Republic ofthe Philippines

Department of Health
OFFICE OF THE SECRETARY
APR lfi 2018

ADMINISTRATIVE ORDER
No. 2018- ()0 l5

SUBJECT: Revised Guidelines on the Management of Rabies Exposures

I. BACKGROUND AND RATIONALE

Rabies is a fatal disease in developing countrieswhere animal immunization and control

of dogs are inadequate. In View of the 100% case fatality of human rabies, the prevention
, of rabies infection after exposure is of utmost importance.

The Department of Health (DOH), having committed itself to the prevention of human
deaths due to rabies, provides vaccines to high—risk exposed patients for Post-Exposure
Prophylaxis (PEP) through the Animal Bite Treatment Centers (ABTCs). In 1997, the
National Rabies Prevention and Control Program introduced the intradermal (ID)
administration of rabies cell culture and embryonated egg—based vaccines (CCEEV), an
economical regimen that reduces the cost of PEP by as much as 60— 80%. The DOH
maintains the use of the intradermal regimen for PEP at the ABTCs. The DOH procures
human anti-rabies vaccines which are registered by the Philippine Food and Drug
Administration (FDA), listed in the Philippine National Drug Formulary and pre-
qualified by the World Health Organization (WHO).

Over the past two years, the number of animal bite Victims seeking PEP has increased
to over 1 Million cases per year. While the demand for human rabies vaccine is
increasing in the country, there is an anticipated global shortage of the said vaccine due
to issues in the production of one WHO prequalified vaccine.

Of recent, WHO provided recommendations on shorter and more feasible protocols for
PEP and Pre—Exposure Prophylaxis (PrEP).

This AD is to update the guidelines on PEP and PrEP and to provide guidance on the
selection and use of human rabies vaccine to help address the global shortage of WHO
pre-qualified human rabies vaccines.

All government health workers at all levels shall adopt these treatment guidelines to
ensure standard and rational management of rabies exposures. Private practitioners in
the country are strongly encouraged to adopt these treatment guidelines.

a)
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II. OBJECTIVE

To update policy guidelines and procedures on provision of PEP and

PrEP to address
the global shortage of human rabies vaccine and immunoglobulins.

III. COVERAGE

All government health workers at all levels shall adopt these

treatment guidelines to
ensure standard and rational management of rabies exposures. Private
practitioners in
the country are strongly encouraged to adopt these treatment
guidelines.

IV. DEFINITION OF TERMS

A. Active Immunization — refers to the administration of vaccine

a to induce protective
immune response.
B. Cell Culture & Embryonated Egg —based Vaccine
(CCEEV) - vaccines that use
mammalian cell lines (cell-culture) as well as embryonated
eggs in the isolation,
titration of animal viruses and cultivation to produce vaccines. CCEEV include
Purified Vero Cell Rabies Vaccine (PVRV), Human Diploid Cell Vaccine
(HDCV)
and Purified Chick Embryo Vaccine (PCEC). CCEEV will
replace everything that
refers to Tissue Culture Vaccine (TCV).
Immunocompromisedhost — refers to patients receiving immunosuppressive drugs
such as systemic steroids (not topical or inhaled) and
chemotherapeutic drugs for
cancer, AIDS and HIV infected patients and patients with immune deficiency. These
patients are expected to have lower immune response to immunization.
Incubation Period — refers to the period from the time of
exposure up to the
appearance of first clinical symptoms of rabies. It is extremely variable ranging from
4 days to 7 years; but generally 20 to 90 days.
Observation Period — refers to animal observation for 14 days from the time
of bite
until the appearance of expected symptoms of rabies.
Passive Immunization — refers to the administration of pre-formed
antibodies
(immune globulins or passive immunization products) to provide immediate
protection. These antibodies come from either human or animal source.
Post-Exposure Prophylaxis (PEP) — formerly post exposure treatment (PET); refers
to anti-rabies treatment administered after an
exposure (such as bite, scratch, lick,
etc.) to potentially rabid animals. It includes local wound
care, administration of
rabies vaccine with or without Rabies Immune Globulin
(RIG) depending on
category of exposure.
Pre-exposure prophylaxis (PrEP) — refers to rabies vaccination administered before
an exposure to potentially rabid animals. This is usually given to those who
are at
high risk of getting rabies such as veterinarians, animal handlers, staff in the
rabies

fl
laboratory, hospitals handling rabies patients and school children from
high risk
areaS, etc.

7‘4“”
 I. Prodromal Period — refers to the period lasting for 10 days with
non—specific
manifestations, which include fever, sore throat, anorexia, nausea, vomiting,
generalized body malaise, headache and abdominal pain. Paresthesia or pain at the
site of the bite is due to viral multiplication at the spinal
ganglionjust before it enters
the brain.
J.Rabid Animal — refers to biting animal with clinical manifestation of rabies and/or
confirmed laboratory findings.
K. Suspected Rabid Animal — refers to biting animal with
a potential to have rabies
infection based on unusual behavior, living condition like stray dogs,
endemicity of
rabies in the area and no history of immunization.
L. Rabies Immunoglobulin (RIG) - is an injectable
preparation of rabies antibody
administered to unvaccinated persons to provide immediate but temporary
protection until the body can actively produce antibodies of its own induced by the
human rabies vaccine.
M. Vaccine Potency ~ refers to the amount of acceptable active
ingredients in a rabies
vaccine which is expected to provide at least minimum protection.

