Animal Epidemiology

A. Agent: The belongs to the order Mononegavirales, viruses with a nonsegmented, negative- stranded RNA genome. Within this group are viruses with a distinct "bullet" shape classified as the Rhabdoviridae family. This family includes at least three genera of animal viruses, Lyssavirus, Ephemerovirus, and Vesiculovirus.1, 2

The genus Lyssavirus includes the rabies virus, Lagos virus, Mokola virus, Duvenhage virus, European bat virus 1 & 2 and Australian bat virus. Lyssavirus viruses are antigenically related, but monoclonial antibody and nucleotide sequencing has revealed differences (i.e., variants) according to animal species.1, 2

B. Clinical Description: Rabies is a preventable viral disease of mammals most often transmitted through the bite of a rabid animal. Today, the vast majority of rabies cases reported each year to the CDC occur in wild animals and only occasionally in domestic pets and livestock. 3, 4

The rabies virus infects the central nervous system, eventually causing disease in the brain and death. The early symptoms of rabies in humans are similar to that of many other illnesses, including fever, headache, and general weakness or discomfort. As the disease progresses, more specific neurologic symptoms appear including anxiety, confusion, slight or partial paralysis, hallucinations, agitation, hypersalivation, difficulty swallowing and hydrophobia. Death usually occurs within days of the onset of symptoms.2, 5, 6 The full range of symptoms associated with rabies is listed in Table 1.2.

Table 1. Specific Symptoms of Rabies*2, 5, 6 Hydrophobia Aggression Lethargy Loss of appetite Change in voice Chewing on bite site Constant growling Dilated pupils Unexplained biting Seizures Biting objects/breaks teeth Salivating/foaming Choking; unable to swallow Unexplained death Dropping of jaw or paralysis of jaw, throat masseters *As determined by a veterinarian.

C. Reservoirs: Over the last 100 years rabies in the U.S. has changed dramatically. More than 90% of all animal cases reported annually to CDC now occur in wildlife whereas before 1960 domestic animals were the leading source of rabies infections. The principal rabies hosts today are wild carnivores and .4, 7

While all mammals are susceptible to infection, only a few species actually serve as reservoirs of the disease. Animals that are rabies reservoirs are capable of maintaining the virus in an endemic or enzootic cycle as well as experiencing occasional outbreaks or epizootics. In the U.S., distinct reservoir rabies virus strains have been identified in insectivorous bats, foxes, , and .2, 8, 9, 10 Rabies Protocol Last Revised: 3/25/2020 In Arizona, the greatest rabies risk to humans, domestic pets and livestock are three wild animal reservoir species: bats, skunks and foxes.11 Together these three animals comprise 93% of the 3,630 lab-confirmed rabid wild animals recorded between 1944 and 2013.12

While the rabies variant is present in the eastern and southeastern U.S., it is not found in Arizona or other western states.7 Rabies has been confirmed in only six raccoons in the state with the last two being reported in 2018. The raccoon in 2005 was shown to be infected with the variant rabies virus; the other three specimens date to 1965 and 1974, before variant testing was available. 12

Several of the state’s non-reservoir wild animal species can also be sources of rabies infections for humans and domestic animals. Coyotes and bobcats are the most common non-reservoir species to be reported rabid and combined represent 6% of the total number of rabid wild animals reported during 1944–2013. The remaining 1% comprises, in descending order of occurrence, the coatimundi, ringtail , javelina, mountain lion, badger, and raccoon.12

Another potential, though infrequent, source of human rabies infections are pets and livestock. During 1944–2013, 989 domestic pets and livestock were confirmed rabid. Of these, 75% were dogs, 12% cattle and 11% . Horses, llamas and pigs compose the remaining 2%. However, the majority (863, or 87%) of rabid domestic animals were identified during 1944–1965, and in the successive decades rabies in dogs, cats and livestock has become increasingly sporadic and rare. Today, when rabid domestic animals are encountered their infections are usually (but not always) associated with epizootics in reservoir species, chiefly skunks and foxes.12

One group of animals (both wild and domestic) that do not generally pose a serious rabies threat is small rodents. This includes squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice and lagomorphs including rabbits and hares. They are rarely found to be infected with rabies and have not been known to transmit rabies to humans as their small size makes it unlikely they would survive a vicious bite by a large rabid mammal to survive and later incubate the rabies virus. 10, 11, 12, 13

However, with greater body mass, large rodent species such as beaver, porcupines and woodchucks (ground hogs) are able to survive attacks and eventually develop rabies. CDC reports that of 737 rabid rodents reported in the U.S. from 1995 to 2010, woodchucks accounted for 663 (90%) of the cases. Beaver accounted for 31 (4%) of cases, while a mixture of smaller rodents and rabbits comprises the remaining 6% of cases.13 Rabid rodents and lagomorphs are primarily associated with areas where raccoon rabies is enzootic.13 In contrast, since raccoon rabies variant is not present in Arizona, the number of confirmed rabid rodents and lagomorphs is exceedingly low. While routine testing of rodents was discontinued in 1994, the lab continued and still continues to test a limited number of specimens under special circumstances and, again, none have ever tested positive.11

D. Mode of Transmission: The most common mode of rabies virus transmission is through the introduction of virus- containing saliva via the bite of an infected host. However, infectious saliva may also be introduced through cuts and abrasion in the skin. Similarly, transmission has occasionally been documented via other routes such as contamination of mucous membranes (i.e., eyes, nose, mouth), aerosol transmission, and corneal and organ transplantations.2, 3, 11, 14, 15

