RABIES

Ragina aguila
History of Rabies Virus
• From latin: rabies
• Rabies (Also known as “hydrophobia”) is a Rhabdovirus disease that
causes acute encephalitis in mammals. It is most commonly caused
by a bite from an infected animal, but occasionally by other forms
of contact.
• 2 types”
• A). Urban- dogs
• B) sylvatic- wild animals
• Lyssavirus is a genus of viruses belonging to the family Rhabdoviridae, in the
order Mononegavirales.
• This group of Rna viruses includes the Rabies virus traditionally associated with the
disease.
RABIES VIRUS
www.lmb.uni-muenchen.de/groups/
Conzelmann/default.htm
WHERE DO WE ACQUIRE
RABIES?
Racoons, Skunks, Foxes and Bats Are Major Rabies Reserviors

Racoon Striped Skunk

Red Fox Silvertailed Bat

Human anatomy of the
central nervous system
Organization of the Nervous
System

Figure 7.2
 Functions of the Nervous System
• Sensory input – gathering information
– To monitor changes occurring inside and outside
the body
– Changes = stimuli
• Integration
– To process and interpret sensory input and decide
if action is needed
 Functions of the Nervous System
• Motor output
– A response to integrated stimuli
– The response activates muscles or glands
 Structural Classification of the
Nervous System

• Central nervous system (CNS)

– Brain
– Spinal cord
• Peripheral nervous system (PNS)
– Nerve outside the brain and spinal cord
 Functional Classification of the
Peripheral Nervous System

• Sensory (afferent) division

– Nerve fibers that carry information to the central
nervous system

Figure 7.1
 Functional Classification of the
Peripheral Nervous System
• Motor (efferent) division
– Nerve fibers that carry impulses away from the
central nervous system

Figure 7.1
 Functional Classification of the
Peripheral Nervous System

• Motor (efferent) division

– Two subdivisions
• Somatic nervous system = voluntary
• Autonomic nervous system = involuntary

Figure 7.1
 Nervous Tissue: Support Cells
(Neuroglia)
• Astrocytes
– Abundant, star-shaped cells
– Brace neurons
– Form barrier
between capillaries
and neurons
– Control the chemical
environment of
the brain

Figure 7.3a
 Nervous Tissue: Support Cells
• Microglia
– Spider-like phagocytes
– Dispose of debris
• Ependymal cells
– Line cavities of the
brain and spinal cord
– Circulate
cerebrospinal
fluid

Figure 7.3b–c
 Nervous Tissue: Support Cells
• Oligodendrocytes
– Produce myelin sheath around nerve fibers in the
central nervous system

Figure 7.3d
 Nervous Tissue: Support Cells
• Satellite cells
– Protect neuron cell bodies
• Schwann cells
– Form myelin sheath in the peripheral nervous
system

Figure 7.3e
 Nervous Tissue: Neurons
• Neurons = nerve cells
– Cells specialized to transmit messages
– Major regions of neurons
• Cell body – nucleus and metabolic center of the cell
• Processes – fibers that extend from the cell body
 Neuron Anatomy
• Cell body
– Nissl substance –
specialized rough
endoplasmic
reticulum
– Neurofibrils –
intermediate
cytoskeleton that
maintains cell
shape

Figure 7.4a
 Neuron Anatomy
• Cell body
– Nucleus
– Large nucleolus

Figure 7.4a–b
 Neuron Anatomy
• Extensions outside
the cell body
– Dendrites – conduct
impulses toward the
cell body
– Axons – conduct
impulses away from
the cell body

Figure 7.4a
 Axons and Nerve Impulses
• Axons end in axonal terminals
• Axonal terminals contain vesicles with
neurotransmitters
• Axonal terminals are separated from the next
neuron by a gap
– Synaptic cleft – gap between adjacent neurons
– Synapse – junction between nerves
 Nerve Fiber Coverings
• Schwann cells –
produce myelin
sheaths in jelly-roll
like fashion
• Nodes of Ranvier –
gaps in myelin sheath
along the axon

Figure 7.5
 Neuron Cell Body Location
• Most are found in the central nervous system
– Gray matter – cell bodies and unmylenated fibers
– Nuclei – clusters of cell bodies within the white
matter of the central nervous system
• Ganglia – collections of cell bodies outside the
central nervous system
 Functional Classification of
Neurons
• Sensory (afferent) neurons
– Carry impulses from the sensory receptors
• Cutaneous sense organs
• Proprioceptors – detect stretch or tension
• Motor (efferent) neurons
– Carry impulses from the central nervous system
 Functional Classification of
Neurons
• Interneurons (association neurons)
– Found in neural pathways in the central nervous
system
– Connect sensory and motor neurons
Neuron Classification

Figure 7.6
 Structural Classification of
Neurons
• Multipolar neurons – many extensions from
the cell body

Figure 7.8a
 Structural Classification of
Neurons
• Bipolar neurons – one axon and one dendrite

Figure 7.8b
 Structural Classification of
Neurons
• Unipolar neurons – have a short single process
leaving the cell body

Figure 7.8c
 Functional Properties of Neurons
• Irritability – ability to respond to stimuli
• Conductivity – ability to transmit an impulse
• The plasma membrane at rest is polarized
– Fewer positive ions are inside the cell than
outside the cell
 Starting a Nerve Impulse
• Depolarization – a
stimulus depolarizes the
neuron’s membrane
• A deploarized membrane
allows sodium (Na+) to
flow inside the membrane
• The exchange of ions
initiates an action
potential in the neuron

