RABIES IN CATS - · PDF fileRABIES IN CATS The following recommendations have been formulated...
Transcript of RABIES IN CATS - · PDF fileRABIES IN CATS The following recommendations have been formulated...
RABIES IN CATS
The following recommendations have been formulated by the
European Advisory Board on Cat Diseases.
The European Advisory Board on Cat Diseases is an independent panel of 17 veterinarians from ten European countries, with an expertise in immunology, vaccinology and/or feline medicine.
The ABCD was set up to compile guidelines for the prevention and management of major feline infectious disease in Europe based on current scientific knowledge and available vaccines.
This work would not have been possible without the financial support of Merial.
© June 2008 by the European Advisory Board on Cat Diseases. All rights reserved.
June 2008
Guidelines on Feline Infectious Diseases
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ABCD Guidelines on Feline Immunodeficiency Virus 1/22
ABCD GUIDELINES ON:
6. RABIES IN CATS..................................................................................3 6.1 Virus properties ..............................................................................................................................3 6.2 Epidemiology ..................................................................................................................................4
6.2.1 Rabies-free Countries ...............................................................................................................4 6.2.2 Developing Countries................................................................................................................4 6.2.3 Industrial Countries ...................................................................................................................5
6.3 Pathogenesis...................................................................................................................................5 6.4 Immunity ..........................................................................................................................................6
6.4.1 Passive immunity acquired via colostrum ...............................................................................6 6.4.2 Active immune response ..........................................................................................................7
6.5 Clinical signs...................................................................................................................................8 6.6 Diagnosis ...................................................................................................................................... 12
6.6.1 OIE recommendations ........................................................................................................... 12 6.6.2 Direct viral detection methods ............................................................................................... 12 6.6.3 Indirect detection methods .................................................................................................... 13
6.7 Rabies control in cats ................................................................................................................. 14 6.7.1 Treatment (post-exposure vaccination) ................................................................................ 14 6.7.2 Prophylaxis (preventive vaccination) .................................................................................... 14
6.8 Disease control in specific situations...................................................................................... 16 6.8.1 Shelters ................................................................................................................................... 16 6.8.2 Breeding catteries .................................................................................................................. 16 6.8.3 Vaccination of immunocompromised cats............................................................................ 16
6.9 References.................................................................................................................................... 18
The following recommendations have been formulated by the
European Advisory Board on Cat Diseases.
The European Advisory Board on Cat Diseases is an independent panel of 17 veterinarians from ten European countries, with an expertise in immunology, vaccinology and/or feline medicine.
The ABCD was set up to compile guidelines for the prevention and management of major feline infectious disease in Europe based on current scientific knowledge and available vaccines.
This work would not have been possible without the financial support of Merial.
© June 2008 by the European Advisory Board on Cat Diseases. All rights reserved.
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ABCD Guidelines on Feline Immunodeficiency Virus 2/22
ABCD Panel members Marian Horzinek Former Head, Dept of Infectious Diseases, div. Immunology & Virology, Faculty of Veterinary Medicine; Director, Graduate School Animal Health; Director, Institute of Veterinary Research; Utrecht, (NL). Founder President European Society of Feline Medicine. Research foci: feline coronaviruses, viral evolution. Diane Addie Director, Feline Institute Pyrenees, France. Honorary Senior Research Fellow, University of Glasgow Veterinary School, UK. Research foci: eradication of feline coronavirus (FIP); cure for / prevention of chronic gingivostomatitis. Interested in all feline infectious diseases. www.catvirus.com Sándor Bélak Full professor, Dept of Virology, Swedish University of Agricultural Sciences (SLU) & The National Veterinary Institute (SVA), Uppsala (S); OIE Expert for the diagnosis of viral diseases (Sweden). Research foci: biotechnology-based diagnosis, vaccine development, the genetic basis for viral pathogenesis, recombination and virus-host interaction. Corine Boucraut-Baralon Associate professor, Infectious Diseases, Toulouse Veterinary School; Head, Diagnostic Laboratory Scanelis, France. Research foci: poxviruses, feline calicivirus, feline coronavirus, and real-time PCR analysis. Herman Egberink Associate professor, Dept of Infectious Diseases and Immunology, Virology division, Faculty of Veterinary Medicine, Utrecht; Member of the national drug registration board, the Netherlands. Research foci: feline coronavirus (FIP) and FIV, vaccine development and efficacy, antivirals. Tadeusz Frymus Full professor, Head, Division of Infectious Diseases and Epidemiology, Dept of Clinical Sciences, Warsaw Veterinary Faculty, Poland. Research foci: vaccines, Feline leukaemia virus (FeLV), Feline immunodeficiency virus (FIV), Feline Coronavirus (FCoV/FIP) Bordetella bronchiseptica infection, and canine distemper. Tim Gruffydd-Jones Head, The Feline Centre, Professor in Feline Medicine, Bristol University, UK; founder member European Society of Feline Medicine. Research foci: feline infectious diseases, in particular coronavirus and Chlamydophila. Katrin Hartmann Head, Dept of Companion Animal Internal Medicine & full professor of Internal Medicine, Ludwig Maximilian University Munich, Germany; AAFP vaccination guidelines panel member. Research foci: infectious diseases of cats and dogs with special interest in diagnosis and treatment.
