Rabies Immune Globulin (RabIg) and Rabies Vaccine Quick Reference Guide to Administration

Key Messages

Rabies is a virus that causes neuroencephalitis and rapid death in humans. It is transmitted via the saliva of infected animals. In Ontario, animals most at risk for having rabies are raccoons, foxes, skunks, and bats. In some areas of the world, rabies in domestic dogs poses a considerable risk.

High risk exposures include bites to the hands, face and neck. Bat bites are not always visible, and direct contact with a bat is sufficient exposure to warrant rabies post-exposure prophylaxis (RPEP).

Rabies is nearly always fatal, but can easily be prevented by encouraging people to vaccinate their pets, avoid touching or interacting with any unknown animals, and seeking proper care for any animal bites or scratches.

As a healthcare provider, you may be asked to administer RPEP, and appropriate administration is vitally important to ensure patients have the necessary immune protection to avoid contracting rabies. This can be accomplished by:

  • Administering rabies immune globulin (RabIg) correctly into the wound(s).
  • Administering the rabies vaccine at a DISTANT site from RabIg, preferably in a different limb.
  • Documenting administration of RPEP thoroughly, including sites of injection and vaccine lot numbers. 
Introduction

Rabies is an acute progressive encephalitis caused by a virus in the genus Lyssavirus, family Rhabdoviridae. It is nearly always fatal. It is most often transmitted to humans through the bite of an infected mammal. The virus in the saliva of an infected animal can be transmitted to humans through a bite or scratch, or contact with broken skin, mucous membranes, or the respiratory tract. In Canada, foxes, skunks, raccoons, and bats may be reservoirs capable of transmitting infection to domestic pets, livestock, and people. Aerosolized rabies virus in bat caves or laboratories and organ transplants are uncommon routes of transmission.

Local Epidemiology 

Human rabies is extremely rare in Ottawa and Canada. The last domestic case of human rabies in Ontario occurred in 1967.

Rabid animals most frequent in Ontario are bats, raccoons, foxes, and skunks. In and around Hamilton, there has been an outbreak of rabies in racoons, skunks, and foxes since 2016.  In Ottawa, confirmed animal rabies cases are most often found in bats (2 bats tested positive for rabies in Ottawa in 2016; one in 2017 to the end of September).There have been no cases of terrestrial rabies locally since 1990 in or around Ottawa. The last case of terrestrial rabies in neighbouring regions was one raccoon in Leeds-Grenville in 2005. However, with raccoon rabies present south of the St. Lawrence River and, more recently, in the area at the western end of Lake Ontario, an introduction of terrestrial rabies by, for example, a hitch-hiking raccoon is always a possibility.

Signs and Symptoms 

Symptoms usually appear approximately 3 to 8 weeks after an exposure, but they can appear as soon as nine days or as long as seven years after a bite. Rabies is usually fatal unless post-exposure prophylaxis is given before symptoms would have appeared.

Early symptoms of rabies may include discomfort, paraesthesia, or pain at the exposure site, as well as headache, malaise, fever, and fatigue, and possibly psychological symptoms such personality changes or apprehension.  More specific symptoms develop after an average of 4 days (up to 10) of prodrome. The fully developed illness typically presents in one of two ways. The more common furious form presents with symptoms of hydrophobia (fear of drinking, difficulty swallowing, foaming at the mouth caused by severe laryngeal or diaphragmatic spasms that cause a sensation of choking when attempting to drink or swallow), aggression and other behavioural changes. The paralytic (or dumb) form of the disease manifests as progressive flaccid paralysis. Both forms of the disease rapidly progress, typically within days, to encephalitis and death.

Risk Assessment 

Factors taken into account during risk assessment:

  • Severity/depth of bites
  • Bites on hands, neck, or face
  • Animal saliva exposure to a pre-existing wound, mucous membrane, or respiratory tract
  • Abnormal or aggressive behaviour in animal
  • Unprovoked attack
  • Prevalence of animal rabies in the area

More severe bites may be more likely to suggest the animal is rabid, and these bites may also provide more opportunity for exposure to and transmission of the virus because of increased exposure to saliva.

Bites on the hands and face are considered high risk exposures because of the high density of nerve endings. Bites to the face and neck are also considered higher-risk exposures because of the proximity to cranial nerves leading directly into the brain.

Ottawa Public Health (OPH) will conduct a risk assessment concerning suspected rabies exposures. However, the ultimate decision regarding administration of rabies post-exposure prophylaxis (RPEP) is based on the informed-consent discussion between the attending health care provider and the patient or parent/guardian.

