Rabies Prevention
FERDINAND S. DE GUZMAN MD, FPAFP, FPAMS, FPSVI
DEPARTMENT OF HEALTH
Guidelines on the
Management of Animal Bite Patients
Epidemiology
Virology
Transmission
Pathogenesis
Clinical Manifestations
Prevention
Epidemiology
An acute encephalitis with a fatal outcome with no
effective cure
Reported from more than 100 countries worldwide
1 death of rabies every 15 minutes
>2.5 million live in rabies endemic areas
Among human infections, the 12th most common cause
of death (WHO)
99% of human rabies occur in Asia, Africa and South
America
Weekly Epidemiological Record, No. 14, 5 April 2002
Epidemiology
Yearly, 50,000 people die from rabies worldwide
31,000 (56%) occur is Asia
Mainly in RURAL areas – 90%
Children and young adults are the most susceptible
age group
Children under 15 years of age account for 30%-
50% of human rabies cases
Preventing the incurable: Asian Rabies Experts advocate rabies control, Vaccine 2005; page 1
Epidemiology
In Asia
More than 2.5 billion people are potentially exposed
to rabies infection
8 million people receive post-exposure treatment
Estimated economic burden of USD 563 million
(95.6% of the total burden of rabies worldwide)
Preventing the incurable: Asian Rabies Experts advocate rabies control, Vaccine 2005; page 1
Epidemiology
In Asia
Main mode of transmission is through dog bites –
96-98% of human rabies deaths
Other animals may also be infected – cats, cattle,
monkeys and mongoose
Serologic evidence of infection in bats has been
documented in Cambodia.
Preventing the incurable: Asian Rabies Experts advocate rabies control, Vaccine 2005; page 1
Epidemiology
In Asia: An economic burden but neglected
disease
Lack of awareness among general public and health
practitioners
Shortage of funds for the modern cell-culture
vaccines and immune globulins
Lack of political will to control canine rabies
Preventing the incurable: Asian Rabies Experts advocate rabies control, Vaccine 2005; page 1
Epidemiology
Philippines
Incidence of 5-8 per million population (One of the
highest rates worldwide)
Around 300-500 cases/year
Males > Females
More common during the summer months
Preventing the incurable: Asian Rabies Experts advocate rabies control, Vaccine 2005; page 1
Epidemiology
Philippines
160000 Launch of Awareness 700
Human Rabies Deaths
140000 Campaign and usage of 600
Animal Bite Victims
ID Regimen
120000 500
100000
400
80000
300
60000
40000 200
20000 100
0 0
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Animal Bite Victims Human Rabies Deaths
The result of yearly rabies awareness campaign:
Improved in the reporting system
Increased knowledge of people about rabies
Department of Health – National Rabies Prevention and Control Program 1992 - 2005
Virology
Structure
Non-segmented negative-stranded RNA
enveloped virus
Bullet shaped: 180nm X 75nm
Have a phospholipid envelope with 10-nm
glycoprotien surface spikes
The RNA genome encodes 5 proteins:
N, NS, M, G and L
Virology
5 Structural protein G protein
Glyco-protein surface spikes
Matrix protein Envelope
M protein
Nucleoprotein
RNA
Virion transcriptase
Nucleocapsid asso.
Protein (NS protein)
Virology
Virology
Rabies Virus
Stable in pH 3-11
Inactivated by
desiccation,
UV and X ray
sunlight
trypsin
b-propiolactone
ether
detergents
Type 1 represents classic rabies virus
Weekly Epidemiological Record, No. 14, 5 April 2002
Virology
Stanley A. Plotkin Clin. Infect. Dis. 2000, 30:4-12
Transmission
Atanasiu P et al. La rage. Etudes medicales 1979; 3 et 4
Transmission
Philippines
98% due to dog bites
–88% pet dogs
–10% stray dogs
2% due cat bites & other domestic
animals
National Rabies Prevention and Control Program, Manual of Operations, 2001
Transmission
Pathogenesis
Clinical Manifestations
Incubation Period
Extraordinarily variable from 4 to 7 years after
exposure
Generally 20 – 90 days
Major influencing factors
the virus load
the virus strain
the severity of exposure
the locality of exposure
Clinical Manifestations
Prodrome Period
Lasts for 2 – 10 days
Non-specific symptoms
Malaise
Fatigue
Headache
Fever
Pain or paresthesia close to the site of exposure
Clinical Manifestations
Clinical Symptoms
Lasts 2 – 12 days
Two clinical forms:
Clinical Manifestations
Coma and Death
Onset: 4 to 10 days after symptoms start
Modern intensive care may prolong life
BUT
Numerous complications occur during coma
Death is inevitable due to complications of
cardiorespiratory failure
Clinical Manifestations
Survival after treatment of Rabies with Induction of
Coma
Patient survive with neurologic impairment
Although patients improvement continued five months after initial
hospitalization, cannot predict the long term outcome
Survival after Treatment of Rabies with Induction of Coma. Willoughby, R et al.
