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Rabies-The Fatal Encounter
“Prevention is the only solution”
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Interesting Historical Facts
One of the oldest disease known to mankind Oriental physicians : 3000 BC Greek physician Democritus in 500 BC and
Celsus in First Century AD In India, rabies is known since Vedic periods as
corroborated in Antherva Veda The Latin word “Rabies” seems to have
originated from the Sanskrit word “Rabhas” which means “to do violence”
The vaccine developed by Dr.Louis Pasteur was first administered on July 6, 1885
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IncidenceWorld
• Canine rabies continues to exist in 87 countries or territories of the world and this accounts for 99 per cent of all human rabies cases.
• Globally each year, 10 million people require Post-Exposure Treatment (PET)
• 70,000 people per annum fall victim to the disease, particularly in developing countries
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India• Estimated 30,000 patients suffer painful
deaths per annum,• More than 67% of all reported cases of
rabies come from India. • Approximately 20 million dogs in India
and in addition there is also threat from cats and other domestic and wild animals
• 5,00,000 undergo anti-rabies immunization
Incidence
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What is Rabies ? Highly fatal viral disease, characterized by
inflammation of the central nervous system (encephalomyelitis)
Known as hydrophobia Primarily a zoonotic disease-All warm-blooded
animals are susceptible to this infection Extremely dangerous disease: characteristic long
and variable incubation period, a short period of illness, highly distressing symptoms and as a rule ending in death
It is the only communicable disease of man that is always fatal.
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Agent factor
The causative agent : Lyssavirus type 1 Belongs to the family Rhabdoviridae –
Serotype 1 Bullet shaped neurotropic RNA containing
virus Two major antigens :
Glycoprotein (gp) – cell membraneNucleoprotein antigen (N protein)
Only gp induces virus-neutralizing antibodies
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Other important properties:
• The virus is highly resistant against cold, dryness, decay, etc.
• It can remain infectious for weeks in cadavers
• Its is inactivated by formaldehyde, sunlight, lipid solvents and antiseptics
Agent factor
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Host or Principal Reservoirs All warm-blooded animals In cities-dogs and cats
Source of infection: -saliva of rabid animals
-virus in saliva: 3-4 days before the onset of symptoms and during the course of illness in dogs and cats
Host and Source of Rabies Infection
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Mode of transmission
Animal bites: 99% rabid dog bites -Others: cat, monkey, horse, sheep, goat
Licks: Abraded skin and mucosa (abraded or unabraded)
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Incubation period
In humans, highly variable : 3-8 weeks post exposure (but may vary from one week to many years)
Factors influencing incubation period: The site of the biteSeverity of the biteNumber of woundsAmount of virus injectedSpecies of the biting animalProtection provided by the clothing and Treatment undertaken, if any.
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Pathogenesis The deadly sequel
Multiplies Locally in Muscle Fiber
Peripheral nerves
Dorsal Root Ganglia
Spinal Cord
BrainTissues
BodyFluids
Glands
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Clinical manifestations
First Warning Sign:Prodromal Symptoms 80% of patients complain of pain or
tingling at the site of the bite-reasonably specific
headache, malaise, sore throat and slight fever lasting for 3-4 days
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Widespread excitation and stimulation of Nervous system :
The sensory system, the motor system, the sympathetic and central nervous system
Intolerant to noise, bright light or a cold draught of air (sensory)
Aerophobia (fear of air) may be present Increased reflexes and muscle spasms (motor) Dilatation of the pupils and increased perspiration,
salivation and lacrimation (sympathetic) Mental changes include fear of death, anger, irritability
and depression
Clinical manifestations
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Hydrophobia: This characteristic symptom of hydrophobia
(fear of water) is pathognomonic of rabies and is not characteristic in animals
Duration of illness is 2-3 days (sometimes 5-6 days)
Rabies can be classified as:- Furious or frank rabies Paralytic or dumb rabies
Clinical manifestations
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Diagnosis On the basis of history of bite by a rabid
animal and characteristic signs and symptoms
Confirmation by laboratory tests: antigen detection : immunofluorescence
of skin biopsy Virus isolation from saliva and other
secretions
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Prevention of rabies in human
WHO EXPERT COMMITTEE ON RABIES
Has issued precise recommendation for the management of rabies in a technical report published in 1996
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WHO Recommendations
• Pre-Exposure Vaccination
• Post-Exposure Treatment (PET)
• Post-Exposure Treatment of persons who have been vaccinated previously
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WHO RecommendationsA. Pre Exposure Vaccination:
High risk group: laboratory staff working with rabies virus, veterinarians, pet
owners, animal handlers, wild life officers, sanitation workers, municipal employees working on rabies
control projects such as dog handlers persons who handle rabies patients, medical and para-medical
staff in communicable disease hospitals, naturalists, rural postmen
slaughter house personnel, taxidermists, tannery workers and those who frequently travel in rabies endemic areas should undertake pre-exposure vaccination.