Note that direct contact with a bat constitutes an exposure. Finding a bat in the room—even if the person was asleep—is therefore generally NOT a reason for prophylaxis UNLESS direct contact is known to have occurred or there is evidence of direct contact with the bat. If the bat was found in the room with a child or adult who is unable to give a reliable history, assessment of direct contact can be difficult.

Please see Public Health Ontario’s Guidance Document on Management of Patients with Suspected Rabies Exposure for further details.

Diagnosis / Labratory Testing 

In animals, the gold-standard diagnostic technique is post-mortem testing of brain tissue by fluorescent antibody test (FAT), which is very sensitive and specific.

There are currently no tests available to diagnose human rabies infection before the onset of clinical disease. Ante-mortem testing (before death) in humans can be performed via RT-PCR on samples of saliva. Serum, saliva, cerebrospinal fluid, and nuchal skin biopsy can be tested for antibodies to rabies virus. Note that no single test is sufficient to rule out rabies, and several tests in combination may be necessary to diagnose ante-mortem rabies in humans. Post-mortem diagnosis is done via FAT.

Please see Guidance for Submission of Human Specimens for Rabies Testing in Canada for further details.

To confirm the effectiveness of pre- or post-exposure vaccination (i.e., a human case of rabies is not suspected), serology can be ordered to determine titres of antibodies to rabies virus. 
Reporting Requirements 

All mammal bites as well as any contact with a mammal that has the potential to transmit rabies to a person must be reported as soon as possible to Ottawa Public Health or your local public health unit (O. Reg. 501/17, s. 1.).

A patient who is suspected to have human rabies must be reported as soon as possible to Ottawa Public Health or your local public health unit (R.S.O. 1990, c. H.7, s. 25; 1998, c. 18, Sched. G, s. 55 (2); O. Reg. 559/91, s. 1).

Call Ottawa Public Health (OPH) at 613-580-2424, ext 24224 or fax 613-580-9640 (Monday to Friday from 8:30 am to 4:30 pm) to report. After hours, on weekends, and on holidays: call 3-1-1 to report. 

Management 

Wash with a mild soap and flush the wound to its depth with copious amounts of water under moderate pressure. Expert opinion suggests washing should be done for at least 15 minutes (NACI 2015). The wound must be carefully cleaned of debris, broken teeth, etc. Some authorities recommend disinfecting the wound with an iodine-containing or alcohol solution or other topical virucidal disinfectant to further decrease the viral load (NACI 2015).

The wound should not be sutured unless indicated for cosmetic or tissue support reasons. Sutures, if required, should be placed after local infiltration of rabies immune globulin (RabIg). They should be loose and not interfere with free bleeding and drainage (Heymann 2008).

As appropriate, follow-up wound care should be undertaken by a physician. Although the risk of rabies may be small, there is a risk of other infections at the wound site. Tetanus-diphtheria vaccination should be updated as required and administration of antibiotics should depend on the clinical picture.

All mammal bites as well as any contact with a mammal that has the potential to transmit rabies to a person must be reported as soon as possible to Ottawa Public Health (OPH) or your local public health unit (O. Reg. 501/17, s. 1.).

Rabies Post-Exposure Prophylaxis (RPEP) of previously unimmunized individuals

Download Rabies Immune Globulin (RabIg) and Rabies Vaccine
Quick Reference Guide to Administration (PDF)

RPEP should be instituted immediately. This consists of rabies immune globulin (RabIg) and 4 to 5 doses of rabies vaccine that should be administered as closely as possible to the recommended schedule (see below).

Please note the importance of appropriate documentation of RPEP, including the exact location of the wound(s), as well as the exact anatomic location(s) of RabIg administration and vaccine administration.

Rabies immune globulin (RabIg) administration

Rabies immune globulin (RabIg) provides immediate passive antibody protection until the exposed person mounts an immune response to the rabies vaccine. These protective antibodies have a half-life of only approximately 21 days. RabIg should be administered as soon as possible after exposure, typically on the same day as the first dose of rabies vaccine (day 0).

