Rabies virus is a neurotropic virus in the Rhabdoviridae family. It is bullet-shaped and enveloped with glycoprotein spikes. It has a single-stranded RNA genome that encodes five proteins. Rabies virus is highly resistant in the environment and transmitted through bites from infected animals. It travels through peripheral nerves to the central nervous system. Clinical features include an incubation period of 1-3 months followed by neurological symptoms such as hyperactivity, paralysis, and eventually coma. Laboratory diagnosis involves virus isolation, antigen detection, antibody detection, and PCR. Prophylaxis includes vaccination both pre- and post-exposure, as well as administration of rabies immunoglobulin.

1. Rabies virus
Dr. Sshrutkirti Gupta

2. Rabiesvirus
Family-Rhabdoviridae- (Rhabdos-rod)
2 genera-Lyssavirus,vesiculovirus
Lyssavirus- (Lyssa- madness) Rabiesvirus,
Lagosbat, Makola,Duvenhage,kotankan,
Obodhiang
Vesiculovirus- Chandipura

3. Morphology
•Shape- Bullet shaped, one end round other end
concave or planer
Knob like surface projections all over the surface
except on concave end
Below the envelop has matrix (M) protein layer –
may project out as bleb from concave end
•Size- length varies
•Enveloped RNA Virus

4. • Genome –SSRNA-unsegmented-
• Codes for 5 proteins-
• Glycoprotein (G),
• Nucleocapsid (N),
• Viral polymerase (L),
• Two smaller nonstructural proteins (NS)
(P)-MW 38000 & (M)-MW 28000

5. Peplomer/spike- Present on surface,
Glycoprotein in nature,9 nm long
Haemagglutinating Property- optimal with goose
cells at 0-40cpH 6.2
Nucleocapsid-165x50nm,30-35 coils

7. Resistance-
highly resistant against dryness, cold
Infective for many wks in cadaver.
Sensitive to lipid solvent-chloroform, acetone,
ether. Ethanol, iodine,soap,phenol,formalin,beta
propiolactone, sunlight, UV

9. • Street virus- isolated from natural human/
animal infection
• Produce fatal encephalitis- after long
incubation period1-12days
• Produced Negri bodies
• Fixed virus- obtained by several intracerebral
passage in rabbits
• More neurotropic- short incubation period
• Negri bodies usually not demonstrated

10. Pathogenesis
Highly neurotropic
•Attachment of virus to host cell after inoculation
Via glycoprotein spike
Site of attachment- nicotinic acetylcholine binding
site of plasma mem. of muscle
cell (myotubule)
•Enters peripheral nerve
(time required depends upon conc. &site of bite)

11. After sufficient multiplication cross myoneural
junction- entry in CNS
(through myelinated sensory and motor axon
terminal)
•Once enter CNS infection cannot be halted by
vaccination
Passage to CNS occurs axonally through
axoplasmic flow (12-24mm/day)until it reaches
next neuron at the level of spinal cord

12. •First symptom appears when virus multiplies in
spinal ganglion- paresthesis or pain
•Rapid dissemination of virus in CNS(200-400mm/day)
•(Initially cell- cell transfer of bare nucleocapsid
•Later free passage of virus in intracellular space)
•Development of progressive encephalitis
•Centrifugal spread of virus along peripheral
nerve throughout the body – most notably
salivary gland

13. Clinical features
Incubation period- 20 days to 3yrs.mean (1-3mo)
Route of entry- bite of rabid animal- dog
(Inhalation of virus aerosols generated in bat
caves,rarely through scratch)
Four stages- prodromal, acute neurologic , coma,
complication, death
Prodromal- Usually nonspecific symptoms-
malaise, fever chills, nausea, vomiting
diarrhea, headache, anxiety,
apprehension, irritability.(lasts for 2-10days)

14. Acute neurologic phase-
Two forms- 1. furious encephalitis (>80%)
2. paralytic (dumb) form (20%)
Furious encephalitis- Hyperactivity, disorientation,
hallucination or bizarre behavior. Hyperactivity
becomes intermittent. Signs of autonomic
instability-often prominent (hyperthermia, tachycardia,
hypertension) Hydrophobia- Attempt of drinking
follows severe spasm of pharynx, larynx.
Aerophobia-due to exaggerated respiratory
irritant reflexes
•Fever, muscle fasciculation, hyperventilation, focal convulsion

