1. Rabies

2. Rabies is the most lethal of all infectious diseases.
Even the most extreme modern medical interventions are usually not successful.
The disease was recognized in Egypt before 2300 B.C. and in ancient Greece, where it was described by Aristotle.
The method of transmission of rabies was not recognized until 1804.
Rabies is thought to be responsible for the origin of vampire legends (bats, biting, hypersexuality are associated with rabies).

3. Rhabdoviridae: A large number of member viruses that are serologically unrelated.
Rabies belongs to the genus lyssa virus (rabies in Greek means mad or frenzy).
It is bullet shaped, enveloped and has a diameter of 75X180 nm.

4. Rabies Virus
G, M, L, N, and NS Proteins

5. transmission
Rabies is transmitted by rabid animals that have the virus in their saliva.
Bites or licks of a rabid animal transmit rabies.
Rabies can be transmitted by moisture droplets in the air.
Unusual modes of transmission (inhalation, aerosoles, ingestion, and corneal and other transplants).

6. Does everyone know what saliva is? Spit, drool.
Can anyone tell me what is on the boy’s blanket? A bat! UGGGGGH!
Does everyone know what saliva is? Spit, drool.
Note: Once an animal dies, the rabies virus does not survive for very long under most environmental conditions. The saliva from animals that have been dead for a while is not infectious. However, since it is not always obvious how long an animal had been dead, the take-home message for the kids is to stay away from dead animals.

7. Girl with ulcerating lymphadenitis due to tularemia, Kosovo, April Image from CDC website: (
Ulceroglandular disease

8. Pathogenesis Exact pathogenic mechanisms are not fully understood.
Following the bite or a lick of a rabid animal, local multiplication takes place in striated muscles.
Virus attaches at neuromuscular junctions via the acetylcholine receptor.
Retrograde axoplasmic transport to the spinal cord.

9. The virus reaches the brain and a wide disseminated encephalitis develops.
Little discernable damage and very little histopathologic changes.
Cytoplasmic inclusions (Negri bodies) are detectable in infected cells.
Centrifugal dissemination of virus via afferent neurons to highly innervated sites.

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CDC

11. Rabies Virus (Rhabdovirus)
Figure 22.12

12. Clinical Features Incubation- mean 30-90 d; range 5days-7years
Stages: incubation, prodrome, acute neurologic period, coma and death or very rarely recovery.
The prodromal phase is characterized by flu-like manifestations, malaise, headache, fever and a profound sense of apprehension and feeling of irritation with paraesthesia at the wound site.
There are complaints of dry throat, cough and thirst but patients will not drink.

13. Difficulty in swallowing and revulsion of water (hydrophobia).
Other manifestations include; photophobia, priapism, increased lipido, insomnia, nightmares and depression.
Frank manifestations of encephalitis including; bizarre behavior, excitement, agitation, hallucinatory seizures, laryngeal spasm, chocking and gagging intermingled with lucid intervals.
This state gradually subsides into delirium, convulsions, coma and death.

14. Signs of rabies in animals
Two clinical forms; furious rabies and dumb or paralytic rabies.
Unusual behavior
Wild animals that appear friendly
Nocturnal animals active during the day
An increase in drool or saliva
Animals that act very sick or mean
Animals that have difficulty moving or are dead
These are some of the most obvious signs that you might see in a rabid animal. However, these are not unique to rabies and might be due to other causes.
Unusual behavior
Wild animals are usually skittish and afraid of people. If they approach people, it would be unusual behavior
Question for kids: What does nocturnal mean?
Answer: Nocturnal animals are animals that are normally active at night and sleep or hide during the day.
Raccoons and skunks are nocturnal animals, so if you see them during the day, they are acting unusually and may be ill.
Important Point:
Remember that some animals that have rabies will look just fine. You can’t always tell just by looking at an animal that they have rabies. However, any time you see an animal acting abnormally, rabies is a possibility.