  • After wound irrigation, cleaning, and disinfection, RabIg should be infiltrated into the depth of each wound and surrounding wound edges.
  • If there are multiple wounds, each wound should be locally infiltrated with a portion of the RabIg using a separate needle and syringe.
  • As much RabIg should be infiltrated into and around each wound as is anatomically feasible, taking care not to let any RabIg escape from the wound. If possible, the FULL dose should be infiltrated into the wound(s).
  • Certain anatomical sites must be infiltrated carefully (e.g., fingers, toes) to avoid increased pressures in the tissue compartment.
  • If the calculated dose of RabIg is insufficient to infiltrate all wounds, sterile normal saline (0.9% sodium chloride solution) may be used to dilute it 2 to 3 fold to permit thorough infiltration of all wounds.
  • If the entire dose of RabIg cannot be infiltrated into and around the wound(s), any remaining RabIg should be injected at an intramuscular site that is anatomically distant from that of the rabies vaccine administration, preferably in a different limb.
  • Keep in mind that rabies vaccine should NEVER be injected into the gluteal region/buttocks due to the uncertainty of ensuring deposition of the entire vaccine dose well into a muscle body (as opposed to adipose tissue). In contrast, concerning RabIg, according to the manufacturer, RabIg can be administered intramuscularly in the gluteal area (or lateral thigh muscle) using a separate syringe and needle; however, because of risk of injury to the sciatic nerve, the central region of the gluteal area MUST be avoided; only the upper, outer quadrant should be used (Grifols Therapeutics Inc., HYPERRAB®S/D product monograph, 2012).
  • If the site of the wound is unknown (for example, some bat exposures), the entire dose should be administered intramuscularly.
    • If the volume of RabIg is large, it might be necessary to use the same muscle to administer more than one injection. If this is the case, the distance separating the two injections should be between 2.5 to 5.1 cm (1 to 2 inches).
    • IMPORTANT: do NOT administer the rabies vaccine in the same anatomical area as RabIg.
      • Example: if wound site is on right hand or arm, administer vaccine into left deltoid muscle.
      • Rabies vaccine and RabIg should never be mixed in the same syringe.

The dose of RabIg in mL can be calculated with the patient's weight (wt) using the following formula:

Wt (____kg) X 0.133 mL/kg =___ mL of RabIg

Ex: A 70 kg adult would require 9.31 mL of RabIg; Wt (70kg) x 0.133 mL/Kg = 9.31 mL of RabIg

Ensure the total calculated dosage is administered. RabIg is supplied in 2 mL vials. OPH will provide the appropriate number of vials according to the dosage calculation above. There may be some RabIg remaining in one of the vials after administration. DO NOT EXCEED THE CALCULATED DOSE, as this might interfere with the immune response to the rabies vaccine.

If RabIg has not been administered as recommended at the initiation of the rabies vaccine series, it should be administered up to and including 7 days after vaccine initiation, but it should not be administered after that time (i.e., day 8 and beyond) since vaccine-induced antibodies begin to appear within one week. Delayed RabIg administration should still preferably be in the site(s) of the wound(s), even if partial healing has taken place.

Rabies Vaccine

In Canada, there are two active rabies vaccines that are currently approved for use. Imovax® (Sanofi Pasteur Ltd.) is prepared from rabies virus grown in human diploid cell culture (HDCV). RabAvert® (Novartis) is prepared from rabies virus grown in primary cultures of purified chick embryo cells (PCECV).

The initial rabies vaccine is administered at the same time as rabies immune globulin (RabIg), using a separate needle, syringe and injection site (preferably a separate limb). It is administered intramuscularly (IM) at a dose of 1.0 mL into the deltoid muscle. For infants and small children, the anterolateral thigh is also an acceptable injection site. The gluteal area should never be used for injections of rabies vaccine, because of variability in uptake at that site which could lead to a lower antibody response. A healthy, immunocompetent individual requires 4 doses of vaccine at the recommended vaccination schedule (see below).

Neutralizing antibodies begin developing 7 to 10 days after the initial rabies vaccine, and persist for at least 2 years.

Schedule for the administration RPEP

Dose number

When to administer

Dose

Administration site

RabIg

Day 0

20 IU/kg

(0.133 mL/kg)

Wound site ensuring distance from vaccine site

1 rabies vaccine

First dose (Day 0)

1.0 mL

IM Deltoid*

2 rabies vaccine

3 days after first dose (Day 3)

1.0 mL

IM Deltoid*

3 rabies vaccine

7 days after first dose (Day 7)

1.0 mL

IM Deltoid*

4 rabies vaccine

14 days after first dose (Day 14)

1.0 mL

IM Deltoid*

* For infants and small children, the anterolateral thigh is an acceptable injection site.

