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Virus / Rhabdoviridae / Type:

Rhabdoviridae: Rabies virus (with special reference to raccoon rabies variant and to the virus in European wildlife)

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INDEX - INFORMATION AVAILABLE

GENERAL & REFERENCES

VIRUS STRUCTURE & IDENTIFICATION

ASSOCIATED HOST SPECIES OF VIRUS AND HAZARD / RISK

VIRUS LIFE CYCLE, TRANSMISSION, PHYSICAL/CHEMICAL FACTORS & BIOGEOGRAPHICAL - CLIMATIC RANGE

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THE FOLLOWING INFORMATION IS HELD ON THE DISEASE INFORMATION PAGE
Rabies (with special reference to raccoons and to rabies in Europe)

  • Epidemiology, Disease Characteristics & Diagnosis
  • Treatment & Control

CLICK THIS LINK FOR Rabies (with special reference to raccoons and to rabies in Europe)

General and References

Virus Summary

Rabies virus is classified within the genus Lyssavirus of the family Rhabdoviridae. (B47, B352.2.w2)

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Alternative Names (Synonyms)

(Classification of virus types is an evolving discipline. The information in Wildpro has been carefully referenced to the source material, as far as possible. Readers requiring further clarification should consult the source materials and more recent publications. Classification information in Wildpro will be altered when clear and scientifically endorsed new information regarding taxonomic divisions becomes available to us.)

  • Classical rabies virus is also known as Lyssavirus serotype 1 or Lyssavirus genotype 1 (B336.76.w76)

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Associated Diseases

Rabies. (B47, B336.76.w76)
Linked Diseases

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TAXA Group (where information has been collated for an entire group on a modular basis)

Parent Group

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References

Species Author

Debra Bourne MA VetMB PhD MRCVS(V.w5)

Referee

Dr Robert G. McLean (V.w42); Dr Claude T Sabeta PhD (V.w167)

References

Detailed references are provided attached to specific sections.

ORGANISATIONS

ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Structure & Identification

Virus Morphology

Shape Rhabdoviridae (Virus Family): Bullet-shaped with one end rounded, the other flattened (B47, B81, B352.2.w2) or bacilliform. (B47)
Size Rhabdoviridae (Virus Family): 50-95nm diameter (B81), 60-95 nm diameter (B47), rabies virus average diameter 75 nm (B352.2.w2); 130-380 nm long (B81, B47); rabies virus 130-300 nm, mean 180 nm, due to differences in strains, also shorter particles may be defective interfering particles, usually with a truncated genome. (B352.2.w2)
  • Surface projections (peplomers) protruding through the unit-membrane envelope are about 5-10 nm long. (B81)
Envelope Rhabdoviridae (Virus Family): Enveloped. (B81

Rabies virus: Lipoprotein membrane or envelope is 7.5-10 nm thick with spike-like projections, with a knob-like distal extremity, 9 nm long at 5 nm intervals extending to the outside; these are not usually found on the planar end of the rabies particle. (B352.2.w2)

No. of particle polypeptides Rhabdoviridae (Virus Family): 5-6 (B81)

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Virus Genome

Nucleic acid type/No. of strands Rhabdoviridae (Virus Family): single-stranded RNA. (B81, B352.2.w2)

Rabies virus: single-stranded RNA. (B352.2.w2)

No. of Molecules / Strandedness
Molecular weight Rhabdoviridae (Virus Family): 3.5-4.5 x 106 (B81); Rabies virus 4.6 x 106 Daltons. (B352.2.w2)
Enzymes Rhabdoviridae (Virus Family): Associated with virion transcriptase. (B81)

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Viral Type Diversity (Sub-type/Subspecies)

Recognised Sub-types 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.

Rabies strains are highly related to one another (90 to 98% amino acid identity between strains). There are a variety of recognised wild strains and also "fixed" laboratory strains. The most variable protein is glycoprotein G, the major viral antigen. Variations develop because the viral polymerase lacks a proof-reading mechanism and fails to produce exact copies of the virus's genetic material.

