RABIES
Definition

-Rabies.

-It is an acute fatal zoonotic disease of
warm-blooded animals particularly
carnivorous such as dogs...
Rabies History
•
•
•
•
•

Usually kills around 70,000 people a year
First appeared in Africa or Asia
Started to spread all...
Louis Pasteur was a French
chemist and microbiologist
born in Dole. he created the
first vaccine for rabies in
1885. His e...
First rabies vaccine was made by
LOUIS PASTEUR .
First patient treated from rabies in
2005
Problem
• Worldwide, more than 55 000 people die of
rabies every year.
• In Africa about 4/100 000 population at risk
• Mo...
GEOGRAPHIC DISTRIBUTION
• rabies of world-wide importance ( IT AN
PANDAMIC DISEASE) mainly distributed in
Australia, china...
Incidince:
world
• Canine rabies continue to exist in 87
countries around world and this accounts
for 99 percent of all hu...
Epidemiology of Rabies Sudan
1992 -2002
• 253 human rabies deaths
• The majority of post-exposures were in
Khartoum State
...
Traveling in Sudan due to rabies
Rabies animal
Foxes maintain rabies from Arctic areas to temperate and tropical latitudes
Gray fox: A surge of rabies cases among gray foxes in Texas in 2002
Arctic fox
The Jackal is an important candid reservoir of rabies in the old world
Mongoose and related species are important in parts of Africa, Asia
& the Caribbean. Transported from Asia for snake contr...
Rabid wolves are associated with severe bites and human deaths
Wolves may not serve as true rabies reservoirs
RABIS
Causative agent
Lyssavirus type1 (is bullet shaped
neurotropic RNA containing virus
> it belong to the family
rhabdovirdae...
• morphology of the virus:_
1/ envelop double membrane (A
lipoprotein antigen  seems to be
the only antigen capable of in...
2/ spikes  glycoprotein
3/ protein deep to the envelop known
as matrix-protein
4/ nucleocapsid  enclose the core
which p...
Resistance of the virus
. sensitive to lipid solvent( alcohol , ether
,acetone and other substance)
. Sensitive to 3 gas...
Antigen of the virus
1/ envelop
_ spikes:It produce haemagglutination antibodies
• The protective antibodies are neutraliz...
HOST FACTORS
• All warm blooded animals including
men are susceptible to rabies but they
vary in their susceptibility.
- C...
Any mammal can get rabies
• Raccoons, skunks, foxes and bats
• Dogs, cats, cattle and ferrets
• Humans
RABIES HOSTS
All(bats)
warm-blooded
vertebrates are susceptible
to experimental infection
Mammals are the natural
hosts of...
Raccoons
Bats
Foxes
Skunks
Ground Hogs
Cats-especially stray and
unvaccinated
Dogs-especially stray and
unvaccinated
Ferrets
• Many people have ferrets as pets
• They should be vaccinated for rabies
Mammals that are LESS likely to give
you rabies
Animals that CANNOT give you rabies
• Recently rabies vaccine done
by, genetically engineered through
cloning in E-coli
• (Street virus  virus recovered from...
• Passage of the street virus in
rabbits modifies the virus such
that its incubation period is
progressively reduced
• Vir...
Fixed virus :- it does not form nigri bodies ,no longer
multiplies in extra neural tissue
- Used to preparation of antirab...
Source of infection
1/ to man saliva of rabid animals
2/ in dog and cats  the virus may
be present in the saliva for 3-4...
RESERVOIR OF INFECTION
– Reservoir Species
• the virus is passed amongst these animals, keeping it
alive in the population...
Mode of transmission
1. Animal bite
- The saliva must contains the virus
at the time of bite, The virus
enters the body through
transdermal ino...
*The rate of mortality increase in
extensive wond
Decrease the rate of mortality from
the bite on hand
*The rate of mortality are highest
from bite on the face & neck.
2.Licks

- licks on abraded skin or mucous membrane
abraded or not.
Through mucous membrane
Through skin
3.aerosols
- respiratory transmission observed certain
cave of rabial bats and also on lab workers by
infected brain
Lab worker
4.Person to person
- although rare but possible a case of children
biting
5.Corneal and organ transplantation.
6. by milk of infected cattle :
• Recent studies demonstrated the presence of
rabies virus in cow's milk. That make
transm...
7.Is the virus transmitted through the meat of
infected cattle?
PATHOGENESIS
• The first event is animal bite
• This depositing the virus in the wound.
• Initial viral replication within striated mus...
p
t

• Then the virus penetrate the nerve ending and
spread through peripheral nerve axoplasm by rate
of 3mm/hr.
• By doing ...
p
p
p
• The incubation period is usually 1—3 month
depending on :1-Amount of virus.
2-Tissue involved.
3-Host defense mechanism....
Histopathology:IN CNS:* It resemble other virus disease of the CNS:
•
•
•
•
•

Hyperemia
Chromatolysis
Pyknosis.
Neurophag...
p

• The pathgnomonic feature of rabies is formation of
cytoplasmic inclusions called Negri body within the
neuron, which ...
Negri body
PATHOGENESIS
• The first event is animal bite
• This depositing the virus in the wound.
• Initial viral replication within striated mus...
p
t

• Then the virus penetrate the nerve ending and
spread through peripheral nerve axoplasm by rate
of 3mm/hr.
• By doing ...
p
p
p
• The incubation period is usually 1—3 month
depending on :1-Amount of virus.
2-Tissue involved.
3-Host defense mechanism....
Histopathology:IN CNS:* It resemble other virus disease of the CNS:
•
•
•
•
•

