RABIES An Introduction

Dangerous zoonotic disease caused by Lyssavirus type 1. One of the oldest diseases known to mankind. Known before 2300 BC. Latin word rabies originated from Sanskrit word Rabhas- to do violence. 100 % fatality rate.

RABIES VIRUS

Bullet Shaped enveloped Virus belongs to Mononegavirales order, Rhabhoviridae & Lyssavirus genus. Measures 75 nm X 100 - 300 nm. Spikes are 10 nm long & the virus moves at speed of 3 mm/ hr. Numerous spikes present on the envelope, these are made up of glycoprotein.

Glycoprotein (G) necessary for viral attachment & also induce protective antibodies.
Other viral proteins are Nucleoprotein (N), Phosphoprotein (P), matrix protein (M) & Polymerase (L)

EPIDEMIOLOGY
Human rabies is mostly confined to some countries in Asia and Africa. The Indian Sub continent account for 80% of the Global human deaths due to Rabies. No age or sex predilections (higher incidence among children
and adult Males).

RABIES Indian Scenario

Highest number of victims from India
(> 17,000 deaths annually).

At least 1 1.5 million people reported to receive PET annually. Dogs constitute nearly 96% of source of infection to human beings (Around 25 million street dogs in India). Reported from all areas except Andaman, Nicobar and Lakshadweep Islands.
APCRI 2003

MODES OF TRANSMISSION
COMMON MODES OF TRANSMISSION ANIMAL BITES: Dogs, Cats, Monkey, Horse, Sheep and
Goat.

LICKS: Licks, Scratch and Bites.

RARE MODES OF TRANSMISSION AEROSOLS: Respiratory aerosol transmission can occur. HUMAN: Man to man transmission. Corneal & Organ
transplants.
Ref:Park text book of preventive medicine - 17th Edition

RESERVOIR of INFECTION
Animals transmitting the disease in India

Frequently

Dogs & cats

RESERVOIR of INFECTION
Animals transmitting the disease in India

Sometimes
Monkeys Horses Foxes Cows & Buffaloes

Donkeys
Pigs Sheep

RESERVOIR of INFECTION
Animals transmitting the disease in India

Occasionally
Camels Mongoose Jackals Bears Other wild animals

RESERVOIR of INFECTION
Animals transmitting the disease in India

Not reported
Bats House Rats Mice Birds

INCUBATION PEROID
3 weeks - 3 months (in > 85% cases). Ranges between 4 days to 4 years. Bites on the head or face - upto 1 month. Bites on the extremities - upto 3 months.
Commonly

Brain

Spinal cord

Dorsal root ganglia

Peripheral nerves

Multiplication locally (in the muscle fibres)

PATHOGENESIS OF RABIES

Virus grows in bites the victim,central A rabid animal the peripheral nervesthe is conducted by nerves migrates throughout themotor to travels from muscle tissuethe salivary infects the sensory and tointroducing virus in gland, saliva nervousthe bite.grows, muscle brain. the central nervous system. nerves serving the thethen is shed area ofwhere it into infected muscle.in from the system, arriving at the tissue. saliva.

PATHOLOGY
Minimal Pathological changes Grossly - Brain is oedematous, congested Histopathologically - Perivascular cuffing, Gliosis Minimal Neuronal Damage (Necrosis) Presence of Negri bodies (Pathognomonic)

CLINICAL MANIFESTATION IN HUMANS

Furious Type (80%) Paralytic Type (20%)

Tingling / numbness at bite site

Non specific symptoms (Fever, malaise, headache,etc.) Hydrophobia, Aerophobia Photophobia

Tingling / numbness at bite site

Non specific symptoms (Fever, malaise, headache etc.) Ascending Paralysis Coma

Death (cardio respiratory failure)

Survival : 3 5 Days

Death (cardio respiratory failure)

Survival : 7 21 Days

WHO Guidelines for Post exposure Prophylaxis

Category Type of contact with a suspect

Recommended Treatment

or confirmed rabid domestic or

wild animal, or animal unavailable for observation

Touching or feeding of animals Licks on intact skin is available.

None, if reliable case history

II

Nibbling of uncovered skin Minor scratches or abrasions without bleeding. Licks on broken skin.

Administer vaccine immediately Stop treatment if animal remains healthy throughout an observation period of 10 days or if animal is euthanised and found to be negative by appropriate laboratory techniques.

WHO Classification of Bite

Guide for Post-Exposure Treatment (Contd)
Recommended Treatment

Category Type of contact with a suspect or confirmed rabid domestic or wild animal, or animal unavailable for observation

III Single or multiple transdermal bites or

scratches. Contamination of mucous membrane with saliva (i.e. licks)

Administer rabies immunoglobulin and vaccine immediately. Stop treatment if animal remain healthy
throughout an observation period of

10 days or if animal is killed humanely and

found to be negative for rabies by appropriate laboratory techniques.

PRINCIPLES OF TREATMENT
Wound Treatment

Anti - Rabies Immunization

Active Immunization: Administration of antirabies vaccine. Passive Immunization: Administration of immunoglobulin (in Category III exposures).
rabies

SIGNS OF RABIES in DOGS/CATS DURING 10 DAY OBSERVATION PERIOD

Any change in behaviour - undue aggression/depression. Running aimlessly and attacking others without any provocation. Becomes too drowsy and withdraws itself to a corner. Excessive Salivation. Change in voice. Refusal to feed or eating unusual objects like stones, papers, wood, metal pieces etc. Death of animal.

