RABIES

SYNONYMS:
Hydrophobia, Lyssa, Mad dog,
Canine badness, Rage, Dropped jaw

Prepared by:
Aabhash Poudel
VMC-M-01-2015
 INTRODUCTION

• An acute, specific infection of the central nervous system of warm blooded

animals and man, characterized by deranged consciousness, marked
irritability, paralysis, and death

• Widespread, neglected and under-reported zoonosis with an almost 100%

case fatality rate in human and animal, and causing a significant social and
economic burden in many countries worldwide (WHO, 2010)
 HISTORY

1. Known in time of Aristotle and Virgil

2. Infectivity of saliva, rabbit transmission, and nerve

relationship was known during the pre-pasteur period of
1800-1880

3. Pasteur showed that continued rabbit passage and drying

weakened the agent and made a vaccine

4. Negri of Italy in 1903 described the inclusion bodies

 RABIES IN NEPAL
• Rabies is a disease of high priority in Nepal

• Prevalence of rabies has been reported throughout the year

• Rabies has been reported in cattle, buffalo, goat, dog and pigs at
44 districts, with 236 outbreaks and 401 animal deaths
(VEC, 2010-2014)
• Around 100 human deaths from rabies every year, mostly
following untreated dog bite
• Incidences of rabies have been reported in all sex and age group
of people
• 35, 000 people get post exposure vaccination every year
 ETIOLOGY

Lyssavirus of the Rhabdoviridae family

• Filterable neurotropic, BULLET SHAPED ss RNA virus

• Two types of virus
a. Street virus - that virus recovered from the usual case of furious
rabies.
b. Fixed virus - which results from the serial intracerebral passage
through rabbits, used for vaccine preparations and characterized
by:
(1)Incubation period shortened from 15-30 days to a limit of 6 to
7 days (exalted virulence).
(2) Paralysis and prostration (dumb type) replacing the vicious
and excitable symptoms (furious type).
(3) Loss of ability to produce Negri bodies
• Rapidly destroyed by light, ultra-violet rays, x-ray, acid,
radium, and many chemical disinfectants
• Iodine and hydrogen peroxide have little effect on virus

• Drying from the frozen state preserves it for long periods

• Resistance to ether and glycerine

• Can be presereved in 50% glycerol

• Survive in tissue culture @ 370 C for a week

 EPIDEMIOLOGY
Distribution
Generally world wide, except for some islands and a few countries that
maintain very rigid laws and quarantines on importing certain pets

Rabies-free Countries
Australia, Finland, Japan, Jamaica, Sweden and the United
Kingdom and several other islands
 TRANSMISSION

• The virus is typically transmitted by being deposited

under the skin, usually through a bite wound

• Contamination of a pre-existing wound is possible but

unlikely because the local inflammatory reaction which
follows a wound, quickly seals the comprised skin and
prevents entry of the virus

• Transmission across mucous membranes is also possible,

but less likely than a bite wound
 Aberrant Routes of Transmission

• A small number of human rabies cases have been reported

following corneal transplants.
– This suggests that human rabies cases may be
underreported.

• Aerosol (airborne) transmission of the virus has also been

reported. However, this is possible only under unusual
circumstances.
– Persons have contracted rabies presumably by airborne
transmission after visiting bat caves (Frio Cave, Texas.)
 Susceptible Animals
1. Warm blooded animals
and birds
2. Reservoir in vampire bats

Rabid Animals By Frequency

• Raccoons (US)
• Skunks (North America)
• Vampire-Bats (South America)
• Foxes (Europe)
• Rodents
• Lagomorphs
PATHOGENESIS
 Bite of the infected Animal

Local Replication of the virus in the epithelial cells or

myocytes

Virion cross NM Jxn ,move centripetally to CNS

Virus invades Ganglion cells & spreads centrifugally to

peripheral nerves
(Facial, Glossopharyngeal, Trigeminal, Olfactory)
Virus reaches Salivary glands, thymus, Lymph nodes,
Taste buds, olfactory cells…

Damages Brain stem and Medulla

Paralysis of muscle of deglutition Unable to

swallow

Paralysis of jaw muscle Dropped jaw

Paralysis of Respiratory muscle Asphyxia &

Death
CLINICAL FINDINGS
Incubation Period:
• Varies with site, severity of the wound and amount of
virus deposited at the site
• incubation period can be as short as two weeks or in
very rare cases as long as one year
*Bites on head and neck have shorter incubation time

Clinical manifestation in Dogs

Furious Form Dumb Form

I. Furious Form:
A. Prodromal stage/ Melancholic stage-

1. Vague changes in animal's temperament, Does not obey its

master
2. Bite inanimate objects, eat non-edible substances
3. Despite friendly actions, animal may be easily irritated,
especially if restrained. If picked up, it will immediately try
to break away and, if not promptly freed, will bite
savagely.
4. Animal becomes restless or unusually quiet.
5. Animal then may develop excitation.
The above period may lasts for 1-3 days
B. Maniacal stage/ Excitation State/ Irritative stage-

