Rabies
What is Rabies

Rabies is a zoonotic disease cause by a
rhabdovirus which infects the central
nervous tissue and salivary gland often
resulting in aggressive altered behaviour
History

One of the oldest infectious
diseases recorded
• 2300 BC Babylonian dog owners fined for deaths
resulting from their dogs biting people (possibly rabies?)
• References are made to “raging dogs” as early as
800BC
• 400BC Aristotle writes that “dogs suffer from the
madness” and that their bite confers disease
How did Rabies get its name

Rabies comes from the Latin word rabere which
means to rage or rave

Latin work has its roots in the sanskrit word rabhas
which means to do violence.

The greeks called rabies lyssa, which means
frenzy or madness.
Epidemiology

Rabies is currently distributed
worldwide except for Antarctica,
Australia and a few island nations.

In developing areas where canine
rabies remains common and there
are a large number of wild dogs,
most human cases results from dog
bites.

In developed nations like Canada
where dogs are immunized, most
human cases follow exposure to
rabid wild animals
Epidemiology


Typical route of infections is
via bites from infected
animals
In many cases the infected
animal exhibits
 Exceptional aggression
 Unprovoked attach behaviour
 General uncharacteristic
behaviour

Transmission between
humans is rare
World Distribution
Epidemiology

The World Health Organization (WHO) estimates that 55 000
people die of rabies annually. It is likely that this number is an
underestimate and annual fatalities may be as high as 100 000.
About 95% of human deaths occur in Asia and Africa.

Most human deaths follow a bite from an infected dog. Between
30% to 60% of the victims of dog bites are children under the
age of 15

Any warm blooded animal can be infected and as such any warm
blooded animal can serve as a reservoir host

Once symptoms of the disease develop, rabies is fatal
Viral Pathogen

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Rhabdovirus family; genus Lyssavirus
Viral envelope bullet shaped
Contains ss RNA
Lipoprotein envelope
Knob like spikes
Mechanism of infection

Viral particles enter through:
 Breaks in the skin (bites, scratches)
 Through mucosal surfaces
 Through the respiratory tract

Virus replicates in muscle cells

Virus then docks with specific neural receptors and enters the
host neurons

Travels within infected neurons directionally towards the CNS

Once in CNS travels to the brain and the rest of the body via
peripheral nerves
Mechanism of Infection

Salivary glands – virus migrates through
peripheral nervous tissue to oral mucosal nerve
endings

Migrating viral pathogens shed into the oral
mucus

Replication also occurs in the salivary glands and
is released with salivation.
Time Line of Infection

Incubation period varies between 20 and 90 days
but can be as long as two years.

Incubation period depend on location of infection
and severity of viral transfer

In humans once incubation period ends flu-like
symptoms appear

Once the first symptoms appear the infection is
effectively untreatable and usually fatal within
days.
Immune Response

There is a measurable antibody response but this
occurs late in the course of infection and is
insufficient.

Altered cytokine release

Some studies suggest the virus may persist in
macrophages and emerge later to produce
disease
Types of Rabies

Furious rabies: Encephalitis form
 Hydrophobia
 Aerophobia
 Cranial nerve lesions
 Spasticity
 Involuntary movements
 Fluctuation body temp
 Sweating
 tachycardia
Types of Rabies

Paralytic Rabies:
 No hydrophobia or aerophobia
 Flaccid paralysis
 Paralysis begins in limb associated with infection and
expands to the rest of the body
 Death usually due to paralysis of the respiratory tract
Altered behaviour

Major characteristic of rabies infection is major
host behavioural changes mediated by the
virus.

Virus alters neuronal transmission of both
infected neurons and uninfected neurons

Neural damage is minimal during migration
 This suggests the virus can target specific neurons
and alter behaviour with out killing
Altered behaviour

Problems
 Not all infections result in aggression some result in
paralysis which would appear to reduce transmission



The virus does not target the areas of the brain
associated with aggression!!!
Furthermore the distribution of the virus in the
brain in both the paralytic and encephalitic
forms of rabies is the same!!!
So how does the virus produce enhanced
aggression?
Altered behaviour



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Suggested that the immunological reactions
provoked by the virus play a role
Altered cytokine release can effect the limbic
system resulting in aggression
This has been observed in other auto immune
disorders
If host immune response determines
aggression then that would explain the varying
behavioural alterations observed
Identifying Infected hosts

Can you pick the rabid animals??
Human Symptoms – Early Stage

Starts as flu-like symptoms and expands to:
 Slight or partial paralysis
 Cerebral dysfunction
 Anxiety
 Insomnia
 Confusion
 Agitation
 Abnormal behaviour
 Paranoia
 Terror
 Hallucinations
 Progression to delirium
Symptoms – Late stage

Production of large quantities of saliva and tears

Inability to speak or swallow

Throat and jaw become paralyzed

Hydrophobia and panic when presented with
water

In animals extreme aggression and risky
behaviour appear
Diagnosis

Biopsies of brain tissue. Can
anyone see the problem with this??

Analysis of saliva, tracheal aspirates
or throat swabs for viral particles

Viral antibody screen

If a human is bitten by suspected
rabid mammal, the usual course of
action is to euthanize the animal
and perform a brain biopsy
Treatment

Critical that treatment is administered as soon
as possible and prior to the onset of severe
symptoms
Two general methods of treatment exist

1.
2.
Wound Care
Post Exposure prophylaxis (PEP) drugs
Treatment
Wound Care


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Probably one of the most basic and important steps in
prevention of rabies
Estimated proper wound care alone can reduce risk by
up to 90%
Virus sensitive to: Ethanol, Iodine, Detergents, general
exposure to temperatures above 50 degrees Celsius >
1hour
Wash wound with any of the above solutions
Irrigation of wound with any virucidal agent
Treatment

Post Exposure Prophylaxis

The following treatment needs to be administered within 10
day following exposure

The Center for Disease Control (CDC) recommends:
○
One dose of human rabies immunoglobulin (HRIG)
○
Followed by four doses of rabies vaccine over 14 days

HRIG should be administered in the transfer site followed by
deep intramuscular injection at site far from the entry point.

Inevitably the best treatment is prevention via immunization
(both human and pet) and not associating with wild animals or
domestic stalk that is acting strange
Ethical Problems
HRIG is extremely expensive costing several
thousand dollars per injection




For this reason there is a debate regarding when the
drug should be administered
Generally it was suggested that any individual that
awakes to find a bat in the room, or has been exposed
to any wild animal while intoxicated or sleeping should
receive PEP
Recently the use of precautionary PEP for individuals
where no contact can be confirmed has been
questioned based on a cost benefit analysis
Case study

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In September 2000 a young boy in Quebec was
found to have been in the presence of a bat
while sleeping
The child was observed and no visible contact
(ie bite marks) with the bat could be identified
PEP was not administered based on the lack of
any marks on the child's skin
3 weeks later the child died from advanced
rabies
The child's doctors criticised the policy that PEP
should only be administered when a visible bite
or overt break in the skin has occurred
Conclusions

Further research is needed to determine the
exact mechanism of altered host behaviour

Where possible vaccination of both humans and
dominant wild host should be preformed

PEP treatment should be administered as soon
as possible after exposure
Questions?