Rabies Protocol Last Revised: 3/25/2020 E. Incubation Period: Rabies-infected animals usually die within a few days after onset of clinical signs. Factors that may contribute to the transmission, incubation period and development of rabies infection include: the amount of viral inoculum (amount of rabies virus introduced into the body) and the anatomic location of the bite.2

The incubation period and duration of rabies in dogs and cats generally involves four phases: (1) An incubation period averaging 2-9 weeks with a range 9 days to 8.5 months (not >6 months in U.S.); (2) A prodromal or initial stage lasting 1-3 days; (3) an excitation (furious) stage lasting an average of 1-7 days (some animals do not exhibit this stage); and (4) a paralytic stage of 1-4 days duration. If a dog or cat has not shown any signs of abnormality on the tenth day after inflicting a bite, it is safe to assume that the animal was not shedding virus in its saliva at the time of the bite.11 The incubation and duration phases for rabies in livestock and other animals are present in Table 2.

Table 2. Incubation Period and Duration of Disease in Other Species11 SPECIES INCUBATION PERIOD DISEASE DURATION Horses / Mules Average 3-14 weeks, range <6 2–8 days months Cattle Average 2-15 weeks, range <6 Usually 1-6 days, rarely as months long as 14 days Sheep / Goats 2-17 weeks 5-7 days Wild / Exotic Unknown Unknown Animals

F. Susceptibility and Resistance: All mammals, including humans, are susceptible.

G. Treatment: There are three facets of medical treatment for animal bites and the prevention of rabies: wound care, post-exposure prophylaxis (PEP) and pre-exposure prophylaxis.

Wound Care Regardless of the risk of rabies, bite wounds can cause serious injury such as nerve or tendon laceration and local and systemic infection. A doctor can determine the best way to care for a wound(s), and will also consider how to treat it for the best possible cosmetic results.16

For many types of bite wounds, immediate gentle irrigation with water or a dilute water povidone-iodine solution has been shown to markedly decrease the risk of bacterial infection.16

Wound cleansing is especially important in rabies prevention since, in animal studies, thorough wound cleansing alone (without other post-exposure prophylaxis) has been shown to significantly reduce the likelihood of rabies.16

Rabies Protocol Last Revised: 3/25/2020 Bite victims should receive a tetanus shot if they have not been immunized in ten years. Decisions regarding the use of antibiotics, and primary wound closure should be decided together with a doctor.16

Rabies Post-Exposure Prophylaxis (see Table 3) For people who have never been vaccinated against rabies previously, post-exposure anti- rabies vaccination should always include administration of both passive antibody and vaccine. Vaccine given after a rabies exposure event is often referred to as post-exposure prophylaxis or PEP for short.11, 16

The combination of human rabies immune globulin (HRIG) and vaccine is recommended for both bite and non-bite exposures, regardless of the interval between exposure and initiation of treatment. However, people who have been previously vaccinated or are receiving pre- exposure vaccination for rabies should receive only vaccine.11, 16

Adverse reactions to rabies vaccine and immune globulin are not common. Newer vaccines in use today cause fewer adverse reactions than previously available vaccines. Mild, local reactions to the rabies vaccine, such as pain, redness, swelling, or itching at the injection site, have been reported. Rarely, symptoms such as headache, nausea, abdominal pain, muscle aches, and dizziness have been reported. Local pain and low-grade fever may follow injection of rabies immune globulin.11, 16

Rabies PEP consists of a dose of human rabies immune globulin and four doses of rabies vaccine. The first day vaccine is given is referred to as ‘day 0’ and it is thereafter administered on days 3, 7, and 14. It is given in a muscle, usually in the upper arm (in the anterolateral part of the upper thigh for small children). This set of vaccinations is highly effective at preventing rabies if given as soon as possible following an exposure.17 The vaccine should be given at the above recommended intervals for best results, per the current guideline published by the Advisory Committee on Immunization Practices (ACIP).18 Patients should talk to their physicians or state or local public health officials if they will not be able to have the vaccine at the recommended interval. Rabies prevention is a serious matter and changes should not be made in the schedule of doses.16, 18

Human rabies immune globulin (HRIG) is only administered once, usually on day 0. It involves local infusion at wound site, with any remaining amount injected intramuscularly in the anterolateral aspect of the upper thigh. If HRIG is not readily available on day 0, it may be administered up to seven days after the initiation of the rabies vaccine (i.e., after 3 vaccinations) as a vaccine-induced immune response should be sufficiently actuated.18, 19

If a person has previously received PEP or pre-exposure rabies vaccinations, only two doses of vaccine (on the day of exposure and then 3 days later) are needed. Human rabies immune globulin is not warranted.16, 18

In the case of immunosuppressed patients, five doses of vaccine should be administered on days 0, 3, 7, 14 and 28. After completing the vaccination series, an immunosuppressed person should have serum tested for rabies virus neutralizing antibody to ensure an acceptable antibody response developed.16, 18

Rabies Protocol Last Revised: 3/25/2020

People cannot transmit rabies to other people unless they are actively sick and symptomatic with rabies. The prophylaxis that bite victims receive will protect them from developing rabies, and therefore they cannot expose other people to rabies. Victims should continue to participate in their normal activities.

