rabies

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RABIES
A fatal disease!

• prepared by
• - ASSABBANE Chayma
• OMARI ahlam
• BENBRAHIM Nadia

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What you should know about rabies
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Contents
Virus life cycle
Introduction
Pathophysiology of rabies
History definition
symptoms of rabies
The rabies virus
Reservoirs of rabies
diagnosis
Treatment Prevention
Transmission
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Introduction

• Rabies is a viral disease of mammals that is
  transmitted from animals to humans.
• Rabies virus attacks nervous system.
• There Is no cure for the disease once manifested
  100 case fatality rate.
• It results in annual loss of more than
• 55000-70000 lives worldwide.
• People at rural areas and children Under
• 15 years are highly affected.

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Risk areas for rabies
56 of deaths from rabies
44 of deaths from rabies
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geographical distribution of animal rabies in
Morocco (19972015)
Rabies is endemic in morocco with all provinces
being affected except the southern desert region,
it has been a notifiable disease in morocco for
more than 10 years
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History of rabies
At the time of the arrival of Islam in, Rabies
was well known by the Arab population of the
Hijaz, it was called "Daou El Kalab" besides
religion, allowed the slaughter of stray dogs to
protect the individuals.
the vaccine tested for the first time on two
children (meister and juvile)
the word rabies finds its origin in the Sanskrit
Rabhas means to do violence
2000 BC
23rd century BC
1822
1888
3000 years BC
7th century AD
July 06,1885
first experimentation of rabies vaccine extracted
from spinal cord of rabbit (Pastor)
The pharaohs believed That rabies was the
punishment of their gods or goddesses
The disease is described for the first time in
the Eshuma code in Babylon, It will then be
described by Hippocrates, Democritus and
Aristotle in antiquity and by Girolamo FRACASTRO
The opening of the first anti-rabies center which
was after the pastor's institute
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Definition of rabies

• Rabies is a viral disease that causes acute
  encephalitis (inflammation of the brain) in
  warm-blooded animals
• Rabies is a zoonotic disease (a disease that is
  transmitted to humans from animals) that is
  caused by a virus

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The rabies virus
virus Classification
Mononigavirales
rhabdoviridae
ephemerovirus
Rabies
Lyssavirus
vesiculovirus
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Morphology of rabies virus

• The virus is in the form of a bullet. It measures
  in average of 180nm long and 175 nm in diameter.
  It composed of 2 essential parts
• The nucleocapsid
• The viral envelope.
• The genetic information is stored in a single
  strand of negative-polarity RNA which is composed
  of about 12000 nucleotides encoding for five
  proteins.

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The Genome of Rabies Virus
Involved in step of replication of the virus in
the body
It is inserted to the surface of the enveloppe
and responsible for the activation of immune
system
That provides a structure to the virus
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reservoirs of rabies
Europ Bat rabies
Europ Wild life rabies
Asia Urban rabies
Central America Urban rabies
North America Wild life rabies
Central America Bat rabies
Africa Urban rabies

South America Urban rabies
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reservoirs of rabies in morocco

• In Morocco, the dog is the main reservoir and the
  source of the majority of rabies contaminations.

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Mode of transmission
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Viral life cycle

1. Attachment
2. Endocytosis
3. membrane fusion
4. Transcription
5. Translation
6. Replication
7. combination
8. budding

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Pathophysiology of rabies
The virus of rabies is most often inoculated to
his host during the bite by contaminated animal
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Pathophysiology of rabies
Entry of rabies virus in man
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Pathophysiology of rabies
Virus replicates in muscle at site of bite
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Pathophysiology of rabies
then gets into sensory and motor nerves and
travels by retrograde axonal transport to the
spinal cord where it jumps across synapses into
the next neurons and then travels up to the
brain
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Pathophysiology of rabies
once in the brain, the virus infects neurons, and
if you were to look at some infected brain tissue
under microscope you might see Negri bodies,
which are eosinophils a grits of viral proteins
in the cell that clump together.
Negri bodies
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Pathophysiology of rabies
so that's how it gets to the brain, but actually
once the virus starts replicating in the brain it
can now spread outwards again along nerves to the
eyes, salivary glands, skin and so on....
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Symptoms of rabies in humans
Early symptoms
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Symptoms of rabies in humans
Late symptoms
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Symptoms of rabies in animals
Seizures
Extreme excitability
Changes in attitude and behaviour
Paralysis
Excessive salivation
Hydrophobia
Dropped jaw
Shyness or aggression
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Aggressive behavior of infected dogs

• Dogs that appear to have Rabies syndrome become
  aggressive.

