RABIES VIRUS

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Rabies virus.

SYNONYM OR CROSS REFERENCE: Rabies, hydrophobia, lyssavirus^(1-9).

CHARACTERISTICS: As a member of the Lyssavirus genus, in the family Rhabdoviridae^{(1,3, 5)}, rabies virus is a bullet-shaped, enveloped virus of approximately 75 nm in diameter by 180 nm in length, and has a single-stranded, negative-sense RNA genome⁽³⁾. The Lyssavirus genus has 7 members, of which only serotype 1 commonly infects humans, while the other 6 are rare causes of human disease⁽⁴⁾.

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Rabies virus can cause an acute infection, marked by progressive encephalomyelitis, and is usually fatal⁽¹⁰⁾. The initial symptoms of rabies resemble those of other systemic viral infections, including fever, headache, malaise, and upper respiratory and gastrointestinal tract disorders^(1,4,7). This prodromal phase typically lasts about 4 days, but can last as long as 10 days before specific symptoms develop^(1-4). Almost all cases of clinical rabies are fatal^(1,2). Human rabies is typically seen in 2 forms: furious and paralytic (or dumb)⁽³⁾.

Furious rabies : Accounts for 80% of rabies cases, is dominated by encephalitis, and presents with hydrophobia, delirium, and agitation^(1,3). Hydrophobia is the symptom most identified with rabies; patients have severe difficulty in swallowing and can become fearful at the sight of water despite an intense thirst. Other manifestations of furious rabies include hyperactivity, seizures, and aerophobia⁽⁴⁾. Hyperventilation is frequently present, presumably reflecting brain stem infection. Patients then fall into a coma and typically die within 1 to 2 weeks, despite maximal intensive care⁽³⁾.

Paralytic (dumb) rabies: In contrast to furious rabies, paralytic rabies patients lack signs of cortical irritation, instead presenting with ascending paralysis or symmetrical tetraparalysis⁽³⁾. As the condition progresses, the patient becomes confused and death preceded by a coma may ensue⁽³⁾.

EPIDEMIOLOGY: Rabies occurs throughout the world except in Antarctica, and a few island nations^(2,3,5). The vast majority of cases occur in areas of uncontrolled domestic dog rabies⁽³⁾. Rabies is divided into two types for epidemiological purposes: urban and sylvan^(1,4).

Urban rabies : Found predominately in developing countries in Asia and Africa⁽⁴⁾.

Sylvan rabies : Mostly seen in developed countries in the northern hemisphere⁽⁴⁾.

Rabies is estimated to cause 55,000 worldwide human deaths per year, the vast majority of which are in Africa and Asia^(6,10). Several countries, most of which are islands, are rabies-free, including the British Isles, New Zealand, Japan, Taiwan, many of the Caribbean islands, Sweden, Norway, and Spain. These countries remain rabies-free due to the stringency of their quarantine laws for imported animals. Australia was at one time believed to be rabies free, but bat-transmitted rabies is now endemic there⁽²⁾. In Canada, a total of 23 people have died of rabies since 1924, and two fatal cases were observed in 2000 and 2003, which were the first cases of rabies in the country since 1985⁽¹¹⁾.

HOST RANGE: Humans, and many mammals, most commonly wild and domestic canids (e.g. dogs, foxes, coyotes), mustelids (e.g. skunks, badgers, martens), viverids (e.g. mongooses, civets, genets), procyonids (e.g. racoons), and insectivorous and haematophagous bats^(1,3,4,8,9).

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Rabies is most commonly transmitted to humans via the bite of a rabies-infected animal^(2-4,7). Bites to the head, neck, and arms are the most likely to lead to transmission⁽¹⁾. The amount of virus reaching the lesion is also a factor in transmission; for example, when a bite has to penetrate clothing, the saliva may be retained in the fabric and be prevented from entering the wound^(2-4). Potential non-bite modes of transmission include contamination of a pre-existing wound, contact of mucous membrane or respiratory tract with the saliva of an infected animal, exposure to aerosolised rabies virus in the laboratory (or from bats), or via organ transplantation from an infected donor^(1-4,7).

