Rhabdoviridae: Rabies virus (with special reference to raccoon rabies variant)

Paratenic Species (Agent can survive on or in the species, but there is no replication or further development)

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Degree of Hazard (Risk to Humans / other Species)

• In developing countries, the incidence of rabies in humans is high and most cases are associated with bites from dogs. (J84.8.w16, J84.9.w25, J133.916.w2, D234)
• In developed countries, an increased proportion of human exposure to rabies is from wild terrestrial animals. (J84.8.w16, J133.916.w2)

Rabies is generally fatal when it occurs. (J15.23.w3)

• Species vary in their susceptibility to the virus. (J15.23.w3)
• Species vary in their tendency to be infected with rabies virus: inquisitive species are more likely to be bitten by a rabid animal than are timid species, and very small species are unlikely to survive a bite from a rabid animal, therefore are unlikely to develop rabies. (J15.23.w3)

Risks in the USA

Rabies is still one of the most important zoonoses in the USA. (J4.215.w4)

• Risks of contracting rabies in the USA are associated with a variety of species, including wild mammals (raccoons, skunks, foxes) and domestic animals (particularly cats and dogs). 
• Risk from bats: The greatest current risk of development of rabies in the USA is associated with rabies in bats, particularly due to unrecognised exposures of humans to rabies in bats. (J4.215.w4, J84.9.w25)
  • Risks may also be associated with increased viral infectivity in strains of rabies associated with rabies virus strains in Lasionycteris noctivagans - Silver-haired bats (Vespertilionidae - Vespertilionid bats (Family)) and Pipistrellus subflavus - Eastern pipistrelles (Pipstrellus - (Genus)). (J84.9.w25, J133.916.w2)
• Risk from raccoons: Raccoons (Procyon lotor - Common Raccoon) are currently the leading reservoir of rabies in the USA. (J4.215.w4)
  • In 2004, 37.5% (2,564 cases) of the 6,844 reported cases of rabies in animals from the 49 states, District of Columbia and Puerto Rico were in raccoons. (J4.227.w1)
  • Requirements for postexposure prophylaxis (PEP) increase greatly in areas undergoing raccoon rabies epizootics. This is due not only directly to direct or indirect contact between rabid, or potentially rabid, raccoons and humans, but also via the increase in the occurrence of rabies in other species, and in particular the increase in exposure of domestic animals to raccoon rabies. (J84.8.w16)
    • In New York State in 1992, before raccoon rabies was present, less than one person per 100,000 required rabies PEP per year. This increased to 35 per 100,000 in 1993 and 52 per 100,000 in 1994. Of the 1,173 individuals receiving PEP during these two years, 67% (783 cases) were associated with exposure to wild animals, and 589 of these (75%) were due to exposure to raccoons. Only 37 PEP cases involved bites from raccoons (34 raccoons); more were due to suspect indirect contact, mainly via saliva from a rabid or suspect rabid animal on the fur of domestic animals. Out of all the PEP cases which were attributed to rabid wild animals, 89% involved raccoons. (J84.5.w4)
    • In New York state, for the period 1993-1998, 18,238 humans received PEP. Potential human exposure occurred associated with 1,666 rabid raccoons, resulting in PEP given to 2,944 individuals (one to 25 potentially exposed individuals per rabid raccoon) - these cases made up 65.2% of all cases in which PEP was given associated with contact (generally with saliva or nervous tissue) of an animal which was then confirmed rabies-positive. Raccoons also made up 10.9 % of animals leading to individuals receiving PEP when the animal was not available for testing, and 11.3% of animals leading to PEP when testing confirmed that the animal was in fact not rabid. (J84.8.w16)
    • In New York state during 1995-2000, 250 of the 1,081 PEP cases attributed to wildlife, including 176 of the 309 cases of PEP (57%) attributed to confirmed rabid wild animals, were due to raccoons; 65% of exposures to raccoons occurred in urban counties. Incidence of PEP was 27 cases per 100,000 population, representing a decrease from earlier in the 1990s, possibly related to improved knowledge about what constitutes exposure from terrestrial mammals, and about avoiding exposures. (J84.11.w1)
    • Note: Risks to humans are increased not only due to rabies in raccoons following arrival of raccoon rabies in an area, but also due to an increase in the occurrence of rabies in other species, such as cats. (J4.202.w2)
  • Until recently, there had not been any reports of fatal rabies in humans due to raccoon rabies.
    • "The reason for the lack of human cases from exposure to rabid raccoons is uncertain, but may be due to improved postexposure treatment during the emergence of raccoon rabies, low titres of rabies virus in saliva, or lower pathogenicity of the raccoon virus." (B358.4.w4)
    • In 2003, the first human death associated with raccoon rabies was reported. Genetic sequencing showed that raccoon rabies virus variant was involved, however it was not determined how the affected person became infected. (N7.52.w7)
  • Risks from ferrets:

    • Ferrets with rabies often do not shed virus, but shedding in the saliva may vary depending on the rabies variant; shedding was more common in ferrets infected with the raccoon rabies variant. (B627.15.w15, J13.59.w1)

Risks in the UK

• In the UK, one case of fatal rabies occurred in 2002 in a bat worker (unvaccinated) who had been bitten by a Myotis daubentonii - Daubenton's bat; this was only the second confirmed case of human European bat lyssavirus type 2 infection (there have also been two confirmed cases of European bat lyssavirus type 1 infection. (J117.71.w1)
• Rabies is preventable by pre-exposure vaccination and by timely correct post-exposure treatment. (P52.2003.w1)
• The risk of European bat lyssavirus (EBL) infection in people handling bats in the UK is thought to be low. (W49.Oct03.w3) However individuals who are at risk of exposure to Lyssaviruses (including bat handlers in the UK) are highly recommended to get and maintain pre-exposure RABV vaccination. (P52.2003.w1, W49.Oct03.w3)
• If bitten by a bat in the UK it is recommended that the bite be washed thoroughly with soap and water, followed by cleansing with an alcohol base or other disinfectant, with immediate medical advice being sought after this. (W66.Oct03.w1)
• Vaccination against rabies is with a vaccine specific for classical rabies virus (RABV); it is thought that the vaccines also give protection against lyssa viruses carried by bats in Europe (EBLV-1, EBLV2); no-one who has either been immunised against rabies pre-exposure or given proper post-exposure treatment, has died of European bat lyssavirus. (W49.Oct03.w3)

Risks from birds

• There are no recorded cases of human rabies from birds. (B13.32.w3)

Risks in the laboratory

• The most likely sources of virus exposure for laboratory and animal care personnel are "Accidental parenteral inoculation, cuts, or sticks with contaminated laboratory equipment, bites by infected animals, and exposure of mucous membranes or broken skin to infectious tissue or fluids." (B418.V11-F.w1)
• The only two documented cases of laboratory-associated rabies infections in humans were both due to presumed exposure to infectious aerosols at high titre. (B418.V11-F.w1)

• Biosafety Level 2 in general. (B418.V11-F.w1)
  • "Additional primary containment and personnel precautions, such as those described for Biosafety Level 3, may be indicated for activities with a high potential for droplet or aerosol production, and for activities involving production quantities or concentrations of infectious materials." (B418.V11-F.w1)

Life Cycle and Transmission (General cycle of replication and mechanisms of moving between hosts and habitats)

The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box. Limited data on rabies virus in general is provided in the literature reports but is not intended to be comprehensive.

Sources of Virus

• The main source of rabies virus is in saliva. Rabies virus is shed by the infected host in large amounts in the saliva, but may be present only intermittently. It is notable that saliva may contain virus several days before the onset of clinical signs. Virus may also be found in other tissues, which may therefore also potentially act as a source of the virus.

Raccoon rabies

• Raccoons infected with rabies have high rabies virus titres in their saliva. The virus may be present in the saliva before the onset of clinical signs in the raccoon. Virus has also been isolated from the bladder, indicating a possible source in urine. Additionally, it is possible that there might be virus in the milk.

Mechanisms of Spread

• The normal mechanism of transmission between hosts is considered to be by direct animal to animal contact, by biting.
• Minor mechanisms of spread involve aerosol transmission, oral transmission, and possibly contamination of mucous membranes or wounds with infected urine or tissues.

Raccoon rabies

• No specific information.

