all about rabies epidemiology of rabies, pathogenesis of rabies, clinical features of rabies, treatment of rabies, prevention of rabies, rabies virus, post exposure prophylaxis, rabies in dogs

1. Vishnu narayanan

2. DEFINITION
• A/c,highly fatal disease of CNS
• Caused by Lyssavirus type 1
• Zoonotic disease of warm blooded animals
• Transmitted by bites of rabid animal
• Long and variable IP with short period of
illness
• no treatment,only prevention

3. EPIDEMIOLOGY

4. Problem statement
• Enzootic as well as epizootic disease
• Occurs in more than 100 countries and territories
• Potential threat to more than 3 billion people
• Incidence --35,000-50,000deaths/Year (WHO)
20,000deaths/yr in India
24,000deaths/yr in Africa
• Age- most common in children below 15years
• Sex- 15 million people receive rabies prophylaxis
annually with majority males

6. Rabies free areas
• Australia
• New zealand
• Taiwan
• Cyprus
• Iceland
• Ireland
• Japan
• U.K.
• Islands of western pacific
• Liberian peninsula
• Finland
• Norway
• Sweden
• Andaman nicobar
• Lakshadweep

7. AGENT-RABIES VIRUS
• Rhabdovirus
• Lyssavirus-type 1
• Bullet shaped virus
• Size is 180 x 75 nm
• Has Lipoprotein envelop
• Knob like spikes
/Glycoprotein G
• M protein layer
• Genome-
unsegmented,Linear, neg
ative sense RNA

9. • Surface spikes composed
of Glycoprotein G
• Produces Pathogenicity
by binding to Acetyl
choline receptors in the
neural tissue
• Stimulate T lymphocytes
Cytotoxic effect.
• Also has hemagglutinating
activity

10. Rabies viruses are sensitive to
common Chemicals
• The virus is sensitive to
Ethanol
Iodine
Soap / Detergents
Ether, Chloroform, Acetone
Destroyed at 500 c in 1 hour
at 600 c in 5 minutes.

11. Types of Rabies virus
STREET VIRUS FIXED VIRUS
Definition: the virus Definition: the virus
recovered from which has a short, fixed
naturally occurring and reproducible
cases of rabies is called incubation period is
“street virus” called “fixed virus
Sources: it is naturally Sources: it is prepared
occurring virus. It is by repeated culture in
found in saliva of brain of rabbit such that
infected animal. its I.P. is reduced &
(continue) fixed

12. Features Features
1. It produces Negri 1. It does not form Negri
bodies bodies
2. Incubation period is 2. Incubation period is
long i.e. 20 to 60 constant between 4-6
days days
3. It is pathogenic for all 3. It can pathogenic for
mammals humans under certain
conditions
4. Cannot be used for 4. Is used for preparation of
preparation of antirabies vaccine
vaccine

13. RESERVOIR OF INFECTION
1) URBAN RABIES:
• From Dogs and
cats.
• 99% cases in
india
• A single infected
dog capable of
transmitting over
an area of 40km

14. 2)WILDLIFE RABIES
• SYLVATIC RABIES
• Unidentified reservoir of
infection
• Foxes,jackals,hynas,skunks
etc
• Enzootic in south america
by mongoose
• Transmit infection among
themselves and to dogs and
man

15. Rabid Bat eared Fox

17. 3)BAT RABIES
• Latin american countries,USA
• Vampire bats-feed on blood of
man and animals
• Found from mexico to northern
argentina
• Cause havoc to cattle population
• Not repotrted in india
• Constant source of infection to
man and animals
• Transmission by bites and
aerosols

18. Source of Infection
• Saliva of Rabid animal
• Dogs and cats-virus in
saliva 3-4 days before
clinical symptoms
• Variable in quantity

19. Carrier state
• Serological survey-anti rabies antibody in
a proportion of unvaccinated animals
• Dogs living for years with virus isolated
from saliva,yet no record of transmission
• Asymtomatic animals-unlikely to infect
man

20. Host Factors
• All warm blooded animals including man.
• Rabies in man is a dead-end infection.
• People at risk-lab workers, veteinerians,
dog handlers, hunters, etc

21. Mode of Transmission
1. Animal bites
2. Licks
3. Aerosol
4. Person to person

22. INCUBATION PERIOD:
• Normally 3 - 8 wks
• May be short that is 4 days or may be 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