INCUBATION PERIOD: Varies from days to more than 7 years, with 75% of patients becoming ill within 90 days of exposure^(1,3-5).

COMMUNICABILITY: Direct human-to-human transmission is theoretically possible but rare and has only been documented in cases of transplants (corneal, kidney, liver, blood vessel)^{(1,4-7, 9,10)}.

SECTION III - DISSEMINATION

RESERVOIR: Urban rabies: stray dogs^(1,4). Sylvan rabies; dogs, foxes, coyotes, wolves, jackals, skunks, racoons, mongooses, and other biting mammals such as bats^(1,5).

ZOONOSIS: Yes, from the bite of an infected animal^(1-9).

VECTORS: None known.

SECTION IV - STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Ribavirin (virazole) has shown some efficacy against rabies virus in vitro, and interferon-γ was shown to be modestly effective in treating rabies-infected cynomolgus monkeys^(12,13).

SUSCEPTIBILITY TO DISINFECTANTS: Rabies virus is inactivated by exposure to 70% ethanol, phenol, formalin, ether, trypsin, β-propiolactone, and some other detergents⁽³⁾.

PHYSICAL INACTIVATION: Rabies virus does not tolerate pH below 3 or above 11, and is inactivated by ultraviolet light⁽³⁾.

SURVIVAL OUTSIDE HOST: This virus does not survive well outside its host (in dried blood and secretions) as it is susceptible to sunlight and desiccation^(3,9).

SECTION V - FIRST AID / MEDICAL

SURVEILLANCE: Monitoring for symptoms is inadequate since, by the time symptoms are apparent, rabies is invariably fatal. No diagnostic methods are available during the incubation period⁽³⁾. Following the incubation period, methods of detection include viral isolation, RT- PCR, and direct immunofluorescence of clinical specimens^(1,4-7).

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

FIRST AID/TREATMENT: First aid for rabies begins with good wound care, which can reduce the risk of rabies by up to 90%. Wash the wound with a soap solution, followed by 70% ethanol or an iodine containing solution^(1,3-5). Following wound care, the clinician must decide whether to institute passive and/or active immunization⁽³⁾.

There is no established treatment for rabies once symptoms have begun; almost all patients succumb to the disease or its complications within a few weeks of onset^(1,3). Supportive therapy includes intubation, sedation, mechanical ventilation, fluid and electrolyte management, nutrition, and management of intercurrent illnesses and complications⁽³⁾.

IMMUNISATION: Pre-exposure immunization of individuals at high risk for exposure (e.g. laboratory workers, veterinarians, and animal handlers) can be done using Imovax Rabies, a human diploid cell vaccine (HDCV), or RabAvert, a purified chick embryo cell vaccine (PCECV)^(2,8). Currently, both have been approved for use in Canada, and may be used as a pre- and post-exposure prophylaxis⁽¹⁴⁾.

PROPHYLAXIS: Post-exposure rabies prophylaxis with HDCV or PCECV together with the administration of rabies immunoglobulin (RIG) is highly effective⁽¹⁴⁾, although this should not be used in persons who have previously received complete vaccine regimens (pre-exposure vaccination) who require vaccination only⁽⁸⁾.

SECTION VI - LABORATORY HAZARDS

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^(7,15). No cases of laboratory-acquired infections have been reported in the last several decades. Pre-exposure vaccination is necessary for any individuals working in the laboratory with live virus or diagnostic specimens.

SOURCES/SPECIMENS: Saliva, cerebrospinal fluid, brain tissue, conjunctival or corneal imprints, throat washings, urine, blood, skin biopsies of infected individuals or animals^(1,4,6,7).

PRIMARY HAZARDS: Infectious droplets and aerosols containing rabies virus^(1-6).

SPECIAL HAZARDS: Fixed tissue preparations can still be infectious so extreme care is needed when handling them⁽⁴⁾.

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTI ON

RISK GROUP CLASSIFICATION: Risk Group 3⁽¹⁶⁾.

CONTAINMENT REQUIREMENTS: Containment Level 3 facilities, equipment, and operational practices for work involving infected or potentially infected materials, animals, or cultures.

PROTECTIVE CLOTHING: Personnel entering the laboratory should remove street clothing and jewelry, 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⁽¹⁷⁾.

OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) or other appropriate primary containment device in combination with personal protective equipment. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are loaded or unloaded in a biological safety cabinet. 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 animals or large scale activities⁽¹⁷⁾.

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, while wearing protective clothing, gently cover the spill with paper towels and apply appropriate disinfectant starting at the perimeter, working inwards towards the centre. Allow sufficient contact time before clean up⁽¹⁷⁾.

DISPOSAL: Decontaminate all materials for disposal by steam sterilisation, chemical disinfection, and/or incineration⁽¹⁷⁾.

STORAGE: In sealed, leak-proof containers that are appropriately labelled and locked in a Containment Level 3 laboratory⁽¹⁷⁾.

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: November 2010

PREPARED BY: Pathogen Regulation Directorate, 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, 2010
Canada

REFERENCES:

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2. Hankins, D. G., & Rosekrans, J. A. (2004). Overview, prevention, and treatment of rabies. Mayo Clinic Proceedings, 79 (5), 671-676.
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4. Krauss, H., Weber, A., Appel, M., Enders, B., Isenberg, H. D., Schiefer, H. G., Slenczka, H. G., von Graevenitz, A., & Zahner, H. (2003). Viral Zoonoses. Zoonoses: Infectious diseases transmissible from animals to humans (3rd ed., pp. 113-119). Washington, D.C.: ASM Press.
5. (2004). In D. L. Heymann (Ed.), Control of Communicable Diseases Manual (18th ed., pp. 438-447). Washington, D.C.: American Public Health Association.
6. Plotkin, S. (2000). Rabies. Clinical Infectious Diseases, 30 (1), 4-12. Retrieved from dx.doi.org/10.1086/313632
7. Anderson, L. J., Nicholson, K. G., Tauxe, R. V., & Winkler, W. G. (1984). Human rabies in the United States, 1960 to 1979: epidemiology, diagnosis, and prevention. Annals of Internal Medicine, 100 (5), 728-735.
8. Human rabies prevention--United States, 1999. Recommendations of the Advisory Committee on Immunization Practices (ACIP).[Erratum appears in MMWR Morb Mortal Wkly Rep 2000 Aug 18;49(32):737]. (1999). Morbidity & Mortality Weekly Report.Recommendations & Reports, 48 (RR-1), 1-21.
9. Rupprecht, C. E., & Gibbons, R. V. (2004). Clinical practice. Prophylaxis against rabies. New England Journal of Medicine, 351 (25), 2626-2635.
10. Heymann, D. L. (2008). Control of Communicable Diseases Manual (19th Edition ed.). Washington, D.C.: American Public Health Association.
11. Public Health Agency of Canada. (2007). Vaccine-Preventable Diseases - Rabies. Retrieved 11/24, 2010, from www.phac-aspc.gc.ca/im/vpd-mev/rabies-eng.php
12. Bussereau, F., & Ermine, A. (1983). Effects of heteropolyanions and nucleoside analogues on rabies virus: In vitro study of syntheses and viral production. Annales De Virologie, 134 (4), 487-506.
13. Weinmann, E., Majer, M., & Hilfenhaus, J. (1979). Intramuscular and/or intralumbar postexposure treatment of rabies virus-infected cynomolgus monkeys with human interferon. Infection and Immunity, 24 (1), 24-31.
14. Public Health Agency of Canada. (2007). Canadian Immunization Guide Seventh Edition - 2006 - Part 4: Active Immunizing Agents. Retrieved 11/24, 2010, from www.phac-aspc.gc.ca/publicat/cig-gci/p04-rabi-rage-eng.php#approve
15. Collins, C. H., & Kennedy, D. A. (1999). Laboratory acquired infections. Laboratory acquired infections: History, incidence, causes and prevention (4th ed., pp. 28). London, UK: Buttersworth.
16. Human Pathogens and Toxins Act. S.C. 2009, c. 24. Government of Canada, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009, (2009).
17. Public Health Agency of Canada. (2004). In Best M., Graham M. L., Leitner R., Ouellette M. and Ugwu K. (Eds.), Laboratory Biosafety Guidelines (3rd ed.). Canada: Public Health Agency of Canada.