Vishnu narayanan

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

EPIDEMIOLOGY

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

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

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, negative sense RNA

• 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

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.

Types of Rabies virusSTREET 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

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

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

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

Rabid Bat eared Fox

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

Source of Infection

• Saliva of Rabid animal• Dogs and cats-virus in

saliva 3-4 days before clinical symptoms

• Variable in quantity

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

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

Mode of Transmission

1. Animal bites

2. Licks

3. Aerosol

4. Person to person

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

PATHOGEN

ESIS

Centrifugal transmission

Centripetal transmission

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

• 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

CLINICAL MANIFESTATIONS

IN MAN

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

Symptoms

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.

1 – Non specific prodrome

2 – Acute neurologic encephalitis

3 – Coma

4 - Death

STAGES OF RABIES INFECTION

DIFFERENT STAGES OF RABIES INFECTION

INVASION PHASE

VIRUS IN SALIVA

EXCITEMENT

INHALED AEROSOLS

INVASION PHASE

VIRUS IN SALIVA

DEATH DEATHPARALYSIS

PARALYSIS

DOGS

B A T S

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.

2 Neurologic phase

ENCEPHALITIC RABIES• 80%

PARALYTIC RABIES• 20%

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

COMPLICATIONS OF ENCEPHALITIS

• Disturbance in water balance

• Noncardiogenic pulmonary edema

• cardiac arrhythmias

• myocarditis.

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.

Rabies can present as Grave condition

Majority will succumb to Disease

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

DIFFERENTIAL DIAGNOSISOther viral encephalitis

Rabies hysteria

Landry/Guillan-barre syndrome

Poliomyelitis

Allergic encephalomyelitis ( rabies vaccine )

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.

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

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

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

Category of bites (WHO)

• Licks on unbroken skin• Touching/ feeding animals

Category I

• Nibble, cuts, scratches without oozing of blood

Category II

• Licks on mucous membrane or broken skin

• Bites with breach of skin, bleeding

Category III

Recommended Treatment

• NoneCategory I

• Local Rx of wounds• Anti rabies vaccine

Category II

• Local Rx of wounds• Anti rabies vaccine• Rabies immunoglobulin

Category III

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

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

IMMUNIZATION

INDICATIONS1. 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

ACTIVE IMMUNIZATION

• Antirabies vaccination• For both category 2 and 3

PASSIVE IMMUNIZATION

• Rabies immunoglobilins• For category 3

ADVICE TO PATIENT

• Treatment-correctly and completely

• Avoid steroids,spicy food,spirit,smoking,strain during treatment period

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

Antirabies vaccines

1. Nerve tissue vaccines

2. Duck embryo vaccine

3. Modern tissue/cell culture vaccine

1.Nerve tissue vaccinea) 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

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

2.Duck embryo vaccine

• Flury’s vaccine

• Vaccine free of neuroparalytic disorder

• Causes allergic reactions in egg protein sensitive individual

• Not used in india

• 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

3.Cell culture vaccine

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

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

DOSAGE SCHEDULES

1. INTRAMUSCULAR SCHEDULE• 2 types

• Essen schedule

• Zagreb schedule

• Site-intramusclarly-deltoid/thigh

• 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

Booster on 90th

day

• Zagreb schedule

2. INTRADERMAL SCHEDULES

A)

B)

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

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

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

RABIES IN DOGS

• 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

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

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.

• DIAGNOSIS1. Fluorescent antibody test

2. Microscopic examination

3. Mouse inoculation test

4. Corneal test

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

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

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

Please have us Vaccinated

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

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

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.