NATIONAL GUIDELINES FOR

H U M A N

RABIES
PROPHYLAXIS
 CONTENTS

Acknowledgement i
Abbreviations ii
Objectives of the Guidelines iii

1. Background 1
1.1 Introduction 1
1.2 Transmission 1
1.3 Symptoms 2
1.4 Diagnosis 2
1.5 Prevention and Control 2
2. Dealing with an Animal Bite Case 4
3. Post-Exposure Prophylaxis 5
3.1 Risk Assessment and Categorization of Exposure 5
3.1.1 Risk Assessment 5
3.1.2 Categorization of Exposure 6
3.2 Management of a Patient Following an Animal Bite 7
3.2.1 Local Treatment of Wound 7
3.2.2 Suturing of Wounds 7
3.2.3 Injection of Tetanus Toxoid 8
3.2.4 Additional Care 8
3.3 Application of Rabies Vaccine and Immunoglobulin 8
3.3.1 Application of Rabies Immunoglobulin 9
3.3.1.1 Rabies Immunoglobulin 9
3.3.1.2 Administration of Rabies Immunoglobulin 11
3.3.2 Application of Rabies Vaccine 12
3.3.2.1 Rabies Vaccine 12
3.3.2.2 Administration of Rabies Vaccine 13
4. Post-Exposure Prophylaxis for Previously Vaccinated Persons 17
4.1 Managing Re-Exposure Following PrEP or PEP with Rabies Vaccine 17
of TCO or EEO
4.2 Managing Re-Exposure Following Post -Exposure Prophylaxis with 17
Rabies Vaccine of NTO
5. Pre Exposure Prophylaxis 18
6. Dog Bite Management in Immuno-compromised patients 19
7. Management of Adverse Effects Following Immunization (AEFI) 21
8. References 22

Annex (1): The modern rabies vaccines of TCO or EEO 23

Annex (2): Proforma for Post-Exposure Management of Animal Bite Cases 24
Annex (3): Requirements for a Dog Bite Treatment Centre 26
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ACKNOWLEDGEMENT

This National Guidelines for Human Rabies Prophylaxis for clinicians and health profes-
sionals is developed by the Department of Public Health to guide the best practice in
human rabies prophylaxis and the efficient utilization of rabies vaccines and
immunoglobulin. This guideline has been resourced from the discussions during the
“National Workshop on Development of Guidelines for Clinical Management of Human
Rabies” conducted in June 2014 and the “Dissemination Workshop on National Guidelines
for Human Rabies Prophylaxis” in October 2015, feedback of the experts and other relevant
reference materials.
Foremost, the Department of Public Health would like to express our sincere gratitude to
the participants of the Workshops: Professor Dr Aung Gyi, Retired Professor from
University of Medicine (Mandalay), Professor Dr Chit Soe, Professor and Head of
Department of Medicine from University of Medicine (2), Professor Dr Nang Phyu Phyu
Aung, Professor and Head of Department of Medicine from University of Medicine
(Magway), Dr Tint Tint Kyi, Senior Consultant Physician from Insein General Hospital,
Lecturers from the Universities of Medicine, Consultant Physicians and Paediatricians from
Hospitals, Epidemiologists from Livestock Breeding and Veterinary Department, Senior
Officials from Department of Medical Services, Virologists from the National Health
Laboratory and experts from the WHO SEARO, WHO Country office of Myanmar and World
Organization for Animal Health (OIE) for providing their valuable technical inputs, insightful
comments and suggestions for finalization of the Guidelines.
Last but not the least, Department of Public Health would like to express gratitude to the
Ministry of Health for the uninterrupted tremendous stewardship for development and
finalization of this Guidelines.
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ABBREVIATIONS

AEFI Adverse Events Following Immunization

AIDS Acquired Immune Deficiency Syndrome
ARV Anti-Rabies Vaccine
BCG Bacillus Calmette-Guerin
EEO Embryonated Egg Origin
ERIG Equine Rabies Immunoglobulin
FAVN Fluorescent Antibody Virus Neutralization Test
HIV Human Immunodeficiency Virus
HRIG Human Rabies Immunoglobulin
ID Intradermal
IDRV Intradermal Rabies Vaccine
IEC Information, Education and Communication
IM Intramuscular
IU International Unit
NTO Nerve Tissue Origin
OIE World Organization for Animal Health
PCECV Purified Chick Embryo Cell-culture Vaccine
PDEV Purified Duck Embryo Vaccine
PVRV Purified Verocell Rabies Vaccine
PEP Post-Exposure Prophylaxis
PrEP Pre-Exposure Prophylaxis
RFFIT Rapid Fluorescent Focus Inhibition Test
RIG Rabies Immunoglobulin
SEARO South-East Asia Regional Office
TCO Tissue Culture Origin
TRC Thai Red Cross
WHO World Health Organization
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OBJECTIVES OF THE GUIDELINES