Hyperemia
Chromatolysis
Pyknosis.
Neurophag...
p

• The pathgnomonic feature of rabies is formation of
cytoplasmic inclusions called Negri body within the
neuron, which ...
Negri body
Clinical features
non specific phase , general
Encephalitic phase, furious rabies
Brain stem phase, paralytic rabies
CLINICAL FEATURES, GENERAL
• Incubation lasts 20 to 90 days.
• Bites close to the face and with a large
inoculum (severe w...
• A prodromal phase lasting 2 to 10 days then
follows.
• The first symptom is an influenza-like
syndrome with moderate fev...
• Sometimes there is moderate muscle
weakness.
• Local myoedema after mucle percussion can
occur.
• Agitation and insomnia...
• furious rabies on the one hand (more
involvement of the brain) and
• paralytic rabies (extensive involvement of the
spin...
CLINICAL FEATURES, FURIOUS RABIES
• This form is more common. There is
increasing
anxiety, excitation, hyperactivity, hype...
• Hyperstimulation occurs as a result of
destruction of inhibitory centres in the brain
stem.
• In approximately half the ...
• These are triggered for instance by seeing or
wanting to drink a glass of water.
• This is associated with painful convu...
• The spasms can also be induced by blowing
air over the face (aerophobia)
• The spasms develop into generalised
convulsio...
• Neck stiffness can occur.
• The patient may sweat and weep
profusely, as well as displaying
hypersalivation, hypothermia...
• Fever can occur. There is a pronounced thirst.
The patient is in agony.
• Hypothalamic involvement can result in
diabete...
• Coma follows within 10 days after the onset
of the acute neurological symptoms and can
persist for hours to months (most...
• Death occurs in 100% of cases, in general 2-7
days after the onset of the disease.
• In the whole of the medical literat...
CLINICAL FEATURES, PARALYTIC
RABIES
• This is the most frequent form after a
vampire bite (South America).
• There is a fl...
• The paralysis often begins in the bitten part
of the body and then ascends further.
• Death follows from general paralys...
Differential Diagnosis

by: Basheir Ahmed
Categorized into;
1)infection.
2)autoimmune.
3)psychosis.
4)other.
Differential Diagnosis
• 1/viral encephalitis:
• *clinical features:
• Fever
,headache, lymphadenopat
hy,nausea and vomiti...
DIFFERENTIATION FROM IT BY RAPID
DOWN HILL COURSE
*BECAUSE THE MEDIAN PERIOD OF
SURVIVAL AFTER INITIATION OF
SYMPTOM ABOUT...
Differentiating test
Brain MRI shows white matter lesions
Herpes virus
Does not show the
relapsing/remitting pattern of
mental lucidity seen in rabies.
d/f:
CSF is bloody.
HSV is d...
Hsv inclusion body
6/Mokola virus
• It is virus firstly isolated in Nigeria which was
related morphologically and serologically to
rabies vir...
4/tetanus
Aerophobia, hydrophobia, and mental state
changes are absent.
The main sign is trismus (which results in a
grima...
d/t
*Detection of tetanus toxin in
plasma or clostridia culture
from wound swab.

*CSF is normal
AUTOIMMUNE
2/ limbic encephalitis
Aerophobia and hydrophobia are
absent, but other clinical features are
very similar to rabies.
Seiz...
Differentiating test
Serum antibodies to N-methyl-Daspartate (NMDA) glutamate
receptor may be positive.
3/Gillian Barrie syndrome
• In dumb rabies there is symmetrical
ascending paralysis seen after bite of
rabies bats.

Note:...
Differentiating test
CSF shows elevated protein with a
normal cell count
(albuminocytological dissociation).
Nerve conduct...
PSYCHOSIS
7/Acute psychosis
Main symptoms are
hallucinations, delusions, and thought
disorder, possibly accompanied by
agitation. Th...
8/Pseudo hydrophobia
• It is hysterical reaction to animal bite due to
fear of rabies infection.
OTHER
5/Delirium tremens
*History of chronic alcohol use and
either reduction or cessation of
drinking before presentation.
Prod...
Clinical features in dogs

Presented by: Mohammed fathi
RABIES IN ANIMAL
HYDROPHOPIA ONLY FOR HUMAN
IN ANIMAL THERE ARE 2 TYBES:
1/furious rabies
2/dumb rabies
Incubation Pe...
In furious rabies:
• Dog start to run about without purpose biting
any things without reasons, his lower jaw
hang down sal...
In dumb rabies(paralytic)
• The dog become huddled and not eat any
thing and has foaming at the mouth but not
bite unless ...
Rabies vaccine
• First dose at 90 days
• And then repeated yearly
Lab Investigation
By. Al khateeb Mohammed Alnoor
Negri body
its pathopnemonic feature of rabies
Found intracytoplasm witch vary in size from
0.25to27micometer.
They most f...
Take fixed smear from brain tissue staining with
mannes ,giemsa ,sellers stain then add
methyl alcohol .
If positive: Negr...
Neuron without Negri bodies

Negri body in infected neuron
Direct fluorescent antibody test
The dFA test is based on the observation that
animals infected by rabies virus have rabie...
• The most important part of a dFA test is
fluorescently-labeled anti-rabies antibody.
When labeled antibody is incubated ...
Negative dFA.