GENERAL GUIDELINES

A. Management of animal bite cases, including provision of human

rabies vaccine, is a
joint responsibility of the Department of Health and the Local Government Units.
B. Rabies Control Program shall be integrated to the
regular health services provided
by local health facilities of bite victims, as a measure.
C. PEP and PrEP shall be carried out by Local Government Units
through the Animal
Bite Treatment Centers with the technical and logistical
assistance from the
Department of Health.
D. Funding requirements needed for management of rabies
exposures and pre-exposure
prophylaxis and for operational systems shall be planned, secured and allotted for
the implementing agencies, particularly, the Department of Health and the by
Local
Government Units.
E. Advocacy through information dissemination and
training of health workers shall be
conducted at all levels.
F. Collaboration and coordination
among government agencies, non-government and
private organizations to ensure successful implementation shall be strengthened.

SPECIFIC GUIDELINES AND PROCEDURE

A. Management of Potential Rabies Exposure
1. Initiation of post-exposure
prophylaxis (PEP) shall not be delayed for any reason
regardless of interval between exposure and consultation as it increases the risk of
rabies and it is associated with treatment failure.
2. Immediate washing of the bite wound/ exposed
area with soap and water and
application of an antiseptic solution reduces the risk of rabies transmission.
3. There are no absolute contraindications to rabies PEP.
Patients allergic to a specific
vaccine/RIG or its components shall be given the alternative vaccine/RIG.
. Table shows the categories of exposure to a rabid animal or to an animal suspected to be
rabid, with their correspondingmanagement guidelines:

Table 1. Categories of Rabies Exposure with CorrespondingManagement

Category of exposure Management

CATEGORY I

a) Feeding/touching an animal 1. Wash exposed skin immediately with soap

and water.
b) Licking of intact skin (with reliable
history and thorough physical 2. No vaccine or RIG needed
examlnation) 3. be
Pre-exposure prophylaxis may
c) Exposure to patient with signs and considered for high risk persons.
symptoms of rabies by sharing of eating or
drinking utensils
(1) Casual contact (talking to, visiting and
feeding suspected rabies cases) and
routine delivery of health care to patient
with signs and symptoms of rabies

CATEGORY II
a) Nibbling of uncovered skin with or 1. Wash wound with soap and water.
w1thout bru1s1ng/hematoma
2. Start vaccine immediately.
b)
Mltrlllor/tsiperglc1al. lsdcratctlllles/abraiswn; 3. Complete vaccination regimen until
W1 ou ee 1ng, me u mg ose 1n uce
Day 7 regardless of the status of the
to bleed . . .
b1t1ng anlmal
c) All Category II exposures on the head and 4. RIG is not indicated
neck area are considered Category III and
shall be managed as such.
 CATEGORY III
a) Transdermal bites (puncture wounds, . Wash wound with soap and water.
lacerations, avulsions) or scratches/ Start the vaccine and RIG immediately.
abrasions with spontaneous bleeding
. Complete vaccination regimen until Day
b) Licks on broken skin or mucous
membrane 7 regardless of the status of the biting
Exposure to a rabies patient through Animal.
bites, contamination of mucous
membranes (eyes, oral/nasal mucosa,
genital/anal mucous membrane) or open
skin lesions with body fluids through
splattering and mouth-to-mouth
resuscitation.
d) Unprotected handling of infected carcass
e) Ingestion of raw infected meat
f) Exposure to bats
g) All Category II exposures on head and
neck area

10. Dog owners have the responsibility to keep their dogs for observation under the Rabies
Act of 2007, with penalties to violators provided for by the law.
11. Only the Intradermal Regimen will be used in the administration of vaccine in all
government facilities except for conditions that require IM administration as described in
Section C. 1 .d Post-ExposureProphylaxis under Special Conditions.

B. Immunization

1. Active Immunization

a. Administration
Vaccine shall be administered to induce antibody and T-cell production in order to
neutralize the rabies virus in the body. It induces an active immune response in 7-10 days
after vaccination, which may persist for years provided that primary immunization is
completed.

b. Types of Rabies Vaccines and Dosage

The National Rabies Prevention and Control Program (NRPCP) shall provide the
following CCEEV a) Purified Vero Cell Rabies Vaccine (PVRV) — 0.5 ml/vial and b)
Purified Chick Embryo Cell Vaccine (PCECV)— 1.0 ml/vial.(Table 2)

ai.
Table 2. List of CCEEV provided by the NRPCP to Animal Bite Treatment Centers
with CorrespondingPreparation and Dose
Generic Name Preparation Dose

Purified Verocell Rabies Vaccine ID - 0.1 m1

0 ' 5 ml /via1
(PVRV) IM - 0.5 m1

Purified Chick Embryo Cell ID — 0.1 ml

1 ml/vial
Vaccine (PCECV) IM — 1.0 ml

c. Recommendations on the intradermal administration of anti-rabies vaccines:

The NRPCP introduced the intradermal (ID) use of rabies tissue culture vaccines in the country
in 1997. The Philippines was among the first countries to adopt this regimen as recommended
by the World Health Organization, in order to totally discontinuethe use of nerve tissue vaccine
(NTV) which was associated with vaccine induced encephalopathy. To mitigate the expected
increase in the cost of PEP with the shift from NTV to CCEEV, the ID use of these vaccines
was introduced. According to WHO, the ID use of CCEEV can decrease the cost of PEP by as
much as 60- 80%.

