Rabies pathogenesis, clinical features, treatment, prophylaxis

1. RABIES
Presented by:
Pukar K.C.
13th Batch MBBS
Kathmandu University School of Medical
Sciences

2. SCENARIO IN WORLD
• Estimated to cause 59,000 human deaths
annually in over 150 countries, with 95% of cases
occurring in Africa and Asia
• 99% of rabies cases are dog-mediated
• Approximately half of cases attributable to
children under 15
• Major burden in Asia, with an estimated 35,172
human deaths per year
• India accounts for 59.9% of rabies deaths in Asia
and 35% of deaths globally

3. Human deaths from Rabies

4. SCENARIO IN NEPAL
• Around 30,000 cases in pets and more than
100 human rabies cases occur each year
• According to the OIE World Animal Health
Information System in 2011 Nepal reported 28
cases of rabies in humans
• In 2012, 11 human rabies cases were
confirmed at the Central Tropical Hospital
• Nawalparasi and Tanahu (45 each) with the
highest number of animal outbreaks

5. Fiscal year No. of cases
of dog bites
No. of cases
of other
animal bites
No. of cases
of animal
bites
No. of ARV
vials
consumed
Deaths
2071/72 17,320 3,290 20,610 273,000 13
2072/73 20,133 2,494 22,627 320,139 6
2073/74 37,226 2,518 39,744 227,639 8
Annual report: 2073/74

6. AGENT
• Bullet shaped virus
• Family: Rhabdoviridae
• Genera: Lyssavirus
• single-strand RNA virus has a non segmented,
negative sense (antisense) genome
• Lipoprotein envelope
• Knob like spikes, glycoprotein

7. HOST
• Rabies virus can infect any mammal (which then can
transmit disease to humans)
• True animal reservoirs that maintain the presence of rabies
virus in the population are terrestrial carnivores and bats.
• Worldwide, transmission from dogs accounts for >90% of
human cases.
• In Africa and Asia, other animals serve as prominent
reservoirs, such as jackals, mongooses, and raccoon dogs
• Rare in small mammals, including mice, squirrels, and
rabbits; to date, no animal-to-human transmission from
these animals has been documented.

8. TRANSMISSION
• Almost exclusively through inoculation of the infected saliva
through a bite or scratch from a rabid mammal.
• Transmission rate is increased if the victim has suffered multiple
bites and if the inoculation occurs in highly innervated parts of the
body such as the face and the hands.
• Infection does not occur after exposure of intact skin to infected
secretions, but virus may enter the body through intact mucous
membranes.
• Inhalational exposure can occur during laboratory accidents.
• Caregivers of a patient with rabies are advised to use full barrier
precautions.
• The virus is rapidly inactivated in the environment, and
contamination of fomites is not a mechanism of spread.

9. PATHOGENESIS
• After inoculation, rabies virus replicates slowly and at low levels in muscle
or skin.
• Virus then enters the peripheral motor nerve, utilizing the nicotinic
acetylcholine receptor
• Once in the nerve, the virus travels by fast axonal transport
• Rapid dissemination occurs throughout the brain and spinal cord before
symptoms appear.
• Infection of the dorsal root ganglia causes characteristic radiculitis.
• Infection concentrates in the brainstem, leads to autonomic dysfunction
and relative sparing of cognition.
• After infection of the central nervous system, the virus travels anterograde
through the peripheral nervous system to virtually all innervated organs,
including salivary glands
• Rabies virus replicates in acinar cells of the salivary glands and is secreted in
the saliva of rabid animals that serve as vectors of rabies

10. • Histopathology reveals limited
damage, inflammation, or
apoptosis
• The pathological hallmark of
rabies is the Negri body
(absent in 20-60%)
• Negri bodies are composed of
clumped viral nucleocapsids
that create cytoplasmic
inclusions on routine
histology.

11. Harrison's Principles of
Internal Medicine (19th Ed)

12. CLINICAL FEATURES
• Incubation period: 1-3
months (5 days – more
than 6 months
• Types
– Encephalitic or “furious”
rabies
– Paralytic or “dumb”
rabies

13. ENCEPHALITIC OR “FURIOUS” RABIES
• Progressive symptoms
• Beginning, non specific symptoms, fever, sore throat, malaise,
headache, nausea and vomiting
• Paresthesia and pruritis at or near the site of bite later involves the
whole limb
• Period of lucidity alternating with the period of encephalopathy
• Demonstrate symptoms of encephalitis, with agitation, depressed
mentation, and seizures
• Hydrophobia and aerophobia are cardinal signs but not specific and
are unique to humans
• Fanning or offering of water causes violent spasm of neck, pharynx
and diaphragm resulting in choking and aspiration
• Death within 1-2 days of hospitalization in developing countries and
by 18 days of hospitalization with intensive care

14. PARALYTIC OR “DUMB” RABIES
• Characterized by fevers and ascending motor
weakness leading to quadriparesis and the
cranial nerves.
• Mild sensory involvement may be present
• Involvement of sphinchter
• Features of encephalitis may be present as
disease progresses

15. DIAGNOSIS
• History and clinical features
• Laboratory
– Reverse transcription polymerase chain reaction, most sensitive,
sample: saliva, skin, brain
– Can be grown in cell cultures but takes time
– Rabies antigen detection through immunofluorescence of saliva
or biopsies , hairy skin or brain.
– Rabies-specific antibody detection in serum or CSF samples,
antibody in CSF is rarely detected after vaccination and is
considered diagnostic of rabies regardless of immunization
status.
– CSF reveals mild mononuclear cell pleocytosis with a mildly
elevated protein level, non diagnostic
– MRI changes are late and non-specific