The New England Journal of Medicine, 352; 24, June 16, 2005, 2508-2514
Prevention
Early intervention
Prevention
Rabies Treatment and Prophylaxis
Local Wound Care
Post exposure Treatment
Pre exposure Prophylaxis
Rabies is 100% FATAL disease
but preventable!
Prevention
Guide for Post-exposure Prophylaxis
WHO recommendation on Rabies 1997 WHO/EMC/ZOO 95.6
Prevention
Local Wound Care
Vigorously washing and flushing with soap or
detergent and water for 10 minutes
Apply alcohol, povidone iodine or any antiseptic
Suturing should be avoided at all times since it may
inoculate virus deeper into the wound
Do not apply any ointment, cream or dressing
Anti-tetanus immunization maybe given, if indicated
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Local Wound Care
Anti microbials are recommended for the following
conditions
All frankly infected wounds
All category III animal bites that are either deep,
penetrating multiple or extensive or located on the hand/
face/ genital area
Recommended Anti microbials
Amoxicillin / Clavulanic
Cefuroxime axetil
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
DOH Guidelines for Post Exposure Treatment
CATEGORY I
Category of exposure Management
a. Feeding/touching an animal Wash exposed skin immediately with
soap and water
b. Licking of intact skin (with
reliable history and thorough No vaccine or RIG needed
physical examination)
c. Exposure to patient with signs
and symptoms of rabies by *Pre exposure vaccination may be
sharing or eating or drinking considered
utensils*
d. Casual contact to patient with
signs and symptoms of rabies*
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
DOH Guidelines for Post Exposure Prophylaxis
CATEGORY II
Category of exposure Management
a.Nibbling / nipping of Start vaccine immediately
uncovered skin with Condition of the animal:
bruising
1. Complete vaccination regimen until day 28/30 if:
b.Minor scratches / a) animal is rabid, killed, died or unavailable for 14 day
abrasions without observation and examination
bleeding* b.) if animal under observation died within 14 days
and was IFAT positive or no IFAT testing was done or
c. Licks on broken skin had signs of rabies
*include wounds that 2.Complete vaccination regimen until day 7 if:
are induced to bleed a.) if animal is alive and remains healthy after 14 day
observation period
b.) if animal under observation died within 14 days,
was IFAT negative and without any signs of rabies.
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
DOH Guidelines for Post Exposure Prophylaxis
CATEGORY III
Category of exposure
a. Transdermal bites or scratches (to include
puncture wounds, lacerations, avulsions)
b. Contamination of mucous membrane with saliva
(ie licks)
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
DOH Guidelines for Post Exposure Prophylaxis
CATEGORY III
Category of exposure
c. Exposure to rabies patient** through bites,
contamination of mucous membranes or open
skin lesions with body fluids (except blood/feces)
through splattering, mouth to mouth
resuscitation, licks of eyes, lips, vulva, sexual
activity, exchanging kisses on the mouth or other
direct mucous membrane contact with saliva
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
DOH Guidelines for Post Exposure Prophylaxis
CATEGORY III
Category of exposure
d. handling of infected carcass or ingestion of raw
infected meat
e. all Category II exposures on head and neck
area
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
DOH Guidelines for Post Exposure Prophylaxis
CATEGORY III
Management
Start vaccine and RIG immediately
Condition of the animal:
1. Complete vaccination regimen until day 28/30 if:
a) animal is rabid, killed, died or unavailable for 14 day observation and
examination
b.) if animal under observation died within 14 days and was IFAT positive or
no IFAT testing was done or had signs of rabies
2.Complete vaccination regimen until day 7 if:
a.) if animal is alive and remains healthy after 14 day observation period
b.) if animal under observation died within 14 days, was IFAT negative and
without any signs of rabies.
