Update in animal bite

management: Take a bite out of

this
Nancy N. Bermal, MD
Fellow- PPS, PIDSP
 Conflict of Interest Disclosure
Currently an employee of Unilab, Inc
Medical Director – ULIV
Head R and D – Synnovate Pharma Corp

PIDSP representative to the NRPCP TWG

 Objectives
• To provide update to rabies status in the Philippines

• To provide an update on the management of rabies

exposures based on the DOH AO no. 0013 S2018 dated Apr
16, 2018

• Issue on counterfeit rabies vaccine – how to address

• True or False? Rabies is 100% fatal but 100%
preventable?
The following are main strategies in rabies
prevention
A. Pre-exposure prophylaxis
B. Post –exposure prophylaxis
C. Dog vaccination program
D. All of the above
• Which of the following is considered category
3 exposure and would require RIG and
vaccine
A. abrasion on the nose induced to bleed
B. superficial scratch on the leg
C. puncture wound on the index finger
D. A and C are correct
You prescribed RIG and vaccine to your patient with
Category 3. However the patient was only able to
afford the RIG after he has completed the day 7
dose. He was afraid to have rabies since he found
out that his neighbor’s dog died and was positive
for rabies. What will be your management.
A. give the RIG since the biting animal is rabid
B. No need to give the RIG since the patient
has protective Rabies Ab from the vaccine
C. give additional dose of rabies vaccine
D. None of the above
Three months later, the patient came back due to
another dog bite this time he sustained a 5 cm
laceration on the left arm. This happened while he
was playing with his pet dog.
A. give complete PEP including RIG since it’s a
Category 3 bite
B. give only complete course of rabies vaccine
C. give booster dose of the vaccine
D. no need to give any, advice patient to
observe the dog for 14 days.
 Rabies Facts

Neglected disease, 100%

Human infection that occurs
after a transdermal bite or fatal though 100%
scratch by an infected
animal preventable
Rabies
40% of human
rabies cases -
children aged
under 15 years.
 Rabies in the Philippines
35
30
25
20
Males > Females
15
10
5
0
0-5 yrs 6-10 yrs 11-20 yrs 21-40 yrs 41-60 yrs > 60 yrs

Males Females

14

Common during the 12

10
summer months 8
6
4
2
0
Jan Feb Mar Apr May Jun Jul Aug Sept Oct Nov Dec
Rabies in the Philippines

Slide courtesy of Dr Ronaldo Quintana, NRPCP

Status of Animal Bites

Slide courtesy of Dr Ronaldo Quintana, NRPCP

 Animal Bite Treatment Centers
ABTCs
Total of 613 in the entire country

Published: July 26, 2018

 Methodology and principal findings

• 53% of households reported at least one

animal bite /scratch injury over the past 3
years, similar across urban and rural
barangays.
• Overall bite/scratch incidences in 2016–17
per 1000 population
67.3 Nueva Viscaya
41.9 Palawan
48.8 Tarlac
 ABTCs Evaluation
• 50% higher amongst those under 15 years of age
• Household awareness of the nearest ABTCs : > 80%,
but only 44.9% sought proper medical treatment ,
traditional remedies still frequently used.
• Proportion of patients seeking PEP not related to the
distance or travel time to the nearest ABTC
– For those that did not seek medical treatment, most cited
a lack of awareness or insufficient funds and almost a third
visited a traditional healer.
• No deaths from bite/scratch injuries were reported
ABTCs Evaluation
 ABTCs Evaluation
• A cohort of 1,105 patients were interviewed at six
ABTCs in early 2017
– OOPE varied across the ABTCs, from 5.53 USD to 37.83 USD per
patient
– primarily dependent on the need to pay for immunization if
government supplies had run out
– Overall, 78% of patients completed the recommended course
– main reason for non-completion was a lack of time, followed
by insufficient funds.
– Dog observation data revealed that 85% of patients were not
truly exposed to rabies, and education in bite prevention might
reduce provoked bites and demand for PEP
Regions with most number of Animal Bites

