Current Issues in Rabies

Rabies Current Issues in Rabies Mira J. Leslie, DVM, MPH April 7, 2008 Among the oldest infectious diseases known. MOST FATAL disease known Prevention costs: health care, animal control, public health, laboratory. ETIOLOGY 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 Very few areas are rabies-free Rabies free means free of terrestrial rabies Surveillance for rabies is passive and variable Rabhas Sanskrit to do violence 30 cent BC Illiad- Hector is mad dog Egyptian dog Siriusfurious dog Celsius, Rome, 1 st cent. AD human rabies Centuries of Fear New causative agents of rabies continue to emerge as shown by the recent description of four novel lyssaviruses from bats in Eurasia, Aravan (ARAV), Khujand (KHUV), Irkut (IRKV), and West Caucasian bat virus (WCBV). Virus Res. 2005 Jul;111(1):44-54. 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 1

Rabies All warm-blooded vertebrates are susceptible to experimental infection Reservoirs consist of Carnivora (canids, skunks, raccoons, mongoose, etc.) and Chiroptera (bats) Burden More than 55,000 human rabies deaths per year Most occur in developing countries Millions of human exposures every year The domestic dog is the single most important animal reservoir Wildlife is an important source, especially in developed countries where canine rabies is controlled Rabies Rabies is a viral disease of the central nervous system. Rabies is transmitted when infective saliva is inoculated under skin or into a mucous membrane. Rabies is fatal once signs develop. Animal bites and rabies Animal bites are common medical conditions. Most often dogs, cats. Some involve exposures to wild mammals (other than rodents and rabbits). Terrestrial rabies reservoirs in North America: (raccoons, skunks, coyote, fox) Non- terrestrial rabies reservoirs: many species of bats. Virus infects and moves retrograde in nerve tissue, to CNS. 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:? 2

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. United States confirmed rabid animals >90% wildlife In the U.S., wildlife reservoirs maintain rabies and infection is transmitted from wildlife to other species. **Grounded bats. Variable symptoms In 2006 N=6940 Foxes transmit rabies to coyotes, bobcat, dogs, horses.llamas, etc Rabies Reservoirs: -terrestrial and non-terrestrial Molecular Epi: Rabies Virus Variants 1980: translocation by hunters started epizootic 3

Raccoons and Rabies Raccoons efficiently transmit rabies to: skunks, beaver, fox, groundhogs, cats, dogs, goats, deer, horses, pigs, sheep, cattle, rabbits, cats One known human infection, VA 2006: N=1494 Skunks and Rabies Skunks transmit rabies to : badgers, raccoons, other wild animals, cats, dogs, humans, cattle, horses, 3 different variants What accounts for this? > 1300 rabid bats reported in US during 2004 (>1400 in 2005; 1694 in 2006) Widespread distribution Most bats are healthy- not rabid No carrier state Predominant cause of human infections in US. Bats and Rabies 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 4

Rabies in Bats Affects many species Big brown (E. fuscus), Mexican free-tail, Myotis. Solitary species (13%)> colonial species (5%) Rabies in Domestic Animals In 2006, 7.9% (547/6943) of reported rabid animals were cats, dogs, cattle, horses, goats, etc. PA>VA>TX> NY>NC Cats are also infected by bats Cats are the domestic animal most commonly recognized as rabid in the US. Walla-Walla: 2002 British Columbia: 2007 The majority of rabies spillover into domestic animals is in areas with terrestrial rabies reservoirs CATS SHOULD BE VACCINATED! [N=71 in 2006] Canine rabies virus variant is eliminated from US! All endemically exposed cases were due to spillover infection of rabies virus variants from wildlife. March 2007 New Delhi, India Washington state veterinarian: volunteer at foreign animal shelters frequently estimates she s been on 60 trips 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 5

