Dr.Kaveh Haratian
Medical Virologist,PhD
Department of Microbiology and Immunology-
ABZUMS
1
 It is an acute
 Highly fatal viral disease : of CNS
Transmitted to man by:
 Bites
OR
 Licks of rabid animals
2
3
Agent Factors:
Agent
(LYSSAVIRUS type I) Rhabdoviridae
type I
4
Bullet shaped
5
 History of Rabies Virus
 Man described the disease in 2300 B.C.
 The origin “rabhas”, meaning “to do
violence” comes from ancient Indian
Sanskrit dating 3000 B.C.
 Rage, frenzy
6
History of the Rabies Virus
•Outbreak of rabies in Europe
in 20th century spawned the
Vampire myth- linked to bats.
•Rabies epidemic in 13th
century France may have
spurred Werewolf myth as
well- linked to wolves.
•Rabies is commonly spread
by bats and wolves and other
wildlife like foxes
7
History of the Rabies Virus
 Since Roman times, man established
the link between the infectivity of a
rabid dogs saliva and the spread of
the disease.
 Because there is no cure for rabies,
those that had been bitten by a rabid
dog would commonly commit suicide
to avoid the painful death that would
inevitably follow.
8
History of the Rabies Virus
 Louis Pasteur was the first person to
diagnose that rabies targeted the
CNS.
 Also determined that nervous tissue
of an infected human or animal also
contained the virus.
 In 1890 created the rabies vaccine
and saved 9 year old Joseph Meister
after he had been bit by a rabid dog.
9
Epidemiology
87 countries contain Rabies, but
more cases are reported in Asia.
In Indo-Pakistan rabies is a major
public health problem mainly due
to presence of a large number of
stray dogs.
More than 30,000 people died of
Rabies every year in Asia. Every
year 10 million people require
treatment and protection from
Rabies which is great Financial
loss.
10
Estimated Annual Human
Rabies Cases 2005
 North America 4 - 8
 Europe 10 - 20
 Latin America 200 - 400
 Africa 500 - 1,000
 Asia 30,000 - 40,000
11
FREE RABIES ZONE:
 Australia
China
Island
Ireland
Japan
New Zealand
etc.
12
Types of Rabies virus
STREET VIRUS
Definition: the virus
recovered from
naturally occurring
cases of rabies is
called “street virus”
Sources: it is naturally
occurring virus. It is
found in saliva of
infected animal.
(continue)
FIXED VIRUS
Definition: the virus
which has a short,
fixed and reproducible
incubation period is
called “fixed virus
Sources: it is prepared
by repeated culture in
brain of rabbit such
that its I.P. is reduced
& fixed
13
Features
1. It produces Negri
bodies
2. Incubation period is
long i.e. 20 to 60
days
3. It is pathogenic for
all mammals
4. Cannot be used for
preparation of
vaccine
Features
1. It does not form Negri
bodies
2. Incubation period is
constant between 4-6
days
3. It can pathogenic for
humans under certain
conditions
4. Is used for preparation
of antirabies vaccine
14
RESERVOIR OF INFECTION
1) URBAN RABIES:
From Dogs and
cats.
15
2) WILD LIFE RABIES:
From jackals and foxes.
16
3) BAT RABIES:
Vampire bats which live on the blood of
animals and men. These are one of the main causes
of the death of bovine, around 0.5 to 1 million per
year.
17
Source of Infection
 Saliva of Rabid animal
18
Host Factors
 All warm blooded animals including
man.
 Rabies in man is a dead-end
infection.
19
Mode of Transmission
1. ANIMAL BITES
2. LICKS
3. AEROSOL
4. PERSON TO PERSON
20
INCUBATION PERIOD:
 normally it is 3 - 8 wks
may be short that is 4 days
 or may be prolonged for years.
21
PATHOGENESIS
Replicate in muscle .. attach
to nerve ending .. CNS ..
than centrifugally in
peripheral nerve to many
tissue including Skeletal
muscle, heart, adrenal gland
and skin .. salivary gland
22
CLINICAL PICTURE
1. Prodromal symptoms
Headache, malaise, sore throat,
low fever, pain at the site of bite
2. Excitation Symptoms
sensory sys: involvement
Aero-hydro phobia, excitation of N.S.