Margaret J. Hosie Institute of Comparative Medicine, Glasgow, UK. RCVS Specialist in Veterinary Pathology (Microbiology) Research focus: Feline immunodeficiency virus pathogenesis and vaccine development, feline calicivirus. Albert Lloret Clinician, Veterinary Teaching Hospital, Barcelona University, Spain. Research foci: feline medicine, molecular diagnostics of feline disease, feline injection site sarcomas. Hans Lutz Head, Clinical Laboratory, Faculty of Veterinary Medicine, University of Zurich, Switzerland. Research foci: feline retro- and coronaviruses (pathogenesis & vaccination), epidemiology and molecular diagnostics of feline infectious diseases. Fulvio Marsilio Dept of Comparative Biomedical Sciences, Div. Infectious Diseases, University of Teramo (I). Research foci: PCR as diagnostic tool for upper respiratory tract disease in cats, recombinant feline calicivirus vaccine. Maria Grazia Pennisi Professor, Clinical Veterinary Medicine. Head, Companion Animal Internal Medicine Clinic, Dept Veterinary Medical Sciences, University of Messina, (I). Research foci: clinical immunology, Bordetella bronchiseptica in cats, FIV. Alan Radford Senior Lecturer & Researcher, Dept Small Animal Studies, Liverpool Veterinary School, UK. Research foci: FCV and FHV-1 virulence genes, Bordetella bronchiseptica in cats, parvoviruses and coronaviruses, immune-response variation. Andy Sparkes Head, Feline Unit, Animal Health Trust; Chairman, Feline Advisory Bureau, UK; Editor, European Journal of Feline Medicine and Surgery; AAFP vaccination guidelines panel member. Research foci: feline infectious diseases, lower respiratory tract disease, oncology. Etienne Thiry Full professor, Head of Veterinary Virology, Dept Infectious Diseases and Virology, Liege Veterinary Faculty (B); Member, Committee of Veterinary Medicinal Products (B); Agencies for animal health and food safety (F, B). Research foci: herpesviruses, caliciviruses, emerging feline viruses, host-virus interactions. Uwe Truyen Head of the Institute for Animal Hygiene & Veterinary Public Health, University of Leipzig, Germany, Head of the German standing vaccination committee Vet. Research foci: Animal Hygiene, epidemiology, parvoviruses, feline calicivirus.
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ABCD guidelines on Rabies in cats 3/22
6. Rabies in cats
6.1 Virus properties
Rabies is the cause of one of the oldest and most feared diseases of humans and animals
- it was recognized in Egypt before 2300 BC and in ancient Greece, where it was well
described by Aristotle. Perhaps the most lethal of all infectious diseases, rabies also has
the distinction of having stimulated one of the great early discoveries in biomedical
science. In 1885, before the nature of viruses was comprehended, Louis Pasteur
developed, tested, and applied a rabies vaccine, thereby opening the modern era of
infectious disease prevention by vaccination.
Rabies virus is one of the Rhabdoviridae, which encompass over 175 viruses of
vertebrates, invertebrates and plants.
Based on virion properties and serologic relationships four genera containing animal
viruses have been recognized in the family Rhabdoviridae.
The rabies virus belongs to the genus Lyssavirus, together with the Mokola virus, Lagos
bat virus and Duvenhage virus from Africa and European bat viruses 1 and 2 and
Australian bat lyssavirus. Each of these viruses is considered capable of causing rabies-
like disease in animals and humans. All lyssaviruses use bats as reservoir hosts.
Rhabdovirus virions consist of an outer envelope with large peplomers and an inner,
helically coiled cylindrical nucleocapsid. The precise cylindrical form of the nucleocapsid
gives the viruses their distinctive bullet or conical shape. The genome is a single
molecule of linear, negative-sense, single-stranded RNA, 11 to 15 kb in size. The genome
encodes 5 genes in the order 3’-N-NS-M-G-L-5’. The viruses generally have 5 proteins.
The glycoprotein that makes up the peplomers contains neutralizing epitopes which are
targets of vaccine-induced immunity as well as epitopes involved in cell-mediated
immunity. Virions also contain lipids, their composition reflecting the composition of host
cell membranes, and carbohydrate side-chains on the glycoprotein. Rhabdoviruses may
be stable in the environment especially at alkaline pH but are thermolabile and sensitive
to the UV irradiation of sunlight. In clinical practice, rabies virus is easily inactivated by
detergent-based disinfectants.
