Transcript Rabies

Rabies
 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).

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.
Rabies Virus
G, M, L, N, and NS Proteins
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).
Ulceroglandular disease
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.

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.
CDC
Rabies Virus (Rhabdovirus)
Figure 22.12
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.

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.
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
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
Diagnosis of Rabies
Negri Body in neuron cell (source: CDC) Positive DFA test (Source: CDC)
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.
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.
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.
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
 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.
Epidemiology

35.000-50.000 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 rabiesfree

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)
Animal Rabies in the USA is Common (n=7560*)
* Current 5 year mean value
Raccoon
Skunk
Bat
Fox
Cat
Cattle
Dog
Equids
Mongoose
Woodchuck
Bobcat
Other Wildlife
Sheep/Goats
Other Domestic
Usually 1-3 human cases per year
Dogs - especially stray &
unvaccinated
Cats - especially stray and
unvaccinated
Raccoons, Skunks, Foxes and Bats Are Major Rabies Reservoirs
Raccoon
Red Fox
Striped Skunk
Silver tailed Bat
Mammals that are less
likely to carry rabies
Animals that don’t carry
rabies
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.