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Passive Immunization Products (RIG)
To provide immediate neutralizing antibodies to cover
the gap until the appearance of vaccine detectable
antibodies.
Given to Category III exposures as quickly as possible
Total computed RIG should be infiltrated around and
into the wound as much as anatomically feasible even if
the lesions has healed.
The remaining RIG should be administered deep IM at a
site distant from the site of vaccine injection
Computation of dosage
HRIG: 20 IU/kg. body weight
ERIG / F(ab’)2: 40 IU/kg. body weight
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Passive Immunization Products (RIG)
Three types of passive immunization products (RIG):
Human Rabies Immune Globulin (HRIG) – derived from
plasma of human donors at 20 IU/ kg body weight.
– Available preparation is 2.0 ml/vial; 150 IU/ml
Highly purified antibody antigen binding fragments
(F(ab’)2) – produced from equine rabies immune globulin (ERIG)
administered at 40 IU/ kg body weight.
– Available preparation is 5.0 ml/vial; 200 IU/ml
Equine Rabies Immune Globulin (ERIG) – derived from horse
serum administered at 40 IU/ kg body weight.
– Available preparation is 5.0 ml/vial; 200 IU/ml
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Passive Immunization Products (RIG)
All imported & locally produced RIG should meet the
following criteria before use in the Philippines:
Testing and evaluation by the WHO or WHO recognized
National Regulatory Authority (NRA) or National Control
Laboratory (NCL) – RFFIT, MNT, pre-clinical safety,
pyrogenicity and product purity
Animal survivorship study maybe required
The results of the clinical trials should conducted on the
product should be published in peer reviewed journal.
The local NRA/NCL should validate the RFFIT and MNT,
purity of the product and require local clinical trials on
safety
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Active Immunization
General Principle
Vaccines should be stored at 2°C to 8°C (in a
refrigerator, not freezer)
Once reconstituted, vaccines should be kept in the
refrigerator and used within 8 hours
Injections should be given on the deltoid area of each
arm in adults or at the anterolateral aspect of the thigh
in infants
Vaccine should never be injected in the gluteal area as
absortion is unpredictable
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Active Immunization
The types of Rabies Vaccine available in the Philippines
Purified Vero Cell Rabies Vaccine (PVRV) – 0.5ml/vial
Purified Chick Embryo Cell Vaccine (PCECV) – 1.0ml/vial
Any of the two vaccines maybe administered either
intramuscularly (IM) or Intradermally (ID).
The potency of vaccine should be at 2.5 iu/IM dose and
0.5 iu/ID dose as evidenced by batch testing performed
by a WHO recognized National Regulatory Authority or
National Control Laboratory
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Active Immunization
Only rabies vaccines which satisfy all the following
criteria can be used in the Philippines:
Produced by a WHO pre-qualified manufacturer
With local clinical trials on Safety, Immunogenicity, Efficacy
(as evidenced by published clinical trials in peer reviewed
journals and local testing studies
Evaluated by the DOH Rabies Technical Group
Registered with and approved by the BFAD
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Post Exposure Vaccination Regimen:
Standard Intramuscular Schedule
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Post Exposure Vaccination Regimen:
Standard Intramuscular Schedule
Day of Site of
PVRV PCECV
Immunization injection
Day 0 0.5 ml 1.0 ml One deltoid
Day 3 0.5 ml 1.0 ml One deltoid
Day 7 0.5 ml 1.0 ml One deltoid
Day 14 0.5 ml 1.0 ml One deltoid
Day 28 0.5 ml 1.0 ml One deltoid
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Post Exposure Vaccination Regimen:
2-1-1 Intramuscular Schedule
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Post Exposure Vaccination Regimen:
