Eastern and Western Equine Encephalitis virus: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Eastern and Western Equine Encephalitis virus

Agent type

Virus

Taxonomy

Family

Togaviridae

Genus

Alphavirus

Species

Alphavirus eastern and Alphavirus western

Subspecies/strain/clonal isolate

Western equine encephalitis virus; Western equine encephalitis virus South American, Eastern equine encephalitis virus; Western equine encephalitis virus North American, Eastern equine encephalitis virus North American^{Footnote 1}.

Synonym or cross-reference

Alphavirus, EEE, WEE, encephalitis, Western equine encephalomyelitis virus, Eastern equine encephalomyelitis virus, and sleeping sickness.

Characteristics

Brief description

Alphaviruses such as Eastern and Western Equine encephalitis virus (E/WEEV) have a positive 12 kb positive-sense single-stranded RNA genome with five structural genes encoding capsid E1, E2, E3, 6K, and Tf, and four non-structural genes encoding nsP1, nsP2, nsP3, and nsP4^{Footnote 2Footnote 3Footnote 4Footnote 5Footnote 6}.

Properties

E/WEEV are transmitted into the subcutaneous tissue of the host via the bite of an infected mosquito^{Footnote 7}. Initial viral replication usually begins in the local lymph nodes. Viremia ensues and, if the viral load is high enough, the virus may translocate into the central nervous system across the blood-brain barrier resulting in cerebral and meningeal inflammation and necrosis^{Footnote 7}. Receptor-mediated endocytosis allows alphavirus particles to enter cells and is facilitated by E1, E2 and E3 proteins^{Footnote 6}. Viral and endosomal membranes undergo fusion upon acidification of the endosome lumen followed by cytosolic release of the nucleocapsid core, disintegration of the core and release of the viral RNA genome. Cytosolic progeny RNA genome synthesis and nucleocapsid core assembly occur in the cytosol, whereas envelope proteins are synthesized in secretory ER and Golgi network of the host cell. Final assembly of alphavirus progeny particles involves the plasma membrane^{Footnote 6Footnote 8}.

Section II – Hazard identification

Pathogenicity and toxicity

Most persons infected with E/WEEV have no apparent illness^{Footnote 9Footnote 10}. However, an estimated <5% of persons infected with EEEV develop meningitis or encephalitis^{Footnote 11}. Systemic infection is characterized by acute onset of fever, chills, malaise, myalgia, and arthralgia^{Footnote 9Footnote 12}. Signs and symptoms in patients with neuroinvasive disease include fever, headache, altered mental status, and seizures^{Footnote 9Footnote 13Footnote 14Footnote 15}. EEEV neuroinvasive disease is estimated to have a 30% fatality rate and results in neurologic sequalae (convulsions, seizures and paralysis) in more than 50%-90% of survivors^{Footnote 9Footnote 13Footnote 16Footnote 17Footnote 18}. WEEV is severely pathogenic in younger patients, with 90% mortality in children less than 1 year old, and an overall mortality rate ranging from 3 to 15%^{Footnote 19Footnote 20Footnote 21} whereas 15-30% of WEEV survivors have confusion, visual disturbances, photophobia, seizures, somnolence coma and spastic paresis. In addition, intellectual disability and behavioural changes are common among E/WEEV infection survivors^{Footnote 19}.

Fatality rates in unvaccinated horses are approximately 90 and 30% for EEEV and WEEV respectively^{Footnote 19Footnote 21}.

Epidemiology

WEEV has historically been reported only in the Western United States and Canada^{Footnote 7}. However, during the past two decades, the number and frequency of human cases have increased in the Northeastern United States, culminating in one of the largest WEEV outbreaks in history in 2019^{Footnote 22Footnote 23}. This outbreak involved 38 human cases nationally, of which 23 occurred in the Northeastern region. The factors causing the increasing trend of WEEV are complex and not entirely clear, but it is suspected to be related to environmental changes that support higher mosquito densities and more intense virus amplification in transmission cycles^{Footnote 23}. EEEV is found in the Eastern part of North America and is largely a seasonal virus, with peaks in summer months^{Footnote 19Footnote 24}. There have been over 600 human WEEV cases reported in the United States (US) from 1964 to 2010 with the frequency decreasing steadily over the last few decades^{Footnote 19Footnote 25Footnote 26}. Horses in Mexico were reported to be infected in 2019^{Footnote 19Footnote 27}.

Host range

Natural host(s)

E/WEEV can be found in horses, some bird species, and in dogs. Horses tend to be the first to develop disease and thus often serve as an indicator of a starting epidemic situation^{Footnote 28}.

Other host(s)

Humans are considered dead-end hosts because they generally do not develop high enough viremia levels to allow virus transmission to feeding mosquitoes^{Footnote 9}.

Infectious dose

Unknown.

Incubation period

The incubation period for EEEV ranges from 3 to 10 days^{Footnote 29Footnote 30} while the incubation period for WEEV is 5 to 15 days^{Footnote 31}.

Communicability

Virus strains are remarkably conserved genetically, suggesting efficient transport by birds during migrations^{Footnote 32}. In the Western US, WEEV is transmitted primarily in agricultural habitats by Culex tarsalis mosquitoes among passerine birds, principally sparrows and house finches. EEEV cycles between Culiseta melanura mosquitoes and birds residing in freshwater hardwood swamps; incidental transmission to other vertebrate species occurs through bridging vectors such as Coqullettidia and Aedes species mosquitoes^{Footnote 33Footnote 34Footnote 35Footnote 36}. In 2017, three organ transplant recipients from a single donor developed fever and encephalitis approximately one week following transplantation^{Footnote 36}. After initial testing for other infectious causes for the encephalitis, EEEV transmission through organ transplantation was identified. E/WEEV are considered potential threats as a bioterrorism agent via aerosol spread when used as a bioweapon or in experimental settings^{Footnote 37}. However, cases of natural infection with E/WEEV require a vector for transmission to occur, meaning person-to-person transmission is highly unlikely and has not been reported^{Footnote 38}. E/WEEV can be infectious to personnel handling E/WEEV-infected tissues and cerebrospinal fluids (CSF).