Rabies is a zoonotic disease of public health importance in Myanmar and dog bite is
primary cause for seeking post exposure rabies prophylaxis. It will remain as a public health
problem unless there will be significant progress in controlling rabies at the source, i.e.
dogs. Rabies Vaccine of Nervous Tissue Origin (NTO) was the sole human rabies vaccine
available for post-exposure rabies vaccination in the public sector till 2012. Although
modern rabies vaccines have been marketed in Myanmar and recommended by private
medical practitioners, high cost is a limiting factor for most victims of animal bite although
they are safe and highly potent modern rabies vaccine. WHO Expert Consultation on
Rabies recommends the use of cost-effective vaccination schedules such as abbreviated
multisite Zagreb protocol (4 doses, 3 visits) and updated Thai Red Cross (TRC) intradermal
regimen to phase out NTO in order to improve accessibility, availability and affordability of
modern rabies vaccines in the public sector. The Strategic Framework for Elimination of
Human Rabies transmitted by Dogs in the South East Asia has set 2014 as a deadline for
phasing out production and use of rabies vaccine of NTO and encouraged Member States
to introduce cost-effective intradermal rabies vaccination as an alternative.
To operationalize the introduction of abbreviated multisite Zagreb protocol and cost-
effective intradermal (ID) route, there is an urgent need to develop National Guidelines for
Human Rabies Prophylaxis with modern rabies vaccines and rabies immunoglobulin
considering latest WHO recommendations on post-exposure rabies prophylaxis. This
National Guidelines has been developed to provide guidance to clinicians and health
professionals to conduct the best practice in human rabies prophylaxis and make cost
effective use of modern rabies vaccines in public as well as in private sectors.
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National Guidelines for Human Rabies Prophylaxis

BACKGROUND
1
1.1 Introduction
Rabies is a neglected zoonotic disease (a disease that is transmitted from animals to
humans), caused by the rabies virus of the genus Lyssavirus, and It is almost always fatal
following the onset of clinical signs.

In more than 99% of human cases, the rabies virus is transmitted by domestic dogs. Rabies
affects domestic and wild animals, and is spread to people through bites or scratches,
usually via saliva.
With the exception of Antarctica, the disease is endemic on all continents. The highest case
incidence occurs in Asia and Africa, where rabies potentially threatens over 3 billion people.
More than 95% of human deaths occur in Asia and Africa.

Rabies is a 100% vaccine-preventable disease. However, despite the availability of tools to

manage the disease, rabies prevails to cause tens of thousands of deaths every year. The
disease disproportionately affects poor, low-resource communities, particularly children with
4 out of every 10 human deaths by rabies occurring in children younger than 15 years.

Rabies is a neglected disease of poor and vulnerable populations whose deaths are rarely
reported and where human vaccines and immunoglobulin are not readily available or
accessible.

1.2 Transmission
People are usually infected following a deep bite or scratch by an infected animal. Dogs are
the main host and transmitter of rabies. They are the cause of human rabies deaths in Asia
and Africa.
Bats are the source of most human rabies deaths in the Americas. Bat rabies has also
recently emerged as a public health threat in Australia and western Europe. Human deaths
following exposure to foxes, raccoons, skunks, jackals, mongooses and other wild carnivore
host species are very rare.
Transmission can also occur when infectious material – usually saliva – comes into direct
contact with human mucosa or fresh skin wounds. Human-to-human transmission by bite is
theoretically possible but has never been confirmed. There has never been a documented
case of human-to-human transmission in hospital settings.
However, human-to-human transmissions through corneal tissue/ organ transplantation
have been reported. Such transmission has occurred among recipients of transplanted
corneas and recently among recipients of solid organs and one vascular tissue.
Investigations revealed each of the donors had died of an illness compatible with or proven
to be rabies. Therefore corneas or organs should not be collected from a patient who died
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National Guidelines for Human Rabies Prophylaxis

due to rabies encephalitis or undiagnosed neurological disease.

Rarely, rabies may be contracted by inhalation of virus-containing aerosol. Ingestion of raw

meat or other tissues from animals infected with rabies is not a source of human infection.

There is no viremia in rabies infection and therefore it is not transmitted through blood and
blood products. There are no evidence-based reports of human rabies due to consumption
of milk. Individuals or professionals who slaughter rabies-infected animals and handle brain
and other infected material may be at risk but there are no human cases due to
consumption of cooked meat.

1.3 Symptoms
The incubation period for rabies is typically 1–3 months, but may vary from <1 week to >1
year. The initial symptoms of rabies are fever and often pain or an unusual or unexplained
tingling, severe itching, pricking or burning sensation (paraesthesia) at the wound site. As
the virus spreads through the central nervous system, progressive, fatal inflammation of the
brain and spinal cord develops.
Two forms of the disease can follow. People with furious rabies exhibit signs of
hyperactivity, excited behaviour, hydrophobia and sometimes aerophobia. After a few days,
death occurs by cardiorespiratory arrest.
Paralytic rabies accounts for about 30% of the total number of human cases. This form of
rabies runs a less dramatic and usually longer course than the furious form. The muscles
gradually become paralyzed, starting at the site of the bite or scratch. A coma slowly
develops, and eventually death occurs. The paralytic form of rabies is often misdiagnosed,
contributing to the under-reporting of the disease.

1.4 Diagnosis
No tests are available to diagnose rabies infection in humans before the onset of clinical
disease, and unless the rabies-specific signs of hydrophobia or aerophobia are present, the
clinical diagnosis may be difficult. Human rabies can be confirmed intra-vitam and post
mortem by various diagnostic techniques aimed at detecting whole virus, viral antigens or
nucleic acids in infected tissues (brain, skin, urine or saliva).

