1. Learning to Make Rabies History!
Rabies: The Disease, The Virus, The Treatment
Title Slide:
Learning to Make Rabies History!
Connecting Classrooms Globally through World Rabies Day!
For more information on World Rabies Day:

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
What is rabies?
Rabies has been around for over 4,000 years! We know this from some of the early artwork and writings (as shown on this slide).
Once symptoms of rabies start, rabies is nearly 100% fatal. (There has only been one person in the United States that has survived rabies virus infection.)
Rabies is caused by a virus.

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
Note – All animal bites do not get medical treatment
All rabid animals don’t get diagnosed

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

5. Illustrations from Centers for Disease Control and Prevention
Rabies Virus
G protein
M protein
Envelope
RNP core
Bullet Shaped Morphology Helical RNP Core RNA Structure And Organization
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

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. Map from Centers for Disease Control and Prevention
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

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
Bats and Rabies
The main source of rabies in humans in the United States is from bats.
Bat bites are so small that some people may not realize they have been bitten by a bat.
Don’t handle bats.
If you discover a bat in the house, especially in the room of a sleeping person or child, treat this situation as though an actual bite may have occurred.
Have an adult safely capture the bat by following the steps on the weblinks below.
Call your local health department and your doctor.
Resources:
For more information on how to remove a bat safely or other facts about bats and rabies, please visit the following Web sites:
CDC Rabies Web site:
Bat Conservation International:

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.
What is the Central Nervous System (continued)?
Watch as an exposure (possibly a bite from a rabid animal) on the leg causes the rabies virus to spread up the spinal cord to the brain and throughout the rest of the body.
NOTE TO TEACHER: the image should light up when it is shown in “slide show” format.
Resources:
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
Symptoms of rabies virus infection
The “incubation period” of rabies can vary from person to person (This is the time between exposure and actually getting symptoms). It may take several weeks to months after an exposure, before people become sick with rabies.
The symptoms can include:
The symptoms start with a headache, fever, and sore throat.
Nervousness and confusion develops.
The patient may experience pain or tingling at the site of the bite.
Many patients have hallucinations which means they see things that are not really there.
Case report: One parent of a patient said the patient was, “Cowering in the corner like a caged animal.”
Hydrophobia is also a symptom. Hydrophobia, or the fear of water, is due to spasms in the throat.
Case report: One patient said, “I throw up every time I try to eat or drink something. I can’t swallow my spit”
Paralysis or the inability to move parts of the body will develop later in the infection.
Eventually, the patient experiences a coma and ultimately 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. 
What to do if you are bitten by an animal:
Wash the wound well with soap and water for at least 5 minutes.
See a doctor about getting rabies vaccinations (post-exposure).
Contact your local health department and animal control officer.
If the animal that bit you is a pet (dog, cat, or ferret), the animal may be watched for signs of rabies for about 10 days. 
If it is a wild animal, the animal control people may need to euthanize the animal to test it’s brain for rabies.

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?
Note: This is the medical care professions quandary!! To treat or not to treat!??
Probably over-treatment vs under-treatment at the hospital level

17. High Risk Animals Raccoon Skunk Groundhog Fox Bat “free-roaming” cats
For the wildlife, always either test animal or treat person.
For cats – if healthy and not showing signs of rabies, can confine for observation x 10 days

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
Dogs and Livestock can be quarantined – or confined for observation
Other wildlife – usually test or treat

19. Low Risk Animal Squirrels, chipmunks Rats Mice, voles
Indoor small caged pet rodents
Logomorphs
- Almost never worry about indoor small caged pet rodents
- Others – only if they are acting rabid & attack someone; usually would die if bitten by a rabid animal – not survive to go on and get rabies
All other animals – risk somewhere in between.

20. WHO Definition of Exposure
Category
Type of contact
Type of exposure
Recommended treatment I
Touching or feeding of animals; Licks on intact skin;
None
None if reliable history is taken II
Nibbling of uncovered skin
Minor scratches or abrasions without bleeding
Minor
Administer vaccine immediately; Stop treatment if animal remains healthy for of 10 days or if animal is proven to be negative for rabies by a reliable laboratory using appropriate diagnostic techniques  
III
Single or multiple transdermal bites or scratches, licks on broken skin; Contamination of mucous membrane with saliva (i.e. licks); Exposures to bats
Severe
Administer RIG and vaccine immediately. Stop if animal remains healthy for 10 days or if animal is negative for rabies

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
Key is healthy – if showing signs of rabies, may not want to wait on treatment. Note – cannot sacrifice owned animal without owners permission.

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
May only show paralysis

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. Essen intramuscular Regimen WHO Recommended PEP Schedule
Standard intramuscular regimen. One dose into deltoid on each of days:
Essen intramuscular Regimen
WHO Recommended PEP Schedule
5 vials
5 visits
day
Rabies immunoglobulin
Start of administration = Day 0 (day treatment is first initiated)
HRIG – administer on Day 0 at a dosage of 20 IU/kg
-Infiltrate as much as possible into and around the wound(s)
-Remaining HRIG – give IM at an anatomical site distant from the vaccine

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
3-dose series intramuscular or intradermal regimen
Pre-exposure
Exposure: No Rabies immunoglobulin needed
day or 28
day
Persons who have completed the PEP series or the preexpsoure protocol are considered ‘pre-immunized’.
No HRIG is administered
Two doses of vaccine administered on days 0 and 3.
Dosage: 1.0 ml administered IM in the upper deltoid

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
Shipping guidelines for diagnostic samples

34. Diagnoses Surveillance Diagnoses provides surveillance data
Surveillance data helps PEP decisions
Diagnoses
Surveillance
Valuable surveillance data is obtained from rabies testing that reveals distribution of rabies in populations and is used for decisions regarding PEP for bites from animals not available for testing.

35. Resources World Rabies Day Website:
US Centers for Disease Control and Prevention (CDC) Rabies Website:
World Health Organization
Pan American Health Organization
Alliance for Rabies Control
Kansas State University Rabies Laboratory
Resources:
World Rabies Day Website:
US Centers for Disease Control and Prevention (CDC) Rabies Website:
CDC’s Kids Rabies Website:
World Health Organization
Alliance for Rabies Control
Kansas State University Rabies Laboratory
If your students have additional questions, they can contact your local or state health department or the U.S. Centers for Disease Control and Prevention