Infectious

Epidemiology of the Rabies Virus

Objectives
Describe epidemiology of rabies virus Describe transmission and pathogenesis of rabies virus Outline management of animals potentially exposed to rabies Outline management of animals that potentially expose humans to rabies

The Rabies Virus

Lyssavirus of the Rhabdoviridae family Bullet-shaped, RNA virus Infects only mammals Various strains of rabies virus exist

RABIES VIRUS

Rabies Epidemiology — World >55,000 deaths worldwideMainly Africa and Asia60–70% of human cases are children 5–15 years of age~98% of human cases caused by dog bites

Rabies Epidemiology — United States Human rabies deaths relatively rare 4 deaths in 2009 >90% of animal rabies cases occur in wildlife 6,690 animal rabies cases in 2009 92% wildlife animals 8% domestic animals Rabies annual prevention costs ~$300 million

one can get Rabies from these animals

* Dogs
Cats
Wolves
Cattle
Monkeys
Sheep / Goats
Mongoose
Pigs
Donkeys
Horses
Foxes / Jackals
Elephants

* In India Humans get Rabies Usually from

Dogs
Cause > 90% of the Human cases
Cats
3 – 5% of Human cases

In India these animals are NOT known to spread Rabies

* Rats
Bats
Birds


Rabies Epidemiology — West Virginia Most animal rabies cases occur in wildlife Cat most common domestic animal to be rabies-positive Raccoon-strain rabies endemic to eastern portion of state Bat strain found throughout state Most cases occur during warm-weather months

Human rabies

Clinical symptoms
Early stage (1-3days) fever(37.5-38) vomit wound: pain, red, itching Exciting stage(1-3days) fever(39-40) hydrophobia: pharyngeal muscle cramp, dyspnea dehydration Paralytic stage(15-20hs) nerve fiber paralysis respiratory and circulatory failure death


Clinical forms of rabies
encephalitic ~ 80% paralytic ~ 20%

Encephalitic rabies

prodromal symptoms paresthesias/pain/pruritus at site of bite episodes of generalized arousal or hyperexcitability separated by lucid periods autonomic dysfunction hydrophobia

Paralytic rabies

Evaluation of Animal
Recommendation
Healthy and available for 10 days observation
No treatment unless animal develops clinical signs of rabies
Rabid or suspected rabid
Immediate treatment*
Unknown (e.g., escaped)
Consult local public health department
*Discontinue treatment if tests on animal prove negative.
Rabies postexposure guide: exposure to dogs, cats, and ferrets

Recommended prophylaxis in exposed individuals not previously vaccinated against rabies

Immediate thorough cleansing of all wounds with soap and water. Tetanus prophylaxis; antibiotics
Wound site(s)
MMWR 48: RR-1, 1999
IM (1 mL) in the deltoid area on days 0, 3, 7, 14, and 28
Rabies Vaccine
20 IU/kg body weight
Human Rabies Immune Globulin (RIG)
As much of the RIG as possible should be infiltrated in wound(s) The remainder should be given IM  at a site distant from vaccine

Rabies Vaccines Available in Canada

MMWR;48:RR-1, January 8, 1999 Product package inserts, 2006
Novartis (Merck Frosst) primary chick embryo fibroblasts PCECV
Sanofi Pasteur MRC-5 human lung cell line HDCV

Manufacturer Cell culture Common designation

Populations at increased risk of exposure to rabies
Rabies research laboratory workers Veterinarians, staff, veterinary students Animal control and wildlife workers Bat handlers Spelunkers Travellers to certain rabies-endemic areas
MMWR 48: (RR-1), 1999

Assessing the Rabies Risk for Travelers

Destination Duration of travel Anticipated activities
Access to medical care and appropriate PEP biologics

Preexposure rabies prophylaxis

3 doses of rabies vaccine (days 0, 7, and 21 or 28)May check rabies antibody titre periodically – want >0.5 IU/mLafter a rabies exposure:2 doses of IM rabies vaccine (days 0 and 3)no HRIG

Day 0 7 21 28

Pre-exposure rabies prophylaxis
Tissue culture vaccine: 1 dose IM or 0.1 ml ID
If CHLOROQUINE malaria prophylaxis, give IM only If immunosuppressed check neut. Antibody titre ≥ 0.5 IU/ml HIV positive patients - CD4 counts <300 may be unresponsive Modified from MJ Warrell, University of Oxford

Photo courtesy of Claudius Malerczyk (Novartis)

Rabies Transmission
Saliva from bite of infected animal Scratch Theoretical risk Saliva or neural tissue contact with mucous membrane (mouth, nose) Saliva or neural tissue introduced into fresh, open wound*
* Fresh, open wound is defined as wound that has bled in past 24 hours



Rabies Pathogenesis
Virus introduced through bite wound, open skin wound, or mucous membrane Travels along nerves from site of bite to brain Virus multiplies in brain leading to inflammation Virus moves from brain to salivary glands and saliva where virus is shed

Rabies Pathogenesis

Virus introduced through bite wound, open skin wound, or mucous membrane Travels along nerves from site of bite to brain Virus multiplies in brain leading to inflammation Virus moves from brain to salivary glands and saliva where virus is shed