Rabies Pre-Exposure Prophylaxis (see Table 4) People who work with rabies in laboratory settings and animal control and wildlife officers are just a few of the people who should consider rabies pre-exposure vaccinations. If people are traveling to a country where rabies is widespread, they should consult their doctor about the possibility of receiving pre-exposure vaccination against rabies.20

Arizona residents should consider pre-exposure vaccination if: (1) their planned activity will bring them into contact with wild or domestic animals (e.g., a biologist, veterinarian, or agriculture specialist working with animals; (2) they will be visiting remote areas where medical care is difficult to obtain or may be delayed (e.g., hiking through remote villages where dogs are common); and (3) they stay longer than 1 month in an area where dog rabies is common. A good rule of thumb to remember is “the longer your stay, the greater the chance of being bitten”.20

Although pre-exposure vaccination does not eliminate the need for additional therapy after a rabies exposure, it simplifies management by eliminating the need for rabies immune globulin and decreasing the number of doses of vaccine needed. This is of particular importance for persons at high risk for exposure to rabies in areas where immunizing products might not be available or where lesser quality biologics might be used which would place the exposed person at increased risk for adverse events.20

Pre-exposure prophylaxis may also protect people whose post-exposure therapy is delayed and provide protection to people who are at risk for unapparent exposures to rabies.20

Primary Vaccination: Three 1.0-mL injections of HDCV or PCEC vaccine should be administered intramuscularly (deltoid area): one injection per day on days 0, 7, and 21 or 28. Vaccine preparations for intradermal administration are no longer available in the United States. Booster doses should be given based on a person’s potential frequency to exposure.20

Continuous risk: People who work with rabies virus in research laboratories or vaccine production facilities are at the highest risk for unapparent exposures. Such persons should have a serum sample tested for rabies antibody every six months. Intramuscular booster doses of vaccine should be administered to maintain a serum titer corresponding to at least complete neutralization at a 1:5 serum dilution by the rapid fluorescent foci inhibition test (RFFIT).20

Frequent risk: This group includes other laboratory workers such as those performing rabies diagnostic testing, spelunkers, veterinarians and staff, and animal-control and wildlife officers in areas where animal rabies is enzootic. The frequent-risk category also includes persons who frequently handle bats, regardless of location in the Unites States. Persons in the frequent risk group should have a serum sample tested for rabies antibody every 2 years; if the titer is less

Rabies Protocol Last Revised: 3/25/2020 than complete neutralization at a 1:5 serum dilution by the RFFIT, the person also should receive a single booster dose of vaccine.20

Infrequent risk: Veterinary students, and terrestrial animal-control and wildlife officers working in areas where rabies is uncommon to rare (infrequent exposure group) and at-risk international travelers fall into this category and do not require routine pre-exposure booster doses of vaccine after completion of primary pre-exposure vaccination.20

H. Clinical Case Management: Management of rabies exposures is twofold: human exposures and pet or livestock exposures. These are not necessarily mutually exclusive, however, as some wild animal encounters can (and often do) involve exposures to both humans and their pets or domestic stock (e.g., when a home owner tries to break up a fight between his dog and a skunk). In such cases management will involve getting the offending wild animal tested for rabies, recommending proper medical treatment for the person and quarantine for the exposed pet.

Public health management of bite cases may have both ADHS and local health department and animal control staff working in conjunction with staff at the Office of the State Veterinarian, Arizona Department of Agriculture (ADA) or the Research Branch of the Arizona Game and Fish Department (AGFD). The state veterinarian, for example, has purview over livestock issues including potential rabies exposures (ARS Title 3, Chapter 2, Article 4, R3-2-408) and also designates the type(s) of rabies vaccines that may be used in the state (ARS Title 11, Chapter 7, Article 6, 11-1002). Similarly, AGFD staff authority over Arizona wildlife (ARS Title 12, Chapter 4) and may be instrumental in recovering wild animals that are ill or have attacked people, pets or livestock.

Because of the crucial role these two state agencies often play in rabies control and prevention, it is suggested that local animal control and health department personnel get to know the livestock and wildlife officers serving in the their jurisdiction. Establishing a working relationship between agency cohorts can go a long way to hasten responses to serious wildlife attacks and rabies epizootics.

Two other agencies are also frequently involved in rabies control in Arizona. The University of Arizona’s Veterinary Diagnostic Laboratory (AVDL) in Tucson, for example, provides assistance with brain extractions from large animals (from large dogs to horses, cattle, etc.) as the state lab does not have that capability. They can also accept animal heads (for a charge) for rabies testing that ADHS or ADA staff deem unnecessary for testing. However, the AVDL does not perform the actual testing but uses a rabies lab located in another state.

The U.S. Department of Agriculture’s Wildlife Services Division, on the other hand, not only provides additional rabies surveillance through their direct rapid immunohistochemical testing (dRIT) services but also plays a critical role during epizootics through distribution of oral rabies vaccine baits (as needed) and vaccinate, trap and release and rabies programs.

