Rabies Presented by- Dr. Mohammad Rehan DNB Medicine SDMH Jaipur Moderator- Dr. Madhulika Sharma HOD (General Medicine)

1. RABIES
Dr. Mohammad Rehan

2. CONTENTS
• Epidemiology
• Causative agent
• Types of Rabies Virus
• Pathogenesis
• Clinical Manifestation
• Investigations
• Differential Diagnosis
• Treatment
• Prevention
• Summary

3. 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.

4. 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.

5. Rabies
Virus

6. Rabies
Virus

7. Types Of Rabies virus
Street Virus
• The virus recovered from naturally
occurring cases of Rabies is k/a
Street Virus
• It is naturally occurring virus. It is
found in saliva of infected animals
• It produces NEGRI BODIES
• IP is long i.e. 20-60 days
Fixed Virus
• The virus which has a short, fixed
and reproducible incubation period
is k/a Fixed Virus
• It is prepared by repeated culture in
brain of rabbit such that its IP is
reduced and fixed
• It does not produce NEGRI BODIES
• IP is constant b/w 4-6 days

8. • It is pathogenic for all mammals
• Cannot be used for preparation
of vaccines
• It can be pathogenic to humans
under certain conditions
• Can be used for preparation of Anti
Rabies vaccine

9. 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

11. Epidermis, mucus membrane
Peripheral nerves
(Centripetally)
CNS (Gray Matter)
(Centrifugally)
Other Tissues
LIVE VIRUS

12. • 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. • Negri bodies in
cytoplasm of a
cerebellar
purkinje cell

14. Clinical Manifestations
Prodromal features :-
• Fever
• Malaise
• Headache
• Vomiting
• Anxiety
• Agitation
• Pain / paresthesias at the site of exposure ( in 50-
80% cases ).

15. Encephalitic Rabies
A. Encephalitic ( 80%) :-
• Fever
• Confusion
• Hallucination
• Combativeness
• Seizures
• Autonomic dysfunction (Hypersalivation , gooseflesh , cardiac arrythmias ,
priapism)
• Hydrophobia
• Aerophobia
• Late complications ( cardiac failure , respiratory failure , multi organ failure )

16. 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.

18. • 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.

19. 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 )

21. Investigations
CSF analysis :-
Mild mononuclear cell
pleocytosis with mildly
elevated protein
Severe pleocytosis
>1000 WBC/mcl
unusual & search
alternate diagnosis.
Rabies virus specific
antibodies in CSF
suggest rabies
encephalitis regardless
of immunisation status.

22.  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.

23. 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.

24. Differential Diagnosis
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.

25. 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.

26. 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

27. Prevention

28. 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.

30. 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 )

31. • 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.

33. Do's
Physical Wash with running water Mechanical removal of virus from
the wound(s)
Chemical Wash the wound(s) with soap and water
Apply disinfectant
Inactivation of the virus
Biological Infiltrate immunoglobulin into the depth and
around the wound(s) in Category III
exposures
Neutralization of the virus
Dont's
Touch the wound(s) with bare hand
Apply irritants like soil, chilies, oil, lime, herbs, chalk, betel leaves,
• Wound
Management

38. Indication of Anti Rabies 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.

40. 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

41. 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.

42. • The currently available vaccines and regimen in India for IM
administration are described below.
Vaccines
1.Cell Culture Vaccines
• Human Diploid Cell Vaccine (HDCV), Liquid (Adsorbed), 1ml:
Produced locally in private sector
• Purified Chick Embryo Cell Vaccine (PCECV), 1ml:
Produced locally in private sector
• Purified Vero Cell Rabies Vaccine (PVRV), 0.5ml and 1ml:
Imported and also produced locally in public & private sectors
2.Purified Duck Embryo Vaccine (PDEV), 1ml:
Produced locally in private sector and is currently being
exported.

43. Intra Dermal Schedule (2-2-2-0-2)
• Updated Thai Red Cross Schedule (2-2-2-0-2)
• 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 & 28.
• Intradermal dose is 1/5 th of intramuscular dose.

44. • Currently, the following vaccines have been approved by DCGI for
use by intradermal route.
• PCECV - Rabipur, Chiron Behring, Vaccines Pvt. Ltd
• Vaxirab N, ZydusCadila
• PVRV - Verorab, Aventis Pasteur (Sanofi Pasteur) India Pvt. Ltd
• Pasteur Institute of India, Coonoor
• Abhayrab, Human Biologicals Institute
• Indirab, Bharat BiotechInternational Ltd.

45. 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.

46. • Local reactions :- pain , erythema , edema , pruritus , mild systemic
reactions (fever , myalgias , headache , nausea )
• 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.

47. 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.

48. 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.

49. 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.

51. 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.

52. Summary
• Rabies is 100% fatal but preventable
• Rabies can be caused by bite or scratch of rabid animals like dogs, cats
etc
• Do not apply chillies, mustard oils or any other irritant on the bite
wounds
• Wash the wound immediately with plenty of soap and water

53. • Do not apply dressing or do not get the wound stitched
• Consult your doctor immediately or rush to the nearest Anti Rabies
clinic
• Complete the course of Anti Rabies Vaccination as advised by your
doctor
• In severe bites, combined anti rabies serum and Vaccine therapy is
recommended
• Vaccinate your pets against rabies every year

54. 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.

56. THANK YOU