Viral entry into host cells occurs via fusion of the viral envelope with the cell membrane;
all replication steps occur in the cytoplasm.
Virions are formed by the budding of nucleocapsids through cell membranes. Rabies virus
budding takes place mostly upon intracytoplasmic membranes of infected neurons, but
almost exclusively upon plasma membranes of salivary gland epithelial cells. The
replication of rabies viruses is slow and usually non-cytopathic because it does not shut
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ABCD guidelines on Rabies in cats 4/22
down host cell protein and nucleic acid synthesis. Rabies virus produces prominent
cytoplasmic inclusion bodies (Negri bodies) in infected cells.
Laboratory-adapted (“fixed”) rabies virus replicates well in Vero (African green monkey
kidney) cells and BHK-21 (baby hamster kidney) cells, which are the most common
substrates for growing animal rabies viruses for vaccine production. Rabies virus also
replicates to high titre in suckling mouse and suckling hamster brain.
6.2 Epidemiology
The disease occurs worldwide, with certain exceptions. Large regions in Europe became
free of terrestrial rabies as a result of wildlife vaccination programmes.
The rabies situation and the regulations are continuously updated on the web sites of OIE
and WHO (see reference section).
The number of human deaths caused each year by rabies is estimated to be
approximately 40, 000 to 100, 000, worldwide, and an estimated 10 million people
receive post-exposure treatments each year after being exposed to rabies suspect
animals [WHO, 2006]. Dog rabies is still very important in many parts of the world and is
the principal cause of human rabies cases. In many countries, wildlife rabies has become
of increasing importance as a threat to domestic animals and humans, and transmission
from vampire bats is an important issue. The red fox, raccoon, skunk and mink are the
main reservoir species of terrestrial rabies in Europe and North and South America.
The control of rabies in various regions of the world poses very different problems,
depending upon the reservoir host and prevalence of infection.
6.2.1 Rabies-free Countries Strictly enforced quarantine of dogs and cats for various periods before entry has been
used effectively to eliminate rabies virus from Japan, the United Kingdom (UK), Australia,
New Zealand and several other islands. Rabies was never endemic in wildlife in the UK
and was eradicated from dogs in the UK in 1902, and again in 1922 after it became
established in the dog population in 1918. Since then, there had been no rabies in the UK
until recently when there were isolated reports of bats infected with European bat virus
1. However, such isolated incidents did not alter the (terrestrial) rabies-free status of the
UK. In contrast, rabies was not recognized in Australia until recently when Australian bat
lyssavirus was discovered, and found subsequently to be endemic in Southeast Australia.
6.2.2 Developing Countries In most countries of Asia, Latin America and Africa, endemic dog rabies is a serious
problem, causing significant domestic animal and human mortality. In these countries,
large numbers of doses of human vaccines are used and there is a continuing need for
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ABCD guidelines on Rabies in cats 5/22
comprehensive, professionally organized and publicly supported rabies control agencies.
That such agencies are not in place in many developing countries is a reflection of their
high cost; nevertheless, progress is being made. For example, a substantial decrease in
rabies incidence has been reported in recent years in China, Thailand and Sri Lanka,
following implementation of dog vaccination programmes and improved post-exposure
prophylaxis of humans. Similarly, the number of rabies cases in Latin America is declining
significantly; the Pan American Health Organization has implemented a vaccination
program to eliminate urban dog rabies from the Southern hemisphere.
6.2.3 Industrial Countries In most industrial countries, even those with modest disease burden, publicly supported
rabies control agencies operate in the following areas: (1) programmes of oral
vaccination of wildlife, in Europe of the red fox; (2) stray dog and cat removal and
control of the movement of pets (quarantine is used in epidemic circumstances, but
rarely); (3) immunization of dogs and cats, so as to break the chain of virus
transmission; (4) laboratory diagnosis, to confirm clinical observations and obtain
accurate incidence data; (5) surveillance, to measure the effectiveness of all control
measures; and (6) public education programs to assure cooperation.
The cat is considered in some European countries to be high-risk species for transmission
to human beings. For example, of more than 20, 000 inhabitants in Switzerland that had
to be vaccinated after exposure to rabies in the years from the late 1960s until the early
1990s, around 70% had been either bitten or in close contact with cats [Hohl et al,
1978].
Even if feline rabies is considered to be a by-product of canine or wild rabies [Blancou &
Pastoret 1990], behavioural characteristics of cats and clinical aspects of the disease in
this species render it important for public health reasons. In fact, despite a lower number
of post-exposure prophylaxis treatment for people following cat bites compared to dog
bites, treatment is justified more often [Blancou & Pastoret 1990].
