Hfzhfskgdkhd

1. RABIES

2. An 11-year-old boy in the US presents to the
emergency department with fever, sore throat, and
vomiting. The only known animal contacts are
house pets.
There is no history of travel abroad, but the
patient attended a summer camp in Alabama 2
months earlier. The patient has never received
rabies immunization. Laboratory tests and CXR are
unremarkable and he is sent home.
Case history #1

3. He returns the same day with additional symptoms
of insomnia, urinary urgency,, paraesthesias of the
scalp and right arm, dysphagia, disorientation, and
ataxia.
He deteriorates rapidly, with slurred speech,
hallucinations, and agitation (excitement) requiring
sedation and intubation. Tests for West Nile virus,
HSV, and enterovirus were negative. The patient
progresses to coma over several days, and develops
autonomic instability. He dies on the 14th day.
Case history #1

4. Rabies
Hydrophobia
also

5. Rabies
is a acute viral disease of nervous
system of humans and mammals.
Rabies causes severe encephalitis
(inflammation of the brain) with
lethal outcome.
Definition

6. Rabies is virtually
100% fatal Infection

7. Etymology
 The term is derived from
the Latin rabies, "madness".
 The Greeks derived the word "lyssa",
from "violent"; this root is used in the
name of the genus of rabies lyssavirus

8. In unvaccinated people, rabies is fatal
due to neurological symptoms.
Timely postexposure prophylaxis is
crucial for stopping disease progression

9. Rabies is a vaccine-preventable viral disease which
occurs in more than 150 countries and territories.
Dogs are the main source of human rabies deaths,
contributing up to 99% of all rabies transmissions to
humans.
Interrupting transmission is feasible through
vaccination of dogs and prevention of dog bites.
Infection causes tens of thousands of deaths every
year, mainly in Asia and Africa.
Key facts

10. Globally rabies causes an estimated cost of US$ 8.6
billion per year
40% of people bitten by suspect rabid animals are
children under 15 years of age.
Immediate, thorough wound washing with soap and
water after contact with a suspect rabid animal is crucial
and can save lives.
WHO leads the collective “United Against Rabies” to
drive progress towards "Zero human rabies deaths
from dog-mediated rabies by 2030".
Key facts

11.  Rabies is Acute rapid progressive & highly fatal viral
disease of CNS
 Zoonotic disease of warm blooded animals (dogs,
cats, bats, racoons, skunks, foxes, wolfs and etc )
 Transmitted to man by bite of rabid animal.
 Non-bite exposures : aerosols; generated in labs, caves
with bats.
 Human to human transmission extremely rare.
 Worldwide endemic canine rabies : 55,000 deaths annually
( India alone 20,000 )
 Louis Pasteur and Emile Roux first developed rabies
vaccine in 1885.
Epidemiology

12. Epidemiology and burden of disease
Rabies is estimated to
cause 59 000 human
deaths annually in over
150 countries, with
95% of cases occurring
in Africa and Asia.
Central Asia and
the Middle East
Africa

13. Etiology

14. The rabies virus
Taxonomy:
Family:
Genus:
Rabdoviridae
Lyssavirus
bullet-shaped,
~180 nm long and
~75 nm wide single-strand, RNA
Species: Rabies virus

15. The rabies virus

16. Transmission

17. 6
Exposure transmission
Bite transmission
Human infection by rabies virus usually occurs as a result
of a transdermal bite from an infected wild or domestic
animal
Non-bite transmission
Scratches from a rabid animal
Saliva from a rabid animal comes into contact with a
victim’s mucous membranes or fresh skin lesions
Rare cases have been reported via:
Inhalation of virus-containing aerosols. Human-to-human

18. Pathogenesis

19. 1) Virus inoculated by bite.
2) Replication in muscles: virus binds to nicotinic
acetylcholine receptors on post synaptic
membranes at NMJ.
3) Retrograde axonal transport: Spreads
centripetally along peripheral nerves towards
CNS (~ 250 mm/day) through local dorsal root
ganglion, spinal cord.
4) CNS dissemination
5) Centrifugal spread along sensory & autonomic
nerves
Steps of Pathogenesis

23. 7

24. Clinical manifestation

25. Diseases Phases

26. Incubation period
20-90 days
No symptoms
This period may be as short as four days or longer than six
years, depending on the location and severity of the wound
and the amount of virus introduced
The incubation period is variable. It is usually 2 weeks to 3 months but
with a range from 5 days to 7 years (very rare). Shorter incubation
periods are associated with severe bites and bites to the head and face.

