Current%20Issues%20in%20Rabies

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Current Issues in Rabies

• Mira J. Leslie, DVM, MPH
• April 6, 2009

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Todays Objectives

• Rabies
• Overview of rabies disease
• Understand the current epidemiology of rabies in
  animals and humans
• Describe the role of public health in rabies
  detection, prevention and policy
• Consider the impact of importation of animals on
  local animal and human health

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Rabies Virus

• Rabies is caused by RNA viruses in the family
  Rhabdoviridae, genus Lyssavirus
• At least 7 Lyssavirus species or genotypes cause
  rabies (disease)
• Recently, 4 new Lyssaviruses collected from
  Eurasian bats have been described

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Rabies Disease

• Acute, progressive viral encephalitis
• Highest case fatality of any infectious disease
• One of the most ancient diseases described
• Model zoonosis

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ZOONOSES Inoculated virus moves in
nerve tissue, not blood.
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Rabies infection

• Long incubation period usually 3-12 weeks
• Dogs 2weeks-6m
• Humans 2 weeks- 6 years (1-4 months usually)
• Wildlife unknown
• Contagious period (viral shedding in saliva)
• Dogs 1-10 days before death
• Humans ?
• Wildlife ?

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Signs of rabies in animals

• Abnormal Behavior
• Nocturnal animals acting sick or active during
  daylight hours.
• Staggering, trembling, weakness, paralysis,
  agitation, confusion, hypersalivation, unprovoked
  aggression, abnormal vocalization, glazed eyes,
  choking.
• Grounded bats.
• Variable symptoms

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Rabies

• Rabies is a viral disease of the central nervous
  system.
• All mammals including humans can be infected.
• Rabies is transmitted when infective saliva is
  inoculated under skin or into a mucous membrane.
• Rabies is fatal once signs develop.

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Rabies
Global Disease

Estimated gt55,000 deaths annually
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Encephalitis Caused by a Lyssavirus in Fruit Bats
in Australia 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
from Pteropid bats in Australia.Gould AR, Hyatt
AD, Lunt R, Kattenbelt JA, Hengstberger S,
Blacksell SD.Virus Res 199854165-87
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Rabies

• Animal reservoirs maintain and transmit different
  rabies virus variants
• TerrestrialCarnivora (canids, skunks, raccoons,
  mongoose, etc.) and non-terrestrialChiroptera
  (bats)

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Source http//www.rbe.fli.bund.de/About_Rabies/Ep
idemiology.aspx
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• United States confirmed rabid animals
• wildlife domesticated
• In the U.S., wildlife reservoirs maintain rabies
  and infection is transmitted from wildlife to
  other species.

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Animal Rabies in North America

• Reportable disease
• US 6500-9500 rabid animals recognized annually
  in all states except Hawaii 93 wild
• Canada 220-280 rabid animals reported annually

N273
N 7258
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Terrestrial and non-terrestrial rabies
reservoirs
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2007 N2658
1980 translocation by hunters started epizootic
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Raccoons and Rabies

• Raccoons efficiently transmit rabies to skunks,
  beaver, fox, groundhogs, cats, deer dogs, goats,
  deer, horses, pigs, sheep, cattle, rabbits,

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2007 N1478
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Skunks and Rabies

• Skunks transmit rabies to
• badgers, raccoons, other wild animals, cats,
  dogs, humans, cattle, horses,

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• Foxes transmit rabies to coyotes, bobcat, dogs,
  horses, etc

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What accounts for this?
3 different variants
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Bats and Rabies

• gt 1900 rabid bats reported in US during 2007
• Widespread distribution
• Many species affected
• Most bats are healthy- not rabid
• No carrier state
• Predominant cause of human infections in US.

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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

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Rabies in Cats and Dogs

• Spillover infection from wildlife reservoirs
• 2007
• 274 cats
• 84 dogs in US
• for gt decade 31
• Why?

