EBOLAVIRUS

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PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Ebolavirus

SYNONYM OR CROSS REFERENCE: African haemorrhagic fever, Ebola haemorrhagic fever (EHF, Ebola HF), filovirus, EBO virus (EBOV), Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV, SUDV), Ivory Coast ebolavirus (ICEBOV), Tai Forest ebolavirus (TAFV), Ebola-Reston (REBOV, EBO-R, Reston Virus, RESTV), Bundibugyo ebolavirus (BEBOV, BDBV), and Ebola virus disease (EVD) ^{Footnote 1 Footnote 2 Footnote 3 Footnote 4}.

CHARACTERISTICS: Ebola was discovered in 1976 and is a member of the Filoviridae family (previously part of Rhabdoviridae family, which were later given a family of their own based on their genetic structure). Five Ebola species have been identified: Zaire ebolavirus (ZEBOV), which was first identified in 1976 and is the most virulent; Sudan ebolavirus, (SEBOV); Tai Forest ebolavirus (formerly Ivory Coast ebolavirus); Ebola-Reston (REBOV), originating from the Philippines; and Bundibugyo ebolavirus (BEBOV), the most recent species discovered (2008) ^{Footnote 1 Footnote 3 Footnote 5 Footnote 6 Footnote 7}.

Ebola is an elongated filamentous virus, which can vary between 800 - 1000 nm in length, and can reach up to 14000 nm long (due to concatamerization) with a uniform diameter of 80 nm ^{Footnote 2 Footnote 5 Footnote 8 Footnote 9}. It contains a helical nucleocapsid (with a central axis), 20 - 30 nm in diameter, and is enveloped by a helical capsid, 40 - 50 nm in diameter, with 5 nm cross-striations ^{Footnote 2 Footnote 5 Footnote 8 Footnote 9 Footnote 10}. The pleomorphic viral fragment may take on several distinct shapes (e.g., in the shape of a "6", a "U", or a circle), and are contained within a lipid membrane ^{Footnote 2 Footnote 5}. Each virion contains a single-strand of non-segmented, negative-sense viral genomic RNA ^{Footnote 5 Footnote 11}.

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Ebola virions enter host cells through endocytosis and replication occurs in the cytoplasm. Upon infection, the virus affects the host blood coagulative and immune defence system and leads to severe immunosuppression ^{Footnote 10 Footnote 12}. Early signs of infection are non-specific and flu-like, and may include sudden onset of fever, asthenia, diarrhea, headache, myalgia, arthralgia, vomiting, and abdominal pains ^{Footnote 13}. Less common early symptoms include conjunctival injection, sore throat, rashes, and bleeding. Shock, cerebral oedema, coagulation disorders, and secondary bacterial infection may co-occur later in infection ^{Footnote 8}. Haemorrhagic symptoms may begin 4 - 5 days after onset, including hemorrhagic conjunctivitis, pharyngitis, bleeding gums, oral/lip ulceration, hematemesis, melena, hematuria, epistaxis, and vaginal bleeding ^{Footnote 14}. Hepatocellular damage, marrow suppression (such as thrombocytopenia and leucopenia), serum transaminase elevation, and proteinuria may also occur. Persons that are terminally ill typically present with obtundation, anuria, shock, tachypnea, normothermia to hypothermia, arthralgia, and ocular diseases ^{Footnote 15}. Haemorrhagic diathesis is often accompanied by hepatic damage and renal failure, central nervous system involvement, and terminal shock with multi-organ failure ^{Footnote 1 Footnote 2}. Contact with the virus may also result in symptoms such as severe acute viral illness, malaise, and maculopapular rash. Pregnant women will usually abort their foetuses and experience copious bleeding ^{Footnote 2 Footnote 16}. Fatality rates range between 50 - 100%, with most dying of hypovolemic shock and multisystem organ failure ^{Footnote 17}.

Pathogenicity between species of Ebola does not differ greatly in that they have all been associated with hemorrhagic fever outbreaks in humans (excluding Reston) and non-human primates. The Ebola-Zaire and Sudan strains are especially known for their virulence with up to 90% fatality rate ^{Footnote 18}, with reduced virulence noted in the Tai Forest ebolavirus and the more recently discovered Bundibugyo strain, which caused a single outbreak in Uganda ^{Footnote 6 Footnote 7}. Bundibugyo was the outbreak virus in Isiro, Democratic Republic of Congo, in 2012. Ebola-Reston was isolated from cynomolgus monkeys from the Philippines in 1989 and is less pathogenic in non-human primates. Ebola-Reston virus appears to be non-pathogenic in humans, with reported health effects limited to serological evidence of exposure as identified in 4 animal handlers working with infected non-human primates ^{Footnote 19}.

