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

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.

Human rabies is extremely rare in Ottawa and Canada. A human case of rabies in Ontario was reported in Brantford-Brant in September 2024 with suspected exposure from a bat in the Timiskaming region. This is the first human case of rabies acquired locally in Ontario since 1967. In all parts of Ontario, bats testing positive for rabies are found intermittently—see Rabies cases | ontario.ca—thereby necessitating a careful assessment of all potential bat exposures.

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.

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.

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.

In situations where patients find a bat in a room in which they have been sleeping, the risk of rabies is considered low if the patient was not woken by direct contact with the bat and there is no identified direct contact and no sign of a bite or scratch or saliva exposure. If the bat was found in the room with a child or adult who is unable to give a reliable history, it may be more difficult to fulfill these criteria and RPEP may be recommended.

Please see Rabies Prevention and Control Protocol, 2023 for further details.

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.

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).

Ottawa Public Health is available to receive animal exposure reports 24 hours a day, 7 days a week:

1. Online: Ottawa Public Health has recently launched a web form to receive reports of potential rabies exposures: Animal Exposure Reporting Form HCP - Ottawa Public Health
2. Phone: 

• • Regular Business Hours (Monday to Friday, 8:30 a.m. to 4:30 p.m.) - 613-580-6744 (after selecting language press 2 to enter the Healthcare stream, 1 to report to OPH, then 1 again to report an animal bite) or: 
  • After Hours/Weekends/Holidays: Please call 3-1-1 and request to speak to a Public Health Inspector  

 3. Fax: A pdf version of our reporting form can be printed off and faxed to 613-580-9648. 

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 - 438 KB)

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 and their volume/dosage and lot numbers.

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. The most effective use of RabIg is in the wound. Correctly administered at the wound site, RabIg neutralizes the virus at the wound site within a few hours. RabIg should be administered as soon as possible after exposure, typically on the same day as the first dose of rabies vaccine (day 0).

• For multiple wound sites, divide the RabIg into separate syringes and needles for each site.

• 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. (See Physician Resources: “Is injecting a finger with rabies immunoglobulin dangerous?”)

• If the calculated volume of the dose of RabIg is insufficient to infiltrate all wounds, the RabIg (specifically, HyperRAB and Imogam) can be diluted according to manufacturers’ instructions in order to provide the full amount of RabIg required for thorough infiltration of all wounds.
• If the entire calculated dose of RabIg cannot be infiltrated anatomically around the wound or site of exposure, give the remainder of the dose intramuscularly (you can use the wounded limb), but reserve a limb free of RabIg, in which to give rabies vaccine. 
• 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 not identifiable (for example, some bat exposures or healed wounds), the entire dose should be administered intramuscularly. Reserve a limb free of RabIg, in which to give rabies vaccine.
• 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.

As of August 2019, RabIg will be available in 2 formulations:

• 2 mL vials containing 150 IU/mL; or
• 1 mL vials containing 300 IU/mL.  

Please ensure the appropriate formula specific to the RabIg formulation being provided is used to calculate the dose required for the individual.

	For 2 mL vials containing 150 IU/mL RabIg: 20 IU/kg x (client wt in kg) ÷ 150 IU/mL = dose in mL  (dose in mL ÷ 2 mL/vial = # of vials to order) 9.09 IU/lb x (client wt in lb) ÷ 150 IU/mL = dose in mL (dose in mL÷ 2 mL/vial = # of vials to order) OR 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
	For 1 mL vials containing 300 IU/mL RabIg: 20 IU/kg x (client wt in kg) ÷ 300 IU/mL = dose in mL  (dose in mL ÷ 1 mL/vial = # of vials to order ) 9.09 IU/lb x (client wt in lb) ÷ 300 IU/mL = dose in mL (dose in mL÷ 1 mL/vial = # of vials to order) OR Wt (____kg) X 0.067 mL/kg =___ mL of RabIg Ex: A 70 kg adult would require 4.69 mL of RabIg: Wt (70kg) x 0.067 mL/Kg = 4.69 mL of RabIg

Note that while the dose in mL to be administered will be different depending on which formulation of RabIg is being used, the number of vials to be dispensed will be the same.

Please use the Table below to determine how many vials are required:

Ensure the total calculated dosage is administered. 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: discard the remainder of the RabIg. 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.

* 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

* 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 5^th 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 5^th 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. A person who has received such a documented complete course within 3 months of a new exposure may not require any post-exposure prophylaxis with this new exposure; please seek advice from Ottawa Public Health about this.

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 two 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 two years for individuals at ongoing high risk of exposure. A booster shot is necessary if antibody titres fall below 0.5 IU/mL.

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. 

Rabies, Ottawa Public Health

General Information on Rabies

Pathogen Safety Data Sheets: Infectious Substances – Rabies virus, Health Canada

Vaccine Administration - Rabies vaccine: Canadian Immunization Guide, Public Health Agency of Canada

Rabies Prevention and Control Protocol, 2023, Ministry of Health

Rabies Immune Globulin (RabIg) and Rabies Vaccine Quick Reference Guide to Administration (PDF - 438 KB), Ottawa Public Health

Short Report: Is injecting a finger with rabies immunoglobulin dangerous?, American Journal of Tropical Medicine and Hygiene

How to Administer Rabies Post-Exposure Prophylaxis, Public Health Ontario (In English only)

Management of Potential Exposure to Rabies Guideline, 2020, Ministry of Health

Lab Testing

Rabies Serology, Public Health Ontario

Rabies Testing at the CFIA: General Information and Submission Guidelines, Canadian Food Inspection Agency [PDF]

Arbovirus, Rabies, Rickettsia and Related Zoonotic Diseases, Public Health Agency of Canada 

Reporting

Communicable Diseases Reporting Page, Ottawa Public Health  

International Resources on Rabies

Rabies, U.S. Centers for Disease Control and Prevention (CDC)

Rabies, World Health Organization (WHO)

Global Alliance for Rabies Control