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Current Issues in RabiesMira J. Leslie, D.V.M., M.P.H.
April 4, 2007
Rabies
• Among the oldestinfectious diseaseknown.
• MOST FATALdisease known
• Prevention costs:health care, animalcontrol, public health,laboratory….
Centuries of Fear
• Rabhas –Sanskrit “todo violence” 30 centBC
• Illiad- Hector is“mad dog”
• Egyptian dog Sirius-furious dog
• Celsius, Rome, 1st
cent. AD humanrabies
Rabies virus• Rhabdoviridae• Bullet shaped• 1 of 7+ Lyssavirus
– Classic Rabies– Lagos bat virus– Mokala– Duvenhage– EBLV1 , EBLV2– Australian bat virus
• Encodes 5 proteins• enveloped
• Very few countries are rabies-free. (Hawaii, Australia, U.K.)• Surveillance for rabies is passive and variable• Animal reservoirs vary from country to country.
Encephalitis Caused by a Lyssavirus in Fruit Bats inAustralia
Graeme C. Fraser,* Peter T. Hooper,† Ross A. Lunt,† Allan R.Gould,† Laurence J. Gleeson,† Alex D. Hyatt,† Gail M. Russell,† and
Jaqueline A. Kattenbelt†EID, Volume 2, No 4, Oct-Dec 1996
Characterization of a novel lyssavirus isolated fromPteropid bats in Australia.Gould AR, Hyatt AD, Lunt R, Kattenbelt JA, Hengstberger S,Blacksell SD.Virus Res 1998;54:165-87
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Rabies: background
• Rabies is a viral disease of the central nervoussystem.
• All mammals including humans can beinfected.
• Rabies is transmitted when infective saliva isinoculated under skin or into a mucousmembrane.
• Rabies is fatal once signs develop.
Virus infects and movesretrograde in nerve tissue,not blood.
Rabies infection
• Long Incubation period: usually 3-12 weeks– Dogs: 2weeks-6m– Humans: 2 weeks- 6 years– Wildlife: unknown
• Contagious period (viral shedding in saliva)– Dogs: 1-10 days before death– Humans: ?– Wildlife: ?
Signs of rabies in animals
Abnormal Behavior :• Nocturnal animals acting sick or
active during daylight hours.• Staggering, trembling, weakness,
paralysis, agitation, confusion,hypersalivation, unprovokedaggression, abnormal vocalization,glazed eyes….
• **Grounded bats.• Variable symptoms
Rabies and Public Health• PH (federal, state, local) is involved in every
aspect of rabies
– Guidelines for control and prevention-animals/humans– Managing animal and human exposures– Laboratory testing– Vaccine supply– Surveillance, epidemiology, …– Animal control- may be health or law enforcement– Provide expert consultation to medical and veterinary
community– Investigation of animal and human cases– Media and public education
• 1955- present: Confirmed Rabid animals– wildlife domesticated
• In the U.S., wildlife reservoirs maintain rabies andinfection is transmitted from wildlife to other species.
What happened to reduce dog rabiesin 1950-60?
3
Rabies in animals and in humans is anationally notifiable condition
• All cases are tested by Public health labs andaffiliates (some universities)
• Reporting system: clinician (vet, medical) tolocal ph state ph CDC
• Complete investigations (to find exposed peopleand animals) are done on every case.
Skunk
Raccoon
Coyote
Skunk
Fox
Skunk
Fox
Fox
Terrestrial and non-terrestrial rabies reservoirs
**There have been majorchanges in this data in thepast 3 decades
1980:translocationby huntersstartedepizootic
Raccoons and Rabies
• Raccoons efficientlytransmit rabies to:skunks, beaver, fox,groundhogs, cats,dogs, goats, deer,horses, pigs, sheep,cattle, rabbits, …
and humans (more later)
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Skunks and Rabies
• Skunks transmitrabies to :badgers, raccoons,other wildanimals, cats,dogs, humans,cattle, horses, …
Skunk
Raccoon
Coyote
Skunk
Fox
Skunk
Fox
Fox
3 different variants
What accounts for this?