Rabies Protocol Last Revised: 3/25/2020 HUMAN EXPOSURES

Exposures: Any bite, scratch, or other incident in which saliva, central nervous system (brain or spinal cord) tissue, or cerebral spinal fluid of a potentially rabid animal enters an open wound, or comes in contact with mucous membranes by entering the eye, mouth, or nose, can be considered a rabies exposure. The species of the animal involved must be considered when determining the exposure risk level. For instance, a bite from a healthy caged rodent is not considered a rabies exposure, while a bite or saliva into wound contact from an untested or rabies positive skunk, bat, or wild carnivore is always considered an exposure. Children that have had direct contact with a bat or have been sleeping in a room with a bat should be considered as exposed unless the bat tests negative for rabies at the ASPHL. People who have been bitten by or exposed to dogs in countries that are endemic for canine rabies should consider prophylaxis unless the dog has either tested negative for rabies or remains healthy upon completing a quarantine of 14 days.2, 3, 11, 14, 15

Non-Exposures: There are several types of human-to-animal interactions that are not considered rabies risks. Some of the more common ones are: 1. Petting or touching the body/fur of a potentially rabid animal (as long as contact with the head is ruled out). 2. Touching an inanimate object that has had contact with a rabid animal does NOT constitute an exposure unless wet saliva or CNS tissue entered a fresh, open wound or contacted a mucous membrane. 3. Being sprayed by a skunk. 4. Having contact with blood, urine, or feces of a rabid or suspect rabid animal does not constitute an exposure. 5. Being in the vicinity of a rabid animal; rabies is not transmitted by aerosols.11, 14

Bat exposures: Bats are increasingly implicated as significant wildlife reservoirs for variants of rabies transmitted to humans in the U.S. Recent epidemiologic data suggest that seemingly insignificant physical contact with bats may result in viral transmission, even without a clear history of animal bite. In all instances of bat-human contact where rabies transmission is under consideration, the bat in question should be collected if possible, and submitted for rabies testing.9 Rabies post exposure prophylaxis is recommended for all individuals with bite, scratch, or mucous membrane exposure to a bat, unless the bat tests negative for rabies. The inability of health care providers to solicit information surrounding potential exposures may be influenced by the limited injury inflicted by a bat bite (in comparison to lesions inflicted by terrestrial carnivores) or by circumstances that hinder accurate recall of events.9, 11

RECOMMENDED VACCINE SCHEDULE FOR PETS AND LIVESTOCK

Determining the rabies vaccine history of pets and livestock is critical in an evaluation of the human and animal medical and prophylactic treatment for wild animal bites and for the appropriate quarantining of domestic species that have bitten humans. For the following discussion please consult the current edition of the ADHS Manual for Rabies and Bite Management, Compendium of Animal Rabies Prevention and Control as well as ARS Title 9, Chapter 6, Article 5: Rabies Control and ARS, Title 11, Chapter 7, Article 6, 11-1001-11-1020.6, 11

Rabies Protocol Last Revised: 3/25/2020

Dog and Cat Rabies Vaccine Schedule: Per the 2016 Compendium, dogs and cats should be initially immunized at 3 months of age and re-immunized 12 months after with either a 1 year or 3 year licensed rabies vaccine. The animal will require boosters according to the vaccine used (e.g., if vaccinated with a 1 year rabies vaccine then a booster is needed annually). In order to improve rabies vaccination coverage, use of 3 year rabies vaccines is encouraged for dogs and cats. Regardless, an animal is not regarded as ‘immunized’ until 28 days after the first vaccine as this is the period of time it takes for the vaccine to reach efficacy.

Ferret Vaccine Schedule: Ferrets should be vaccinated annually against rabies. The first vaccination of ferrets is recommended at 3 to 4 months of age.

Livestock Vaccine Schedule: Rabies vaccines are available for cattle, horses, and sheep and they should be vaccinated annually against rabies. There are no rabies vaccines currently licensed for use in swine, goats, camelids (llamas, alpacas), bison, red deer, fallow deer, elk or exotic species of livestock, although rabies vaccines have been off-label by licensed veterinarians. A veterinarian and livestock owner should decide whether rabies vaccinations are warranted in a herd or in valuable individual animals. In Arizona, livestock maintained in areas with epizootic rabies activity in foxes or skunks should be considered for vaccination.

Special Note: Any animal that has an unknown, undocumented or questionable vaccination history should be vaccinated immediately and then again in 12 months by a veterinarian licensed in the state of Arizona.

It is especially important to bear in mind animals inoculated by their owners even with an approved anti-rabies vaccine are still not considered ‘vaccinated’ in the state of Arizona. According to ARS, Title 11, Chapter 7, Article 6, 11-1001, an animal is not considered vaccinated unless it was vaccinated by a veterinarian licensed to practice in the state of Arizona “or any veterinarian employed in this state by a governmental agency.” This is why it is so important when discussing rabies vaccinations with the public to take every opportunity to remind them to get their pets and livestock immunized against rabies by a licensed vet and to keep their animal current!

For information on vaccine names, manufacturers, schedules, and dosages available for species for which a vaccine has been approved (dogs, cats, cattle, horses, ferrets and sheep) please refer to the current NASPHV Compendium of Animal Rabies Prevention and Control.

When assessing if an animal is considered currently immunized against rabies, remember the following criteria must be met: 1. The animal was vaccinated with a product that was approved for use in the species. 2. The vaccine was listed in the current Compendium. 3. A licensed veterinarian administered the vaccine, and the licensed veterinarian administering the vaccine signed a certificate. 4. Vaccines were given at the recommended schedule. 5. It is at least 28 days past administration of the first rabies immunization.

Rabies Protocol Last Revised: 3/25/2020

QUARANTINE FOR ANIMALS THAT HAVE BITTEN OR EXPOSED A HUMAN6, 11

Dogs and Cats: Dogs and cats are occasionally infected with rabies in Arizona. It is important to collect information about the animal (e.g. stray vs. owned), and the circumstances of the bite or exposure (provoked vs. unprovoked) to assess the risk of rabies and the potential need for PEP.

