Rabies

Hydrophobia, Lyssa, Rage

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 RABIES
Rabies is an acute viral encephalomyelitis
infection in man and warm blooded animal.

Characterized by signs of abnormal behaviour,

nervous disturbances such as increased
excitability and irritability, impairment of
consciousness, ascending paralysis and death.

It is a highly fatal disease, mortality rate being

close to 100%.
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• New Zealand and Australia never had the
disease.
• Britain, Hawaii, Japan and Scandinavia are
currently free of the disease.
• It is also known as Hydrophobia, Lyssa and
Rage.

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 ETIOLOGY
• Rabies virus is a bullet shape, RNA genome,
neurotropic Lyssa virus serotype1 of the family
Rhabdoviridae.

• The antigenic structure of rabies virus has remained

stable
• It is one of the larger viruses (180 nm long and 80
nm wide), and is relatively highly fragile.
• It is susceptible to most disinfectants, and dies in
dried saliva in a few hours.
• Street viruses refer to those strains isolated from
naturally infected cases.
• Fixed strains are those that have been adapted to
secondary hosts for experimental use in
laboratory.
• Flury strain refers to strains isolated from the brain
of a human patient and it is the base strain from
which most modern vaccines are derived

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 Host range
Any mammal can get rabies.
Humans,
Dogs,
Cats,
Horse,
Pigs,
Ruminants (Cattle, Buffalo, Sheep and goat),
Foxes, Skunks, Wovles, Coyotes, Vampire,
insectivorous and frugivorous Bats, Mongoose,
Squirrels and Raccoons

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• The disease is endemic in wildlife, particularly
foxes, skunks, raccoons, and bats and become
source of infection

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Raccoons
Bats
Cats - especially stray and
unvaccinated
Dogs - especially stray &
unvaccinated
 Incubation period
• Incubation period of 1 week to 1 year
– Virulence of the strain
– Quantity of infectious virus in saliva
– Susceptibility of the species
– Anatomical distance between bite site and CNS
– Severity of the bite

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 Methods of Transmission

• By biting of infected animal

• By Inhalation
• By ingestion
• In rare cases, corneal transplant or transplant of other
tissues, or through contact of infected saliva with mucosal
membranes or an open wound in the absence of a bite.
• Saliva is rich in virus.
• Contamination of skin wounds by fresh saliva
• Aerosol transmission to man in the laboratory (breathing
the air in a cave where thousands of bats were living)
 Pathogenesis
• After entry virus first replicates in the muscle cells
• Virus enters into nervous system at motor end plates
• Binds to receptors for acetylcholine (Ach)
• Virus spreads within nerve cells @ 3-4 mm/hour
• Virus multiplication occurs first in the spinal cord and
brain

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 PATHOGENESIS
Multiplication locally Neuromuscular Spindle
(Striated Muscle Fibres) Site of entry in nervous tissue
BITE
Olfactory organ is in direct
contact to neuroepithelial cell
Peripheral nerves
Passive movement within axon

Destruction of spinal neurons results in paralysis but when

virus invades brain irritation of higher centers produces Dorsal root ganglia
mania, excitation and convulsions occur

Spinal cord

The virus is neurotropic and there is no Brain

viremia in rabies.

