RABIES VACCINE

Type of vaccine
Rabies vaccine (Fig. 4.14) is a killed vaccine. verorab insert
Two types of rabies vaccines are available; cell culture vaccines (CCVs) or Embryonated egg-based vaccine (EEV).

1. Cell Culture Vaccines
a) Human Diploid Cell Vaccine (HDCV), Liquid (Adsorbed), I.M dose; 1ml
b) Purified Chick Embryo Cell Vaccine (PCECV), I.M dose; 1ml
c) Purified Vero Cell Rabies Vaccine (PVRV), I.M. 0.5ml or 1ml (depends on the manufacturer)

2. Embryonated egg-based vaccine
a) Purified Duck Embryo Vaccine (PDEV): dose1ml, intramuscular

Diluent:
The diluent provided with the vaccine
Some vaccines have 0.5ml diluents and others have 1ml diluents as per the manufacturer of the brand, and this cannot be altered. It is crucial that the instructions accompanying the vaccine are carefully read and adhered to.

Storage:
+2 - +8ºC and protected from sunlight.
Freezing may not damage the lyophilized vaccine but the accompanying diluent ampoule may crack
Liquid rabies vaccines (Human Diploid Cell vaccine) should never be frozen. nat GL

Dose
1 mL or 0.5 ml (as per manufacturer’s instructions) for intramuscular route
0.1 mL per site, for intradermal (ID) route

Site
For Intramuscular injection:
• Deltoid;
• Antero-lateral part of the thigh, in infants and young children
Gluteal region is not recommended because the fat present in this region retards the absorption of antigen and hence impairs the generation of optimal immune response

For intradermal injection:
• Deltoid area
If for some reason the deltoid region cannot be used for injection, then the alternative sites are;
• The suprascapular area or
• The anterolateral thigh.

Route of administration
Intramuscular or intradermal
For IM regimen, any of the two available types of vaccine (CCVs and PDEV) can be used.
However for Intra-Dermal (ID) regimen, only those cell culture vaccines (CCVs) which are approved for ID use shall be used.

Side effects
Headache, local pain, and redness

Contraindication
• For post-exposure prophylaxis there is NO contraindication, as it is treated as an emergency since rabies has unacceptably high mortality rates
• For pre-exposure prophylaxis
- Previous severe reaction to any components of the vaccine
- People on chloroquine treatment should receive the vaccine ONLY Intramuscularly. This is because they may have a reduced response to intradermal rabies vaccination.

Potency of approved vaccines
The vaccines should have stated potency of ≥ 2.5 IU per IM dose, which may be either 1ml or 0.5ml, as mentioned by the manufacturer.
Adequacy of the stated potency is to be especially checked for ID use
Currently, the following vaccines have been approved by DCGI for use by intradermal route.
• Rabipur,
• Vaxirab
• Verorab,
• Abhayrab,
• Indirab,
• Antirabies Vaccine by - Pasteur Institute of India, Coonoornat GL

Whether part of NIS?
No

Indication
• Post-exposure prophylaxis against rabies
• Pre-exposure prophylaxis for those at high risk for exposure

How will you categorize animal bite?
Types of contact (category of bite) are as follows:
• Category I—Touching or feeding animals, licks on intact skin
• Category II—Nibbling of uncovered skin, minor scratches or abrasions without bleeding
• Category III—Single or multiple transdermal bites or scratches, licks on broken skin, contamination of mucous membrane with saliva from licks, contact with bats

Post exposure prophylaxis (PEP)
Postexposure prophylaxis depends upon the category of the animal bite.
• Category I animal bite: None

• Category II animal bite:
1. Local treatment of the wound
2. Active immunization with rabies vaccine
3. Investigate the biting animal for rabies or observe for 10 days after the bite.

• Category III animal bite:
1. Local treatment of wound and
2. Active immunization with rabies vaccine
3. Rabies immunoglobulin
4. Investigate the biting animal for rabies or observe for 10 days after the bite.
Vaccine regimen in any category may be discontinued if the biting animal:
• Is humanely killed and declared negative for rabies by a WHO prescribed laboratory test or
• Remains healthy after 10 days of observation (only in case of domestic dog, cat or ferret)

Post – exposure prophylaxis for class III animal bite:

Local treatment of the wound
1. Washing thoroughly with plenty of soap and water, for at least 15 minutes, followed by
2. Cleaning with alcohol or povidone iodine and then
3. Passive immunization with antirabies serum
4. Antitetanus prophylaxis as indicated

Passive immunization with rabies immunoglobulin
1. Dose of immunoglobulin: human origin – 20 IU per kg; equine origin – 40 IU per Kg
2. All or as much as anatomically possible (avoiding a compartment syndrome) of the total dose is to be infiltrated into and around the wound and the remaining (if any) is to be administered IM in the gluteal region.
3. Sensitivity testing is not recommended prior to the administration. Instead, the treating physician should be prepared to manage anaphylaxis