Regardless, any dog or cat (vaccinated or unvaccinated) that bites a person must be confined and observed for 10 days. The quarantine period starts on the day of the bite or exposure. If the dog or cat is currently vaccinated against rabies, a home quarantine is permitted at the discretion of the animal control official. Owners should be given clear instructions including the clinical signs of rabies to be reported. If the animal is not currently vaccinated or has an unknown vaccination status, the quarantine may be done in an animal control facility or veterinary clinic.

If the animal does not die or develop clinical signs of rabies infection during the quarantine period, the dog/cat did not have rabies virus in its saliva at the time of the exposure, and there is no further risk to the person. The person should not receive post-exposure treatment. If an animal develops signs of rabies infection during the quarantine period, humanely euthanize the animal and submit the head for testing. If an animal dies during the quarantine period, submit the head for rabies testing.

Ferrets: There is a licensed rabies vaccine for ferrets. Ferrets should be vaccinated annually. In the event a ferret bites a human, it should be quarantined and observed for signs of rabies or sudden death for 14 days regardless of its rabies vaccination status. Just like dogs and cats, if signs of rabies develop or the ferret dies during the quarantine period, it should be tested for rabies.

Canine/-Hybrids and Feline Hybrids: Offspring of any non-domesticated animal crossbred to a domestic animal are considered to be ‘wild animals’, and should be managed as wild animals in the event of a bite to a human. Currently there is no rabies vaccine approved for use in dog/wolf hybrids or in cat/wild cat hybrids. Hybrids may be vaccinated with a vaccine approved for use in domestic dogs/cats although the efficacy in these animals has not been determined. Note to veterinarians: The administration of rabies vaccines to wolf hybrids or feline hybrids is considered discretionary or off-label use. This practice is not discouraged in Arizona (other state and local laws vary). It is strongly suggested that veterinarians vaccinating wolf hybrids obtain owner initials in the medical record or a signed release form from owners stating that they understand the vaccine is not licensed for use in their animal, that it may not be effective if the animal is exposed to rabies, and that a hybrid pet will be considered an unvaccinated wild animal if it should bite a person.

It is the owner’s responsibility to prevent any situation where their hybrid may expose a person to its saliva. Studies have not been done on how long wolf or feline hybrids may excrete virus in their saliva in the advanced stages of rabies. Therefore, quarantine periods for wolf or feline hybrids after they have bitten a person, have not been established. Until more data are available, a wolf or feline hybrid should be handled the same as a wild animal in the event of a human exposure, regardless of its vaccination history.

Rabies Protocol Last Revised: 3/25/2020

If a hybrid bites a human (regardless of the hybrid's vaccination history) it should be treated as a wild animal exposure. This includes humanely euthanizing the hybrid and submitting the head for rabies testing regardless of its vaccination history. If it is not available for testing, consider PEP for the bite victim.

Wild Animals: Incubation periods for species of wild animals are not known (they are highly variable at best) and quarantines therefore cannot be established for them. Consequently, wild animals involved in biting events to humans, pets and livestock CANNOT BE QUARANTINED AND SHOULD BE ROUTINELY EUTHANIZED AND SUBMITTED FOR RABIES TESTING. . The only exception to this is rodents and rabbits. These small mammals are at low risk of contracting or transmitting rabies and do not need to be routinely tested for rabies. Rodents may be submitted for rabies testing if: there has been an unprovoked human exposure and; the rodent is exhibiting signs of possible rabies infection and; the rodent is from a rabies epizootic area.

Non-Mammals: Rabies is a disease of mammals only and therefore bites to humans, pets or stock by non-mammals (e.g., birds, turtles, snakes, etc.) are not a rabies issue.

DETERMINING PET EXPOSURE TO WILD ANIMALS6, 11

When a domestic animal has direct wild animal, it is considered to have had a potential exposure to rabies. It is very important to capture and submit the offending animal for rabies testing if possible. Wild mammals that are not available for laboratory testing should be presumed rabid. Domestic animals that bite other domestic animals are not usually considered as potentially rabid unless they are exhibiting signs compatible with the disease.

Assessing the risk of exposure and the proper quarantine and prophylactic routine for pets: Determine whether the dog or cat is vaccinated against rabies: 1. Find out if the wild animal to which the dog/cat was exposed is available for rabies testing. 2. If the wild animal is not available for testing, presume the wild animal is positive. 3. If the wild animal tests positive for rabies (or presumed positive), proceed as follows:

If the dog/cat is currently vaccinated against rabies (ARS Title 9, Chapter 6, Article 5, R9-6-502): 1. Notify local animal control. 2. Immediately take the dog/cat to a veterinarian for a booster rabies vaccination. 3. Confine the dog or cat under the owner’s control and observe closely for 45 days. The animal should be kept in a building, pen, or escape proof enclosure. The animal should only be removed from confinement on a leash and under supervision of a responsible adult. (Some town or county ordinances may be more restrictive than state law and not allow home quarantine). 4. At the first sign of illness or behavioral change, the animal should be taken to a veterinarian, and the health department and animal control should be contacted IMMEDIATELY.

If the exposed dog/cat has never been vaccinated against rabies: (ARS Title 9, Chapter 6, Article 5, R9-6-502):

Rabies Protocol Last Revised: 3/25/2020 1. Notify local animal control. 2. Consider immediate humane euthanasia OR; 3. Animal control will quarantine the animal for 180 days (6 months) in an approved facility run by either a veterinarian or an animal shelter. 4. The owner is responsible for payment of all expenses related to the quarantine. 5. A veterinarian should vaccinate the animal against rabies upon entry into isolation or one month prior to release to comply with pre-exposure vaccination recommendations (See Part I B.5 of Compendium). The quarantine is completed 180 days after the exposure. 6. Animals that have been vaccinated in the past but are overdue for rabies boosters should be handled on a case-by-case basis, upon consultation with the local animal control agency and/or the local health agency. Factors to consider include severity of exposure, time elapsed since last vaccination, number of previous vaccinations, current health status, and local rabies epidemiology.