Positive dFA
Antigen detection by dFA
The rabies antibody used for the dFA test is
primarily directed against the nucleoprotein
(antige...
Immunohistochemistry (IHC)
IHC methods for rabies detection provide sensitive
and specific means to detect rabies in forma...
This slide shows a rabiesinfected neuronal cell
with intracytoplasmic
inclusions. The red
stain indicates areas of
rabies ...
Viral isolation
Specimens: saliva, CSF, urine and brain tissue.
By inoculate there in tissue culture (WI38, MRCs, BUK-21)....
PCR
• This set was found to be efficient for all
tested fixed rabies virus strains or
wild rabies virus isolates as well a...
In Dogs
Which it died from the disease.
If the dog is available, keep it in custody for 10 days, send
the whole animal to ...
TRATMENT
-There

is no specific treatment for rabies
infection.
•A small number of people have survived
from rabies, the disease is...
• If the treatment begun prior to the
appearance of symptoms, the
prognosis is excellent.
• When treatment is started afte...
Treatment is classified into two
groups:
-(I) pre-exposure prophylaxis.

-(II) post exposure prophylaxis.
-(I) pre-exposure prophylaxis:-It’s treatment for people in high-risk groups .These groups
include:
-Veterinarians, animal...
-(ii) post exposure prophylaxis.
*Administration of prophylaxis after exposure to
rabies can prevent the onset of symptoms...
*Local treatment:-Removing the rabies virus at the site of the wound
by chemical or physical agent (an effective means of
...
*General Treatment:-An one dose of rabies immunoglobulin and five
doses of the rabies vaccine over a 28-day period.
--Doct...
Rabies immune globulin
•It’s contains antibodies from blood donors who
were given rabies vaccine.
• The antibodies provide...
Vaccination of rabies
• Rabies vaccine is defined as fluid or dried
preparation of rabies (fixed) virus grown in the
neural tissues of rabbits ;...
• antirabies tretment should started
immediately:-
• 1-if animal shows signs of rabies or dies within
10 day observation
• 2-if biting animal can not be traced or
identified
• 3-unprovoed bites
• 4 -labrotory test eg:flouescent rabies antibody
test or negribodies +ve for rabies
• 5-all bites by ...
• Flowing pasteur,s initial development of rabies
vaccines avariety of rabies vaccine have been
developed of vaccine curre...
Type of vaccine:• A-nervous tissue vaccine.
• B-non neural vaccine.
A-Nervous tissue vaccine
• 1-semple vaccine : “ use brain of sheep” use
fixed virus intracerbral 3 days collect in brain, ...
If the dog died or lost 
complete the
vaccine.
Sever bites on the face and neck 
Give 10
ml of the vaccine for 14 days a...
• 2-Modified simple vaccine:• Use B-propriolactone (B.P.L) to kill the fixed virus .
• This vaccine more potent than sempl...
Complication of those two
vaccine:• * Neuro-paralytic accident
encephalomyelitis ,1-4 weeks after
administration of vacci...
• 3-Infant brain vaccine:• Use new born animals either mice
,rabbits, rats , because brain of new born
animals does’t cont...
B- Non Neural vaccine
1-chick embryo vaccine:*It’s devided into:(A)Killed duck embryo vaccine
*Fixed virus inject in yolk ...
• (B)Life attenuated vaccine
• Produce in chick embryo using fluri-virus
• (anthor fixed virus).it’s of two types:
•
1- lo...
• A-Low egg passage :
• 50 x this is called (LEP). It’s has been used as live
attenuated vaccine for dogs .
• B-high egg p...
2-Tissue culture vaccine
There are more potent and much safer than
brain tissue vaccine
Immunization requred fewer injecti...
Two type:
• 1.human diploid cell vaccine(HDCV)

• 2.”second generation” tissue culture vaccines
1-human diploid cell vaccine
It is prepared by fixed virus in human diploid
cells
It is safe and highly potent
Use in pre ...
2-second generation tissue culture
vaccines
It is potency and low cost vaccine are being
preferred
It derived from non hum...
Usage:
for adult ;children
-- Dose 0.5ml—1.0ml (IM OR S/C)
For pre exposture: police at high risk givan at
day “0,7,21” bo...
CONT..
If bitten again befor 5 years ,2booster 0,3days
2-post exposure:
6doses on 1.3.7.14.30.90 .
0.5-1.0ml intramuscular...
3-sub unit vaccine
Gp on spike
Produced by genetic enginering by cloning
The gp gene in yeasts
Rabies prevention
• Educating children to avoid contact with
stray or wild animals
• Avoid trying to capture or provoke st...
Problem of rabies in sudan
•There is Lack of comprehensive management
on dog breeding
•The city implemented
registration, ...
Prevention generally
1/animal vaccination
• Immunization of 70% of the dog population to stop
circulation of the virus at ...
the first dose at 90 days and then
repeated yearly
2/ people immunization
• Safe, effective vaccines also exist for human
use.
• Pre-exposure immunization in people is
recom...
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Rabis communti

