Transcript Rhabdoviruses

Rhabdoviruses
Rhabdoviridae
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Rhabdos (greek)
rod
Pathogens of mammals, birds, fish, plants
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Rhabdoviridae
Rhabdoviridae
Vesiculovirus (VSV)
Lyssavirus (rabies & rabies-like V)
Plant rhabdovirus group
Ungrouped rhabdoviruses
Rabies virus
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Unique features of Rhabdoviruses
Bullet-shaped
Enveloped
Negative, single-stranded RNA
Prototype for (-) RNA viruses
Replication in the cytoplasm
Rabies virus/Disease Mechanisms
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Rabies is usually transmitted in saliva and is
acquired from the bite of a rabid animal
Virus is not very cytolytic and seems to
remain cell-associated
Virus replicates in the muscle at the site of
the bite with minimal or no symptoms
The length of the incubation phase is
determined by the infectious dose and the
proximity of the infection site to the CNS and
brain
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Rabies virus/Disease Mechanisms
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After weeks to months, the virus infects the
peripheral nerves and travels up the CNS to
the brain (prodrome phase)
Infection of the brain causes classic
symptoms, coma, and death (neurologic phase)
During the neurologic phase, the virus spread
to the glands, skin, and other body parts,
including the salivary glands, from where it is
transmitted
Rabies virus/Disease Mechanisms
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Antibody response at the late stages
Antibody can block the progression of the
virus
The long incubation period allows active
immunization as a postexposure treatment
Rabies virus/Epidemiology
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Disease/Viral factors
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Virus induced aggressive behavior in animlas
promotes virus spread
Disease has long asymptomatic period
Rabies virus/Epidemiology
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Transmission
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Zoonosis
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Reservoir: wild animals
Vector: wild animals and unvaccinated dogs and
cats
Source of virus:
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Major: saliva in bite of a rabid animal
Minor: aerosols in bat caves containing rabid bats
Rabies virus/Epidemiology
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At risk:
 Veterinarians and animal handlers
 Person bitten by a rabid animal
 Inhabitants of countries with no pet
vaccination program
Rabies virus/Epidemiology
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Geography/Season
 Worldwide
 Except in some island nations
 No seasonal incidence
Rabies virus/Epidemiology
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Modes of control
 Vaccination
For pets
 For at-risk personnel
“Vaccination program have been implemented to
control rabies in forest mammals”
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Rabies virus/Laboratory diagnosis
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Occurence of neurologic symptoms in a
person who has been bitten by an animal
... too late...
Laboratory tests are usually performed to
confirm the diagnosis and to determine
whether a suspected individual or animal is
rabid
post mortem
Rabies virus/Laboratory diagnosis
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Ag detection (IF)
Isolation
Serologic
In:
CNS or Skin
Negri bodies:intracytoplasmic inclusions
consisting of aggregates of viral nucleocapsids in
affected neurons.
Rabies virus/Treatment & Prophylaxis
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Clinical rabies is almost always fatal unless
treated
Only hope:
 Post exposure prophylaxis
 For anyone exposed by bite or by
contamination of an open wound or
mucous membrane to the saliva or brain
tissue of an animal suspected to be
infected with the virus
Rabies virus/Treatment & Prophylaxis
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First protective measure
 Local treatment
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Washing(soap and water)
Rabies antiserum
Then
 Vaccination
 Ig -human rabies immunoglobulin (HRIG) or
equine antirabies serum (EAS)
Rabies virus/Treatment & Prophylaxis
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Vaccine
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Cell culture vaccine
HDCV
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On, 0-3-7-14-28 days
Treatment
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Clinical rabies is almost always fatal unless treated.
Once the symptoms have appeared, little other than supportive
care can be given.
Postexposure prophylaxis is the only hope for preventing overt
clinical illness in the affected person. Although human cases of
rabies are rare, approximately 20,000 people receive rabies
prophylaxis each year in the United States alone. Prophylaxis
should be initiated for anyone exposed by bite or by
contamination of an open wound or mucous membrane to the
saliva or brain tissue of an animal suspected to be infected with
the virus, unless the animal is tested and shown not to be rabid.
Prophylaxis
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The first protective measure is local treatment of the wound. The wound
should be washed immediately with soap and water or another
substance that inactivates the virus.
The World Health Organization Expert Committee on Rabies also
recommends the instillation of antirabies serum around the wound.
Subsequently, immunization with vaccine in combination with
administration of one dose of human rabies immunoglobulin (HRIG) or
equine antirabies serum is recommended. Passive immunization with
HRIG provides antibody until the patient produces antibody in response
to the vaccine. A series of five vaccinations is then administered over
the course of a month. The slow course of rabies disease allows active
immunity to be generated in time to afford protection.
The rabies vaccine
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is a killed-virus vaccine prepared through the chemical
inactivation of rabies infected-tissue culture human diploid cells
(HDCV) or fetal rhesus lung cells.
These vaccines cause fewer negative reactions than the older
vaccines (Semple and Fermi), which were prepared in the brains
of adult or suckling animals.
The HDCV is administered intramuscularly on the day of
exposure and then on days 3, 7, 14, and 28 or intradermally with
a lower dose of vaccine to multiple sites on days 0, 3, 7, 28, and
90.
There is one case of successful cessation of disease progression
by postexposure ribavirin treatment.
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Preexposure vaccination should be
performed on animal workers, laboratory
workers who handle potentially infected
tissue, and people traveling to areas where
rabies is endemic.
HDCV administered intramuscularly or
intradermally in three doses is recommended
and provides 2 years of protection.
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Ultimately the prevention of human rabies hinges on the effective
control of rabies in domestic and wild animals. Its control in domestic
animals depends on the removal of stray and unwanted animals and
the vaccination of all dogs and cats.
A variety of attenuated oral vaccines have also been used successfully
to immunize foxes. A live recombinant vaccinia virus vaccine
expressing the rabies virus G protein is in use in the United States. This
vaccine, which is injected into bait and parachuted into the forest,
successfully immunizes raccoons, foxes, and other animals.
Accidental injection of a woman with this vaccinia-rabies hybrid vaccine
resulted in immunization against both smallpox and rabies viruses (see
references).
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