I. Laboratory Criteria for Diagnosis: In animals, rabies is diagnosed using the direct fluorescent anti-body (dFA) test, which looks for the presence of rabies virus antigens in brain tissue, particularly the cerebellum, brain stem and hippocampus. The brain is the ideal tissue to test for rabies antigen because rabies virus is present in nervous tissue but not in blood like many other viruses. The most important part of a dFA test is flouresecently-labeled anti-rabies antibody. When labeled antibody is incubated with rabies-suspect brain tissue, it will bind to rabies antigen. Unbound antibody can be washed away and areas where antigen is present can be visualized as fluorescent apple-green areas using a fluorescence microscope. If rabies virus is absent there will be no staining.

Rapid and accurate laboratory diagnosis of is essential for timely administration of PEP. Within a few hours, a diagnostic laboratory can determine whether or not an animal is rabid and inform the responsible medical personnel. The laboratory results may save a patient from unnecessary physical and psychological trauma, and financial burdens, if the animal is not rabid. It can also save a pet or valued stock animal from being quarantined or even euthanized.

Once the test is performed lab staff will confirm the specimen as either confirmed positive or negative. On some occasions, however, the lab may deem an animal ‘not testable’ due to insufficient preservation of the brain. In such cases the investigating public health worker or animal control officer proceeds as if the specimen was positive.

J. Classification of Import Status: Rabies is found on all continents except Antarctica, and Arizona residents may suffer biting events while travelling outside of the U.S. This information is usually quickly communicated to public health staff by the victims themselves. However, it is important to ask which country they were visiting when they were bitten, what type of animal bit them, and what kind of prophylaxis or other medical care, if any, they received. If post-exposure prophylaxis was received internationally, try to ascertain information about the type of vaccine and vaccine schedule to determine if an approved vaccine was used. If not, the full PEP series should be re- started to ensure the person is protected against the virus.

Rabies Protocol Last Revised: 3/25/2020 Dog bites are the most common bites reported by travelers, and pose a serious rabies risk in some parts of the world. It is important to remember that while canine rabies has been eliminated in the U.S., Canada and much of the industrialized world, this form of rabies is still common in other parts of the world. In fact, exposure to rabid dogs remains the cause of over 90% of human rabies exposures and of over 99% of human deaths worldwide. Because vaccines to prevent human rabies have been available for more than 100 years, most deaths from rabies occur in countries with inadequate public health resources and limited access to preventive treatment. These countries also have few diagnostic facilities and limited rabies surveillance.

It is prudent to remember that the key to preventing rabies is the same in foreign countries as it is in Arizona and the U.S, which is to be on guard and avoid approaching any domestic or wild animal.

K. Laboratory Testing: Rabies testing in Arizona is performed in accordance with the established national standardized protocol for rabies testing by the virology section Arizona State Public Health Laboratory (ASPHL), located in Phoenix. The direct fluorescent antibody test (dFA), the most frequently used test to diagnose rabies, is the test performed by ASPHL. This test has been thoroughly evaluated for more than 40 years, and is recognized as the most rapid and reliable of all the tests available for routine use. All rabies laboratories in the United States perform this test on animals suspected of having rabies. 21

The dFA test requires brain tissue (primarily the cerebellum, brain stem and hippocampus) from suspect rabid animals and can only be performed post-mortem after the suspect animal must be euthanized (there are currently no reliable, standardized ante-mortem or ‘live animal’ tests that can be used to determine if an animal is rabid). Euthanasia should be accomplished in such a way as to maintain the integrity of the brain so that the laboratory can recognize and extract the cerebellum, brain stem and hippocampus.22

ASPHL Submission Guidelines11 The ASPHL is the only laboratory in the state that is able to confirm rabies infection in animals where exposures to humans or animal have occurred. It is important the brain tissue be maintained fresh or frozen in good condition and NOT placed in formalin or alcohol (questions regarding testing of fixed tissues should be directed to the local rabies laboratory or public health department). Potentially decomposed or destroyed brains should be submitted to the laboratory for evaluation of whether they can be tested if there was a human or pet exposure. Any animal that is excreting rabies virus in their saliva should have detectable virus by dFA examination. Always bear in mind that ASPHL staff should make the final decision as to whether a specimen is testable or not. DO NOT MAKE THIS DECISION IN THE FIELD!

Animals that should be submitted for testing are: (1) wild animals involved in human exposures (bites or otherwise); or (2) pet exposures or domestic animals showing neurological symptoms of rabies that have become ill or died during quarantine.

As of June 1, 2011 all animal specimens must have approval by the appropriate public health agency after a rabies risk assessment has been conducted. This is usually done at ADHS, however, first review of specimens may be delegated to the epidemiology staff at a local health

Rabies Protocol Last Revised: 3/25/2020 department or animal control agencies. Regardless, final approval authority rests with the ADHS (call 602 364-3676 or 602-364-4562 for assistance). It is imperative to have submittal forms be filled-out as thoroughly as possible. The form is available at: http://azdhs.gov/oids/vector/rabies/forms.htm. Similarly helpful submission algorithms can found at http://www.azdhs.gov/oids/vector/ rabies/statelab.htm.