1.5 Prevention and Control

Post-exposure prophylaxis (PEP)
Post-exposure prophylaxis (PEP) means the treatment of a bite victim that is started
immediately after exposure to rabies in order to prevent rabies infection. This consists of:
 local treatment of the wound, initiated as soon as possible after exposure;
 a course of potent and effective rabies vaccine that meets WHO standards; and
 the administration of rabies immunoglobulin, if indicated.
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National Guidelines for Human Rabies Prophylaxis

Immediate wound cleansing with soap and water after contact with a suspect rabid animal
can be life-saving.
Effective treatment soon after exposure to rabies can prevent the onset of symptoms and
death.
In developing countries, the vaccination status of the suspected animal alone should not be
considered when deciding whether to initiate prophylaxis or not.
Human rabies prevention is promoted through the elimination of rabies in dogs as well as a
wider use of the intradermal route for PEP which reduces volume and thereby the cost of
cell-cultured vaccine by 60% to 80%.
Every year, more than 15 million people worldwide receive a post-bite vaccination to
prevent the disease; this is estimated to prevent hundreds of thousands of rabies deaths
annually.
Eliminating rabies in dogs
Rabies is a vaccine-preventable disease. Vaccinating dogs is the most cost-effective
strategy for preventing rabies in people. Dog vaccination will drive down not only the deaths
attributable to rabies but also the need for PEP as a part of dog bite patient care.
Preventive immunization in people
Pre-exposure vaccination/ prophylaxis (PrEP) is recommended for anyone who is at
continual, frequent or increased risk of exposure to the rabies virus, either as a result of
their residence or occupation.

Rabies Elimination
Stockpiles of dog and human rabies vaccine have had a catalytic effect on rabies
elimination efforts in countries.
Rabies transmitted by dogs has been eliminated in many Latin American countries,
including Chile, Costa Rica, Panama, Uruguay, most of Argentina, the states of São Paulo
and Rio de Janeiro in Brazil, and large parts of Mexico and Peru.
Many countries in the WHO South-East Asia Region have embarked on elimination
campaigns in line with the target of regional elimination by 2020. Bangladesh launched an
elimination programme in 2010 and, through the management of dog bites, mass dog
vaccination and increased availability of vaccines free of charge, human rabies deaths
decreased by 50% during 2010–2014
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National Guidelines for Human Rabies Prophylaxis

DEALING WITH AN ANIMAL BITE CASE

2
Rabies is almost always a fatal disease but it is preventable disease. Thus it is important to
prevent occurrence by active and passive immunization after exposure to rabies virus. The
vaccines and rabies immunoglobulin (RIG) used for rabies prophylaxis should comply with
the WHO recommendations for production and control as well as immunogenicity and
safety.

Exposure to a biting dog is a frightening experience in itself; hence all dog bite victims are
anxious and should be handled gently. Reassurance and counselling by a physician is
invaluable in this scenario. Children should be handled with particular care.
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National Guidelines for Human Rabies Prophylaxis

POST-EXPOSURE PROPHYLAXIS
3
Post-exposure prophylaxis (PEP) against rabies takes preference over any other
consideration since it is a life-saving procedure. Moreover, rabies vaccine of TCO or EEO
does not have any adverse effect on fetus, mother-to-be and the course of pregnancy, and
lactating mothers.
PEP consists of three activities:
1. Risk assessment and categorization of exposure
2. Management of a patient following an animal bite
3. Application of rabies vaccine and/or immunoglobulin

3.1 Risk Assessment and Categorization of Exposure

3.1.1 Risk assessment

Observation of biting dog or cat

The PEP should be started immediately after the bite. However if the animal remains
healthy throughout the observation period of 10 days, post-exposure prophylaxis
may be modified to pre-exposure vaccination. The observation period is valid for
dogs and cats only. The natural history of rabies in mammals other than dogs or cats is
not fully understood and therefore the 10-day observation period may not be applicable.

Unvaccinated dogs are more likely to transmit rabies, but one must be absolutely certain of
a dog vaccination status before making a decision. Vaccination cards recording previous
immunizations are valuable for making correct decisions. Dog vaccine failures may occur
because of improper administration or poor quality vaccine.

Bite by wild animals or rodents

Bite by all wild animals should be treated as category III exposure. It should be noted that
bites by domestic rats, mice, squirrel, hare and rabbits does not routinely require PEP
except proper wound care.

Human-to-human transmission
The risk of rabies transmission to other humans from a human rabies case is minimal.
However, people who have been exposed closely to the secretions of a patient with rabies
may be offered PEP as a precautionary measure.
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National Guidelines for Human Rabies Prophylaxis

3.1.2 Categorization of exposure

Risk assessment leads to the categorization of wound according to category of exposure
developed by WHO as shown in Table 1.

Table 1: WHO guidelines for risk assessment of rabies exposure

Category Severity and Site of the Wound Action

Category I:  Touching or feeding of animals  Reassurance only

No Risk
 Lick on intact skin  No vaccine needed

Category II:  Nibbling of uncovered skin  Wound management

Moderate Risk
 Minor scratches or abrasion without  Start Vaccination
bleeding Day 0*

Category III:  Single or multiple wounds on head and neck  Wound management
High Risk
 Single or multiple transdermal bites/  Infiltrate RIG into
scratches/ laceration with bleeding wound

 Scratches with bleeding  Start Vaccination at

same time: Day 0*
 Licks on broken skin

 Contamination of mucous membrane of

eyes, mouth, nose or wounds with saliva or
discharges from rabid animals

Day 0* denotes day of first vaccination, not necessarily day of bite.

Note: Administer RIG along with vaccine in all category II bites and category III bites in case
of immune-compromised / immune-suppressed patients (persons on steroids, chloroquine
and chemotherapy for malignant diseases, and HIV/AIDS patients).
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National Guidelines for Human Rabies Prophylaxis

3.2 Management of a Patient Following an Animal Bite

Human rabies caused by classical rabies virus continues to be a 100% fatal disease with no
specific treatment available anywhere in the world. Fortunately, if a person is bitten or
scratched by a suspected rabid animal, immediate thorough cleansing of the wound,
multiple rabies vaccine injections and, in severe exposures, administration of rabies
immunoglobulin can save precious life.

