Rabies Vaccine

Sayenna Uduman
Sayenna A Uduman MD, FAAP
Visiting Professor, Infection Control Committee & ID Division of the KIMS
Thiruvananthapuram, Kerala, India

First Created: 02/01/2016 

Rabies Vaccine - Epidemiology

According to WHO, the actual number of rabies deaths in India may be far higher than we know because of unreported or untreated cases and the paucity of literature at the national level. The Global Alliance for Rabies Control (GARC) states India bears the world’s heaviest rabies burden, accounting for 35% of all deaths due to the disease. Worldwide, most human rabies result from dog bites in areas where canine rabies is enzootic, accounting around 59 000 dies of rabies each year and nearly half of whom are children. Most rabid dogs, cats, and ferrets shed virus for a few days before there are obvious signs of illness. No case of human rabies has been attributed to a rabid animal that has remained healthy throughout the standard 10-day period of confinement after an exposure.

Rabies Vaccine - Pathogenesis

Rabies is caused by RNA viruses in the family Rhabdoviridae, genus lyssavirus. The virus is transmitted in the saliva of rabid animals after a bite or through contamination of an open wound or mucous membrane. The predominant reservoir of rabies in India, with most cases occurring in dogs and rarely in cats. The incubation period (1-3 months but ranges from days to years) is long enough to render immunization a highly effective strategy for post-exposure prophylaxis (Post EP), which is an emergency.

Key interventions for rabies control include vaccination for high-risk individuals, surveillance of human cases, post-exposure prophylaxis following animal bites, vaccination and/or culling of the canine population, and other animal reservoirs. In India, especially animal rabies is common and education of children to avoid contact with stray or wild animals is of primary importance.

Rabies Vaccine - IAP Recommendations

The Indian Academy of Pediatrics has now identified & recommend that all children need vaccination against rabies especially for those high-risk categories of children with the following environmental situations namely: (i) children having pets at home; and (ii) children perceived with a higher threat of being bitten by stray-dog while going outdoor walk and playing. These children should be offered preventive, pre-exposure prophylaxis (Pre-EP) against rabies after a thorough discussion with the parents. This should be encouraged and targeted to children & adults at high risk for potential exposure to a rabid animal due to occupation or travel to an area with uncontrolled enzootic rabies in animals.

Anyone who has been bitten by an animal, or who otherwise may have been exposed to rabies, should clean the wound and see a doctor immediately to determine if they need to be vaccinated. This is called post-exposure prophylaxis (Post EP) which is an emergency and as a general rule, should not be delayed or deferred.

WHO strongly advocates the safest and most effective vaccines; these are the intramuscular use of human diploid cell vaccine (HDCV), purified chick embryo cell culture (PCEC), and rabies vaccine adsorbed (RVA). The production and use of highly reactogenic multi-dose, older nerve-tissue-vaccines (NTV), has been discontinued since December 2004 in our country.

Intradermal Immunization

WHO recommends the intradermal route as an acceptable alternative to standard intramuscular administration and this alternative should thus be considered in settings constrained by cost and/or supply issues.

Rabies Vaccine - Post EP

Both rabies vaccine and rabies immune globulin (RIG) are used simultaneously with appropriate regimens and routes of administration that have been proven to be safe and effective.

  • Wounds should be washed/flushed and disinfected immediately. Vaccine and immunoglobulin therapy instituted as soon as possible,
  • A person who is exposed and has never been vaccinated against rabies should get 4 doses of rabies vaccine - one dose right away, and additional doses on the 3rd, 7th, and 14th days.
  • Human RIG should be used concurrently with the first dose of rabies vaccine and should be injected at a different site.
  • If RIG is not available on the first visit, its use can be delayed by a maximum of 7 days from the date of the first vaccine injection.
  • A person who has been previously vaccinated should get 2 doses of rabies vaccine - one right away and another on the 3rd day. The concomitant RIG is not needed.
  • initiation of Post EP should not await the results of laboratory diagnosis or be delayed by dog observation when rabies is suspected,
  • Although the safety of rabies vaccine during pregnancy has not been studied pregnancy & infancy should not be considered a contraindication to use of vaccine or RIG after exposure.
  • Persons who present for evaluation and rabies post-exposure prophylaxis even months after having been bitten should be dealt with in the same manner as if the contact occurred recently.
  • Post EP may be discontinued if the animal involved is a dog or cat that remains healthy for an observation period of 10 days after the exposure occurred; or if the animal is humanely killed and proven to be negative for rabies by a reliable diagnostic laboratory using a prescribed test.
  • If the animal inflicting the wound is suspected of being rabid and is not detained, post EP should be instituted immediately.
  • In areas where canine or wildlife rabies is enzootic, adequate laboratory surveillance is in place, and data from laboratory and field experience indicate that there is no infection in the species involved, local health authorities may not recommend anti-rabies prophylaxis.