Foxes transmit rabies tocoyotes, bobcat, dogs,horses….llamas, etc
Bats and Rabies• > 1300 rabid bats reported
in US during 2004 (>1400in 2005)
• Widespread distribution• Many species affected• Most bats are healthy- not
rabid• No ‘carrier’ state• Predominant cause of
human infections in US.
Bats with rabies
• Appear injured• Found flapping or dead on ground• Flying during the day• When in urban area, often expose
human and/ or pets– Found in pets mouth– Child finds bat
[269 in 2005]
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Walla, Walla: Sept. 2002
CATS SHOULDBE
VACCINATED![N=76 in 2005]
Rabid puppy: Tucson 2002
• 3-4 month old stray• Given to Humane
Society 3/11• Animal Rescue 3/17• PETsMART 3/22 &
3/24• Euthanized March 29• Rabies test April 2
Rabid Puppy: Follow up• Count back 14 days from
death.• Identify all human and animal
exposures.• Press release, hotline, …• Emergency room notification.• 105 human exposures, 1
unvaccinated animal contactCost of PEP: $250,000?
Rabid puppy• This pup was
vaccinated 2weeksbefore it became ill:what happened?
Incubation period = weeksContagious (shedding)period = days
March April
RabiesExposure
Symptomatic
Vaccination at Humane society & Rescue
Euth/testPetsmart
6
Immunology
• A puppy receiving an initial rabies vaccinewill take about 28 days to developimmunity. Subsequent vaccines are“boosters”.
• After being exposed to a rabid animal a petshould have an immediate booster rabiesvaccine (to mount optimal virus neutralizingantibody) .
Pets or feral and stray animals may beexposed to a wild animal
• Test wild animal ifexposure is seen andanimal is available.
Cattle are usually infected by rabid skunks or raccoons,bats, foxes.
DeriengueImported cases of Bovine Paralytic Rabies transmitted by vampire bats in Central America
ARIZONA
MEXICO
Rupprecht C and Gibbons R. N Engl J Med 2004;351:2626-2635
Rabies surveillance is mostly passive and notstandardized among states or counties. Datais not comparable.
Skunk
Raccoon
Coyote
Skunk
Fox
Skunk
Fox
Fox
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Rabies: Evolving Epidemiology
Human factors:1. Importation of foreign
dogs, exotic animals,livestock
2. Interstate movement ofrabies reservoirs
3. Better diagnostics4. Improved surveillance of
wildlife5. Canine vaccination
Animal factors1. Evolutionary adaptation
of virus in new hosts2. Population density3. Susceptibility4. Reservoir range
Translocation of Coyote Rabies -- Florida,1994
– November- December 1994. Rabies was diagnosed infive dogs from two associated kennels in Florida.
– The virus recovered from the five dogs was identified asa variant not previously found in Florida but endemic incoyotes (Canis latrans) in south Texas.
– The source of infection was a group of coyotes that weremoved from Texas to Florida for hunting in a 320 acrefenced foxpen for sport.
MMWR August 11, 1995 / 44(31);580-581,587
Rabies diagnostic tests:
• Direct Fluorescent antibody• Monoclonal antibody test• RT-PCR• EM• Histopathology• IHC•Virus isolation in cell culture•Serology- VNA
Rabies Testing: Direct Fluorescent antibody•DFA: Gold standard diagnostic- veryreliable test. [Only performed at PublicHealth and few university labs]
•Cross sections of fresh brainstem,hippocampus, cerebellum.
Monoclonal antibody and PCR toidentify rabies virus variant.
Rabies Transmission inWashington
Other wildlife and pets
Rabies in WA
• In 2006: 15 rabid / 244tested bats.
• Multiple human andpet exposures
• 5-10% of tested batsare rabid.
