnote 1 referrer

Footnote 2

Ebola virus disease - Fact Sheet [Internet]. [updated 12 February 2018; ]. Available from: http://www.who.int/news-room/fact-sheets/detail/ebola-virus-disease.

Return to footnote 2 referrer

Footnote 3

Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, et al. Emergence of Zaire Ebola virus disease in Guinea. N Engl J Med. 2014 Oct 9;371(15):1418-25.

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Footnote 4

Situation Report. Ebola Virus Disease (10 June 2016) [Internet].; 2016 []. Available from: http://apps.who.int/iris/bitstream/handle/10665/208883/ebolasitrep_10Jun2016_eng.pdf?sequence=1

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Footnote 5

Centers for Disease Control and Prevention. Lack of secondary transmission of ebola virus from healthcare worker to 238 contacts, United Kingdom, December 2014. EID. 2017;23(12).

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Footnote 6

Disease outbreak news. Ebola virus disease - Italy [Internet].; 2015 []. Available from: http://www.who.int/csr/don/13-may-2015-ebola/en/.

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Footnote 7

Chevalier MS, Chung W, Smith J, Weil LM, Hughes SM, Joyner SN, et al. Ebola virus disease cluster in the United States--Dallas County, Texas, 2014. MMWR Morb Mortal Wkly Rep. 2014 Nov 21;63(46):1087-8.

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Footnote 8

Disease Outbreak news. Ebola virus disease - Spain. [Internet].; 2014 [updated 9 October 2014; ]. Available from: http://www.who.int/csr/don/09-october-2014-ebola/en/.

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Footnote 9

Disease outbreak news. Ebola virus disease - United Kingdom [Internet].; 2014 [updated 30 December 2014; ]. Available from: http://www.who.int/csr/don/30-december-2014-ebola/en/.

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Footnote 10

Virus Taxonomy. Ebolavirus. [Internet].; 2013 []. Available from: http://www.ictvonline.org/virusTaxonomy.asp.

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Footnote 11

Sanchez A. Filoviridae: Marburg and Ebola Viruses. In: Knipe D, Howley P, editors. Fields virology. 4th ed. Philadelphia, PA.: Lippencott-Ravenpp; 2001. p. 1279-304.

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Footnote 12

Takada A, Kawaoka Y. The pathogenesis of Ebola hemorrhagic fever. Trends Microbiol. 2001 Oct;9(10):506-11.

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Footnote 13

Lefebvre A, Fiet C, Belpois-Duchamp C, Tiv M, Astruc K, Aho Glele LS. Case fatality rates of Ebola virus diseases: a meta-analysis of World Health Organization data. Med Mal Infect. 2014 Sep;44(9):412-6.

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Footnote 14

Leroy EM, Kumulungui B, Pourrut X, Rouquet P, Hassanin A, Yaba P, et al. Fruit bats as reservoirs of Ebola virus. Nature. 2005 Dec 1;438(7068):575-6.

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Footnote 15

Leroy EM, Epelboin A, Mondonge V, Pourrut X, Gonzalez JP, Muyembe-Tamfum JJ, et al. Human Ebola outbreak resulting from direct exposure to fruit bats in Luebo, Democratic Republic of Congo, 2007. Vector Borne Zoonotic Dis. 2009 Dec;9(6):723-8.

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Footnote 16

Expert Working Group for the Canadian Guidelines on Sexual Transmitted Infections. EWG Statement on Sexual Transmission of Ebola Virus. Unpublished. August 2014.

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Footnote 17

Chertow DS, Kleine C, Edwards JK, Scaini R, Giuliani R, Sprecher A. Ebola virus disease in West Africa--clinical manifestations and management. N Engl J Med. 2014 Nov 27;371(22):2054-7.

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Footnote 18

Moreau M, Spencer C, Gozalbes JG, Colebunders R, Lefevre A, Gryseels S, et al. Lactating mothers infected with Ebola virus: EBOV RT-PCR of blood only may be insufficient. Euro Surveill. 2015 Jan 22;20(3).

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Footnote 19

Interim guidance for management of survivors of Ebola virus disease in U.S. healthcare settings [Internet].; 2018 []. Available from: https://www.cdc.gov/vhf/ebola/clinicians/evaluating-patients/guidance-for-management-of-survivors-ebola.html.

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Footnote 20

Kreuels B, Wichmann D, Emmerich P, Schmidt-Chanasit J, de Heer G, Kluge S, et al. A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med. 2014 Dec 18;371(25):2394-401.

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Footnote 21

Bausch DG, Towner JS, Dowell SF, Kaducu F, Lukwiya M, Sanchez A, et al. Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. J Infect Dis. 2007 Nov 15;196 Suppl 2:S142-7.

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Footnote 22

Rowe AK, Bertolli J, Khan AS, Mukunu R, Muyembe-Tamfum JJ, Bressler D, et al. Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidemies a Kikwit. J Infect Dis. 1999 Feb;179 Suppl 1:S28-35.

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Footnote 23

Subissi L, Keita M, Mesfin S, Rezza G, Diallo B, Van Gucht S, et al. Ebola Virus Transmission Caused by Persistently Infected Survivors of the 2014-2016 Outbreak in West Africa. J Infect Dis. 2018 Jun 18.

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Footnote 24

Subtil F, Delaunay C, Keita AK, Sow MS, Toure A, Leroy S, et al. Dynamics of Ebola RNA Persistence in Semen: A Report From the Postebogui Cohort in Guinea. Clin Infect Dis. 2017 Jun 15;64(12):1788-90.

Return to footnote 24 referrer

Footnote 25

Ebola situation assessment. What we know about transmission of the Ebola virus among humans [Internet].; 2014 [updated 6 October 2014; ]. Available from: http://www.who.int/mediacentre/news/ebola/06-october-2014/en/.

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Footnote 26

Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011 Mar 5;377(9768):849-62.

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Footnote 27

Undurraga EA, Carias C, Meltzer MI, Kahn EB. Potential for broad-scale transmission of Ebola virus disease during the West Africa crisis: lessons for the Global Health security agenda. Infect Dis Poverty. 2017 Dec 1;6(1):159,017-0373-4.

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Footnote 28

Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011;204(Suppl 3):S810-6.

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Footnote 29

Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, Guimard Y, et al. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: Clinical observations in 103 patients. J Infect Dis. 1999;179(Suppl 1):S1-7.

Return to footnote 29 referrer

Footnote 30

Formenty P, Hatz C, Le Guenno B, Stoll A, Rogenmoser P, Widmer A. Human infection due to Ebola virus, subtype Côte d'Ivoire: Clinical and biologic presentation. J Infect Dis. 1999;179(Suppl 1):S48-53.

Return to footnote 30 referrer

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