27. • Fever
• Malaise
• Headache
• Nausea,
• Vomiting
• Anxiety
• Agitation
• Pain / paresthesiasat the site of
exposure ( in 50- 80% cases ).
Prodromal period
2-10 days

28. Furious rabies (aggressive) accounts for about 80% of the
total cases. Results in signs of hyperactivity, excitable
behavior, hydrophobia (fear of water) and sometimes
aerophobia (fear of drafts or of fresh air). Death occurs after a
few days due to cardio-respiratory arrest.
Paralytic rabies accounts for about 20% of the total number
of human cases. This form of rabies runs a less dramatic and
usually longer course than the furious form. Muscles
gradually become paralyzed, starting at the site of the bite or
scratch. A coma slowly develops, and eventually death
occurs.
Two forms of the disease:
Acute neurologic disease

29. A. Encephalitic ( 80%)
 Fever
 Confusion
 Hallucination
 Combativeness
 Seizures
 Autonomic dysfunction (Hypersalivation ,
gooseflesh, cardiac arrythmias , priapism)
 Hydrophobia
 Aerophobia
 Late complications ( cardiac failure ,
respiratory
failure , multi organ failure )
Acute neurologic disease

30. CLINICAL MANIFESTATIONS
• Excessive motor activity, Excitation, Agitation
• Confusion, Hallucinations, Delirium,
• Bizarre aberrations of thought, Seizures,
• Muscle spasms, Meningismus,
• Opisthotonic pose
• Mental aberration (Lucid period  coma )
• Hypersalivation, Aphasia, Pharyngeal spasms
• Incordination, Hyperactivity,

31. Hydrophobia : ("fear of water").
 Later stages of infection. The patient has difficulty
swallowing. Painful contractions of diaphragm, laryngeal
muscles in response to swallowing fluids.
 Drinking, may cause painful spasms of the muscles in
the throat and larynx.
 The patient shows panic when presented with liquids to
drink, and cannot satisfy their thirst.
 Saliva production is greatly increased.
Aerophobia:
 Same features caused by stimulation from a draft of
air.

32. Acute neurologic disease
B. Paralytic Rabies (20%)
 Muscle weakness predominates.
 Early & prominent flaccid muscle weakness
often in bitten extremity & spreading to
produce quadriparesis & facial weakness.
 Sphincter involvement common.
 Sensory involvement mild
 Lacks cardinal features ( hyperexcitability ,
hydrophobia , aerophobia )

33.  Presents as atypical encephalitis with relative
preservation of consciousness.
Episodes of hyper excitability followed
by complete lucidity (clarity) (as
disease progress interval between them
shortens)
 Progress rapidly to coma followed within a day by
death. (as a rule unless course prolonged by supportive
measures).

37. Diagnosis of rabies

38. • Epideliological anamnesis
• Clinical symptoms
• viral antigen detection,
• viral antibody detection,
• viral RNA detection, or virus isolation.
• Pathology
Diagnosis of rabies
Diagnosis based on:

39. It is important to establish whether the patient has had a
documented or likely exposure from a known vector.
Known vectors include dogs, bats, raccoons, skunks, foxes,
jackals, and mongooses.
Most patients in the US contract rabies from bats.
Dogs are the main vectors in most rabies-endemic
developing countries.
The red fox is the main vector in Western Europe.
History (Anamnesis)

40. Children are at highest risk of infection because
of their height, developmental skills, and proximity to dogs
in the street.
Those at higher risk of occupational exposure to rabies
include veterinary workers, animal rescuers, wildlife
personnel, workers in rabies laboratories, hikers, and field
military or non-governmental organisation personnel in
rabies-endemic countries.
History (Anamnesis)