Rabid Puppy Import Timeline 2 pups and vet arrive in Seattle, pass through US Customs Taken to Olympic Penninsula Pup 1 begins to regurgitate Bites vet & 2 nd puppy Pup 1 gnaws on kennel, losing multiple deciduous teeth Adopted & certified for interstate travel to AK Flown to Juneau Dies and is tested for rabies. Results are positive Neuro signs noticed Source: http://www.rbe.fli.bund.de/about_rabies/epidemiology.aspx 14 15 16 19 20 21 22 23 March, 2007 Imported rabid puppy 2007 Canine Rabies Importation, 2004 Second pup euthanized and tested 8 people received PEP Customs protocols reviewed Health certificate for interstate travel should not have been given June MA May Laredo, March Documented rabid dog/cat importation 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 Dog imports raise fears of a resurgence of disease ABC NEWS: Oct 24, 2007 300,000 Imported Puppies Prompt Rabies Concerns CDC, After Declaring Canine Rabies Eradicated, Now Looks at New, Stricter Rules By SUSAN DONALDSON JAMES Oct. 24, 2007 Just last month the Centers for Disease Control and Prevention declared victory over canine rabies in the United States -- a fatal virus that kills 55,000 people a year globally. That declaration may have been premature. By Alan Gomez,USA Today: Oct 21, 2007 When animal shelters started going overseas to fill their emptying kennels, some worried the imported strays would bring foreign diseases and even rabies into the USA. 6

Imported Pets a Growing Business in U.S. Dec. 17, 2007 The Associated Press The Internet is full of sites that claim to be selling healthy local puppies, but actually deal in imports from Eastern Europe, Russia, Asia, and Central America. Rescue groups tapping Central America for dogs. Groups of unaccompanied pups coming in from rabies endemic areas. The Border Puppy Task Force in California estimates that 10,000 puppies entered San Diego County from Mexico in just one year. These puppies are sold in shopping center parking lots, on the street, and in pet stores. Rabies Vaccines- Animals Domestic: parenteral vaccines for dog, cat, ferret, horse, cattle, sheep (see Compendium for list). Wild: Oral recombinant DNA bait vaccine for raccoon, coyote, fox (ORV used in major rabies control programs) Exotic/wild: No licensed vaccine for bats, monkeys, llamas, wolfhybrid (off- label use by veterinarians) Deriengue Imported cases of Bovine Paralytic Rabies transmitted by vampire bats in Central America Cattle are usually infected by rabid skunks or raccoons, bats, foxes. ARIZONA MEXICO Rabies surveillance is mostly passive and not standardized among states or counties. In 2006, the range of rabid animal reports/state is 0 (Hawaii) to 890 (Texas). 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 http://www.cdc.gov/rabies/docs/rabies_surveillance_us_2006.pdf 7

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 Rabies in animals and in humans is a nationally notifiable condition All suspected animal and human cases are tested by Public health labs and affiliates (some universities) Reporting system: clinician (vet, medical) to local ph state ph CDC Confirmed cases have complete investigations (to identify exposed people and animals). 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 for rabies: Gold standard diagnostic- very reliable test. [Only performed at public health and few university labs] Cross sections of fresh brainstem, hippocampus, cerebellum. Monoclonal antibody and PCR to identify rabies virus variant. Rabies Transmission in Washington Rabies in WA Bats are only reservoir. 98% of recognized rabid animals in WA are bats. From 1990 through 2007: 317 rabid/4584 tested bats. (6.9%) Other wildlife and pets This is a skewed population of sick and injured bats; less than 1% of healthy bats are infected with rabies. 8

Rabies testing varies from state to state. Differences in findings often due to different systems WA Resources limit animal rabies testing to human exposures- No surveillance testing 300-500 animals tested annually Arizona Surveillance submissions encouraged 2500 animals tested annually Zoonotic Disease Surveillance Surveillance in wildlife is challenging Resource intensive For rabies, medical decisions should be based on surveillance data if animal not available to test, however that data may not be available. Terrestrial carnivores (not rodents, rabbits, squirrel) WA data rabies testing: <3 skunk/year (27/10yrs) <10 raccoon/year (91/10 yrs) < 4 other carnivore (coyote, fox, bobcat)/year (34/10yrs) Rabies surveillance is not Testing road-kill except in the face of ongoing epizootic Trapping animals for testing Testing nuisance animals (wild or domestic) (In OR: 27% of tested foxes are rabid) Rabies surveillance is Routine laboratory testing of animals that have potentially exposed people AND neurologically impaired animals; AND wildlife that expose pets, AND wildlife reported to be sick or freshly dead without trauma. Surveillance infrastructure Requires citizen awareness reporting of sick and dead wildlife, pet-wildlife interaction. Animal control capacity for timely response. Ability to transport animal heads from rural areas. Laboratory capacity for testing. 9