6.3 Pathogenesis
Rabid animals are the only source of virus. Virus is shed in the saliva some days before
the onset of clinical signs and virus is transmitted through a bite or a scratch of the skin
or mucous membranes (eyes, nose, mouth). The blood of rabid animals is not considered
infectious. The average incubation period in cats is two months but may vary from 2
weeks to several months or even years depending on the dose of virus transmitted and
the severity and site of the wound [Jackson 2002, Charlton et al, 1997].
The incubation period is variable because the virus moves along peripheral nerves with
the normal axoplasmic flow from the inoculation site to the central nervous system
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ABCD guidelines on Rabies in cats 6/22
(CNS): hence the greater the distance from the CNS, the longer the incubation period;
and the greater the density of innervation of the inoculated tissue the shorter this
duration [Greene and Rupprecht, 2006]. Very long incubation periods have been
described in some experimental cases [Murphy et al, 1980], and this must be taken into
account when evaluating wound history, especially in free-roaming cats exhibiting
sudden behavioural change and/or signs of motor neuron dysfunction that may initiate
the clinical phase.
The virus replicates in striated muscle and in connective tissue at the site of inoculation
and then enters the peripheral nerves through the neuromuscular junction [Murphy et al,
1973]. Alternatively, it can infect directly the peripheral nerves, spreading to the central
nervous system via the axonal route. The virus can then travel to the salivary glands by
the retrograde axonal route. At this time, the animal becomes infectious, i.e. about 3
days before the first clinical signs appear. By the time clinical signs appear, the virus is
widely disseminated throughout the organs. In most cases, death occurs within 5 days so
that a cat or a dog will be shedding the virus in saliva for about 8 days in total.
Most clinical signs are related to the virus-induced central and peripheral nervous system
dysfunction rather than neuronal death and abnormalities in neurotransmission have
been described [Jackson 2002]. Rabies glycoprotein probably plays an important role in
the trans-synaptic spread of the virus between neurons and in the topographic
distribution of virus infections through the nervous system [Etessami et al, 2000].
6.4 Immunity
6.4.1 Passive immunity acquired via colostrum
Kittens from vaccinated queens obtain maternal antibodies (MDA) via colostrum. The
MDA titre in kittens depends on both the antibody titre of the queen as well as the
amount of colostrum ingested during the first day of life. In most kittens, MDA will not
persist for longer than 12 weeks.
MDA have been demonstrated even in sera of fox cubs whelped by orally immunized
vixens [Vos et al, 2003].
Passive immunity may neutralize vaccine antigens, thereby inhibiting the immunoglobulin
production, interfering in the immunization process during the first weeks of life.
Therefore, it is generally recommended to perform the primary vaccination against rabies
in kittens not earlier than at 12 weeks of age.
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ABCD guidelines on Rabies in cats 7/22
6.4.2 Active immune response
Although rabies antigens are highly immunogenic and capable of eliciting the full
spectrum of protective immune responses, the virus is not highly cytopathic, since no cell
lysis occurs during replication or maturation. Therefore, little antigen is presented to the
immune system. Neither humoral nor cell-mediated specific responses can be detected
during the early stages of movement of virus from the site of the bite to the central
nervous system [Green 1997]. Hence, infection of naive animals with rabies virus most
often results in disease and death. Such sequelae may be averted by prompt
immunization following exposure, demonstrating that the development of anti-rabies
viral immunity prior to extensive infection of neurons is protective. It is well documented
that virus neutralizing antibody is a crucial factor in this immunity. Rabies is an example
of a “Th-2 healing disease” in which activation of B lymphocytes, with the help of CD4 T
cells, is important for protection [Garenne and Lafon 1998]. When activated, primarily by
the N protein of the rabies virus, CD4 T cells produce cytokines (i.e. IL-4) that stimulate
B cells to produce antibodies. In contrast, rabies-specific CD8 T cells cause neuronal
damage when a Th-1 response (IFN-γ and TNF-α) predominates [Lafon 2002, Hooper
2005]. However, published reports exist that describe vaccinated animals that had no
detectable virus neutralizing antibody and yet survived rabies challenge, indicating that
other mechanisms may also protect against this disease [Aubert 1992, Hooper et al,
1998].