15. Paralytic (dumb) rabies- initially patient is
mentally intact. No hyperactivity as in furious type
Fever, headache frequently present
Paralysis- maximal at bitten extremity,may be
diffuse& symmetric or may be ascending type
neck stiffness
Mental condition gradually deteriorate from
confusion to disorientation, stupor & finally coma
•Last for 2-7 days
•Abrupt death due to respiratory or cardiac arrest

16. Coma- develops in about 10 days after onset of
symptoms
Lasts for few hours to month
Complications- Neurologic, Pitutary, Pulmonary
Cardiovascular, other
Death due to respiratory or cardiac failure

17. Laboratory diagnosis
Specimens-
Antimortem- Saliva, CSF, Corneal impression
smear, biopsy from neck( above
hair line) , facial skin biopsy
Postmortem- CSF, brain biopsy.
1.Isolation of virus-
a. intracerebral inoculation in the mice
observe brain tissue for inclusion bodies on
28th day

18. b. Tissue culture- cell lines used-WI 38, BHK21 --
detection of virus by immunofluorescence-
Results available in 2-4days
2. Demonstration of viral antigen-
By immunofluorescence
3. Detection of inclusion bodies-(Negri bodies)
Intracytoplasmic, oval/ round, purple-pink
characteristic basophilic inner grannules
Size- 3-27 mm, eosinophilic
Stain- Seller’s technique, immunofluorescence

19. Common- hippocampus, horns of Ammon
Purkingie’s cells of cerebellum
20% of absent
Demonstration of Antibodies
Neutralising antibodies- high titre- in CSF
appear around 6th day
2- 25 times more than serum titre
Detection of Nucleic acid- RT PCR

20. Prophylaxis-
Preexposure- lab workers
Post exposure- local treatment, vaccination,
hyperimmune sera
Local treatment- soap and water.
Treatment with cetavalon- quaternary ammonium
compound,tincture iodine, alcohol
In severe wound- antirabic serum –infiltrated
around the wound. Excision of damaged tissue
Anti-titanus& antibiotics

21. Vaccines- 2 types
Neural-
1.semple vaccine- 5% suspension of infected brain.
Inactivated by 5%Phenol
2.Beta propiolactone vaccine(BPL)- 5%
Suspension of infected brain inactivation by BPL –
mainly Indian manufacturing
3.Infant brain vaccine- sucking mice brain.Inactivation
by UV radiation, BPL or phenol

22. Vaccination Schedule
Semple vaccine BPL vaccine
Class I 2ml x 7days 2ml x 7days
Class II 5ml x 14 days 3ml x 10days
Class III 10ml x 14 days 5ml x 10days
Booster required for BPL vaccine for Class II& III
Class II- 1 dose 3wks after last 10th injection
ClassIII- 2 doses- 1 7days after 10th injection 2nd 2wks
after 1st booster

23. Non-neural-
1.Duck egg vaccine- discontinued
2.Tissue culture- fixed virus grown in HDCS,WI-38,
MRC-5Inactivation by BPL-no side
effect, highly antigenic
3. Chick embryo vaccine
a.Low egg passage- 40-50 passages- live attenuated-
use for dogs
b.High egg passage- about 180 passages- live
attenuated-use for cattle, cat
Subunit vaccine- Surface glycoprotein G – cloned-
recombinant- under trial.

24. cell culture Vaccine schedule
•Same for children and adult
•Same for all three available vaccines
•Pre-exposure-
•Three doses- 0,7,21 dose-1ml Route- IM
•Booster after 1 yr & then every 5 yr.

25. Post exposure prophylaxis
• Local treatment of wound
• Passive immunization-Hyperimmune sera
• Active immunization- vaccination
• Cell culture vaccine- 1.oml- IM- adult- deltoid
• Children-anteriolateral aspect of thigh
• Five doses-
• 0,3,7,14,30 optional 90- protective for 5 yrs- during
this period 1or2 doses required on further exposure

26. Passive immunisation- Hyperimmune serum
1.Human antirabies immunoglobulin- (HRIG)
20 IU/kg body wt- half dose is infiltrated
locally in wound and other half administered- IM
•Should not be given to individual who had prior
active immunization
2.Equine/ horse hyperimmune serum-(ERIG)
40 IU /kg body wt
risk of hypersensitivity