3.2.1 Local treatment of wound

Since the rabies virus enters the human body through a bite or scratch, it is vital to remove
as much saliva, as is possible. Prompt local treatment of all bite wounds and scratches
that might be contaminated with rabies virus is a very important step of PEP.
Recommended first-aid procedures include immediate and thorough flushing and washing
of the wound with soap and water, detergent, povidone iodine or other substances with
virucidal activity on rabies virus. If soap or an antiviral agent is not available, the wound
should be thoroughly and extensively washed with plain water.
Early wound washing can reduce chances of developing rabies at least by 50% as it
reduces viral load. Wound washing should be taught in the community to save time
and improve outcome before the victim reaches a health care facility. Home remedies
like chewed rice, salt, chillies, oil, etc. should not be used on the wound, as these
substances push the virus deeper into the tissues. Touching of wounds with bare hands
should be avoided. Wound washing should include the following steps:
 Thorough but gentle washing with soap or detergent and flushing the wound with
running water for a minimum of 15 minutes. Rabies virus is a fragile virus and any
soap will denature the virus protein and destroy the virus. If soap and detergent
are not immediately available, wash with clean running water for at least 15 minutes.
 If the wound is deep or in absence of running water, flush with a saline filled syringe to
remove dirt and saliva. After thorough washing and drying of the wound, any one of the
available antiseptics should be applied.

3.2.2 Suturing of wounds

Wounds should not be sutured as surgical manipulation can further traumatize the
tissues and push the virus deeper. Occasionally, as in the case of severe facial bite, e.g.
a torn pinna, nose or eyelid, RIG should be infiltrated and loose sutures may be applied.
Most severe bite wounds are best treated by daily dressing followed by secondary suturing
where necessary. If suturing after wound cleansing cannot be avoided, the wound should
first be infiltrated with human or equine rabies immunoglobulin and suturing delayed for
several hours. This will allow diffusion of the rabies immunoglobulin to occur through the
tissues before minimal sutures are applied. Proper suturing may be done after 2-3 days.
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National Guidelines for Human Rabies Prophylaxis

3.2.3 Injection of tetanus toxoid

Injection of Tetanus toxoid should be given to the un-immunized individual. Give tetanus
toxoid series at the same time according to national immunization schedule.

3.2.4 Additional care

To prevent sepsis in the wound, a suitable course of antibiotic (amoxicillin or doxycycline)
should be given for at least 5 days.

In a rabies endemic country, every dog bite should be suspected as a rabies expo-
sure, and PEP should be started immediately. However, people who present for PEP
even months after a possible rabies exposure should be treated as if the event has
occurred today; this is because of the long incubation period of the disease that may
extend to six months or more.

3.3 Application of Rabies Vaccine and Immunoglobulin

After completing wound cleansing to all injuries, active with/ without passive immunization is
given according to the category of the wound.

Category Action
Category I: No Risk No Vaccine/ Immunoglobulin
Category II: Moderate Risk Vaccine only
Category III: High Risk Immunoglobulin + Vaccine

Pregnancy, lactation, infancy, old age and concurrent illness are no contraindications for
rabies post-exposure prophylaxis in the event of an exposure.

For Category III Exposure, RIG should be administered before starting anti-rabies
vaccination or at the same time. If RIG was not administered when vaccination was begun,
it can be administered up to the seventh day after the administration of the first dose
of vaccine. Beyond the seventh day, RIG must not be given since an antibody response
to vaccine is presumed to have occurred and further response would be stunted. RIG
should never be administered in the same syringe or at the same anatomical site as
vaccine.

As with all other immunizations, person vaccinated with rabies vaccine should be kept
under medical supervision for at least 15–20 minutes following vaccination. Previous severe
reaction to any component of a vaccine is a contraindication to the use of the same vaccine
for PEP or PrEP.
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National Guidelines for Human Rabies Prophylaxis

3.3.1 Application of Rabies Immunoglobulin

3.3.1.1 Rabies Immunoglobulin

Rabies immunoglobulin (RIG) should be administered in all patients with category III
exposure. The rabies immunoglobulin provides passive immunity in the form of ready-made
anti-rabies antibody to tide over the initial phase of the infection. The RIG has the property
of binding with the rabies virus, thereby resulting in the loss of infectivity of the
virus.

RIG should always be brought to room temperature (20 – 25ºC) before use.

Types of Rabies Immunoglobulin

Two types of RIGs are available:

1. Human Rabies Immunoglobulin (HRIG):
Human rabies immunoglobulin has a relatively slow clearance (the half-life is about 21
days), so it is the preferred product, particularly in cases of multiple severe exposures
and bites on the head, face and hands. HRIG are free from the side effects en-
countered in a serum of heterologous origin, and because of their longer half-life, are
given in half the dose of ERIG.
However, owing to its short supply and high price, equine immunoglobulin should be
used.
2. Equine Rabies Immunoglobulin (ERIG):
Most of the new equine immunoglobulin preparations are potent, highly purified, safe
and considerably less expensive than human rabies immunoglobulin. However they
are of heterologous origin raised by hyper-immunization of horses, and carry a small
risk of anaphylactic reaction (1/45,000 cases).
Since the serum for ERIG is prepared from horses there are chances (although rare)
of anaphylactic reaction. There are no scientific grounds for performing a skin test
prior to administering equine immunoglobulin because testing does not predict
reactions, and it should be given irrespective of the test result. WHO does not
recommend skin sensitivity test. It is therefore important that medicines are readily
available to treat an anaphylactic shock. The treating physician should be prepared to
manage anaphylaxis which, although rare, could occur during any stage of
administration.