EPIDEMIOLOGY: Occurs mainly in areas surrounding rain forests in equatorial Africa ^{Footnote 10} with the exception of Reston, which has been documented to originate in the Philippines ^{Footnote 7}. No predispositions to infection have been identified among infected persons.

The largest recorded ebolavirus outbreak to date began in March 2014, with initial cases reported in Guinea and then additional cases identified in the surrounding regions (Liberia, Sierra Leone, Nigeria). A new strain of the ZEBOV species was identified as the causative agent of the outbreak ^{Footnote 16 Footnote 21 Footnote 22}.

HOST RANGE: Humans, various monkey species, chimpanzees, gorillas, baboons, and duikers are natural animal hosts for ebolavirus ^{Footnote 1 Footnote 2 Footnote 5 Footnote 22 Footnote 23 Footnote 24 Footnote 25 Footnote 26 Footnote 27 Footnote 28 Footnote 29 Footnote 30 Footnote 31}. Serological evidence of immunity markers to ebolavirus in serum collected from domesticated dogs suggests asymptomatic infection is plausible, likely following exposure to infected humans or animal carrion ^{Footnote 32 Footnote 33}. The Ebolavirus genome was discovered in two species of rodents and one species of shrew living in forest border areas, raising the possibility that these animals may be intermediary hosts ^{Footnote 34}. Experimental studies of the virus have been done using mouse, pig, guinea pig, and hamster models, suggesting wild-type ebolavirus has limited pathogenicity in these models ^{Footnote 35 Footnote 36}.

Bats are considered to be a plausible reservoir for the virus. Serological evidence of infection with ebolavirus (antibody detection to EBOV, ZEBOV, and/or REBOV) has been reported in fruit bats collected from woodland and forested areas near Ghana and Gabon, with reduced frequency of isolation from bats collected in mainland China and Bangladesh ^{Footnote 37 Footnote 38 Footnote 39 Footnote 40}.

INFECTIOUS DOSE: Viral hemorrhagic fevers have an infectious dose of 1 - 10 organisms by aerosol in non-human primates ^{Footnote 41}.

MODE OF TRANSMISSION: In an outbreak, it is hypothesized that the first patient becomes infected as a result of contact with an infected animal ^{Footnote 22}. Person-to-person transmission occurs via close personal contact with an infected individual or their body fluids during the late stages of infection or after death ^{Footnote 1 Footnote 2 Footnote 22 Footnote 42}. Nosocomial infections can occur through contact with infected body fluids for example due to the reuse of unsterilized syringes, needles, or other medical equipment contaminated with these fluids ^{Footnote 1 Footnote 2}. Humans may be infected by handling sick or dead non-human primates and are also at risk when handling the bodies of deceased humans in preparation for funerals ^{Footnote 2 Footnote 10 Footnote 43}.

In laboratory settings, non-human primates exposed to aerosolized ebolavirus from pigs have become infected, however, airborne transmission has not been demonstrated between non-human primates ^{Footnote 1 Footnote 10 Footnote 15 Footnote 44 Footnote 45}. Viral shedding has been observed in nasopharyngeal secretions and rectal swabs of pigs following experimental inoculation ^{Footnote 29 Footnote 30}.

INCUBATION PERIOD: Two to 21 days ^{Footnote 1 Footnote 15 Footnote 17}.

COMMUNICABILITY: Communicable as long as blood, body fluids or organs, contain the virus. Ebolavirus has been isolated from semen 61 to 82 days after the onset of illness, and transmission through semen has occurred 7 weeks after clinical recovery ^{Footnote 1 Footnote 2 Footnote 59 Footnote 60}.

SECTION III - DISSEMINATION

RESERVOIR: The natural reservoir of Ebola is unknown ^{Footnote 1 Footnote 2}. Antibodies to the virus have been found in the serum of domestic guinea pigs and wild rodents, with no relation to human transmission ^{Footnote 34 Footnote 47}. Serum antibodies and viral RNA have been identified in some bat species, suggesting bats may be a natural reservoir ^{Footnote 37 Footnote 38 Footnote 39 Footnote 40}.

ZOONOSIS: Zoonosis between humans and animal is suspected ^{Footnote 2 Footnote 22 Footnote 37}.

VECTORS: Unknown.

SECTION IV - STABILITY AND VIABILITY

All information available on stability and viability comes from peer-reviewed literature sources depicting experimental findings and is intended to support local risk assessments in a laboratory setting.