24. Centripetal
transmission
Centrifugal
transmission

29. PATHOLOGICAL LESIONS IN CNS
• Mild inflammatory changes neuronal
dysfunction
• Mononuclear inflammatory inflammation
• Degenerative changes not prominent
• Neuronophagia-observed ocassionally
• Microglial nodules-BABES NODULES
• Pathognomonic lesion-NEGRI BODIES

30. • NEGRI BODIES
• EOSINOPHILIC CYTOPLASMIC INCLUSIONS in brain
neurons
• Randomly oriented rabies virus nucleocapsids
embedded in the matrix
• Seen mainly in purkinje cells of cerebellum
pyramidal cells of hippocampus
• Absence of negri bodies-not an exclusion to rabies

32. Symptoms
• Headache, fever, sore throat
• Nervousness, confusion
• Pain or tingling at the site of the bite
• Hallucinations
• Hydrophobia
• Paralysis
• Coma and death

33. Clinical Findings
• Bizarre behavior.
• Agitation
• Seizures.
• Difficulty in drinking.
• Patients will be able to eat solids
• Afraid of water - Hydrophobia.
• Spasms of Pharynx produces choking
• Death in 1 -6 days.
• Respiratory arrest / Death / Some may survive.

34. STAGES OF RABIES INFECTION
1 – Non specific prodrome
2 – Acute neurologic encephalitis
3 – Coma
4 - Death

36. DIFFERENT STAGES OF RABIES
INFECTION
D B
O A
G T
S S
VIRUS IN SALIVA INHALED AEROSOLS
VIRUS IN SALIVA
INVASION PHASE
INVASION PHASE
EXCITEMENT
PARALY
SIS
PARALY
DEATH SIS DEATH

37. 1. Non specific prodrome
 1 - 2 days  1 week
Fever, headache, sore throat
Anorexia, nausea, vomiting
Agitation, depression
Pain/tingling sensation at bitten site
Due to infection of dorsal root or cranial sensory ganglia.

38. 2 Neurologic phase

39. Encephalitic rabies
• Fever, confusion, hallucinations, combativeness,
• Muscle spasms, hyperactivity, seizures.
• Autonomic dysfunction hypersalivation,
Excessive perspiration, gooseflesh, pupillary dilation,
Priapism.
• Hyperexcitability followed by periods of complete lucidity
• Hydrophobia and aerophobia
• “Foaming at the mouth”
• Due to dysfunction of infected brainstem neurons
• Severe brainstem damage coma death

41. COMPLICATIONS OF ENCEPHALITIS
• Disturbance in water balance
• Noncardiogenic pulmonary edema
• cardiac arrhythmias
• myocarditis.

42. Paralytic rabies
• Early and prominent muscle weakness,
• Quadriparesis and facial weakness.
• Sphincter involvement is common,
• Sensory involvement is usually mild.
• Guillain-barré syndrome is a common misdiagnosis.
• Patients survive a few days longer
• Multiple-organ failure even with aggressive
supportive care.

43. Rabies can present as Grave
condition

44. Majority will succumb to Disease

45. DIAGNOSIS
1. History
2. Signs and symptoms
3. Clinical examination
4. Detection of antigen by taking skin biopsy using
immunofluorescence
5. virus isolation from saliva & other secretions.
6. CSF analysis and CT scan
7. ELISA
8. RT-PCR
9. DFA testing
10. Negri bodies

46. DIFFERENTIAL DIAGNOSIS
Other viral encephalitis
Rabies hysteria
Landry/Guillan-barre syndrome
Poliomyelitis
Allergic encephalomyelitis ( rabies vaccine )

47. TREATMENT
• No established treatment for rabies.
• Recent treatment failures of antiviral
therapy,ketamine, and therapeutic coma-milwaukee
protocol
• Expert opinion to be sought before any experimental
therapy
• A palliative approach may be appropriate for some
patients.

