1. Epidemiology of the Rabies Virus

2. 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

3. The Rabies Virus Lyssavirus of the Rhabdoviridae family
Bullet-shaped, RNA virus
Infects only mammals
Various strains of rabies virus exist

4. RABIES VIRUS

7. Rabies Epidemiology — World
>55,000 deaths worldwide
Mainly Africa and Asia
60–70% of human cases are children 5–15 years of age
~98% of human cases caused by dog bites

8. 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

9. Map of terrestrial rabies reservoirs in the United States during 2009
Map of terrestrial rabies reservoirs in the United States during Raccoon rabies virus variant is present in the eastern United States, Skunk rabies in the Central United States and California, Fox rabies in Texas, Arizona, and Alaska, and Mongoose rabies in Puerto Rico.

11. one can get Rabies from these animals
Dogs
Cats
Monkeys
Wolves
Cattle
Sheep / Goats
Mongoose
Pigs
Donkeys
Horses
Foxes / Jackals
Elephants

12. In India Humans get Rabies Usually from
Dogs
Cats
3 – 5% of Human cases
Cause > 90% of the Human cases

13. In India these animals are NOT known to spread Rabies
Birds
Rats
Bats

14. 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

16. Human rabies
Unusual – consciousness preserved until relatively late. Almost always fatal. In North America, there is usually no history of an animal bite.

17. 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

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

19. Encephalitic rabies prodromal symptoms
paresthesias/pain/pruritus at site of bite
episodes of generalized arousal or hyperexcitability separated by lucid periods
autonomic dysfunction
hydrophobia
Autonomic features: hypersalivation, gooseflesh, cardiac arrhythmias, and priapism in males.

20. Paralytic rabies paresthesias/pain/pruritus at site of bite
early flaccid muscle weakness
often begins in bitten extremity
progresses to produce quadriparesis
bilateral facial weakness
sensory examination is usually normal
sphincter involvement
fatal outcome
often misdiagnosed as Guillain - Barré syndrome

21. Rabies postexposure guide:
exposure to dogs, cats, and ferrets
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*
Consult local public health department
Unknown (e.g., escaped)
*Discontinue treatment if tests on animal prove negative.

22. Recommended prophylaxis in exposed individuals not previously vaccinated against rabies
Wound site(s)
Immediate thorough cleansing of all wounds with soap and water.
Tetanus prophylaxis; antibiotics
Human Rabies
Immune Globulin
(RIG)
20 IU/kg body weight
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 Vaccine
IM (1 mL) in the deltoid area on days 0, 3, 7, 14, and 28
MMWR 48: RR-1, 1999

23. Rabies Vaccines Available in Canada
4/28/2017
Rabies Vaccines Available in Canada
RabAvert® Imovax ®
Manufacturer
Cell culture
Common designation
Novartis
(Merck Frosst)
primary chick embryo fibroblasts
PCECV
Sanofi Pasteur
MRC-5 human lung cell line
HDCV
SLIDE 42
RABIES VACCINES AVAILABLE IN THE US
Three rabies vaccines are available in the US: RabAvert®, produced by Chiron; Imovax®, produced by Pasteur Mérieux Connaught; and Rabies Vaccine Adsorbed (RVA), produced by BioPort. One of the several features that distinguishes these vaccines from one another is the cell culture method used to produce the vaccine viruses. RabAvert® is produced in primary cultures of chick embryo fibroblasts; Imovax® is produced in an MRC-5 human diploid cell line; and Rabies Vaccine Adsorbed virus is produced in the FRhL-2 cell line developed from fetal rhesus lung cells.
The final method of purification also distinguishes these vaccines: RabAvert is purified by continuous zonal ultracentrifugation over a sucrose gradient; Imovax is purified by ultrafiltration; and RVA is purified by centrifugation and concentrated by adsorption onto aluminum adjuvant.
MMWR;48:RR-1, January 8, 1999
Product package inserts, 2006

24. 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

25. Assessing the Rabies Risk for Travelers
4/28/2017
Assessing the Rabies Risk for Travelers
Destination
Duration of travel
Anticipated activities
Access to medical care and
appropriate PEP biologics
SLIDE 46
ASSESSING THE RABIES RISK FOR TRAVELERS
International travelers might be candidates for preexposure rabies vaccination if they are likely to come in contact with animals in areas where dog rabies is enzootic and immediate access to appropriate medical care, including appropriate rabies post-exposure prophylaxis biologics, might be limited. Assessing this is an important component of the pre-travel interview.

26. 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/mL
after a rabies exposure:
2 doses of IM rabies vaccine (days 0 and 3)
no HRIG

27. Pre-exposure rabies prophylaxis
Tissue culture vaccine: 1 dose IM or 0.1 ml ID
Day
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

28. Photo courtesy of Claudius Malerczyk (Novartis)
0.5 cc U-100 insulin syringe fitted with a 28 gauge needle
Photo courtesy of Claudius Malerczyk (Novartis)

29. 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*
The top of this slide lists the transmission routes that should be considered exposures. Rabies is spread through saliva or CNS tissue from an infected animal and is most commonly transmitted through bite exposures. Scratches are another potential exposure. Also, if infectious saliva or CNS tissue has contact with mucous membranes or a fresh, open wound this would also be considered an exposure. A fresh, open wound which is a wound that has bled in the past 24 hours.
Other possible but rare transmission routes include aerosol transmission and corneal and organ transplantation from an infected donor.
* Fresh, open wound is defined as wound that has bled in past 24 hours

30. 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

31. 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

32. 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

33. 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

34. 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

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

36. 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

37. 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

38. 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

39. 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

40. Management of Animals Potentially Exposed to Rabies
Vaccinated cats, dogs, ferrets
Rabies booster immediately
45 day observation
Under owner’s control
Any sign of illness should be reported and animal evaluated by a veterinarian

41. 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

42. 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

43. 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

44. 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

45. Management of Animals Potentially Exposed to Rabies
Other animals
Consider on case by case basis
Euthanasia generally recommended

46. 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.

47. 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

48. 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

49. 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

50. 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

51. 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)

52. 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

53. 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