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WHO Recommendations
The advantages of pre-exposure vaccination It prepares immune system to have anaemnestic
response when the actual bite takes place. It will reduce the necessity of immunoglobulin
requirements as the active immunity is triggered immediately.
It will reduce the risk, in case, Post- Exposure Treatment (PET) is delayed due to non-availability of vaccine in remote areas.
It reduces the number of Post-Exposure Treatment doses to three instead of the usual six.
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Dosage Schedule for pre-exposure vaccination three injections of cell culture vaccines
(abhayrab) with a potency of at least 2.5 IU
WHO Recommendations
Continued immune status can be maintained by a booster after one year and there after a booster once in every three years
Day 0 Day 7 Day 28 1 year every 3 years
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Important: Reduces the number of vaccinations(PET)
considerably. High risk groups: Test the antibody titres every six
months. Revaccination is recommended, if the serum antibody titre falls below 0.5 IU/ml.
A rabies vaccination pre-exposure certificate should be obtained by such persons and the following details should be provided in the certificate:-1. Type of vaccine, 2. Origin-The manufacturer, 3. Schedule used along with dates, 4. Batch number, 5. Anti- body titres (if determined)
WHO RecommendationsPre-exposure Vaccination
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WHO Recommendations
B. Post Exposure Treatment (PET)“Factors that should be considered in deciding whether
or not to initiate post-exposure treatment are”: The nature of exposure The presence of reported cases of rabies in the area The species of animal involved The clinical and vaccination status of the biting animal The availability of the animal for observation The results of laboratory testing of the animal, if
available
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Guide For Post-exposure Treatment
Administer vaccine immediately.
Stop treatment, if animal remains 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.
Nibbling of uncovered skin.
Minor scratches or abrasions without bleeding.
Licks on broken skin
II
None, if reliable case history is available.
Touching or feeding animals. Licks on intact skin.
I
Recommended treatment Type of contact with a suspect or confirmed rabid domestic or wild animal or animal unavailable for observation
Category
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Administer rabies immunoglobulin and vaccine immediately.
Stop treatment, if animal remains 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.
Single or multiple transdermal bites or scratches.
Contamination of mucous membrane with saliva (i.e. licks).