(References are available in the detailed literature reports linked below)

In vitro differences (Laboratory test: differentiation) Strains of rabies virus may be distinguished by indirect fluorescent antibody testing using a panel of monoclonal antibodies (antigenic typing), or by nucleotide sequence analysis following extraction of RNA and amplification by RT-PCR. In antigenic typing, a panel of monoclonal antibodies against the nucleocapsid (N) protein has been used most commonly, although antibodies against the phosphoprotein or glycoprotein antigens have been used by some researchers. 
Raccoon rabies virus variant
  • Using a panel of monoclonal antibodies to nucleocapsid (N) proteins, raccoon rabies virus variant can be distinguished from other terrestrial variants (and bat rabies variants) in the USA. It has been shown that raccoon rabies virus variant from the mid-Atlantic raccoon rabies outbreak is the same as that of the southeastern raccoon rabies endemic area, and that rabies isolates from other terrestrial hosts within the raccoon rabies area are raccoon rabies virus variant. Differentiation between raccoon rabies virus variant and other rabies virus variants has also been demonstrated using a multiplex PCR protocol. Phylogenetic analysis has shown that raccoon rabies virus variant is well separated from other rabies virus variants. Further information, with references, is provided in the Literature Report - Rabies virus - Viral Type Diversity (Viral Reports)

(References are available in the detailed literature reports linked below)

In vivo differences (Affected animal: variation in infectivity and target Different strains of rabies virus are characteristic of different host species, vary in their infectivity and pathogenicity in a given host species, and may result in different clinical features in a given host species. A virus strain may be maintained within a host species due to adaptation of that strain to the particular host, as well as because contact between hosts occurs more commonly within the host species than between species. "Spillover" cases of rabies from the reservoir host into other species do not generally result in sustained transmission in the other species. The genetic changes in the rabies virus associated with adaptation to different hosts are not known. 
Europe
  • Previously dog rabies was important in Europe but this is now seen only in Turkey and in imported dogs.
  • Mainly fox-associated variants are found in Europe, with a specific variant of this associated with Nyctereutes procyonoides - Raccoon dog in north-eastern Europe. Phylogenetic analysis indicates dispersal of the virus from the north-east to the south-west of Europe, with changes in host preference from dog to fox in Eastern Europe and later from foxes to raccoon dogs in north-eastern Europe. There appear to be groups from Eastern Europe, Central Europe, Western Europe (two separate groups) and North-eastern Europe; the North-eastern Europe strains are fund in foxes and in raccoon dogs.
  • Additionally, European bat lyssaviruses (mainly EBLV1, EBLV2) occur, with very occasional spillover into other species.
Raccoon rabies virus variant
  • The raccoon rabies variant is adapted to raccoons (Procyon lotor - Common Raccoon), but spillover occurs into a wide variety of other species. In vivo differences have been documented for this rabies strain compared to other rabies strains in various species including raccoons (higher susceptibility of raccoons to raccoon rabies than to skunk rabies), skunks (shorter duration of clinical signs for skunks with raccoon rabies than with an Ontario skunk rabies strain) and squirrels (lower infective dose with the raccoon rabies strain than one bat rabies strain).

(References are available in the detailed literature reports linked below)

CLICK THE LINKS FOR Literature Reports 

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Virus Detection and Identification

Editorial Comment

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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.

Sample Collection and Shipping
  • For virus detection in dead animals, the whole body (for small animals), whole head, whole brain, or for large animals a complete cross section of the brainstem plus either cerebellum or hippocampus are collected In situations where opening the skull is not appropriate, samples can be taken via the occipital foramen or (after making a hole with a trochar) the retro-orbital route, using a 5 mm diameter drinking straw (or a "brain scoop"). In living individuals saliva, CSF, swabs from the throat, nasal mucosa or eye, eyeball impression smears and nuchal or facial skin biopsies may be tested. Samples are usually sent refrigerated and should reach the laboratory within 48 hours. Samples may be frozen but repeated freeze-thaw cycles must be avoided. 
  • For antibody detection, blood is usually collected for testing of serum. Serum is stored frozen until it is tested. CSF can also be tested.
  • In Procyon lotor - Common Raccoon:
Antibody Detection

The mouse neutralisation test, serum neutralisation tests in cell culture, such as the rapid fluorescence focus inhibition test (RFFIT), or ELISA can be used for detection of antibodies to rabies virus, indicating either prior exposure to the virus, or vaccination. Mouse neutralisation, RFFIT and ELISA generally provide concordant results, although there may be discrepancies with sera of low titre, close to the cut-off points of the tests. (J93.27.w1)