Motor sys: involvement:
increase reflexes, muscle spasm,
Symp involvement: dilatation of Pupils. increase perspiration,
salivation, and Lacrimation,
Mental changes: fear of death, anger, irritability and depression
23
Hydrophobia ( Fear of water)
sight or sound of water may
produce spasm
the duration of illness is 2-3 days
may be prolonged to 5-6 days
Stage of paralysis & coma
DEATH / Recovery
24
25
(summary)
 The rabies infection and the symptoms
that accompany it is classified by five
stages:
1. Incubation (1-3 months)
2. Prodromal, where first symptoms
occur
3. Acute neurological phase
4. Coma
5. Death or recovery
26
DIAGNOSIS
1. History
2. Sign and symptom
3. Examination
4. Detection of Antigen by taking Skin
Biopsy using Immunofluorescence
5. by virus isolation from Saliva &
other secretions.
27
Control Measures
 Notification
 Isolation
 Disinfection
 Immunization
28
Prevention of human rabies
post Exposure prophylaxis
1. General consideration:- Aim is to neutralize virus before entering
CNS
2. LOCAL WOUND TREATMENT
a, Cleansing of wound(soap & water)
b, Chemical treatment:
 Either Alcohol 400-700 ml /liter
 Tincture Iodine
 No more treatment with Ammonium
compound
 No Carbolic acid and Nitric acid as it leave
very bad scar
29
c, Suturing
d, Anti Rabies Serum
e, Antibiotic
f, Observe the animal for 10 days
30
 Immunization
1,NERVOUS TISSUE
VACCINE (NTV)
2, Human diploid cell vaccine
(HDCV)
31
Vaccines for immunization
Definition:
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 32
Nervous Tissue
vaccine
Duck embryo
vaccine
Cell culture
vaccine
preparation From fixed virus grown in
brain of sheep or other
animals
potency Low or variable Eliminate Neuroparalytic
factors
More potent
more safer
Doses Large doses are required Fewer doses of small
volume
Side effects Severe & fatal reactions Allergic risks Fewer
Uses Exposed subjects Used in UK,USA in past 1, (HDC) safe, potent
Pre & post
expos:Immunization
Suckling mouse brain V
Devoid of Neuroparalytic
effect
Used in Latin America
Improvement over adult
animal nervous tissue V
Now purified DEV
developed
Improvement over adult
animal nervous tissue
Not available in India &
Pakistan
2Tissue culture 2nd G
(Non-human)
Potent, low cost
WHO recommendatio
33
Type of Vaccine
NERVOUS TISSUE VACCINE (NTV)
a. Derived from adult animal
nervous tissue eg. Sheep
b. Derived from suckling mouse
brain
Type: Killed viral vaccine
Dose: 2.5 ml S/C (Ant. Abdominal
wall)
Schedule: 14 doses
34
Type of Vaccine (conti)
Duck Embryo Vaccine (DEV)
Type:Killed viral vaccine
Dose:1 ml S/C ( Ant. Abdominal
wall)
Schedule: 14 doses OD
not available in Pakistan
35
Type of Vaccine (cont)
CELL CULTURE VACCINES
a. Human diploid cell vaccine
(HDCV)
b. Second generation tissue
culture vaccine (non- Human)
Type: Killed viral vaccine
Dose: 1 ml IM
Schedule: on 0, 3, 7, 14, 28 day,
booster on day 90
36
PASSIVE IMMUNIZATION
 Horse Anti Rabies serum: 40 iu /
kg at 0 day
 Human rabies immunoglobin
(HRIG): 20 iu / kg around the
wound and rest in IM on 0 day
 Booster doses are essential
whenever anti rabies serum is
given with the vaccine
37
Classification Of Exposures
1. Class I (slight Risk) 07 injection
a. Licks on healthy unbroken skin.
b. Scratches without oozing of blood.
2. Class II (Moderate Risk) according to the Schedule plus one
booster dose after 3 week
a. Licks on fresh cuts.
b. Scratches with oozing of blood.
c. All bites except those on head, neck, face, palms and fingers.
d. Minor wounds less than 5 in number.
