This particular presentation includes slide on basic virology about rabies virus, pathogenesis of rabies and it's management specially emphasized on guide of pre and post exposure vaccination.

1. RABIES
Dr. Tarek Mahbub Khan

2. RABI
ES
TLO:
The virus
Animal susceptibility
Street and fixed virus
Replication
Pathogenesis of rabies
encephalitis
Clinical features of rabies
Outline of lab diagnosis
Prevention: Vaccines

3. Salient features of Rabies
 Rabies is an acute infection of the CNS
 Rabies is caused by rabies virus (Rabdoviridiae
family)
 Transmission: Through saliva of infected animal
 Mode of transmission: Animal bites, licks on
abrasion
 Incubation period: 4 to 8 weeks (9-90 days)
 Variation of incubation period: depends on site of
bite
 Human is dead end host

4.  Family: Rhabdoviridae
 Genus: Lyssavirus
 Shape: Rod or bullet shaped
 Nucleocapsid: Helical
 Genome: Single stranded RNA with negative
polarity, hence posses their own RNA
depended RNA polymerase. Replicates in cell
cytoplasm
 Envelope: contains virus encoded
glycoproteins
The Virus

5. Diagrammatic structure of the
virus

6. Antigenic properties of the virus
 Single serotype
 Antigenically different strains are prevalent in
various geographical location due to:
 Epitopes difference in nucleoprotein
 Epitopes difference in surface glycoprotein

7. The virus susceptibility to
environmental factors
 Heat: 500 C for 1 hour
 Ultraviolet light
 Inactivated by CO2 (e.g., dry ice)
 Chemicals: Ether, alcohol, detergents, trypsin
 Extreme of pH

8. Animal susceptibility
VERY HIGH HIGH MODERATE LOW
Foxes,
Jackals,
Wolves,
Cotton rats
Hamster,
Cat, Bats,
Rabbit, Cattle
Dogs, Sheep,
Goats,
Horse, non-
human
primates
Opossums

9. Shunk and Raccoon

10. Hamster and Opossum

11. Street virus versus Fixed virus
STREET VIRUS FIXED VIRUS
Freshly isolated from the
infected samples
Propagated in serial
passage in the rabbit brain
Variable incubation period
(21-60 days)
Fixed incubation period
(varies between 5-10 days
Inclusion bodies are
commonly formed
Not commonly formed

12. STREET VIRUS FIXED VIRUS
Wide host range Host range becomes
diminished
Extra-neuronal multiplication
occurs
Extra-neuronal multiplication
does not occur
Can not be used in vaccine Used in vaccine
Street virus versus Fixed virus

13. Replication
BINDS WITH Ach-Choline
receptor
RNA-RNA pol transcribe
mRNA
Five virion proteins
Replications: RNA(-)--RNA(+)---
RNA(-)
Assemble and release by
budding
Endosomal fusion and
uncoating

14. Rabies encephalitis
Viral entry: Initial multiplication in the muscles and
connective tissues
Retrograde neuronal
transmission
Reach CNS:
Encephalomyelitis
Spread through peripheral
nerves
Muscles of
pharynx
Salivary
gland
Salivation Hydrophobia
Pancreas,
Kidney
Heart, Retina
and cornea

15. Pathogenesisof
Rabies

16. Pathology
 Neuronal death and deyelination
 Brain edema
 Vascular congestion
 Accumulation of inflammatory cells
(lymphocytes)
 Presence of eosinophilic, cytoplasmic
inclusion body

17. Negri body & Perivascular infiltration of
lymphocytes

18. Susceptibility to infection and
incubation period depends on:
 Host factors:
 Age, genetic configuration, immune status,
degree of laceration, site of bite
 Viral factors:
 Viral strain
 Amount of inoculum

19.  Average incubation period:
 1-3 months in human
 Shorter among children than adults
 Prodromal period(2-10 days)
 Anorexia, nausea, sore throat, photophobia and
change in the sensation of skin at the bite site
Clinical presentation

20.  Acute neurological phase (2-7 days)
 Occurs 80% of the cases and is ‘Furious’ form
 Nervousness, hallucination, bizarre behavior
 Increase sympathetic activity:
 Lacrimation pupillary dilatation, salivation
 Hydrophobia: Due to painful spasm of throat
muscles
 Aerophobia: breathing difficulty against blowing
air
Clinical presentation

