Transcript Rabies - Winnipeg Health Region

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
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encephalitic = furious
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~ 80%
paralytic = dumb
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~ 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
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Paralytic rabies
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paresthesias/pain/pruritus at site of bite
early flaccid muscle weakness
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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
10 days observation
No treatment unless
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
Immune Globulin
(RIG)
20 IU/kg body weight
Rabies Vaccine
IM (1 mL) in the deltoid area on
days 0, 3, 7, 14, and 28
• As much of the RIG as possible
should be infiltrated in wound(s)
• The remainder should be given IM
at a site distant from vaccine
MMWR 48: RR-1, 1999
Rabies Vaccines Available in Canada
RabAvert®
Imovax ®
Manufacturer
Novartis
(Merck Frosst)
Sanofi Pasteur
Cell culture
primary chick
embryo
fibroblasts
MRC-5 human
lung cell line
PCECV
HDCV
Common
designation
MMWR;48:RR-1, January 8, 1999
Product package inserts, 2006
Adverse Reactions to Rabies Vaccines
Most common side-effects of rabies vaccines:
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Systemic reactions such as headache,
myalgia, malaise (5-40%)
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Mild to moderate local reactions at injection
site (30-74%)
Populations at increased risk of
exposure to rabies
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Rabies research laboratory workers
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Veterinarians, staff, veterinary students
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Animal control and wildlife workers
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Bat handlers
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Spelunkers
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Travellers to certain rabies-endemic
areas
MMWR 48: (RR-1), 1999
Assessing the Rabies Risk for Travellers
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Destination
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Duration of travel
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Anticipated activities
 Access to medical care and
appropriate PEP biologics
Preexposure rabies prophylaxis
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3 doses of rabies vaccine (days 0, 7, and 21
or 28)
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May check rabies antibody titre periodically –
want >0.5 IU/mL
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after a rabies exposure:
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2 doses of IM rabies vaccine (days 0 and 3)
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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
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Gold standard is IM administration of rabies
vaccine
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ID regimen is an acceptable alternative
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Uses one-tenth the dose
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Comparable degree of protection
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Economical and widely accepted
Can Comm Dis Rep 31:1, 2005
Intradermal use of rabies vaccine
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Pre-exposure = three 0.1 mL doses on days 0,
7, and 21 or 28 intradermally on upper arm
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After reconstitution of 1.0 mL dose, may store
at 4 – 8 degrees C for up to 8 hours with
proper aseptic precautions
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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
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Neutralization titres after ID vaccination are
lower than after IM, but adequate protective
levels
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Briggs found that after 2-2.5 years:
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79% of IM vs. 51% of ID had satisfactory titres
ACIP, at 2 years:
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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
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6-12 mo after 3rd dose:
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95% >0.5 IU/mL
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Median 2.7 IU/mL
Ontario and Alberta
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favourable, but smaller experience
Can Comm Dis Rep 31:1, 2005
Intradermal use of rabies vaccine
Manitoba n=1000 as of 2008
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1 year after 3rd dose: 92% >0.5 IU/mL
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2 years after 3rd dose: 87% >0.5 IU/mL
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3 years after 3rd dose: 80% >0.5 IU/mL
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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
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The response to booster doses is
predictable and rapid.
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In ‘low responders’ the antibody response
may not be so high (significance unknown).
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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
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Pre-exposure vaccine followed by postexposure boosters – no deaths reported
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If no previous vaccine: optimal postexposure treatment highly effective, but
deaths occur with delay or incomplete
treatment
Modified from MJ Warrell, University of Oxford
Rabies prevention - Summary
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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