48. Case management
• Isolation of the patient
• Post-exposure prophylaxis
• Antianxiety drugs and sedatives
• Muscle relaxants with curare like action
• Ensure hydration and diuresis
• Cardiac and respiratory support

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

51. 1.POST-EXPOSURE PROPHYLAXIS
• To reduce viral load by elimination from the wound
• To neutrilise the virus at site of entry
• To prevent nerve infection
• To induce systemic immunity
• Includes -1.wound treatment
2.observation of the animal
3.immunization
4.advice to patient

52. Category of bites (WHO)
Category • Licks on unbroken skin
• Touching/ feeding animals
I
Category • Nibble, cuts, scratches without
oozing of blood
II
Category • Licks on mucous membrane or
broken skin
III • Bites with breach of skin, bleeding

53. Recommended Treatment
Category • None
I
Category • Local Rx of wounds
II • Anti rabies vaccine
• Local Rx of wounds
Category • Anti rabies vaccine
III • Rabies immunoglobulin

54. WOUND MANAGEMENT
Cleansing-with soap and water (minimum 10min)
punctured wound irrigated with catheters
Chemical treatment-virucidal agents-
70%alcohol, povidine iodine, tincture iodine, etc
Local adminisration of rabies antiserum
Suturing -done after 24-48hrs with antiserum locally
Antibiotics
Immunization against tetanus
Wound not to be dressed or bandaged

58. OBSERVATION OF ANIMAL
• To determine the risk of infection
• For 10 days
• Look for any abnormal behavior of animal
• If animal died, look for negri bodies
• If possible do FRA test
• If animal healthy and alive after 10 days-no treatment
• If animal cannot be observed-suspected to be rabid

59. IMMUNIZATION
INDICATIONS
1. Immediately started when a person bitten,scratched or
licked by animal
2. If animal not available for observation
3. Bites
4. If animal is suspected to be rabid
5. If the animal is confirmed rabid
6. Person drinking raw milk of rabid animal
7. If patient comes late

60. ACTIVE IMMUNIZATION
• Antirabies vaccination
• For both category 2 and 3
PASSIVE IMMUNIZATION
• Rabies immunoglobilins
• For category 3

61. ADVICE TO PATIENT
• Treatment-correctly and completely
• Avoid steroids,spicy
food,spirit,smoking,strain during treatment
period

62. Vaccines for immunization
It is fluid or dried preparation of Rabies
“Fixed” virus grown in the Neural tissue of
Rabbits,
Sheep,
Goats,
Mice or Rats
OR in embryonated duck eggs
OR in cell culture

63. Antirabies vaccines
1. Nerve tissue vaccines
2. Duck embryo vaccine
3. Modern tissue/cell culture vaccine

64. 1.Nerve tissue vaccine
a) BPL-vaccine
• Prepared by inoculating fixed virus into nervous system of
sheep,goat,rabbit,mice
• Killed on 7th or 8th day, brain removed
• 5% emulsion prepared with saline
• Virus killed by BPL
• If sheep is employed-semple vaccine
• Dosage schedule-1ml to 5ml,s/c around the umbilicus,7-10 days
• Demerits-killed vaccine
only 50%effective
slow immunity, which lasts for only 6 months
neuroparalytic reactions
• Not recommended by WHO

65. b) Suckling mouse vaccine
• Prepared by inoculating fixed virus into brain of young
suckling mice less than 9 days old
• Safer than semple vaccine
• No neuroparalysis
• Extensive use in latin america
• Not recommended by WHO
Govt of india stopped nerve tissue vaccine production
by 2004

66. 2.Duck embryo vaccine
• Flury’s vaccine
• Vaccine free of neuroparalytic disorder
• Causes allergic reactions in egg protein
sensitive individual
• Not used in india

67. 3.Cell culture vaccine
• Great advance in rabies prophylaxis
• More potent,safer,stable,effective
• Less reactogenic
• Less dose required, painless
injection, irrespective of age and sex
• Freeze dried vaccines supplied with diluent and
syringe
• Includes HDCV
PCEC-V second generation vaccines
PVRV

68. HUMAN DIPLOID CELL VACCINE
• By propogating fixed rabies virus in human
diploid fibroblast cells
• Generally safe and highly potent
• Available as liquid vaccine
• Gold standard anti rabies vaccine
• Costly

69. SECOND GENERATION VACCINES
• Purified chick embryo cell vaccine-from chick
embryo fibroblast with diluent-sterile distilled
water
• Purified vero-cell rabies vaccine-from vero cells
with sterile normal saline as diluent
• Less cost,highly potent
• WHO reference vaccine