However, only a limited number of commercially available rabies vaccines have been proven,
to date, as safe and efficacious for PEP when administered by the ID route. Recently, local
manufacturers in rabies-endemiccountries have started to produce rabies vaccines. The ID use
of these vaccines shall be based on adherence to WHO requirements for that route and approval
by national health authorities as follows, “New vaccine manufacturers should provide clinical
evidence that their products are immunogenic and safe when used intradermally. Clinical
evidence should include clinical trials involving a vaccine of known immunogenicity and
efficacy when used by this route as control, serological testing with rapid fluorescent focus
inhibition test, and publication in internationallypeer-reviewedjournals”.

To ensure compliance to these recommendations and guarantee that animal bite patients seeking
treatment in government Animal Bite Treatment Centers receive only CCEEVs that have been
proven to be safe and effective, the program shall utilize for its intradermal regimen only
CCEEVs that satisfy the following criteria :

C1 The vaccine is WHO prequalified (http://www.who.int/immunization standards/

vaccine guality/ PQ_vaccine_1ist_en/en/index.html) and registered and approved by
FDA;
c.2 For vaccines that are non-prequalified, the vaccine shall be registered with and approved
by the Food and Drug Administration;
C3. The vaccine must have gone through clinical trials on safety, immunogenicity and
efficacy in comparison with a vaccine of demonstrated efficacy which are published in
peer reviewed trials;
//10/

7% 6
 c.4 The potency of vaccines for ID use shall be at least 0.5 IU/ID dose as evidenced by their
lot release certificate. The potency of the vaccine batch shall be provided by the
manufacturer;
c.5 The product insert shall contain the vaccine’s approved ID dose and consistent with its
Certificate of Registration (CPR); and
c.6. Non-WHO prequalified vaccines may be used only during shortage of WI-.O
prequalified vaccines. The same criteria shall apply except for c.1.

2. Passive Immunization

Rabies immunoglobulin or RIG (also called passive immunization products) shall be given in
combinationwith rabies vaccine to provide the immediate availability of neutralizing antibodies
at the site of the exposure before it is physiologicallypossible for the patient to begin producing
his or her own antibodies after vaccination. This is especially important for patients with
Category III exposures. RIGs have a half-life of approximately 21 days.

a. Types of Rabies RIG

a. 1. Human Rabies Immune Globulin (HRIG) derived from plasma of human donors
administered at a maximum of 20 IU per kilogram body weight. Available preparation
is 2 ml/vial; 150 IU/ml

a.2 Highly purified antibody antigen binding fragments [F(ab’)2] produced from equine
rabies immune globulin (ERIG) administered at a maximum of 40 IU per kilogrambody
weight. Available preparation is 5 ml/vial; 200 IU/ml

a.3 .Equine Rabies Immunoglobulin(ERIG) derived from purified horse serum administered
at 40 IU per kilogram body weight. Available preparation is 5 ml/vial; 200 IU/ml

Table 3. List of Rabies Immunoglobulins provided by the NRPCP to

Animal Bite Treatment Centers
Generic Name Preparation Dose
Human Rabies Immune Globulin 150 IU/ml at
20 IU/kg
(HRIG) 2 ml/vial

Equlne Rables Immune Globuhn 200 IU/ml at

40 IU/kg
(ERIG, a.2 or a.3) 5 ml/vial

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b. Rabies Immunoglobulin Criteria:
To ensure that only safe and efficacious RIG are provided by the National Rabies
Prevention and Control Program to all ABTCs, the program shall be guided by following
criteria in procuring the RIG :

b.l RIG must be registered and approvedby FDA;

b.2 RIG must be proven to be safe and effective when used together with human rabies
vaccine as evidenced by publication on peer reviewed journals. These include
studies on:
Safety;
Efficacy;
Immunogenicityon non- interference when used with anti-rabies vaccine;
Animal survivorship, if any; and
Post-marketing surveillance

b.2.3. Results of RFFIT showing antibody content as claimed by the manufacturer

c. Who should be prioritized to be given RIG

c.1. Even if RIG is not available or affordable, prompt local treatment of all bite
wounds or scratches, and for category II and III exposures a complete course of
rabies vaccine is indicated.
c.2. For patients who can reliably document previous post exposure prophylaxis (PEP
of 6 doses (3 visits) or PrEP of 4 doses (2 visits) using WHO pre-qualifled
CCEEV or PEP of 8 doses (4 visits) or PrEP of 6 doses (3 visits) using non-WHO
pre-qualified CCEEV, RIG is not indicated.
0.3. In cases of shortage or unaffordability,the following groups should be prioritized
for RIG allocation:
- Multiple bites
- Deep wounds
- Highly innervated parts of the body, as head, neck, hands, genitals
- Immunocompromisedpatients
- History of biting animal indicative of confirmed or probable* rabies
- A bite or scratch or exposure of a mucous membrane by a bat can be
ascertained

d.3 Computation and Dosage of Rabies Immune Globulin

o HRIG at 20 IU/kg. body weight (150 IU/ml)
50 kg. patient x 20 IU/kg. = 1000 IU
1000 IU + 150 IU/ml
= 6.7 ml.

