RABIES

Presented by
Angshumaan Goswami
Vanlalremruati

1
2 Flow of Presentation

▹ Introduction ▹ Pathogenesis
▹ Classification ▹ Clinical syndrome
▹ Morphology ▹ Epidemiology
▹ Resistance ▹ Diagnosis
▹ Viral replication ▹ Signs and symptoms
▹ Transmission ▹ Prevention
▹ Vaccination
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INTRODUCTI
ON
4
▹ Rabies is a fatal viral infection of the central
and peripheral nervous system that causes
encephalitis.
▹ It is caused by rabies virus.
▹ The virus is transmitted to humans from the
bite of a rabid animal. It can affect all
mammals and is transmitted between them
by infected secretions, most often by bite.
▹ Rabies is a zoonosis.
 CLASSIFICATI
ON

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6

▹ The rhabdoviruses are widely distributed in nature, infecting

vertebrates, invertebrates and plants. Rabies is the major medically
important rhabdovirus
 MORPHOLOG
Y

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▹ Bullet shaped virus with one end rounded or conical
and the other end planar or concave.
▹ negative-sense, non-segmented, single-stranded
RNA virus measuring approximately 75 X 180 nm.
▹ It is composed of an internal protein core or
nucleocapsid, which contain nucleic acid. It also
consists of an outer envelope which contain
haemagglutinating peplomer spikes, composed of
glycoprotein G spikes.
9
RESISTANCE
 ▹ Highly resistant against dryness, cold, decay etc. and
11 remains infective for many weeks in the cadevar.

▹ It survives at 4°C for weeks and at -70°C for years.

▹ Being enveloped virus, it is sensitive to lipid solvents such

as ether, chloroform and acetone. The virus is sensitive to
quartenary ammonium compounds, ethanol and iodine
preparations, soaps and detergents.

▹ It is inactivated by CO2 . Rabies virus is killed rapidly by

ultraviolet radiation or sunlight, by heat (1 hour at 50°C),
by lipid solvents (ether, 0.1% sodium deoxycholate), by
trypsin, by detergents, and by extremes of pH.
VIRAL
REPLICATION
13 1. Glycoprotein attachment
2. Endocytosis
3. Fuse with endosome
4. Uncoating
5. Transcription/ Translation
6. Genome replication
7. Virion assembly
8. Virion assembly
9. Budding
TRANSMISSIO
N
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Bite of an infected animal

Inhaling aerosolized virus

Organ transplant with infected tissue

Inoculation through mucosal surfaces

16 Animals that can spread rabies
▹ Pets and farm animals
Cat Dogs Goats
Cows Ferrets Horses
▹ Wild animals
Bats Monkeys
Beavers Raccoons
Cayotes Skunks
Foxes Woodchunks
17 ▹ The domestic dog (Canis familiaris) is the most important vector.

I WILL KEEL
YOU!!
ANIMAL
SUSCEPTIBILITY
AND CULTURE
19 Animals

▹ All warm blooded animals including man are susceptible to rabies infection.
▹ Experimental infection can be produced in many animals but rat is the
animal of choice. They can be infected by any route. Intracerebral
inoculation leads to encephalitis and the animal dies within 5-30 days.
20 Chick embryos
▹ The rabies virus grows in chick embryo and the usual mode of
inoculation is into the yolk sac.
▹ Live attenuated vaccine strains, Flury and Kelev, have developed by this
method.
21 Tissue Culture
▹ The rabies virus can grow in chick embryo fibroblast, hamster kidney
cells, human diploid cells and vero cell cultures.
▹ The fixed virus strains are grown in human diploid cells, chick embryo
and vero cell cultures for the production of vaccines.
PATHOGENESIS
 Pathogenesis of Rabies
23
Inoculation of the virus Epidermis

replicates initially in muscle

enters peripheral
nervous system

spreads to CNS gray matter

autonomic nerves to reach other tissues (salivary glands,

adrenal medulla, kidneys and lungs)
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 ▹ The pathognomonic lesion is the Negri body, an eosinophilic cytoplasmic
inclusion distributed throughout the brain, particularly in the hippocampus,
25 cerebral cortex, cerebellum and dorsal spinal ganglia. The presence of such
inclusions is not observed in at least 20% of cases. Therefore, absence of Negri
bodies does not rule out rabies as diagnosis.
26 Host Immunity

▹ Production of cytokines (such as interferon),

induced during rabies infection or
vaccination, has been reported to abort the
disease if it occurs shortly after viral
infection.
▹ Recently it has been demonstrated that
animals immunized with purified RNP
complexes or recombinant nucleoprotein
vaccines resisted lethal challenge with rabies
virus.
CLINICAL
SYNDROME
 No specific antirabies agents are useful once clinical signs or
symptoms develop.
28 In general, FOUR stages of rabies are recognised in
humans.

 Incubation
 Prodromal period
 Acute neurologic period
 Coma

INCUBATION PERIOD:

• Average incubation period is 20-90 days

• In 90% of cases , incubation is less than 1 yr.
• Patient remain asymptomatic during this period
• Incubation period depends on the severity of the wound and place
of the bite

PRODROMAL PERIOD:

• Virus enters CNS during this period

• Duration 2-10 days
• Pain develops at site of inoculation( pathognomonic for rabies)
 ACUTE NEUROLOGIC PERIOD:

29 • Signs of Developing CNS disease

• Duration is 2-7 days
• Patient develop agitation , hyperactivity, thrashing, biting or
hallucinations Furious
• This becomes episodic and interspersed with calm and lucid rabies
periods.
• Furious periods last for less than 5 mins.
• In some other cases , the patient is relatively calm
• Fever , headache, are prominent Paralyti
• Calmness and clarity gradually deteriorates to stupor and then c rabies
coma.