Anaphylactic reactions should be treated promptly with adrenaline. The dose is 0.5 ml
(1:1000, 1mg/ml) for adults and 0.01 ml/kg body weight for children, injected
subcutaneously or intramuscularly.
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National Guidelines for Human Rabies Prophylaxis

Dosage Calculation

Both HRIG and ERIG are equally effective. The HRIG is being more expensive. The doses
are calculated according to the body weight.

Table 2: HRIG calculated as per body weight

Weight in Kg IU ml No. of vials of HRIG

15 300 2 1

30 600 4 2

45 900 6 3

60 1200 8 4 (maximum)

A 2 ml vial of HRIG contains 300 IU. Dose is 20 IU/kg.

(maximum dose is 1200 IU or 4 vials)

Table 3: ERIG calculated as per body weight

Weight in Kg IU ml No. of vials of ERIG

25 1000 5 1

50 2000 10 2

75 3000 15 3

100 4000* 20 4 (maximum)*

A 5 ml vial of ERIG contains 1000 IU. Dose is 40 IU/kg.

(*Maximum dose varies from 3000 to 4000 IU, depending on the preparation. Check the
prescriber’s leaflet.)
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National Guidelines for Human Rabies Prophylaxis

3.3.1.2 Administration of Rabies Immunoglobulin

Infiltrate the calculated dose of RIG (whether HRIG or ERIG) into and around the
wounds. Multiple needle injections into the wound should be avoided. After all wounds
have been infiltrated, remaining RIG, if any, should be administered by deep intramuscular
injection at an injection site distant /away from the vaccine injection site.
Animal bite wounds can be severe and multiple, especially in small children. In such cases,
the calculated dose of the rabies immunoglobulin may not be sufficient to infiltrate all
wounds (Figure. 1). In these circumstances, it is advisable to dilute the immunoglobulin in
sterile normal saline 2 to 3 fold to be able to permit infiltration of all wounds. The total
recommended dose of immunoglobulin must not be exceeded as it may suppress the
antibody production by the vaccine.

Figure 1: Administering RIG into the wound

Precautions to be taken while administering RIGs

 All emergency drugs and facilities for managing any adverse reactions must be
available.
 The RIG vial(s) taken out from refrigerator should be kept outside for a few minutes
before administration to the patient (to warm it to room/body temperature).
 RIG should be administered before starting anti-rabies vaccination or at the same
time.
 RIG should not be administered in the same syringe as the vaccine or at the same site
as vaccine.
 While infiltrating RIG into bite wounds, care must be taken to avoid injecting into blood
vessels and nerves. Anatomical feasibility must always be kept in mind while injecting
RIG.
 While injecting into finger tips, care must be taken to avoid compartment syndrome.
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National Guidelines for Human Rabies Prophylaxis

3.3.2 Application of Rabies Vaccine

3.3.2.1 Rabies Vaccine

Active immunization is achieved by administration of safe and potent rabies vaccine of
tissue-culture origin (TCO) or embryonated egg origin (EEO). Currently available rabies
vaccines of TCO or EEO could be administered by Intramuscular (IM) or Intradermal (ID)
regimen.

Since their development over four decades ago, rabies vaccines of TCO or EEO have
proved to be highly effective in preventing human rabies, both when administered as pre-
exposure prophylaxis (PrEP) and when used in association with RIG for post-exposure
prophylaxis (PEP).

Rabies vaccine of TCO or EEO consists of inactivated rabies virus that has been
propagated in cell substrates such as Vero cells (kidney cells from the African green
monkey), primary Syrian hamster kidney cells, and primary chick embryo cells or in
embryonated duck eggs. The vaccines based on chick embryo cells and Vero cells have
safety and efficacy records comparable to those of the human diploid cell vaccines and are
less expensive.

Rabies vaccines are not supplied in multi dose vials for intramuscular injection. Rabies
vaccines prequalified by WHO do not contain preservatives such as thiomerosal. The shelf-
life of these vaccines is ≥2 years, provided they are stored at +2°C to +8°C and protected
from sunlight. Following reconstitution with the accompanying sterile diluents, the
vaccines should be used immediately, or within 6 hours because of contamination not
coaxing efficacy if kept at the correct temperature. All rabies vaccines of TCO or EEO
should comply with the WHO recommended potency of ≥2.5 IU per single intramuscular
dose (0.5 ml or 1.0 ml volume after reconstitution, depending on the type of vaccine).

Storage and transportation

Although most Rabies Vaccine of TCO or EEO are marketed in freeze dried (lyophilized)
form, yet it is recommended that these vaccines should be kept and transported at a
temperature range of + 2 to + 8ºC.

Reconstitution and storage

The lyophilized vaccine should be reconstituted with the diluents provided with the vaccine
immediately prior to use. However, in case of unforeseen delay it should not be used after
6 hours of reconstitution.

Site of inoculation
Intramuscular vaccine should be injected only in the deltoid area. Gluteal region is not
recommended because the presence of fat decreases the absorption of antigen leading to
impaired immune response. Antero-lateral part of the thigh is the preferred site in infants
and young children.
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National Guidelines for Human Rabies Prophylaxis

Limitations and interchangeability

Currently available rabies vaccines of TCO or EEO are to be administered through IM or ID
route. In patients on chloroquine, vaccine should be given by the intra muscular route only.
Interchangeability of modern rabies vaccine is not recommended. When completion of PEP
with the same modern rabies vaccine is not possible, the switch can be done provided that
it is one of the WHO recommended cell culture vaccine. This practice should be the
exception.
No study has been done yet on vaccine immunogenicity and change of the route of vaccine
administration (e.g. from intramuscular to intradermal) during PEP. It is not recommended
during the course of vaccination.

