1. Rabies

2. The Virus • Lyssavirus • Rhabdoviridae • Enveloped, bullet shaped RNA viruses • Viral amplification • in brain or spinal cord • Destroyed by • Disinfectants, UV light, heat • Viable in carcass less than 24 hours • Longer if refrigerated • Does not survive in dried saliva

3. How is Rabies Transmitted? • Bite of infected animal • Skunk, raccoon, bat, fox, coyote • Dog, cat, ferrets • Contact with saliva or brain tissue • Into mucous membranes or open wound • Cattle, horses, pigs, sheep, goats • Rare • Dam to offspring • Ingestion and transplacental • Unpasteurized milk • Aerosol? • Corneal transplant • Organ transplants

4. The Infectious Pathof Rabies Virus 4. The virus incubates in the body for approximately 3-12 weeks. There are no signs of illness during this time and animal is not able to spread virus. 5. When the virus reaches the brain, it multiples rapidly – then passes to the salivary glands. Signs of the disease begin to show, virus can now be spread. 3. Rabies virus spreads through the nerves to the spinal cord and brain. 2. Rabies virus enter through infected saliva. 6. The infected animal usually dies within 7 days of becoming sick. 1. Raccoon is bitten by a rabid animal.

5. Factors influencing length of incubation period • Bite location • Severity of bite • Innervation of bite site • Dose – quantity of virus inoculated • Age and immune status • Incubation in children shorter than adult

6. Epidemiology

7. Rabies Worldwide (2005) 40,000-60,000 deaths annually -- 90% in Asia30-60% children <15 yo age

8. Human Rabies Deaths, 2004

9. What is the only U.S. State that is rabies-free?

10. JAVMA. Sept 15, 2008. Vol 233, No 6.

11. 2007 7,259

15. Worldwide Reservoirs

16. Raccoons

17. Skunks

18. Bats

20. Cats

21. Dogs

24. Bats • Cryptic cases • Bites can occur while sleeping • No sign of bite • Big brown bat species • Common in older homes & buildings • Rarely transmit rabies to humans • Silver-haired/Eastern pipestrelle bat • Solitary tree dwellers, rarely found in homes

25. Iowa Most cases were animals NOT vaccinated!

26. Disease in Humans

27. Human Disease • Incubation in humans • Variable (30-60 days) • As long as 1 year • Record: 17 years • Duration of disease: 2-5 days • 100% fatal without treatment • PEP 100% effective

28. What are the clinical signs seen in humans?

29. Human: Clinical Signs • Non-specific signs • Headache, fever, aches, pain • Weakness, tired, loss of appetite • Itching or numbness at the site of bite • Acute nervous system dysfunction • Extreme excitement, restlessness, delerium • Followed by lucidity and comprehension • Hydrophobia, aerophobia • Laryngeal spasms – at site of water • Photophobia • Hallucinations • Unconsciousness, convulsions, paralysis, coma • Death from respiratory arrest

30. Human Case-Wisconsin • September 2004 • 15-year old girl at church service – bit by bat • 1-month later developed numbness in left hand, ataxia, double vision • Rabies diagnosed • No prophylaxis given; drug induced coma, mechanical ventilation and combination of antivirals • 3 months later went home • Some residual neurological manifestations • 7th person to survive rabies – 1st person without PEP

31. Disease in Animals

32. What are the forms of rabies seen in animals? What are the corresponding clinical signs?

33. Animal: Clinical Signs • Forms of rabies in animals • Dumb (paralytic) • Furious • Combination of two • Behavioral changes • Lick or chew at inoculation site • Neurological signs • Paralysis • Confusion or disorientation • Death 2-7 days after onset of illness

34. Dumb (Paralytic) Rabies • Dogs (75% of cases) • Lethargic • Incoordination • Rapid deterioration • Mandibular paralysis • “dropped jaw” • Laryngeal paralysis • Loss of swallowing reflex – frothing/hypersalivation • Change in bark tone • Quadriplegia • Death

35. Furious Rabies • Cats (25% of dogs) • Change in facial expression • Frequent vocalization • Repeated extension/retraction of claws • Restless movement of forefeet • Vicious striking movements • Bite/scratch at imaginary objects • Hypersensitivity to external stimuli • Isolation – dark, quiet • Pica – eat unusual things • Paralytic (dumb) form usually follows

36. Livestock and Horses • Anorexia, depression, ataxia • Muscle twitching • Voice changes • Excessive salivation • Hypermetra, proprioceptive deficits • Regional pruritus • Possibly belligerent, run frantically through fences, charge objects, bite • Flaccid tetraparesis, recumbency

37. VIDEOS

38. Wildlife • Combination of forms • Behave “tame” or unusual • Active during daylight • Hypersensitive to external stimuli • Attack/bite anything that moves • Hold with tenacity • Pruritus at bite site – lick/chew at it • Seizures • Death

39. Bats • Active during day • Found in places not typically seen • Homes, lawns • Paralysis • Unable to fly • Easily approached

40. Diagnosis How is rabies diagnosed?

41. Direct Fluorescence Antibody • Rapid and sensitive • Detectible if animalexcreting virus • Most widely used • Ante-mortem human • Nuccal biopsy • Nerve endingsof hair follicles • 25-50% • Impression smears • Brain tissue

43. Mouse Inoculation • Intracerebral inoculation of mice • Confirmatory test • Being replaced by tissue culture • Amplification method • Mouse neuroblastoma cells • Baby hamster kidney cells

44. Histopathology • Nonspecific, nondiagnostic • Encephalitis and myelitis • Perivascular cuffing • Negri bodies • Cytoplasmic inclusion bodies • Sites of active viral replication • Not detectable until neurological signs • In neuronal cells • Pyramidal cells of hippocampus • Purkinje cells of cerebellum

45. Negri Bodies Normal

46. Other Tests • Immunohistochemistry • Formalin fixed tissue • Rabies virus inclusions • PCR • Monoclonal antibody • Genetic sequencing

47. Treatment

48. After Possible Exposure • Exposure • Bite, scratch or other situation in which saliva or CNS tissue of potentially rabid animal enters open wound or mucous membrane • Wash wound thoroughly • Soap and Water • Iodine • Seek medical attention immediately

49. History of incident • Animal species • Vaccination status • Of animal • Of person • Bite occurrence • Provoked or not • Neurological signsin animal attime of bite • Has animal been captured • Test or observe • Prevalence in area