Rabies in dogs and humans

1. Infectious Disease
Report: Rabies
By: Anu Gandhi and Val Riguero

2. What are Rabies?
 Rabies virus causes an acute encephalitis
(inflammation of the brain) in all warm-blooded
hosts.
 Rabies is not, in the natural sense, a disease of
humans.
 The impact of rabies on public health includes an
estimate of the animal population that is affected
and the steps involved in preventing transmission of
rabies from animals to humans.
 Raccoons, skunks, foxes, coyotes, and several
species of insectivorous bats have been identified
as reservoirs for the disease.

3. Rabies in History
 Rabies cases have been reported since
before 2300 BC.
 1st century AD a Roman scholar named
Aulus Cornelius Celsus gave the first
accurate description of the disease
 1st scientist to test rabies infection
through inoculation of saliva was a
German scientist named Zinke in 1804

4. Pasteur’s Contribution
 1885 he published a method for protecting
dogs against rabies
 A dog exposed to rabies was protected by
inoculation with an emulsion prepared from
the dried spinal cord of a diseased rabbit
 Pasteur had the chance to test this same
method on humans when Joseph Meister, a
nine-year-old boy who was bitten by a rabid
dog was brought to him in July of 1885

5.  Joseph was injected over several days
with the emulsions prepared from
animal spinal cord material
 After 2 weeks, Joseph was given an
injection of virus that had maximal
virulence when tested in a rabbit
 Joseph survived as did thousands of
others treated by the same procedure.

6. Epidemiology
 In 2001, 49 states, the District of Colombia, and
Puerto Rico reported 7,437 cases of rabies in
animals to the Center of Disease Prevention and
Control and no cases in humans were reported.
 Pennsylvania reported the largest number of rabid
domestic animals (46) for any state, followed by
New York (43)
 The number of rabies-related human deaths in the
U.S. has declined from 100 or more each year at
the turn of the century to an average of 1-2 each
year in the 1990’s

8. Morphology
 Order- Mononegavirales
 Nonsegmented
 Negative stranded RNA
genome
 “Bullet” shaped-
Rhabdovirus 180nm x75nm
 400 trimeric spikes on
surface of virus
 2 major structural
components
– Helical RNP core
– Surrounding envelope

9. Physiology
 Genome encodes 5 proteins:
– Nucleoprotein- encases RNA
– Phosphoprotein- associated with ribonuceoprotein core
– Matrix protein- central protein of rhabdovirus assembly
– Glycoprotein- forms 400 trimeric spikes
– Polymerase- transcribes genomic strand of rabies RNA

10. Virulence
 Depends on severity of bite
 If treatment is given and when
 Once the disease manifests in CNS:
ultimate death

11. Pathogenicity
 Defined by encephalitis and myelitis
 Perivascular infiltration throughout entire
central nervous system
 Causes cytoplasmic eosinophilic inclusion
bodies (Negri bodies) in neuronal cells
 Several factors may affect outcome of rabies
exposure.
– Rabies variant
– Dose
– Route
– Location of exposure
– Individual host factors

12. Transmission
 Begins when infected saliva of host is
passed to uninfected animal.
 Scratches
 Bites

13. Discharge and
Intermediate Hosts
 Infection of new host via saliva
 Death of host
 Wild rabid animals may infect domestic
animals/people
– Cattle, horses, pigs, dogs, cats
– Humans
 Rabid domestic animals may infect
humans

14. Vehicles of Transmission
 Saliva
 Mucous membranes
 Aerosol transmission
 Corneal transplantations

15. Symptoms of Rabies
 The first symptoms of rabies may be non-
specific flu- like signs, such as malaise, fever
or headache which may last for days.
 There may be discomfort or paresthesia at
the site of exposure (bite) progressing
within days to symptoms of cerebral
dysfunction, anxiety, confusion, and
agitation which eventually progress to
delirium, abnormal behavior, hallucinations,
and insomnia.

16. Rabies Diagnosis in
animals
 The direct fluorescent
antibody test (dFA) is the
test most frequently used to
diagnose rabies. This test
requires brain tissue from
animals suspected of being
rabid.
 The dFA test is based on
the fact that infected
animals have rabies virus
proteins (antigen) present
in their tissues.
Positive dFA
Negative dFA

17. Rabies Diagnosis in
humans
 Saliva can be tested by virus isolation
or reverse transcription by polymerase
chain reaction (RT-PCR).
 Serum and spinal fluid are tested for
antibodies to rabies virus.
 Skin biopsy specimens are examined
for rabies antigen in the cutaneous
nerves at the base of hair follicles.

18. Methods of Cure
 Rabies Vaccine: A killed virus vaccine
(Human Diploid Cell Vaccine, HDCV) grown
in human fibroblasts is available for safe use
in humans.
 The unusually long incubation period of the
virus permits the effective use of active
immunization with vaccine post-exposure.
 If rabies has not been diagnosed and the
victim is not treated with a vaccine and the
clinical disease manifests, it is nearly always
fatal, and treatment is typically supportive.

19. Related Studies
 In the journal Antibiotics and
Chemotherapy, an article was published
which presented the results of an
experimental study of the action of
rifampicin on the process of rabies infection
in albino mice contaminated with 1-10 LD50
of the fixed rabies virus.
 Exposure to rifampicin in doses of 250-500
mg/mouse resulted in survival of 66.7-
83.4% of the animals respectively while the
controls did not exceed 16.6-25%.

20.  The infection of target cells by rabies is effected
through membrane receptors; it has been
suggested that nicotonic receptors could be used by
the virus.
 In a study published in Neuroscience Letters,
mouse dorsal root ganglia cells were treated with
various nicotonic antagonists (mecamailamine, d-
tubocurarin, hexametonium, etc.).
 After incubation the cultures were infected with the
rabies virus, the cells were then processed for
immunodetection of rabies virus.
 Treatment with mecamilamine or d-tubocurarine
reduced the % of infected neurons.

21. Control and Prevention
 Pre-exposure prophylaxis vaccination
 Post-exposure prophylaxis
 If you are exposed to a possible rabid
animal:
– Wash wound with soap and water
– Seek medical attention immediately

22. Control and Prevention
 Be a responsible pet owner
– Keep vaccinations up to date
– Keep pets under direct supervision
– Spay and neuter pets
 Enjoy wild animals from far away
 Don’t adopt wild animals
 “Love your own, leave others alone”
policy

23. References
 National Center for Infectious Diseases
 Microbial Life, Perry
 Keen, Anthony
 Rabies.com
 Antibiotiki Khimioterapiia
Zubovich,I K Volume 34, Issue 2, Feb 1989, 123-125
 Partial inhibition of the in vitro infection of adult
mouse dorsal root ganglion neurons by rabies virus
using nicotinic antagonists
Castellanos, J E, Neuroscience Letters, Volume 229, Issue 3,
July 4, 1997