Rabies virus: Infectious substances pathogen safety data sheet

For more information on Lyssavirus rabies, see the following:

• Rabies: Travel health advice
• Rabies: Symptoms and treatment

Section I – Infectious agent

Name

Rabies virus

Agent type

Virus

Taxonomy

Family

Rhabdoviridae

Genus

Lyssavirus

Species

Lyssavirus rabies

Subspecies/strain/clonal isolate

Phylogroup I: Lyssavirus aravan Aravan virus (ARAV), Lyssavirus australis Australian bar lyssavirus (ABLV), Lyssavirus bokeloh Bokeloh bat lyssavirus (BBLV), Lyssavirus duvenhage Duvenhage virus (DUVV), Lyssavirus hamburg European bat lyssavirus type I (EBLV-1), Lyssavirus Helsinki European bat lyssavirus type II (EBLV-2), Lyssavirus gannoruwa Gannoruwa bat lyssavirus (GBLV), Lyssavirus irkut Irkut virus (IRKV), Lyssavirus khujand Khujand virus (KHUV), and Lyssavirus formosa Taiwan bat lyssavirus (TWBLV).

Phylogroup II: Lyssavirus lagos Lagos bat virus (LBV), Lyssavirus mokola Mokola virus (MOKV), and Lyssavirus shimoni Shimoni bat virus (SHIBV).

No Phylogroup: Lyssavirus ikoma Ikoma lyssavirus (IRKV), Lyssavirus lledia Lledia bat lyssavirus (LLEBV), and Lyssavirus caucasicus West Caucasian bat virus (WCBV)^{Footnote 1}.

Synonym or cross-reference

Hydrophobia^{Footnote 2}.

Characteristics

Brief description

Lyssaviruses are bullet-shaped, single-stranded, negative-sense RNA viruses^{Footnote 3}. Their genome is non-segmented, linear, and is approximately 12kb in length. It includes five major genes that are arranged in the conserved linear order 3'-N-P-M-G-L-5'^{Footnote 4}. Lyssaviruses consist of two units, the external unit being a lipid membrane with protruding spikes of glycoprotein and the internal unit a nucleocapsid core which consists of a ribonucleoprotein complex (the genomic RNA bound to the nucleoprotein), viral polymerase, and phosphoprotein^{Footnote 3}. The N protein encapsulates the virus RNA, the P and L protein form the ribonucleoprotein (RNP) complex, which can initiate viral transcription and replication^{Footnote 5Footnote 6}. M proteins condense the RNP into the bullet-shape and recruits RNP to the cellular membrane during replication. The M protein is also important for the budding of the enveloped virus from the cell and interacts with the G protein^{Footnote 5Footnote 7Footnote 8}.

Properties

Lyssavirus rabies (RABV) enters the body via transdermal inoculation, usually through the bite of an infected animal, or direct contact with infectious materials (saliva, cerebrospinal fluid, nerve tissue) on mucous membranes or skin lesions^{Footnote 9}. Virus replication begins in non-nervous tissues such as muscle cells, where it can survive for long periods of time, which leads to variability in incubation period^{Footnote 9Footnote 10}. As the virus is neurotropic, it must enter into the peripheral nervous system, followed by further dissemination to the central nervous system (CNS) via retrograde axonal transport to cause severe disease. The virus continues to replicate and spread throughout the CNS, and eventually travels via peripheral nerves to various tissues throughout the body, particularly the salivary glands where the transmission cycles repeats^{Footnote 9}.

