Transcript Rhabdoviridae

Rhabdoviridae
Bullet-shaped RNA viruse
Rhabdoviridae encompasses more than 175 viruses of
vertebrates, invertebrates, and plants.
Most famous member is rabies virus.
It causes one of the oldest and most feared disease
Rhabdoviridae
Medium size 70 nm in diameter and 170 nm long
Enveloped with large peplomers
Helical cylindrical nucleocapsid-giving the virus the
bullet (conical) shape
Non segmented single-stranded negative-sense RNA
Genome is encoding 5 genes.
[Principles of Virology, 2000-ASM Press, Washington DC]
Structure and genomic organization of Rhabdovirus (VSV)
Rhabdoviridae Classification
Four genera
Lyssavirus is the most important
genus.
Rabdovirus has different serotypes
Each of these viruses is considered capable of causing
rabies-like disease in animals and humans
WHAT IS A FIXED VIRUS
• One whose virulence and incubation period have been
stabilized by serial passage and remained fixed during
further transmission.
• Rabies virus that has undergone serial passage
through rabbits, thus stabilizing its virulence and
incubation period and called as fixed virus
Batvirus - negri bodies brain
Bovine ephemeral fever virus
VSV- ocassional elongated form of virion
Sawgrass virus –isolated from tick-unassigned
RABIES VIRUS (RV)
EPIDEMIOLOGY
Rabies can infect all warm-blooded animals, and in
nearly all animals, the infection is fatal.
Dogs are the most important source of human
rabies infection.
Disease is worldwide, except Japan, United
Kingdom, Antarctica, Hawaii and some Caribbean
islands.
Epidemiology
Bat Rabies in USA
Worldwide, 40,000 to 50,000 people die of rabies/year
approx 10 million receive post-exposure treatment.
Bats in USA and Europe is the source of most human
rabies cases. In many cases there is no history of bite.
RV Pathogenesis
Transmitted by bite or scratch from a rabid animal.
However, in bat caves the infectious virus concentration
may be high resulting in aerosol transmission.
Incubation period: 14 to 90 days (in humans can be more
than 2 years after exposure).
RABIES
AS A CNS DISEASE
Development of overt rabies depends on:
(a) Location of the bite – virus must enter the
peripheral nerves to travel to brain
(b) Severity of bite
(c) Species of animal involved (E.g. foxes carry
up to 106 infectious particles of rabies virus/ml of
saliva)
RV Pathogenesis
RV enters peripheral nerves through sensory and motor
nerve endings – primarily through neurotransmitter
acetylcholine as receptor. Also uses gangliosides and
phospholipids.
Sequential event following Rabies
virus infection in a dog
RV PATHOGENESIS
• Virus enters the brain through the limbic system
where it replicates extensively – affecting the cortical
control of behavior and leading to the furious form of
disease.
• As the virus continues to spread within the CNS, it
reaches the neocortex – resulting in change in clinical
disease from fury to dumb or paralytic form.
RV Pathogenesis
Virus moves centrifugally from the CNS through the peripheral
nerves to:
 Adrenal cortex
 Pancreas
 Salivary glands
Virus release
In CNS, virus is released from cells by budding into
intracytoplasmic membrane. However, in the salivary glands,
the virus buds at the apical surface of mucous cells resulting
in release of large amounts of virus in saliva. By the
time when furious form of disease is evident and animals bite
indiscriminately, the saliva is highly infectious.
Clinical disease
There is a prodromal (warning) phase before clinical
disease that is characterized by change in temperament.
NOTE: Higher proportion of dogs, cats, and horses exhibit
the furious form than ruminants and lab animals.
RABIES CLINICAL FORMS:
FURIOUS AND DUMB (PARALYTIC)
• Furious form – Animal is restless, nervous,
aggressive, and dangerous (fearless). Inability to
swallow water (hydrophobia), excessive salivation,
exaggerated response to light and sound,
hyperesthesia (animals commonly bite or scratch
themselves).
• Dumb or paralytic form - As encephalitis progresses,
fury gives way to paralysis. Convulsive seizures,
depression, coma, and respiratory arrest resulting in
death 2 to 14 days after onset of clinical signs.
MAJORITY WILL SUCCUMB TO DISEASE
Rabid dog 4 days after
developing clinical signs.
Rough hair coat,
exudates in the eyes,
contracted pupils.