  1. 1. RABIES
  2. 2. Definition -Rabies. -It is an acute fatal zoonotic disease of warm-blooded animals particularly carnivorous such as dogs, cats, jackals and wolves caused by lyssa virus type 1 it transmitted to man usually by bites or licks of rabid animals . -It is the only communicable disease of man that is always fatal.
  3. 3. Rabies History • • • • • Usually kills around 70,000 people a year First appeared in Africa or Asia Started to spread all around the world Vaccine made by Louis Pasteur in 1885 Mistakenly called “hydrophobia” because the victims have a fear of water
  4. 4. Louis Pasteur was a French chemist and microbiologist born in Dole. he created the first vaccine for rabies in 1885. His experiments supported the germ theory of disease.
  5. 5. First rabies vaccine was made by LOUIS PASTEUR .
  6. 6. First patient treated from rabies in 2005
  7. 7. Problem • Worldwide, more than 55 000 people die of rabies every year. • In Africa about 4/100 000 population at risk • More than 95% of human deaths occur in Asia and Africa. Once symptoms of the disease develop, rabies is nearly always fatal..
  8. 8. GEOGRAPHIC DISTRIBUTION • rabies of world-wide importance ( IT AN PANDAMIC DISEASE) mainly distributed in Australia, china (TAIWAN), Cyprus, Iceland, Ireland Japan, Malta, new Zealand, the U.K. and the Islands at western pacific are all free of the disease
  9. 9. Incidince: world • Canine rabies continue to exist in 87 countries around world and this accounts for 99 percent of all human rabies cause. The human death in developing countries.
  10. 10. Epidemiology of Rabies Sudan 1992 -2002 • 253 human rabies deaths • The majority of post-exposures were in Khartoum State • Most of human deaths (78) were in Central States. • Dogs, goats and donkeys were the main animals involved in rabies epidemiology.
  11. 11. Traveling in Sudan due to rabies
  12. 12. Rabies animal
  13. 13. Foxes maintain rabies from Arctic areas to temperate and tropical latitudes
  14. 14. Gray fox: A surge of rabies cases among gray foxes in Texas in 2002
  15. 15. Arctic fox
  16. 16. The Jackal is an important candid reservoir of rabies in the old world
  17. 17. Mongoose and related species are important in parts of Africa, Asia & the Caribbean. Transported from Asia for snake control in sugarcane plantations.
  18. 18. Rabid wolves are associated with severe bites and human deaths Wolves may not serve as true rabies reservoirs
  19. 19. RABIS
  20. 20. Causative agent Lyssavirus type1 (is bullet shaped neurotropic RNA containing virus > it belong to the family rhabdovirdae serotype 1
  21. 21. • morphology of the virus:_ 1/ envelop double membrane (A lipoprotein antigen  seems to be the only antigen capable of inducing the formation of virus-neutralizing antibodies.
  22. 22. 2/ spikes  glycoprotein 3/ protein deep to the envelop known as matrix-protein 4/ nucleocapsid  enclose the core which posses RNA(helical in arrangement) 5/ size  180nm X 75 nm
  23. 23. Resistance of the virus . sensitive to lipid solvent( alcohol , ether ,acetone and other substance) . Sensitive to 3 gases:1/ formaldehyde 2/glutraaldhyde 3/ B- PROPIO- LACTONE  sun light  ultraviolet light ionizing radiation  Temperature
  24. 24. Antigen of the virus 1/ envelop _ spikes:It produce haemagglutination antibodies • The protective antibodies are neutralization antibodies 2/ core antigens - Nucleoprotein - Produce complement antibodies which are not protective - Group specific for diagnosis
  25. 25. HOST FACTORS • All warm blooded animals including men are susceptible to rabies but they vary in their susceptibility. - Cattle + cats  very susceptible - Birds  least susceptible - Human +dogs more susceptible - Rabies in man is a dead end infection and has no survival value for the virus .
  26. 26. Any mammal can get rabies • Raccoons, skunks, foxes and bats • Dogs, cats, cattle and ferrets • Humans
  27. 27. RABIES HOSTS All(bats) warm-blooded vertebrates are susceptible to experimental infection Mammals are the natural hosts of rabies Reservoirs consist of the Carnivora (canids, skunks, raccoons, m ongoose, etc.) and Chiroptera (bats)
  28. 28. Raccoons
  29. 29. Bats
  30. 30. Foxes
  31. 31. Skunks
  32. 32. Ground Hogs
  33. 33. Cats-especially stray and unvaccinated
  34. 34. Dogs-especially stray and unvaccinated
  35. 35. Ferrets • Many people have ferrets as pets • They should be vaccinated for rabies
  36. 36. Mammals that are LESS likely to give you rabies
  37. 37. Animals that CANNOT give you rabies
  38. 38. • Recently rabies vaccine done by, genetically engineered through cloning in E-coli • (Street virus  virus recovered from naturally occurring cases of rabies it is pathogenic for all mammals and show along variable incubation period
  39. 39. • Passage of the street virus in rabbits modifies the virus such that its incubation period is progressively reduced • Virus isolated from this period called ( fixed virus)
  40. 40. Fixed virus :- it does not form nigri bodies ,no longer multiplies in extra neural tissue - Used to preparation of antirabies vaccine
  41. 41. Source of infection 1/ to man saliva of rabid animals 2/ in dog and cats  the virus may be present in the saliva for 3-4 days (occasionally 5-6 days before the onset of clinical symptoms and during the course of illness till death.
  42. 42. RESERVOIR OF INFECTION – Reservoir Species • the virus is passed amongst these animals, keeping it alive in the population for long periods of time • These are called “high risk” animals and are “reservoir species” – Dog (wild or domestic – fox, coyote, wolf, etc.) – Raccoon, Skunk, Mongoose – Cow (South America only) – Bat (vampire, insectivorous, not vegetarian) • Cats, bobcats and cougars can also be vectors – Vector – animal that actively or passively transmits a disease