41. History and exam: Key diagnostic factors
COMMON
UNCOMMON
• Presence of risk factors
• Hydrophobia
• Aerophobia
• Limb numbness, pain and paresthesia
• Pruritus
• Dysphagia
• Fever
• Change in behavior
• Agitation and confusion
• Hallucination
• Signs of autonomic instability
• Rapid progression of symptoms
• Weakness and paralysis
Abdominal pain
Insomnia
Seizures
Slurred or stutters speech
Ataxia

43. • viral antigen detection,
• viral antibody detection,
• viral RNA detection, or virus isolation.
• Pathology
The virus is more likely to be detected at the beginning of the clinical
course.
Laboratory diagnosis

44. Diagnosis of rabies
Several tests are necessary to
diagnose rabies ante-mortem
(before death) in humans; no single
test is sufficient
Samples: saliva, serum, spinal fluid,
and skin biopsies of hair follicles at
the nape of the neck.

45.  Serum and spinal fluid are tested for
antibodies to rabies virus
 Skin biopsy specimens are examined for
rabies antigen
 Saliva can be tested by virus isolation or
polymerase chain reaction (RT-PCR)
Diagnosis of rabies

46. Post mortem (after death), the standard
diagnostic technique is to detect
rabies virus antigen in brain tissue by
fluorescent antibody test.
Diagnosis of rabies

47. CSF examination:
A lymphocytic pleocytosis is detectable in 60% of patients
in the first week and 85% of patients in the second week.
CSF protein levels may be mildly elevated (>0.5 g/dL
[>50 mg/dL]), with a low to normal glucose
concentration.
Diagnosis of rabies

48. The microscopic pathology of rabies is typically
encephalitis with Negri bodies.
Negri bodies are round or oval, usually eosinophilic,
cytoplasmic inclusions, 1 to 7 μm across, and they contain
viral nucleocapsids.
Pathology
Negri bodies : pathognomonic inclusion bodies
found in the cytolpasm of certain nerve cels
containing the virus of rabies,

49. Negri bodies.

51. PREVENTION

52. PREVENTION
Preexposure Prophylaxis
Postexposure Prophylaxis

53. HUMAN RABIES BIOLOGICS
PRODUCT
Rabies Vaccine
(Killed/Inactivated)
 Rabies immune globulin:

54. HUMAN RABIES BIOLOGICS PRODUCT
Vaccine:
Human diploid cell vaccine (HDCV)
Purified chick embryo cell vaccine (PCEC)
Purified Vero cell vaccine (PVRV)
Purified duck embryo vaccine (PDEV)

55. HUMAN RABIES BIOLOGICS PRODUCT
Rabies immune globulin:

56. The first rabies vaccine was introduced in
1885, by two French scientists, Louis
Paster and Emile Roux, and was
followed by an improved version in
1908.
Millions of people globally have been
vaccinated and it is estimated that this
saves more than 250,000 people a year

57. • There are a number of vaccines, that are both safe and
effective.
• They can be used to prevent rabies before and for a
period of time after exposure
• The immunity that develops is long lasting after a full
course.
• Doses are usually given by injection into the skin or
muscle.
• After exposure vaccination is typically used along
with rabies immunoglobulin.
• Vaccines are effective in humans and other animals.
• Rabies vaccines may be safely used in all age groups.
Rabies vaccine

58.  Pre-exposure prophylaxis
 Post-exposure prophylaxis
local wound care
Rabies immuneglobulin
vaccine administration
Approaches
Anti Rabies Immunisation

59. Preexposure Prophylaxis
• Pre-exposure rabies immunization is used for people at
increased risk of contracting rabies:
• For people with occupational/recreational risk
of rabies including, veterinarians and their staff,
animal handlers, workers in rabies laboratories,
wildlife personnel or nongovernmental organization
personnel in rabies-endemic countries.
• Additional candidates for pre-exposure vaccination are
international travelers (e.g., if they are likely to come into
contact with animals in areas where rabies is enzootic and
access to medical care may be limited) and children living
in or visiting rabies-affected areas.