[Link] stage may be wholly absent or may be very obvious

2. Restlessness and excitement
3. Eyes glazed and constantly wide open, Photophobia
4. Often an altered voice - peculiar howl-(paralysis of vocal cord)
5. Usually wanders away from home during this stage - roaming
the countryside, and attacking any person or animal it
sees.
6. May lick genitalia, Bitch may show signs of heat and accepts
male
7. At the end, dog looses ability to bark, lower jaw will hang,
drooling of saliva, tongue will protude and head will
drop down; dog will develop dyspnoea, ascending paralysis,
coma and death.

Total episode may last as long as 10 days

II. Paralytic Form/Dumb Form

1. Paralysis of lower jaw, tongue, larynx and hind quarter

2. Bizzare mental behavior

3. Throat muscles paralysed - HOWLING voice

4. Unable to close mouth- Open mouth, Hanging Jaw

5. Incoordination

6. Recumbency

7. Death in 4-7 days

Cows
1. Restless and excitable
2. May attach objects - chase chickens, dogs and may run at man
3. Twitching of muscles
4. Hoarse bellow, seldom bites
5. Inability to eat - unable to swallow
6. Cease rumination - impaction with tympanies
7. Often show signs of sexual excitement even when pregnancy is well
advanced
Horses
1. Intense itching of bite wound
2. Often more vicious than cattle - may break halter
3. Bite manager, man, themselves, or anything in reach
4. Paralysis of throat followed by paralysis of legs, recumbency and death
5. Genital excitement
Sheep and Goat
1. About same as the cow
2. May charge caretaker or battle one another
3. Pulling of wool
4. Increased sexual desire - attempt to mount others
5. As a rule, unable to rise 1-4 days after appearance of symptoms
6. Death within 2 days after onset of locomotor paralysis
7. No opisthotonos

Swine
1. Irritation of bite wound
2. Salivation, root and jump excitably
3. Down in front and push with hind legs
4. General paralysis and death
 DIAGNOSIS
• Based on history and symptoms

• Laboratory examination of brain

Brain should not be destroyed by shot or blow
Skull is best container for transporting brain
Place head in watertight container which, in turn, should
be packed in a larger receptacle containing an equal
mixture of packing and ice.

• Recent studies - Corneal scrapings and skin

Demonstration of Rabies virus antigen in corneal
epithelium and saliva- only test can be done prior death
• Histopathology
-Formation of cytoplasmic inclusions:Negri bodies
(Ammon’s horn, Cerebral cortex, Brainstem,
Hypothalamus,Purkinje,Dorsal spinal ganglia)
-Stained with Seller's Stain (Carbolfuchoin and
methylene blue dissolved in methyl alcohol)

• Mouse inoculation test:

5% suspension of brain(hippocampus), salivary glands, saliva-
0.03ml inoculated intracerebrally

5-7 days

Mouse Sacrificed Presence of Negribodies

• Fluoroscent antibody test (FAT)
(Gold standard technique)
 Method recommended by WHO and
OIE for fresh or glycerol samples, but
is less sensitive in formalin-fixed
tissues. It provides a reliable
+ve samples have nearly round
diagnosis in 95% to 99% of cases particles of various size which
exhibit a bright yellow-green
fluorescence
Other tests:
• CFT
• PCR
• Immuno Peroxidase (IP) test
• Seroneutralisation
• ELISA
Differential diagnosis:
 PROGNOSIS

• Unfavorable

• An animal showing definite symptom dies

• No treatment for an active case is effective.

TREATMENT
- No specific treatment for clinical rabies
- Some chemotherapeutic agents like vinkristin,
scopolamide hydrobromide, Dihydroxypropyladenine have
given good response in experimental animals
- Site of bite should be washed with running water and soap
- Alkali (sodium bicarbonate/ caustic soda) prevents viral
multiplication
- Antirabies serum may be infiltrated around the wound

The post-exposure management of animal cases depends 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 dogs/cats, so treatment is not recommended.
(Greene & Rupprecht, 2006)
 PREVENTION & CONTROL
Vaccines
1. Inactivated Vaccine of Nervous tissue origin- Seldom used
2. Modified Live Vaccine (MLV)
3. Inactivated Cell Culture origin- Most popular