//
0 ERIG/ F(ab’)2 at 40 IU/kg. body weight (200 IU/ml)
50 kg. patient x 40 IU/kg. = 2000 IU
2000 IU + 200 IU/ml
10 ml.

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e.4 Administration

0.4. l. The totalcomputed RIG shall be infiltrated around and into the wound as much as
anatomically feasible, even if the lesion has healed. In case some amount of the total
computed dose of RIG is left after all wounds have been infiltrated, the remaining
volume of RIG that is not infiltrated into the wound does not need to be injected IM.
It may be reserved for the next patient who needs RIG, ensuring aseptic retention of
the RIG i.e. fractionated in smaller individual syringes.
c.4.2. A gauge 23 or 24 needle, 1 inch length shall be used for infiltration. Multiple needle
injections into the same wound shall be avoided.
c.4.3 Equine immunoglobulins (ERIG) are clinically equivalent to human rabies
immunoglobulins (HRIG) and are considered safe and efficacious life- and cost-
saving biologics. Skin testing for ERIG is highly recommended.
c.4.4 If a finger or toe needs to be infiltrated, care shall be taken to ensure that blood
circulation is not impaired. Injection of an excessive amount may lead to cyanosis,
swelling and pain.
c.4.5 RIG shall not exceed the computed dose as it may reduce the efficacy of the vaccine.
If the computed dose is insufficient to infiltrate all bite wounds, it may be diluted
with sterile saline 2 or 3-fold for thorough infiltration of all wounds.
c.4.6. RIG shall always be given in combination with rabies vaccine. RIG shall be
administered at the same time as the first dose of rabies vaccine (Day 0). In case RIG
is unavailable on DAY 0, it may still be given until 7 days after the first dose of the
vaccine. Beyond Day 7, regardless of whether day 3 and day 7 doses were received,
RIG is not indicated because an active antibody response to the rabies CCEEV has
already started and interferencebetween active and passive immunization may occur.
c.4.7. In the event that RIG and vaccine cannot be given on the same day, the vaccine shall
be given before RIG because the latter inhibits the level of neutralizing antibodies
induced by immunization.
c.4.8. RIG shall be given only once during the same course of PEP.
c.4.9 All bite centers shall be equipped to handle allergic reactions, should they occur.
c.4. 10. Patient shall be observed for at least one hour after injection of ERIG for immediate
allergic reactions.
c.4.11 Severe adverse events or perceived lower efficacy of RIG (e.g. batches of insufficient
potency or lower purification degree) should be monitored, recorded and reported,
so that biological producers receive immediate feedback and can respond
accordingly. A classification of adverse events is available in Table 6. Post—
marketing surveillance is recommended.
 c.5 Management of Adverse Reactions
Adverse reactions shall be managed as follows:

c.5.1 Anaphylaxis
Give 0.1% adrenaline or epinephrine (121,000 or 1mg/ml) underneath the skin or
into the muscle.
Adults - 0.5 ml
Children 0.01ml/kg, maximum of 0.5 ml
—

Repeat epinephrine dose every 10-20 minutes for 3 doses

Give steroids after epinephrine

c.5.2. Hypersensitivity reactions

Give antihistamines, either as single drug or in combination
If status quo for 48 hrs despite combination of antihistamines, may give short course
(5-7 days) of combined oral antihistamines plus steroids
If patient worsens and condition requires hospitalizationor becomes life threatening,
may give IV steroids in addition to antihistamines
C. Treatment
1. Post— Exposure Prophylaxis

a. Local Wound Treatment

a.1.1. Wounds shall be immediately and vigorously washed and flushed with soap or
detergent, and water preferably for 10 minutes. If soap is not available, the wound
shall be thoroughly and extensively washed with water.

a.1.2. Apply alcohol, povidone iodine or any antiseptic.

a.1.3. Suturing of wounds shall be avoided at all times since it may inoculate Virus deeper
into the wounds. Wounds may be coaptated using sterile adhesive strips. If suturing
is unavoidable, it should be delayed for at least 2 hours after administration of RIG
to allow diffusion of the antibody to occur through the tissues.
. Any ointment, cream or wound dressing shall not be applied to the bite site because
it will favor the growth of bacteria and will occlude drainage of the wound, if any
. Anti-tetanus immunization may be given, if indicated. History of tetanus
immunization (TT/DPT/Td) should be reviewed. Animal bites shall be considered
tetanus prone wounds. Completion of the primary series of tetanus immunization is
recommended.
 Table 4. Guide to Tetanus Prophylaxis in Routine Wound Management
Vaccination History
. .
for TT
indication . Unknown or <3 Doses 3 or More Doses
mmumzatlon
Td* TIG/ATS Td* TIG/ATS
All Animal Bites YES YES NO** NO
*Tdap may be substitutedfor Td if the person has not received Ta'ap and is 1 0 years or older;
DPT may be given for patients < 7 years old; TT may be given if Td not available
**Yes, if more than 5 years since last dose