Section II – Hazard identification

Pathogenicity and toxicity

RABV causes viral encephalitis which kills up to 70,000 people/year worldwide^{Footnote 11}. Following viral entry, the virus travels through the peripheral nervous system targeting the central nerves, leading to encephalomyelitis^{Footnote 11}. Once clinical features are observed, rabies is universally fatal^{Footnote 11Footnote 12}. Rabies has five phases of development: 1) Incubation, 2) Prodromal, 3) Acute neurologic, 4) Coma, and 5) Death^{Footnote 13}. It typically takes 30-90 days for rabies to develop, although it can take anywhere from 5 days to more than 2 years after initial exposure^{Footnote 14}. The closer the bite is to the brain, the more quickly symptoms will appear^{Footnote 15}. During the prodromal phase the first signs and symptoms appear and include: fever, fatigue, sore throat, cough, dyspnea, anorexia, dysphagia, nausea, vomiting, abdominal pain, diarrhoea, headache, vertigo, anxiety, irritability, and anxiousness^{Footnote 14}. The neurologic phase can be classified into one of three categories:

Encephalitic (furious) – This is the most common presentation of rabies, present in approximately 80% of cases. Patients may exhibit hydrophobia or aerophobia, causing spasms to develop as a result of stimuli such as swallowing liquids. Agitation and changes in mental activity, autonomic dysfunction, increased deep tendon reflexes, and nuchal rigidity can occur^{Footnote 16}.

Paralytic (dumb) – A less common presentation of rabies, occurs in approximately 20% of cases. Hydrophobia and irritability are not observed in these patents. Weakness, altered mental activity, ongoing fevers, and bladder dysfunction are the main symptoms^{Footnote 16}.

Non classic – This form of rabies is very rare. It is generally associated with seizures and more profound motor and sensory symptoms^{Footnote 16}.

During the acute neurological phase, the disease spreads through the brain resulting in central nervous system dysfunction, anxiety, insomnia, disorientation, agitation, paranoia, terror and hallucinations and delirium^{Footnote 14}. Additionally, a significant amount of saliva is produced, coupled with an inability to swallow, resulting in hydrophobia due to paralysed throat and jaw. The cause of death can be blockage of airways, seizures, exhaustion, or widespread paralysis^{Footnote 15}.

Epidemiology

Developing countries are more affected than developed countries due to the widespread use of post-exposure prophylaxis and many prevention programs in place. In developed countries, domesticated animals have only been responsible for approximately 10% of rabies transmission, while wild animals are responsible for the remainder^{Footnote 16}. RABV affects all mammals and is prevalent throughout the world, and endemic in many countries, except in islands such as Australia and Antarctica^{Footnote 17}. The disease constitutes a major public health problem globally and in more than 150 countries and territories^{Footnote 18Footnote 19}. RABV is considered endemic in humans in various areas in Asia, Africa, South America, and North America, with specifically 26, 41, 2, and 3 countries afflicted, respectively^{Footnote 19}.

Human rabies in Canada is extremely rare, however, in 2019, a 21 year-old man had an encounter with an infected bat in B.C., ultimately leading to his death^{Footnote 20}. In 2024, Vietnam recorded 22 rabies-related deaths in the first two months of the year. This is two times higher than the same period in the previous year and has been attributed to poor vaccination rates among dogs and cats. Many patients were children under five years old who were bitten by dogs and cats in the head and face areas^{Footnote 21}. There was a sudden spike in rabies cases and dog-bite-induced deaths in India and many other countries after the COVID-19 pandemic^{Footnote 22Footnote 23}. This was due to a number of factors including COVID-19 hindering the availability of pre-and post-exposure prophylactic measures, implementation of mass vaccination for dogs, increased aggressiveness in dogs, an altered dog population, risky human-dog encounters, and disrupted surveillance systems^{Footnote 23Footnote 24}.

RABV are maintained in two types of cycles, urban and sylvatic.

Urban rabies – Dogs act as the host for a rabies variant that circulates in canine populations, and most cases occur in impoverished regions, specially in Africa and Asia. Previously the urban cycle was found in most of the world; however, is now usually only seen where vaccination rates in dogs are inadequate. Canine rabies can be found in foxes and skunks in North America^{Footnote 25}.