3. Class III (Severe Risk) according to the Schedule plus Two
booster dose one after one week and another 2 week
a. all bites or scratches with oozing of blood on neck, head,
face, palms and fingers.
b. Lacerated wounds on any part of the body.
c. Multiple wounds 5 or more in number.
d. Bites from wild animals.
38
IMMUNITY
 Duration of Immunity is up to 6
months
 If again bite by rabid animal than
dose according to blood titre
if more than 0.5 i.u. / ml than only
two dose 0, 3 day
if less than 0.5 i.u. / ml than 0, 3, 7
day
39
General measures
 Regist:,licensing & taxation of dog.
 Muzzling of dogs
 Yearly mass vaccination of dog
 Destruction of stray dogs
 Facilities for diagnosis of rabies in dogs
 Destruction of wildlife where the animals
are known to be the reservoir of infection.
 Publicity
40
Pre-Exposure Prophylaxis
 It is done in persons who have high risk of
repeated exposures.
Animal Handlers
Wildlife officers
Veterinarians
Lab: staff working with rabies virus
Protected by:- Cell-culture vaccine 1ml I/M
OR 0.1ml I/D ( 0,7& 28day)
Post-exposure R/ of persons
(who have been vaccinated previously)
HDC vaccine (1ml I/M 0,3 & 7 day 0
41
Rabies in Dogs
 Incubation period: 3-8 wks.
 Clinical features: Rabies in dogs may manifest
itself in two forms.
a. Furious Rabies.
This the typical mad-dog syndrome characterized by.
i. change in behavior.
ii. Tendency to run away from home, wander aimlessly
and biting humans and animals.
iii. Change in voice due to paralisis of laryngeal muscles.
iv. Excessive salivation & foaming at the angle of the
mouth.
v. Paralysis of the whole body leading to coma & death.
42
b. Dumb Rabies.
i. The excitative or irrigative stage is
lacking.
ii. The disease is predominantly paralytic.
iii. Dog withdraws itself from being seen
or disturbed.
iv. It elapses into a stage of sleepiness
and dies in about 3 days.
43
44

Rabies, Rhabdoviridae

  • 1.
    Dr.Kaveh Haratian Medical Virologist,PhD Departmentof Microbiology and Immunology- ABZUMS 1
  • 2.
     It isan acute  Highly fatal viral disease : of CNS Transmitted to man by:  Bites OR  Licks of rabid animals 2
  • 3.
  • 4.
    Agent Factors: Agent (LYSSAVIRUS typeI) Rhabdoviridae type I 4
  • 5.
  • 6.
     History ofRabies Virus  Man described the disease in 2300 B.C.  The origin “rabhas”, meaning “to do violence” comes from ancient Indian Sanskrit dating 3000 B.C.  Rage, frenzy 6
  • 7.
    History of theRabies Virus •Outbreak of rabies in Europe in 20th century spawned the Vampire myth- linked to bats. •Rabies epidemic in 13th century France may have spurred Werewolf myth as well- linked to wolves. •Rabies is commonly spread by bats and wolves and other wildlife like foxes 7
  • 8.
    History of theRabies Virus  Since Roman times, man established the link between the infectivity of a rabid dogs saliva and the spread of the disease.  Because there is no cure for rabies, those that had been bitten by a rabid dog would commonly commit suicide to avoid the painful death that would inevitably follow. 8
  • 9.
    History of theRabies Virus  Louis Pasteur was the first person to diagnose that rabies targeted the CNS.  Also determined that nervous tissue of an infected human or animal also contained the virus.  In 1890 created the rabies vaccine and saved 9 year old Joseph Meister after he had been bit by a rabid dog. 9
  • 10.
    Epidemiology 87 countries containRabies, but more cases are reported in Asia. In Indo-Pakistan rabies is a major public health problem mainly due to presence of a large number of stray dogs. More than 30,000 people died of Rabies every year in Asia. Every year 10 million people require treatment and protection from Rabies which is great Financial loss. 10
  • 11.
    Estimated Annual Human RabiesCases 2005  North America 4 - 8  Europe 10 - 20  Latin America 200 - 400  Africa 500 - 1,000  Asia 30,000 - 40,000 11
  • 12.
