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RABIES

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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.

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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

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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.

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First rabies vaccine was made by LOUIS PASTEUR .

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First patient treated from rabies in 2005

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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..

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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

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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.

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Epidemiology of Rabies Sudan1992 -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.

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Traveling in Sudan due to rabies

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Rabies animal

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Foxes maintain rabies from Arctic areas to temperate and tropical latitudes

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Gray fox: A surge of rabies cases among gray foxes in Texas in 2002

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Arctic fox

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The Jackal is an important candid reservoir of rabies in the old world

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Mongoose and related species are important in parts of Africa, Asia & the Caribbean. Transported from Asia for snake control in sugar-

cane plantations.

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

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RABIS

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Causative agent

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

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•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.

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2/ spikes glycoprotein3/ protein deep to the envelop known as matrix-protein4/ nucleocapsid enclose the core which posses RNA(helical in arrangement)5/ size 180nm X 75 nm

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Resistance of the virus. sensitive to lipid solvent( alcohol ,

ether ,acetone and other substance). Sensitive to 3 gases:-1/ formaldehyde2/glutraaldhyde3/ B- PROPIO- LACTONE sun light ultraviolet lightionizing radiation Temperature

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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

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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 .

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Any mammal can get rabies

• Raccoons, skunks, foxes and bats• Dogs, cats, cattle and ferrets• Humans

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Mammals that can give you rabies

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RABIES HOSTS(bats)All warm-blooded

vertebrates are susceptible to experimental infection

Mammals are the natural hosts of rabies

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

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Raccoons

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Bats

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Foxes

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Skunks

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Ground Hogs

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Cats-especially stray and unvaccinated

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Dogs-especially stray and unvaccinated

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Ferrets

• Many people have ferrets as pets• They should be vaccinated for rabies

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Mammals that are LESS likely to give you rabies

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Animals that CANNOT give you rabies

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• 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

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• 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)

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Fixed virus :-

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

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Source of infection1/ to man saliva of rabid animals2/ 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.

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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

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Mode of transmission

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- 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.

1. Animal bite

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*The rate of mortality increase in extensive wond

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Decrease the rate of mortality from the bite on hand

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*The rate of mortality are highest from bite on the face & neck.

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- licks on abraded skin or mucous membrane abraded or not.

2.Licks

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Through mucous membrane

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Through skin

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

3.aerosols

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Lab worker

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- although rare but possible a case of children biting

4.Person to person

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5.Corneal and organ transplantation.

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• 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.

6. by milk of infected cattle :

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

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PATHOGENESIS

PRASENTED BY ALAA ABD ALHABEB

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Pathogenesis:- • The first event is animal bite • This depositing the virus in the wound.• Initial viral replication within striated muscle atThe sites of inoculation,& the continuo for 2--3 days.• Then the virus adhere to the nicotinic Ach receptor

of NMJ.

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p

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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.

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INCUPATION PERIOD

• 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).

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

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

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• 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.

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Negri body

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PATHOGENESIS

PRASENTED BY ALAA ABD ALHABEB

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Pathogenesis:- • The first event is animal bite • This depositing the virus in the wound.• Initial viral replication within striated muscle atThe sites of inoculation,& the continuo for 2--3 days.• Then the virus adhere to the nicotinic Ach receptor

of NMJ.

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p

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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.

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INCUPATION PERIOD

• 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).

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

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

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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.

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Negri body

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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

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• 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

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• 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

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• furious rabies on the one hand (more involvement of the brain) and

• paralytic rabies (extensive involvement of the spinal cord) on the other.

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CLINICAL FEATURES, FURIOUS RABIES

• This form is more common. There is increasing anxiety, excitation, hyperactivity, hyperventilation, disorientation and/or hallucinations.

• Symptoms occur intermittently and persist for 1 to 5 min, followed by a period of mental calm

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• 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)

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• 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)

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• 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

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• 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)

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• 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

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• Coma follows within 10 days after the onset of the acute neurological symptoms and can persist for hours to months (mostly short-lasting).

• Finally, cardiac and respiratory arrest follow.

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• 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.