Section III – Dissemination

Reservoir

E/WEEV are maintained within a bird-mosquito-bird enzootic cycle, whereby passerine birds are the primary reservoirs^{Footnote 38}. In South America, other mammals, such as rodents, bats, turtles, and ungulates, may play a role as significant reservoirs of the virus^{Footnote 32}.

Zoonosis

E/WEEV are maintained in an enzootic transmission cycle between passerine birds and C. melanura, with transmission to human though mosquitoes and not through zoonosis^{Footnote 39}.

Vectors

The vectors for transmission to human of WEEV are the Culex tarsalis, Culiseta spp., and Aedes mosquito species^{Footnote 7}. C. melanura is the primary vector for EEEV^{Footnote 38}.

Section IV – Stability and viability

Drug susceptibility/resistance

No antiviral drug has proven to be beneficial in treating E/WEEV^{Footnote 7Footnote 30}.

Susceptibility to disinfectants

E/WEEV are susceptible to disinfectants such as 1% sodium hypochlorite, 4% formaldehyde, 2% glutaraldehyde, 70% ethanol and 3-6% hydrogen peroxide^{Footnote 40}.

Physical inactivation

WEEV requires around 90 minutes to be completely inactivated at 56°C. Alphavirus virions are stable at pH 7-8. They are susceptible to radiant sunlight, moist or dry heat and drying^{Footnote 41}.

Survival outside host

Alphaviruses exhibit poor stability outside of the host: virion half-life is 7 hours at 37°C, and these viruses are susceptible to radiant sunlight, moist or dry heat, and drying^{Footnote 41}.

Section V – First aid/medical

Surveillance

Diagnosis of infection requires confirmation through laboratory techniques as clinical presentation is not specific^{Footnote 13Footnote 14}. These laboratory methods may be direct virological diagnostic methods such as nucleic acid amplification or cell culture, or indirect serological methods such as detecting antibodies produced against the viruses.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (Canadian Biosafety Handbook).

First aid/treatment

Like all diseases caused by alphaviruses, E/WEEV have no specific treatment^{Footnote 33Footnote 42}. Management is done primarily with supportive and preventive measures. Pharmacologic therapy consists of antipyretics, analgesics, and anticonvulsants.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

No approved antiviral drugs or vaccines for E/WEEV are available for humans^{Footnote 37}. A vaccine for equines is available as well as one investigational vaccine primarily used for laboratory personnel that shows moderate immunogenicity^{Footnote 43Footnote 44}. Live-attenuated and formalin-inactivated vaccines utilized for alphaviruses have limitations due to side effects or lack of efficacy^{Footnote 44}.

Several vaccine combinations have been approved and are available for equids in Canada^{Footnote 45}.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

None.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI – Laboratory hazard

Laboratory-acquired infections

Before 1967 only two cases of laboratory-acquired EEEV occurred, neither of which was fatal^{Footnote 46 Footnote 47}. For WEEV, five cases of laboratory-acquired infections have been reported, two of which were fatal.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

Fresh biological samples, of any type, should be considered potentially infectious^{Footnote 48}. Tissues used for diagnosis include blood, cerebrospinal fluid and tissues such as the brain and pancreas^{Footnote 41Footnote 42}.

Primary hazards

Bites of an infected mosquito is the primary hazard associated with exposure to E/WEEV.

Special hazards

E/WEEV can become infectious upon aerosolization^{Footnote 19}.

Section VII – Exposure controls/personal protection

Risk group classification

Alphavirus eastern and Alphavirus western are Risk Group 3 Human Pathogens and Risk Group 3 Animal Pathogens^{Footnote 49}.

Alphavirus eastern and Alphavirus western are Security Sensitive Biological Agent (SSBA).

Containment requirements

Containment Level 3 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

Protective clothing

The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects are to be strictly limited. Additional precautions must considered with work involving animals or large scale activities.

Proper precautions should be considered when working with infected arthropods. This might include implementing a program to prevent escapes and monitor any escaped arthropods, as well as using suitable personal protective equipment (PPE), among other measures^{Footnote 50 Footnote 51}.

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time with disinfectant before clean up (Canadian Biosafety Handbook).

Disposal

Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 3 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.

SSBA: Containers of security sensitive biological agents (SSBA) stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.

An inventory of RG3 and SSBA toxins in long-term storage, to be maintained and to include:

• specific identification of the regulated materials
• a mechanism that allows for the detection of a missing or stolen sample in a timely manner

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with Alphavirus eastern and/or Alphavirus western require a Pathogen and Toxin licence issued by the Public Health Agency of Canada (PHAC). Alphavirus eastern and/or Alphavirus western are terrestrial animal pathogens in Canada; therefore, importation of Alphavirus eastern and/or Alphavirus western requires an import permit under the authority of the Health of Animals Regulations (HAR). The PHAC issues a Pathogen and Toxin Licence which includes a Human Pathogen and Toxin Licence and an HAR importation permit.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations
• Immediately notifiable disease (animal)

Last file update

June, 2024

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright^©Public Health Agency of Canada, 2024, Canada