Routes of Infection

• The usual route of infection is via a bite, inoculating saliva; an associated route is by saliva from an infected animal entering an existing fresh, open wound.
• Rare routes of infection include via scratches, mucosal membrane contamination, intranasal (from aerosol, seen only with bat rabies or in the laboratory), transplacental, ingestion (including ingestion of infected carcasses or tissues, or by suckling an infected dam), per rectum (demonstrated experimentally) and iatrogenic transmission (including transplants of cornea, solid organs or tissues), and potentially needlestick injuries.

Raccoon rabies

• It is assumed that the main route of transmission for raccoon rabies variant is biting. However, the possibility of transmission, at least occasionally, by other routes - mutual grooming leading to ingestion of saliva, contact with the urine of an infected raccoon, transplacental transmission and transmission via the milk from mother to cubs should also be considered.
  • Further discussion of the behavioural aspects of rabies transmission in raccoons is provided in Behavioual Aspects of Raccoon Rabies Transmission

Spread within the Vertebrate Host

• Initially, rabies virus replicates at the site of inoculation, for example in striated muscle cells, or it may enter nerves at the inoculation site directly. Once inside peripheral nerves, virions are transported passively by retrograde axoplasmic flow to the central nervous system. Infection via the nasal route leads to infection in the olfactory bulb prior to infection in other brain areas, but virus may also travel from the nasal mucosa to fibres of the trigeminal nerve and thence to the gasserian and superior cervical ganglia, and to the brain. Spread in the CNS is mainly by intra-axonal. Infection in the brain is widespread by the time of death. 
• Haematogenous spread is not significant in rabies infection although experimentally injection into the blood can cause infection.
• At the same time as spread in the CNS, virus spread by anterograde axonal flow towards the periphery into certain sites and organs including the retina, sensory nerve endings of the skin of the head in many species, pancreas, brown fat, myocardium, adrenal, and salivary gland. Virions bud into the secretory granules of the mucous cells of salivary glands and other secretory tissues.

Raccoon rabies

• Rabies virus has been detected in various tissues of rabid raccoons include brain, spinal cord, salivary glands, pancreas, adrenals, kidney, spleen and bladder.

Cell Infection and Virus Replication

• Virus replication occurs in the cytoplasm. Genomic RNA, which is of negative polarity, is transcribed into complementary positive sense molecules which can produce viral proteins. Five monocistronic mRNAs are produced, via a virus-encoded RNA-dependent RNA polymerase, and are then translated into the five major rhabdovirus proteins. For replication of the viral RNA, a full length positive sense genome is synthesised, which is then copied to amplify full length negative strand genomes which may be encapsulated into progeny virions.

Raccoon rabies

• No specific information.

• Rabies - Life Cycle and Transmission (Viral Reports) [For rabies virus in raccoons]

Chemical Toxicities / Disinfectants

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Physical Susceptibility (Inactivation)

• Heat;
• Ultraviolet light, including sunlight;
• Lipid solvents;
• Strong acids;
• Strong alkalis;
• Drying;
• Freeze-thaw cycles.

(B47, B209.1.w1, B336.76.w76, J15.23.w3)

Note: 

• The virus may remain infectious for months in a carcass which remains frozen (e.g. in the Arctic tundra). (B209.1.w1, J14.15.w2)
• In summer in a hot climate, the virus may be inactivated inside a carcass within hours. (B209.1.w1)

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Environments - External Habitats (Biogeographical / Climate Type)

• Rabies virus is adapted for replication within the neural tissue of mammals. It does not persist in the environment. (B209.1.w1)

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Distribution and Geographical Occurrence

Rabies virus general

Worldwide

• Rabies is found practically worldwide. A few areas, such as Australia, New Zealand and many Caribbean and Pacific Ocean islands, have never reported indigenous classical rabies virus infections, and classical rabies virus has been eliminated from some isolated areas such as the UK and Japan.

USA

• In the USA, different variants of rabies are found in different discrete geographical areas of the USA, associated with specific carnivore host species, including foxes, coyotes, raccoons and skunks. 
• Additionally, different strains of rabies genotype 1 viruses, hosted by various bat species in the US, are found across the continent.