    FREE RABIES ZONE: Australia China Island Ireland Japan New Zealand etc. 12
  • 13.
    Types of Rabiesvirus STREET VIRUS Definition: the virus recovered from naturally occurring cases of rabies is called “street virus” Sources: it is naturally occurring virus. It is found in saliva of infected animal. (continue) FIXED VIRUS Definition: the virus which has a short, fixed and reproducible incubation period is called “fixed virus Sources: it is prepared by repeated culture in brain of rabbit such that its I.P. is reduced & fixed 13
  • 14.
    Features 1. It producesNegri bodies 2. Incubation period is long i.e. 20 to 60 days 3. It is pathogenic for all mammals 4. Cannot be used for preparation of vaccine Features 1. It does not form Negri bodies 2. Incubation period is constant between 4-6 days 3. It can pathogenic for humans under certain conditions 4. Is used for preparation of antirabies vaccine 14
  • 15.
    RESERVOIR OF INFECTION 1)URBAN RABIES: From Dogs and cats. 15
  • 16.
    2) WILD LIFERABIES: From jackals and foxes. 16
  • 17.
    3) BAT RABIES: Vampirebats which live on the blood of animals and men. These are one of the main causes of the death of bovine, around 0.5 to 1 million per year. 17
  • 18.
    Source of Infection Saliva of Rabid animal 18
  • 19.
    Host Factors  Allwarm blooded animals including man.  Rabies in man is a dead-end infection. 19
  • 20.
    Mode of Transmission 1.ANIMAL BITES 2. LICKS 3. AEROSOL 4. PERSON TO PERSON 20
  • 21.
    INCUBATION PERIOD:  normallyit is 3 - 8 wks may be short that is 4 days  or may be prolonged for years. 21
  • 22.
    PATHOGENESIS Replicate in muscle.. attach to nerve ending .. CNS .. than centrifugally in peripheral nerve to many tissue including Skeletal muscle, heart, adrenal gland and skin .. salivary gland 22
  • 23.
    CLINICAL PICTURE 1. Prodromalsymptoms Headache, malaise, sore throat, low fever, pain at the site of bite 2. Excitation Symptoms sensory sys: involvement Aero-hydro phobia, excitation of N.S. Motor sys: involvement: increase reflexes, muscle spasm, Symp involvement: dilatation of Pupils. increase perspiration, salivation, and Lacrimation, Mental changes: fear of death, anger, irritability and depression 23
  • 24.
    Hydrophobia ( Fearof water) sight or sound of water may produce spasm the duration of illness is 2-3 days may be prolonged to 5-6 days Stage of paralysis & coma DEATH / Recovery 24
  • 25.
  • 26.
    (summary)  The rabiesinfection and the symptoms that accompany it is classified by five stages: 1. Incubation (1-3 months) 2. Prodromal, where first symptoms occur 3. Acute neurological phase 4. Coma 5. Death or recovery 26
  • 27.
    DIAGNOSIS 1. History 2. Signand symptom 3. Examination 4. Detection of Antigen by taking Skin Biopsy using Immunofluorescence 5. by virus isolation from Saliva & other secretions. 27
  • 28.
    Control Measures  Notification Isolation  Disinfection  Immunization 28
  • 29.
    Prevention of humanrabies post Exposure prophylaxis 1. General consideration:- Aim is to neutralize virus before entering CNS 2. LOCAL WOUND TREATMENT a, Cleansing of wound(soap & water) b, Chemical treatment:  Either Alcohol 400-700 ml /liter  Tincture Iodine  No more treatment with Ammonium compound  No Carbolic acid and Nitric acid as it leave very bad scar 29
  • 30.
    c, Suturing d, AntiRabies Serum e, Antibiotic f, Observe the animal for 10 days 30
  • 31.
     Immunization 1,NERVOUS TISSUE VACCINE(NTV) 2, Human diploid cell vaccine (HDCV) 31
  • 32.
    Vaccines for immunization Definition: itis 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 32
  • 33.