b. Routine Wound Management

b.1. The most common organism isolated from dog and cat bites is Pasteurella multocida.
Other organisms include S. aureus, Bacteroia’es Sp, Fusobacteriumand Capnocytophaga.
Antimicrobials shall be recommended for the following conditions:
b. 1.1. All frankly infected wounds
b.l.2. All category III cat bites
b. 1 .3. All other category 111 bites that are either deep, penetrating, multiple or extensive
or located on the hand/face/genital area

b.2. Recommended antimicrobials for frankly infected wounds include:

b.2. 1. Amoxicillin/clavulanic
I Adults - 500 mg p.o. TID
I Children - 30-45 mg/kg/day in 3 divided doses
b.2.2. Cloxacillin
I Adults - 500 mg p.o. QID
I Children - 10-150-100 mg/kg/day in 4 divided doses
b.2.3. Cefuroxime axetil
I Adults - 500 mg p.o. BID
I Children - 10-15 mg/kg/day in 2 divided doses
b.2.4. For penicillin allergic patients
I Adults - Doxycycline
I Children — Erythromycin
b.2.5. For those instances where there are no obvious signs of infection, amoxycillin as
prophylaxis may suffice
I Adults - 500 mg p.o. TID
I Children - 30-45 mg/kg/day in 3 divided doses

0 The public shall be educated in simple local wound treatment and warned not to use
procedures that may further contaminate the wounds (e.g. tandok, bato, rubbing
garlic on the wounds and other non-traditional practices)

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c. Vaccination

c.l. General Principles

c.1.1. Storage
c.1.1.1. Vaccines shall be stored at +2 to + 8 °C in a refrigerator, not freezer
c.1.1.2. Once reconstituted, vaccines shall be kept in the refrigerator and used
within 8 hours
c.1.2. Administration Area
0.1.2.1. Injections shall be given on the deltoid area of each arm in adults or at
the anterolateral aspect of the thigh in infants.
0.1.2.2. Vaccine shall never be injected in the gluteal area as absorption is
unpredictable

c.2. Treatment Regimen Schedule

c.2.1. Updated 2-Site Intradermal Schedule (2-2-2-0-2)

0.2.1.1. One dose for ID administration is equivalent to 0.1 ml for

PVRV and PCECV
0.2.1.2 One dose shall be given on each deltoid on Days 0, 3, 7 and 28
C213 One intradermal dose should have at least 0.5 [U vaccine
potency

Table 5. Updated 2-Site Intradermal Schedule

Day of PVRV/ Site of injection

immunization PCEV
Day 0 0.1 ml Left and right deltoids or anterolateral thighs in infants
Day 3 0.1 ml Left and right deltoids or anterolateral thighs in infants
Day 7 0.1 m1 Left and right deltoids or anterolateral thighs in infants
Day 28* 0.1 ml Left and right deltoid or anterolateral thighs in infants

* For WHO pre-qualified vaccines, the day 28 dose may be omitted following the IPC
Institute Pasteur du Cambodge (IPC) Intradermal regimen (2-2-2-0-0)

Table 6. IPC Institute Pasteur du Cambodge (IPC) Intradermal regimen (2-2-2-0-0)

Day of PVRV/ Site of injection

immunization PCEV
Day 0 0.1 m1 Left and right deltoids or anterolateral thighs in infants
Day 3 0.1 m1 Left and right deltoids or anterolateral thighs in infants
Day 7 0.1 ml Left and right deltoids or anterolateral thighs in infants
 c.2.1.4.The ID injection shall produce a minimum of 3 mm wheal. In the
event that a dose of vaccine is inadvertently given subcutaneouslyor
IM, the dose shall be repeated
c.2.1.5 A one (1) m1 syringe with gauge 27 needle, preferably auto-
disposable syringe, shall be used for ID injection
c.2.1.6 Should a vaccine dose be delayed for any reason, the PEP regimen
should be continued (not restarted).

c.2.3. Intramuscular Regimens approved by WHO

c.2.3.1 Zagreb Regimen Schedule (2-0-1—0-1) Intramuscular Schedule

Table 7. Zagreb Regimen Schedule (2-0-1-0-1) Intramuscular Schedule

Pay 0f
. . PVRV PCECV Site ofinjection
Immunization
DayO 0.5 ml 1.0 ml Left and right deltoids or
anterolateral thigh in infants
Day7 0.5 ml 1.0 ml One deltoid or anterolateral
thigh in infants
Day 21 0.5 ml 1.0 ml One deltoid or anterolateral
thigh in infants

c.2.3.2. Shortened Intramuscular Schedule (CDC) (1-1-1-1-0)

Table 8. Shortened Intramuscular Schedule (CDC) (1-1-1-1-0)

Pay .
immunization
.°f PVRV PCECV Site ofinjection

DayO 0.5 ml 1.0 ml One deltoid or anterolateral

thigh in infants
Day3 0.5 ml 1.0 ml One deltoid or anterolateral
thigh in infants
Day7 0.5 ml 1.0 ml One deltoid or anterolateral
thigh in infants
Day 14 0.5 ml 1.0 ml One deltoid or anterolateral
thigh in infants

d. Post-Exposure Prophylaxis under Special Conditions

d.1. Pregnancy and infancy shall NOT be contraindications to treatment with purified
CCEEV (PVRV, PCECV) and RIG.
d.2. Babies who are born of rabid mothers shall be given rabies vaccination as well as
RIG as early as possible at birth.

