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: [Link]
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
[Link]
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
Can Comm Dis Rep 31:1, 2005
Intradermal use of rabies vaccine
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)
Can Comm Dis Rep 31:1, 2005
Intradermal use of rabies vaccine
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
Can Comm Dis Rep 31:1, 2005
Intradermal use of rabies vaccine
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
Can Comm Dis Rep 31:1, 2005
Intradermal use of rabies vaccine
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
3 years after 3rd dose: 80% >0.5 IU/mL
5 years after 3rd dose: 75% >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.
Modified from MJ Warrell, University of Oxford
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
Modified from MJ Warrell, University of Oxford
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
Modified from MJ Warrell, University of Oxford
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.
Modified from MJ Warrell, University of Oxford