Figure 7.9a–c
 The Action Potential
• If the action potential (nerve impulse) starts, it
is propagated over the entire axon
• Potassium ions rush out of the neuron after
sodium ions rush in, which repolarizes the
membrane
• The sodium-potassium pump restores the
original configuration
– This action requires ATP
 Nerve Impulse Propagation
• The impulse continues
to move toward the
cell body
• Impulses travel faster
when fibers have a
myelin sheath

Figure 7.9d–f
 Continuation of the Nerve Impulse
between Neurons

• Impulses are able to cross the synapse to

another nerve
– Neurotransmitter is released from a nerve’s axon
terminal
– The dendrite of the next neuron has receptors
that are stimulated by the neurotransmitter
– An action potential is started in the dendrite
How Neurons Communicate at
Synapses

Figure 7.10
After a typical human infection by bite
through
An infected animal is exceptionally aggressive,
may attack without provocation, and exhibits otherwise
uncharacteristic behavior.

The virus is usually present in the nerves and saliva of a

symptomatic rabid animal.
It travels along the Central nervous
system

During this phase, the virus

cannot be easily detected within
the host, and vaccination may
still confer cell-mediated
immunity to prevent symptomatic rabies.
When the virus reaches the brain,
it rapidly causes encephalitis.
This is called the prodromal phase, and is the
beginning of the symptoms. Once the patient
becomes symptomatic, treatment is almost never
effective. Rabies may also inflame the spinal cord
producing transverse myelitis

Causes perivascular infiltration

throughout the CNS

Disrupts the functioning of the CNS

 Brain death

death
Sign & Symptoms
• Beginning stages of rabies, the
symptoms are malaise, headache, and
fever.
• 2nd stages it includes acute pain, violent
movements, and the inability to swallow
water (hence the name hydrophobia).
• Final stages, the patient begins to have
periods of mania and lethargy, and
coma. Death generally occurs due to
respiratory insufficiency.
 DIAGNOSTIC TEST:

Direct microscopic demonstrate of

virus antigen by: Direct
immunofluorescence staining  detect
virus in brain tissue and corneal
scrapings.

Brain biopsy histologic staining

of brain tissue (seller stain).
 Animal inoculation  tissue or saliva inoculated
intracerebral into mice
presence of rabies virus is indicated by
1. flaccid paralysis of leg
2. encephalitis
3. death

Serological
detect rabies antibodies by
1. Immunofluorescence test
2. Complement fixation test
3. Neutralization test
Antibodies are developed during progression
of the disease.
•PREVENTION
• Pre-exposure prophylaxis:
vaccination: intramuscular, 1ml (3
doses): at 0, 7, 21-28 days
• Antibodies usually persist for 2 yrs
• Repeat titers q6-24 months
depending on level of exposure
 Post-exposure wound care
• Prevent virus in wound from reaching
neural tissue
• Prompt and thorough cleaning: flush
wound with soap and water
• Benzalkonium chloride not superior
to soap
• Update tetanus immunization
• Treat secondary bacterial infection
• Do not suture wound if possible
Post-exposure immunoprophylaxis

• Passive and active

• RIG and rabies vaccine
• Vaccine : one of the 3 types (5
doses), same dose for all ages
• 1.0 ml IM at 0, 3, 7, 14, 28 d
• Intradermal regimens:used in some
countries, not USA
• Avoid gluteal injection: less antibody
response than deltoid or AL thigh
 TREATMENT
• Human Diploid Cell Vaccine (HDCV)
• Vaccine : one of the 3 types (5 doses), same dose
for all ages
• 1.0 ml IM at 0, 3, 7, 14, 28 d
• Intradermal regimens:used in some countries, not
USA
• Avoid gluteal injection: less antibody response than
deltoid or AL thigh

• Rabies Vaccine adsorbed (RVA)

• Purified chicken embryo cell (PCEC)
 Prognosis

• In unvaccinated humans, rabies is almost always fatal

after neurological symptoms have developed, but
prompt post-exposure vaccination may prevent the
virus from progressing. Rabies kills around 55,000
people a year, mostly in Asia and Africa.There are
only six known cases of a person surviving
symptomatic rabies, and only one known case of
survival in which the patient received no rabies-
specific treatment either before or after illness
onset.
 China firms fined over rabies shots:
state media
july 01,2010
• Chinese authorities have fined two drug companies, including one
authorised to make swine flu vaccines, for producing substandard rabies
shots, state media said Monday.

• China firms fined over rabies shots: state media

• Ealong Biotech Company was fined 25 million yuan (3.6 million dollars) and
Bioforwell Company was told to pay five million yuan for producing
210,000 units of a rabies vaccine in 2008, the Global Times newspaper
reported.
• The companies had reduced the level of a key ingredient to cut costs,
rendering the jabs ineffective, it quoted the State Food and Drug
Administration as saying.
• Ealong Biotech, based in eastern Jiangsu province, is one of a handful of
companies authorised to produce the nation's vaccines for swine flu, or the
A(H1N1) virus.
The government also has revoked the two companies' licenses to
produce rabies vaccines, the report said.
There have been no reports of the vaccines causing health
problems, according to state media reports.
Rabies has emerged as a major public health concern in China.
The government said last year China was second only to India in
annual human deaths from rabies, averaging more than 2,000
per year in recent years.
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