Rabis communti

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.

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

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.

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
• More than 95% of human deaths occur in Asia
and Africa. Once symptoms of the disease
develop, rabies is nearly always fatal..

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

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.

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.

Traveling in Sudan due to rabies

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

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 control in sugarcane plantations.

Rabid wolves are associated with severe bites and human deaths
Wolves may not serve as true rabies reservoirs

Causative agent
Lyssavirus type1 (is bullet shaped
neurotropic RNA containing virus
> it belong to the family
rhabdovirdae serotype 1

• 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.

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

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

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

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 .

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 rabies
Reservoirs consist of the
Carnivora
(canids, skunks, raccoons, m
ongoose, etc.) and
Chiroptera (bats)

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
naturally occurring cases of rabies it is
pathogenic for all mammals and show
along variable incubation period

• 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)

Fixed virus :- it does not form nigri bodies ,no longer
multiplies in extra neural tissue
- Used to preparation of antirabies vaccine

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.

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

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.

*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.

3.aerosols
- respiratory transmission observed certain
cave of rabial bats and also on lab workers by
infected brain

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
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.

7.Is the virus transmitted through the meat of
infected cattle?

• 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.

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.

• 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).

Histopathology:IN CNS:* It resemble other virus disease of the CNS:
•
•
•
•
•

Hyperemia
Chromatolysis
Pyknosis.
Neurophagia of the neuron.
Microglia infiltration.

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.

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 wounds) are associated
with the shortest incubation times

• 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

• 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

• furious rabies on the one hand (more
involvement of the brain) and
• paralytic rabies (extensive involvement of the
spinal cord) on the other.

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

• 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)

• 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)

• 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

• 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)

• 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

• 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.

• 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.

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

• 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.

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 vomiting.
Few days develop :
• lethargy
• irritability
• Agitation
• personal changes seizures

DIFFERENTIATION FROM IT BY RAPID
DOWN HILL COURSE
*BECAUSE THE MEDIAN PERIOD OF
SURVIVAL AFTER INITIATION OF
SYMPTOM ABOUT 4DAYS

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 detected in CSF

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 .

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.

d/t
*Detection of tetanus toxin in
plasma or clostridia culture
from wound swab.

*CSF is normal

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

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:
(firstly discovered in person to person corneal
transplantation which isolate the negri body
from frozen eye )

CSF shows elevated protein with a
normal cell count
(albuminocytological dissociation).
Nerve conduction studies show
slowing of nerve conduction
velocities.

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.

8/Pseudo hydrophobia
• It is hysterical reaction to animal bite due to
fear of rabies infection.

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

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 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 :

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.

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.

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 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.

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%.

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 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.

• 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.

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

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.

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.

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

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.

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.

-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.

• 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.

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 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.

-

-(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.

*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.

*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.

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.

• 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.

• 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 wild animals

• Flowing pasteur,s initial development of rabies
vaccines avariety of rabies vaccine have been
developed of vaccine currently or recently in
use are :-

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, 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.

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.
• .

• 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

Complication of those two
vaccine:• * Neuro-paralytic accident
encephalomyelitis ,1-4 weeks after
administration of vaccine due to immune
response (Basic protein joint myelin).
•

• 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

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.

• (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.

• 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.

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 .

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 and post exposure immunization

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”

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

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.

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 stray
animals
• Avoid touching animal carcasses
• Secure garbage
• Chimneys, other entrances should be
covered
• International travelers: avoid contact
with stray dogs, consider rabies vaccine

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)

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

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
recommended for:
• laboratory workers dealing with live rabies virus
• veterinarians and animal handlers in rabiesaffected areas.

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