16. TREATMENT
• Fatal
• Antiviral treatment not effective
• Rabies immunoglobulin (RIG), rabies vaccine
are not beneficial once symptoms appear
• Appearance of the normal antibody response
by 7 days is associated with clearance of
salivary viral load and survival

17. PREVENTION
• Vaccination of domestic dogs
• Education to avoid wild animals, stray animals,
and animals with unusual behavior
• Post exposure prophylaxis

18. Post exposure prophylaxis
• Indicated to bites in
– By wild lives unless proved non rabid by testing brain
– By domestic pets depending upon the statistics of rabies in the
area, signs of rabies in animals in 10 days observation period
and the vaccination status
• In case of bats
– CDC recommended that rabies PEP be considered after any
physical contact with bats and when a bat is found in the same
room as persons who may not be able to accurately report a
bite, assuming that the animal is unavailable for testing. Such
people include young children, the mentally disabled, and
intoxicated individuals.
• Non bite cases such as handling of carcass or blood do not
need PEP

19. • Animal should be put on observation for the
signs of rabies
• PEP should be established as soon as possibile
• Rabies vaccine and rabies immunoglobulins
are contraindicated once the signs and
symptoms of rabies develop

20. The WHO rabies exposure categories are:
Category of
exposure
Description Post- exposure prophylaxis
Category I Touching or feeding animals, licks on
intact skin
Not regarded as exposures,
therefore no PEP required
Category II Nibbling of uncovered skin, minor
scratches or abrasions without bleeding
Vaccine should be injected
as soon as possible
Category III Single or multiple transdermal bites or
scratches, contamination of mucous
membrane or broken skin with saliva from
animal licks, exposures due to direct
contact with bats
Vaccine and rabies
immunoglobulin should be
administered at distant sites
as soon as possible.
Immunoglobulin can be
administered up to 7 days
after injection of the first
dose of vaccine

21. STEPS OF PEP
• Wound washing
• Rabies immunoglobulin
• Rabies vaccine

22. WOUND CLEANING
• All bite wounds and scratches should be attended
to as soon as possible after the exposure
• Thorough washing and flushing of the wound for
approximately 15 minutes, with soap or
detergent and copious amounts of water
• Where available, an iodine-containing, or
similarly virucidal, topical preparation should be
applied to the wound
• Tetanus toxoid

23. IMMUNOGLOBULIN
• Human immunoglobulin at the
dose of 20IU/kg
• Should be in infused as soon
as possible but can be delayed
upto 7 days
• As much of the dose is infused
around the wound as possible,
and the remainder is injected
intramuscularly distant from
the limb one used for killed
vaccine
• Equine immunoglobulin can
also be used, but has higher
adverse effects

24. INACTIVATED VACCINE
• A series of rabies vaccine injections should be
administered promptly after an exposure.
• TYPES:
– Nerve culture vaccine
– Cell culture vaccine
• purified chick-embryo cell cultivated vaccine
• human diploid cell cultures vaccine

25. • Dose: 1 ml
• Site: deltoid region or
anterolateral aspect of
thigh in children less than
2 years
• Gluteal is avoided as
there is blunted antibody
response
• Intramuscular Regimen: 5
dose regimen
– One dose of the vaccine
should be administered on
days 0, 3, 7, 14 and 28

26. OTHER REGIMEN
• Intramuscular
– 2-1-1 regimen
• Two doses are given on day 0 in the deltoid muscle, right and left
two more doses on day 7 and day 21
• Intradermal
– Dose: 0.1 ml
– Vaccine administered ID must raise a visible and palpable
“bleb” in the skin
– The 2-site intradermal method: (2-2-2-0-2)
– deltoid muscle on the left and right upper arm and
suprascapular area
– Given on days 0, 3, 7 and 28.

27. Short rabies PEP
of previously vaccinated persons
• Schedule 1:
– One dose to be injected intramuscularly or
intradermally on days 0 and 3
• Schedule 2:
– A “4-site” intradermal (ID) PEP can be used
– Consists of 4 injections of 0.1 mL equally
distributed over left and right deltoids, thigh or
suprascapular areas during a single visit

28. PRE-EXPOSURE PROPHYLAXIS
• Indicated in those with continued risk of
rabies
– Groups of persons at high risk of exposure to live
rabies virus (laboratory staff, veterinarians, animal
handlers and wildlife officers)
– Children living in or visiting rabies affected areas
– Travellers to rabies-affected areas according to the
level of risk in that area.

29. Intramuscular:
• One intramuscular dose is given on each of days 0, 7 and 21 or 28
• Site of injection: deltoid area for adults; anterolateral area of the thigh is
recommended for children aged less than 2 years
Intradermal:
• One intradermal injection of 0.1 ml is given on each of days 0, 7, and 21 or
28
If antimalarial chemoprophylaxis is applied concurrently, intramuscular
injections must be used
Professionals Serum sample Booster dose if
Laboratory workers Every 6 months Antibody titre falls below
0.5 IU/ml
veterinarians, animal
handlers, wildlife
officers etc working in rabies
endemic areas
Every 2 years Antibody titre falls below
0.5 IU/ml

32. REFRENCES
• Nelson Textbook of Pediatrics 20th Edition
• Harrison's Principles of Internal Medicine
(19th Ed)
• WHO Guide for Rabies Pre and Post Exposure
Prophylaxis in Humans Updated 2014

33. THANK YOU!!