RABIES

It is highly fatal viral disease affecting the

central nervous system of all warm-blooded
animals including human.
Cause
•The disease is caused by an enveloped
neurotropic RNA Lyssa virus a member of
Rhabdoviridae.
•There are two strain of virus; street strain
and fixed strain.
 General Discussion
•Rabies virus is a lyssavirus in the family
Rhabdoviridae that causes a lethal nonsuppurative
encephalomyelitis and ganglionitis of mammals.
•Viral tropism for the neural and salivary tissues;
zoonotic
•Reservoir hosts include foxes, skunks, raccoons
and bats.
 Pathogenesis

Rabies pathogenesis. bite wound (1), replicates in muscle (2),

enters neuromuscular junction (3), ascends (retrograde
axonal transport) the peripheral nerve (4), dorsal root
ganglion (5); the spinal cord (6); brain (7), salivary glands (8)
 Pathogenesis
Transmitted through infected saliva in a bite
wound; occasionally by aerosol
Inoculation of virus into a wound > viral
glycoprotein binds to the acetylcholine receptor site
at the neuromuscular junction > primary viral
replication in myocytes > virus enters sensory axon
terminal > moves centripetally by retrograde
axoplasmic flow in the motor neuron to the spinal
cord ventral horn or to brain stem nuclei
 Pathogenesis
virus enters the central nervous system >
multiplies in neurons > virus migrates via
peripheral nerves to the salivary gland > virus
replicates in salivary acinar epithelial cells and is
released directly into ducts.
Virus often concentrates in the limbic system,
thereby causing the behavior abnormalities that
favor its spread to other hosts.

Virus causes minimal immunologic response.

 Clinical Findings
Incubation period varies with anatomic
location of inoculation, virus strain, quantity
of virus, host age, and host immune status
Furious form: Aggressive, destructive,
ataxia, hypersalivation
Dumb form: Stuporous, lethargic,
paralysis, abnormal vocalization
 Clinical Findings
Cattle and sheep
Animals may attack other animals, bit
themselves, bellow besides tenasmus and
paralysis of the anus, knuckling of hind
quarters and terminate with paralysis.

Horse:

The rabid animal usually express signs of

colic besides mania and eating its muscle.
 Clinical Findings

Dog and cat

A- Furious form:
rages, highly excitable, biting and slashing
at any moving objects even inanimate
object and run aimlessly with dribbling of
saliva. The eyes appeared red beside lose
of corneal reflex.
 Clinical Findings
B- Dumb form
Stupor, does not obey orders, rarely bites
and not recognize its owner. The lower jaw
showed paralysis besides dribbling of saliva.
Death occurs in 3 to 4 days after onset of
signs and usually within 10 days.
paralysis usually follows both forms and
death occurs within 10 days of the first signs
 Gross Findings
Often no gross lesions
Cattle and horses may have hemorrhage in
the spinal cord.
Evidence of injury or self-mutilation, or
alimentary foreign bodies raises suspicion of
rabies.
 Microscopic Findings
Nonsuppurative polioencephalomyelitis with
ganglioneuritis
Lesions most severe from the pons to the
hypothalamus, and the cervical spinal cord;
medulla generally spared
Perivascular lymphocytic cuffing;
perivascular hemorrhage; leptomeningitis
Glial nodules (focal gliosis); Babes nodules
are composed of microglia, and they occur in
both white and gray matter.
 Microscopic Findings
Neuronal degeneration is most severe in
carnivores and mild in pigs and herbivores.
Negri bodies are round to oval, 2-8 um,
eosinophilic cytoplasmic inclusions.
Negri bodies
Aggregations of strands of viral
nucleocapsid; transforms into a granular
matrix
Negri bodies are most common in the
hippocampal neurons in carnivores and
the Purkinje cells in herbivores and are the
hallmark of rabies infection.
 Negri bodies
They are plastic, their shape being molded
to their environment. Those in the dendrites,
seldom observed except in Purkinje cells, are
oval and those in the cell body are usually
rounded.
There may be one or more per cell, and
affected cells are otherwise only little
changed. The inclusions are surrounded by a
clear thin halo.
 Negri bodies
Negri bodies tend to be scarce where the
inflammatory reaction is severe. Indeed Negri
bodies may be found only in neurons that are
otherwise histologically normal; they are not
present in degenerate neurons.
Negri bodies are rarely found in the ganglion
cells of the adrenal medulla, salivary gland and
retina.
Early infections and 15-30% of rabies
infections fail to incite Negri bodies
Equine Rabies - The two panels in this image depict caudal
brainstem and illustrate perivascular cuffing by
mononuclear cells, with infiltration of the parenchyma and
gliosis. See also the following figure
Equine Rabies - This image is at high
magnification to show the nature of the
infiltrating cells depicted in the previous figure.
Equine Rabies - In the right panel two neurons containing
Negri bodies (arrows) are evident. Large Negri bodies, such
as in the upper neuron here are easy to see; smaller ones,
such as in the lower neuron are less distinct. The left panel
shows the same two cells at lower magnification.
Equine Rabies - Negri bodies (arrows) in large neurons of
the caudal brainstem. In the right panel the neuron with the
inclusion body is clearly degenerate but commonly neurons
Equine Rabies - At low and high magnification, specific
immunocytochemical staining reveals large amounts of viral
antigen within the cytoplasm of neurons in the brainstem.
Equine Rabies - Trigeminal ganglion. There is dense
mononuclear inflammatory cell infiltration and
degeneration of individual neurons. No Negri bodies are
evident. See also the following figure
Equine Rabies - Trigeminal ganglion. This is a detail from
the previous figure to show a lympho-plasmacytic
infiltrate amongst myelinated axons.
Bovine Rabies - Low and high magnification views of
bovine cerebellum. In the left panel the minimal
inflammatory response is indicated by a few cells in the
leptomeninges. A Purkinje cell containing multiple Negri
bodies is identified by arrows in each panel.
Caprine Rabies - In these figures are illustrated mild non-
suppurative inflammation in the spinal cord (top two panels)
and the presence of a Negri body (arrow) in a Purkinje cell
(lower left panel). The abundance of virus is emphasized by
the specific immunocytochemical stain of Purkinje cells in
the lower right panel. Post-mortem artifact, common along
the Purkinje zone,is present in the lower left panel.
Equine Rabies - Cervical spinal cord. Same case and
anatomic area as the previous figure. There is extensive
acute hemorrhage and moderate perivascular lymphoid
cell cuffing. See also the following two figures.
Equine Rabies - Trigeminal ganglion. Same case as the
previous two figures. Low magnification view to show
Equine Rabies - Trigeminal ganglion. Same case as the
previous three figures. Higher magnification illustrating
lymphoid, plasmacytoid and histiocytoid cells in the
infiltrate. Satellitosis around degenerate neurons is also in
evidence.
Bovine Rabies - High magnification image to show three
large Negri bodies in a neuron from the brain of a calf.
Negri bodies: The cytoplasm of rare hippocampal neurons contains one
or multiple, round to oval, eosinophilic intracytoplasmic inclusions.