Vaccine efficacy and immunogenicity

All rabies vaccines of TCO or EEO induce a prompt and high rabies-virus neutralizing
antibody response to the viral G protein. WHO’s specified minimum titre of 0.5 IU/ml of
serum, measured by the rapid fluorescent focus inhibition test (RFFIT) or the fluorescent
antibody virus neutralization test (FAVN) is a widely used reference. In healthy people, this
level should be achieved in most individuals by day 14 of a post-exposure regimen, with or
without simultaneous administration of rabies immunoglobulin and irrespective of age.
When new rabies vaccines are introduced, their immunogenicity is evaluated by comparing
the rabies-virus neutralizing antibody titres induced by the vaccine being tested with those
induced by a vaccine of demonstrated efficacy.

Studies from Thailand and other countries in South-East Asia have established the
immunogenicity and effectiveness of rabies vaccines of TCO or EEO for both pre-exposure
and post-exposure prophylaxis. The feasibility of using PVRV and PCECV either
intramuscularly or intradermal in all age groups, including infants, has been clearly
demonstrated. In both pre-exposure and post-exposure use, these vaccines induce an
adequate antibody response in almost all individuals. Prompt post-exposure use of rabies
vaccines of TCO or EEO combined with proper wound management and simultaneous
administration of rabies immunoglobulin is almost invariably effective in preventing rabies,
even following high-risk exposure. However, delays in starting or failure to complete correct
prophylaxis may result in death, particularly following bites in highly innervated regions,
such as the head, neck, finger tips or genitals, or following multiple bites.

3.3.2.2 Administration of Rabies Vaccine

The cost of rabies vaccines of TCO or EEO for intramuscular administration limits their
widespread use in many countries where dog rabies is endemic. Intradermal
administration of rabies vaccine of TCO or EEO (PCECV only) offers an equally safe
and immunogenic alternative that requires only 1–2 vials of vaccine to complete a
full course of post-exposure prophylaxis, thereby reducing the volume used and the
direct cost of vaccine by 60–80% compared with standard intramuscular schedule.
There is no evidence that intradermal administration requires vaccines with potency higher
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National Guidelines for Human Rabies Prophylaxis

than that recommended for intramuscularly administered rabies vaccines. Intradermal

regimens have been successfully introduced for post-exposure prophylaxis in countries
such as Bangladesh, India, Philippines, Sri Lanka and Thailand. However, in addition to
using vaccines explicitly authorized for the intradermal route, proper delivery of the vaccine
requires sufficient staff training to ensure correct storage, reconstitution and injection.

Intramuscular regimen (Zagreb regimen) and intradermal regimen (Thai Red Cross
Schedule) are cost-effective way of using rabies vaccines of TCO or EEO and both
regimens have been successfully used in rabies endemic countries of Asia.

The decision on using these regimens depends on numbers of patients and availability of
trained health professionals for ID regimen. If the number of patients per day is less
than 3, then Zagreb regimen is the preferred choice because of cost effectiveness and
lesser number of visits. If the daily turn-out of dog bite victims is 3-5, Thai Red Cross
intradermal regimen is preferred because it is safe, effective and economical.

Intramuscular Regimen

All age groups of dog bite victims of Category II and III require the same number of injec-
tions and dose per injection.

Zagreb Regimen (2-1-1)

The four dose Zagreb regimen is administered as two doses on day 0 (one dose in the right
and one in the left deltoid), and then one dose on each of days 7 and 21 into the deltoid
muscle (Figure. 2).

One injection = One vial of rabies vaccine

Figure 2: Zagreb Schedule

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National Guidelines for Human Rabies Prophylaxis

Intradermal regimen
In this regimen, (0.1ml) of rabies vaccine is administered on multiple sites in the dermis of
skin. Until ID injection devices become available proper administration of a fraction of the
vaccine contained in the vial requires knowledge and skill of the technique of intradermal
injection. Not all WHO prequalified rabies vaccines can be used by the intradermal route.
PCECV and PVRV as mentioned in Annex ( 2 ) are recommended for ID route.

Thai Red Cross Regimen (2-2-2-0-2)

Injection of 0.1 ml of reconstituted vaccine is given per ID site one on each deltoid area (left
and right arms), one inch above the insertion of deltoid muscle on days 0, 3, 7 and 28
(Figure.3). Day 0 is the day of first dose administration of IDRV and may not be the day of
rabies exposure/dog bite.

One injection = 0.1 ml of rabies vaccine

Figure 3: Thai Red Cross Regimen

General guidelines for use of intradermal vaccination

 Intradermal injections must be administered by trained staff.
 1ml syringe with hypodermic needle (e.g. Insulin Syringe) should be used for intra-
dermal administration.
 Always use a new syringe for each patient.
 Reconstituted vaccines must be used as soon as possible or within 6 hours if kept at +2
to + 8ºC. Vaccine when given intradermal should raise a visible and palpable bleb in the
skin. If a bleb is not raised, repeat the injection slightly away from the first one. (The
technique is similar to BCG inoculation).
 If the dose is inadvertently given subcutaneously or intra-muscularly or in the event of
spillage, a new dose should be given intradermal in nearby site.
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National Guidelines for Human Rabies Prophylaxis

 Dog bite victims who are immune-compromised or immune-suppressed (patients on

chloroquine, steroids and chemotherapy for malignant diseases, and HIV/AIDS patients)
should not be given vaccine by ID route. They should be given rabies vaccine of TCO or
EEO by intramuscular route.
 A timetable for return visits should be given to the patient for better compliance.