Rabies Vaccine - Pre-EP

Pre-EP should be encouraged and targeted to children & adults at high risk for potential exposure to a rabid animal due to occupation or travel to an area with uncontrolled enzootic rabies in animals. The pre-exposure schedule for rabies vaccination is 3 doses, to be given intramuscularly at the following times: Dose 1: As appropriate; 2nd dose to be given 7 days and the 3rd dose to be given 21 days or 28 days after dose 1 injection.

Rationale For Pre-Exposure Prophylaxis

  • Provides protection for in-apparent & or inadvertent exposures to rabies virus, as in high risk children, travelers to high enzootic rabies area and for laboratory workers
  • Eliminates the need for RIG for post-exposure prophylaxis; this is particularly important in areas where RIG may be unavailable or unsafe
  • Affords some protection when post-exposure prophylaxis may be delayed.

Rabies Vaccine - Booster Doses

Booster doses of vaccine are recommended when there is ongoing high-risk exposure. Serologic testing to document seroconversion after administration of a rabies vaccine series usually is not necessary but occasionally has been advised for recipients who may be immune-compromised or for people with deviations from the recommended vaccination schedule. The immune response should be assessed by performing serologic testing 7 to 14 days after administration of the final dose in the series.

Rabies Vaccine - Conclusion

  • The coverage & usage of immunogenic vaccines and RIGs need to be improved and should be available for clinician use consistently.
  • Should facilitate to improve the reporting systems, all confirmed and suspect cases to local health department
  • There is an urgent need to tackle the menace of stray dog population by vaccination of the pet animals, at the least.
  • The main constraint to rabies elimination in India is the lack of a comprehensive national program & coordinated approach.

Table: US FDA Licensed Rabies Vaccines and Rabies Immune Globulin Products

Vaccines & Rabies Immune Globulin Dose & route of administration* (same for children & adults) Vaccination regimen in immune-competent children & adults *
Vaccines: 1. Human diploid cell vaccine (HDCV) (Imovax Sanofi Pasteur)

2. Purified chicken embryo cell vaccine (PCECV) (RabAvert, Novartis)

3. Rabies vaccine adsorbed (RVA) is licensed but no longer is distributed in the United States
1 mL, IM

1 mL, IM

1 mL, IM

Post EP: 0 day, 3rd, 7th & 14th

Pre EP: 0 day, 7th and 21st day

As above

As above
Human Rabies Immune globulin
1.Imogam Rabies-HT (Sanofi Pasteur).

2. HyperRab S/D (Talecris Biotherapeutics)
20 IU/kg, infiltrate around wound

20 IU/kg, infiltrate around wound
Any remaining volume should be administered intramuscularly.

RIG not to be used during re-exposure therapy.
Equine RIG (outside USA) 40 IU/kg < 1% chance of serum sickness, may require desensitization
*the volume of the dose is not decreased for children. ** For a person with altered immunocompetence, post EP should include a 5-dose vaccination regimen (i.e., 1 dose of vaccine on days 0, 3, 7, 14, and 28), with 1 dose of RIG.

Rabies Vaccine - Adverse Reactions

Adverse reactions are uncommon in children. In adults, mild local reactions, such as pain, erythema, and swelling or itching at the injection site, are reported in 15% to 25%

1. The recommendations of the Advisory Committee on Immunization Practices (ACIP) for rabies post-exposure prophylaxis can be accessed through the CDC & P website at http://www.cdc.gov/rabies/ and should be checked periodically for updates.
2. Indian Academy of Pediatrics (IAP) recommended immunization schedule for children aged 0 through 18 years, India, 2013 and updates on immunization. Indian Pediatr. 2013;50:1095-108.
3. www.globalrabiescontrol.org4. http://www.who.int/immunization/topics/rabies/en/

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