  • Mouse protection test
    • The mouse protection test was the first serological test developed for rabies antibody detection but is now outdated and should not be used. It involves mixing dilutions of serum and virus before inoculating the mixture into mice and noting whether or not the mice die from rabies.
      • This test is no longer recommended by the OIE or the WHO.
    • In Procyon lotor - Common Raccoon:
      • A study comparing antibodies in raccoon sera as detected by mouse inoculation and the RFFIT found that more sera were positive with the RFFIT than with the mouse protection test. Another study found that in general the mouse protection test and RFFIT test results correlated well with one another.
  • Fluorescent Antibody Virus Neutralization Test (FAVNT)
    • The fluorescent antibody virus neutralisation test can be used for detection of rabies antibodies in serum samples.
    • The FAVN is a prescribed test for international trade.
    • It gives comparable results to the rapid fluorescent focus inhibition test (RFFIT).
  • Indirect fluorescent antibody test (IFA)
    • The indirect fluorescent antibody test can be used for detection of rabies antibodies in serum samples.
    • In Procyon lotor - Common Raccoon:
      • An indirect fluorescent antibody test, has been used for detection of rabies virus antibodies in raccoons. 
  • RFFIT
    • The RFFIT (rapid fluorescent focus inhibition test) can be used for determination of rabies virus neutralizing antibodies. It uses a standard dose of rabies virus, to be neutralised by test serum prior to inoculation of susceptible cells. Unfortunately, non-specific cytotoxicity may affect the results of this test.
    • The RFFIT is a prescribed test for international trade.
    • In Procyon lotor - Common Raccoon:
      • The RFFIT has been used for detection of virus neutralizing antibodies in raccoons.
  • FIMT
    • The fluorescence inhibition microtest (FIMT) can be used for determination of rabies antibodies in sera of various species. Unfortunately, non-specific cytotoxicity may affect the results of this test.
    • In Procyon lotor - Common Raccoon:
      • The FIMT can be used for the determination of virus neutralizing antibodies in raccoons. However, cytotoxicity of raccoon sera may interfere with the results of this assay.
  • ELISA
    • ELISAs have been developed for the detection of antibodies to either whole rabies virus or the envelope glycoprotein (G) of rabies virus. An indirect ELISA, using anticanine immunoglobulin, has been shown to be useful for the measurement of rabies-specific antibody in sera of a variety of carnivores.
    • ELISA is a prescribed test for international trade (if a test kit is used which has been validated and adopted on the OIE register).
    • In Procyon lotor - Common Raccoon
      • Cross-reaction of the anticanine immunoglobulin in the indirect ELISA was demonstrated for raccoons. (J1.24.w6)
Antigen Detection

A variety of methods may be used to detect rabies virus or virus antigen.

  • Light microscopy/Detection of Negri bodies
    • Histological examination of brain sections or impression smears by light microscopy, in particular detection of characteristic Negri bodies, was the standard method of rabies diagnosis for many years. This has been replaced by the direct fluorescent antibody test, but is still used routinely in some developing countries. It has the advantages of requiring little equipment and giving a rapid result (within a couple of hours) but it is much less sensitive than immunological methods, particularly for partially autolysed samples. Additionally, false positive results may occur if nonspecific inclusion bodies are present. The OIE no longer recommends histopathology for the diagnosis of rabies.
  • Electron microscopy
    • Examination by electron microscopy can be used to detect viral inclusions (corresponding to Negri bodies) and virus particles. 
  • Antigen ELISA
    • Antigen-ELISA can be useful for large-scale epidemiological surveys, but must be properly validated first, including testing of the conjugates against locally predominating rabies virus variants.
  • Mouse inoculation test
    • For many years, mouse inoculation was considered the most sensitive way to detect rabies virus. However, it has now been superseded by modern methods for routine diagnosis. Several days are required for a diagnosis by this method. It is still used occasionally to confirm a test result, for example following human exposure to a suspect rabid animal which is negative by other tests. 
  • Virus isolation in cell culture
    • Cell culture is not commonly used for virus isolation but can be useful in cases where immunofluorescence is inconclusive. It can be used for testing saliva and cerebrospinal fluid samples from living individuals as well as for testing brain and salivary gland tissues post mortem. Murine blastoma cells are recommended for cultivation of street rabies strains. Immunofluorescence is used to detect virus antigen in the cultured calls. While a positive cell culture result in a sample from a living animal allows a definite diagnosis of rabies, a negative result in samples from a live animal is not conclusive. A plaque assay has been developed using chicken embryo cells.
  • Fluorescent Antibody Test (FAT)
    • The direct fluorescent antibody test (FAT) is presently the standard test for rabies virus detection. It is fast and reliable (sensitive and specific) for use on fresh or frozen tissue, and may be used on tissue which is degraded. It can be carried out on histological sections or on impression smears. In large animals, distribution of virus within the CNS may vary considerably and it is important to examine the cerebellum, brain stem and hippocampus using the FAT. Recently, a procedure has been developed allowing the use of FAT on formalin-fixed tissues.
  • Immunoperoxidase
    • An immunoperoxidase method, using the streptavidin-biotin complex and polyclonal or monoclonal antibodies may be used for detection of rabies in formalin fixed paraffin embedded tissue sections.
    • Raccoon rabies variant:
      • The monoclonal antibody (mAb) 802-2 was shown in a study to detect rabies antigen in paraffin embedded tissue sections from rabid raccoons.
  • Direct rapid immunohistochemical Test (dRIT)
    • This test can be used on brain touch impressions and the reaction product is visible under an ordinary light microscope (magenta inclusions, while the neuronal background is blue). The test allows diagnosis within one hour. It can be used on frozen samples or samples preserved in glycerol, and has a sensitivity similar to that of the direct fluorescent antibody test.
  • RT-PCR
    • RT-PCR to detect lyssavirus nucleic acid is not used in routine rabies diagnosis but is useful for confirmation of IFA test results in formalin-fixed or decomposed material unsuitable for virus isolation, and has been used in antemortem diagnosis. This method may be used on samples of brain tissue, saliva or CSF, and may allow detection of very small amounts of viral material, in tissues which are fresh, degraded or fixed.
  • NASBA
    • NASBA is able to detect very small amounts of rabies virus RNA and has been used to test the saliva and CSF in humans with clinical illness.