Intradermal injection technique

 Using aseptic technique, reconstitute the vial of freeze-dried vaccine with the diluents
supplied by the manufacturer. With 1 ml syringe draw 0.2 ml (i.e. 0.1 ml per ID site X 2
sites).
 Using the technique of BCG inoculation, stretch the surface of the skin and insert the tip
of the needle with bevel upwards, parallel to the skin surface (Figure. 4). Slowly inject
half the volume of vaccine (i.e. 0.1 ml) into the intradermal layer of skin, over the deltoid
area. A raised bleb (Figure. 5) should begin to appear causing an orange peel
appearance (peau d’ orange). Similarly inject 0.1ml intradermally on the other deltoid
area.

Figure 4: Intradermal injection technique

Figure 5: Raised bleb on intradermal inoculation

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National Guidelines for Human Rabies Prophylaxis

POST - EXPOSURE PROPHYLAXIS FOR

4 PREVIOUSLY VACCINATED PERSONS

4.1 Managing Re-Exposure Following PrEP or PEP with Rabies

Vaccine of TCO or EEO

In case of re-exposure, for persons who have previously received full post-exposure
prophylaxis (either by IM or ID route) with a potent rabies vaccine of TCO or EEO, perform
wound cleansing and give rabies vaccine (TCO or EEO) boosters on Day 0 and Day 3 intra
muscularly or intradermally.

4.2 Managing Re-Exposure Following PEP with Rabies

Vaccine of NTO
Personal who have previously received full post- exposure treatment with rabies vaccine of
NTO, should be treated as fresh case and may be given PEP as per merits of the case.
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National Guidelines for Human Rabies Prophylaxis

PRE-EXPOSURE PROPHYLAXIS
5
Pre-exposure vaccination/ prophylaxis (PrEP) is recommended for anyone who is at
continual, frequent or increased risk of exposure to the rabies virus, either as a result of
their residence or occupation.

The same safe and effective vaccines can be used for pre-exposure immunization. This is
recommended for travellers spending a lot of time outdoors, especially in rural areas,
involved in activities such as bicycling, camping, or hiking as well as for long-term travellers
living in areas with a significant risk of exposure.
Pre-exposure immunization is also recommended for people in certain high-risk
occupations such as laboratory workers dealing with live rabies virus and other rabies-
related viruses (lyssaviruses), and people involved in any activities that might bring them
professionally or otherwise into direct contact with bats, carnivores, and other mammals in
rabies-affected areas. As children are considered at higher risk because they tend to play
with animals, may receive more severe bites, or may not report bites, their immunization
could be considered if living in or visiting high-risk areas.
Pre-exposure vaccination is administered as one full dose of vaccine intramuscularly or
0.1 ml intradermally on days 0, 7 and either day 21 or 28.
PrEP is especially recommended for the following:
 Laboratory staff handling the rabies virus and infected material
 Clinicians and nurses attending to human rabies cases
 Veterinarians
 Dog catchers
 Wildlife wardens
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National Guidelines for Human Rabies Prophylaxis

DOG BITE MANAGEMENT IN IMMUNO-

6 COMPROMISED PATIENTS

Rabies Post-Exposure Prophylaxis for Immuno-compromised Persons

In patients with compromised immune status, care of the wound is the same as with the
immuno-competent individuals but there are some variations with regard to vaccination and
administration of RIG.

Vaccination of these individuals should be done by IM route. In an unvaccinated person a

full course of Essen Regimen (Day 0, 3, 7, 14, 28) should be used. In previously vaccinated
persons, vaccination regimen is the same as with the immuno-competent persons.

Regarding RIG, it should be given to all patients with category II & III exposure if they are
not vaccinated previously. HRIG should preferably be used.

It is essential to check whether these patients achieve protective level of rabies antibody
after the completed course of prophylaxis.
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National Guidelines for Human Rabies Prophylaxis

Table 4: Rabies Post-Exposure Prophylaxis for Immuno-compromised Persons

Treatment/ Dosage/ Administration Day of

Vaccination Status
Testing Guidelines for all Ages Regimen
 Wound cleaning
 Tetanus toxoid  Indicated if last tetanus
booster vaccine was more than
5 years prior to
exposure
 Human rabies  20 IU/kg body weight Day 0
immune globulin  Infiltrate HRIG into and (can be given
(HRIG) around wound up to day 7)
Immuno-compromised,
 Remaining HRIG given
Unvaccinated Persons
IM at a site distant from
the vaccination site
 Rabies vaccine  Five 1 vial doses, IM Day
 Adults/ older children: 0, 3, 7, 14, 28
deltoid area
 Young children:
anterolateral thigh
 Never in gluteals
 Wound cleaning
 Tetanus toxoid  Indicated if last tetanus
booster vaccine was more than
5 years prior to
exposure
Immuno-compromised,  DO NOT give
Previously Vaccinated HRIG
Persons  Rabies vaccine  Two 1 vial doses, IM Day 0, 3
 Adults/ older children:
deltoid area
 Young children:
anterolateral thigh
 Never in gluteals
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National Guidelines for Human Rabies Prophylaxis

MANAGEMENT OF ADVERSE EFFECTS

7 FOLLOWING IMMUNIZATION (AEFI)

Once initiated, rabies prophylaxis should not be interrupted or discontinued because of

local or mild systemic adverse reactions to rabies vaccine. Mild systemic adverse events,
such as transient fever, headache, dizziness and gastrointestinal symptoms, have been
observed in 5–15% of vaccinated people, usually such reactions can be successfully
managed with anti-inflammatory and antipyretic agents, such as ibuprofen or
acetaminophen.
When a person with a history of serious hypersensitivity to rabies vaccine must be
revaccinated, antihistamines can be administered. Adrenaline and other lifesaving drugs
should be readily available to counteract anaphylactic reactions, and the person should be
observed carefully immediately after vaccination. Such persons should preferably be
vaccinated under medical supervision.
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National Guidelines for Human Rabies Prophylaxis