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 Results provided to state and local public health agencies and the submitter (animal control, veterinarian) Local, state and national rabies databases updated Human Rabies Rabies virus not detected No further follow-up No Rabies virus detected Public health calls citizen to assess any potential human exposure(s). Potential human exposure to rabies Animal control evaluates and regulates management of pet animal exposure(s). Yes Refer to healthcare provider Worldwide, rabies causes an estimated 30,000-70,000 human deaths annually. India, China, 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, 16 th century Human Rabies, U.S. 1980-2006 WA cases Human rabies deaths, US, 2006 IN:10 year old F - bat in house handled by the child 3-4 months prior to clinical illness TX: 16 year old M- bat in bedroom 4 wks prior to illness CA: 11 year old M- bitten by dog in Philippines 2 years prior to illness. 10

Human Rabies Very difficult to recognize early Monitoring for unexplained illness and death- rapidly progressive encephalitis Can involve many health care worker exposures (low risk) Often are diagnosed post mortem May be missed if no autopsy on brain Human Rabies Cases, U.S. 1990-2006 Only one human rabies death raccoon RV variant 37/51 (72.5%) associated with insectivorous bat rabies virus variants Many 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 May/June 2004,TX 20 yr M Donor Human Rabies Via Transplanted Organs/Tissues Lung (died during surgery) Liver Kidney Kidney Arterial Graft Dec 2004-2005: Germany 26 yr F donor exposed to rabid dog in India. Transplant lung, kidneys, pancreas = 3 rabies deaths Transplanted corneas and liver recipients survived Human rabies exposure/transmission Not all animal bites are rabies exposures. However all bites should be evaluated. Careful exposure assessments and public education especially in situations where large # people exposed. Mass exposure events 465 PEP: County fair- goat, NYS, 1996 665 PEP: Pet shop kitten, NH 1994 >100 PEP: Petsmart puppy, AZ 2002 >120 PEP: Raw milk- dairy cows, OK 2005, MA 1996 and 1998 Tennessee Walking Horse competition, 2006, (only 24) Schools (raccoon, bats), roadside zoo (bear), campgrounds... ** PEP availability issues Many exposures, little disease Rabies is preventable through evaluation/management 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)? 11

Rabies PEP Potential Human Rabies Exposures Individuals without previous vaccination Wound care 5 doses rabies vaccine day 0,3,7,14,28 One dose HRIG by body weight Only 2 manufacturers Issues with vaccine supply- recalls Recent workgroup to develop guidance for use during shortages International travelers/foreign nationals can be exposed to canine rabies Some areas are HIGH RISK. U.S.: wildlife exposures, mass exposures to domestic rabid animals Cryptic human exposure (unknown history of rabid animal contact) Rabies Control and Prevention Public Education Animal Bites: Wash wounds and seek medical consultation. Higher risk from bats/wild animals and foreign dogs Control rabies in pets: Vaccinate pets Keep pets away from wildlife (bats, raccoons..) Follow leash laws Control feral and stray animals Wildlife: Avoid contact with sick and injured wild animals. Don t feed, handle or translocate wildlife National Rabies Management Guidance documents Compendium of Animal Rabies Prevention and Control- annual update www.nasphv.org ACIP- Human Rabies Prevention- New version imminent (1999 latest) Summary Summary Rabies circulates in reservoir species of wildlife, (U.S.= insectivorous bats, skunks, raccoons, foxes) and spills over into other mammals. Reservoirs of rabies do not carry rabies- they become infected and effectively transmit virus before they die. Public health has a role in every aspect of this complex zoonoses. Rabies is a model for zoonotic disease prevention and control. Movement of animals globally and nationally presents constant risk. 12

PH Response to a Rabid Kitten, 2007 Softball tournament 60 teams x 12 players Spectators, friends, families, coordinators Rabid kitten +2 others? PH Response to Rabid kitten Impressions/observations? How did this unfold? What were the challenges? 38/60 teams reported exposure; 27 individuals received PEP 13