(References are available in the detailed literature reports below)

CLICK THE LINKS FOR Literature Reports
  •  --
Types of Techniques recorded as useful for viral identification
ANTIBODY DETECTION
  • Mouse Protection Test
  • Indirect fluorescent antibody test
  • Rapid fluorescent focus inhibition test (RFFIT)
  • Fluorescence inhibition microtest (FIMT
  • Enzyme-linked Immunosorbent Assay (ELISA)
ANTIGEN DETECTION
  • Light Microscopy/Detection of Negri Bodies
  • Mouse inoculation tst
  • Cell Culture and Plaque assay
  • Fluorescent Antibody Test (FAT)
  • Immunoperoxidase
  • Direct rapid immunohistochemical Test (dRIT)
  • Reverse Transcriptase - Polymerase Chain Reaction (RT-PCR)
  • Nucleic Acid Sequence-Based Amplification (NASBA)

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Associated Host Species and Hazard / Risk

Definitive Host Species (Agent undergoes final stage of replication for transmission)

Editorial Summary for Degree of Infectivity for other Species 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.
Mammals

All mammals may be hosts for rabies virus, although a variety of small- to medium-sized carnivores, and some bats, are the main reservoir hosts of classical rabies virus strains.

Raccoon rabies virus variant

Raccoon rabies virus variant has been detected in a variety of other species. Although some of these cases may represent transmission from one non-raccoon to another non-raccoon, the fact that raccoon rabies virus variant is involved indicates that the rabies was initially transmitted from a raccoon. 

  • The species (other than raccoons) in which raccoon rabies in which raccoon rabies virus variant is found most often are skunks (Mustelidae - Weasels (Family)). 
  • Raccoon rabies has been detected in rodents and lagomorphs, most commonly the woodchuck (Marmota monax - Woodchuck). Nearly all cases of rabies in woodchucks occur within the raccoon rabies endemic area and few cases occur in the skunk-endemic area, which may indicate that these cases are due to transmission from raccoons rather than via skunks. However, there may also be other non-biological reasons (e.g. which species are reported and tested, and human population density which affects likelihood of individuals being reported) why rabies in woodchucks is not reported from skunk-rabies endemic areas. 
  • Among domestic animals, raccoon rabies is commonly detected in cats and cattle. Most cases of rabies in cats in the US occur within the raccoon rabies area and most cases in cattle occur in the raccoon and skunk rabies areas. 
  • Raccoon rabies has also been confirmed in a number of the cases of rabies in miscellaneous carnivorous mammals, not considered as major rabies hosts, within the raccoon rabies areas. 
  • In 2003, the first case of fatal raccoon rabies in a human was confirmed.
  • Strain typing using monoclonal antibodies to epitopes on the rabies virus N protein has confirmed that isolates from other species within the raccoon rabies areas are identical with raccoon rabies virus variant. 

Detailed information on host species of raccoon rabies variant has been provided in the literature reports linked below.