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Rabid catsWalla, Walla 2002British Columbia
2007
All pets including cats SHOULD BE VACCINATED!
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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

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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
  contact
• Cost of PEP 250,000?

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Rabid puppy

• This pup was vaccinated 2weeks before it became
  ill what happened?

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Contagious (virus shedding) period 0-10 days
Rabies Exposure
Symptomatic
Vaccination at Humane society Rescue
Euth/test
Petsmart
Feb/ March
April
Incubation period weeks
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Vaccinate pets before exposure

• A dog, cat, ferret receiving an initial rabies
  vaccine will take about 28 days to develop
  immunity. Subsequent vaccines are boosters.
• After being exposed to a rabid animal a
  vaccinated pet should have an immediate booster
  rabies vaccine (to mount optimal virus
  neutralizing antibody) .

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Rabies Vaccines- Animals

• Domestic parenteral vaccines for dog, cat,
  ferret, horse, cattle, sheep (see Compendium).
• Wild Oral recombinant DNA bait vaccine for
  raccoon, coyote, fox (not used in WA)
• Exotic/wild No licensed vaccine for bats,
  monkeys, llamas, wolf-hybrid(off- label use by
  veterinarians)

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Pacific Northwest(OR, WA, BC) Bat reservoirs of
rabies

• So far, no terrestrial rabies reservoirs
• Spillover infection from bats into other mammals
  including humans

Other wildlife and pets
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Rabies Surveillance

• Rabies surveillance is mostly passive and not
  standardized among states or counties.
• In 2007, the range of rabid animal reports/state
  is 0 (Hawaii) to 969 (Texas)
• reported cases is only fraction of actual
  cases- no accurate incidence or prevalence

http//www.cdc.gov/rabies/docs/rabies_surveillance
_us_2007.pdf
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Rabies Evolving Epidemiology

• Human factors
• 1. Importation of foreign dogs, exotic animals,
  livestock
• 2. Interstate movement of rabies reservoirs
• 3. Better diagnostics
• 4. Improved surveillance of wildlife
• 5. Canine vaccination

• Animal factors
• Evolutionary adaptation of virus in new hosts
• Population density
• Susceptibility
• Reservoir range

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Spit Happens

• History Veterinarian examined, sedated and
  euthanized a llama that was exhibiting abnormal
  behavior.
• Brain tissue sent to veterinary diagnostic lab.
• Laboratory confirmed rabies.

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Site visit to small ranch 5 llamas 2 have
wounds.
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Investigation

• Another llama from same pen died 2 weeks earlier
  of undiagnosed acute illness.
• Exhume for testing.

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Investigation

• Brain tissue from exhumed llama tests positive
  for rabies

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30 days later Three llamas remained
healthyThree 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 nerveall died within
  one month.

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Human Rabies
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• Worldwide, rabies causes an estimated
  30,000-70,000 human deaths annually.
• Asia, Africa,

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• the patient can neither stand nor lie down
  like a madman he flings himself hither and
  tither, tears his flesh with his hands, and feels
  intolerable thirst. This is the most distressing
  symptom for he so shrinks from water and all
  liquids that he would rather die than drink or be
  brought near to water it is then that they bite
  other persons, foam at the mouth, their eyes look
  twisted, and finally they are exhausted and
  painfully breath their last.
• Girolamo Francocastro, 16th century

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Human Rabies, U.S. 1980- 2006N59
WA cases


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Temporal Trends in the Diagnosis of Rabies in the
United States, 1944 to 2002
Rupprecht C and Gibbons R. N Engl J Med
20043512626-2635
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Human Rabies

• Minnesota
• 46 year old male
• Paresthesia RH
• Unsteady gait
• Fever, resp failure
• Steady neuro decline- death 22d
• Handled bat with bare hands 2 months prior

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Rabies

• 10 year old died Sept. 27,2005
• (post hurricane) Mississippi
• No history of sick pets, no animal bite
• Bats in and around home
• Post mortem history bat in bedroom released
  outdoors by the child

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Exposure of hospital staff and family

• 23 family members (including one who was bitten
  by case)
• 32 of 79 health care workers (19 nurses, 4
  physicians, 5 resp therapists, 2 XR techs, 2 lab
  staff)

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Human Rabies Cases, U.S.1980-2005

• 36/56 (64) associated with insectivorous bat
  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

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Human rabies exposure/transmission

• Not all animal bites are rabies exposures.
  However all bites should be evaluated.
• Potential rabies exposure infectious saliva into
  skin or on mucous membrane.