    Nervous Tissue vaccine Duck embryo vaccine Cellculture vaccine preparation From fixed virus grown in brain of sheep or other animals potency Low or variable Eliminate Neuroparalytic factors More potent more safer Doses Large doses are required Fewer doses of small volume Side effects Severe & fatal reactions Allergic risks Fewer Uses Exposed subjects Used in UK,USA in past 1, (HDC) safe, potent Pre & post expos:Immunization Suckling mouse brain V Devoid of Neuroparalytic effect Used in Latin America Improvement over adult animal nervous tissue V Now purified DEV developed Improvement over adult animal nervous tissue Not available in India & Pakistan 2Tissue culture 2nd G (Non-human) Potent, low cost WHO recommendatio 33
  • 34.
    Type of Vaccine NERVOUSTISSUE VACCINE (NTV) a. Derived from adult animal nervous tissue eg. Sheep b. Derived from suckling mouse brain Type: Killed viral vaccine Dose: 2.5 ml S/C (Ant. Abdominal wall) Schedule: 14 doses 34
  • 35.
    Type of Vaccine(conti) Duck Embryo Vaccine (DEV) Type:Killed viral vaccine Dose:1 ml S/C ( Ant. Abdominal wall) Schedule: 14 doses OD not available in Pakistan 35
  • 36.
    Type of Vaccine(cont) CELL CULTURE VACCINES a. Human diploid cell vaccine (HDCV) b. Second generation tissue culture vaccine (non- Human) Type: Killed viral vaccine Dose: 1 ml IM Schedule: on 0, 3, 7, 14, 28 day, booster on day 90 36
  • 37.
    PASSIVE IMMUNIZATION  HorseAnti Rabies serum: 40 iu / kg at 0 day  Human rabies immunoglobin (HRIG): 20 iu / kg around the wound and rest in IM on 0 day  Booster doses are essential whenever anti rabies serum is given with the vaccine 37
  • 38.
    Classification Of Exposures 1.Class I (slight Risk) 07 injection a. Licks on healthy unbroken skin. b. Scratches without oozing of blood. 2. Class II (Moderate Risk) according to the Schedule plus one booster dose after 3 week a. Licks on fresh cuts. b. Scratches with oozing of blood. c. All bites except those on head, neck, face, palms and fingers. d. Minor wounds less than 5 in number. 3. Class III (Severe Risk) according to the Schedule plus Two booster dose one after one week and another 2 week a. all bites or scratches with oozing of blood on neck, head, face, palms and fingers. b. Lacerated wounds on any part of the body. c. Multiple wounds 5 or more in number. d. Bites from wild animals. 38
  • 39.
    IMMUNITY  Duration ofImmunity is up to 6 months  If again bite by rabid animal than dose according to blood titre if more than 0.5 i.u. / ml than only two dose 0, 3 day if less than 0.5 i.u. / ml than 0, 3, 7 day 39
  • 40.
    General measures  Regist:,licensing& taxation of dog.  Muzzling of dogs  Yearly mass vaccination of dog  Destruction of stray dogs  Facilities for diagnosis of rabies in dogs  Destruction of wildlife where the animals are known to be the reservoir of infection.  Publicity 40
  • 41.
    Pre-Exposure Prophylaxis  Itis done in persons who have high risk of repeated exposures. Animal Handlers Wildlife officers Veterinarians Lab: staff working with rabies virus Protected by:- Cell-culture vaccine 1ml I/M OR 0.1ml I/D ( 0,7& 28day) Post-exposure R/ of persons (who have been vaccinated previously) HDC vaccine (1ml I/M 0,3 & 7 day 0 41
  • 42.
    Rabies in Dogs Incubation period: 3-8 wks.  Clinical features: Rabies in dogs may manifest itself in two forms. a. Furious Rabies. This the typical mad-dog syndrome characterized by. i. change in behavior. ii. Tendency to run away from home, wander aimlessly and biting humans and animals. iii. Change in voice due to paralisis of laryngeal muscles. iv. Excessive salivation & foaming at the angle of the mouth. v. Paralysis of the whole body leading to coma & death. 42
  • 43.
    b. Dumb Rabies. i.The excitative or irrigative stage is lacking. ii. The disease is predominantly paralytic. iii. Dog withdraws itself from being seen or disturbed. iv. It elapses into a stage of sleepiness and dies in about 3 days. 43
  • 44.