If person is immunocompromised or on anti-malarial drugs or taking chloroquine

Dose number

When to administer

Dose

Administration site

5 rabies vaccine

28 days after first dose (Day 28)

1.0 mL

IM Deltoid*

* For infants and small children, the anterolateral thigh is an acceptable injection site.

Missed Doses of Rabies Vaccine

Every attempt should be made to adhere to the recommended vaccination schedule. Doses should not be given sooner than the minimum time interval as lower neutralizing antibody titres may result. A dose given too soon will not count towards the series and must be replaced by a dose given at the correct interval. A delayed or missed dose should be given as soon as possible, and then the subsequent doses should have the same minimum interval between doses as in the original schedule. For example, a patient who misses the day 7 dose and presents on day 9 should have the day 7 dose administered that day and the day 14 dose given 7 days later (on day 16) and the following dose (if there is a 5th dose) 14 days after that (on day 30).

Immunocompromised Persons

Patients who are immunocompromised, including those on corticosteroids or other immunosuppressive drugs, chloroquine, antimalarials, and those with immunosuppressive illnesses will require a 5th dose of rabies vaccine on day 28. The ordering physician determines if the patient is considered immunocompromised and informs Ottawa Public Health.

Drug Interactions

Rabies immune globulin (RabIg) can interfere with vaccine effectiveness when given within 14 days after receiving the varicella or MMR vaccines. After receiving RabIg, administration of varicella or MMR vaccines should be postponed for 4 months.

Rabies Post-Exposure Prophylaxis Previously Vaccinated Persons

A person who has been previously vaccinated should get 2 doses of rabies vaccine – one right away and another on Day 3. Rabies immune globulin (RabIg) is not needed.

Note that appropriate documentation of a complete course of pre-exposure (see “Prevention” below) or post-exposure prophylaxis with HDCV or PCECV is required.

Prevention

Most humans are given rabies post-exposure prophylaxis (RPEP) as a result of exposure to domestic animals, therefore it is important to emphasize keeping rabies vaccinations up-to-date for all domestic cats, ferrets, and dogs. Also, maintaining control of pets by keeping cats and ferrets indoors and keeping dogs under direct supervision outdoors is important to prevent their exposure to wild animals with rabies.

Finally, it is important to call animal control if you encounter a stray animal or sick or injured wild animal. Do not approach, touch, or feed wild or stray animals. Teach children not to touch animals, including dogs and cats, even if they appear friendly.

Advise your patients who are at higher-risk of exposure to consider pre-exposure vaccine for rabies, particularly if they have occupational exposures (such as lab workers, veterinarians, animal control or wildlife workers) or are travellers who will spend more than one month in a country where rabies is endemic.

Pre-exposure prophylaxis of high-risk individuals consists of rabies vaccine administered at Day 0, 7 and 21–28. The vaccine is 100% effective immediately after all the doses have been given and persists for up to 2 years after immunization. (Recall that exposure to a potentially rabid animal still requires 2 doses of rabies vaccine post-exposure.) However, protection wanes over time, and this varies from individual to individual, which is why post-exposure vaccines are always given and serologic testing is required every 2 years for individuals at ongoing high risk of exposure. A booster shot is necessary if antibody titres fall below 0.5 IU/mL.

Public Health Role 

Ottawa Public Health (OPH) is contacted by a health care provider who has assessed a patient with a potential exposure to the rabies virus after a bite or contact with an animal's saliva. OPH will deliver rabies post-exposure prophylaxis (RPEP: rabies vaccine and rabies immune globulin) to the health care provider. Following the rabies vaccine schedule from the Canadian Immunization Guide is very important. OPH will call you to make sure that you receive the right doses on the right days. 

Patient Information 

Information for the public can be found on the OPH website and the Health Canada website.

Physician Resources 

Canadian Immunization Guide

PHO Rabies Guidance Document

Rabies Immune Globulin (RabIg) and Rabies Vaccine Quick Reference Guide to Administration (PDF)

Lab Testing

Public Health Ontario – Lab Requisition

Public Health Ontario – Testing Information for Rabies Serology

Canadian Food Inspection Agency CFIA Rabies Testing Animals [PDF]

Human Rabies Testing Information

Reporting

Ottawa Public Health – Communicable Diseases Reporting Page

General Information on Rabies

CDC

International Resources on Rabies

CDC

WHO

Rabies Alliance

Contact Us

If you have questions regarding rabies, or want to notify Ottawa Public Health about an animal bite or potential exposure to rabies, please contact us at 613-580-2424, ext. 24224. 

Communicable Disease Reporting Form

Contact Us