After intramuscular infection, the virus replicates locally for several weeks in the
myocytes or nervous tissue. In vaccinated cats with adequate serum antibody titres, the
virus is often neutralized during this early incubation period. In contrast, unvaccinated
cats exposed to rabies virus can produce an antiviral immune response, usually late in
the clinical course, that fails to prevent disease [Johnson et al, 2006]. However,
protection against the early stages of infection is provided by non-specific immunity, in
which interferon seem to play a critical role. High levels of interferon are detectable in
sera of mice inoculated with rabies virus by peripheral or intracerebral routes [Marcovistz
et al, 1984, 1994; Johnson et al, 2006]. It is not clear how effective these mechanisms
are in naturally exposed naive cats. It is believed that factors, determining morbidity
include the amount and strain of the virus, the age and immunocompetence of the cat
and the bite, such that in unvaccinated cats the risk of developing rabies is higher (and
the incubation period shorter) in a young animal that has been bitten severely in the
head, with a high saliva deposit in the wound, compared to the risk for an adult cat,
bitten in a limb, especially after extensive bleeding [Pastoret et al, 2004].
In natural infections of unvaccinated animals, neutralizing antibody appears usually after
the virus has entered the central nervous system. Hence, once symptoms are evident,
recovery from rabies is exceedingly rare, although there have been reports of humans
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ABCD guidelines on Rabies in cats 8/22
and animals that have recovered following confirmed clinical rabies [Bernard 1985,
Fekadu 1991]. Furthermore, antibodies to lyssaviruses have been detected occasionally
in domestic or wild cats with no history of vaccination, consistent with a non-fatal disease
or subclinical infection [Tjørnehøj et al, 2004; Deem et al, 2004].
6.5 Clinical signs
Aggressive behaviour towards humans is
unusual in healthy cats, so any unjustified
aggressive behaviour in cats must be
considered highly suspicious.
Rabies should be suspected not only when
there has been a recent history of a bite
by or exposure to a rabid animal but also
where an unvaccinated cat may have
been in contact with potentially infected
wildlife, such as bats. Indeed, only
recently (November 2007), a cat in France
died of rabies as a result of infection with
bat lyssavirus. However, although rabid bats having been reported in the UK [Johnson et
al, 2003; Fooks 2003; Harris et al, 2007] and the Mammal Society estimates that British
cats could be killing 230, 000 bats a year [Fooks, personal communication], no cases of
cat rabies have been documented in the UK. These findings indicate that the risk of cats
becoming infected with rabies from bats may be low.
Two disease forms can be identified in cats: the furious and the paralytic one. The furious
form of rabies has three clinical phases (prodromal, furious or psychotic and paralytic or
dumb) but they are not always clearly distinct in cats. The other has only two phases:
prodromal and paralytic. During the very short prodromal phase (12-48 hours) of both
forms, a wide range of quite non-specific clinical signs (fever, anorexia, vomiting,
diarrhoea) may occur, sometimes accompanied by neurological signs. Marked
behavioural changes may be noticed at first, such as unusually friendly or shy or irritated
behaviour or increased vocalization. Altered behaviour depends on forebrain involvement
and may be associated with other neurological signs reflecting the inoculation site. If the
bite occurs in the face, clinical signs reflect cranial nerve and forebrain involvement: the
former may produce depressed or absent reflexes (palpebral, corneal, pupillary, etc.),
strabismus, dropped jaw, inability to move whiskers forward, dysphagia, laryngeal
paralysis, voice change, tongue paralysis. Forebrain involvement is responsible for
seizures, muscular twitching or tremors, aimless pacing, exaggerated emotional
responses (irritability, rage, fearfulness, photophobia, attacking inanimate objects, etc).
The tendency to bite may be the consequence of the loss of inhibitory control by cortical
A rabid cats with typical clinical signs of
encephalitis: Seizures, salivation, pupil
dilatation (Courtesy Dr Veera Tepsumethanon).
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ABCD guidelines on Rabies in cats 9/22
neurons over the subcortical bite reflex whereby dogs and cats turn and snap at anything
that touches them around the mouth [O’Brien and Axlund, 2005]. If this is the case, the
animal snaps without warning or showing any emotion when doing it. Pruritus at the bite
site can be observed. If the infecting bite was on the limbs, neurological signs start from
the spinal cord and an ascending lower motor neuron (LMN) paralysis occurs before the
brain signs. The encephalitis rapidly spreads throughout the CNS producing severe
ataxia, disorientation, paralysis, seizures, status epilepticus eventually followed by coma
and death from respiratory arrest.
The furious phase is more consistently developed in cats showing behaviour
abnormalities (described above) [Fogelman et al, 1993]. The paralytic phase
(paraparesis, incoordination, generalized paralysis, coma and death) usually begins after
five days of starting first clinical signs.
Isolated reports of survival after a confirmed clinical disease are available in cats, dogs
and humans [Bernard 1985, Fekadu 1991], but death usually occurs after a clinical
course of 1-10 days. Cats often die in 3-4 days [Rupprecht and Childs, 1996] and
according to a more recent report, 25% of deaths occur in cats within 4 days of clinical
course, while in dogs within 2 days only [Tepsumethanon et al, 2004].