III
Recommended treatmentType of contact with a suspect or confirmed rabid domestic or wild animal or animal unavailable for observation
Category
Guide For Post-exposure Treatment
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1. Local Treatment of Wound- First Aid: Animal bite wound should be washed with copious
amount of running water and mild soap immediately
Wound can be cleaned using ethanol, tincture iodine/ aqueous solution of iodine
Suturing of wounds should be avoided Suturing; if at all required: wound should be
infiltrated with rabies immunoglobulin of human or equine origin before suturing
WHO RecommendationsB. Post Exposure Treatment (PET)
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2. Administration of rabies immunoglobulin:• Should be given for all Category III
exposure(severe bites), irrespective of interval between exposure and beginning of treatment
• Human rabies immunoglobulin(HRIG) OR Equine rabies immunoglobulin(ERIG) may be used
• A skin test must be performed prior to the administration of Equine rabies immunoglobin, ERIG
WHO RecommendationsPost Exposure Treatment (PET)
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2. Administration of rabies immnoglobins:• As much as possible , the recommended dose should be
infiltrated around the wounds, if anatomically feasible• The remainder should be administered IM(into gluteal
region ) in a single dose
The WHO recommended dose : 40 IU/kg body weight, for rabies immunoglobulin of equine
origin 20 IU/kg body weight, for immunoglobulin of human origin
WHO RecommendationsPost Exposure Treatment (PET)
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3. Vaccine Administration:(Tissue-Culture) The vaccine used should have a potency of at
least 2.5 IU per dose Intramuscular Schedule One dose of vaccine should be administered on
days 0,3,7,14 , 28 & 90
WHO RecommendationsPost Exposure Treatment (PET)
Day 0 D 3 D 7 D 14 D 28 D 90
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3. Vaccine Administration:(Tissue-Culture)• All intramuscular injections must be given into
deltoid region• In small children, into the anterolateral area of the
thigh muscle• Vaccine should never be administered in the
gluteal region• A certificate of PET should be filled in and given
to each vaccinee
WHO RecommendationsPost Exposure Treatment (PET)
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Pre and Post-Exposure Treatment for Immunocompromised Pateints or cases of delayed treatment
• Day 0:- 2 or 3 doses IM
• No change for other administrations concerning vaccine and RIG
WHO Recommendations
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WHO RecommendationsC. Post-Exposure Treatment of persons who have
been vaccinated previously
Local treatment of wounds should be carried out
Persons who have previously received full pre- or post exposure treatment with a potent cell-culture vaccine
Only two doses are needed (days 0 to 3) No rabies immunoglobulin recommended
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Persons who have previously received full per- or post exposure treatment with vaccine of unproven potency, and/or low anti-body titre (<0.5 IU)
Should receive a complete post-exposure treatment course, including rabies immunoglobin if indicated
WHO RecommendationsC. Post-Exposure Treatment of persons who have
been vaccinated previously
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Composition per single dose:
• Freeze-dried vaccine: One immunizing dose contains the protective activity of equal to or greater than 2.5 International Units (IU) even after exposure at 37 degrees centigrade for one month.
abhayrab-prescribing information
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Composition per single dose:Rabies Virus (L.Pasteur 2061/Vero) propagated on Vero cell line, inactivated with beta-propiolactone(BPL).Thiomersol @ 0.015% added as preservativeMaltose……………………………….q.s. per
immunizing doseHuman Serum Albumin ……………..q.s. per
immunizing dose.Sodium Chloride (0.9%) for Injection I.P.- 0.5 ml.
abhayrab-prescribing information
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abhayrab-prescribing information
INDICATIONS:For active immunization against rabies both for
prophylaxis and post-bite therapy in all age groups of humans
• For prophylactic immunization of all high risk group of persons such as veterinarians, municipal workers, medical and paramedical personnel, forest and zoo personnel, hunters, laboratory personnel working with suspected rabies material and pet owners.
• For immunization against rabies after exposure (after contact with a rabid or suspected rabid animal)
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DOSAGE: Prophylaxis: Three immunizing doses on 0,7
and 28 (21) days followed by one annual booster and subsequently every three years
Post exposure: One immunizing dose on post exposure days 0,3,7,14,28 (30) and 90 each. (Day 0 is the day of first vaccination and not the day of bite.)
abhayrab-prescribing information
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ADMINISTRATION:• Reconstitute the freeze dried vaccine with the
diluent supplied in the ampoule• Administer the reconstituted vaccine (entire
quantity of the vial) by deep intramuscular route in the deltoid region or in small children, into the anterolateral region of the thigh muscle. The reconstituted vaccine should be used immediately and not to be stored for administration later.
abhayrab-prescribing information
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CONTRAINDICATIONS:In principle, there are no contraindications for administering the vaccine as the high risk of death outweighs all other considerations, specially in case of post-bite therapy.
CAUTIONS:• Concurrent use of immunosuppressive agents like
corticosteroids shall be avoided as it may hamper in the development of protective antibodies.
• In case of severe bites, local infiltration of the wounds with antirabies immunoglobulin is recommended.
• Delay in the commencement of post-bite therapy, incomplete and irregular therapy can cause failure of protection.
abhayrab-prescribing information
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STORAGE: To be stored at temperature between 2 to 8 degrees
centigrade. Do not store the vaccine in deep freezer.
