DEPARTMENT OF MICROBIOLOGY

FACULTY OF MEDICAL SCIENCES

UNIVERSITY OF SRI JAYEWARDENEPURA

RABIES
 Zoonotic viral disease causing acute encephalitis in warm blooded animals commonly following a bite
of an infected subject.
 Human rabies is fatal if post exposure prophylaxis is not administered prior to the onset of symptoms.
 The rabies virus infects the central nervous system and subsequently causes encephalomyelitis and death.

Incidence:
 Human cases have reduced in Sri Lanka following introduction of post - exposure treatment of
humans and vaccination of dogs.
 Rabies is also 100% preventable in humans.
 In Sri Lanka, 20 to 30 cases of rabies are reported annually.
 Human to human transmission has not been documented.

Incidence of rabies in Sri Lanka (WER), 2019

Microbiological basis of pathogenesis

Source of infection
Rabid animal

Causative Organism:

Electron microscopic view

Department of Microbiology, FMS, USJ

updated at the handout consensus meeting July 2020
Bullet shaped enveloped RNA virus belonging to Family Rhabdoviridae.
Mode of transmission

 Bite of a rabid animal mostly dogs, cats

Any warm-blooded animal – Mongoose, Jackals, Polecats, Bandicoots, Rocksquirrelles etc.
(House rats have not been implicated in the transmission of rabies in Sri Lanka )
 Licks on abraded skin or intact mucosa
 Drinking unboiled milk from a rabid cow or goat
 Rarely by inhalation - in caves with bats

Incubation period – Highly variable

Man - 2 to 12 weeks, up to 2 years (commonest between 1-3 months)
(Shorter I.P - in children, bites on head, neck and highly innervated areas. eg: fingers)

Microbiological mechanism of pathogenesis

Virus multiplies near the bite site, takes 1 to 3 days or may be longer

Enter nerves by attaching via envelope glycoprotein at neuromuscular junction – motor end
plate

Spread of virus in nervous tissue (out of reach of circulating antibodies)

Once in the brain, the virus spread from cell to cell, causing dysfunction of the cell rather than
damaging the cell.

From the brain, virus spread through efferent nerves to most body tissues.
eg: Salivary glands and conjunctival cells

Clinical features
Human
 Prodromal stage - flu like illness, sensory changes at the site of bite
 Two main forms
o Dumb rabies (paralytic)
o Furious rabies (hyperactive)

 Convulsions coma death

 Death occurs during the first seven days of illness without intensive care
Dogs
 Prodromal stage - fever, sudden change of temperament
 Two forms
o Aggressive stage
o Paralytic disease
 Progressive paralysis - begins in hind legs

Department of Microbiology, FMS, USJ updated at the handout consensus meeting July 2020
  Coma death

Laboratory diagnosis of rabies

Specimens and investigations

Ante-mortem (Rarely done)

Human:

Specimen Investigation
CSF Antibody detection
-Rapid fluorescent focus inhibition test (RFFIT) -
Done at MRI

RT-PCR – Done at MRI

Serum Antibody detection
Impression smears of cornea Antigen detection
Skin biopsy Antigen detection, RT-PCR
Saliva RT -PCR

Post-Mortem

Human:

Specimen Investigation Interpretation

Brain tissue (Hippocampus, Antigen detection by Highly sensitive and specific
Brain stem, cerebellum) Fluorescent antigen test(FAT) Confirmatory test (Gold
standard)

Animal :

Specimen Investigation Interpretation

Brain tissue (Hippocampus, Direct smear with special Sensitivity - 75% thus
Brain stem, cerebellum) stain (Sellar’s stain) – considered as a screening test
detection of Negri bodies
(intra cytoplasmic
eosinophilic bodies with If Negri bodies are seen
basophilic stippling) diagnosis of rabies is
confirmed as it is a very
specific test.

As the sensitivity of the test

is low, a negative smear
cannot rule out rabies.

Antigen detection by Done when negative for

Fluorescent Antigen Negri bodies;
test(FAT)
Highly sensitive and specific
Confirmatory test (Gold
Department of Microbiology, FMS, USJ updated at the handout consensus meeting July 2020
 standard)

Transport :

Head of the animal placed in water tight metal container (or thick polythene bag / plastic
container), which is sealed tightly and then placed in larger water tight insulated container.
Place ice in between the two containers (should reach the MRI as soon as possible)

Ice cubes Head of the animal placed in water tight thick polythene bag

Rabies post exposure prophylaxis

In a patient bitten by a rabid animal, post exposure therapy is aimed at preventing entry of the
virus in to the nervous system by inducing an early immune response.