Rabies Incubation Period

Time between bite and appearance of symptoms Weeks to months No risk of rabies transmission from infected animal during incubation period Used to establish confinement periods for animals exposed to potentially rabid animals

Rabies Diagnosis

Animal diagnosis Post-mortem testing Direct Fluorescent Antibody (DFA) test Antigen of virus in brain tissue Human diagnosis Several tests required for ante-mortem diagnosis Saliva, serum, cerebrospinal fluid, hair follicle from nape of neck

Rabies Treatment and Prevention in Humans

No effective treatment once clinical signs appear Rabies post-exposure prophylaxis (PEP) given before onset of symptoms is nearly 100% effective Rabies PEP Wound cleansing Rabies Immunoglobulin (RIG) Rabies Vaccination No time limit to give PEP


Rabies PEP — Wound Cleansing Should occur as quickly as possible after wound received Soap and water or povidone-iodine


Rabies PEP — RIG Given only once with first vaccine dose If not given with first vaccine dose, can be given up to 7 days after first vaccine dose received If person has previously received PEP or pre-exposure prophylaxis, RIG should not be given

Rabies PEP — Vaccination Previously unvaccinated persons get 4 doses Days 0, 3, 7, and 14 5th dose dropped from vaccine schedule Intramuscular injections Previously vaccinated persons get 2 doses Days 0 and 3 No RIG given

Rabies Pre-exposure Prophylaxis

Recommended for certain high-risk groups Veterinarians, wildlife biologists, animal control personnel 3 vaccine doses Days 0, 7, and 21 or 28 Does not eliminate need for medical care after an exposure

Rabies Treatment and Prevention in Animals

No treatment for animal rabies No post-exposure prophylaxis for animals Routine vaccination is the only way to prevent animal rabies Vaccination schedule for dogs and cats First vaccine at 3 months of age Booster vaccine 1 year later Vaccinate every 3 years after this

Management of Animals Potentially Exposed to Rabies

Vaccinated cats, dogs, ferretsRabies booster immediately45 day observationUnder owner’s controlAny sign of illness should be reported and animal evaluated by a veterinarian

Management of Animals Potentially Exposed to Rabies

Unvaccinated dogs, cats, ferrets Euthanasia Strict isolation for 6 months Confinement in an enclosure that precludes direct contact with people or other animals Rabies vaccine upon entry or 1 month prior to release Any sign of illness should be reported and animal evaluated by a veterinarian

Management of Animals Potentially Exposed to Rabies

Expired vaccinations in dogs, cats, ferrets Evaluated on a case-by-case basis Information to consider Severity of exposure Time lapsed between vaccinations Number of previous vaccinations Current health status Rabies epidemiology

Management of Animals Potentially Exposed to Rabies

Vaccinated livestock Rabies booster vaccine immediately 45 day observation Multiple rabid animals in a single herd is unusual Restriction of entire herd usually not necessary Coordinate with WV Dept. of Agriculture

Management of Animals Potentially Exposed to Rabies

Unvaccinated livestock Euthanasia Confined under close observation for 6 months Any signs of illness should be reported and animal euthanized and tested for rabies Vaccination during confinement can be done Coordinate with WV Dept. of Agriculture

Management of Animals Potentially Exposed to Rabies

Other animals Consider on case by case basis Euthanasia generally recommended

Management of Animals that Potentially Expose Humans

Dogs, Cats, Ferrets Owned animals should be observed for 10 days Rabies vaccination not recommended during this time Strays should be euthanized and tested 10 day quarantine can be done if resources allow If not available for testing, PEP should be considered based on rabies epidemiology of area, bite circumstances, etc.

Management of Animals that Potentially Expose Humans

Exotic mammalian pets No established rabies observation period for animals except dogs, cats, ferrets Consider on case-by-case basis Information to consider Type of animal Rabies epidemiology of area Bite circumstances

Management of Animals that Potentially Expose Humans

Livestock Not high risk for transmitting rabies Healthy and available animals can be observed for 14 days Unknown shedding period of rabies virus in saliva Euthanasia and testing is other option Coordinate with WV Dept of Agriculture

Management of Animals that Potentially Expose Humans

Wildlife If available, euthanize and test immediately If unavailable, PEP should be considered based on Type of animal Rabies epidemiology of area Bite circumstances

Management of Animals that Potentially Expose Humans

Small mammals are considered low risk for rabies Not been found to cause human rabies in US PEP not usually recommended for these exposures unless animal was sick and rabies activity is high in the area Groundhogs/woodchucks may pose greater risk Special consideration for bats

Rabies Resources

www.cdc.gov/rabies ACIP recommendations Compendium of Animal Rabies Prevention and Control, 2008 WV Rabies Surveillance, Management, and Control Manual (DC-4)

Rabies Summary

Human rabies rare in US and WV Most rabies cases occur in wildlife in US and WV Transmission occurs through introduction of infectious saliva or neural tissue into the body Human prevention based on rabies PEP Animal prevention based on rabies vaccination

Animal Management Summary

Management of animals potentially exposed to rabies depends on vaccination status and type of animal exposed Management of animals that expose humans to rabies depends on type of animal, ownership status of animal, and other factors