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Rabies testing in WA
• WA Public Health Lab: Testinglimited to human exposures- nosurveillance testing done.
• 300-500 animals tested annually• ~50%Domestic/ 50% wild• 98% of positive in WA are bats• 92% of positive nationwide are
wildlife.
Rabies virus variant identificationavailable on cases in unusualspecies and humans.
Spit Happens
•History: Veterinarianexamined, sedated andeuthanized a llama that wasexhibiting abnormalbehavior.Brain tissue sent to veterinarydiagnostic lab.
• Laboratory confirmedrabies.
Site visit to small ranch;5 llamas; 2 have wounds.
Investigation
• Another llama fromsame pen died 2weeks earlier ofundiagnosed acuteillness.
• Exhume for testing.
Investigation• Brain tissue from
exhumed llama testspositive for rabies
One week later:
Wounded llama dies.
Rabies Confirmed.
Summary: 30 days later.Three llamas remained healthy
Three llamas died of fox variant of rabiesOne llama was euthanized due to wound/exposure
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Three rabid llamas in 30 days
• Unusual for rabies to affect group of animals• Llama to llama transmission? Not likely.• What happened?
– River/Wildlife corridor adjoining ranch– Probable single attack by rabid fox on the three male
llamas sharing one pen;– Variable incubation according to amount of viral
inoculum and proximity to nerve–all died within onemonth.
Rabies Vaccines- Animals
• Domestic: parenteral vaccines fordog, cat, ferret, horse, cattle,sheep (see Compendium).
• Wild: Oral recombinant DNAbait vaccine for raccoon, coyote,fox (not used in WA)
• Exotic/wild: No licensed vaccinefor bats, monkeys, llamas, wolf-hybrid…(off- label use byveterinarians)
Citizen finds sick or deadbat or wild carnivore; callsanimal control agency
Animal control picks up animaland submits brain tissue topublic health laboratory.
Rabies virus not detected
Results provided to state and local public health agencies andthe submitter (animal control, veterinarian)
Rabies virus detected
Potential human exposure to rabies
Yes
No
Local, state and nationalrabies databases updated
Veterinarian suspects rabies in a domesticanimal; animal is euthanized or dies; requestspublic health laboratory rabies test
No furtherfollow-up
Public health calls citizen to assessany potential human exposure(s).
Animal control evaluates andregulates management of petanimal exposure(s).
Example of a rabies surveillance and control system
Public health laboratoryperforms rabies test
Refer to healthcare provider
Human Rabies
• Worldwide,rabies causes anestimated30,000-70,000human deathsannually– India, China,…
• “… the patient can neither stand nor lie down;like a madman he flings himself hither andtither, tears his flesh with his hands, and feelsintolerable thirst. This is the most distressingsymptom for he so shrinks from water and allliquids that he would rather die than drink or bebrought near to water; it is then that they biteother persons, foam at the mouth, their eyeslook twisted, and finally they are exhaustedand painfully breath their last.”– Girolamo Francocastro, 16th century
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Human Rabies, U.S. 1980- 2006
N=59
0
1
2
3
4
5
6
7
8
9
80 82 84 86 88 90 92 94 96 98 20 200220042006
Transplant
Raccoon
Bat
ForeignDog
WA cases
Rupprecht C and Gibbons R. N Engl J Med 2004;351:2626-2635
Temporal Trends in the Diagnosis of Rabies in the United States, 1944 to 2002
Rupprecht C and Gibbons R. N Engl J Med 2004;351:2626-2635
Human Rabies
• California• 66 year old male• Hospitalized -chest pain, 2
wk mild headache,drowsy…5d arm pain, 1dhand weakness.
• Steady neuro decline• Died seven days after
hospitalization.
Human Rabies, CA
• Exposure: Bat bite onright index fingerwhile in bed 5 weeksearlier.
• Threw bat out window• Washed wound• Did not seek medical
care or consult publichealth despite advise.