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Post exposure prophylaxis

• Rabies is preventable if vaccine is administered
  before the virus gets into nerve tissue.
• Administration of PEP is not reportable. Approx
  30,000? series/year in US.

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Potential Human Rabies Exposures

• International travelers can be exposed to canine
  rabies
• Some areas are HIGH RISK.
• (2008 Oaxaca exposed case)
• Bites in U.S. risk varies with species, test
  status, and location
• Cryptic human exposure (unknown history of
  rabid animal contact)

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Rabies Post-Exposure Prophylaxis (PEP)

• Vaccine supply has been limited reserve for
  truly exposed
• Cleanse wound immediately.
• When needed, administer PEP as soon after
  exposure as possible.
• Rabies immunoglobulin one dose
• 5 doses of rabies cell culture vaccine

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Rabies and Public Health

• PH (federal, state, local) is involved in every
  aspect of rabies
• Investigation of animal and human cases
• Laboratory testing
• Disease reporting Surveillance, epidemiology
• Animal control may be health or law enforcement
• Provide expert consultation to medical and
  veterinary community
• Media and public education
• Policy, guidelines for control and
  prevention-animals/humans
• Vaccine supply

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Rabies in animals and in humans is a nationally
reportable condition

• All suspected animal and human cases are tested
  by Public health labs and affiliates (some vet
  universities for animal)
• Reporting system clinician (vet, medical) to
  local ph? state ph ? CDC
• Complete investigations (to find exposed people
  and animals) are done on every case.

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Rabies is preventableMedical/ public health
evaluation of animal bites

• Species?
• Bite? Non-bite?
• Place of exposure
• Foreign travel?
• Other US, local
• How was the animal acting?
• Provoked/unprovoked?
• Is animal available for observation- (domestic
  animal)or testing (wild)?

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Encephalitis of unknown origin

• Medical consultation
• Physicians often have ruled out many common
  etiologies
• Rapid, progressive, compatible with rabies-
  transport of test samples to CDC

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Public HealthRabies Control and
PreventionCoordination/partnership

• Health Care Providers
• Veterinarians
• Animal Control
• Wildlife officials and rehabilitators
• Schools, Public, Media.

• Animal Bites Wash wounds and seek medical
  consultation - especially those from 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.
• Dont feed, handle or translocate wildlife

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Example of a rabies surveillance and control
system
Citizen finds sick or dead bat or wild carnivore
calls animal control agency
Veterinarian suspects rabies in a domestic
animal animal is euthanized or dies requests
public health laboratory rabies test
Animal control picks up animal and submits brain
tissue to public health laboratory.
Public health laboratory performs rabies test
Local, state and national rabies databases updated
Results provided to state and local public health
agencies and the submitter (animal control,
veterinarian)
Rabies virus detected
Rabies virus not detected
Animal control evaluates and regulates management
of pet animal exposure(s).
Public health calls citizen to assess any
potential human exposure(s).
No further follow-up
No
Potential human exposure to rabies
Yes
Refer to healthcare provider
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Public Health Rabies Testing

• Direct Fluorescent antibody Gold standard
  diagnostic- very reliable test. Only performed
  at Public Health and few university labs
• Cross sections of fresh brainstem, hippocampus,
  cerebellum.
• Molecular monoclonal antibody and PCR to
  identify rabies virus variant.

