Current Issues in Rabies Mira J. Leslie, DVM, MPH

April 6, 2009

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

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

Rabies Disease

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

ZOONOSES

Inoculated virus moves in nerve tissue, not blood.

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: ?

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

Rabies

•

                                                      

                                                                                   

                                                      

                                                                                  

Global Disease

Estimated >55,000 deaths annually

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

Rabies

• Animal reservoirs maintain and transmit different rabies virus variants

• TerrestrialCarnivora (canids, skunks, raccoons, mongoose, etc.) and non-terrestrialChiroptera (bats)

Source: http://www.rbe.fli.bund.de/About_Rabies/Epidemiology.aspxSource: http://www.rbe.fli.bund.de/About_Rabies/Epidemiology.aspx

United States confirmed rabid animals wildlife domesticated

• In the U.S., wildlife reservoirs maintain rabies and infection is transmitted from wildlife to other species.

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

Terrestrial** and non-terrestrial rabies reservoirs

1980: translocation by hunters started epizootic

2007: N=2658

Raccoons and Rabies

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

2007: N=1478

Skunks and Rabies

• Skunks transmit rabies to :

badgers, raccoons, other wild animals, cats, dogs, humans, cattle, horses, …

Foxes transmit rabies to coyotes, bobcat, dogs,

horses, etc

SkunkRaccoon

Coyote

Skunk

Fox

Skunk

Fox

Fox

3 different variants

What accounts for this?

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.

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

Rabies in Cats and Dogs

• Spillover infection from wildlife reservoirs

• 2007: – 274 cats – 84 dogs in US

• for > decade 3:1

• Why?

Rabid catsWalla, Walla: 2002

British Columbia: 2007

All pets including cats SHOULD BE VACCINATED!

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 contact

Cost of PEP: $250,000?

Rabid puppy• This pup was

vaccinated 2weeks before it became ill: what happened?

Contagious (virus shedding) period = 0-10 days

April

RabiesExposure

Symptomatic

Vaccination at Humane society & Rescue

Euth/testPetsmart

Incubation period = weeks

Feb/ March

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) .

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)

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

• 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

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

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.

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

Investigation

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

• Exhume for testing.

Investigation• Brain tissue from

exhumed llama tests positive for rabies

One week later: Wounded llama dies. Rabies Confirmed.

30 days later: Three llamas remained healthy

Three llamas died of fox variant of rabiesOne llama was euthanized due to wound/exposure

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.

Human Rabies

• Worldwide, rabies causes an estimated 30,000-70,000 human deaths annually.

– Asia, Africa,…

• “… 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

Human Rabies, U.S. 1980- 2006

N=59

0

1

2

3

4

5

6

7

8

9 Transplant

Raccoon

BatForeignDog

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

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

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

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)

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

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.

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.

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)

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

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

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.

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)?

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

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….

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

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.

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

    tragic fact that every day approximately 100 children die of rabies. 

www.rabiescontrol.net - Alliance for Rabies Control

Global Health

Importation of Animals

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

Source: http://www.rbe.fli.bund.de/About_Rabies/Epidemiology.aspxSource: http://www.rbe.fli.bund.de/About_Rabies/Epidemiology.aspx

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

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

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

• 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.

DeriengueImported cases of Bovine Paralytic Rabies transmitted by vampire bats in Central America

ARIZONA

MEXICO

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

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.

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