Special Cautionary Note: 1. County epidemiologists and animal control officers should NOT tell clients that rabies testing will be done. Inform them that there is a provisional period that involves submitting the completed for to the correct authority and for ADHS to make final approval. 2. PETS MAY BE REJECTED FOR TESTING AT THE ASPHL FOR THE FOLLOWING REASONS: - There was no bite to a human or other exposure. - The animal was up-to-date with its rabies vaccinations or has a history of rabies vaccination. - The animal was an indoor pet or lived in a highly urbanized area with little or no potential for interaction with wild animals. - The animal did not exhibit neurological symptoms or other signs of rabies, or its symptoms can reasonably be explained by another condition (e.g., injury, cancer, or other diagnosis). - The bite was clearly provoked (i.e., it involved someone harming or antagonizing the animal, or the animal was protecting its territory, its owner or its young). - The animal was unavailable for quarantine or quarantine was otherwise not performed. - Insufficient information has been provided to make a rabies risk determination. 3. Animal heads arriving at the ASPHL without prior approval WILL NOT be tested until such time as an approved form is submitted to lab staff. If a form is not received the lab will automatically hold the specimen for 10 days in order for the submitter to redeem it for submittal elsewhere. After the 10 day period the head will be destroyed; there is no funding for shipping specimens back to submitters.

Remember: When determining whether a domestic animal should be submitted for testing, consider the following: 1. If an animal bites a human, and the animal is healthy, it should be quarantined and not euthanized. 2. Determine if the animal is currently vaccinated for rabies. 3. Determine if the animal could have come in contact with a potentially rabid wild animal in the past six months. 4. Determine if the animal is exhibiting signs consistent with rabies infection. 5. Determine if the animal is from an urban or rural area.

When investigating animal bite cases epidemiologists and animal control staff can always use the data fields on the submittal form as an outline of the kinds of questions they should ask victims or animal owners.

When there is very low suspicion of rabies or when there are no human or pet exposures, a domestic animal does not need to be submitted for rabies testing. In the case of a vaccinated, indoor only animal that has bitten someone or an animal exhibiting neurologic signs consistent with rabies but without exposure, the animal can be submitted to an alternative lab at a cost to the submitter (see below).

Rabies Protocol Last Revised: 3/25/2020 Removal of Animal Heads: Only veterinarians, animal control officers, Arizona Game and Fish officials, and others who have been appropriately trained and have pre-exposure prophylaxis should remove animal heads. For recommendations on the decapitation procedures, including supplies needed and clean-up methods, consult the state rabies manual located at: https://azdhs.gov/preparedness/epidemiology-disease-control/rabies/#manual

With the exception of bats, the ASPHL requires the submittal of pet and wild animal heads ONLY (the entire carcass is needed to accurately identify the bat species but not for other animals). The rest of the body should be incinerated. However, the ASPHL does not have the ability to remove brain material from larger animals such as horses or cattle (or any other similarly sized species) due to their dense, thick cranial bones. THEREFORE FOR LARGE ANIMALS THE ASPHL REQUIRES SUBMITTAL OF BRAINS ONLY. . If veterinarians or animal control agencies cannot remove an animal’s brain they should consult the Arizona Veterinary Diagnostic Laboratory in Tucson (520-621-2356). The Office of the State Veterinarian in cooperation with ADHS will have to arrange for brain removal for livestock.

Refrigeration versus freezing head: Refrigeration and immediate shipment is preferred. The head of a freshly euthanized/killed animal will store well in a refrigerator for 3-4 days. If shipment will be delayed due to weekend or holidays, refrigeration of the head and shipment with ample ice on Monday for receipt by Tuesday is recommended. If the animal is starting to decompose or has been dead for more than one day, has not been refrigerated and shipping will be delayed, then freezing the head is recommended. Freezing of the head will only delay the results due to allowance for thawing at the lab. Freezing should not affect the performance of the dFA test, as long as the head has not been repeatedly frozen and thawed.

Packing, storing and shipping samples: 1. The head of the animal (except bats which should be submitted whole) should be removed from the body and placed in a plastic bag. Seal the bag. NOTE: The specimen should be refrigerated until time of shipment and be properly labeled with the correct (and legible) specimen id number(s). 2. Place the bag containing the animal head inside a larger plastic bag. 3. Place at least two FROZEN gel packs on top of the specimen and seal this bag. 4. Place the double-bagged head in a sturdy, LEAKPROOF container (preferably metal or styrofoam). 5. Fill out the submission form and place it in an envelope and tape onto the outside of the container/box (NOT on the inside of box). Address the box (see below). 6. IF MORE THAN ONE HEAD IS SENT IN A CONTAINER, MAKE SURE LAB STAFF ARE ABLE TO PROPERLY MATCH THE FORMS WITH THE SUBMITTED HEADS. BEFORE TESTING PROCEEDS LAB STAFF MUST RESOLVE ANY AMBIGUITY WHICH WILL RESULT IN TEST RESULTS DELAYS. 7. Specimens should be shipped or delivered to the lab as quickly as possible (overnight mail or same-day bus service are commonly used transport methods). 8. Notify the lab when high priority (human or pet exposure) specimens are being shipped (phone number below).

Specimen Submission & Shipping: Routine submissions can be received at the laboratory between 8AM and 4:30PM Monday - Friday.