COMA

• Patient may go into coma within 10 days of onset

• Coma leads to respiratory failure within a week of neurologic
symptoms
• Without intensive supportive care, respiratory depression, arrest
and death occur shortly after coma.
EPIDEMIOLO
GY
31 ▹ Rabies virus is present in all parts of the world except Australia, Antarctica and some
islands like United Kingdom.
▹ Most human cases follow dog bites but in endemic areas almost any animal can
transmit rabies.
▹ In India, antirabies treatment is to be considered following the bite of any animal
except rats. Direct man to man transmission, although rare, is possible.
▹ In India, reservoir of infection in wild life are the jackal, foxes, hyena and other wild
life carriers. These animals can transmit the infections to dogs and other domestic
animals and also maintain a life cycle among themselves.
▹ Majority of human deaths (99%) due to rabies occur, mainly in Africa and Asia.
▹ The World Health Organization (WHO) estimates an annual toll of 55000 deaths
following human infection with rabies virus.
▹ Worldwide occurrence of rabies- 15,000 cases per year, highest attack rates in
Southeast Asia, the Philippines and the Indian sub-continent.
 ▹ Rabies exists in two epizootic forms- urban and sylvatic.
32 ▹ Urban form- associated with unimmunized dogs or cats.
▹ Sylvatic forms- occurs in wild skunks, foxes, wolves, racoons and
bats but not rodents or rabbits.
33 Death rate in INDIA due
to rabies
• Highest in Chhattisgarh

• Lowest in Gujarat, Himachal

Pradesh

• 0.51 – 1.5 in most of the

northeastern states.

• No reports of cases in
Mizoram.
LABORATORY
DIAGNOSIS
35 DIAGNOSIS IN HUMANS

▹ Antemortem/Postmortem diagnosis
Corneal impression smears, facial skin
biopsies or saliva are important specimens
for antemortem diagnosis using
immunofluorescence test.

Salivary glands, brain tissue,

hippocampus or cerebellum are used for
postmortem diagnosis by antigen detection,
demonstration of negri bodies and isolation
of virus
36 (i) Immunofluorescence test
▹ Viral antigens can be detected in corneal
impression smears and facial skin
biopsies or saliva by direct
immunofluorescence using antirabies
serum tagged with fluorescein
isothiocyanide.
▹ Postmortem diagnosis can be made using
brain as a specimen.
(ii) Demonstration of Negri Bodies
▹ This is demonstrated in brain but absent in
20% of human cases.
▹ Negri bodies appear as intracytoplasmic, oval
or round, purplish pink (3-27mm) bodies with
characteristic basophilic inner granules.
▹ Seller’s technique is used to demonstrate
these bodies.
▹ The advantage of this technique is that
fixation and staining are done
simultaneously.
SIGNS AND
SYMPTOMS
 SYMPTOMS OF RABIES
38 IN HUMANS

▹ The first symptoms of rabies may be very similar to those of

flu and may last for days.

Later signs and symptoms may include:

▹ Fever Hyperactivity
▹ Headache Difficulty swallowing
▹ Nausea Excessive salivation
▹ Vomiting Hydrophobia
▹ Agitation
▹ Anxiety
▹ confusion
39 Why does rabies cause hydrophobia?

▹ People used to call rabies hydrophobia because it

appears to cause a fear of water. The reason is that
the infection causes intense spasms in the throat
when a person tries to swallow. Even the thought of
swallowing water can cause spasms , making it
appear that the individual is afraid of water.
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 A SPECIAL CASE
41
 In some rare cases
reported, patient of
rabies was seen barking
like a dog, this is not
a common representation
of rabies

 However sometimes the

rabies virus enters the
brain and start to form
these symptoms.in such
cases chances of
survival are
negligible.
PREVENTIONS
 HOW TO PREVENT RABIES?
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 First of all, do not panic after the animal bite.It is
important to stay calm.

 Instantly wash the wound with soap and water

thoroughly

 Disinfect the wound using iodine tincture.

 Go for medical help and take rabies vaccination.

 If possible try to observe the biting animal for 10

days
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• Rabies in human is 100% preventable
through prompt appropriate medical care.

• Vaccinate your pets to protect them and your

family.

• If possible try to eliminate exposure to rabid

animals.
VACCINATION
46
 Rabies vaccine is given to persons who
have been exposed to an animal that is
known , or thought to have rabies.

 This is called Post- exposure prophylaxis.

 Rabies vaccine may also be given ahead

of time to persons who have high risk of
getting infected with rabies virus.

 This is called pre-exposure prophylaxis.

 VACCINES FOR RABIES VIRUS:
47 The first human vaccination with a rabies virus
attenuated by exposure to dry air started on 6 th
July,1885.
Common rabies vaccines

HDC(Human diploid cell culture) VACCINE

 Imovax
 Sanofi Pasteur

 PCECV VACCINE

 RabAvert
 Novartis

 COMMONLY USED VACCINES IN INDIA

 Rabivax
 Rabipur
 Abhayarab
 POST-EXPOSURE & PRE-EXPOSURE VACCINATION GUIDELINE.

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 Normally when used appropriately with
timely wound care, the administration of
4 doses of vaccines is likely to induce
adequate, long lasting antibody response
to neutralize rabies virus and prevent
disease in exposed patients.

 However, 5 doses can also be prescribed

as per requirement.
REFERENCES
  Textbook of microbiology by C.P Baveja

50  Microbiology and immunity by Subhash Chandra Parija (2 nd edition)

 Sherris medical microbiology

 Jawetz and Adelberg Medical Microbiology (26 th edition)

 E-resources
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