Rabies is a fatal viral disease of the central nervous system transmitted through the bites of rabid animals. It is endemic in many parts of the world including India, where an estimated 20,000 deaths occur annually from canine rabies. The rabies virus infects neurons and spreads via retrograde axonal transport to the central nervous system. This typically causes encephalitis, with symptoms including hydrophobia, aerophobia, and autonomic dysfunction. While treatment is supportive once symptoms begin, post-exposure prophylaxis including wound cleansing, rabies vaccine, and rabies immunoglobulin can prevent the disease if administered promptly after exposure. Rabies remains an important public health problem but is preventable through vaccination of animals
1. Dr Sujith Chadala ,
Resident in Internal Medicine ,
Osmania General Hospital.
2. Epidemiology
Acute rapid progressive & highly fatal viral disease of CNS
caused by Lyssavirus type 1.
Zoonotic disease of warm blooded animals (dogs, cats ,
bats, racoons, skunks, foxes )
Transmitted to man by bite of rabid animal.
Non-bite exposures : aerosols; generated in labs , caves
with bats , corneal transplantation.
Human to human transmission extremely rare.
Worldwide endemic canine rabies : 55,000 deaths annually
( India alone 20,000 )
Louis Pasteur and Emile Roux first developed rabies
vaccine in 1885.
3. Causative agent
Rabies virus belongs to family Rhabdoviridae , genus
Lyssavirus & serotype 1.
Bullet shaped neurotropic single stranded RNA non-
segmented antisense genome consists of 11,932
nucleotides and encodes 5 proteins.
Six other non-rabies virus species in Lyssavirus genus
have been reported to cause a clinical picture similar to
rabies.
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8. Pathogenesis
Incubation period : 20-90 days.
STAGES:
1) Virus inoculated by bite.
2) Replication in muscles: virus binds to nicotinic
acetylcholine receptors on post synaptic membranes at
NMJ.
3) Retrograde axonal transport :Spreads centripetally along
peripheral nerves towards CNS( ~ 250 mm/day) through
local dorsal root ganglion, spinal cord.
4) CNS dissemination
5) Centrifugal spread along sensory & autonomic nerves
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11. Most characteristic pathologic finding – Negri body
i. Eosinophilic cytoplasmic inclusion in neurons
composed of rabies virus proteins & viral RNA.
ii. Not observed in all cases of rabies.
iii. Commonly seen in hippocampus & cerebellum.
Basis for behavioural changes including aggressive
behaviour is not well understood.
Lack of prominent degenerative neuronal changes
has led to concept that neuronal dysfunction (rather
than neuronal death) responsible for clinical disease
in rabies.
13. Clinical Manifestations
A. Prodromal features :-
• Fever
• Malaise
• Headache
• Vomiting
• Anxiety
• Agitation
• Pain / paresthesias at the site of exposure ( in 50-
80% cases ).
15. Hydrophobia :-
Involuntary painful contractions of diaphragm ,
accessory respiratory , laryngeal muscles in response
to swallowing fluids.
Dysfunction of infected brainstem neurons that
normally inhibit inspiratory neurons near Nucleus
Ambiguus resulting in exaggerated defense reflexes
that protect respiratory tract.
Pathognomic of rabies and absent in animals.
Aerophobia :-
Same features caused by stimulation from a draft of
air.
16.
17. Presents as atypical encephalitis with relative
preservation of consciousness.
Episodes of hyper excitability followed by complete
lucidity ( as disease progress interval between them
shortens )
Progress rapidly and coma followed within a day by
death is rule unless course prolonged by supportive
measures.
Difficult to recognise late in clinical course when
progression to coma has occured.
18. B. Paralytic Rabies (20%) :-
Muscle weakness predominates.
Early & prominent flaccid muscle weakness often
in bitten extremity & spreading to produce
quadriparesis & facial weakness.
Sphincter involvement common.
Sensory involvement mild
Lacks cardinal features ( hyperexcitability ,
hydrophobia , aerophobia )
19.
20. Investigations
CSF analysis :-
i. Mild mononuclear cell pleocytosis with mildly
elevated protein
ii. Severe pleocytosis >1000 WBC/mcl unusual & search
alternate diagnosis.
iii. Rabies virus specific antibodies in CSF suggest rabies
encephalitis regardless of immunisation status.
21. RT – PCR amplification :-
Highly sensitive & specific in rabies virus detection
in fresh saliva , skin , CSF & brain tissues.
Direct Fluorescent Antibody testing :-
Highly sensitive & specific in testing rabies virus
antibodies conjugated to fluorescent dyes.
Quickly performed & applied to skin biopsies and
brain.
22. Skin biopsy :-
Obtained from nape of neck.
Demonstration of virus in cutaneous nerves at base of
hair follicles.
Corneal impressive smears – low diagnostic yield.
MRI brain – variable & non-specific.
EEG – non-specific abnormalities.
23. Differential Diagnois
Guillian Barre Syndrome :-
Paralytic rabies mimic GBS
Fever , bladder dysfunction , CSF pleocytosis favour
rabies.
Rabies Hysteria :-
Characterised by shorter incubation period , inability
to communicate , aggressive behaviour , long course
with recovery.
24. Allergic Encephalomyelitis :-
• History of rabies vaccine.
Tetanus :-
• Presence of hydrophobia , aerophobia favours rabies.
Poliomyelitis :-
• Acute onset of flaccid paralysis in one or more limbs
with decreased / absent tendon reflexes & without
sensory or cognitive loss.
25. Treatment
No established treatment.
Isolation in quiet room ( as bright light , noise , cold
draughts precipitates spasms / convulsions )
Sedatives to relieve anxiety.
