This presentation explains about Rabies virus and rabies.

1. Rhabdovirus
Dr Rachna Tewari
15/6/2020

2. Objectives
After studying this topic student should be able
to
1) Describe about Rabies and its epidemiology.
2) Describe about structure , pathogenicity of
Rabies virus.
3) Differentiate street and fixed virus.
4) Describe prophyllaxis and vaccines of Rabies
5/6/2020 2

3. What is Rabies
5/6/2020 3

4. History of Rabies
• Man described the disease in 2300 B.C. -
Atharvaveda .
• The word ‘Rabies’ originated from “rabhas”,
meaning “to do violence”.
• Since Roman times, man established the link
between the infectivity of a rabid dogs saliva
and the spread of the disease.
45/6/2020

5. Rabies widely spread in Asia and Africa
• Most human deaths follow
a bite from an infected dog.
Because there is no cure, those
that had been bitten by a rabid
dog would commonly commit
suicide to avoid the painful death
that would inevitably follow.
55/6/2020

6. 5/6/2020 6

7. Global Burden
A very wide distribution-
150 countries , on all continents
except for Antarctica.
Human mortality is highest in
Asia with highest incidence
and deaths reported in India
followed by Africa.
Children are at more risk in India .
5/6/2020 7

8. 8
Rabies
• Family - Rhabdovirus
• Genus - Lyssavirus.
5/6/2020 8

9. Rabies virus
• Bullet shaped virus.
• Size is 180 x 75 nm.
• Has lipoprotein
envelop.
• Knob like spikes
/Glycoprotein S
• Genome
unsegmented.
• Linear negative
sense RNA.
95/6/2020

10. Structure of the rabies virus
10
Insert figure 25.8
Structure of rabies virus
105/6/2020

11. 5/6/2020 11

12. Rerservoir
• The rabies virus can infect all
mammals.
• Mammals are warm-blooded
animals that have hair and
mammary glands to produce
milk for their babies.
• Animals like frogs, birds, and
snakes do not get rabies.
125/6/2020

13. Any mammal can get rabies.
5/6/2020 13

14. INCUBATION PERIOD
• Normally 3-8 weeks
• Maybe short that is 4 days or
maybe prolonged for years.
• Depends on site of bite
✓ Severity of bite
✓ Number of wounds
✓ Amount of virus injected
✓ Species of biting animal
✓ Protection provided by clothing
Treatment taken or not.
145/6/2020

15. Resistance
• The virus is sensitive to chemicals -
Ethanol ,Iodine , Soap / Detergents , Ether,
Chloroform, Acetone
• Temperature sensitivity -
500 c in 1 hour
600 c in 5 minutes.
155/6/2020

16. Antigenic properties
• Surface spikes composed
of Glycoprotein G.
• Produces Pathogenicity
by binding to Acetyl
choline receptors in the
neural tissue.
• Stimulate T- lymphocytes
Cytotoxic effect.
165/6/2020

17. Transmission
• Abrasions or scratches on skin.
• Mucous membrane exposed to saliva.
• Most frequently via deep penetrating bite wounds.
• Other routes.
Inhalation in bat infected caves.
Ingestion of dead /infected animal meat
Corneal transplantation
175/6/2020

18. 185/6/2020

19. Pathogenesis of Rabies
• Bite by Rabid dog or other animals.
• Viruses are carried in saliva virus deposited
on the wound site.
• If untreated 50% will develop rabies.
• Rabies can be produced by licks and corneal
transplantation.
• Virus multiply in the muscle ,connective
tissue, nerves after 48 – 72 hours.
• Penetrated nerve endings.
5/6/2020 19

20. PATHOGENESIS
Live virus→ Epidermis, Mucus membrane
Peripheral nerve
CNS ( gray matter )
Other tissue (salivary glands,…)
centripetally
centrifugally
205/6/2020

21. Rabies in man
• Know as hydrophobia (fear of water)
• Duration of disease: 2-3 days prolonged to 5-6
days (exceptional cases)
• Prodromal symptoms (3-4 days)
• Headache • Malaise • Sore throat • slight fever
• Followed by excitation and stimulation off all
parts of nervous system
✓ Sensory system
✓ Nervous system
✓ Motor system
✓ Sympathetic system
✓ Mental system
5/6/2020 21

22. Clinical Findings
• Bizarre behavior.
• Agitation
• Seizures.
• Even sight of sound disturbs the patient.
Afraid of water - Hydrophobia
• Difficulty in drinking.
• But suffer with intense thirst.
• Spasms of Pharynx produces choking
• Death in 1 -6 days.
• Respiratory arrest / Death / Some may survive.
225/6/2020

23. Category as per WHO
• Category I: touching or feeding suspect animals, but
skin is intact .
• Category II: minor scratches without bleeding from
contact, or licks on broken skin.
• Category III: one or more bites, scratches, licks on
broken skin, or other contact that breaks the skin; or
exposure to bats.
235/6/2020

24. Diagnosis of Rabies
• On basis of clinical history of bite by rabid
animal
• Characteristic signs and symptoms
• Confirmatory tests
Antigen detection by immunofluroscence (skin biopsy).
Virus isolation (saliva and other secretions)
• Immunofluroscence of corneal impression
smears proven unreliable.
245/6/2020

25. Lab Diagnosis
• The standard premortem test
fluorescent antibody test - viral antigen.
ELISA - specific antibody detection.
• The standard postmortem test
biopsy brain - examination for Negri bodies.
• PCR - emerging method.
255/6/2020