Sylvatic rabies – Can be found in much of the world, though a few countries have controlled wildlife rabies with oral vaccines. One to a few wildlife species perpetuate a particular variant in each area, either as hosts or important secondary hosts, the disease pattern can be relatively stable, or occur as a slow moving epidemic^{Footnote 25}.

Host range

Natural host(s)

Reported natural hosts include domestic dogs^{Footnote 25Footnote 26}, jackals, bat-earned foxes^{Footnote 25}, skunks, domestic cats, raccoon dogs, raccoons, mongooses, goats^{Footnote 26}, donkeys, red foxes, cattle^{Footnote 27}, equine, badgers^{Footnote 18}.

All species of mammals are thought able to contract rabies, but only a limited number also act as hosts^{Footnote 27}. The domestic dog is the primary RABV host species responsible for human infections; however, there are over 30 recognized RABV host species globally, and many more are presumed to be unrecognized due to poor-quality surveillance infrastructure^{Footnote 28}. Other hosts include bats, wolves, livestock, cats, coati, marmoset, and coyotes^{Footnote 29}.

Other host(s)

Experimental hosts infected with EBLV1 include mice, marmosets, ferrets, and sheep^{Footnote 30}. Additional natural hosts have also been reported to be experimentally infected as well, specifically cats and dogs^{Footnote 30}. Birds can also be infected with RABV experimentally within studies including orally or parenterally inoculated animals^{Footnote 27}. Experimentally infected birds, can shed live virus in saliva with minimal or no clinical signs^{Footnote 27}.

Infectious dose

Unknown.

Incubation period

The incubation period is highly variable from 2 weeks to 6 years (avg. 2-3 months), which depends on the concentration of the virus inoculated, inoculation site, and density of innervations^{Footnote 31Footnote 32}. The greatest risk factor is bites on the hands, neck, face, and head, with bleeding which leads to shorter incubation period. RABV can persist in the muscle for prolonged durations, which is also a factor contributing to this highly variable incubation period^{Footnote 29Footnote 31}.

Communicability

The virus can be easily passed from one mammal to another, whether they are of the same species or not^{Footnote 9}. The most common way to contract the virus is through a bite from a rabid animal. However, infection can also be spread through skin wounds contaminated by infected saliva and through direct contact with mucous membranes. The virus cannot pass through intact skin. The chance of contracting rabies from a bite is 5-80% which is at least 50 times higher than the risk of contraction by a scratch (0.1-1%). Inhalation of aerosolised RABV is another non-bite route of infection, although most people, except for laboratory personnel, are unlikely to encounter an aerosolised RABV. Rare cases of humans contracting rabies through breathing air from a cave of infected bats has been reported. Rabies can also be found in the milk of infected animals. Transmission between humans is extremely rare, although it can happen through transplant surgery or more rarely, kisses or sexual activity^{Footnote 9}.

Section III – Dissemination

Reservoir

None. Once clinical symptoms of rabies appear, rabies is virtually 100% fatal if left untreated^{Footnote 33}. Therefore, animals would be considered to be hosts and not asymptomatic reservoirs.

Zoonosis

Rabies is usually transmitted to humans through the bite of an infected animal. Bats, skunks, foxes, and raccoons are the most common animals to have rabies in Canada^{Footnote 34}.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

None.

Susceptibility to disinfectants

RABV can be inactivated by a number of disinfectants including 70% isopropyl alcohol, ethanol, iodides, quaternary ammonium compounds, formaldehyde, phenol based disinfectant and some other agents^{Footnote 27}.

Furthermore, a 4% chlorohexidine scrub can also disinfect RABV^{Footnote 35}. Sodium hypochlorite commonly known as bleach at 0.05% followed by 70% ethanol will disinfect RABV^{Footnote 35}.

Physical inactivation

RABV is not infectious when dried out or exposed to sunlight^{Footnote 36}. It is also inactivated by low (<3) or high (>11) pH and by UV irradiation^{Footnote 27}.