Dog paralysed for 4 hr
and died 8 hr later
Rabid dog - marked mandibular paralysis
Rabid African ox
(furious
form)
Excessive salivation and
loss of body condition
(top)
Excessive salivation
continued until death
(below)
Control and prevention
Developed countries
Stray dog and cat removal and control of movement of pets
Immunization of dogs and cats
Routine laboratory diagnosis to obtain accurate incidence
data
Surveillance to assess the effectiveness of all control
measures
Public education to ensure cooperation
Vaccines
Inactivated and attenuated RV vaccines are efficacious
and safe in animals.
IF YOU ARE BITTEN OR SCRATCHED
Tell an health care worker
immediately
Wash the wound out with
soap and water
Inform the doctor right
away
POSTEXPOSURE PROPHYLAXIS
Wound cleaning & treatment
PREVENTION
• No effective treatment exists.
• Postexposure Prophylaxis/PEP: 3 steps
• 1. Wound care: immediate thorough washing
with soap and water and a virucidal agent such as
povidine-iodine or 1-2% benzalkonium chloride.
• Shown to be protective if performed within 3
hours of exposure
• If puncture, swab deeply in wound and around
edges
PREVENTION
• 2. Passive Immunization: Human rabies
immunoglobulin (HRIG) 20 IU/kg ASAP, but not longer
than 7 days after vaccine given. Infiltrate entire dose
around wound, any remaining IG inject IM at a site
distant from the vaccine.
• 3. Human diploid cell vaccine (HDCV): 1 ml (deltoid)
on days 0,3,7,14,28. do not give in gluteal. If injected
into fat, no antibodies formed.
PREVENTION
 (HRIG and HDCV: give in different anatomical sites
and never in the same syringe.
If previously vaccinated - no rabies Ig + vaccine at 0,
3 days only)
Guides to Human Post-exposure Prophylaxis
Dog, cats
Healthy and available for observation
Rabid or suspected
Unknown
Bat
Regard as rabid and consider that exposure
occurred even if a bite wound is not
evident. Unless lab results negative
Skunk, fox, coyote Regard as rabid unless proven
Bobcat, woodchuck,
negative
other carnivores
Livestock, rodents,
rabbits, hares
Case by case-judgment call
None
Rabies Ig + vaccine
Consult PH official
Rabies Ig + vaccine
Rabies Ig + vaccine
PREVENTION
Pre-exposure vaccination
Veterinarians
Lab workers working with RV
wildlife workers in endemic areas
Pre-exposure vaccination regime – 0, 7, 28 days
‫‪Lab Diagnosis‬‬
‫كشتن حيوان مشكوك به هاري و ارسال سر حيوان‬
‫به انستيتو پاستور( بريدن سر حيوان بايد بوسيله‬
‫مامورين دامپزشكي يا بهداشت با استفاد هاز‬
‫وسائل كامل خفاظتي انجام مي گيرد و در يك كيسه نايلوني‬
‫ضخيم غير قابل نفوذقرار داده و آن را در يك يخدان‬
‫پر از يخ قرار مي دهند )‪.‬‬
‫نمونه برداري از بافت مغز با استفاد ه از‬
‫كيت هاي مخصوص نمونه برداري‪.‬‬
1. The standard
premortem test is a
fluorescent antibody
test to demonstrate the
presence of viral
antigen. The standard
postmortem test is
biopsy of the patient's
brain and examination
for Negri bodies.
Autopsies are rarely
performed.
Lab Diagnosis
1. Immunofluorescence - Suspected animals must be killed
and brain tissues collected for testing. Diagnosed by direct
immunofluorescence showing RV antigens in medulla,
cerebellum, or hippocampus.- observe Negri
bodies in neurons.
2. RT-PCR – test for RV-RNA in brain
3. Antemortem diagnosis – only done in suspect human
cases. Skin biopsy, corneal impressions, or saliva specimens
are used.
Only positive results are significant in this method because
negative results could be due to the fact that these
negative results could be due to the fact that these samples
are not optimal.
NEGRI BODIES – A GOLD
STANDARD IN DIAGNOSIS
Inclusion bodies called
Negri bodies are 100%
diagnostic for rabies
infection, but found
only in 20% of cases
NEGRI BODIES
IN BRAIN TISSUE
• Negri bodies round or
oval inclusion bodies seen
in the cytoplasm and
sometimes in the processes
of neurons of rabid animals
after death.
• Negri bodies are
Eosinophilic, sharply
outlined, pathognomonic
inclusion bodies (2-10 µm
in diameter) found in the
cytoplasm of certain nerve
..
Light microscopic photograph of multiple
intracytoplasmic rabies virus inclusions in a neuron
from the brain of a naturally infected bison
Negri bodies – collection of RV
nuclocapsids in neurons