Learning to Make Rabies History!

1. Learning to Make Rabies History! Rabies:The Disease, The Virus, The Treatment

2. Rabies – The Disease • Rabies has been around for centuries; described as early as 2300 B.C. • Transmission is direct, primarily via inoculation by bite, with infectious virus present in saliva. • The reservoir for rabies is the animal pool that circulates rabies virus (diverse species of mammals each with a specific strain). • Rabies is >99% fatal once symptoms occur

3. Still Considerable Concern About Rabies In The US: • CDC estimates that more than 1 million people per year require medical attention for animal bites (far fewer than occur) • Over 7,000 cases of rabies in animals are reported to the CDC annually • Although the number of post exposure treatments given in the United States each year is unknown, it is estimated to be about 40,000

4. Rabies is caused by a virus • Family Rhabdoviridae – ‘bullet’ shaped • Genus Lyssavirus • Rabies • Lagos bat strain • Mokola • Duvenhage • EBL-1 • EBL-2 • ABLV Picture from Centers for Disease Control and Prevention www.cdc.gov/ncidod/dvrd/rabies

5. Envelope M protein G protein RNP core Bullet Shaped MorphologyHelical RNP CoreRNA Structure And Organization Rabies Virus • Five proteins • Ribonucleoprotein (RNP) Core: • Nucleocapsid protein (N) • Nucleocapsid phosphoprotein (NS or P) • RNA polymerase (L) • Matrix protein (M) • Glycoprotein (G) Cross Sectional G protein RNA Envelope (membrane bilayer) M protein RNP Illustrations from Centers for Disease Control and Prevention www.cdc.gov/ncidod/dvrd/rabies

6. How is rabies contracted • Rabies is most commonly spread by bite contact between the rabid animal and the recipient animal or human • In rabies infection, the virus present in the CNS and other organs • Average incubation period (the time between an initial exposure to the virus and the development of symptoms of disease) is 4 weeks

7. 2 main ecologic cycles: • Bat – all over U.S. except Hawaii • Terrestrial (ground animals) – raccoon, skunk, fox, coyote Map from Centers for Disease Control and Prevention www.cdc.gov/ncidod/dvrd/rabies

8. Rabies Virus Distribution Worldwide • Major animal reservoirs causing human death • Africa: Dog • Americas: Dog/Bat • Asia: Dog • Europe: Fox

9. Bats & Rabies • 80% of human rabies cases acquired in US. are bat-associated strains • A history of a definite bat bite was documented in only 5% of these cases; 60% had bat contact but no known bite or scratch • Bite wounds from bats are extremely small and may be nearly undetectable within hours. Person sleeping may not wake up or otherwise be aware of a bite from a bat. A small bat bite on a finger

10. Rabies Infection • Virus-laden saliva or other infectious material from the rabid animal must be introduced through a break in skin (bite) or onto mucous membranes • Virus binds to a nerve cell & migrates to spinal cord to brain (centripetal spread), then viral replication occurs & produces encephalitis

11. Rabies attacks the Central Nervous System • Watch as the rabies virus from an exposure on the leg spreads up the spinal cord to the brain and throughout the rest of the body. Rabies virus entering the body.

12. Transmission/Pathogeneis • Viral particles travel out from brain (centrifugal spread) via nerve cells to salivary glands, where further replication occurs & secretion in saliva, rendering the person or animal to be infectious • At the time it gets to the salivary glands, this is the end stage of the disease, and death usually occurs shortly thereafter – within several days • Incubation period: Usually 4 weeks; can range from 10 days to a year or more (??)

13. Symptoms • Headache, fever, sore throat • Nervousness, confusion • Pain or tingling at the site of the bite • Hallucinations • Seeing things that are not really there • Hydrophobia • “Fear of water" due to spasms in the throat • Paralysis • Unable to move parts of the body • Coma and death

14. Rabies Human Deaths • Annual human deaths worldwide are approximately 55,000; every 15 minutes a patient dies of rabies. • 40-70% rabies victioms are children under 15 years of age • Modern cell culture vaccines and animal control measures in developed countries have reduced the incidence of rabies deaths. • In the United States, there has been a mean of 3 deaths per year since 1990.

15. Prevention steps after an animal bite: • Wash the wound well with soap and water • Have the animal tested for rabies • See a Doctor, even if the bite is very small. • Contact your local health department and animal control officer. 

16. Should Anti-Rabies Prophylaxis be Administered? CONSIDERATIONS: • High or lower risk animal? • Was there an exposure? • Likelihood & timing for animal capture for confinement or testing?