Survival outside host

RABV is fragile under most normal conditions. It is destroyed within a few minutes at temperatures greater than 50℃, and survives no more than a few hours at room temperature. The virus is no longer infectious once the material containing the virus is dry^{Footnote 37}.

Section V – First aid/medical

Surveillance

Several tests are necessary to diagnose rabies in humans; no single test is sufficient. Tests are performed on samples of saliva, serum, spinal fluid, and skin hair follicles at the nape of the neck. Saliva can be tested by virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR). Serum and spinal fluid are tested for antibodies to RABV while skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of the follicles^{Footnote 35}.

Diagnosis in animals: A diagnosis of rabies can be made after detection of RABV from any part of the affected brain, but in order to rule out rabies, the test must include tissue from at least two locations in the brain, preferably the brain stem and cerebellum. The test requires that the animal is euthanized. For animals with low probability of rabies such as dogs, cats, and ferrets, observation period (10 days) may be appropriate to rule out the risk of potential human rabies exposure^{Footnote 37}.

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.

First aid/treatment

After an animal bite, the region should be cleaned extensively with soap and water to help reduce the risk of bacterial infection. Povidone solutions or 70% alcohol may reduce viral transmission from a bite^{Footnote 27}.

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

Pre-exposure rabies immunization with either IMOVAX^®Rabies (HDCV) or RABAVERT^® (PCECV) should be offered to people at high risk of close contact with rabid animals or the RABV for example:

• Laboratory workers who handle the RABV.
• Veterinarian, veterinary staff, animal control and wildlife workers.
• Certain travelers.
• Hunters and trappers in areas with confirmed rabies.
• Spelunkers^{Footnote 38}.

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

Prophylaxis

Post-exposure prophylaxis of previous unimmunized individuals should consist of both rabies immunoglobulins (RabIG) and rabies vaccine. The RabIg provides immediate passive protection until the exposed person mounts an immune response to the rabies vaccine. Four doses of HDCV or PCECV should be administered intramuscularly (IM). The first dose (day 0) of the four-dose course of rabies vaccine should be administered as soon as possible after exposure. Additional doses should be administered on days 3, 7, and 14, after the first vaccination^{Footnote 35}. Rabies prophylaxis must be considered in every incident in which human exposure to potentially rabid animals has occurred, unless rabies is known to be absent from the local animal population^{Footnote 39}.

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

Two cases of laboratory-acquired rabies infections have been reported and are thought to have been acquired via aerosolized virus across mucous membranes. No cases of laboratory-acquired infections have been reported in the last several decades. Pre-exposure vaccination is strongly recommended for any individual working in the laboratory with live virus or diagnostic specimens^{Footnote 40}.

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

Sources/specimens

Brain tissue, skin, saliva, concentrated urine^{Footnote 41}.

Primary hazards

Bites or scratches of an infected animal is the primary hazard associated with exposure to Lyssavirus rabies^{Footnote 27}.

Special hazards

Inhalation of aerosolised RABV is a potential route of exposure^{Footnote 41}.

Section VII – Exposure controls/personal protection

Risk group classification

Lyssavirus rabies (RABV) is a Risk Group 3 Human Pathogen^{Footnote 42Footnote 43} and a Risk group 3 Animal Pathogen^{Footnote 41Footnote 43}.

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.

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 be considered with work involving animals or large scale activities.

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 the 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.

An inventory of RG3 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 Lyssavirus rabies require a Pathogen and Toxin licence issued by the Public Health Agency of Canada (PHAC). Lyssavirus rabies is a terrestrial animal pathogen in Canada; therefore, importation of Lyssavirus rabies requires an import permit under the authority of the Health of Animals Regulations (HAR). The PHAC issues a Pathogen and Toxin Licence that includes an HAR importation permit.

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
• National notifiable disease (human)
• Reportable disease (animal)

Last file update

August, 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, directives and standards applicable to the import, transport, and use of pathogens and toxins 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