Rabies and Intradermal Rabies Vaccination: Alan C. Jackson, MD

Rabies and Intradermal
Rabies Vaccination
Alan C. Jackson, MD
Professor of Medicine (Neurology)
and of Medical Microbiology
Head, Section of Neurology
University of Manitoba
Winnipeg, Manitoba, Canada
Rabies virus structure
Matrix protein
Envelope
Glycoprotein
Nucleocapsid protein
Source: http://www.cdc.gov
Human rabies
Photo courtesy of David Warrell, UK

Clinical forms of rabies
 encephalitic = furious
 ~ 80%
 paralytic = dumb
 ~ 20%
Encephalitic rabies
 prodromal symptoms
 paresthesias/pain/pruritus at site of bite
 episodes of generalized arousal or
hyperexcitability separated by lucid
periods
 autonomic dysfunction
 hydrophobia
Paralytic rabies
 paresthesias/pain/pruritus at site of bite
 early flaccid muscle weakness
 often begins in bitten extremity
 progresses to produce quadriparesis
 bilateral facial weakness
 sensory examination is usually normal
 sphincter involvement
 fatal outcome
 often misdiagnosed as Guillain - Barré syndrome
Geographic distribution of rabies - 2000
No information: DRC, Benin ,Burkina, Sierra Leone, Liberia, Gambia,

Mauritania, Somalia, Yemen, Malaysia, Laos, Myanmar, Vietnam
Cambodia, North Korea
DALY (disability-adjusted life year) scores =
years of life lost + years of life with a disability
Disease Total DALYs lost (X 1000)
Malaria 42,280
Tuberculosis 36,040
Lymphatic filariasis 5,644
Leishmaniosis 2.357
Schistosomiasis 1,760
Trypanosomiasis 1,598
Rabies 1,160
Onchocerciasis 987
Dengue 653
Chagas 649
Leprosy 177
Emerg Inf Dis 10, 2004
Human rabies prevention
United States
Recommendations of the CDC’s
Advisory Committee on Immunization Practices
MMWR Recommendations and Reports
January 8, 1999
http://www.cdc.gov/mmwr
Rabies postexposure guide:
exposure to dogs, cats, and ferrets
Evaluation of Animal Recommendation

Healthy and available for No treatment unless
10 days observation animal develops clinical
signs of rabies
Rabid or suspected rabid Immediate treatment*
Unknown (e.g., escaped) Consult local

public health
department
*Discontinue treatment if tests on animal prove negative.
Recommended prophylaxis in exposed individuals
not previously vaccinated against rabies
Wound site(s) Immediate thorough cleansing of
all wounds with soap and water.
Tetanus prophylaxis; antibiotics
Human Rabies 20 IU/kg body weight

Immune Globulin • As much of the RIG as possible
(RIG) should be infiltrated in wound(s)
• The remainder should be given IM
at a site distant from vaccine
Rabies Vaccine IM (1 mL) in the deltoid area on

days 0, 3, 7, 14, and 28
MMWR 48: RR-1, 1999
Rabies Vaccines Available in Canada
RabAvert® Imovax ®
Manufacturer Novartis Sanofi Pasteur
(Merck Frosst)
Cell culture primary chick MRC-5 human
embryo lung cell line
fibroblasts
Common PCECV HDCV

designation
MMWR;48:RR-1, January 8, 1999

Product package inserts, 2006
Adverse Reactions to Rabies Vaccines
Most common side-effects of rabies vaccines:
 Systemic reactions such as headache,
myalgia, malaise (5-40%)
 Mild to moderate local reactions at injection
site (30-74%)
Populations at increased risk of
exposure to rabies
 Rabies research laboratory workers
 Veterinarians, staff, veterinary students
 Animal control and wildlife workers
 Bat handlers
 Spelunkers
 Travellers to certain rabies-endemic areas
MMWR 48: (RR-1), 1999
Assessing the Rabies Risk for Travellers
 Destination
 Duration of travel
 Anticipated activities
 Access to medical care and