PRESENTATION:
• The vaccine is supplied as a single dose vial in a carton and the diluent for reconstitution is supplied separately in ampoules along with syringe & needles.
abhayrab-prescribing information
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Advantages of Vero cell vaccine over Nervous tissue
1. Highly potent and immunogenic2. High titres of antibodies are obtained3. Virtually free of side-effects ; No neuroparalytic
complications4. Lesser number of injections per course, which are
spaced and not given daily5. Dose per injection is also much less – 0.5ml compared to
2 to 5 ml6. No variation in dose according to age or body weight7. Convenient site of inoculation: Deltoid region is
preferred
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8. Sterile disposable syringe or pre-filled syringe are provided with the vaccines
9. Longer shelf life10. Freeze-dried formulation, therefore better
temperature resistant11. Can be used for pre-exposure vaccination12. Immunity lasts up to 3-5 years13. Can be used to immunize patients who develop
allergy to nervous tissue vaccines
Advantages of Vero cell vaccine over Nervous tissue
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Advantages Over PCEC
Relevant abhayrab benefits:• Abhayrab is manufactured using vero cell line as
a substrate and is virtually free of side effects • PVCV is the latest reference vaccines by WHO• Abhayrab is available as single dose vials, which
can be conveniently used by the doctors• Abhayrab is much economical• Abhayrab is an indigenous product and thus offers
assured supplies.• Abhayrab requires only 0.5 ml diluent to be
administered to the patients
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HBI-AbhayrabTechnological Expertise
• Nestled atop the Niligiri hills in Ooty, the ‘state-of-the-art’ vaccine production facility of Human Biologicals Institute is designed strictly as per the WHO norms
• Each batch of Abhayrab goes through a battery of tests at every stage ensuring that the vaccine consistently exceeds all WHO norms for purity, potency and immunogenic activity
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Human Biologicals Institute
Immunity Made Affordable
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Human Biologicals Institute - Lineage
Established by National Dairy Development Board
White revolution and operation flood
Cooperative movement in India
India-largest producer of Milk and milk products in the World
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Division of Indian Immunologicals Limited :-Division of Indian Immunologicals Limited :-
Experience and expertise of two decades in vaccine productionExperience and expertise of two decades in vaccine production
India’s first tissue culture rabies vaccine for veterinary useIndia’s first tissue culture rabies vaccine for veterinary use
Asia’s largest and World’s second largest manufacturers of Asia’s largest and World’s second largest manufacturers of veterinary vaccinesveterinary vaccines
State-of-the-art manufacturing facilities-WHO and ISO-9002 State-of-the-art manufacturing facilities-WHO and ISO-9002 approvedapproved
Human Biologicals Institute
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An ISO-9002 company
World class manufacturing facilities at Ooty
ISO-9002 and WHO GMP approved
India’s first and most affordable PVRV
World’s second manufacturing facility of PVRV
Capacity to produce 3 million doses of PVRV
Human Biologicals Institute
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Abhay ClinicAbhay ClinicThe one stop vaccination centre
ObjectiveObjective
To provide quality vaccinationTo provide quality vaccination
To ensure potency and safety of the vaccinesTo ensure potency and safety of the vaccines
To ensure reliable and dependable servicesTo ensure reliable and dependable services
To ensure vaccines are provided under strict cold To ensure vaccines are provided under strict cold chain maintenance systemchain maintenance system
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Nation wide network of vaccination centre for all Nation wide network of vaccination centre for all immunization needsimmunization needs
Range of world class quality, vaccinesRange of world class quality, vaccines
Information nodesInformation nodes
Strict cold chain maintenanceStrict cold chain maintenance
Affordable vaccinationAffordable vaccination
Free antibody titre tests, to guarantee the performance Free antibody titre tests, to guarantee the performance of the vaccineof the vaccine
Only company in world to provide antibody titre tests at Only company in world to provide antibody titre tests at field levelfield level
Abhay ClinicAbhay ClinicThe one stop vaccination centre
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abhayrabIndia’s first PVRV
Abhay ClinicAbhay ClinicThe one stop vaccination centre
The most affordable anti-rabies vaccine