• But, there are many triggers for the aggressive
  behavior that causes epileptic disorder or rabies
  syndromes.

• Aggressive behavior could be associated to others
  situations that might elicit an attack or a
  threat.

So, how to distinguish between aggressive
behavior related to the protection of resources,
territory or status and infection of the rabies
virus?
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Clinical diagnosis
Rabies is an acute progressive encephalomyelitis.

• Clinical diagnosis is simple in case of person
  presenting with a compatible illness (aerophobia,
  and hydrophobia) after documented animal exposure
  history.
• But, in the absence of the history of exposure
  or paramount signs, diagnosis on clinical grounds
  alone is difficult.

Laboratory testing is necessary to establish the
diagnosis.
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Emerging Laboratory Diagnosis
Although, no possible diagnosis of virus
infection during the incubation period, two
methods are approved and widely used by World
Health Organization (WHO) to detect the virus

• In Human alive

• Diagnosis is by performing RT-PCR of viral RNAs
  from saliva, urine, cerebrospinal fluid
  samples.But, it is not as sensitive.
• Detection of rabies antigen in skin biopsy from
  the neck using direct immunofluorescent technique
  (IF).

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Emerging Laboratory Diagnosis

• In dead animals

• Detection of rabies antigens in brain tissue
  using direct immunfluorescent technique (IF),
• Demonstration of cytoplasmic bodies inclusions
  (2-10µm in diameter) called negribodies in the
  brain tissue confirm the diagnosis (100).
• But, there have been found in only 20 of cases
  

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Pathogenesis
Category I Slight risk Touching or feeding
suspect animals bat skin is intact, Category
II Moderate risk Minor scratches without
bleeding from contact, or licks on broken skin,
Category III Great risk One or more bites,
scratches, licks on broken skin, or other contact
that breaks the skin,
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Incubation phases of Rabies virus
The incubation period of rabies virus in human
body

• Typically is 3 - 8 weeks, but may vary from less
  than one week to over than one year.

The incubation period depends on

• Importance of the inoculums,
• Depth of bite(s),
• Number and position of bites relative to the
  central nervous system (CNS),

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Clinical manifestations

• Clinically, the disease at human level might be
  divided into four phases
• Non specific Prodrome phase,
• Excitement phase,
• Paralytic phase,
• Coma death phase.

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1. Clinical features of Prodrome phase

• Prodrome period

• Last a few days, generally not more than a week.
• During this period, the virus moves centripetally
  from the periphery to dorsal root ganglia and
  causes neuropathic pain at the bite site,
  presenting as burning, itching, or as prurities.

• Symptoms of Prodrome period

weariness
Fever
Headache
Nausea
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Clinical features

1. Excitement phase

1. Paralytic phase

• Anxiety Agitation,
• Increased nervousness,
• Hyper reactivity,
• Papillary dilation,
• Increased salivation,
• Painful laryngeal and pharyngeal spasms triggered
  by swallowing saliva (hydrophobia).

• Soon, a wide variety of the CNS signs appear
  including
• Hallucination,
• Lack of coordination,
• Mental confusion,
• and Paralysis,

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1. Clinical features of Coma death

• Persistent fever (Tgt40.6C) from the onset of
  limb weakness
• Intact sensory function of all modalities except
  at the bitten region
• Percussion myœdema and,
• Bladder dysfunction.

• Recovery from rabies is extremely rare, Only six
  documented cases of human survival from clinical
  rabies have been reported,
• Finally, the patients become comatose after 1-2
  weeks of acute neurological phase and die without
  vaccine of arrhythmia or myocarditis.

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Clinical features of Acute neurological phase

• Two clinical forms
• Encephalitic form.
• Paralytic form.
• Both forms are fatal for human once clinical
  signs are reported in less than 15 days without
  intensive care conditions.

