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Dr.Kaveh Haratian Medical Virologist,PhD Department of Microbiology and Immunology - ABZUMS 1

Rabies, Rhabdoviridae

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Dr.Kaveh Haratian

Medical Virologist,PhD

Department of Microbiology and Immunology-

ABZUMS

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It is an acute

Highly fatal viral disease : of CNS

Transmitted to man by:

Bites

OR

Licks of rabid animals

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Agent Factors:

Agent

(LYSSAVIRUS type I) Rhabdoviridae

type I

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Bullet shaped

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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

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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

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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.

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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.

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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.

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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

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FREE RABIES ZONE:

Australia

China

Island

Ireland

Japan

New Zealand

etc.

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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

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Features

1. It produces Negribodies

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

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RESERVOIR OF INFECTION

1) URBAN RABIES:

From Dogs and

cats.

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2) WILD LIFE RABIES: From jackals and foxes.

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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.

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Source of Infection

Saliva of Rabid animal

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Host Factors

All warm blooded animals including

man.

Rabies in man is a dead-end

infection.

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Mode of Transmission

1. ANIMAL BITES

2. LICKS

3. AEROSOL

4. PERSON TO PERSON

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INCUBATION PERIOD:

normally it is 3 - 8 wks

may be short that is 4 days

or may be prolonged for years.

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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

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CLINICAL PICTURE

1. Prodromal symptomsHeadache, malaise, sore throat, low fever, pain at the site of bite

2. Excitation Symptomssensory 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

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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

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(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

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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.

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Control Measures

Notification

Isolation

Disinfection

Immunization

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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

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c, Suturing

d, Anti Rabies Serum

e, Antibiotic

f, Observe the animal for 10 days

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Immunization

1,NERVOUS TISSUE

VACCINE (NTV)

2, Human diploid cell vaccine

(HDCV)

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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 culture32

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

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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

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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

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Type of Vaccine (cont)

CELL CULTURE VACCINESa. 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

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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

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Classification Of Exposures1. 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.

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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

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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

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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

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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.

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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.

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