15. Laboratory Diagnosis LP, imaging: nonspecific, antibodies: appear late
Identification of rabies antigen by DFA (Salivary, corneal or conjunctival smears or biopsy of neck nape >5 days, 2/3 +).
PCR saliva for rabies- > 5days
Virus Isolation: from saliva or CSF
Serology: ELISA

16. Diagnosis of Rabies Negri Body in neuron cell (source: CDC)
Positive DFA test (Source: CDC)

17. Prognosis and Treatment
Death from asphyxia, exhaustion, or general paralysis usually occurs within 3 to 10 days after onset of symptoms.
However, recovery of one patient has occurred after aggressive, vigorous, supportive treatment to control respiratory, circulatory, and CNS symptoms.
If rabies develops, treatment is symptomatic.
The case fatality ratio approaches unity. Consultation should be sought to assist in management.

18. Treatments: old myths to cure rabies
Eating liver of a rabid dog.
Eating a paste made from the eyes of a crayfish.
Drenching wound with acid or burning area with a red hot iron.
Sprinkling wound with gun powder and lighting it.

19. Management Proper care of wounds
Immunoprophylaxis (Rabies human immunoglobulin)
Vaccination as soon you the patient is bitten (HDCV at 0, 3, 7, 14, 28 and 90 days after exposure).
Putting patient on respirator and maintaining support of vital functions.
Reality: Once the virus attacks the brain, family should organize the funeral because the patient is going to DIE.

20. Rabies Vaccines for Humans
Inactivated whole virus vaccines are available for humans.
Nervous Tissue Preparations are associated with the rare complication of demyelinating allergic encephalitis.
Duck Embryo Vaccine is grown in embryonated duck eggs. The vaccine has a lower risk of allergic encephalitis but is considerably less immunogenic

21. Human Diploid Cell Vaccine (HDCV) - this is currently the best vaccine available with an efficacy rate of nearly 100% and rarely any severe reactions. However it is very expensive.
Other Cell culture Vaccines - because of the expense of HDCV, other cell culture vaccines are being developed for the developing countries.
However recent data suggests that a much reduced dose of HDCV given intradermally may be just be effective.

22. Epidemiology
cases are reported annually worldwide with the highest numbers in Asia, particularly in India. In Asia 90% of cases result from dog bites.
UK, Japan, Cyprus, Iceland, Australia, Taiwan and Hawaii are rabies-free
Among animals the disease may spread via two pathways, urban and sylvatic.
Urban mode: among domestic dogs and cats, a situation prevailing in the third world.
Sylvatic mode: Foxes ( Europe, Canada and Northern USA), Raccoons ( Eastern seaboard, USA), Skunks (Southern USA), Mongoose (West Indies)

25. Animal Rabies in the USA is Common (n=7560*)
* Current 5 year mean value
Usually 1-3 human cases per year

26. Dogs - especially stray & unvaccinated
Question for students: How many of you own dogs?
The dog on the left looks very mean but not all animals with rabies will look like that when they are sick! Sometimes you just can’t tell if an animal has rabies.
Important Point:
What we said about cats is the same for dogs—it is VERY important to vaccinate them for rabies and to keep them up-to-date on their rabies vaccinations.

27. Cats - especially stray and unvaccinated
Important Point:
Cats can get rabies if they haven’t been vaccinated and a rabid animal attacks them. Cats can then pass rabies on to you or another animal. That’s why you should be sure to get your cat vaccinated and keep your cat up-to-date on its rabies vaccinations.
Question for students: How many of you own cats?
Fun Fact:
Did you know that more people own cats than dogs in Massachusetts?
Does anyone know what a stray (or feral) cat is?
Answer: A cat that is wild and doesn’t have a home.

28. Raccoons, Skunks, Foxes and Bats Are Major Rabies Reservoirs
Striped Skunk
Red Fox
Silver tailed Bat

29. Mammals that are less likely to carry rabies

30. Animals that don’t carry rabies
Question for students: Ask the students to identify these animals
A: Clockwise from top left: bird, snake, turtle, bees, tick
Are these animals mammals? NO, then they can not get rabies.

31. Control
Rabies has been controlled among dogs in the developed countries by vaccination.
Control of stray dogs and cats and dissemination of vaccine virus among animals is very important.
Vaccination of groups at risk; Lab. workers, those who handle animals (Zoo workers, vets, quarantine workers, hunters), and those traveling to endemic areas.
Wildlife - Rabies in wild animals is much more difficult to control than canine rabies. However, on-going trials in the USA and Europe using bait containing rabies vaccine given to foxes and raccoons reduces rabies levels.