appropriate PEP biologics
Preexposure rabies prophylaxis
 3 doses of rabies vaccine (days 0, 7, and 21 or
28)
 May check rabies antibody titre periodically –
want >0.5 IU/mL
 after a rabies exposure:
 2 doses of IM rabies vaccine (days 0 and 3)
 no HRIG
Pre-exposure rabies prophylaxis
Tissue culture vaccine: 1 dose IM or 0.1 ml ID
Day 0 7 21 28
• If CHLOROQUINE malaria prophylaxis, give IM only
• If immunosuppressed check neut. Antibody titre ≥ 0.5 IU/ml
HIV positive patients - CD4 counts <300 may be unresponsive
Modified from MJ Warrell, University of Oxford
Photo courtesy of Claudius Malerczyk (Novartis)
Can Comm Dis Rep 31:1, 2005
Intradermal use of rabies vaccine
 Gold standard is IM administration of rabies
vaccine
 ID regimen is an acceptable alternative
 Uses one-tenth the dose
 Comparable degree of protection
 Economical and widely accepted
 Pre-exposure = three 0.1 mL doses on days 0,
7, and 21 or 28 intradermally on upper arm
 After reconstitution of 1.0 mL dose, may store
at 4 – 8 degrees C for up to 8 hours with
proper aseptic precautions
 PCECV shown to be immunogenic 7 days
after reconstitution with storage in a clinic
refrigerator (Khawplod et al. CID 2002)
 Neutralization titres after ID vaccination are
lower than after IM, but adequate protective
levels
 Briggs found that after 2-2.5 years:
 79% of IM vs. 51% of ID had satisfactory titres
 ACIP, at 2 years:
 93-98% for IM vs. 83-95% for ID
Manitoba n=488 in 2005
 6-12 mo after 3rd dose:
 95% >0.5 IU/mL
 Median 2.7 IU/mL
Ontario and Alberta

 favourable, but smaller experience

Manitoba n=1000 as of 2008
 1 year after 3rd dose: 92% >0.5 IU/mL
 2 years after 3rd dose: 87% >0.5 IU/mL
Preliminary data from Drs. O. Larios and F. Aoki

Importance of maintaining the
antibody level is unknown
 The response to booster doses is
predictable and rapid.
 In ‘low responders’ the antibody response

may not be so high (significance unknown).
 Detectable antibodies may not be

necessary for protection if booster doses
are given promptly after exposure.

Approach to immunization of travellers
3 dose pre-exposure course
If risk of exposure continues, then booster dose at
1 – 2 years
Travellers with access to vaccine: If exposed to
rabies need no further boosters
Travellers to remote areas with no access to
vaccine: Should repeat booster dose before
departure if last dose was > 3 - 5 years
previously (if antibody < 0.5 IU/ml)
Ensure booster doses if rabies exposure ASAP
Efficacy of prophylaxis
 Pre-exposure vaccine followed by post-
exposure boosters – no deaths reported
 If no previous vaccine: optimal post-

exposure treatment highly effective, but
deaths occur with delay or incomplete
treatment
Rabies prevention - Summary
 Rabies is a preventable disease.
 Failure to recognize a risk of infection results in
human deaths.
 Increased awareness of sources and routes of
virus transmission could save lives.
 Pre-exposure vaccination should be used widely.
 Post-exposure treatment is urgent.
 For previously vaccinated people post -exposure
treatment is simpler, cheaper and more effective.

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Rabies and Intradermal

Photo courtesy of David Warrell, UK

No information: DRC, Benin ,Burkina, Sierra Leone, Liberia, Gambia,

Lymphatic filariasis 5,644

Evaluation of Animal Recommendation

Rabid or suspected rabid Immediate treatment*

Unknown (e.g., escaped) Consult local

Human Rabies 20 IU/kg body weight

Rabies Vaccine IM (1 mL) in the deltoid area on

Common PCECV HDCV

MMWR;48:RR-1, January 8, 1999

 Access to medical care and

Ontario and Alberta

Can Comm Dis Rep 31:1, 2005

Preliminary data from Drs. O. Larios and F. Aoki

 In ‘low responders’ the antibody response

 Detectable antibodies may not be

Modified from MJ Warrell, University of Oxford

 If no previous vaccine: optimal post-

Modified from MJ Warrell, University of Oxford

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