21.  Neurological deficit(‘dumb’):
 Involves spinal cord
 Ascending paralysis
 Coma
Clinical presentation

22. Laboratory diagnosis
A. SPECIMEN
 HUMAN:
 Skin biopsy from hair line
 Corneal and brain tissue impression
 CSF and blood
 Saliva
 ANIMAL: Brain biopsy of dead animal

23. Laboratory diagnosis
 MICROSCOPY: of skin biopsy and corneal smear
 Rabies antigens by IF method
 Negri body by giemsa stain
 SEROLOGY: Detects viral antibody
 Serum antibodies are detected by IF and Nt test
 Vaccination induces antibody in serum but not in
CSF

24.  Definitive diagnosis in brain and spinal cord
 STRUCTURE:
 Shape: Spherical and sharply demarcated
 Size: 2-10 µm
 Internal structure: Basophilic granules in
eosinophilic matrix
 Contents: Sub-viral particles-viral nucleocapsids
Laboratory diagnosis (Negri
body)

25.  VIRAL CULTURE and ISOLATION
 Infected tissue material is inoculated into the mice
brain or hamster and mouse cell line
 Viral growth is identified by Negri body, IF
Laboratory diagnosis

26.  ANIMAL OBSERVATION:
 All suspected animals should be sacrificed to
recover the virus from the brain tissue
 1O days observation for otherwise apparently
healthy animals
Laboratory diagnosis

27. Management (Treatment)
 ESTABLISHED CASE
 Anti-Rabies serum( Immunoglobulin): high dose
 Anti-convulsant and sedatives
 Antibiotics: to prevent bacterial wound infection
 Parenteral nutrition

28. Management (Vaccination)
 PRE-EXPOSURE PROPHYLAXIS: Day 0,7,21 or 28
 Booster dose may need to maintain the antibody
titer of 1:5
 POSTEXPOSURE PROPHYLAXIS: Day 0,3,7,14
and 28
 Wound cleaning with soup and water, DO NOT
STICH
 Anti rabies Immunoglobulin and vaccine
 Tetanus prophylaxis

29.  CATEGORY I:
 Touching or feeding animals, licking of intact
skin
 CATEGORY II:
 Nibbling of uncovered skin, minor scratch,
abrasions without bleeding, licks on broken
skin
 CATEGORY III:
 Single or multiple transdermal bites or
scratches, contamination of mucous
membrane with saliva, bites of bat
Types of exposures

30. Management according to category
 CATEGORY I:
 No treatment is required
 CATEGORY II:
 Only vaccination is required
 CATEGORY III:
 Vaccination and Immunoglobulin are required
 Intramuscular administration of 1ml or 0.5 ml
HDCV preferably in deltoid region or
anterolateral aspect of thigh (in children)

31. Vaccine Candidate
 Preexposure:
 Rabies virus contacts: Research and laboratory
workers
 Rabid animal contacts: Veterinarians, zoo
keepers
 Postexposure: depends on
 Nature of biting animal
 Provocative or unprovocative bite
 Severity of the bite
 Availability of the animal

32. Types of vaccines
 Human diploid cell vaccine (HDCV):
 Virus grown in MRC-5 human diploid cell line
 Virus is inactivated by β-propiolactone
 Purified chick embryo cell vaccine(PCEC):
 Grows in chicken fibroblast
 Inactivated by β-propiolactone
 Duck embryo vaccine
 Nerve tissue vaccine: causes allergic
encephalomyelitis

33. REFERENCES
 Jawetz, Melnick, Adelberg. Medical Microbiology. 25th
ed. Lange publication; 2010.
 Kenneth J.R, C. George Ray, editors. Sherris Medical
Microbiology.4th edition. McGraw-Hill, Inc; 2004.
 Alan L. Rothman. Current topics in Microbiology and
Immunology, vol 336: Springer-Verlag Berlin Heidelberg,
2010.
 Nipah virus infection: WHO
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Dr. Tarek/SSMC/2016 2/18/2018