Management of a case of animal bite

 Wash wound/s immediately with soap and flowing water, 70% alcohol or any antiseptic
o To reduce the viral load at the site in order to minimize entry of virus
o Soap and antiseptics inactivate enveloped viruses

 Anti Tetanus immunization where indicated

o Since a contaminated wound could also have a risk of contamination with C. tetani

Department of Microbiology, FMS, USJ updated at the handout consensus meeting July 2020
 Antibiotics if necessary
o To prevent secondary infections
 If animal is suspected of rabies, post exposure therapy should be given
 Active immunization for all categories of exposure
o To induce immune response - Since the incubation period is relatively
long, this enables viruses which have not entered the nervous system to
be neutralized
 Passive immunization with rabies specific immunoglobulins given in major
exposure at the bite site (around the bite wound)
o To neutralize the rabies virus at the site of entry and for immediate protection

Anti Rabies Vaccines available in Sri Lanka at present

1. Purified Vero cell rabies vaccine – PVRV (Verorab)

2. Purified chick embryo cell vaccine – PCEC

Post exposure anti rabies therapy

Two categories of patients:

1. Major exposures
2. Minor exposures

Major exposures Minor exposures

 Includes single or multiple bites with  Includes single superficial bites or

bleeding
 on head, neck, face, hands, chest,
upper arms,
 palms, tips of fingers and toes ,
genitals;
 licks on mucus membranes;
 Single or multiple deep bites on any
part of the
Immunization
both active and passive immunization
(rabies immunoglobulin + anti rabies
vaccine)
scratches on the lower limbs, upper
limbs (excluding upper arm, palms and
finger tips), abdomen and back;
 licks on open wounds
 drinking of unboiled milk of rabid cow
or goat;
 nibbling of uncovered skin
 superficial bites & scratches of wild
animals without bleeding
active immunization (anti rabies vaccine)
only

Department of Microbiology, FMS, USJ updated at the handout consensus meeting July 2020
Rabies Immunoglobulin (RIG)

 Two types of immunoglobulins are available;

o Human (HRIG) - only given in special situations, very expensive
o Equine (ERIG) - available in government hospitals, routinely administered
 Serum should be given preferably as early as possible within 72 hours, but could be
given up to 03 months.
 RIG should be infiltrated as much as possible to the site of all the wounds.
 A course of ARV (anti rabies vaccine) should always follow the infiltration of RIG

Anti rabies vaccines

 Vaccine is given on the same day after serum therapy, but at a different site.
 According to the exposure type, the vaccine regime will vary.
 Administration could be intramuscular or intradermal.

Advantage of ID Schedule

 Considerably lowers the cost of vaccine,

o as the total volume used is lower than in IM schedule

Disadvantages of ID Schedule

 ID injections should only be administered by trained staff, under supervision.

 Should not be used in immuno-compromized patients.
 After reconstitution of the vaccine, the contents should be used as soon as possible

Anti-rabies pre exposure therapy

Persons at high risk of exposure

 Lab staff working with rabies virus

 Veterinarians and their support staff
 PHIs and animal vaccinators working for rabies control programme
 Animal handlers
 Wild life officers
 Individuals living or travelling to rabies endemic areas

 Antibody levels should be checked every 6 months after completing the course of
vaccination
 If antibody levels fall below 0.5 IU/ml another booster should be given.
 In Sri Lanka since facilities are not available for routine antibody testing, one booster is
given every 05 years.

Department of Microbiology, FMS, USJ updated at the handout consensus meeting July 2020
IMPORTANT POINTS TO BE NOTED

1. Suturing of wounds should be done only after infiltration with serum when indicated
2. Pregnancy is not a contra indication to start immunoglobulin or vaccine
3. In small children with multiple bites dilute serum with sterile normal saline if volume is
insufficient for infiltration of all wounds – serum can be diluted 2 to 3 times with normal
saline
4. Store serum and vaccine at 2 - 8 0C and maintain adequate cold chain
5. After 14 days of observation, if the dog remains healthy we can discontinue the vaccination
6. If bitten by an apparently healthy animal who has been regularly vaccinated (min. of 2
vaccinations with the last rabies vaccine given within the last year- Rabies PET is delayed
and observe the dog for 14 days after the bite.

 If you have any doubts please contact the Dept. of Rabies and Vaccines, M.R.I.
i

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References;
1. Vaccines and rabies immunoglobulins for humans, WHO Expert Consultation on Rabies, WHO
Technical Report Series:2018:1012 (3)
2. Rabies vaccines: WHO position paper, Weekly epidemiological record, WHO, 20 April 2018,No
16,2018,93, 201-220

Department of Microbiology, FMS, USJ updated at the handout consensus meeting July 2020