Hydration.
Intensive respiratory & cardiac support
26. Prevention
Health personnel should wear face masks , gloves ,
goggles , & aprons (saliva , vomits , tears , urine or
other body fluids of rabies patient contain virus )
Persons having bruises , cut or open wounds not
entrusted to look after patient.
Pre-exposure prophylaxis.
Post exposure prophylaxis.
27. Post Exposure Prophylaxis
Local wound care ( all bite wounds/scratches washed
with soap and water ) reduces chances up to 80%.
Devitalised tissues debrided.
Tetanus prophylaxis given.
Suturing delayed( if necessary done after 24-48
hours later )
Antibiotic treatment whenever indicated.
Active immunisation by Rabies vaccine.
Passive immunisation by Human Rabies Immuno
Globulins (HRIG )
28.
29. Recommended Post Exposure Prophylaxis :-
Administration of single dose of anti-rabies serum
with course of vaccine together with local treatment of
wound is best specific prophylactic treatment after
exposure of man to rabies.
• Stop treatment if dog remains healthy or proven to be
negative for rabies by reliable lab using diagnostic
techniques.
30. Indication of AntiRabies Treatment
• If animal shows signs of rabies / dies within 10 days of
observation.
• If biting animal cannot be traced / identified.
• Unprovoked bite.
• All bites by wild animals.
• Lab tests ( Flourescent Rabies antibody test , Test for
Negri bodies in brain of biting animal ) positive for
rabies.
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32. Types of Rabies Vaccine
Nervous Tissue Vaccine
Suckling Mouse Brain Vaccine
Duck Embryo Vaccine
Purified Duck Embryo Vaccine
Human Diploid Cell Vaccine
2nd Gen. Tissue culture Vaccine
a. Purified Chick Embryo Cell Vaccine
b. Purified Vero Cell Vaccine
In Govt. Of India stopped producing Neural Tissue Vaccine
since 2004.
Purified Duck Embryo Vaccine & Purified Chick Embryo
Vaccine available in India.
Cell Culture
Vaccine
33. Intra Muscular Regimen ( 0-3-7-14-
28)
Standard WHO Intra Muscular Regimen ( Essen
Schedule ) :-
i) 1ml doses given IM deltoid ( children antero-lateral
aspect of thigh )
ii) Five doses of vaccine should be given on
day 0 , 3 , 7 , 14 , 28.
34. Intra Dermal Schedule (0-3-7-28-
90)
Two site Intra Dermal Vaccination has been used in
India , endorsed by WHO Expert Committee on
rabies.
0.2ml doses given at each two sites on day 0 , 3 , 7 &
one site on days 28 , 90.
Intradermal dose is 1/5 th of intramuscular dose.
35. Rabies Vaccine
In previously unvaccinated , five IM doses
day 0 , 3 , 7 , 14 , 28.
In previously immunised , two booster doses day 0 , 3
given.
In pregnancy , not a contraindication for
immunisation.
Glucocorticoids / Immunosuppressant , should not be
administered during PEP unless essential.
36. Local reactions :- pain , erythema , edema , pruritus ,
mild systemic reactions (fever , myalgias , headache ,
nausea )
Anti-inflammatory & anti-pyretics may be used.
Immunisation should not be discontinued.
Systemic allergic reactions uncommon but anaphylaxis
rarely occur ( treated with epinephrine and
antihistamines )
Risk of rabies development should be completely
considered before decision is made to discontinue
vaccine because of adverse reaction.
37. HRIG
Human RIG is purified from serum of hyperimmunised
human donors.
Single administration at site of bite (virus present at bite
site during most of the incubation period)
Given in < 7 days after 1st vaccine dose.
(After day 7 , endogenous antibodies produced & passive
immunisation may be counterproductive)
Human RIG much tolerated than Equine derived.
Doesn’t require prior sensitivity testing.
Local pain & low grade fever may occur.
Severe adverse effects are uncommon.
38. i) Previously unvaccinated :-
HRIG 20 I/U (40 I/U purified Equine RIG after test
dose if human RIG not available ) should be
infiltrated at site of bite.
Remaining given IM ( at distant site from bite )
If mucous membrane involved entire dose should
be given IM.
If multiple & large wounds RIG should diluted to
obtain sufficient volume for adequate infiltration.
ii) Previously immunised :-
RIG should not be given.
39. Pre Exposure Prophylaxis
• For people with occupational / recreational risk of
rabies including travellers to rabies endemic areas have
primary schedule consists of three doses 0 , 7 , 21/28
day.
After one month if virus neutralising titre <0.5 IU/ml ,
booster dose given.
Further at intervals of two years as long as exposed
person at risk.
40.
41. Rabies in dogs
Incubation period : 3 – 8 weeks
Manifests in two forms
Furious Rabies :-
Mad dog syndrome characterised by change in
behaviour , run away from home , wander aimlessly ,
biting humans & animals , excessive salivation from angle
of mouth , progressive paralysis leading to coma and
death.
• Dumb Rabies :-
Paralytic predominantly , dog withdraws itself from
being disturbed , elapses into stage of sleepiness and dies.
42. Summary
Almost uniformly fatal disease.
Nearly preventable with appropriate PEP during early
incubation period.
Most patients with rabies die within days of onset of
illness despite aggressive care in critical care unit.
Rabies vaccine & RIG never given at same site or same
syringe.
Rabies has no cure but can be prevented.
43. World’s Rabies Day- September 28
• Co-operative global
event planned to
reduce suffering
from rabies.
•This day celebrates
Dr Louis Pastuer ‘s
vision of rabies free
world.