REFERENCES
8
 http://www.who.int/rabies/human/postexp/en/index.html
 http://www.who.int/mediacentre/factsheets/fs099/en/
 http://www.searo.who.int
 WHO Expert Consultation on Rabies. Second Report 2012 Geneva
 National Guidelines for Rabies Prophylaxis and Intradermal Administration of Cell
Culture Rabies Vaccines 2007. National Institute of Communicable Diseases.
Government of India
 National Guideline for Rabies Prophylaxis and Intra-dermal Application of Cell Culture
Rabies Vaccines. June 2010. Disease Control Unit. Ministry of Health & Family Welfare
Bangladesh.
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National Guidelines for Human Rabies Prophylaxis

Annex (1): The modern rabies vaccines of TCO or EEO

Volume after Approved route of WHO

Generic Brand Name
reconstitution administration Pre-qualified

Verorab® 0.5 ml IM or ID Yes

Purified Vero Cell
Rabies Vaccine Speeda® 0.5 ml IM No
(PVRV)
Indirab® 0.5 ml IM No

Purified Chick
Embryo Cell Vaccine Rabipur® 1.0 ml IM or ID Yes
(PCECV)
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National Guidelines for Human Rabies Prophylaxis

Annex (2): Proforma for Post-exposure management of animal bite cases

Section I – History Taking

Referred by: __________________________________________________________________________

Date: ______________________________ Registration Number: ___________________________

Name: ________________________________________________ Age: _____________________

Sex: Male Female Occupation ______________________________________
Complete home address: ________________________________________________________________
_____________________________________________________________________________________
Phone Number: __________________________

Date of bite: _____________________________ Time lapse: ___________________________

Locality of biting episode: ________________________________________________________________

Biting animal: Dog Cat Monkeys Others

Animal Status: Pet Stray
If pet, Vaccinated Non Vaccinated

Outcome of the biting animals: Under observation Observed for 10 Days

Killed Escaped Healthy

Section II – Physical Examination

Category Severity and Site of the Wound

Category I:  Touching or feeding of animals

No Risk  Lick on intact skin

Category II:  Nibbling of uncovered skin

Moderate Risk  Minor scratches or abrasion without bleeding

Category III:  Single or multiple wounds on head and neck

High Risk  Single or multiple transdermal bites/ scratches/ laceration with bleeding
 Scratches with bleeding
 Licks on broken skin
 Contamination of mucous membrane of eyes, mouth, nose or wounds with saliva or
discharges from rabid animals

Wound Category: Category I Category II Category III

Sites of Wounds: _________________________________________________________________________
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National Guidelines for Human Rabies Prophylaxis

Section III – Management

Previous history of animal bite/ exposure: Yes No

If yes, When: ______________________ Place: ____________________________________
PEP given: Yes No

Past and present medical history: Immuno-compromised Yes No

Currently taking chloroquine therapy Yes No

Patient’s Weight: ______________ kg

Thorough washing of bite wound: Yes No

Rabies Immunoglobulin (RIG) for category III bite: Human RIG: Equine RIG:
Number of vials administered: ______________ Date administered: ________________________

Brand Name of Rabies Vaccine: ____________________________________________________________

Intradermal (Thai Red Cross Regimen)

Day Doses Site Date

Day 0 2

Day 3 2

Day 7 2

Day 28 2

OR
Intramuscular (Zagreb Regimen)

Day Doses Site Date

Day 0 2

Day 7 1

Day 21 1

Any side effects of vaccine if reported: ________________________________________________________

_______________________________________________________________________________________

Remarks: _______________________________________________________________________________

_______________________________________________________________________________________
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National Guidelines for Human Rabies Prophylaxis

Annex (3): Requirements for a dog bite treatment centre

The following are the recommended guidelines for physical facilities and staff requirements
for a dog bite treatment centre

I. Accommodation
 Treatment room 20’ X 15’ (minimum) and waiting hall
 Wound washing area with running tap water
 Small Water Tank (In case of shortage of water in the Centre)

II. Staff
 Medical Officer – 1
 Staff Nurses – 3
 Attendant – 1

III. Furniture
 Office Table – 1 (Medical Officer)
 Arm chairs – 2
 Revolving stools – 3
 Bed for examining the patient -1

IV. Equipment and Instruments

 Refrigerator
 Weighing machine – 1
 BP apparatus
 Washing Area
 Safety Box to dispose of used syringes

V. IEC materials
 National Guidelines for Human Rabies Prophylaxis Book
 Standard Operating Procedures for Human Rabies Prophylaxis Book
 Information booklet
 Vaccination Cards
 Sign Board
 Treatment Proforma
 Entry Register
 Schedule Calendar
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National Guidelines for Human Rabies Prophylaxis

VI. Drugs (Injectable and Applicants)

 Rabies vaccine
 Rabies immunoglobulin
 Injection Adrenaline
 Injection Antihistamine
 Injection Steroid
 Povidone Iodine
 Normal Saline
 Anti Tetanus toxoid
 Emergency Kit

VII. Other Supplies and Consumables

 Cotton
 Adhesive plaster
 Dressing material
 Liquid Soap
 Surgical gloves
 Insulin syringes with 26G needles
 20 mL and 50mL syringes for wound toilet in absence of running water
 Kidney tray
 Dressing bin
 Covered waste bin