  43. 43. Mode of transmission
  44. 44. 1. Animal bite - The saliva must contains the virus at the time of bite, The virus enters the body through transdermal inoculation (wound) The virus cannot penetrate intact skin.
  45. 45. *The rate of mortality increase in extensive wond
  46. 46. Decrease the rate of mortality from the bite on hand
  47. 47. *The rate of mortality are highest from bite on the face & neck.
  48. 48. 2.Licks - licks on abraded skin or mucous membrane abraded or not.
  49. 49. Through mucous membrane
  50. 50. Through skin
  51. 51. 3.aerosols - respiratory transmission observed certain cave of rabial bats and also on lab workers by infected brain
  52. 52. Lab worker
  53. 53. 4.Person to person - although rare but possible a case of children biting
  54. 54. 5.Corneal and organ transplantation.
  55. 55. 6. by milk of infected cattle : • Recent studies demonstrated the presence of rabies virus in cow's milk. That make transmission of rabies virus from consuming unpasteurized milk from an infected animal is possible. • Milk that has been pasteurized/boiled presents no risk for rabies virus transmission.
  56. 56. 7.Is the virus transmitted through the meat of infected cattle?
  57. 57. PATHOGENESIS
  58. 58. • The first event is animal bite • This depositing the virus in the wound. • Initial viral replication within striated muscle at The sites of inoculation,& the continuo for 2--3 days. • Then the virus adhere to the nicotinic Ach receptor of NMJ.
  59. 59. p
  60. 60. t • Then the virus penetrate the nerve ending and spread through peripheral nerve axoplasm by rate of 3mm/hr. • By doing so it ascend to spinal cord and brain where it replicate excessively within the gray matter . • The virus from the brain it descend center fugally to all parts of all the body. • It reach the salivary gland and replicate within it leading to further transmission via infected saliva.
  61. 61. p
  62. 62. p
  63. 63. p
  64. 64. • The incubation period is usually 1—3 month depending on :1-Amount of virus. 2-Tissue involved. 3-Host defense mechanism. 4-Distance from brain:(7 days when the bite within the neck &face).
  65. 65. Histopathology:IN CNS:* It resemble other virus disease of the CNS: • • • • • Hyperemia Chromatolysis Pyknosis. Neurophagia of the neuron. Microglia infiltration.
  66. 66. p • The pathgnomonic feature of rabies is formation of cytoplasmic inclusions called Negri body within the neuron, which is eosinophilic mass contain matrix and rabies virus. This inclusion body distributed throughout the brain particularly:• Cerebral cortex. • Brain stem. • Hypothalamus. • Cerebellum.
  67. 67. Negri body
  68. 68. PATHOGENESIS
  69. 69. • The first event is animal bite • This depositing the virus in the wound. • Initial viral replication within striated muscle at The sites of inoculation,& the continuo for 2--3 days. • Then the virus adhere to the nicotinic Ach receptor of NMJ.
  70. 70. p
  71. 71. t • Then the virus penetrate the nerve ending and spread through peripheral nerve axoplasm by rate of 3mm/hr. • By doing so it ascend to spinal cord and brain where it replicate excessively within the gray matter . • The virus from the brain it descend center fugally to all parts of all the body. • It reach the salivary gland and replicate within it leading to further transmission via infected saliva.
  72. 72. p
  73. 73. p
  74. 74. p
  75. 75. • The incubation period is usually 1—3 month depending on :1-Amount of virus. 2-Tissue involved. 3-Host defense mechanism. 4-Distance from brain:(7 days when the bite within the neck &face).
  76. 76. Histopathology:IN CNS:* It resemble other virus disease of the CNS: • • • • • Hyperemia Chromatolysis Pyknosis. Neurophagia of the neuron. Microglia infiltration.
  77. 77. p • The pathgnomonic feature of rabies is formation of cytoplasmic inclusions called Negri body within the neuron, which is eosinophilic mass contain matrix and rabies virus. This inclusion body distributed throughout the brain particularly:• Cerebral cortex. • Brain stem. • Hypothalamus. • Cerebellum.
  78. 78. Negri body
  79. 79. Clinical features non specific phase , general Encephalitic phase, furious rabies Brain stem phase, paralytic rabies
  80. 80. CLINICAL FEATURES, GENERAL • Incubation lasts 20 to 90 days. • Bites close to the face and with a large inoculum (severe wounds) are associated with the shortest incubation times
  81. 81. • A prodromal phase lasting 2 to 10 days then follows. • The first symptom is an influenza-like syndrome with moderate fever and malaise lasting a few days. • This can be associated with severe local pruritus leading to scratching , headache, pain or paraesthesia at the site of the bite
  82. 82. • Sometimes there is moderate muscle weakness. • Local myoedema after mucle percussion can occur. • Agitation and insomnia can occur at a very early stage. • Afterwards the disease can take two different courses, depending on which features predominate
  83. 83. • furious rabies on the one hand (more involvement of the brain) and • paralytic rabies (extensive involvement of the spinal cord) on the other.
  84. 84. CLINICAL FEATURES, FURIOUS RABIES • This form is more common. There is increasing anxiety, excitation, hyperactivity, hyperventil ation, disorientation and/or hallucinations. • Symptoms occur intermittently and persist for 1 to 5 min, followed by a period of mental calm
  85. 85. • Hyperstimulation occurs as a result of destruction of inhibitory centres in the brain stem. • In approximately half the patients, painful spasms of the larynx and throat muscles occur (swallowing and vocal chord spasms)