Atypical forms with chronic course have been described after experimental infection in
cats [Murphy et al, 1980].
The severe public health risk (veterinarians included!) requires that differential diagnosis
of CNS diseases characterized by sudden onset and rapidly evolving clinical signs, always
includes rabies for free roaming, unvaccinated cats living in endemic areas or travelling
there. In this case, the clinical approach must make safety the priority because the
manipulation and restraint of the cat easily may provoke biting at the time when salivary
Box 1. Clinical signs of rabid cats infected by classical rabies virus (Genotype I) History and clinical signs by the owner: 1. Dramatic changes from normal behaviour. 2. Very aggressive, biting human and/or animal with no apparent reason. http://www.oie.int/eng/normes/mmanual/A_summary.htm General appearance and clinical signs at observation: 1. 90% of rabid cats show clinical signs of the furious form. 2. Thin (the cat cannot eat) 3. Ruffled and dirty coat. (the cat cannot clean itself) 4. Mucous membranes, tongue, nose and footpads are reddish pink, high fever. 5. The chin and front legs are wet from saliva (salivation). 6. Permanent movement and excitement (restlessness). 7. Imbalanced gait due to paresis of the hind legs. 8. Pupil dilatation unresponsive to light. 9. Abnormal water uptake (water runs back out of mouth). (Courtesy Dr Veera Tepsumethanon)
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ABCD guidelines on Rabies in cats 10/22
glands are usually already infected and rabies virus is shed in saliva. Guidelines
indicating that a clinical diagnosis of rabies should be included in the differential
diagnosis in live cats with suspected encephalitis based on history and observation of the
cat inside the carrier would help to reduce the risk of exposure for the veterinary team
(see the flow chart below that was adapted for cats from Tepsumethanon et al, 2003).
Vaccine-induced rabies in cats was observed in the past when modified-live vaccines
were available. Neurological signs occurred several weeks after vaccination and were
characterized mostly by progressive upper motor neuron (UMN) limb paralysis and
cranial nerve deficits.
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ABCD guidelines on Rabies in cats 11/22
Is the cat from or near to an endemic area, or traveling from there?
Does the cat have outdoor access?
Has the cat been vaccinated against rabies?
Is the cat less than 1 month of age?
Is the cat sick?
Does the cat show at least 1 of the following clinical signs?
• Behavioural changes • Cranial nerve deficits • Seizures • Muscular twitching or tremors • Aimless pacing • Tendency to bite • LMN paralysis • Severe sensorial ataxia • Depressed sensorium
RABIES POSSIBLE
NO
NO YES or unknown
NO or unknown
YES
NO or unknown
YES
YES or unknown NO
YES
NO
Has the onset been sudden (<1 day)?
The clinical signs have progressed (worsened) in the last 3-5 days?
NO or unknown
YES or unknown
yes
NO
RABIES UNLIKELY
YES or unknown
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ABCD guidelines on Rabies in cats 12/22
6.6 Diagnosis
Because clinical diagnosis of rabies is not reliable, a definitive diagnosis can only be
obtained by laboratory investigations post-mortem.
However, serological tests are used for surveys and post-vaccinal control in order to test
immunity level in vaccinated animals, especially in the context of international
movements.
6.6.1 OIE recommendations The recommendations from the experts of the OIE First International Conference “Rabies
in Europe” Kiev, Ukraine, 15-18 June 2005 are the following:
i) Routine laboratory diagnosis should be undertaken using only the techniques specified
by the OIE (Terrestrial Manual) and the WHO (Laboratory Techniques in Rabies).
ii) The FAT (Fluorescent antibody test) is the primary method recommended.
iii) The confirmation test should use rabbit tissue culture inoculation test (RTCIT). The
mouse inoculation test can be used only if rabbit tissue culture is not available.
iv) PCR is presently not recommended for routine diagnosis but may be useful for
epidemiological studies or for confirmatory diagnosis only in reference laboratories.
Reference laboratories: The list of reference experts and laboratories can be found on
the OIE web site (http://www.oie.int/eng/OIE/organisation/en_listeLR.htm).
6.6.2 Direct viral detection methods
Only direct detection methods are recommended to confirm rabies in human beings and
animals.
Samples (animal heads, brain tissues or other organs) should be sent according to the
national and international shipping regulations and care should be taken in order to avoid
potential human contamination. Because rabies virus is rapidly inactivated, the specimen
should be shipped (preferably) refrigerated or at room temperature in 50% glycerine in
phosphate buffered saline solution.
Brain tissue (especially thalamus, pons and medulla) is the preferred sample for post-
mortem diagnosis but other organs such as salivary glands can also be used.