Salivary glands
Virus transmission from bite to CNS
• The only lesions produced are in the central
nervous system
• Brain stem, cerebral cortex, and hippocampus
are susceptible to rabies infection
• Destruction of neurons in these regions gives rise
to clinical symptoms of rabies.
• When irritation phenomena (induced by the virus
in the nerve cells) occur it leads to “ furious
form”
• When destruction of spinal neurons results occur,
then it leads to "paralytic (dumb) form" of the
disease
• Death is usually due to respiratory paralysis
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• Centrifugal spread: via nerves throughout the
body to other tissues, including the salivary
glands, cornea, and tonsils
• Viral replication in salivary gland occurs
rapidly and infected saliva is the major source
of infection.
• The IP in naturally occurring cases in about 3
weeks, but varies from 2 weeks to several months
in most species.
• In any animal, the first sign is a change in
behavior.
• Animals usually stop eating and drinking
• The disease progresses rapidly after the onset of
paralysis
• Death is virtually certain within 10 days of the
first signs.
– 1) “Dumb or paralytic form'"
– 2) “Furious form".
 Dumb or paralytic form
• The animal falls into a stupor (unconsciousness) and has a peculiar
staring expression
• Paralysis of the throat and muscles of mastication
• Profuse salivation and inability to swallow
• Dropping of the lower jaw is common in dogs
• In this form, there is paralysis of the lower jaw result in hanging so
unable to close mouth,
• Dog are not capable to bite but their saliva remain infective
• Paralysis of tongue result to protruding
• Paralysis of larynx and throat muscle caused to change in voice
known as howl.
• In the terminal stages, there is progressive weakness and paralysis
starting from hindquarters which progresses rapidly to all parts of
the body, and coma and death follow in a few hours
 Furious form
• The animal becomes irrational and viciously aggressive.
• This form is the classical "mad-dog syndrome".
• The animal goes into rages (violent anger),
• Biting and slashing at any moving Object or even inanimate
objects, such as sticks and trees.
• The furious champing of the jaws(i.e., chewing noisely) is
accompanied by excessive salivation.
• The saliva flows from the mouth or is churned into foam, which
may adhere to the lips and face.
• Wild animals (which normally avoid humans) go into the open and
attack humans.
• As the disease progresses, muscular incoordination and seizures
become common.
• Death occurs within 10 days of the first symptoms.
• Cattle-
• Animals with the furious form are dangerous,
attacking and pursuing man and other animals.
• Lactation stops abruptly in dairy cattle.
• Characteristic bellowing (making a deep loud
cry).
• Horses and mules- show extreme agitation
evidenced by rolling as with colic.
• They may bite or strike viciously, and because of
size and strength, become unmanageable in a
few hours.
 CLINICAL FINDINGS
SHEEP
• Vigorous wool pulling, sudden falling after
violent exertion, muscle tremor and salivation
are characteristic.
• Most of sheep are silent and anorectic
• Goats are commonly aggressive and
continuous bleating is common
 Macroscopic features
• No gross lesions except non food items present in
the stomach of dog
• In other animals, lesions of bite on skin must be
present

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 Microscopic features

• Mainly confined to CNS

• Changes are particularly prominent in the
brain stem, hippocampus and the gasserian
ganglia.
• Necrosis of neurons, neuronophagic nodules
• The main lesion consists of the collections of
proliferating glial cells encroaching on the
neurons and replacing them. These
collections of proliferating glial cells are
known as "Babes' nodules".
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• Perivascular cuffing with lymphocytes in brain
particularly hippocampus
• Intra cytoplasmic eosinophilic inclusions ‘Negri
bodies’
• In the dog, they are found mostly in the
hippocampus, but in cattle they are more
numerous in the Purkinje cells of the cerebellum
• Negri bodies are not always present in rabies
• In fixed tissue, H and E, Mann’s stain as well as
Schleifstein modification of Wilhite stain
• In impression smears, Seller's stain is effective

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NEGRI BODIES
BABES NODULES CONSISTING OF GLIAL CELLS
(LYMPHOCYTIC FOCI )
PERIVASCULAR CUFFING OF LYMPHOCYTES OR
POLYMORPHONUCLEAR CELLS OR
INFLAMMATION AROUND A BLOOD VESSEL
Histopathology of rabies, brain. Characteristic Negri bodies are
present within a Purkinje cell of the cerebellum in this patient
who died of rabies
A neuron from a formalin-fixed section of a brain from a patient with rabies, showing
reddish-brown viral inclusions in the cytoplasm. Processed by immunohistochemistry.
Rupprecht CE, The Lancet Infectious Diseases Vol 2 June 2002
Neuron without Negri bodies
 Specimens required for diagnosis
• Brain samples (hippocampus- Dog, Cerebellum –
cattle)
• Either in a solution of 50% glycerol in phosphate
buffered saline (BPS) which allows to perform Direct
Fluorescence Antibody test, Immunohistochemistry,
histology or isolation.
• or in formalin(10%) but then the virus is inactivated
and isolation is no longer possible.
• Preferably Zenker’s fluid is used followed by
preservation in ethyl alcohol for demonstration of
negri bodies.
 Diagnosis
• History of bite
• Symptoms and lesions
• Serological tests include Virus Neutralization, Rapid
Fluorescent Focus Inhibition Test (RFFIT) and ELISA.
• Immunodiagnostic tests
– ELISA
– FAT (Gold standard for rabies)
– Peroxidase-anti peroxidase staining technique
– IFT
• Isolation of virus
• Histopathology
• Mouse inoculation test
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Viral inclusions in the cytoplasm of neurons

Negri bodies
 Differential diagnosis
• Canine distemper and infectious canine hepatitis,
• Aujeszky's disease
• Borna disease,
• Equine viral encephalomyelitis
• Equine encephalosis
• Bacterial and mycotic diseases of the central nervous
system including listeriosis and
cryptococcosis.