Schedules for active immunization with rabies vaccine
All animal bite victims of Category II and III exposures, irrespective of age and body weight, require the same number of injections and dose per injection.nat GL

Any of the following schedules may be used: (two are IM and one is ID)

1. IM: Five doses of cell culture vaccine, 1 mL or 0.5ml each, intramuscular on days 0, 3, 7, 14 and 28 (Essen regimen)
2. IM: Abbreviated (4 doses in 3 visits) multisite schedule, i.e., the 2-1-1 regimen (Zareb regimen): 2 intramuscular doses on day 0 (one on each side) followed by 1 IM dose each on day 7 and day 21
3. The intradermal schedules is:
Two- site ID injections of 0.1ml each, on days 0, 3, 7 and 28; the day 14 dose is missed (2-2-2-0-2 regimen)

Pre-exposure prophylaxis:
• One dose (IM or ID) each on day 0, 7, and 21 (or 28)
• Booster doses of rabies vaccines are not required after a complete pre or post exposure prophylaxis with a CCV
Instead of routine boosters, antibody monitoring of personnel at risk is preferred, a booster is recommended only if the antibody titers fall to < 0.5 IU/ml

Management of re-exposure in previously vaccinated individuals
Those who can document full pre- or post-exposure prophylaxis (either by IM or ID route) with a cell-culture vaccine or PDEV:
• Two booster doses IM or CCVs ID (0.1 ml at 1 site) on days 0 and 3.
• Proper wound toilet should be done.
• Treatment with RIG is NOT required

Those who have previously received full post-exposure treatment with Nerve Tissue vaccine or vaccine of doubtful potency or cannot document complete prophylaxis previously
• Should be treated as fresh case and given treatment

Who are the candidates for Pre-Exposure Prophylaxis (PrEP)?
Pre-exposure vaccination may be offered to high risk groups like
• laboratory staff handling the virus and infected material,
• clinicians and persons attending to human rabies cases,
• veterinarians,
• animal handlers and catchers,
• wildlife wardens,
• quarantine officers and
• Travellers from rabies free areas to rabies endemic areas. park, nat GL

The Indian Academy of Pediatrics (IAP) has recommended preexposure prophylaxis of children. This may be considered on voluntary basis.GL

Pre-exposure vaccination is administered as one full intramuscular dose or 0.1 ml intra-dermally on days 0, 7 and either day 21 or 28

Which types of vaccines are recommended for the intradermal schedules?
Only cell culture vaccines are recommended for the intradermal schedules.

What needs to be done if an intradermal injection becomes subcutaneous?
If the vaccine is injected too deeply into the skin (subcutaneous), the classical bleb is not seen.
Then the needle needs to be withdrawn and another ID dose should be given at an adjacent siteNat GL

Is it recommended to switch over from IM to ID route of administration or vice versa during PEP?
Shifting from one route to other i.e. IM to ID or vice-versa during post exposure prophylaxis is not recommended as there is no sufficient scientific evidence on vaccine immunogenicity following changes in the route of vaccine administration during PEPGL

References:
Park’s Textbook of PSM, 24th edition, 2017

Rabipur package insert. Immunization standards, WHO website. Available at: http://www.who.int/immunization_standards/vaccine_quality/Rabipur_Produc... accessed on 11th November 2017

National Guidelines on Rabies Prophylaxis 2015; National Rabies Control Programme. National Centre for Disease Control (Directorate General of Health Services) New Delhi - 110 054

National Immunization Schedule in India; 2017: http://www.ihatepsm.com/blog/national-immunization-schedule-india-2017

Rotavirus vaccine: http://www.ihatepsm.com/blog/rotavirus-vaccine

Pentavalent vaccine: http://www.ihatepsm.com/blog/pentavalent-vaccine

BACILLE CALMETTE GUERIN (BCG) VACCINE: http://www.ihatepsm.com/blog/bacille-calmette-guerin-bcg-vaccine

IPV (INACTIVATED POLIOVIRUS VACCINE): http://www.ihatepsm.com/blog/ipv-inactivated-poliovirus-vaccine

DT & TT Vaccines: http://www.ihatepsm.com/blog/dpt-and-tt-vaccines

Oral Polio Vaccines (OPV): http://www.ihatepsm.com/blog/oral-polio-vaccines-opv

Measles Containing Vaccines (MCV): http://www.ihatepsm.com/blog/measles-containing-vaccines-mcv

HEPATITIS B VACCINE: http://www.ihatepsm.com/blog/hepatitis-b-vaccine

JAPANESE ENCEPHALITIS (JE) VACCINE: http://www.ihatepsm.com/blog/japanese-encephalitis-je-vaccine

Pneumococcal Conjugate Vaccine (PCV): http://www.ihatepsm.com/blog/pneumococcal-conjugate-vaccine-pcv

RABIES VACCINE: http://www.ihatepsm.com/blog/rabies-vaccine