Slide courtesy of Dr Ronaldo Quintana, NRPCP

Regions with most number of
human rabies

Slide courtesy of Dr. Ronald Quintana, NRPCP

Provinces/Cities with Most Number
of Animal Bites

Slide courtesy of Dr. Ronald Quintana, NRPCP

Disease Free Zone Initiative Rabies Free Areas
Jointly Declared by DOH and DA
 Rabies prevention
• 2 main strategies:
– Dog Vaccination to interrupt virus transmission
to humans
– Human Vaccination
• Pre-exposure prophylaxis (PrEP) – before exposure,
to high risk individuals
• Post-exposure prophylaxis (PEP) – for exposed
individuals
• Others
– Education, Legislation, Dog population control
22
 Management Guidelines
• DOH Administrative Order on animal bite management
1. AO no. 27 S1996, dated July 26, 1996
2. AO no. 15A S1997, dated Aug. 15, 1997
3. AO no. 164 S2002 dated Oct 16, 2002
4. AO no. 0022 S2005, dated Aug 25, 2005
5. AO no. 0029 S2007 dated Sept 2007
6. AO no. 0027 S2009 dated June 8, 2009
7. Joint DA-DOH AO 0002 S 2011 dated Feb 2, 2011
8. AO no. 0012 S2014 dated March 17, 2014
9. AO no. 0013 S2018 dated Apr 16, 2018
23
 Rationale
AO no. 0013 S2018 dated Apr 16, 2018

• Increase demand on human rabies vaccine

• Global shortage of vaccine due to production
issue of one WHO pre-qualified vaccine
• Update the guidelines on PreP and PEP –
based on WHO recommendation on shorter
and more feasible regimens
• Provide guidance on the selection and use of
human rabies vaccine
Post-exposure Prophylaxis

• Components:
• Wound washing and care
• Vaccination = Active immunization
• Administration of RIG = Passive
immunization

25
 Wound Care
As much as 40% of rabies
infection rate can be
reduced by energetic
wound cleaning
Kaplan MM, Cohen D, Koprowski H, et al Studies on the local
treatment of wounds for the prevention of rabies. Bull WHO 1962;26:765-75

An iodine-containing or similarly
viricidal topical preparation should
be applied to the wound

Wounds that require suturing should be sutured loosely and

only after RIG infiltration
26
 Category 1
Description Treatment
Touching or Wound Care
feeding
animals, licks
on intact skin,
exposure to
rabid patient
(sharing of
eating/ drinking
utensils, casual
contact)
 Category 2

Treatment
Description
Nibbling of Wound care
uncovered skin,
minor scratches Rabies
or abrasions vaccine
without bleeding Observe
including those
induced to bleed biting animal
All Category II
exposures on the
head and neck
 Category 3
Description Treatment
Single or multiple Wound care
transdermal bites
or scratches; Rabies
contamination of Vaccine
mucous RIG
membrane with
saliva from licks; Observe
licks on broken biting animal
skin; exposure to
bat bites or
scratches
Passive Immunization
RIG Recommendation
• should be given as a single dose for all Category III
exposures, in combination with anti-rabies vaccine
• Administer as soon as possible and not beyond 7 days
after the first vaccine dose
• Skin test to eRIG is NOT NECESSARY
• Maximum dose (there is no minimum dose)
– hRIG – 20 iu/kg
– eRIG- 40 iu/kg
• should be infiltrated around and into the wound as
much as anatomatically feasible, even if the lesion has
begun to heal
• Remaining dose does NOT need to be administered IM
at a distant site but can be fractionated in smaller
syringes to be used for other patients aseptically
Passive Immunization
RIG Allocation
– Multiple bites
– Deep wounds
– Bites in highly innervated parts of the body
such as head, neck, hands and genitals
– Patients with severe immunodeficiency
– Hx of biting animal indicative of confirmed or
probable rabies
– Bite or scratch or exposure of mucous
membrane by a bat that can be ascertained for
rabies testing
 Passive Immunization
 RIG provides immediate protection but is short-lived
(half-life 21 days)
 Vaccines provide long term protection but Ab appear
7-14 days after the 1st dose

100
Geometric mean RVNA (IU/mL)

Vaccine
10

1
0.5 iu/mL
0.5 IU/mL RVNA
considered adequate
by WHO/ACIP
0.1
RIG CL184 + PVRV
HRIG + PVRV
0.01
0 3 7 14 21 28 35 42
Time (days)
 Management of the Biting Animal

