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PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCESSECTION 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) Footnote1 Footnote2 Footnote3 Footnote4.

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) Footnote1 Footnote3 Footnote5 Footnote6 Footnote7.

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 Footnote2 Footnote5 Footnote8 Footnote9. 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 Footnote2 Footnote5 Footnote8 Footnote9 Footnote10. 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 Footnote2 Footnote5. Each virion contains a single-strand of non-segmented, negative-sense viral genomic RNA Footnote5 Footnote11.

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 Footnote10 Footnote12. 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 Footnote13. 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 Footnote8. 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 Footnote14. 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 Footnote15. Haemorrhagic diathesis is often accompanied by hepatic damage and renal failure, central nervous system involvement, and terminal shock with multi-organ failure Footnote1 Footnote2. 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 Footnote2 Footnote16. Fatality rates range between 50 - 100%, with most dying of hypovolemic shock and multisystem organ failure Footnote17.

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 Footnote18, with reduced virulence noted in the Tai Forest ebolavirus and the more recently discovered Bundibugyo strain, which caused a single outbreak in Uganda Footnote6 Footnote7. 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 Footnote19.

EPIDEMIOLOGY: Occurs mainly in areas surrounding rain forests in equatorial Africa Footnote10 with the exception of Reston, which has been documented to originate in the Philippines Footnote7. 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 Footnote16 Footnote21 Footnote22.

HOST RANGE: Humans, various monkey species, chimpanzees, gorillas, baboons, and duikers are natural animal hosts for ebolavirus Footnote1 Footnote2 Footnote5 Footnote22 Footnote23 Footnote24 Footnote25 Footnote26 Footnote27 Footnote28 Footnote29 Footnote30 Footnote31. 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 Footnote32 Footnote33. 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 Footnote34. 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 Footnote35 Footnote36.

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 Footnote37 Footnote38 Footnote39 Footnote40.

INFECTIOUS DOSE: Viral hemorrhagic fevers have an infectious dose of 1 - 10 organisms by aerosol in non-human primates Footnote41.

MODE OF TRANSMISSION: In an outbreak, it is hypothesized that the first patient becomes infected as a result of contact with an infected animal Footnote22. 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 deathFootnote1 Footnote2 Footnote22 Footnote42. 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 Footnote1 Footnote2. 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 Footnote2 Footnote10 Footnote43.

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 Footnote1 Footnote10 Footnote15 Footnote44 Footnote45. Viral shedding has been observed in nasopharyngeal secretions and rectal swabs of pigs following experimental inoculation Footnote29 Footnote30.

INCUBATION PERIOD: Two to 21 days Footnote1 Footnote15 Footnote17.

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 Footnote1 Footnote2 Footnote59 Footnote60.

SECTION III - DISSEMINATION

RESERVOIR: The natural reservoir of Ebola is unknown Footnote1 Footnote2. Antibodies to the virus have been found in the serum of domestic guinea pigs and wild rodents, with no relation to human transmission Footnote34 Footnote47. Serum antibodies and viral RNA have been identified in some bat species, suggesting bats may be a natural reservoir Footnote37 Footnote38 Footnote39 Footnote40.

ZOONOSIS: Zoonosis between humans and animal is suspected Footnote2 Footnote22 Footnote37.

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) Footnote48 Footnote49 Footnote50 Footnote62 Footnote63. 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) Footnote62. 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 Footnote10 Footnote48 Footnote50. Ebolavirus has also been determined to be moderately sensitive to UVC radiation Footnote51.

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) Footnote52 Footnote61. One study could not recover any Ebolavirus from experimentally contaminated surfaces (plastic, metal or glass) at room temperature Footnote61.  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) Footnote53. When dried in tissue culture media onto glass and stored at 4 °C, Zaire ebolavirus survived for over 50 days Footnote61. 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 Footnote64. 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 Footnote1 Footnote2 Footnote14 Footnote41. It is useful to note that the Marburg virus is morphologically indistinguishable from the ebolavirus, and laboratory surveillance of Ebola is extremely hazardous Footnote1 Footnote2 Footnote14 Footnote54. 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 Footnote27 Footnote37. Instead, treatment is supportive, and is directed at maintaining organ function and electrolyte balance and combating haemorrhage and shock Footnote22 Footnote55.

IMMUNIZATION: None Footnote27.

PROPHYLAXIS: None. Management of the Ebola virus is solely based on isolation and barrier-nursing with symptomatic and supportive treatments Footnote8.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: One reported near-fatal case following a minute finger prick in an English laboratory (1976) Footnote56. A Swiss zoologist contracted Ebola virus after performing an autopsy on a chimpanzee in 1994 Footnote2 Footnote57. 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 Footnote8.

SOURCES/SPECIMENS: Blood, serum, urine, respiratory and throat secretions, semen, and organs or their homogenates from human or animal hosts Footnote1 Footnote2 Footnote53. Human or animal hosts, including non-human primates, may represent a further source of infection Footnote54.

PRIMARY HAZARDS: Accidental parenteral inoculation, respiratory exposure to infectious aerosols/droplets, and/or direct contact with skin or mucous membranes Footnote54.

SPECIAL HAZARDS: Work with, or exposure to, infected non-human primates, rodents, or their carcasses represents a risk of human infection Footnote54.

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 4 Footnote58.

CONTAINMENT REQUIREMENTS: Containment Level 4 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, and cultures. Please see theinterim 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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