2-1-1 Intramuscular Schedule
Day of Site of
PVRV PCECV
Immunization injection
Left and right
Day 0 0.5 ml 1.0 ml
deltoids
Day 7 0.5 ml 1.0 ml One deltoid
Day 21 0.5 ml 1.0 ml One deltoid
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Post-Exposure Vaccination Regimen:
Updated 2-site Intradermal Schedule (2-2-2-0-2)
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Post-Exposure Vaccination Regimen:
Updated 2-site Intradermal Schedule (2-2-2-0-2)
Day of Site of
PVRV PCECV
Immunization injection
Day 0 0.1 ml 0.1 ml Left and right deltoids
Day 3 0.1 ml 0.1 ml Left and right deltoids
Day 7 0.1 ml 0.1 ml Left and right deltoids
Day 14 None None None
Day 30 0.1 ml 0.1 ml Left and right deltoids
Each intradermal dose should have at
least 0.5 IU per 0.1 ID dose vaccine
potency to achieve protection
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Post-Exposure Vaccination Regimen:
Updated 2-site Intradermal Schedule (2-2-2-0-2)
Importance of Rabies Vaccine Potency
1.0 ml vaccine 0.5ml vaccine
Reconstituted Reconstituted 0.5 ml
VACCINE POTENCY
1.0 ml vaccine vaccine
IM dose > 2.5 IU > 2.5 IU
0.2ml/ID dose 0.1ml/ID dose
ID dose volume – 1/5th
0.5 IU/ID dose 0.5 IU/ID dose
0.1ml/ID dose N/A
ID dose volume – 1/10th
0.25 IU/ID dose N/A
5.0 IU/IM dose is required to support the 0.1 ml/ID dose of
1.0ml rabies vaccine
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Post Exposure Vaccination Regimen
8-site Intradermal Regimen
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Post Exposure Vaccination Regimen
8-site Intradermal Regimen
Day of Number
PCECV Site of injection
Immunization of doses
Deltoid (2), anterolateral thigh
Day 0 0.1 ml 8 (2), lower quadrant of abdomen
(2), suprascapular region (2)
Day 7 0.1 ml 4 Deltoid (2), anterolateral thigh (2)
Day 30 0.1 ml 1 Deltoid (1)
Day 90 0.1 ml 1 Deltoid (1)
Not an optimum regimen for Category III animal bites.
Can be used when RIG is not available
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Post Exposure Vaccination Regimen
Previously Immunized Animal Bite Patients
Interval from last dose Vaccination (ID or IM)
<than 1 month No booster dose
1 – 6 months 1 booster
>6 months to 3 years Two booster doses (D0, D3)
Full course of active
>than 3 years
immunization
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Post Exposure Vaccination Regimen
Under Special Conditions
Pregnancy and infancy is NOT contraindicated to treatment
Babies who are born of rabid mothers should be given vaccine
and RIG as early as possible at birth
Patients taking chloroquine, anti-epileptic drugs and systemic
steroid as well as alcoholic patients should be given standard
IM regimen
Immunocompromised individuals should be given vaccine using
standard IM regimen + RIG for both Category II and III
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Pre Exposure Vaccination
Pre Exposure Vaccination Benefits
The need for passive immunization product (RIG) is
eliminated
PET vaccine regimen is reduced from five to two doses
Protection against rabies is possible if PET is delayed
Protection against inadvertent exposure to rabies is possible
The cost of PET is reduced
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Pre Exposure Vaccination
Prophylactic immunization is recommended to
individuals at high risk of exposures
Personnel in rabies diagnostic laboratories
Veterinarians and veterinary students
Animal handlers
Health care workers directly involved in care of rabies
patients
Individuals directly involved in rabies control
Children 2 – 10 years old
Field workers
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Prevention
Pre Exposure Vaccination Schedule
Schedule PVRV/PCEC PVRV/PCECV
Day Day
Day 0 Day 7 Day 0 Day 7
21/28 21/28
Intradermal 0.1 ml 0.1 ml 0.1 ml 0.1 ml 0.1 ml 0.1 ml
Intramuscular 0.5 ml 0.5 ml 0.5 ml 1.0 ml 1.0 ml 1.0 ml
Department of Health, Revised Guidelines on Management of Animal Bite Patients, 2005
Thank You