(References are available in the detailed literature reports below)

Birds
  • Birds can be infected with rabies. (B102.29.w2, B416.44.w44, J1.12.w8, J1.12.w9, J1.24.w7)
    • A variety of birds have been infected with rabies experimentally, sometimes with development of nervous signs, often without development of clinical signs, or with recovery from clinical signs. However, "very little definite proof of the occurrence of spontaneous rabies in fowl can be found in published reports." There is a report of a patient injured by a rabid hen. (B102.29.w2)
    • Transmission to the domestic chicken by a naturalistic route (having a rabid dog bite the chicken on its comb) has been carried out successfully. (B102.29.w2)
    • Rabies has been reported occasionally in birds, including domestic chickens. (B416.44.w44)
    • In one study, low levels of antibodies to rabies virus were detected by the passive haemagglutination test in birds of prey (both owls and diurnal raptors) and some other species (starlings, crows and ravens). (J1.12.w9)
  • A Bubo virginianus - Great horned owl was successfully infected with rabies by feeding it with the head and then the rest of the carcass of an experimentally-infected spotted skunk (Spilogale putorius) (Mustelidae - Weasels (Family)). (J1.12.w8)

[Literature reports have not been provided for birds as definitive hosts because there is no information available specifically for raccoon rabies virus variant]

In Waterfowl:

  • Reported in ducks and geese. (B12.55.w1, B13.32.w3, B16.19.w1)
CLICK THE LINKS FOR Literature Reports of Species Infected
ORDERS recorded overall as containing Definitive Host Species (incl. Experimental, captive and free-ranging) (Not including infection unconfirmed by Laboratory diagnosis)
MAMMALS BIRDS

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Intermediate Host and Vector Species (Agent uses an intermediate species for development and/or specific indirect transmission)

Editorial Summary for Degree of Infectivity for other Species
  • Arthropods do not play any role in rabies transmission. (J63.5.w1)
  • [Note: The term "vector" or "vector species" is sometimes used to describe vertebrate host species which are important in the epidemiology of rabies, i.e. major species transmitting the virus. The term "reservoir species" is also used to indicate the host species in which rabies is maintained. (B209.1.w1, J64.7.w4)]
CLICK THE LINKS FOR Literature Reports of Species Infected
  • --
Species ORDERS Reported (Not including infection unconfirmed by Laboratory diagnosis)
--

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

Editorial Summary for Degree of Infectivity for other Species Not applicable. 
CLICK THE LINKS FOR Literature Reports of Species Infected
  • --
Species ORDERS Reported (Not including infection unconfirmed by Laboratory diagnosis)
  • --

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Degree of Hazard (Risk to Humans / other Species)

Rabies is an important zoonosis
  • 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)
  • 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)
Biological Containment Level - USA
  • 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)

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Virus Life Cycle, Transmission, Physical/Chemical Factors and Biogeographical - Climatic Range

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

Editorial Comment

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.
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.
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Editorial Overviews Available

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Chemical ToxicitiesDisinfectants

Editorial Comment Rabies virus is destroyed by most detergents and many disinfectants, including ether, formalin and quaternary ammonium compounds (B47, B209.1.w1, B336.76.w76, B352.2.w2, J15.23.w3)
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Physical Susceptibility (Inactivation)

Editorial Comment Rabies virus is readily inactivated by:
  • 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)

Editorial Overview
  • 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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Habitat Biomes where virus appears to be able replicate and transfer between species sufficiently well to become permanently established in Biome (Become Endemic)
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Distribution and Geographical Occurrence

Editorial Overview 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.
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.
Europe
  • Much of Europe has become "rabies free" over the past few decades, following prolonged campaigns to vaccinate the main host, free-ranging foxes.
  • Rabies remains endemic in several countries in southeast Europe, including Bulgaria, Bosnia & Herzegovina and Turkey, with foxes as the main reservoir in Romania; in Bulgaria, it is brought to livestock and humans mainly by dogs. In Turkey, dog rabies is still a problem, although the disease is also in foxes, while in Croatia it is mainly in wildlife but sporadic in domestic animals.
  • 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. 
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.

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.

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General Regions with literature reports of virus in last three years (not including experimental)

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Authors & Referees

Author Debra Bourne MA VetMB PhD MRCVS (V.w5)
Referee Suzanne I. Boardman (V.w6);  Dr Robert G. McLean (V.w42); Dr Claude T Sabeta PhD (V.w167)

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