DRUG SUSCEPTIBILITY: Unknown. Although clinical trials have been completed, no vaccine has been approved for treatment of ebolavirus. Similarly, no post-exposure measures have been reported as effective in treating ebolavirus infection in humans although several studies have been completed in animals to determine the efficacy of various treatments.

DRUG RESISTANCE: There are no known antiviral treatments available for human infections.

SUSCEPTIBILITY TO DISINFECTANTS: Ebolavirus is susceptible to 3% acetic acid, 1% glutaraldehyde, alcohol-based products, and dilutions (1:10-1:100 for ≥10 minutes) of 5.25% household bleach (sodium hypochlorite), and calcium hypochlorite (bleach powder) ^{Footnote 48 Footnote 49 Footnote 50 Footnote 62 Footnote 63}. The WHO recommendations for cleaning up spills of blood or body fluids suggest flooding the area with a 1:10 dilutions of 5.25% household bleach for 10 minutes for surfaces that can tolerate stronger bleach solutions (e.g., cement, metal) ^{Footnote 62}. For surfaces that may corrode or discolour, they recommend careful cleaning to remove visible stains followed by contact with a 1:100 dilution of 5.25% household bleach for more than 10 minutes.

PHYSICAL INACTIVATION: Ebola are moderately thermolabile and can be inactivated by heating for 30 minutes to 60 minutes at 60°C, boiling for 5 minutes, or gamma irradiation (1.2 x106 rads to 1.27 x106 rads) combined with 1% glutaraldehyde ^{Footnote 10 Footnote 48 Footnote 50}. Ebolavirus has also been determined to be moderately sensitive to UVC radiation ^{Footnote 51}.

SURVIVAL OUTSIDE HOST: Filoviruses have been reported capable to survive for weeks in blood and can also survive on contaminated surfaces, particularly at low temperatures (4°C) ^{Footnote 52 Footnote 61}. One study could not recover any Ebolavirus from experimentally contaminated surfaces (plastic, metal or glass) at room temperature ^{Footnote 61}.  In another study, Ebolavirus dried onto glass, polymeric silicone rubber, or painted aluminum alloy is able to survive in the dark for several hours under ambient conditions (between 20 and 250C and 30–40% relative humidity) (amount of virus reduced to 37% after 15.4 hours), but is less stable than some other viral hemorrhagic fevers (Lassa) ^{Footnote 53}. When dried in tissue culture media onto glass and stored at 4 °C, Zaire ebolavirus survived for over 50 days ^{Footnote 61}. This information is based on experimental findings only and not based on observations in nature. This information is intended to be used to support local risk assessments in a laboratory setting.

A study on transmission of ebolavirus from fomites in an isolation ward concludes that the risk of transmission is low when recommended infection control guidelines for viral hemorrhagic fevers are followed ^{Footnote 64}. Infection control protocols included decontamination of floors with 0.5% bleach daily and decontamination of visibly contaminated surfaces with 0.05% bleach as necessary.

SECTION V - FIRST AID / MEDICAL

SURVEILLANCE: Definitive diagnosis can be reached rapidly in an appropriately equipped laboratory using a multitude of approaches, including RT-PCR to detect viral RNA, ELISA based techniques to detect anti-Ebola antibodies or viral antigens, immunoelectron microscopy to detect ebolavirus particles in tissues and cells, and indirect immunofluorescence to detect antiviral antibodies ^{Footnote 1 Footnote 2 Footnote 14 Footnote 41}. It is useful to note that the Marburg virus is morphologically indistinguishable from the ebolavirus, and laboratory surveillance of Ebola is extremely hazardous ^{Footnote 1 Footnote 2 Footnote 14 Footnote 54}. Please see the interim biosafety guidelines for laboratories handling specimens from patients under investigation for EVD for more information.

Note: All diagnostic methods are not necessarily available in all countries.

FIRST AID/TREATMENT: There is no effective antiviral treatment ^{Footnote 27 Footnote 37}. Instead, treatment is supportive, and is directed at maintaining organ function and electrolyte balance and combating haemorrhage and shock ^{Footnote 22 Footnote 55}.

IMMUNIZATION: None ^{Footnote 27}.

PROPHYLAXIS: None. Management of the Ebola virus is solely based on isolation and barrier-nursing with symptomatic and supportive treatments ^{Footnote 8}.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: One reported near-fatal case following a minute finger prick in an English laboratory (1976) ^{Footnote 56}. A Swiss zoologist contracted Ebola virus after performing an autopsy on a chimpanzee in 1994 ^{Footnote 2 Footnote 57}. An incident occurred in Germany in 2009 when a laboratory scientist pricked herself with a needle that had just been used on a mouse infected with Ebola; however, human infection was not confirmed. Additional incidents were recorded in the US in 2004, and a fatal case in Russia in 2004 ^{Footnote 8}.