Oral vaccination
Unique concept : as stray or wild animals are out of physical
reach, dropping vaccine baits into their environment is the only
way to immunise them. Recommended by Veterinary Public
Health Department of WHO for both the target species (red fox,
raccoon dog, skunk, dog, etc.) and nontarget species, namely
wild rodents and any other wild and domestic species that
might be in contact with baits or a recently vaccinated animal
 IMMUNITY:
• Some vaccines protect against virulent rabies virus
challenge for 3 years or longer, but national or local
legislation may call for annual boosters.
• The presence of a serum antibody titre of ≥0.5 IU/ml in
an actively immunized dog over the age of 16 weeks is
correlated with protection.
• Achieving this titre (≥0.5 IU/ml) is also considered a legal
requirement for pet travel for some countries
 Pre-exposure Prophylaxis

Cell Culture Vaccine

 In general for cattle, sheep, horse:

Primary vaccination @ 3 month age
Booster annually

 Dogs and cats:

Primary vaccination @ 3 month age, Booster annually
Dose – 1 ml sub cutaneously

NeJaRab
 Multidose 5 % suspension of sheep brain

Weight of Pre - exposure Post- exposure

Animals
Less than 15 kg 2 ml for 7 days 2 ml for 14 days

15 - 100 kg 5 ml for 7 days 5 ml for 14 days

100 – 800 kg 15 ml for 7 days 15 ml for 14 days

> 800kg 30 ml for 7 days 30 ml for 14 days

 Post-exposure Prophylaxis

1. Includes immediate vaccination against rabies

2. A strict isolation period of 90 days
3. Administration of booster vaccinations during 3rd and 8th
week of isolation period

 This protocol has been effective in dogs, cats, cattle and horse
 RABIES – HUMAN INTERFACE

• Population at risk- Veterinarian, Cave explorers,

Lab workers, Animal handlers…
(Needs pre exposure prophylaxis)

• Although pre-exposure vaccination does not eliminate the

need for additional therapy after a rabies exposure, it
simplifies management by eliminating the need for rabies
immune globulin and decreasing the number of doses of
vaccine needed
• Once symptoms occur: fatal in 3-10 days
• Six patients have survived clinical rabies: 5 had pre or
postexposure prophylaxis before onset of symptoms
• Postexposure Prophylaxis/PEP: 3 steps

1. Wound care
2. Passive Immunization: Human rabies
immunoglobulin (HRIG) 20 IU/kg
3. Human diploid cell vaccine (HDCV): 1 ml (deltoid) on
days 0,3,7,14,28
 CONTROL MEASURES
• Strict quarantine

• Stray dog population control program- Animal Birth Control

• Proper carcass disposal

• Dog and cat immunization to break transmission

• Laboratory diagnosis of suspected clinical cases to obtain accurate surveillance data

• Surveillance to measure the effectiveness of control measures

• Public education to increase public awareness and cooperation- responsible pet

ownership
 REFERENCES
Blood, D.C. and V.P. Studdert. 1999. Saunders Comprehensive Veterinary Dictionary, 2nd edition.
Philadelphia, W.B. Saunders Co.

Canadian Boadcasing Corporation: Alberta has first human case of rabies in 2 decades. 2007.
[Link]

Canadian Food Inspection Agency – Animal Health – Positive Rabies in Canada.

[Link]

CDC : [Link]
[Link]

Coetzer, J.A.W. and Tustin, R.C. 2004. Infectious Diseases of Livestock. Cape Town: Oxford
University Press.

Compendium of Animal Rabies Prevention and Control, 2005 National Association of State Public
Health. [Link]
Greene, C.E. 2006. Infectious Diseases of the Dog and Cat. 3rd edition. Philadelphia, W.B. Saunders
Co.
OIE : Rabies. In Manual of Diagnostic Tests and Vaccines for Terrestrial Animals.
[Link]

Merck Veterinary Manual 9th ed: Rabies: Introduction. Retrieved March 22, 2006:
[Link]

Murphy, F.A., Gibbs, E.P.J., Horzineck, M.C. and Studdert, M.J. 1999. Veterinary Virology. 3rd Edition.
San Diego, California. London Academic

OSH Answers: Rabies. Retrieved March 29, 2007:

[Link]

Radostits, O.M., Gay, C.C., Blood D.C., Linchcliff, K.W. 2000. Veterinary Medicine: A Textbook of
Diseases of Cattle Sheep, Pigs, Goats and Horses. 9th edition. London: WB Saunders Corp. Ltd,

Smith, B. P. 2002. Large Animal Internal Medicine. 3rd edition. St. Louis: Mosby.

Smith, JS. Fishbein, DB. Rupprecht CE. Clark K. 1991. Unexplained rabies in three immigrants in the
United States. A virologic investigation. New England Journal of Medicine 324: 205-211

Tizard, R. I. 2000. Veterinary Immunology An Introdcution. 6th edition. Philadelphia, W.B. Saunders
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World Health Organization: Rabies. [Link]