  86. 86. • These are triggered for instance by seeing or wanting to drink a glass of water. • This is associated with painful convulsive contractions of the respiratory muscles. • The patient is therefore afraid of this situation (hydrophobia or fear of water)
  87. 87. • The spasms can also be induced by blowing air over the face (aerophobia) • The spasms develop into generalised convulsions. • There is no trismus or muscle rigidity between convulsions
  88. 88. • Neck stiffness can occur. • The patient may sweat and weep profusely, as well as displaying hypersalivation, hypothermia, hypertension and tachycardia (involvement of the autonomic nervous system)
  89. 89. • Fever can occur. There is a pronounced thirst. The patient is in agony. • Hypothalamic involvement can result in diabetes insipidus (insufficient ADH) or hypersecretion of antidiuretic hormone (SIADH). • Myocarditis can cause cardiac arrhythmias
  90. 90. • Coma follows within 10 days after the onset of the acute neurological symptoms and can persist for hours to months (mostly shortlasting). • Finally, cardiac and respiratory arrest follow.
  91. 91. • Death occurs in 100% of cases, in general 2-7 days after the onset of the disease. • In the whole of the medical literature, only 3 people have been described who have ever survived clinical rabies.
  92. 92. CLINICAL FEATURES, PARALYTIC RABIES • This is the most frequent form after a vampire bite (South America). • There is a flaccid paralysis (no tendon reflexes). • There are often mild sensory disorders
  93. 93. • The paralysis often begins in the bitten part of the body and then ascends further. • Death follows from general paralysis. • This course is less rapid than in the furious form.
  94. 94. Differential Diagnosis by: Basheir Ahmed
  95. 95. Categorized into; 1)infection. 2)autoimmune. 3)psychosis. 4)other.
  96. 96. Differential Diagnosis • 1/viral encephalitis: • *clinical features: • Fever ,headache, lymphadenopat hy,nausea and vomiting. Few days develop : • lethargy • irritability • Agitation • personal changes seizures
  97. 97. DIFFERENTIATION FROM IT BY RAPID DOWN HILL COURSE *BECAUSE THE MEDIAN PERIOD OF SURVIVAL AFTER INITIATION OF SYMPTOM ABOUT 4DAYS
  98. 98. Differentiating test Brain MRI shows white matter lesions
  99. 99. Herpes virus Does not show the relapsing/remitting pattern of mental lucidity seen in rabies. d/f: CSF is bloody. HSV is detected in CSF
  100. 100. Hsv inclusion body
  101. 101. 6/Mokola virus • It is virus firstly isolated in Nigeria which was related morphologically and serologically to rabies virus and has the classical symptom of rabies in which we isolate granular cytoplasmic inclusion which distinguishable from negri body in neuron . • Differentiated by histological studies .
  102. 102. 4/tetanus Aerophobia, hydrophobia, and mental state changes are absent. The main sign is trismus (which results in a grimace described as 'risus sardonicus' or sardonic smile) associated with muscle rigidity, spasms, respiratory embarrassment, dysphagia, or autonomic dysfunction.
  103. 103. d/t *Detection of tetanus toxin in plasma or clostridia culture from wound swab. *CSF is normal
  104. 104. AUTOIMMUNE
  105. 105. 2/ limbic encephalitis Aerophobia and hydrophobia are absent, but other clinical features are very similar to rabies. Seizures are common with limbic encephalitis with N-methyl-D-aspartate glutamate receptor (NMDAR) antibodies
  106. 106. Differentiating test Serum antibodies to N-methyl-Daspartate (NMDA) glutamate receptor may be positive.
  107. 107. 3/Gillian Barrie syndrome • In dumb rabies there is symmetrical ascending paralysis seen after bite of rabies bats. Note: (firstly discovered in person to person corneal transplantation which isolate the negri body from frozen eye )
  108. 108. Differentiating test CSF shows elevated protein with a normal cell count (albuminocytological dissociation). Nerve conduction studies show slowing of nerve conduction velocities.
  109. 109. PSYCHOSIS
  110. 110. 7/Acute psychosis Main symptoms are hallucinations, delusions, and thought disorder, possibly accompanied by agitation. The prodrome and physical manifestations of rabies are absent. Other clinical features depend on the cause.
  111. 111. 8/Pseudo hydrophobia • It is hysterical reaction to animal bite due to fear of rabies infection.
  112. 112. OTHER
  113. 113. 5/Delirium tremens *History of chronic alcohol use and either reduction or cessation of drinking before presentation. Prodromal illness is absent. Fever is rare. *d/t: the diagnosis is clinical
  114. 114. Clinical features in dogs Presented by: Mohammed fathi
  115. 115. RABIES IN ANIMAL HYDROPHOPIA ONLY FOR HUMAN IN ANIMAL THERE ARE 2 TYBES: 1/furious rabies 2/dumb rabies Incubation Period: from 10 days up to 1year  usually dogs bite by another infected dog  in both cases there is aprodromal stage in which the dog become anxious ,alert, licks at his bite site for (2-3)days after that :
  116. 116. In furious rabies: • Dog start to run about without purpose biting any things without reasons, his lower jaw hang down saliva running out of corner's of the mouth • During this stage dog may go coma and death within 3to5 days.
  117. 117. In dumb rabies(paralytic) • The dog become huddled and not eat any thing and has foaming at the mouth but not bite unless any person came near to it (eg. for feeding). • It under go paralysis and dies within 3to5 days.
  118. 118. Rabies vaccine • First dose at 90 days • And then repeated yearly
  119. 119. Lab Investigation By. Al khateeb Mohammed Alnoor