Human Rabies, CA
• Due to bat bite history,rabies diagnosis wasimmediately considered.
• Aggressive Treatment:Vaccine, IG, anti-virals,…
• All treatments failed.
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Case #2
• 10 year old child : died Sept. 27,2005 (post hurricane) Mississippi• No history of sick pets, no animal bite• Bats seen in and around home• Post mortem history; one bat in bedroom
released outdoors by the child• Epidemiology of rabies in Mississippi: bats
are reservoir.
Case #2:Exposure of hospital staff and family• 23 family members including one who was
bitten• 32 of 79 health care workers (19 nurses, 4
physicians, 5 resp therapists, 2 XR techs, 2lab staff)
Human Rabies Cases, U.S.1980-2005
• 36/56 (64%) associated with insectivorousbat rabies virus variants
• Most do not have history of bat bite– Unreported minor bites– Hard to get history from rabies infected people– Unrecognized bites?– Teeth are small- no large wounds
Human rabies exposure/transmission
• Not all animal bites arerabies exposures.However all bites shouldbe evaluated … why?
• Transmission: infectious
saliva into skin or mucousmembrane.
Rabies is preventableEvaluation of animal bites
• Species?• Bite? Non-bite?• Place of exposure
– Foreign travel?– Other US, local
• How was the animalacting?
• Provoked/unprovoked?• Is animal available for
observation- (domesticanimal)or testing (wild)?
Post exposure prophylaxis
• Rabies is preventableif vaccine isadministered beforethe virus gets intonerve tissue.
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Unique rabies case, WI
• A 15 year old girl developed fatigue,tingling, numbness left hand; she becameunsteady and had double vision.
• Day 4: Worsening symptoms-hospitalization
• Day 6: history of unevaluated bat bite inchurch 4 weeks earlier
Recovery from rabies:
• Supportive care; infection control• Drug induced coma for 7 days, …
– Rise in neutralizing antibodies 1:32---1:2,048
• Day 33: Removed from ventilator• Day 36: Discharged to rehab unit• Slow recovery- learn to walk, speak, feed herself, …• Home ~ 3 months later.• She has neurological deficits
Potential Human Rabies Exposures
• International travelers can beexposed to canine rabies– Some areas are HIGH RISK.
• U.S.= National variability:- Some states report hundreds(NC=659; TX=913) of rabidanimals annually/ some report <10(WY, UT, OR, NV, LA, HI, ID)
Rabies Post-ExposureProphylaxis (PEP)
• Cleanse wound immediately.• When needed, administer PEP as soon after
exposure as possible.• Rabies immunoglobulin: one dose• 5 doses of rabies cell culture vaccine
Rabies Control and PreventionPublic Education
Animal Bites: Wash wounds and seekmedical consultation - especially thosefrom bats/wild animals and foreign dogs
Control rabies in pets:• Vaccinate pets• Keep pets away from wildlife (bats,
raccoons..)• Follow leash laws• Control strays
Wildlife:• Avoid contact with sick
and injured wild animals.• Don’t feed, handle or translocate
wildlife
Summary
• Rabies circulates in natural cycles in reservoir species ofwildlife, (U.S.= insectivorous bats, skunks, raccoons,foxes) and “spills over” into many other species.
• Reservoirs of rabies do not “carry” rabies- they becomeinfected and effectively transmit virus before they die.
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Summary• Rabies is a fatal disease- All animal bites
should be assessed carefully.
• Any potential human contact with a bat needstimely response.
• Be responsible about pets: vaccinate them.You don’t know when or where they’ll beexposed. (hiking, traveling, or even in thehouse!)
Summary
• Our understanding of the pathology andepidemiology of rabies is incomplete.
• Public health has a role in every aspect of thiscomplex zoonoses.
• Rabies is a model for zoonotic disease preventionand control.
• Movement of animals globally and nationallypresents constant risk.
http://www.cdc.gov/ncidod/dvrd/rabies/
Thanks