26. Negri bodies in Brain Tissue
Negri bodies
Eosinophilic, sharply outlined, round or
oval inclusion bodies (2-10 µm in
diameter)
Seen in the cytoplasm
Processes of neurons of rabid animals
after death.
265/6/2020

27. PREVENTION
❖This may be considered under 3 heads
• Post-exposure prophylaxis.
• Pre-exposure prophylaxis.
• Post-exposure treatment of persons who have
been vaccinated previously
275/6/2020

28. Preexposure vaccination
• Indicated in
Laboratory workers.
Veterinarians and
technical staff.
Animal handlers.
285/6/2020

29. Post exposure prophyllaxis
Anti Rabies vaccines are given when person is
1 Bitten
2 Scratched
3 Licked by Rabid animal.
295/6/2020

30. Post exposure Prophylaxis
1. General consideration
2. Local treatment of wound
(a) Cleansing
(b) Chemical treatment
(c) Suturing
(d) Antibiotics and anti-tetanus measure
3. Immunization
305/6/2020

31. • Tell an adult
immediately
• Wash the wound
out with soap
and water
• Call your doctor
right away
If you are bitten or scratched
315/6/2020

32. 325/6/2020

33. 335/6/2020

34. 5/6/2020 34

35. 5/6/2020 35

36. Passive Immunization
• Rabies immunioglobulins (RIG)
bind with the rabies virus, resulting in neutralization and thus
loss of infectivity of the virus.
• Two types :
Equine rabies immunoglobulin (ERIG):
40 IU/kg. Being heterologous in origin (horse), associated with
serum sickness.
Human rabies immunoglobulin (HRIG):
20 IU/kg. Devoid of side effects.
5/6/2020 36

37. Active immunization
• Rabies vaccine can be categorized into-
Neural and Nonneural vaccine.
Neural Vaccines - derived from the nervous
tissues of animals infected with the fixed rabies
virus.
Developed by Louis Pasteur and modified later.
Encephalitogenic, poorly immunogenic
They are no longer in use since 2004 and have
been replaced by non-neural vaccines.
5/6/2020 37

38. Ist Vaccine for Rabies
• Prepared by Pasteur by drying
various pieces of spinal cord
of Rabbits infected with fixed
virus.
• 1885 Joseph Meister 9 year
boy vaccinated 13 injections
were given.
• Patient saved.
385/6/2020

39. Vaccines
Semple vaccine: It is derived from infected
sheep brain, inactivated with phenol.
Beta propiolactone (BPL) vaccine: It is a
modified Semple vaccine which is inactivated
with beta propiolactone instead of phenol.
Infant mouse brain vaccines: lt is derived from
infected neural tissue of newborn mice.
395/6/2020

40. Non-neural Vaccines
1. Egg derived - Allantoic cavity.
Purified duck embryo vaccine (PDEV):
Being larger, higher yield.
Less reactogenic, less antigenic too.
It is no longer manufactured.
Live attenuated chicken embryo vaccine :
Flury strain was in use before for vaccinating animals, but
obsolete.
5/6/2020 40

41. Recombinant viral vaccine
Vaccinia virus carrying the rabies surface
glycoprotein gene has been developed.
given orally, has been successful for immunizing
animals, bur still in experimental stage for
human use.
Human diploid cell (HDC)vaccine: His derived
from 'A~-38 (human embryonic lungfibroblasr
cell line).
5/6/2020 41

42. Cell culture Vaccines in
India
Most recommended
Highly immunogenic
No neurological complicarions
1 Human diploid cell vaccine.
Derived from WI -38 (human embryonic
lung fibroblast cell line).
2 Purified chick embryo cell vaccine
prepared from chicken fibroblast cell line.
3.Purified Vero cell vaccine: prepared
from Vero cell line.
425/6/2020

43. Preexposure prophylaxis doses
435/6/2020

44. Post exposure Prophylaxis
445/6/2020

45. Human Diploid Cell
Vaccine
• Koprowsky, Viktor, Plokin
• Inactivated in Betaproprionate.
• No serious side effects.
• Human Diploid cell vaccines purified .
• Sub Unit vaccines in progress/developed.
455/6/2020

46. World's Rabies Day (on September 28)
• World Rabies Day is
a cooperative global
event planned to
reduce the suffering
from rabies. This day
celebrates Dr. Louis
Pasteur’s vision of a
rabies free world.
465/6/2020

47. Multiple Choice Questions (MCQs):
1. Anti-rabies vaccine is prepared from:
a. Street virus
b. Fixed virus c. Live virus
d. Wild virus
2. For the treatment of case of class lll dog bite, all of the
following are correct except:
a.Give immunoglobulin for passive immunity
b.Give anti-rabies vaccine
c. Immediately stitch wound under antibiotic coverage
d. Immediately wash wound with soap and water
5/6/2020 47

48. 3. All of the following rabies vaccines are
commercially available for human use except:
a. Purified chick embryo cell vaccine (PCEQ
b. Human diploid cell vaccine
c. Vero continuous cell vaccine
d. Recombinant glycoprotein
4. Rabies is identified by:
a. Guarneri bodies
b. Negri bodies
c. Cowdry A bodies
d. Paschen body
Answer, 1. b 2. C 3. d 4. b
5/6/2020 48

49. In spite of Health Education several die due to Rabies
infection in Developing world
495/6/2020