• Observe biting animal for 14 days

• During 14 days observation period:
– Provide adequate care/food/drink during
observation period
– Consult veterinarian if animal becomes sick
– If the animal dies or sickens, sacrifice the animal
and submit the head for testing

33
 Types of Rabies Vaccines

Generic Name Preparation Dosage

Purified Vero cell 0.5 ml/vial ID – 0.1 ml

Rabies Vaccine (PVRV) IM – 0.5 ml

Purified Chick Embryo 1.0 ml/vial ID – 0.1 ml

Cell Vaccine (PCECV) IM – 1.0 ml

34
 WHO Pre-Qualified Rabies
Vaccines
Generic Name WHO PQ Non WHO PQ
Purified Vero cell Sanofi - Liaoning Chengda Co,
Rabies Vaccine LTD (Speeda)
(PVRV) - Changchun Changsheng
Life Sciences Ltd –
Rabiesvax -
- Indian Immunologicals

Purified Chick GSK

Embryo Cell
Vaccine (PCECV)
35
 Non WHO-prequalified vaccines
• Recommended only during shortage of WHO-PQ
vaccines
• Conditions
– Vaccine is registered with and approved by FDA
– Vaccine proven safe and efficacious for PEP when
administered by ID route using WHO recommended
schedule (published clinical trials on safety and
immunogenicity)
– Potency of 0.5 iu/ID dose (shown in lot release
certificate)
– Product insert contains approved ID dose in CPR

36
 PEP Regimens - Intramuscular
IM Day 0 Day 3 Day 7 Day 14 Day 21 Day 28

5 dose IM

4 dose lM

2-1-1 IM

For WHO PQ and non WHO PQ vaccines

37
 PEP Regimens - Intradermal

ID Day 0 Day 3 Day 7 Day 28

TRC

IPC*

ID dose = 0.1 ml for all vaccines

*IPC regimen - *IPC – Institute Pasteur Cambodge

for WHO PQ vaccines only
38
 Vaccination Regimens
Regimen # vaccine # Clinic # Days
vials Visits Completed
OLD
5 dose IM 5 5 28
2 dose ID 1-2 4 28
NEW
4 dose IM 4 4 14
2-1-1 IM 4 3 21
IPC ID* 1-1.5 3 7
*IPC regimen - for WHO PQ vaccines only
39
 Guidelines
• Changes in the vaccine product and/or route of
administration, if unavoidable during the same
PEP course, are acceptable to ensure PEP
course completion
• Should a vaccine dose be delayed for any
reason, the PEP regimen should be resumed,
(not restarted)
• Individuals with immunodeficiency should be
evaluated in a case-by-case basis and receive a
complete course with RIG

40
 Previously Immunized
Animal Bite Patients
Risk of Criteria – ANY ONE OF THE Recommendation
Exposure FOLLOWING:
High Risk 1. Biting animal cannot be Immediately provide
observed, dies or is sick the booster injections
2. Site of bite is in highly to the patient
innervated parts of the body – Booster doses:
neck, head, genital area, 0.1 ml ID at 4 sites on
hands and toes day 0
3. Multiple deep bites OR
0.1 ml ID/IM at 1 site on
4. Patient is coming from GIDA*
days 0 and 3
areas, i.e. infrequent
transportation to and from
ABTC/ABC
GIDA – geographically isolated and disadvantaged area
41
 Previously Immunized
Animal Bite Patients
Risk of Criteria Recommendation
Exposure
Low - Last dose of vaccine was within the Observe biting
previous 3 months animal for 14 days.
Risk AND If animal remains
- Biting animal is healthy, owned, kept
on a leash or can be confined and is
healthy, withhold
available for observation booster dose
AND ANY ONE OF THE FF:
1. Biting animal is the same animal that
bit the patient previously OR
2. Biting animal is previously immunized
OR
3. Bite is on the extremities
42
 Previously Immunized
Animal Bite Patients
LOCAL WOUND TREATMENT

PEP/PrEP History Give RIG Management

Patients received
complete PrEP or at least
day 0 and 3 doses of PEP Yes if Give full course
AND indicated PEP
Immunocompromised
OR bitten by bat