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Local, State, National Regulation, policy and
guidance

• Local and state regulations- pet vaccination,
  disease reporting, animal bite reporting, rabies
  exposed pets
• U.S. Animal import regulations
• Guidelines
• Compendium of Animal Rabies Prevention and
  Control
• ACIP- Human Rabies Prevention

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    tragic fact that every day approximately 100
children die of rabies. 
www.rabiescontrol.net - Alliance for Rabies
Control
Global Health
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Importation of Animals
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March 2007

• New Delhi, India
• Veterinarian from WA state volunteer at animal
  shelter
• Adopts 2 street puppies
• Unvaccinated (gt 12 weeks old)
• Unknown health histories
• Acting normally at time of rescue
• Reports of puppy being picked on by other
  street dogs

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Source http//www.rbe.fli.bund.de/About_Rabies/Ep
idemiology.aspx
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Timeline
Taken to Olympic Penninsula
Bites vet 2nd puppy
Dies. Rabies test positive
Pup 1 gnaws on kennel, breaking/losing deciduous
teeth
Neuro signs noticed
2 pups and vet arrive in Seattle, pass through US
Customs
Pup 1 begins to regurgitate
Pup 1 adopted certified for interstate travel
Flown to Juneau
14 15 16 19
20 21 22 23
March, 2007
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Imported rabid puppy, 2007

• Second pup euthanized and tested
• 8 people received PEP
• Customs protocols reviewed
• Health certificate for interstate travel should
  not have been given

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Importation of rabid dogs/cats to US

• 1986 New York Dog, 4 months old, West Africa
  (http//www.cdc.gov/mmwr/preview/mmwrhtml/00000874
  .htm)
• 1987 New Hampshire Dog, 5 months old, Mexico
  (http//www.cdc.gov/mmwr/preview/mmwrhtml/00001275
  .htm)
• 1987 California Cat, unknown age, Mexico
  (http//www.cdc.gov/mmwr/preview/mmwrhtml/00001275
  .htm)
• 1995 California Dog, 4 weeks old, Mexico
• 2004 California Dog, 3 months old, Thailand
• 2004 Massachusetts Dog, 3 months, Puerto Rico
• 2007 WA and Alaska Dog, 3 months, India

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• There is a thriving international trade in exotic
  pets, birds, and puppies (gt280,000
  dogs and 183,000 wild animals imported to US
  annually).
• Imported pets may be infected with diseases that
  put animals or the public at risk.
• Current federal regulations are inadequate for
  preventing the introduction of animal-borne
  diseases.
• Veterinarians and others must remain vigilant so
  they can recognize potential threats quickly.
• The public and health care costs of combating
  rabies once it is established in a new area are
  very high.

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Deriengue Imported cases of Bovine Paralytic
Rabies transmitted by vampire bats in Central
America
ARIZONA
MEXICO
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Rabies translocation/exportation events
Coyote RVV Texas to Florida 1994 Raccoon RVV
Florida to Virginia, 1978 Hunters Coyote
RVV Texas to Alabama (1993) E. fuscus Canada
to Germany (1986) E. fuscus Massachusetts to
Denmark (1994) Researchers E. fuscus MI/CA car
container to Hawaii, (1991) Rupprecht CE, Smith
JS, Fekadu M, Childs JE. The ascension of
wildlife rabies a cause for public health
concern or intervention? Emerg Infect Dis
19951107--14. 1995-2000 AZ- 2 steers with
deriengue (Mexico-separate incidents) Dairy cow,
horse from midwest
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Summary

• Rabies is an important zoonoses worldwide
• Global reservoirs dogs, wildlife, bats
• North America reservoirs raccoon gtbatgtskunkgtfox
• Spillover Cats 1
• Public health has a primary role laboratory
  testing, surveillance, investigation, prevention,
  education, control, regulation, and policy.
• Movement of animals globally and nationally
  presents constant risk of introduction of rabies
  virus variants to new geographic areas.

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• http//www.cdc.gov/ncidod/dvrd/rabies/