6.6.2.1 Fluorescent antibody test Fluorescent antibody test (FAT) is the method recommended by WHO and OIE for fresh
or glycerol samples [Bourhy et al, 1989, Birgham & van der Merwe 2002], but is less
sensitive in formalin-fixed tissues. FAT provides a reliable diagnosis in 95% to 99% of
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ABCD guidelines on Rabies in cats 13/22
cases for all genotypes and in fresh samples. It can also be used for rabies detection in
cell cultures and in brain tissue of mice that have been inoculated for diagnosis.
6.6.2.2 Immunochemical methods Other methods available include immunochemical tests (e.g. avidin-biotin peroxydase
system, ELISA, direct blot enzyme immunoassay). The rapid rabies enzyme
immunodiagnosis (RREID) is an alternative to FAT but detects only one genotype.
Correlation between FAT and RREID is between 96 and 99% [Barrat 1993].
6.6.2.3 Inoculation to laboratory animals and cell cultures These tests are used to confirm inconclusive results with FAT in organs or when FAT is
negative if human exposure has been reported.
Intracerebral inoculation of mice is performed in newborn or 3 to 4 week-old mice. FAT is
used to detect virus 5 days to 11 days post-inoculation. Ideally, these inoculation tests
should be replaced by cell culture tests, which are as sensitive, less time-consuming and
more ethical. Neuroblastoma cell lines may be used and presence of the rabies virus is
revealed by FAT, with results being available within 2 to 4 days.
6.6.2.4 Histology – Immunochemistry Since histology and immunohistochemistry to detect Negri bodies are less sensitive
methods than FAT, especially in autolysed tissues, these methods are not recommended
for routine diagnosis.
6.6.2.5 Other direct methods Reference laboratories may identify rabies virus, and especially some variants, using
monoclonal antibodies, nucleic probes or PCR and sequencing. These techniques can
distinguish vaccine and field strains and may identify the geographic origin of the strain.
6.6.3 Indirect detection methods
6.6.3.1 Seroneutralisation Seroneutralisation tests in cell cultures, such as fluorescent antibody virus neutralisation
(FAVN) or rapid fluorescent focus inhibition test (RFFIT) are widely used.
The principle of FAVN is neutralisation in vitro of a rabies CVS strain before inoculating
BHK-21 C13 cells. The titre is expressed in IU/ml and is the reciprocal value of the
dilution at which 100% of the virus is neutralised in 50% of the wells. RFFIT and FAVN
give equivalent results. A titre of 0.5 IU/ml of serum antibodies is considered to be the
minimum titre to correlate with immune protection.
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ABCD guidelines on Rabies in cats 14/22
6.6.3.2 ELISA ELISA has recently been developed and is used for testing vaccinated animals.
Commercial kits are now available for the detection of antibodies in sera from vaccinated
cats and dogs. ELISA tests do not require the culture of live virus and the result can be
obtained within 4 hours. The sensitivity and specificity of ELISA tests still need to be
confirmed before it can be accepted as an official method [Servat et al, 2006].
For further details, refer to Barrat et al, [2006] and the OIE Manual of Diagnostic Tests
and Vaccines for Terrestrial Animals [OIE 2007].
6.7 Rabies control in cats
6.7.1 Treatment (post-exposure vaccination) The post-exposure management of cats depend on the national public health regulations,
but is forbidden in many countries. Usually, it is not authorised in case of clinical
suspicion. No supportive or specific treatment has proved to be effective in rabid cats, so
treatment is not recommended [Greene & Rupprecht, 2006].
6.7.2 Prophylaxis (preventive vaccination) Rabies in cats is usually controlled by traditional inactivated vaccines [OIE 2007] and at
present, several inactivated rabies vaccines are available commercially. These products
have been shown to induce protective immune responses following a single vaccination
[Fu 1997, Perez and Paolazzi 1997]. In cats and dogs, the peak of rabies neutralizing
antibodies is generally reached between 4 to 6 weeks after the first immunization
[Cliquet 2006]. Currently available inactivated vaccines are very efficient. Cats and dogs
with a neutralization titre above 0.5 IU/ml, regardless of the period of time elapsed since
vaccination have a very high probability of survival after a rabies infection [Cliquet,
2006]. Cats respond better to rabies vaccination than dogs and as much as 97.4% of
them develop a titre of 0.5 IU/ml or higher after the first vaccination, many even above 5
IU/ml [Cliquet, 2006]. A very small proportion of cats identified with rabies have had at
least one rabies vaccination during their lifetime [Greene et al, 2006]. Since the new EU
regulations in pet movement were put in place in 1993, no single case of vaccine failure
has been documented [Cliquet 2006]. Rabies vaccines are generally considered to be
safe, even in neonatal kittens.