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 d.3. Patients with hematologic conditions where IM injection is contraindicated shall
receive rabies vaccine by ID route.
d.4. Patientswith chronic liver disease and those taking chloroquine, and systemic steroids
shall be given standard IM regimen as the response to ID regimen is not optimum for
these conditions. Vaccination shall not be delayed in these circumstances as it
increases the risk of rabies.
d.5. Immunocompromisedindividuals (such as those with HIV infection, cancer/transplant
patients, patients on immunosuppressivetherapy etc.) shall be given vaccine using
standard IM regimen and RIG for both Category II and III exposures.
d.6. Exposed persons who present for evaluation or treatment weeks or months after the
bite shall be treated as if exposure has occurred recently. However, if the biting
animal has remained healthy and alive with no signs of rabies until 14 days after the
bite, no treatment shall be needed.
d.7. Changes in the human rabies vaccine product and/or the route during the same PEP
course are acceptable, if unavoidable to ensure PEP course completion. Restarting
PEP is not necessary.
d.8. Bites by rodents, guinea pigs and rabbits shall not require rabies post-exposure
prophylaxis.
d.9. Bites by domestic animals (dog, cat) and livestock (cows, pigs, horses, goats etc) as
well as wild animals (bats, monkeys, etc) shall require PEP.

e. Post-Exposure Prophylaxis of Previously Immunized Animal Bite Patients

e.1. Local wound treatment shall always be carried out.

e.2. Persons with repeat exposure after having previously received complete primary
immunization or Pre- Exposure Prophylaxis against rabies with CCEEV shall be
given a booster dose of 0.1 ml ID dose at 1 site on DO and D3 or 4 ID doses on Day
0. To maximize use of CCEEV, the use of an IM booster dose is discouraged.
Table 9a. Management of Previously Vaccinated Individuals

PEP/PrEP History RIG Management

Patient received complete PrEP (Day 0 and 7) OR No Determine if high or low
Patient received at least days 0 and 3 doses of PEP risk bite (see Table 9b)
ID/IM
Patient received complete PrEP (Day 0 and 7) OR Yes, if Give full course PEP
Patient received at least days 0 and 3 doses of PEP indicated
ID/IM AND
Patient is immunocompromisedOR bitten by a bat
Patient did not complete PrEP OR Patient received Yes, if Give full course PEP
only 1 dose of PEP indicated

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Table 9b. Criteria for high and low risk exposures
Risk of Criteria Recommendation
exposure
High Risk ANY ONE OF THE FOLLOWING: Immediately provide the
1.Biting animal cannot be observed, dies booster injections to the
or is sick patient
2. Site of bite is in highly innervated parts Booster doses:
of the body — neck, head, genital area, 0.1 m1 ID at 4 sites on day 0
hands and toes OR
3.Multiple deep bites 0.1 ml ID/IM at 1 site on days
4.Patient is coming from GIDA* areas, 0 and 3
Le. infrequent transportation to and
'-
from ABTC/ABC
5.* GIDA — Geographically Isolated and
Disadvantaged areas
Low Risk Last dose of vaccine was within the previous Observe biting animal for 14
3 months AND days.
Biting animal is healthy, owned, kept on a If animal remains healthy,
leash or can be confined and is available for withhold booster dose
observation
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/trunk

e.3. Patients who have previously received complete primary immunization with rabies
vaccine have the advantage that booster doses will rapidly induce a large increase in
antibodyproduction (a “secondary response”). Therefore, there is no need to give RIG.
e.4 Patients who have not completed the primary immunization as described above shall
receive full course including RIG if needed.
I

f. Management of Rabies Exposures from bites of animals vaccinated against rabies:

f.1. For Category 1

exposure, PEP is not needed.

f.2. For Category II exposures, the following are recommended:

f.2.1 Immediate washing of the bite wound for ten minutes and application of an
antiseptic solution.
f.2.2 No human rabies vaccine shall be provided, provided that ALL of the
following conditions are satisfied:

W
 f.2.2.1 Dog/cat is healthy and available for observation for 14 days
£2.22. Dog/cat was vaccinated against rabies for the past 2 years:
i. Dog/cat shall be at least 1 year 6 months old and has updated vaccination
certificate from a duly licensed veterinarian for the last 2 years
ii. The last vaccination shall be within the past twelve (12) months, the
immunization status of the dog/cat shall not be considered updated if
the animal is not vaccinated on the due date of the next vaccination
f. 2.3. If the biting animal starts to show signs of rabies, immediately give
vaccine and RIG.
f.2.4. If the biting animal remains to be healthy within 14 days, there is no need to
administer CCEEV against rabies.

f.3. For Category III exposures, the following are recommended:

f.3.1 Immediate washing of the bite wound for ten minutes and application of
an antiseptic solution.
f.3.2 CCEEV and RIG are immediately administered regardless of the status
of the biting animal.
f.4. PEP shall not be required for bite/s of the followingbiting animals: rats, mice, guinea
pigs, hamsters, rabbits, snakes and other reptiles, birds and other avians, insects and
fish.

