RABIES IMMUNOGLOBULINS

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RABIES IMMUNOGLOBULINS
Dr.P.SANGRAM, MBBS, MD MRC PATH (LONDON)
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Treatment of Rabies
WHO Recommendations ( based on category of dog
bites)
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Treatment of Rabies
WHO Recommendations ( based on category of dog
bites)
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WHO RECOMMENDS FOR ALL CATEGORY III EXPOSURES
Indication
Single or multiple transdermal bites or
scratches Contamination of mucous membrane with
saliva (licks)
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RIG in India

• Rabies takes 20000 lives every year.
• More than 70 victims are of category-III bites
• Awareness of RIG is still poor
• Only 6 victims gets complete treatment

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RABIES IMMUNOGLOBULINS

• Rabies Immunoglobulins are special neutralizing
  antibodies that immediately neutralize virus on
  contact.
• Rabies Immunoglobulin gives a coating to the
  virus so that it cannot enter the nerve ending
  resulting in reduction or total obliteration of
  inoculated virus.

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RABIES IMMUNOGLOBULINS

• There are two types of specific rabies
  immunoglobulins
• Human Rabies Immunoglobulin (HRIG)
• Equine Rabies Immunoglobulin (ERIG)

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HUMAN RABIES IMMUNOGLOBULINS

• It is a liquid of Freeze-Dried preparation
  containing Immunoglobulins mainly IgG obtained
  from plasma or serum of donors immunized against
  rabies and contains specific antibodies that
  neutralize the rabies virus.
• It is prepared from plasma of more than 1000
  donors.
• It provides passive protection when given
  immediately to individuals exposed to rabies
  virus.

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EQUINE RABIES IMMUNOGLOBULINS

• It is produced by immunizing horses with low
  concentrations of rabies vaccines. The
  antibodies produced in the blood of these horses
  are then purified and filtered.
• The modern automated ultra filtration technology
  reduces the time it takes to purify
  immunoglobulins from one week to one day while
  increasing yield levels.
• Thailand (Thai Red Cross) produces and
  distributes over 100,000 doses of ERIGS per year

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GLOBAL STANDARDS

• A combination of rabies immunoglobulin and
  vaccine together with prompt and appropriate
  wound care, has become the Global Standard for
  prevention after human exposure.
• Administration of rabies immunoglobulin as a part
  of routine post-exposure treatment is intended to
  provide a passive source of antibodies before
  endogenous development by vaccination.
• The need for rabies immunoglobulin appears to be
  on the rise, because of the ubiquity of human
  exposure to rabies virus from uncontrolled canine
  sources in developing countries.

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HUMAN RABIES IMMUNOGLOBULINS

• Advantages
• Element of purity
• Minimal or no foreign protein
• No chance of immediate hypersensitivity
• Negligible side effects
• Disadvantages
• Expensive proposition
• Existence of adventitious viral agents like
  HIV, Hepatitis-B, Hepatitis-C
• Shortage because of low yield
• Not readily available

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EQUINE RABIES IMMUNOGLOBULIN

• Advantages
• Massive Yield
• Much affordable than Human Rabies Immunoglobulin
  (low cost)
• Widely available
• Modern purification and ultra filtration
  technologies has made it safer.
• Disadvantages
• Presence of foreign protein
• Chances of immediate hypersensitivity

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INDICATIONS FOR USE OF RABIES IMMUNOGLOBULINS

• All category III bites (WHO classification)
• Licks on mucous membranes by wild or pet animals
• Category II III bites in case AIDS patients
  with grossly reduced CD4 count
• Varicella (can cause transient immunodeficiency
  in children)
• Patients on long term Corticosteroids
• Long term Chemotherapy
• Radiation Therapy
• Wound suturing (pre-infiltration)

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DOSAGE AND ADMINISTRATION

• Human Rabies Immunoglobulin
• 20 Units per kg of body weight
• Equine Rabies Immunoglobulin
• 40 Units per kg of body weight
• Maximum dosage for HRIG 2000 IU and ERIG
  4000 IU

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RIG INFILTRATION
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DOSAGE AND ADMINISTRATION

• As much as anatomically feasible the RIG should
  be infiltrated into and around the wound.
• The remaining portion of the calculated amount of
  the RIG, whatever is left over, to be injected in
  the deltoid / gluteal region away from the site
  of vaccine administration to prevent on site
  neutralization of vaccine antigen.
• RIGs should never be administered intravenously
  because of the potential for serious reactions.

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DOSAGE AND ADMINISTRATION

• The dose should not exceed the calculated
  recommended dose since RIG may partially suppress
  active production of rabies antibody.
• RIG should be administered only once usually at
  the beginning of the post-exposure regimen and
  beyond the 7th day RIG is not indicated as it may
  interfere with endogenous antibody response.

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ADMINISTRATION PRECAUTIONS

• Warm the ampoule to body temperature before
  intramuscular injection.
• Do not administer with the same syringe or into
  the same anatomical site as the rabies vaccine,
  discard any unused portion.
• Care is needed to avoid RIG seeping out of wounds
  during infiltration. If such a loss does occur,
  the volume should be estimated and replaced.
• Caution is needed if injecting into a tissue e.g.
  finger pulp, excess fluid can result in increased
  compartmental pressure and lead to necrosis.

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RIG TREATMENT - CHILDREN

• For small children The calculated dosage of RIG
  may be insufficient to infiltrate all wounds.
• Sterile saline can be used to dilute the volume 2
  or 3 fold to permit thorough effective
  infiltration.
• Under any circumstances the total dose of RIG
  should not be increased for the fear of reducing
  the vaccine induced response.