SOURCES/SPECIMENS: Blood, serum, urine, respiratory and throat secretions, semen, and organs or their homogenates from human or animal hosts ^{Footnote 1 Footnote 2 Footnote 53}. Human or animal hosts, including non-human primates, may represent a further source of infection ^{Footnote 54}.

PRIMARY HAZARDS: Accidental parenteral inoculation, respiratory exposure to infectious aerosols/droplets, and/or direct contact with skin or mucous membranes ^{Footnote 54}.

SPECIAL HAZARDS: Work with, or exposure to, infected non-human primates, rodents, or their carcasses represents a risk of human infection ^{Footnote 54}.

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 4 ^{Footnote 58}.

CONTAINMENT REQUIREMENTS: Containment Level 4 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, and cultures. Please see the interim biosafety guidelines for laboratories handling specimens from patients under investigation for EVD for more information.

PROTECTIVE CLOTHING: Personnel entering the laboratory must remove street clothing, including undergarments, and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashes.

OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) in combination with a positive pressure suit, or within a class III BSC line. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are unloaded in a biological safety cabinet. The integrity of positive pressure suits must be routinely checked for leaks. The use of needles, syringes, and other sharp objects should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings. Additional precautions should be considered with work involving animal activities.

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean-up.

DISPOSAL: Decontaminate all materials for disposal from the containment laboratory by steam sterilisation, chemical disinfection, incineration or by gaseous methods. Contaminated materials include both liquid and solid wastes.

STORAGE: In sealed, leak-proof containers that are appropriately labelled and locked in a Containment Level 4 laboratory.

SECTION IX - REGULATORY AND OTHER INFORMATION

REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

UPDATED: August 2014.

PREPARED BY: Centre for Biosecurity, Public Health Agency of Canada.

Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright ©

Public Health Agency of Canada, 2014
Canada

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Footnote 2

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Footnote 11

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Footnote 14

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Footnote 17

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Footnote 21

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Footnote 23

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Footnote 24

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Footnote 25

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Footnote 26

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Footnote 27

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Footnote 28

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Footnote 29

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Footnote 30

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Footnote 31

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Footnote 32

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Footnote 33

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Footnote 34

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Footnote 35

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Footnote 36

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Footnote 37

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Footnote 38

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Footnote 39

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Footnote 40

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Footnote 41

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Footnote 42

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Footnote 43

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Footnote 44

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Footnote 45

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Footnote 46

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Footnote 47

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Footnote 48

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Footnote 49

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Footnote 50

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Footnote 51

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Footnote 52

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Footnote 53

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Footnote 54

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Footnote 55

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Footnote 56

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Footnote 57

Formenty, P., Hatz, C., Le Guenno, B., Stoll, A., Rogenmoser, P., & Widmer, A. (1999). Human infection due to Ebola virus, subtype Cote d'Ivoire: Clinical and biologic presentation. Journal of Infectious Diseases, 179(SUPPL. 1), S48-S53.

Footnote 58

Human pathogens and toxins act. S.C. 2009, c. 24, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009. (2009).

Footnote 59

Rowe AK, Bertolli J,Khan AS,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 à Kikwit. J Infect Dis 1999;179 (Suppl 1):S28-35.

Footnote 60

Rodriguez LL, De Roo A, Guimard Y, et al. Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis 1999;179 (Suppl 1):S170-6.

Footnote 61

Piercy, T.J., Smither, S.J., Steward, J.A., Eastaugh, L., Lever, M.S. (2010) The survival of filoviruses in liquids, on solid substrates and in a dynamic aerosol. J Appl Microbiol. 109(5): 1531-9.

Footnote 62

World Health Organization (2010). WHO best practices for injections and related procedures toolkit. March 2010. http://whqlibdoc.who.int/publications/2010/9789241599252_eng.pdf?ua=1

Footnote 63

World Health Organization (2014). 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. August 2014.
http://www.who.int/csr/resources/who-ipc-guidance-ebolafinal-09082014.pdf

Footnote 64

Baush, D.G., Towner, J.S., Dowell, S.F., Kaducu, F., Lukwiya, M., Sanchez, A., Nichol, S.T., Ksiazek, T.G., Rollin, P.E. (2007) Assessment of the Risk of Ebola virus Transmission from Bodily Fluids and Fomites. JID. 196 (Suppl 2).