17. High Risk Animals • Raccoon • Skunk • Groundhog • Fox • Bat • “free-roaming” cats

18. Intermediate Risk Animals • Dogs • Cats – vaccinated or non-roaming • Livestock – horses, cattle, pigs • Other non-rodent wild animal species i.e, opossum, bear, deer, coyote, etc

19. Low Risk Animal • Squirrels, chipmunks • Rats • Mice, voles • Indoor small caged pet rodents • Logomorphs

20. WHO Definition of Exposure

21. Was There An Exposure? • A bite (penetration of the skin by teeth) from a known or suspect rabid animal • Scratches, abrasions, open wounds (bleeding within 24 hrs), or mucous membranes (eyes) contaminated with saliva or other potentially infectious material from a known or suspect rabid animal • Other contact - such as petting an animal or contact with urine, feces or skunk spray - does NOT constitute an exposure

22. Can The Biting Animal Be Confined & Observed? • Healthy dogs, cats, ferrets and livestock may be confined and observed for 10 – 14 days • Raccoons, skunks, fox, groundhogs and other wildlife may excrete rabies virus while asymptomatic for extended periods and cannot be safely confined & observed. Testing of the animal - or prophylaxis of bite victim - is always recommended

23. 10 Day Confinement & Observation Period • In domestic animals the virus usually appears in the saliva at the onset of clinical signs – so if animal healthy, probably not rabid • Rarely, the virus can appear in the saliva 1 to 3 days prior to onset of illness, so thus an observation period created • Clinical course usually less than 7 days - animal dead before end of 10 days

24. Rabies Vaccination Status Of Animal • Lower risk if animal has been regularly vaccinated • But NO vaccine is 100% effective • Put as much weight on animal behavior & health status

25. Animal Behavior/Health Risk Factors To Consider • Was the bite or exposure provoked? • Did the animal escape in a normal manner? • Rabies is characterized by abnormal behavior with neurologic impairment. • There is often a period of aggression that progresses to paralysis, although aggression may not always occur

26. Rabies Virus Survival • If saliva or other material potentially containing the rabies virus is dry to the touch, the virus can be considered noninfectious. • Stability of the virus in the environment • Strong soaps, detergents, acids and alkalis all inactivate the virus • Heat inactivates the virus • Radiation destroys the virus • Lipid solvents inactivate the virus

27. WHO Recommended Post-exposure prophylaxis • Immediate flushing and washing of the wound with soap and water, or other detergent • If soap or detergent are not available, flush extensively with water • Passive immunization: Administration of Rabies immune globulin for Category III contacts/exposures • Active immunization: Administration of tissue culture vaccine according to one of WHO regimens

28. Rabies Postexposure (PEP) • Two biologics are administered: • Human Rabies Immunoglobulin (HRIG) – confers immediate protection with antibodies vs rabies • Rabies Vaccine - patient develops antibodies over a 2 to 4 week period

29. WHO Recommended PEP Schedule Essen intramuscular Regimen Standard intramuscular regimen. One dose into deltoid on each of days: 5 vials 5 visits day 0 3 7 14 28 Rabies immunoglobulin

30. Preexposure Vaccination • Recommended for veterinarians, veterinary technicians, animal control officers, animal shelter workers, rabies lab personnel and person working with wildlife. • Provides protection from unapparent exposures and when treatment is delayed • Also recommended for persons spending 1 month or more in countries with endemic dog rabies and in which PEP would likely be significantly delayed to geographic distances/ lack of medical infrastructure

31. Pre-exposure Vaccination Protocol • Three doses of vaccine administered on days 0, 7 and 21 or 28 • Dosage: 1.0 ml administered IM in the upper deltoid • Test serum every 2 years to determine if an adequate antibody level persists. If absent, administer booster

32. WHO Recommended Pre-exposure Pre-exposure 3-dose series intramuscular or intradermal regimen day 0 3 day 0 7 21 or 28 Exposure: No Rabies immunoglobulin needed

33. Rabies Specimen Testing • Only the head or brain of an animal larger than 2 pounds (squirrel) should be submitted • Brain tissue to include: Brain Stem, Cerebellum, Hippocampus • Submitted specimens cannot be returned • Specimen should be kept refrigerated but not frozen

34. Diagnoses Surveillance Diagnoses provides surveillance data Surveillance data helps PEP decisions

35. Resources • World Rabies Day Website: • www.worldrabiesday.org • US Centers for Disease Control and Prevention (CDC) Rabies Website: • www.cdc.gov/rabies • World Health Organization • www.who.int • Pan American Health Organization • http://www.paho.org/english/ad/dpc/vp/rabia.htm • Alliance for Rabies Control • www.rabiescontrol.net • Kansas State University Rabies Laboratory • www.vet.ksu.edu/depts/dmp/service/rabies/index.htm