Transcript No Slide Title

Rabies
September 30, October 5,
2010
“IF A DOG IS MAD THE AUTHORITIES
HAVE BROUGHT THE FACT TO THE
KNOWLEDGE OF ITS OWNER; IF HE
DOES NOT KEEP IT IN, IT BITES A MAN
AND CAUSES HIS DEATH, THEN THE
OWNER SHALL PAY TWO THIRDS OF A
MINA (40 SHEKELS) IN SILVER. IF IT BITES
A SLAVE AND CAUSES HIS DEATH HE
SHALL PAY FIFTEEN SHEKELS OF
SILVER.”
Eshnunna Code (pre 23rd century BC)
Viruses with -ve RNA genomes
influenzaviruses
Orthomyxoviridae
parainfluenza virus
canine distemper virus
Paramyxoviridae
respiratory syncytial virus
rabies virus
Rhabdoviridae
vesicular stomatitis virus
Filoviridae
Ebola virus
Bunyaviridae
Haantan virus
Rhabdoviruses
• Genus Lyssaviruses (neurological)
• Genus Vesiculovirus (epithelial)
• Genus Ephemerovirus
Lyssavirus structure
P
P
Genotypes of Lyssavirus
•
•
•
•
•
•
•
1. Classical rabies (genotype 1)
2. Lagos bat virus
3. Mokola virus
4. Duvenhage virus
5. European bat virus
6. European bat virus
7. Pteropus Lyssavirus
Global distribution of rabies
UK
Japan
New Zealand
World wide, EXCEPT
“pteropus lyssavirus” in Australia
and UK
• political considerations
Epidemiology of rabies
Species selection and variants of
genotype 1 rabies virus
• suggests that each variant circulates mainly
in one species
• occasional spillover
• may explain minor differences in
susceptibility but virus just as fatal
Differences between variants
• Monoclonal antibody typing
• Sequencing of PCR products
Rabies variants in North America
• Terrestrial
–
–
–
–
–
Skunk
Fox - red and arctic
Grey fox
Raccoon
Coyote
• Bat (most of the unexplained human cases
in N.America)
distribution of reservoir selected
terrestrial rabies in N. America
rabies transmitted by bites……
but what if……
Bat-associated rabies virus in Skunks.
Leslie MJ, Messenger S, Rohde RE, Smith J, Cheshier R,
Hanlon C, Rupprecht CE.
Emerg Infect Dis. 2006 Aug;12(8):1274-7
Rabies was undetected in terrestrial wildlife of northern Arizona until 2001,
when rabies was diagnosed in 19 rabid skunks in Flagstaff. Laboratory
analyses showed causative rabies viruses associated with bats, which
indicated cross-species transmission of unprecedented magnitude. Public
health infrastructure must be maintained to address emerging zoonotic
diseases.
Bat rabies
• In N. America - 700 to
800 encounters per year
• source of most human
cases
• 70% of human cases and
75% of cryptic deaths
• vampire bats in Mexico
Derek Donald
silver-haired bat
(Lasionycteris
noctivagans)
Lasionycteris noctivagans (silver
haired bat)
Pipistrellus subflavus (eastern
pipstrelle)
Rabies cases in Canada 2008
http://www.inspection.gc.ca/english/anima/disemala/rabrag/statse.shtml#a2009
Was the
Rabid ?
The story begins…..
“Las resultas” (Goya)
vampires appear in the form
of dogs, wolves or bats
bite turns person into
vampire
rabies is zoonotic, animals
most likely to be affected by
“furious form” are canids and
felids. Isosymptomatic
spread by bite
aggressive, violent,
libidinous
nocturnal
protective measures - garlic,
strong smelling substances,
crucifixes, mirrors, water.
Vampires grimace and are
repulsed by these objects
virus causes lesions in
“limbic” areas of CNS
(hypothalamus,
hippocampus, amygdaloid
complex) -> loss of control,
insomnia
hyperesthesia, painful spasms
of facial, laryngeal, pharyngeal
muscles - precipitated by bright
objects, strong smells, water
on exhumation vampires
look alive, drool blood,
scream when pierced
through heart with stake
after death by asphyxia blood
remains fluid for some time
burial in cold, wet locations
leads to saponification
putrification leads to gas
buildup
Symptoms of rabies
• Loss of appetite, anxiety, insomnia
• Infection of the limbic system
(hypothalamus, hippocampus, amygadala)
– Restlessness, wandering,
– Hypersensitivity to stimulus
– Hydrophobia, muscular spasms of facial,
laryngeal, pharyngeal muscles
• Triggered by light, odors, water
– Blood in vomit, inability to swallow saliva
– hypersexuality
Pathogenesis: infection and
incubation period
bites
infection
other
(transplants,
ingestion)
mucosal exposure
No antibody
(antibody can
prevent further
replication at site spread - post
exposure vaccination)
Incubation period 14-90 days (7 years!)
