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
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