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1- Encephalitic Form

• About two-thirds of patients have an encephalitic
  form and manifest as
• Hyperactivity,
• Confusion,
• Spasm,
• Autonomic stimulation signs
• (hyper-salivation, anti-socoria).
• The spasms can be incited by tactile, auditory,
  visual or olfactory stimuli (aerophobia, and
  hydrophobia)

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2 - Paralytic Form
The remainder present with paralysis they
generally start in the bitten limb but progress
to all limbs, the bulbar and respiratory muscles.
Phobic spasms may appear in only 50 of such
patients and the presentations mimics other
neurological disorders.
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Treatment of rabies

• No proven standard therapy Mortality rate of
  rabies is extremely high,
• How to manage rabies infection ??
• Current management for rabies patients is mostly
  symptomatic and palliative,
• Some therapeutic agents had been advocated with
  limited success
• Combination therapy with immunoglobulin plus
  vaccination,
• Ketamine and interferon-a,
• Large doses of intravenous human rabies
  immunoglobulin.

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Conclusion

• Despite the high fatality of rabies,
• Rabies disease can be prevented with adequate
  post-exposure prophylaxis,
• The burden of rabies can be reduced if people are
  capable of recognizing the exposure risks and are
  familiar with prophylactic measures.
• Just following the World Health Organization
  (WHO) Guidance established for PEP taking in
  account categories of exposure and types of
  exposing animals

Prevention

• Stray animals should be destroyed,
• Vaccination of pet dogs and animals should be
  mandatory,
• A live attenuates vaccine is available for
  immunizing dogs and cats.

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1- Pre-exposure immunization

• Generally confined to those occupationally at
  risk such as veterinarians, animal holders and
  long term visitors to endemic areas.

• They should be given
• 3-doses of the human diploid vaccine on a month
  apart
• with a booster dose two years later.
• Two booster doses should be given if they are
  exposed to infection.

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2- post-exposure prophylaxis or suspicion of
exposure

• Timely wound should be washed thoroughly with
  soap, water and alcohol or iodine solution as
  prevention actions after suspect or proven
  exposure to the rabies virus.

• Patients should be given combined passive and
  active immunization,
• Passive immunization (Rabies Immunoglobulin
  (RIG)
• Active immunization

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2.1. Passive immunization Rabies
Immunoglobulin(RIG)

• By injecting 20µl/kg of human anti-rabies
  immunoglobulin
• Half given around the bite wound,
• Half given in intramuscularly.
• RIG provides rapid immunity to tide over the
  initial phase after vaccination before
  neutralizing antibodies inducted,
• RIG should be administered at a site distant from
  the first vaccine dose site as it may suppress
  the antibody production,
• RIG is not indicated beyond the seventh day after
  vaccination since an antibody response to vaccine
  is presumed to have occurred.

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2.2. Active immunization

• The administration of Rabies vaccines should be
  done as soon as possible after exposure to induce
  active neutralizing anti-rabies antibodies,
• The main vaccine is the human diploid cell
  vaccine, It contains an inactive virus disrupted
  into subunits.
• It is prepared in human embryo lung cell and
  administered in intramuscularly in 5-doses spaced
  at 0/3/7 /14 and 30 days.
• For previously vaccinated persons, whether
  complete pre-exposure (PrEP) or post-exposure
  prophylaxis (PEP), who are exposed to rabies,
  should be re-vaccinated regardless of the last
  vaccination date or the neutralizing antibody
  titer.

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Conclusion

• Despite the high fatality of rabies,
• Rabies disease can be prevented with adequate
  post-exposure prophylaxis,
• The burden of rabies can be reduced if people are
  capable of recognizing the exposure risks and are
  familiar with prophylactic measures.
• Follow the World Health Organization (WHO)
  Guidance established for PEP taking in account
  categories and types of exposing animals

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Perspectives Novel rabies vaccines

• A number of experimental vaccines are under
  development that might provide alternative safe
  and potent but less expensive vaccine options.
• These include DNA vaccines, and recombinant
  protein vaccines.
• Further testing is needed to determine if and
  which one of these novel vaccines will make their
  way into mass production and application in the
  future

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World Rabies Day

• This day Celebrates Dr Pasteur's vision of
  Rabies free World
• Co-operative global event planned to reduce
  suffering from rabies.

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Protect your pet
Thank you for your attention