Pathogenesis: Spread to the brain,
clinical signs
infection of neurons
centripetal spread to
neurons in DRG or
spinal cord, spread to
brain
centrifugal spread
to sal. glands, skin
Furious (limbic
System)
death
clinical signs
Dumb
(neocortex)
2-3 days
Virus shedding
what causes behavioural changes,
paralysis, death?
rabies-infected neurons are
negative for apoptotic markers
H&E
caspase 3
Jackson et al. 2008, J. Neurovir. 14:368-375
anti-rab
TUNEL
rabies histopathology
• mononuclear
infiltration
• perivascular
cuffing
(lymphocytes
and PMN)
• Babes nodules
(glial cells)
• Negri bodies
http://www.cdc.gov/rabies/diagnosis.html
Negri Bodies
Negri body in
a neuron cell body
In the trigeminal ganglion
An electron micrograph
of a Negri body with
budding virus particles
human case
Vaccines
• inactivated virus vaccines
• modified-live (wild-life baits)
• vectored vaccines
rabies vaccines licensed in
Canada (2009)
http://active.inspection.gc.ca/scripts/database/vetbio_submit.asp
?lang=e&species=11&manufacturer=all
Vaccines for control in wild-life
• Modified live
• Vectored (vaccinia or canary-pox virus)
– monitoring (tetracyclin, antibodies)
Prevention, management and control of
rabies - Definitions
• Domestic animals – livestock and pets
• Pets – dogs, cats, ferrets (or case by case basis)
• Currently vaccinated – if primary vaccinated >30 days previously
or vaccination status current based on duration of vaccine used (3
vs 1)
• Not vaccinated – pet not vaccinated or adult animals only
vaccinated once (no boosters)
• Expired vaccination – 2 or more documented vaccinations but
currently overdue.
• Home quarantine – physically confined (fence, chain, cage,
indoors etc). Contact minimized, can not leave property. Bites of
behaviour changes reported immediately.
• Home observation – monitored by owner for signs consistent with
rabies.
Compendium of Animal Rabies Prevention and Control,
JAVMA, 2008, 232:1480- 1486
Vaccine Administration
All animal rabies vaccines should be restricted to use by,
or under the direct supervision of a veterinarian.
Vaccine Selection
In comprehensive rabies-control programs, only vaccines
with a 3-year duration of immunity should be used. This
constitutes the most effective method of
increasing the proportion of immunized dogs and cats in any
population. No lab or epi. data to support annual or biannual
admin. of 3-year vaccines following initial series.
Preexposure Vaccination and Management.
Dogs, cats, and ferrets. All dogs, cats, and ferrets should
be vaccinated against rabies at 3 months of age and
revaccinated with a single dose of vaccine and placed
on an annual or triennial schedule, depending on the
type of vaccine used.
Postexposure Management. Any animal potentially exposed to
rabies virus by a wild, carnivorous mammal or a bat that is not
available for testing should be regarded as having been exposed to
rabies.
• Vaccinated pet (options)
– Immediate revaccination (if within 5 days of exposure).
45 day observation
– Immediate titre check (if within 5 days of exposure).
Observation until results obtained
• >0.5IU/ml. 45 day owner observation
• <0.5IU/ml. pet not deemed vaccinated
– Three month quarantine (or if >5 days following
exposure
– Euthanasia
Postexposure Management:
• Primary vaccinated pet (options)
– Immediate revaccination (if within 5 days of exposure).
45 day observation
– Three month quarantine (or if >5 days following
exposure
– Euthanasia
• Non-vaccinated pet (no vaccine or initial vaccine<30 days)
– Immediate euthanasia
– Six month quarantine, vaccinated at end
• “exotic” species (wolf, hybrids etc)
– Euthanize despite vaccination status
Livestock. All species of livestock are susceptible to rabies;
cattle and horses are among those most frequently infected.
Livestock exposed to a rabid animal and currently vaccinated
with a vaccine approved for that species should be
revaccinated immediately and observed for 45 days.
Unvaccinated livestock should be slaughtered immediately. If
the owner is unwilling to have this done, the animal should be
kept under close observation for 6 months.
Management of animals that bite humans
• healthy dog, cat, ferret
– 10 day observation period
– do not vaccinate during observation
– report any clinical signs to dist. vet.
• animal showing suspicious signs
– report to dist. vet.
– euthanize and test
Memo from CFIA, May 2005
Where possible biting dogs, cats or ferrets should not be
euthanized but observed for 10 days.
1.To avoid needless euthanasia of rabies free animals (from
1999-2003, CFIA tested 6,695 dogs and 5,538 cats. Of
these only 7 dogs and 11 cats tested positive (all had
displayed abnormal behaviour).
2.High cost for testing animals that are of negligible risk
3.Human health consideration - possibility of false negative
test on asymptomatic animals.
Canadian - Health of animals Act
(Section 5)
• A person who owns or has the possession, care or control
of an animal shall notify the nearest veterinary inspector of
the presence of a reportable disease or toxic substance, or
any fact indicating its presence, in or around the animal,
immediately after the person becomes aware of the
presence or fact.
• Immediately after a person who is a veterinarian or who
analyzes animal specimens suspects that an animal is
affected or contaminated by a reportable disease or toxic
substance, the person shall so notify a veterinary inspector.
A suspect case/exposure - What
steps to take
• duties as veterinarian
– initial assessment and reporting
– collection and submission of specimen
• if person exposed (or suspected)
– wash wound
– notify dist. veterinarian
• if animal exposed
– notify dist. vet.
– post exposure management
– management of animals that bite
Bats
• “in situations in which a bat is physically
present and the person(s) cannot exclude the
possibility of a bite, postexposure treatment
should be considered unless prompt testing
of the bat has ruled out rabies infection”.
(CDC)