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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

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• 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.

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Differential Diagnosis

by: Basheir Ahmed

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Categorized into;1)infection.

2)autoimmune.3)psychosis.

4)other.

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Differential Diagnosis• 1/viral encephalitis:• *clinical features:

• Fever ,headache, lymphadenopathy,nausea

and vomiting. Few days develop :

• lethargy• irritability• Agitation• personal changes seizures

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

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Differentiating testBrain MRI shows white matter lesions

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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

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Hsv inclusion body

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• 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 .

6/Mokola virus

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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.

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d/t

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

*CSF is normal

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AUTOIMMUNE

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2/ limbic encephalitisAerophobia 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

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Differentiating test

Serum antibodies to N-methyl-D-aspartate (NMDA) glutamate receptor may be positive.

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• 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 )

3/Gillian Barrie syndrome

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Differentiating test

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

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PSYCHOSIS

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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.

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8/Pseudo hydrophobia

• It is hysterical reaction to animal bite due to fear of rabies infection.

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OTHER

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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

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Clinical features in dogs

Presented by: Mohammed fathi

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RABIES IN ANIMAL

HYDROPHOPIA ONLY FOR HUMANIN ANIMAL THERE ARE 2 TYBES:1/furious rabies 2/dumb rabiesIncubation 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 :

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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.

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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.

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Rabies vaccine

• First dose at 90 days • And then repeated yearly

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Lab Investigation

By. Al khateeb Mohammed Alnoor

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Negri body

its pathopnemonic feature of rabiesFound 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.

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Take fixed smear from brain tissue staining with mannes ,giemsa ,sellers stain then add methyl alcohol .

If positive: Negri body appear dark blue in colorIf negative: no change (gives same color of

reaction)As final important point presences of Nigre

body diagnosis rabies 100%.

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Neuron without Negri bodies Negri body in infected neuron

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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.

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• 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 fluorescent-apple-green areas using a fluorescence microscope. If rabies virus is absent there will be no staining.

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Negative dFA. Positive dFA

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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

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Immunohistochemistry (IHC)

IHC methods for rabies detection provide sensitive and specific means to detect rabies in formalin-fixed 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.

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This slide shows a rabies-infected neuronal cell with intracytoplasmic inclusions. The red stain indicates areas of rabies viral antigen by using IHC or avidin-biotin complex (ABC) technique.

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Viral isolation

Specimens: saliva, CSF, urine and brain tissue.By inoculate there in tissue culture (WI-38, 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 isolation1. Tissue culture.2. Mice

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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.

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In DogsWhich 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.

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TRATMENT

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-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.

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• 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.

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Treatment is classified into two groups:

-(I) pre-exposure prophylaxis.

-(II) post exposure prophylaxis.

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-(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.

-

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-(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.

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*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.

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*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.

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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.

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Vaccination of rabies

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• 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.

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• antirabies tretment should started immediately:-

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• 1-if animal shows signs of rabies or dies within 10 day observation

• 2-if biting animal can not be traced or identified

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• 3-unprovoed bites• 4 -labrotory test eg:flouescent rabies antibody

test or negribodies +ve for rabies • 5-all bites by wild animals

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

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Type of vaccine:-

• A-nervous tissue vaccine.

• B-non neural vaccine.

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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.

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• If the person bite again before six month end two booster dose one week interval.

• .

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.

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• 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

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Complication of those two vaccine:-

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

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• 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

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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 B-propriolactone.

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• (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.

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• 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.

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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 .

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Two type:

• 1.human diploid cell vaccine(HDCV)

• 2.”second generation” tissue culture vaccines

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1-human diploid cell vaccine

It is prepared by fixed virus in human diploid cells

It is safe and highly potentUse in pre and post exposure immunization

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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”

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Usage: for adult ;children1.--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

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CONT..

If bitten again befor 5 years ,2booster 0,3days2-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.

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3-sub unit vaccine

Gp on spikeProduced by genetic enginering by cloning The gp gene in yeasts

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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

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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)

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Prevention generally1/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

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the first dose at 90 days and then repeated yearly

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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 rabies-

affected areas.

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