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RABIES IMMUNOGLOBULINS MECHANISM OF ACTION
EFFECT

• Following intramuscular administration Rabies
  immunoglobulin provides immediate passive
  antibodies for a short period of time. This
  protects the patient until the patient can
  produce antibodies from the rabies vaccine.
• An adequate titre of passive antibody is present
  24 hours after RIG administration.
• Duration of Protective Effect
• Short Rabies immunoglobulin has a half-life of
  approximately 21 days.
• Cross sensitivity and/or related problems
• Patients sensitive to other human immune
  globulin products may be sensitive to Rabies
  Immunoglobulin also.

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RABIES IMMUNOGLOBULINS PREGNANCY AND LACTATION

• Pregnancy has not been considered to be a
  contraindication
• No harmful effect on the foetus or neonate.
• A study done on 202 women and their infants at
  Queen Saovobha Memorial Institute, Bangkok,
  Thailand (WHO collaborating center for Rabies) by
  Henry Wilde confirms this finding (during
  1987-1989 2 year study).
• Breastfeeding No problems have been documented
  in Humans. In fact Immunoglobulins are excreted
  into the milk and may contribute to the transfer
  of protective antibodies to the neonate.

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RABIES IMMUNOGLOBULINS SIDE / ADVERSE EFFECTS

• Severe adverse systemic effects to Rabies
  Immunoglobulin are rare.
• Side effects of Less Frequency
• Local Pain, tenderness may occur at injection
  site cutaneous reactions.
• Systemic Headache, Fever, Chills, Flushing,
  Backache, Nausea have been reported.
• Persons with selective IgA deficiency may develop
  antibodies to the small amount of IgA in this
  preparation, leading to sensitization and
  subsequent reaction to IgA containing material,
  such as blood and plasma derived medical
  products.

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DRUG INTERACTIONS AND/OR RELATED PROBLEMS

• Immunoglobulin administration may impair for a
  period of at least 6 weeks and up to 3 months,
  the efficacy of live attenuated virus vaccines
  such as Measles, Mumps, Rubella and Varicella.
• Hence these vaccines should be administered at
  least 14 days prior to or 3 months after
  administration of Rabies Immunoglobulin.
• Over dosage may result in significant depression
  of active immunity.
• Repeated doses should not be administered once
  the rabies vaccine treatment has been started,
  because this could prevent full development of
  the active immunity expected from the vaccine.

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STORAGE AND OTHER PRECAUTIONS

• Store between 20C - 80C (350F - 460F)
• Do not freeze
• The solution should not be used if it is
  discoloured or contains particulate matter
• RIG should not be heated
• RIG should not be administered in the same
  syringe or into the same body site as the rabies
  vaccine.

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ABHAYRIG ADMINISTRATION INTRADERMAL TEST

• Since AbhayRIG is Equine Rabies Immunoglobulins,
  it is mandatory to carry out an intradermal test
  to know the sensitivity status of the individual.
• Test 0.1 ml of 110 diluted AbhayRIG with normal
  saline is given intradermally on the left
  forearm.
• Observation A patient is observed for 15 minutes
  for local /systemic reactions.

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RIG INFILTRATION

• Positive test reaction Induration gt10mm
  with or without
• constitutional symptoms.
• If skin test is positive HRIG is preferred
  (affordability, availability)
• If ERIG has to be administered then pre treat
  with Adrenaline/
• Epinephrine and with Antihistamine before
  administering full dose.

Note A negative test is not a guarantee that
Anaphylaxis will not occur.
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ABHAYRIG ADMINISTRATION INTRADERMAL TEST

• Local Erythema, Wheal, Severe pain at the local
  site.
• Systemic Giddiness may lead to mild circulatory
  collapse with fall of BP.
• Precaution Patients giving history of
  sensitization to other vaccines or
  immunoglobulins may be given anti- histamines
  prior to administration.

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ABHAYRIG ADMINISTRATION INTRADERMAL TEST

• Management Post Reaction
• 1) Mild Local Reaction Anti histamines
• 2) Systemic reaction EPINEPHRINE 11000 (Aqueous)
  0.01ml / Kg per dose repeated every 10 20
  minutes.
• Usual Dose
• Infants 0.05ml 1ml
• Children 0.1 - 0.3 ml
• Adolescents 0.3 0.5 ml

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ABHAYRIG ADMINISTRATION INTRADERMAL TEST

• 3) SEVERE CASES
• HYDROCORTISONE I.V 100 200 Mg / Kg

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Therefore,

• Provide Complete Treatment and
• Protection against deadly Rabies
• with ARV (Abhayrab) and RIG
• (Abhay RIG) and save lives !!

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Human Biologicals Institute

• Biotechnology in healthcare made affordable and
  accessible

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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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Human Biologicals Institute

• Division of Indian Immunologicals Limited -
• Experience and expertise of two decades in
  vaccine production
• Indias first tissue culture rabies vaccine for
  veterinary use
• Asias largest and Worlds second largest
  manufacturers of veterinary vaccines
• State-of-the-art manufacturing facilities-WHO and
  ISO-9001 approved

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Human Biologicals Institute

• An ISO-9001 company
• World class manufacturing facilities at Ooty
• ISO-9001 and WHO GMP approved
• Indias first and most affordable PVRV
• Worlds second manufacturing facility of PVRV

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THANK YOU..!