43
 Previously Immunized
Animal Bite Patients
LOCAL WOUND TREATMENT

PEP/PrEP History Give RIG Management

Patient did not

complete PrEP
OR Yes, if indicated Give full course
Patient received only PEP
1 ID/IM dose of PEP

44
 PrEP Regimens
ImmunoCOMPETENT Day 0 Day 7 Day 21/28
OLD
Intramuscular - 1 site
Intradermal - 1 site
NEW
Intramuscular - 1 site
Intradermal - 2 sites

45
 PrEP Regimens
ImmunoCOMPROMISED Day 0 Day 7 Day 21/28

OLD

Intramuscular - 1 site

NEW

Intramuscular - 1 site

Intradermal - 2 sites

ID dose = 0.1 ml
46
 Management
For patients who are suspected or confirmed to have been
given a counterfeit human rabies vaccine
• No need to give further doses
Animal is • If re-exposed , give full course of the
vaccine +/- RIG

healthy

Potentially • Bitten within the past 6 months: Give a full

course of vaccine or do Ab test if + - give
PreP, if – give full course
rabid , can’t • > 6 months : Give 2 extra doses of vaccine,
day 0 and 7 so that they have Pre-exposure
be observed Prophylaxis (PrEP) and will need only
boosters if bitten again
Counterfeit Registered Product

For more information, inquiries and eReport, www.fda.gov.ph

reporting: Center for Drug Regulation and
[email protected] Research at telephone number
[email protected] (02)809-5596.
• Increased vigilance should include hospitals, clinics,
health centres, wholesalers, distributors, pharmacies
and any other suppliers of vaccines.
• All medical products must be obtained from authentic
and reliable sources
– authenticity and condition should be carefully checked
– Seek advice from a healthcare professional in case of
doubt.
Top Provinces with Most Number of
Human Rabies

Slide courtesy of Dr. Ronald Quintana, NRPCP

 Intradermal Regimen
• Multisite vaccination technique - elicits a
prompt and highly protective immune
response with a small dose
• Immune response induced by ID rabies
vaccination is the same as with the IM
regimens
– Rabies antigen is inoculated into the dermis of the
skin which helps trigger a high immune response
– Ag presenting cells in the skin are more effective
than the ones in muscle 56
Counterfeit Registered Product
Pre-exposure prophylaxis
• Given prior to exposure
• Benefits
• The need for RIG is eliminated
• PEP vaccine regimen is reduced from five to two
doses
• Protection against rabies is possible if PEP is
delayed
• Protection against inadvertent exposure to rabies
is possible
• The cost of PEP is reduced

58
 Rabies Virus
• Bullet-shaped single-stranded RNA-virus
belonging to the genus Lyssavirus, family
Rhabdoviridae
• Sensitive to heating/ boiling, drying, UV and x-
ray, sunlight, ether, detergents. Rabies virus
becomes noninfectious when it dries out and
when it is exposed to sunlight
• Cannot cross intact skin
 Dog Vaccination
Region 2014 2015 2016
I 29.50% 35.28% 34.14%
II 28.19% 63.69% 53.44%
III 44.20% 60.98% 54.48%
IV-A 31.72% 38.49% 39.01%
IV-B - 39.70% 31.51%
V 53.15% 71.29% 63.91%
VI 71.95% 44.40% 53.42%
VII 73.00% 74.74% 73.88%
VIII 40.75% 39.84% 44.91%
IX 75.11% 31.19% 27.65%
X - 38.44% 44.77%
XI 31.92% 34.52% 48.81%
XII 31.15% 34.45% 47.35%
CARAGA 30.04% 46.15% 49.82%
CAR 64.95% 67.37% 57.76%
NCR - 28.51% 33.58%
NIR still with Reg6 71.45% 78.17%
ARMM 36.03% 21.16% 53.40%
Total 33.48% 45.50% 47.43%
DA-BAI and BMGF projectt\
 Rabies in the Philippines
VECTORS
• Majority due to exposure to dogs
• No bats found to have active infection
although 9.5% of bat sera were positive
for neutralizing Ab against ABLV
(Australian Bats Lyssavirus), which
causes indistinguishable clinical
syndromes in infected mammals

Arguin PM et al. Emerging Infectious Diseases 8(3): 2002: 258-262