  120. 120. Negri body its pathopnemonic feature of rabies Found intracytoplasm witch vary in size from 0.25to27micometer. They most frequently found in brain tissue like pyramidal cell of Amman's and cells of medulla. Its also found in neurons of salivary gland. But some experimentally infected cause of rabies display Negri body found in brain tissue other do not.
  121. 121. Take fixed smear from brain tissue staining with mannes ,giemsa ,sellers stain then add methyl alcohol . If positive: Negri body appear dark blue in color If negative: no change (gives same color of reaction) As final important point presences of Nigre body diagnosis rabies 100%.
  122. 122. Neuron without Negri bodies Negri body in infected neuron
  123. 123. Direct fluorescent antibody test The dFA test is based on the observation that animals infected by rabies virus have rabies virus proteins (antigen) present in their tissues. Because rabies is present in nervous tissue (and not blood like many other viruses), the ideal tissue to test for rabies antigen is brain. The best specimen is saliva, corneal smear, skin biopsy this usually from the neck and face.
  124. 124. • The most important part of a dFA test is fluorescently-labeled anti-rabies antibody. When labeled antibody is incubated with rabies-suspect brain tissue, it will bind to rabies antigen. Unbound antibody can be washed away and areas where antigen is present can be visualized as fluorescentapple-green areas using a fluorescence microscope. If rabies virus is absent there will be no staining.
  125. 125. Negative dFA. Positive dFA
  126. 126. Antigen detection by dFA The rabies antibody used for the dFA test is primarily directed against the nucleoprotein (antigen) of the virus (see The Virus section on viral structure). Rabies virus replicates in the cytoplasm of cells, and infected cells may contain large round or oval inclusions containing collections of nucleoprotein (N) or smaller collections of antigen that appear as dust-like fluorescent particles if stained by the dFA procedure
  127. 127. Immunohistochemistry (IHC) IHC methods for rabies detection provide sensitive and specific means to detect rabies in formalinfixed tissues. These methods are more sensitive than histological staining methods, such as H&E and Sellers stains. Like the DFA test, these procedures use specific antibodies to detect rabies virus inclusions. The techniques use enzyme-labeling systems that increase sensitivity. In addition, monoclonal antibodies may be used to detect rabies virus variants.
  128. 128. This slide shows a rabiesinfected neuronal cell with intracytoplasmic inclusions. The red stain indicates areas of rabies viral antigen by using IHC or avidinbiotin complex (ABC) technique.
  129. 129. Viral isolation Specimens: saliva, CSF, urine and brain tissue. By inoculate there in tissue culture (WI38, MRCs, BUK-21). Then an diploid cells in the tissue culture the rulers doesn’t produce CPE or less significant the viral growth is detected by IF. Rabies virus isolation 1. Tissue culture. 2. Mice
  130. 130. PCR • This set was found to be efficient for all tested fixed rabies virus strains or wild rabies virus isolates as well as the rabies-related Mokola virus. We describe a progressive characterization of the strain that could be extended from rapid typing by a limited panel of restriction enzymes, to the ultimate identification of the nucleotide sequence by an original direct sequencing technique of amplified segments.
  131. 131. In Dogs Which it died from the disease. If the dog is available, keep it in custody for 10 days, send the whole animal to the lab, divided the brain in to halves. If the place is too far: • putting on portion in 50c glycerin saline ( for viral isolation). • Putting in formaldehyde (histopathology). • Salivary gland: 1. IF : detection of Ag. 2. Histopathology: Negri bodies. 3. Virus isolation from glycerol portion in tissue culture and mice.
  132. 132. TRATMENT
  133. 133. -There is no specific treatment for rabies infection. •A small number of people have survived from rabies, the disease is usually fatal. • For that reason, anyone have been exposed to rabies receives a series of shots to prevent the infection from taking hold.
  134. 134. • If the treatment begun prior to the appearance of symptoms, the prognosis is excellent. • When treatment is started after rabies symptoms begin, the prognosis is poor. • Death is almost certain to occur within one to two weeks.
  135. 135. Treatment is classified into two groups: -(I) pre-exposure prophylaxis. -(II) post exposure prophylaxis.
  136. 136. -(I) pre-exposure prophylaxis:-It’s treatment for people in high-risk groups .These groups include: -Veterinarians, animal handlers, and certain laboratory workers. -Pre-exposure rabies treatment consists of three doses of the rabies vaccine given on days 0, 7, and 21 or 28. -
  137. 137. -(ii) post exposure prophylaxis. *Administration of prophylaxis after exposure to rabies can prevent the onset of symptoms and death. *It consists of:-Local treatment. -General treatment.
  138. 138. *Local treatment:-Removing the rabies virus at the site of the wound by chemical or physical agent (an effective means of protection). -first aid: done immediate washing of the wound for at least 15 minutes with soap and water, detergent , iodine or other substances that kill the rabies virus. -the second aid : cauterization of site of the bite. -finally local infiltration of rabies Ig around the wound.
  139. 139. *General Treatment:-An one dose of rabies immunoglobulin and five doses of the rabies vaccine over a 28-day period. --Doctors administer the rabies immune globulin and the first dose of the vaccine as soon as possible after exposure. - Normally, additional doses of rabies vaccine follow on days 3, 7, 14, and 28 after the first vaccination.
