current issues in rabies mira j. leslie, dvm, mph april 6, 2009
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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
•
Global Disease
Estimated >55,000 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 1998;54:165-87
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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/Epidemiology.aspxSource: http://www.rbe.fli.bund.de/About_Rabies/Epidemiology.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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N= 7258
N=273
Reportable disease
•US: 6500-9500 rabid animals recognized annually in all states except Hawaii; 93% wild
•Canada: 220-280 rabid animals reported annually
Animal Rabies in Animal Rabies in North AmericaNorth America
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Terrestrial** and non-terrestrial rabies reservoirs
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1980: translocation by hunters started epizootic
2007: N=2658
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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: N=1478
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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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SkunkRaccoon
Coyote
Skunk
Fox
Skunk
Fox
Fox
3 different variants
What accounts for this?
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Bats and Rabies• > 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 > decade 3:1
• Why?
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Rabid catsWalla, Walla: 2002
British 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
April
RabiesExposure
Symptomatic
Vaccination at Humane society & Rescue
Euth/testPetsmart
Incubation period = weeks
Feb/ March
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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 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
Rabies Surveillance
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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
1. Evolutionary adaptation of virus in new hosts
2. Population density
3. Susceptibility
4. 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
One week later: Wounded llama dies. Rabies Confirmed.
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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 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- 2006
N=59
0
1
2
3
4
5
6
7
8
9 Transplant
Raccoon
BatForeignDog
WA cases
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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
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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 Prevention
Coordination/partnership
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.• Don’t feed, handle or translocate wildlife
•Health Care Providers•Veterinarians•Animal Control•Wildlife officials and rehabilitators•Schools, Public, Media….
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Citizen finds sick or dead bat or wild carnivore; calls animal control agency
Animal control picks up animal and submits brain tissue to public health laboratory.
Rabies virus not detected
Results provided to state and local public health agencies and the submitter (animal control, veterinarian)
Rabies virus detected
Potential human exposure to rabies
Yes
No
Local, state and national rabies databases updated
Veterinarian suspects rabies in a domestic animal; animal is euthanized or dies; requests public health laboratory rabies test
No further follow-up
Public health calls citizen to assess any potential human exposure(s).
Animal control evaluates and regulates management of pet animal exposure(s).
Example of a rabies surveillance and control system
Public health laboratory performs rabies test
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 (> 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/Epidemiology.aspxSource: http://www.rbe.fli.bund.de/About_Rabies/Epidemiology.aspx
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Timeline
14 15 16 19 20 21 14 15 16 19 20 21
22 23 22 23
March, 2007 March, 2007
Taken to Olympic
Penninsula
Pup 1 begins to regurgitate
Bites vet & 2nd puppy
Pup 1 gnaws on kennel,
breaking/losing deciduous
teeth
Flown to Juneau
Pup 1 adopted & certified for
interstate travel
2 pups and vet arrive in Seattle,
pass through US
Customs
Neuro Neuro signs signs
noticednoticed
Dies. Rabies test positive
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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 (>280,000 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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DeriengueImported cases of Bovine Paralytic Rabies transmitted by vampire bats in Central America
ARIZONA
MEXICO
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Coyote RVV: Texas to Florida 1994 Raccoon RVV: Florida to Virginia, 1978 HuntersCoyote RVV: Texas to Alabama (1993) E. fuscus Canada to Germany (1986)E. fuscus Massachusetts to Denmark (1994) ResearchersE. 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 1995;1:107--14.
[1995-2000: AZ- 2 steers with deriengue (Mexico-separate incidents); Dairy cow, horse from midwest]
Rabies translocation/exportation events
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Summary• Rabies is an important zoonoses worldwide
– Global reservoirs: dogs, wildlife, bats
– North America reservoirs: raccoon >bat>skunk>fox
– 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/