1. Rabies

2. 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

3. 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

4. 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.

5. 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

6. 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

7. World Distribution

8. Epidemiology
The World Health Organization (WHO) estimates that people die of rabies annually. It is likely that this number is an underestimate and annual fatalities may be as high as 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

9. Viral Pathogen Rhabdovirus family; genus Lyssavirus
Viral envelope bullet shaped
Contains ss RNA
Lipoprotein envelope
Knob like spikes

10. 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

11. 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.

13. 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.

14. 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

15. Types of Rabies Furious rabies: Encephalitis form Hydrophobia
Aerophobia
Cranial nerve lesions
Spasticity
Involuntary movements
Fluctuation body temp
Sweating
tachycardia

16. 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

17. 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

18. 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?

19. Altered behaviour
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

20. Identifying Infected hosts
Can you pick the rabid animals??

21. 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

22. 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

23. 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

24. Treatment
Critical that treatment is administered as soon as possible and prior to the onset of severe symptoms
Two general methods of treatment exist
Wound Care
Post Exposure prophylaxis (PEP) drugs

25. Treatment
Wound Care
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

26. 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

27. 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

28. Case study
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

29. 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

30. Questions?