Inactivated vaccines may carry a risk due to the remote possibility of incomplete
inactivation of the virus and the inadvertent spread of residual pathogenic particles of
rabies virus [Schneider, 1995]. Furthermore, inactivated rabies vaccines may be
associated with the development of injection site sarcomas in cats [Dubielzig et al,
1993].
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ABCD guidelines on Rabies in cats 15/22
Such problems led to continued efforts to develop safer rabies vaccines. New vaccines
include recombinant subunit proteins [Wunner et al, 1983], recombinant viral vectors
[Paoletti 1996, Xiang et al, 1996] and deoxyribonucleic acid (DNA) based vaccines
[Osorio et al, 1999, Cupillard et al, 2005]. Recombinant live vector vaccines have some
advantages over traditional vaccines: they are innocuous, they induce suitable humoral
immune responses and they do not require rabies virus to be handled [Paoletti 1996].
They also induce less inflammation at the site of injection [Day et al, 2007].
Fortunately, current vaccines are also cross-protective against a number of other
Lyssavirus genotypes. All cat and dog sera with a titre above 5 IU/ml neutralize EBL-1
and EBL-2 regardless of vaccine/virus strain and among sera with a titre between 0, 5
and 5 IU/ml 87% neutralize EBL-1 and 53% EBL-2 [Fooks, personal communication].
However, against some novel lyssaviruses isolated from bats in Eurasia the protection
may be reduced or negligible depending on the genetic distance between the new isolate
and traditional rabies viruses [Hanlon et al, 2005].
Because of the public health risk associated with susceptible domestic cats becoming
infected following exposure to rabid wild or domestic animals, rabies virus vaccines
should be considered as core vaccines in countries where rabies is endemic and should
be administered in accordance with local or state regulations.
In countries where rabies is not present, rabies vaccination may be considered optional,
to be recommended by the veterinarian if the cat should move to an endemic rabies
area.
6.7.2.1 Primary vaccination course In contrast to all other inactivated vaccines, a single rabies vaccination induces a long-
lasting immunity due to the immunogenic properties of the vaccinal antigen.
Kittens should be vaccinated at 12 to 16 weeks of age to avoid interference from
maternal antibodies, with revaccination one year later (depending on data sheet
recommendations for each brand of vaccine). With this schedule, a single vaccination is
sufficient. However, national or regional legislation regarding vaccination type and
interval should be adhered to.
6.7.2.2 Booster vaccinations Although some commercial vaccines provide protection against virulent rabies challenge
for 3 years or longer [Lakshmanan et al, 2006], national or local legislation may require
annual boosters.
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ABCD guidelines on Rabies in cats 16/22
6.8 Disease control in specific situations
6.8.1 Shelters
In endemic areas, stray cats should be always considered at exposure risk and handling
and nursing of rescued animals should be considered dangerous even if they are
asymptomatic.
6.8.2 Breeding catteries
Risk exposure is generally almost nil in breeding catteries because usually pedigree cats
are kept strictly indoors, but their vaccination is under local or state regulation.
6.8.3 Vaccination of immunocompromised cats
6.8.3.1 FIV-positive cats
FIV-positive cats should be kept confined indoors to avoid transmission to other cats, to
protect them from other infections and to slower the progression of FIV infection itself.
This is an efficient preventive measure for rabies in areas at risk, but national or regional
legislation should be adhered to. In outdoor cats with risk of exposure to rabies,
vaccination is strongly advised.
6.8.3.2 FeLV-positive cats
In vaccination studies it was demonstrated that FeLV-infected cats may not be able to
mount adequate immune response to some rabies vaccines [Franchini 1990]. FeLV-
infected cats should be confined strictly indoors to prevent spread to other cats in the
neighbourhood: if cats are allowed to go outside in area at risk for rabies, more frequent
vaccination may need to be considered (e.g. every 6 months).
6.8.3.3 Chronic disease
There is general agreement that cats with acute illness should not be vaccinated but cats
with chronic illness such as renal disease, diabetes mellitus or hyperthyroidism should be
vaccinated regularly if they are at risk of exposure.
6.8.3.4 Cats receiving corticosteroids or other immunosuppressive drugs
In cats receiving corticosteroids, every vaccination should be considered carefully.
Depending on dosage and duration of treatment, corticosteroids may cause functional
suppression of immune responses, particularly cell-mediated immune responses, but
studies exploring rabies vaccine efficacy in cats receiving corticosteroids are lacking. In
dogs, corticosteroids do not appear to result in ineffective immunizations if given for
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ABCD guidelines on Rabies in cats 17/22
short periods of time at low to moderate doses [Nara et al, 1979]. However, concurrent
use of corticosteroids at the time of vaccination should be avoided if practical.
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ABCD guidelines on Rabies in cats 18/22
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