Table 10. Clinical Signs of Animal Rabies

Prodromal Stage (usually lasts 2-3 days; sometimes only a few hours)
A. Changes in attitude/behavior/temperamentsuch as unusual shyness or aggressiveness
Friendly animal becomes aggressive
Solitude
Restlessness
rune-99‘s»

Snapping at imaginary objects

Apprehension
Nervousness
Anxiety
P‘QQ

Barking/vocalizationat the slightest provocation

B. Dilated pupils; become myotic in advance state
C. Mydriasis and/or sluggish palpebral or corneal reflexes
D. Slight rise in body temperature (slight fever)
Clinical Rabies
Furious Stage (usually lasts 1-7 days) Paralytic (dumb) stage (develops 2-10
days after clinical signs; usually last 2-4
days)
I. Increased response to auditory and Visual Paralysis
stimulation such as o Paralysis may begin at the bite area
0 Restlessness and progress until entire CNS
0 Photophobia involvement
0 Hyperaesthesia, 0 Following paralysis of the head and
0 Eating unusual objects neck, the entire body becomes
0 Aggression paralyzes

7? 16
 o Attacking any live or inanimate objects 0 Change in tone of
II. Erratic behavior vocalization/barking (indicative of
Biting or snapping laryngeal/pharyngealparalysis)
Licking 0r chewing of wound/bite site 0 Hypersalivation or frothing ;
If caged, biting of their cage drooling/slobbering of saliva
Wandering and roaming (indicative of laryngeal/pharyngeal
Excitability; paralysis)
Irritability; Dysphagia/difficulty/inability to
Viciousness swallow (indicative of
III. Self—mutilation laryngeal/pharyngealparalysis)
IV. Muscular in-coordination and seizures “Jaw drop”/Dropped jaw due to
V. Disorientation masseter muscle paralysis (suspects
o Roams and bites inanimate object and also foreign body in mouth or
other animals including man esophagus)
Pupil dilation or pupil constriction
Protrusion of third eyelid
Ataxia, progressive paralysis and
cannibalism (terminal stage)
Coma and/0r respiratory paralysis
resulting in death within 2-4 days

D. Pre—exposure Prophylaxis
a. 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 PEP is reduced

b. Target population
Personnel in rabies diagnostic laboratories
Veterinarians and veterinary students
Animal handlers
Health care workersdirectly involved in care of rabies patients
Individuals directly involved in rabies control
Field workers
It is recommendedthat children 2-10 yrs old also be immunized because of the
increased risk and severity of animal bites in this age group
 c. Regimen:
Table 11. Pre-exposure Prophylaxis Schedule
PVRV PCECV
Regimen Day 0 Day 7 Day Day 0 Day 7 Day
21/28** 21/28**
Intradermal 0.1 ml 0.1 ml 0.1 ml 0.1 ml 0.1 ml 0.1 ml
(2 doses)
Intramuscular* 0.5 ml 0.5 ml 0.5 ml 1.0 ml 1.0 ml 1.0 m1

* Immunocompromisedindividuals should receive the full intramuscular regimen (Day

0, 7 and 21/28).
** For Immunocompetentindividuals given WHO Pre-qualified CCEEV, Day 21/28 is not
given.
For Immunocompetentindividuals given non-WHO prequalified CCEEV, Day 21/28 is
given)

(1. Routine booster schedule for individual given Pre- Exposure Prophylaxis: (Table 12)

Not all individuals who have completed the PrEP shall receive routine booster doses of
anti- rabies vaccine. Only high risk individuals whose exposures may not be known are
recommended to have routine booster doses.

Table 12. Routine booster Schedule for individuals given Pre- Exposure Prophylaxis
(PreP)

. . . Recommended Booster Schedule

Type of RlSk Population at RlSk
(Without definite exposure)
High Risk 1. Health workers
( exposures handling rabies -1 Booster dose 1
year after primary
may not be cases immunization:
known) 2. Workers in rabies a .One (1 site) 0.1 m1 ID dose of
laboratories, PVRV or PCEC on DO; OR
3. Veterinarians, b. One (lsite) Vial of 0.5 m1 PVRV
4. Veterinary or 1.0 ml PCEC given
students, intramuscularlyon DO
5. Animal handlers
(dog trainers, -Thereafter, 1 booster, if Ab titers
workers in pet fall below 0.5 IU/ml
shops, zoos, etc.)
OR
In the absence of serologic testing,
-
booster dose every 5 years
1

Low Risk General Population No routine booster after primary

( exposures are immunization
known)

7e 18
E. Management of the Biting Animal

1. The biting animal shall be observed for 14 days. Adequate animal care shall be provided
during the observation period.

