RABIES

Key Facts
[WHO]
Rabies is a vaccine-preventable viral disease which occurs in more than 150
countries and territories.
Dogs are the source of the vast majority of human rabies deaths.
Rabies elimination is feasible by vaccinating dogs.
Infection causes tens of thousands of deaths every year, mostly in Asia and
Africa.
40% of people who are bitten by suspect rabid animals are children under 15
years of age.
Immediate wound cleansing with soap and water after contact with a suspect
rabid animal can be life-saving.
[DOH]
Rabies is a human infection that occurs after a transdermal bite or scratch by an
infected animal, like dogs and cats.
It can be transmitted when infectious material, usually saliva, comes into direct
contact with a victims fresh skin lesions.
Rabies may also occur, though in very rare cases, through inhalation of viruscontaining spray or through organ transplants.
Rabies is considered to be a neglected disease, which is 100% fatal though
100% preventable.
It is not among the leading causes of mortality and morbidity in the country but it
is regarded as a significant public health problem because:
(1) it is one of the most acutely fatal infection and
(2) it is responsible for the death of 200-300 Filipinos annually
Vision: To Declare Philippines Rabies-Free by year 2020
Goal: To eliminate human rabies by the year 2020
To attain its goal, the program employs the following strategies:
1. Provision of Post Exposure Prophylaxis (PEP) to all Animal Bite Treatment
Centers (ABTCs)
2. Provision of Pre-Exposure Prophylaxis (PrEP) to high risk individuals and
school children in high incidence zones
3. Health Education
Public awareness will be strengthened through the Information, Education, and
Communication (IEC) campaign. The rabies program shall be integrated into the
elementary curriculum and the Responsible Pet Ownership (RPO) shall be promoted.
In coordination with the Department of Agriculture, the DOH shall intensify the

promotion of dog vaccination, dog population control, as well as the control of stray
animals.
In accordance with RA 9482 or The Rabies Act of 2007, rabies control
ordinances shall be strictly implemented. In the same manner, the public shall be
informed on the proper management of animal bites and/or rabies exposures.
4. Advocacy
The rabies awareness and advocacy campaign is a year-round activity
highlighted on two occasions March as the Rabies Awareness Month and September
28 as the World Rabies Day.
5. Training/Capability Building
Medical doctors and Registered Nurses are to be trained on the guidelines on
managing a victim.
6. Establishment of ABTCs by Inter-Local Health Zone
7. DOH-DA joint evaluation and declaration of Rabies-free islands

Background
Rabies is a viral disease that affects the central nervous system (CNS).
Genus Lyssavirus is the prototypical human pathogen
There are 10 viruses in the rabies serogroup, most of which only rarely
cause human disease.
The genus Lyssavirus, rabies serogroup, includes the classic rabies virus,
Mokola virus, Duvenhage virus, Obodhiang virus, Kotonkan virus,
Rochambeau virus, European bat Lyssavirus types 1 and 2, and
Australian bat Lyssavirus.
The rabies virus is a bullet-shaped virion with a single-stranded ribonucleic acid
(RNA) nucleocapsid core and lipoprotein envelope. Its nucleocapsid material
consists of Negri bodies, which are observed in the cytoplasm of infected
neurons (see the image below). The virus is transmitted in saliva or in
aerosolized secretions from infected animals, typically via a bite. The virus is not
hardy and is quickly inactivated by drying, ultraviolet rays, x-rays, trypsin,
detergents, and ether.

Transmission
People are usually infected following a deep bite or scratch by an infected
animal.
Dogs - the main host and transmitter of rabies. They are the cause of human
rabies deaths in Asia and Africa.
Bat - the source of most human rabies deaths in the Americas, 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.
Rarely, rabies may be contracted by inhalation of virus-containing aerosol or via
transplantation of an infected organ.
Ingestion of raw meat or other tissues from animals infected with rabies is not a
source of human infection.
Prevention
Eliminating rabies in dogs

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

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 and expatriates

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.

Pathophysiology
Rabies is a highly neurotropic virus that evades immune surveillance by its
sequestration in the nervous system.
Inoculation
enters the peripheral nerves
prolonged incubation follows
(the length of which depends on the size of the inoculum and its proximity to the CNS)

amplification occurs until bare nucleocapsids spill into the myoneural junction and enter
motor and sensory axons
(at this point, prophylactic therapy becomes futile, and rabies can be expected to follow
its fatal course, with a mortality rate of 100%).
The rabies virus travels along these axons at a rate of 12-24 mm/d to enter the
spinal ganglion.
Its multiplication in the ganglion is heralded by the onset of pain or paresthesia
at the site of the inoculum, which is the first clinical symptom and a hallmark
finding.
From here, the rabies virus spreads quickly, at a rate of 200-400 mm/d, into the
CNS, and spread is marked by rapidly progressive encephalitis.
Thereafter, the virus spreads to the periphery and salivary glands.
Death occurs from global neurologic and organ dysfunction.
The virion acts in the synaptic space, where homology in amino acid
sequences between neurotransmitter receptors for acetylcholine, GABA,
and glycine may afford a mechanism for viral binding of these receptors.
Thus, its action is neurotoxic, rather than direct damage.

