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: www.worldrabiesday.org

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.

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

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

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 www.cdc.gov/ncidod/dvrd/rabies

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

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 www.cdc.gov/ncidod/dvrd/rabies

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

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: http://www.cdc.gov/ncidod/dvrd/rabies/bats_&_rabies/bats&.htm Bat Conservation International: http://www.batcon.org/home/default.asp

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

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: http://www.cdc.gov/ncidod/dvrd/kidsrabies/TheVirus/rabvir.htm Rabies virus entering the body.

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 (??)

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.

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.

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.

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

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

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

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.

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

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

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.

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

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

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

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

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

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

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 0 3 7 14 28 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

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

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

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

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 http://www.cdc.gov/ncidod/dvrd/rabies/Professional/publications/DFA_diagnosis/DFA_protocol-b.htm#IV_B

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.

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 Resources: World Rabies Day Website: www.worldrabiesday.org US Centers for Disease Control and Prevention (CDC) Rabies Website: www.cdc.gov/rabies CDC’s Kids Rabies Website: http://www.cdc.gov/ncidod/dvrd/kidsrabies/ World Health Organization www.who.int Alliance for Rabies Control www.rabiescontrol.net Kansas State University Rabies Laboratory www.vet.ksu.edu/depts/dmp/service/rabies/index.htm 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 (rabies@cdc.gov).