WOUND TREATMENT
Dos

Wash under Running tap water Soap (Preferably detergent) Disinfectants - Povidone Iodine, Spirit, household antiseptics
Note:
Suturing only if required (1 - 2 loose sutures) and only after administration of RIGs.

Donts

Apply Irritants Cauterize

POST EXPOSURE PROPHYLAXIS

Points to remember

Day 0 (D0) - Day of 1st dose of vaccine given, not the day of bite.
All modern ANTI RABIES Vaccines are equally effective and safe.

Never inject the vaccines into the gluteal region.

Interchange of vaccines acceptable in special circumstances but not to be done routinely. Reconstituted vaccine to be used immediately. Vaccine dosage is same for all age groups.

CLASSIFICATION OF RABIES VACCINES

Can be classified as

Nerve Tissue Vaccines (NTVs)

e.g. Semple vaccine

New Generation Vaccines Purified Duck Embryo Vaccine (PDEV) Purified Chick Embryo Vaccine (PCEV) Purified Vero Cell Vaccine (PVRV) Liquid Human Diploid Cell Vaccine (HDCV)

PDEV Purified Duck Embryo Vaccine

Highly purified innovative rabies vaccine developed in virus grown in specific pathogen free (SPF) duck eggs. Introduced in 1985. Millions of doses administered around the world successfully. Patented method developed with technical collaboration of world renowned Berna Biotech, Switzerland (earlier known as Swiss Serum Institute) - European leaders in sera & vaccines. Well appreciated in many international publications.

Composition of VaxiRab
The antigenic value of the reconstituted 1 ml dose is not less than 2.5 IU as per WHO recommendations

Each vial contains

Inactivated purified rabies virus Lyophilized powder Viral Strain and Inactivation Stabilizer (1 dose) Solvent Potency >2.5 IU

For one immunizing dose (1 ml) Pitman Moore strain propagated in duck embryo Beta propiolactone inactivation Gelatin, L-cystine HCl, 0.1 mg Thiomersal q.s Water for Injection

VaxiRab Unique Features

Inactivated Rabies virus - Pitman Moore strain. Highly purified viral antigen ensures high G - protein content. Intact, inactivated rabies virions for better immunogenicity. High content of N protein for enhancing protective activity of vaccine.

Trial Design
Design
Open-label, non-comparative multicentric trial in post-exposure animal bite cases

Number of subjects
150

Age Group
Between 5 - 60 years (either sex)
Category of exposure
WHO Category II or III

GMT on Day 14, 30, 90, 180 and 365

GEOMETRIC MEAN TITRE IU/mL
16.00 14.00 12.00 10.00 8.00 6.00 4.00 2.00 0.00 Day 14 Day 30 Day 90 Day 180 Day 365

15.87

10.00

9.83 5.77

1.33

0.5

Pre Exposure Prophylaxis

21/28

Post Exposure Prophylaxis

3
0

7
3

14

28

Re Exposure Prophylaxis

Note - Rabies vaccine must never be given in gluteal region.

PASSIVE IMMUNIZATION

PASSIVE IMMUNIZATION

RIG is indicated as per WHO recommendations in all category III exposures

According to the WHO grade III bite is defined as a single or multiple transdermal bites or scratches. Contamination of mucous membrane with saliva of animal i.e licks

RABIES IMMUNOGLOBULINs (RIG)

Equine antirabies immunoglubulin (ERIG) Human antirabies immunoglubulin (HRIG)

40IU/Kg 20IU/Kg

ERIG must be administered only after the Test dose

SPECIAL SITUATIONS

Severe Class III exposures, Sutured wounds Proven rabid animal exposures Exposure in immune compromised persons Pregnancy and Lactation Extremes of age

BITES IN IMMUNE COMPROMISED PERSONS

Persons on: Antimalarials Steroids Anticancer drugs HIV/AIDS Malnourishment
Wound Toilet and RIGs are lifesaving, specially in situations where the immune response is doubtful.

PREGNANCY AND LACTATION

NOT a Contraindication Routine schedule Routine dose

MTP is not indicated

SEVERE EXPOSURES
Bites on the Head, Face, Hands, Genitalia Multiple bites Extensive lacerations Bites by proven rabid animals animals not available for observation more than one animal wild animals

ADVICE TO PET OWNERS

Get the pet regularly examined. Get the pet vaccinated at three months of age and again one month later, boosters must be given every year subsequently.

Obtain a municipal license, put a collar and leash.

Do not allow the pet to come in contact with stray dogs/ cats or other animals. Ensure removal of stray dogs / animals.

PERSONAL SAFETY
Do not touch animal bite wounds with bare hands. Do not touch fomites (chain, food plates etc.) of an animal suspect or proven rabid. Do not touch stray / sick animals. Do not stare at or provoke any animal. Take pre-exposure vaccination if you are in constant touch with animals.

Avoid contact with saliva, urine, tears and other secretions of a patient of hydrophobia.

MEDICAL ADVICE TO VACINEES

No dietary restriction. No restriction of physical exercise. Avoid immunosuppressants:
(Steroids, anti-malarials).

Avoid alcohol consumption. Complete the course of vaccine.