70. DOSAGE SCHEDULES
1. INTRAMUSCULAR SCHEDULE
• 2 types
• Essen schedule
• Zagreb schedule
• Site-intramusclarly-deltoid/thigh

71. • Essen schedule
• First 3 doses to be given at correct date
• Dose-1/0.5 ml in deltoid
• Stopped after 3 doses if bitten animal remain
asymptomatic after 10 days

72. • Zagreb schedule

73. 2. INTRADERMAL SCHEDULES
A)
B)

74. Anti-rabies serum
• Equine Anti Rabies serum: 40 IU/kg
• Human rabies immunoglobin : 20 IU/kg
• Recommended dose around the wound and rest
in IM on 0 day
• Booster doses are essential whenever anti
rabies serum is given with the vaccine
• ARG-local viricidal/neutrilising effect

76. 2.PRE-EXPOSURE PROPHYLAXIS
• Done in persons who have high risk of repeated
exposures.
Animal Handlers
Wildlife officers
Veterinarians
Lab: staff working with rabies virus
• Cell-culture vaccine 1ml I/M OR
0.1ml I/D ( 0,7& 28day)
• Booster dose every 2 years

77. 3.PEP FOR PREVIOUSLY VACCINATED
PEOPLE
• If antibody titre unknown or bite severe-1ml HDC
vaccine 0,3,7 days
• If antibody titre>0.5IU/ml and bite not severe-0,3
days
• Rabies immunoglobulin not to be administerd
• if re-exposure within 1 yr of PEP-no treatment
• If re-exposure after 3 yrs-full schedule PEP

79. RABIES IN DOGS

80. • INCUBATION PERIOD:
• 3-8 wks.
• Range from 10 days to 1year
• CLINICAL FEATURES:
• Rabies in dogs may manifest itself in two forms.
• Furious rabies
• Dumb rabies

81. a. Furious rabies-
Typical mad-dog syndrome
i. Change in behavior.
ii. Running amuck.
iii. Change in voice due to paralysis of
laryngeal muscles.
iv. Excessive salivation & foaming at the
angle of the mouth.
v. Paralytic stage

82. b. Dumb rabies.
i. No excitative or irritative stage
ii. Predominantly paralytic.
iii.Dog withdraws itself from being seen or
disturbed.
iv. Elapses into a stage of sleepiness and
dies in about 3 days.

83. • DIAGNOSIS
1. Fluorescent antibody test
2. Microscopic examination
3. Mouse inoculation test
4. Corneal test

84. IMMUNIZATION OF DOGS
• Most important weapon in rabies control
• 80-90% dog popoulation-accesible for
vaccination
• Mass vaccination-effective tool
• Primary immunization-age-3 to 4 months
• Booster dose-regular interval based on type of
vaccine

85. VACCINES FOR DOGS
1. BPL inactivated nervous tissue vaccine
• 20% suspension of infected sheep brain
• Dose-5 ml
• Revaccination-after 6 months followed by every year
• Low efficacy-not recommended

86. 2. Modified live virus vaccine
• 33% chick embryo suspension infected with
modified virus
• Dose-3ml by single injection
• Booster-every 3 years
• Raksharab,Nobivac-R,Robigen,Rabisin

89. URBAN RABIES CONTROL
• Elimination of stray and ownerless dogs
• Swift mass immunization of dogs
• Registration and licensing of all domestic dogs
• Restraint of dogs in public places
• Immediate destruction of dogs and cats bitten by rabid
animals
• Quarantine for about 6 months of imported dogs
• Health education of people
• Oral vacine baits-succesful control of wildlife
rabies,particularly fox

91. RABIES CONTROL UNITS IN INDIA
• Launched by agriculture ministry of india in 6th five year
plan aiming 100%rabies free india by 13th 5 year plan
• 30 rabies control units where set up
• Overall charge-senior officer of animal husbandry dept
• Each unit-veterinary surgeon,supervisor,10 dog catchers
• Each unit provided with a diesel van, cold storage
system for vaccines, equipments for catching dogs
• Immunization and sterilization of dogs
• No merciless killing after prevention of cruelty against
animals act was implemented
• Only rabid and seriously ill dogs are killed

92. 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.