1. RHABDOVIRIDAE E-mail Web site
PETER H. RUSSELL, BVSc, PhD, FRCPath, MRCVS
Department of Pathology and Infectious Diseases, The Royal Veterinary College,
Royal College Street,
London NW1 OTU.
Web site
This lecture is the part of THE VIROLOGY COURSE, (The aim of this foundation course is to link the structure, diagnosis and control of the different families of veterinary viruses in an up-to-date and well-paced manner). This lecture has been updated by Dr Janice Bridger.
COURSE OBJECTIVES - hyperlinks to course.htm
BOOK LIST - hyperlink to book.htm
USEFUL WEBSITES- hyperlink to websites.htm
INDEX OF ABBREVIATIONS - hyperlink to index.htm

2. LEARNING OBJECTIVES Students should be able to:
Describe rabies pathogenesis in mammals, including bats
Relate rabies epidemiology in different countries to the control measures used.
Name the four requirements in the rabies control strategy recently introduced as an alternative to quarantine in the UK.

3. FAMILY CHARACTERISTICS:
- Large, enveloped, bullet-shaped, RNA virions (~60 x 180nm) with short glycoprotein spikes.
- Moderately resisitant; survive well in dark places at low temperatures (burrows, caves, soil).
- Includes a wide range of pathogens infecting many species eg: Vesicular Stomatitis Virus (cannot be differentiated clinically from foot-and-mouth disease virus; insect transmission); Ephemeral Fever (infection of tropical cattle; insect transmission); Fish Rhabdoviruses (mortality often high where intensive fish farming practised).
(Rhabdo = rod )

4. DISEASE & PATHOGENESIS
RABIES
DISEASE & PATHOGENESIS
Notifiable; zoonotic; rare in UK but several cases have been veterinarians!
Usually fatal. Two main forms are seen:
Furious: Most common form in canidae, felidae and mustelidae: abnormal aggression, drool excessive saliva, attack without provocation. Territorial behaviour diminished resulting in disordered wandering. Inco-ordination, convulsions, coma and death follow within days.
Dumb or paralytic: Most common in ruminants and horses but does also occur in dogs: paralysis of the lower jaw and drooling saliva, tremors and progressive paralysis then coma and death. In cattle there is ruminal tympany, tenesmus, sometimes diarrhoea. In dogs, a change in voice may be noted in howling or bellowing.
Hydrophobia: Seen only in man

5. DISEASE & PATHOGENESIS
RABIES
DISEASE & PATHOGENESIS
Non-fatal infections are rare but skunks and foxes may recover; dogs can have mild symptoms, recover and remain as excretors. Recovered animals have antibodies. These infections are important in spreading the virus in the environment.
Bats are susceptible to infection, may be persistently viraemic and shed virus in saliva. They are the only species where rabies is always avirulent.
- Incubation period variable but can be long (10 days to 12 months; usually less than 3 months); increases with the distance of the bite from the CNS.
- Primary replication occurs in the muscle fibres at the site of inoculation then gains access to the nerve fibres where the virus travels towards the brain (centripetal migration) where it replicates followed by "centrifugal" migration down the cranial nerves replicating in the salivary gland and cornea.
- Virus excretion in saliva and tears. Virus may be shed before classical symptoms, that is, when there is fever, slight changes in temperament and dilation of pupils. Overt clinical signs develop after salivary excretion of virus.

6. ANTIGENICITY: only one type required in vaccine
RABIES
ANTIGENICITY: only one type required in vaccine
DIAGNOSIS
1) Isolate animals with suggestive clinical signs.
2) Handle with great care (ie use protective clothing to avoid contamination of skin wounds or by aerosol)
3) Remove brain and conduct tests on material stored in 50% glycerol:
(a) Immunofluorescence on smears/frozen sections of hippocampus or cerebellum will show diffuse intracytoplasmic fluorescence or focal fluorescence in Negri bodies (= rabies intracytoplasmic inclusion bodies which can be detected both in vivo and in vitro).
(b) Histological detection of Negri bodies using Mann's stain or silver stains.
(c) Intracerebral inoculation of mice with brain homogenate. Incubation period days. Immunofluorescence on CNS sections to confirm.

7. HOST RANGE: All mammals are susceptible including bats
RABIES
HOST RANGE: All mammals are susceptible including bats
EPIDEMIOLOGY
- Transmitted by bites through infected saliva (and by aerosols where high concentrations of virus eg in caves where there are high concentrations of bats).
- Found throughout the world but some countries free.
- Wildlife act as important reservoir hosts; the species involved varies with continent:
Europe - Fox, [badger, weasel, stoat ]
Russia and the Middle East - Wolf [dog]
U.S.A. - Fox, skunk [ wildcat]
Africa, India - Dog
S. America - Bat - vampire.

8. Virus-free countries:
RABIES
CONTROL:
The strategy depends on whether rabies is endemic or whether the country is free of virus.
Virus-free countries:
-- Six months quarantine of carnivores & ruminants (but cases have occurred after 6 months) in Norway, Sweden, Portugal, Australia and New Zealand.
-- In the UK, quarantine has been replaced by the Pet Travel Scheme (PETS) but only for travel between specified countries (at present specified Western European countries and some rabies-free islands). The schemes requires the following to be done in the UK:
- Identification of each animal by microchipping
- Vaccination against rabies
- Testing for an adequate antibody response 30 days later.
- Certification of the above
Also, before re-entering the UK, each animal must be treated for specified parasites & this must be certified.

9. CONTROL: Virus endemic countries:
RABIES
CONTROL:
Virus endemic countries:
Two approaches in Europe -
(1) vaccination of domestic animals with inactivated or live attenuated vaccines
(2)
a. control of the wildlife reservoir: population density of reservoir species reduced by gassing & shooting. It has been estimated that if the fox population was <1/4 sq.km. then virus does not spread.
b.Vaccination of wildlife. Has been effective in reducing the prevalence of rabies but as a consequence the fox population is increasing! Vaccines are either attenuated virus or a recombinant vaccinia vaccine. Fed in bait. A successful strategy in Europe.

10. RABIES CONTROL: In humans:
- Prophylactic vaccination is available for those at risk.
- In unvaccinated individuals with suspected rabies hyperimmune equine serum can be given at the site of entry as soon as possible. A programme of intradermal vaccination is followed.

11. Summary
Rabies targets the nervous system and brain causing a fatal infection; transmitted by biting as virus in saliva; zoonotic.
Rabies-free countries aim to keep rabies out by quarantine; countries with endemic rabies in wildlife control rabies by reducing wildlife numbers +/- vaccination of wildlife.
In the UK, the Pet Travel Scheme has been introduced to replace quarantine but for movements between specified countries only.