Slide 1:Current Issues in Rabies

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

Slide 2: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

Slide 3: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

Slide 4:Rabies Disease

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

Slide 6: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: ?

Slide 7: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

Slide 8: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.

Slide 9:Rabies

Global Disease Estimated >55,000 deaths annually

Slide 10: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

Slide 11: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.aspx

Slide 13:United States confirmed rabid animals wildlife domesticated In the U.S., wildlife reservoirs maintain rabies and infection is transmitted from wildlife to other species.

Slide 15:Terrestrial** and non-terrestrial rabies reservoirs

Slide 17:Raccoons and Rabies

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

Slide 19:Skunks and Rabies

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

Slide 20:Foxes transmit rabies to coyotes, bobcat, dogs, horses, etc

Slide 22: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.

Slide 23: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

Slide 24:Rabies in Cats and Dogs

Spillover infection from wildlife reservoirs 2007: 274 cats 84 dogs in US for > decade 3:1 Why?

Slide 25:Rabid catsWalla, Walla: 2002British Columbia: 2007

All pets including cats SHOULD BE VACCINATED!

Slide 26: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

Slide 27: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?

Slide 28:Rabid puppy

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

Slide 29:Contagious (virus shedding) period = 0-10 days

April Rabies Exposure Symptomatic Vaccination at Humane society & Rescue Euth/test Petsmart Incubation period = weeks Feb/ March

Slide 30: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) .

Slide 31: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)

Slide 32: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

Slide 33:Rabies Surveillance

Slide 34: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

Slide 35: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.

Slide 36:Site visit to small ranch; 5 llamas; 2 have wounds.

Slide 37:Investigation 

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

Slide 38:Investigation

Brain tissue from exhumed llama tests positive for rabies

Slide 39: 30 days later: Three llamas remained healthyThree llamas died of fox variant of rabiesOne llama was euthanized due to wound/exposure

Slide 40: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.

Slide 41:Human Rabies

Slide 42:Worldwide, rabies causes an estimated 30,000-70,000 human deaths annually. Asia, Africa,…

Slide 43:“… 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

Slide 44:Human Rabies, U.S. 1980- 2006N=59

WA cases

Slide 45:Figure 1. Temporal Trends in the Diagnosis of Rabies in the United States, 1944 to 2002.Figure 1. Temporal Trends in the Diagnosis of Rabies in the United States, 1944 to 2002.

Slide 46: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

Slide 47: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

Slide 48: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)

Slide 49: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

Slide 50: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.

Slide 51: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.

Slide 52: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)

Slide 53: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

Slide 54: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

Slide 55: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.

Slide 56: 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)?

Slide 57: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

Slide 58:Public HealthRabies Control and PreventionCoordination/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….

Slide 60: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.

Slide 61: 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

Slide 63:Importation of Animals

Slide 64: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.aspx

Slide 66:Timeline

14 15 16 19 20 21 22 23 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 signs noticed Dies. Rabies test positive Very depressed T: 98.6? P: 100-110 R: 40 No PLR; pupils fixed and dilated No palpebral reflex Later that night: Unable to ambulate due to severe ataxia, periods of continuous unprovoked barking followed by unsuccessful attempts to stand and labored respirations Episodes lasted several minutes; then longer periods of relative calm CDC results—canine rabies variant found in N. India 8 persons prophylaxed, 2nd puppy euthanizedVery depressed T: 98.6? P: 100-110 R: 40 No PLR; pupils fixed and dilated No palpebral reflex Later that night: Unable to ambulate due to severe ataxia, periods of continuous unprovoked barking followed by unsuccessful attempts to stand and labored respirations Episodes lasted several minutes; then longer periods of relative calm CDC results—canine rabies variant found in N. India 8 persons prophylaxed, 2nd puppy euthanized

Slide 67: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

Slide 68: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

Slide 69: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.

Slide 71:Rabies translocation/exportation events

Slide 72: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.

Slide 73: http://www.cdc.gov/ncidod/dvrd/rabies/