UK

• The UK is “rabies free” and has been free of classical rabies (RABV, Lyssavirus genotype 1) since 1902. However the possibility of rabies entering the country should never be forgotten. Among wildlife species, rabies is most likely to be encountered in bats. European bat lyssa virus type 2 (EBLV-2) has been detected in bats in the UK and has caused one human fatality in the UK. 

Raccoon rabies/Rabies in Procyon lotor - Common Raccoon

USA General

Rabies was first reported in a raccoon in California in 1936. Rabid raccoons have been reported in other areas where raccoons are found, presumably due to infection with the local terrestrial, or occasionally bat, rabies variant. This has been confirmed where studies using monoclonal antibodies to distinguish between rabies strains have been carried out. Increased numbers of cases have occurred on occasion in association with outbreaks in other species. Rabid raccoons continue to be reported sporadically throughout the range of the raccoon within the USA, but the vast majority of cases occur in the raccoon rabies endemic area of the eastern US. 

Florida and the South-eastern States

Rabies in raccoons in Florida was first recorded in 1947. Initial reports of rabies in raccoons without reports in foxes in the same areas were considered to be possibly an ecological phenomenon; later the emergence of a raccoon rabies strain was recognised. For several years raccoon rabies was, for reasons not properly understood, confined to the Florida peninsula. Raccoon rabies then spread north, reaching Georgia by 1962, but westward spread into the Florida panhandle occurred only in 1970; the reason for this delay is unknown. Nor is it known why rabid raccoons were reported in the Georgia/South Carolina border area in 1971-72, but the disease appears to have spread in South Carolina only starting in 1977-1978, or why the raccoon rabies only started spreading in Alabama 1977-78. Raccoon rabies spread north to reach southern counties of North Carolina in 1992.

• 1947: Florida
• 1962: Georgia
• 1972/1977: South Carolina
• 1977: Alabama
• 1992: North Carolina (southern counties)

Several localised outbreaks of raccoon rabies have been recorded, including one in 1955-56 and several in 1967-1970, all along the coastal habitat of the Gulf Coast of Florida. Common features of these localized outbreaks in raccoons in Florida included:

• high density populations;
• areas of recent habitat destruction;
• food available from human sources.

North-eastern and Mid-Atlantic states

Raccoon rabies was first detected in contiguous counties of West Virginia and Virginia in 1977 and 1978 respectively. The disease then spread across northern Virginia and north and south into other states along the Atlantic seaboard as follows:

• 1977: West Virginia
• 1978: Virginia
• 1981: Maryland
• 1982: Pennsylvania; Washington, District of Columbia
• 1987: Delaware
• 1989: New Jersey
• 1990: New York
• 1991: Connecticut, North Carolina - northern counties (southern counties of North Carolina were first affected by spread northwards from South Carolina in 1992)
• 1992: New Hampshire, Massachusetts
• 1994: Rhode Island, Vermont, Maine
• 1996: Ohio (there was a single report in 1992 but no further cases reported until 1996)
• 2003: Tennessee

Speed of Spread of Raccoon Rabies

Where the speed of spread of raccoon rabies has been estimated, rates of about 15 to 50 miles per year (25 - 80 km per year) have been reported.

Raccoons infected with Other Rabies Strains in the USA

Rabid raccoons are and have been reported sporadically in areas of the USA affected by other rabies strains.

Rabies in Raccoons in Canada

As in the USA, rabies has been recorded in Canada as spillover from rabies in other species. In 1999 raccoon rabies variant was first detected in Ontario. A separate crossing of the St Lawrence river is thought to be responsible for raccoon rabies on Wolfe Island, Ontario, and another focus was first detected in September 2000 in New Brunswick.  Control measures appear to have been effective in New Brunswick: no raccoon rabies cases were detected during 2003, 2004 or to August 2005.

Rabies in Raccoons Outside North America

To date [November 2007] there are no reports of raccoon variant rabies in raccoons in countries outside North America.

Detailed information on the distribution and geographical occurrence of raccoon rabies variant has been provided in the literature reports linked below.

• Rabies virus - Distribution and Geographical Occurrence (Viral Reports) [For raccoon rabies variant]
• Maps - Spread of Raccoon Rabies in the USA (1977-2005)