60. Preexposure Prophylaxis
The Centers for Disease Control and Prevention (CDC)
recommends a 3-dose intramuscular regimen
days 0, 7, and 21 or 28.
The World Health Organization (WHO) recommends two
regimens:
• Intradermal dose (2-site) given on days 0 and 7; or
• Intramuscular dose (1-site) given on days 0 and 7.
• Immunocompromised patients should be assessed on a
case-by-case basis and receive an additional third dose
between days 21 to 28.

61.  After one month if virus neutralising titre <0.5
IU/ml, additional booster dose given.
 Further at intervals of two years as long as exposed
person at risk.
Preexposure Prophylaxis

62.  Indicated when person has been bitten , scratched , or
licked by an animal
 Aims at neutralizing the inoculated virus before it enters
the nervous system
Post exposure prophylaxis

63. POSTEXPOSURE PROPHYLAXIS
1 – Wound cleaning & treatment
(Tetanus & Antibiotics)
2 – Passive immunization
3 – Active immunization

64.  Post-exposure prophylaxis
local wound care
Rabies immuneglobulin
vaccine administration
• Pre-exposure prophylaxis
• Post-expore treatment of persons who
Approaches
Anti Rabies Immunisation

65.  Pre-exposure prophylaxis
 Post-exposure prophylaxis
local wound care
Rabies immuneglobulin
vaccine administration
Approaches
Anti Rabies Immunisation

66. POSTEXPOSURE PROPHYLAXIS
1 – Wound cleaning & treatment

69. POSTEXPOSURE PROPHYLAXIS
2 – Passive immunization
HIG 20IU/Kg IM on day 0

70.  Cell culture and purified duck embryo vaccine
with a potency of at least 2.5 IU should be
applied .
A. Intramuscular schedule
B. Intradermal schedule

71.  Vaccine used: HDCS vaccine(tissue culture
vaccine)
 Site: deltoid
 Dose: 1 ml
Day
0 3 7 14 28
Rabies Ig
Standard WHO vaccination regimen

72.  Vaccine used: HDCV, PCECV and PVRV
 Site: ID on anterior abdominal wall
 Dose : 0.2 ml of HDCV and PCEC and 0.1 ml
of PVRV
 REGIMEN: 2 doses simultaneously on two
sites on days 0,3,7. no dose on day 14 and
one dose each on day 28 and 90.
Day7 Day28 Day 90
Day0 Day3
Rabies Ig

73.  If antibody titre is unknown , or if wound is
severe, three 1ml doses of HDC vaccine are
given
Day0 Day3 Day7
 If antibody titre is known and is more than
0.5IU/ml and bite is not severe only 2 doses are
needed
Day0 Day 3

74. A 52-year-old man, recently arrived from India,
presents after 3 days of restlessness (anxiety) and
intermittent abdominal pain. Examination shows
only diaphoresis and mild distress. He is admitted
for possible bowel obstruction.
Over 12 hours, he develops cardiac arrhythmia,
fever, and increased diaphoresis (abnormal
sweating).
He is unable to ingest (swallow) liquids.. The
following day he exhibits strange behaviour and
leg numbness (insensitivity).
Case history #2

75. Later he develops hallucinations, aggressive behaviour,
hypersalivation, and cardiac arrest.
The patient was admitted to the ICU. He has
tachycardia, muscular rigidity, and body tremor. An
MRI of the brain is unremarkable.
A detailed history reveals that the patient had bites
from a puppy in India to the right hand and leg 3
months ago and has never received a rabies
immunisation. At this point, rabies is suspected. The
patient becomes comatose and dies 2 days later.
Case history #2

76.  Rabies vaccine is defined as fluid or dried preparation of
rabies “fixed” virus grown in neural tissues of
rabbits,sheep,goats,rats or in embryonated duck eggs or in
cell cultures
 inactivated by a suitable method
Rabies Vaccine