  140. 140. Rabies immune globulin •It’s contains antibodies from blood donors who were given rabies vaccine. • The antibodies provide interim protection until an exposed person's own antibodies develop in response to the vaccine. •Immune globulin at the site of injury reduces the amount of virus that is able to enter the nerve cells and potentially initiate an active infection.
  141. 141. Vaccination of rabies
  142. 142. • Rabies vaccine is defined as fluid or dried preparation of rabies (fixed) virus grown in the neural tissues of rabbits ;sheep ;goats; mice or rates or in embryonated duck eggs or in cell culture and in activated by treatment with phenol or B.proprioloacton all vaccines are tested in accordance with the control procedures laid down by WHO.
  143. 143. • antirabies tretment should started immediately:-
  144. 144. • 1-if animal shows signs of rabies or dies within 10 day observation • 2-if biting animal can not be traced or identified
  145. 145. • 3-unprovoed bites • 4 -labrotory test eg:flouescent rabies antibody test or negribodies +ve for rabies • 5-all bites by wild animals
  146. 146. • Flowing pasteur,s initial development of rabies vaccines avariety of rabies vaccine have been developed of vaccine currently or recently in use are :-
  147. 147. Type of vaccine:• A-nervous tissue vaccine. • B-non neural vaccine.
  148. 148. A-Nervous tissue vaccine • 1-semple vaccine : “ use brain of sheep” use fixed virus intracerbral 3 days collect in brain, 5% suspension in phenol saline (it’s killing vaccine, at 37C from 2—3 hr). • Dose:• Give 5ml s/c on the anterior abdomen 14 days . • If the dog stay alive after 10 days vaccine should be stopped.
  149. 149. If the dog died or lost  complete the vaccine. Sever bites on the face and neck  Give 10 ml of the vaccine for 14 days and give protection for six month only. • If the person bite again before six month end two booster dose one week interval. • .
  150. 150. • 2-Modified simple vaccine:• Use B-propriolactone (B.P.L) to kill the fixed virus . • This vaccine more potent than semple vaccine. • Give 3 ml for 10 days s/c in the anterior abdominal wall. • Sever bites in the face and neck give 6 ml for 10 days
  151. 151. Complication of those two vaccine:• * Neuro-paralytic accident encephalomyelitis ,1-4 weeks after administration of vaccine due to immune response (Basic protein joint myelin). •
  152. 152. • 3-Infant brain vaccine:• Use new born animals either mice ,rabbits, rats , because brain of new born animals does’t contain basic protine so there is no encephalomyelitis
  153. 153. B- Non Neural vaccine 1-chick embryo vaccine:*It’s devided into:(A)Killed duck embryo vaccine *Fixed virus inject in yolk sac ,killed by Bpropriolactone.
  154. 154. • (B)Life attenuated vaccine • Produce in chick embryo using fluri-virus • (anthor fixed virus).it’s of two types: • 1- low egg passage • 2- high egg passage.
  155. 155. • A-Low egg passage : • 50 x this is called (LEP). It’s has been used as live attenuated vaccine for dogs . • B-high egg passage:• 180 x .protection of cattle and cats.
  156. 156. 2-Tissue culture vaccine There are more potent and much safer than brain tissue vaccine Immunization requred fewer injection of smaller volume with relatively few side effect .
  157. 157. Two type: • 1.human diploid cell vaccine(HDCV) • 2.”second generation” tissue culture vaccines
  158. 158. 1-human diploid cell vaccine It is prepared by fixed virus in human diploid cells It is safe and highly potent Use in pre and post exposure immunization
  159. 159. 2-second generation tissue culture vaccines It is potency and low cost vaccine are being preferred It derived from non human source either: A-vero cell like monkey. B-Primary cell substract: “foetal bovine kidney ,chick embryo fibrobast, dog kidney cell or hamster”
  160. 160. Usage: for adult ;children -- Dose 0.5ml—1.0ml (IM OR S/C) For pre exposture: police at high risk givan at day “0,7,21” booster after 1years then every 5-years
  161. 161. CONT.. If bitten again befor 5 years ,2booster 0,3days 2-post exposure: 6doses on 1.3.7.14.30.90 . 0.5-1.0ml intramuscular Given protect for 5 year. *if bitten again within 5 years :2 booster dose 0,3 days.
  162. 162. 3-sub unit vaccine Gp on spike Produced by genetic enginering by cloning The gp gene in yeasts
  163. 163. Rabies prevention • Educating children to avoid contact with stray or wild animals • Avoid trying to capture or provoke stray animals • Avoid touching animal carcasses • Secure garbage • Chimneys, other entrances should be covered • International travelers: avoid contact with stray dogs, consider rabies vaccine
  164. 164. Problem of rabies in sudan •There is Lack of comprehensive management on dog breeding •The city implemented registration, immunization, but there are large amount of dog breeding household which are unregistered dogs •Rural areas is almost no regulation on dog breeding, in the free status •In spite of increase the cost of vaccine(the one dose about 40 pound)
  165. 165. Prevention generally 1/animal vaccination • Immunization of 70% of the dog population to stop circulation of the virus at source. • Rabies is a vaccine-preventable disease. • The most cost-effective strategy for preventing rabies in people is by eliminating rabies in dogs through vaccination. • Vaccination of animals (mostly dogs) has reduced the number of human (and animal) rabies cases in several countries
  166. 166. the first dose at 90 days and then repeated yearly
  167. 167. 2/ people immunization • Safe, effective vaccines also exist for human use. • Pre-exposure immunization in people is recommended for: • laboratory workers dealing with live rabies virus • veterinarians and animal handlers in rabiesaffected areas.

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