2. It is advisable for patients to consult a veterinarian, whenever possible, regarding

biting animal management especially when any of the following is observed:
sudden change of behavior (from mild to vicious temperamentor vice versa)
9‘s»
characteristic hoarse howl
watchful, apprehensiveexpression of the eyes, staring, blank gaze
9.0
drooling of saliva
rm
paralysis or uncoordinated gait of hind legs
marked restlessness,pacing in cage
if at large runs aimlessly, biting anything in its way
depraved appetite, self-mutilation
in some cases, lies quiescent, biting when provoked
FF'T'F‘P‘GP

snaps at imaginary objects

paralysis of lower jaw and tongue; inability to drink
sudden death without associated S/Sx

3. PEP utilizing non-WHO prequalified vaccine shall be discontinued if the biting animal
remains healthy after the 14—day observation period. If the animal dies or gets sick, the
head shall be submitted to the nearest rabies diagnostic laboratory for testing.

F. Dispensing of Anti-Rabies Immunizing Agent

1. Patients needing PEP shall be referred to the nearest Animal Bite Treatment
Center/Animal Bite Clinic where anti-rabies immunizing agents (vaccines and RIG) are
administered.

2. The following procedures shall be observed when assessing animal bite patients and
dispensing anti-rabies immunizing agents:
a. Assess the victim thoroughly and record in the Municipal/City/HospitalRabies
Surveillance Form (Facility-based form).
b. Decide whether or not to initiate treatment using the Revised Guidelines on the
Management of Animal Bite Patients as reference.
c. If the situation warrants immunization (Category II and Category III), the patient
shall be given the intradermal regimen. The other approved regimens may be
used if the ID regimen is not feasible
d. If indicated, the patient shall be provided the required dose of passive
immunization products/RIG, if available, preferably ERIG or F(ab’)2.
e. Explain your decision to the patient with particular emphasis on adherence to
treatment schedules, if immunization is indicated.

“7? .9
 f. Observe courtesy and tactfulness when dealing with patients particularly among
individuals who need not be immunized.
g. Give advice on the practice of Responsible Pet Ownership.

G. Priorities for Dispensing Vaccines

The following shall be the program’s order of priority for dispensing vaccines:
a. Patients bitten by animals found to be positive by IFAT or for “Negri bodies”
regardless of type of bite exposure
b. Patients with Category III exposure
c. Patients bitten by animals that are not available for observation (stray/slaughtered)
d. Individuals exposed to human rabies patients through bite/non—bite exposure as defined
in table 1.
e. Patients with Category 11 exposure

H. Injection Safety:
A safe injection is defined by the World Health Organization as an injection that:
0 Does not harm the recipient
a Does not expose the health staff to any avoidable risks
0 Does not result in waste that is dangerous to the community.

1. Injection Equipment
b. Auto-Disable (AD) Syringes— are disposable injection devices that are especially
made to prevent re—use and are therefore less likely than standard disposable
syringes to cause person-to-person transmission of blood-borne diseases.

The program recommends that health workers shall use AD syringe in their
respective ABTC.

c. Conventional Syringes— are plastic syringes with steel needles that are provided
usually by the manufacturer in sterile package. The needle may either be fixed to
the syringe when it is produced or attached by the health staffjust before use.

2. Management of Sharp Wastes

Used syringes and needles shall never be dumped in open areas where people might pick
them up, step on them, or come in contact with them in any way.

The need to better manage used or contaminated sharps shall be through the use of safety
boxes or sharp containers. These are puncture-resistant containers where used syringes
and needles can be immediately and temporarily stored after use until its final disposal.

3. Waste Disposal
Collector boxes filled with used syringes and needles shall be immediately brought to
its final disposal. The program recommends the following methods of disposal:
0 Use of septic vault

t
l
20
 o Pit burial; and
0 Waste treatment and final disposal to landfill

I. Roles and Responsibilities

1. Central Office
The Disease Prevention and Control Bureau shall be responsible for procurement,
allocation and distribution of vaccines and RIG and shall augment vaccine requirements
for low — income municipalities with high incidence of rabies.
All DOH Regional Offices shall be given allocation every quarter subject to availability of
the immunological products.

DOH Regional Office

The Regional Office, through the Director and the Rabies Control Program Coordinator
shall be responsible for distribution of vaccines to the Provincial/City Health Offices.

3. Local Government Units (LGUs)

The LGUs shall be encouraged to enact and strictly enforce ordinance relevant to rabies
control. The Provincial Rabies Control Coordinators shall distribute the augmented
vaccines of the Department of Health to the established Animal Bite Treatment Centers
where human anti-rabies immunizing agents (vaccines and RIG) are administered. The
LGUs shall encourage to allocate funds for its procurement.

VII. TRANSITORY PROVISION

Procurement of NON—WHO PREQUALIFIED CCEEV for government agencies shall

cease when WHO pre-qualified vaccines become available and supplies become stable
in the market.

VIII. REPEALING CLAUSE

Administrative Order No. 2014-0012 entitled “New Guidelines on the Management of

Rabies Exposures” and all other issuances inconsistent or contrary to the provisions of
this Order are hereby repealed or modified.

IX. EFECTIVITY

This Order shall take effect immediately.

FRAN SC . DUQ , M.D., M.Sc.

Secre ry of Health

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