Symptoms
The Incubation period for rabies is typically 13 months, but may vary from <1
week to >1 year.
The infected individual remains asymptomatic during this period.
The average duration of incubation is 20-90 days. In more than 90% of
cases, incubation is less than 1 year.

The incubation period is less than 50 days if the patient is bitten on the
head or neck or if a heavy inoculum is transferred through multiple bites,
deep wounds, or large wounds. A person with a scratch on the hand may
take longer to develop symptoms of rabies than a person who receives a
bite to the head.
The rabies virus is segregated from the immune system during this period,
and no antibody response is observed.

Prodromal period: the virus enters the CNS.

The duration of this period is 2-10 days.
Nonspecific symptoms and signs develop.
Paresthesia, pain, or intense itching at the inoculation site is
pathognomonic for rabies and occurs in 50% of cases during this phase;
this may be the individuals only presenting sign.
Symptoms may include the following:
Malaise
Anorexia
Headaches
Fever
Chills
Pharyngitis
Nausea
Emesis
Diarrhea
Anxiety
Agitation
Insomnia
Depression
Acute neurologic period

This period is associated with objective signs of developing CNS disease.

The duration is 2-7 days.
Symptoms include muscle fasciculations, priapism, and focal or
generalized convulsions.
Patients may die immediately or may progress to paralysis, which may be
present only in the bitten limb at first but usually becomes diffuse.
2 forms of disease may follow:
1. Furious rabies may develop during this period, patients develop
agitation, hyperactivity, restlessness, thrashing, biting, confusion,
or hallucinations. After several hours to days, this becomes episodic
and interspersed with calm, cooperative, lucid periods. Furious
episodes last less than 5 minutes. Episodes may be triggered by
visual, auditory, or tactile stimuli or may be spontaneous. Seizures may
occur. This phase may end in cardiorespiratory arrest or may progress
to paralysis.
2. Paralytic rabies, is also known as dumb rabies or apathetic rabies,
because the patient is relatively quiet compared with a person with the
furious form. Twenty percent of patients do not develop the furious
form. Paralysis occurs from the outset, and fever and headache are
prominent. A coma slowly develops, and eventually death occurs. The
paralytic form of rabies is often misdiagnosed, contributing to the
under-reporting of the disease.

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).
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.

Effective treatment soon after exposure to rabies can prevent the onset of symptoms
and death.
Local treatment of the wound
This involves first-aid of the wound that includes immediate and thorough
flushing and washing of the wound for a minimum of 15 minutes with soap and
water, detergent, povidone iodine or other substances that kill the rabies virus.

Table: Categories of contact and recommended postexposure prophylaxis (PEP)

Categories of contact with

suspect rabid animal

Post-exposure
prophylaxis measures

Category I touching or feeding

animals, licks on intact skin

None

Category II nibbling of
uncovered skin, minor scratches
or abrasions without bleeding

Immediate vaccination and

local treatment of the
wound

Category III single or multiple

transdermal bites or scratches,
licks on broken skin;
contamination of mucous
membrane with saliva from licks,
contacts with bats.

Immediate vaccination and

administration of rabies
immunoglobulin; local
treatment of the wound

 All category II and III exposures assessed as carrying a risk of developing

rabies require PEP. This risk is increased if:
the biting mammal is a known rabies reservoir or vector species;
the animal looks sick or displays an abnormal behaviour;
a wound or mucous membrane was contaminated by the animals
saliva;
the bite was unprovoked; and
the animal has not been vaccinated.
Intramuscular schedules
One dose of the vaccine should be administered on days 0, 3, 7, 14 and
30.
All intramuscular injections must be given into the deltoid region or, in
small children, into the anterolateral area of the thigh muscle.
Vaccine should never be administered in the gluteal region.
Intradermal schedule
WHO recommended the following intradermal regimen and vaccines for
use by the intradermal route:

2-site intradermal method (2-2-2-0-1-1) for use with PVRV (Verorab TM,
Imovax TM, Rabies vero TM, TRC Verorab TM) and PCECV (Rabipur TM)
For 2-site intradermal method (2-2-2-0-1-1)
The volume per intradermal site is:

0.1 ml for PVRV (Verorab TM, Imovax TM, Rabies vero TM, TRC
Verorab TM)

0.1 ml for PCECV (Rabipur TM)

Combined immunoglobulin-vaccine

Combined immunoglobulin-vaccine treatment was considered in the eighth

report of the WHO Expert Committee as the best specific systemic
treatment available at that time for the post-exposure prophylaxis of rabies
in humans, although experience indicated that vaccine alone was sufficient
for minor exposures (category II).

Immunoglobulin should be given in

a single dose of 20 IU per kg of body weight for human anti-rabies
immunoglobulin (HRIG), and
40 IU per kg of body weight
immunoglobulin (ERIG);

for

heterologous

(equine)

the first dose of vaccine should be inoculated at the same time as

the immunoglobulin, but in a different part of the body.

Administration of rabies immunoglobulin (RIG) should be infiltrated into the

depth of the wound and around the wound as much as anatomically
feasible.

Any remainder should be injected at an intramuscular site distant from that

of vaccine inoculation e.g. into the anterior thigh.

Treatment should be started as early as possible after exposure, but in no

case should it be denied to exposed persons whatever time interval has
elapsed.

JI Calimbas, Alyssa Ann s.