Rabies Protocol Last Revised: 3/25/2020

Ship specimens to: Arizona State Public Health Laboratory VIROLOGY 250 N. 17th Ave Phoenix, AZ 85007 (602) 542-6134

For convenience the lab address is presented at the very top of page 1 of the ADHS submittal form ABOVE the letter head and again at the very bottom of page 2. Please DO NOT ship specimens to ADHS offices as this may lead to a delay in delivery to the lab especially if personnel are not readily available.

After hours and weekend rabies testing: Samples can be submitted after hours and on weekends only if there is human exposure to a suspected rabid animal. Contact ADHS at (602) 364-4562 and listen to the instructions regarding the after-hours answering service.

Other Testing Options11 Another testing mechanism available to Arizona animal control agencies is the direct rapid immunohistochemical test (dRIT). This is an unlicensed procedure designed for consideration as a potential confirmatory measure of the direct fluorescent antibody test, according to the national standard operating procedure for the diagnosis of rabies in animals. In addition, dRIT may be used to enhance field surveillance among suspect wildlife, particularly in support of national, regional, state, or local oral vaccination programs. This type of testing, however, is not to be used when human or veterinary exposures have occurred or are suspected (these cases should be tested by at ASPHL).

Currently in Arizona the USDA’s Wildlife Service is the only agency that has dRIT capability. Only wild animals may be submitted for testing and again should be free of any human, pet or livestock contact as are not as judicious as those from ASPHL. Indeed, results may not be reported out for several weeks. Regardless, they are accurate and reliable. If here is any question regarding the extent of human or animal contact with a wild animal, confer with ADHS (602-364-3676 or 602-364-4562) or USDA staff (To submit a specimen for dRIT testing (call 602- 870-2081).

For domestic pets rejected for rabies testing at the ASPHL there are alternative labs that can perform DFA testing for a fee. These are listed below. Prior to submission, please contact each laboratory to obtain their respective submission form, instructions, and fees for DFA. Estimate for cost of testing is $60 - $65 per animal head.

Colorado State University - Veterinary Diagnostic Laboratory 300 West Drake Fort Collins, CO 80523 Phone: 970-297-1281 Fax: 970-297-0320 http://dlab.colostate.edu Colorado Department of Public Health - Virology Lab 8100 Lowry Blvd Denver, CO 80230-6928 Phone: 303-692-3485

Rabies Protocol Last Revised: 3/25/2020 http://www.cdphe.state.co.us

Oregon State University – Veterinary Diagnostic Laboratory 30th & Washington Way - Magruder Hall – Room 134 PO Box 429 Corvallis OR 97339-0429 Phone: 541-737-3261 Fax: 541-737-6817 http://oregonstate.edu

L. Assessing Laboratory Results: The submitter of an animal(s) for rabies testing will receive one of the following results: (1) confirmed positive, (2) confirmed negative and (3) not testable.

Confirmed Positive: The public health or animal control authority in charge of the case proceeds with either PEP for an exposed human or place the exposed pet or livestock under the appropriate quarantine period or, if warranted, euthanize the animal.

Confirmed Negative: The patient does not need to start PEP or continue the series if they have already started. Similarly, pets or livestock do not need to be placed under quarantine or may be released from quarantine.

However, when relaying the fortunate news to a bite victim or pet owner that a submitted animal is negative for rabies, public health workers and ACOs should take the opportunity (when appropriate) to turn the event into a ‘learning experience’. For example, if the case involves an individual who works with wild animals on a regularly basis (e.g., veterinarians, veterinary or laboratory technicians, wildlife managers, biologists, rehabilitators, etc.), they should be urged to consider pre-exposure prophylaxis. Likewise, immediate vaccination of unvaccinated domestic animals should be recommended to owners of pets or livestock that have just avoided quarantine or euthanasia. Equally important, emphasize the need to keep animals current on their vaccines.

Not Testable: This designation is given when there is the submitted animals is too decomposed for testing purposes, namely insufficiently preserved brain material. Consequently, the public health worker or animal control officer must proceed as if the specimen was positive. To do otherwise may place a bite victim or exposed animal at risk of developing rabies.

M. Outbreak Definition: In Arizona enzootic rabies in wildlife may result in periodic epizootics. When they become widespread, it may be necessary for county authorities to invoke a county-wide quarantine.

Local authorities will establish control of the area affected through quarantine under authority of the state laws, regulations and ordinances, in cooperation with appropriate state, county, municipal authorities.

Increase vaccination of dogs and cats through officially sponsored, free or low-cost rabies vaccination clinics in community locations. Livestock should also be vaccinated, particularly those that are important for work and recreation (e.g., horses and mules) as well as other valued livestock.

Rabies Protocol Last Revised: 3/25/2020

In urban areas strict enforcement of regulations requiring collection, detention and euthanasia of ownerless or stray/feral dogs and cats, and of non-vaccinated pets found off premises.

N. Bioterrorism Potential: The CDC currently does not list the rabies virus as a potential bioterrorism agent.

O. Reporting Time Frame: Immediately.

P. Investigation Form: http://www.azdhs.gov/lab/documents/microbiology/rabies-lab-submission-form.pdf

Q. Control Measures listed in Rules: None.

Investigator Roles and Responsibilities:

Local animal control agency (most often the first responder): • Communicate with ADHS to coordinate the investigation of animal bites/saliva exposures involving humans or pets. • Fill-out and submit lab form to ADHS. • As needed: impound, euthanasia, decapitation, and shipping of animal heads (wild or domestic) for shipment to ASPHL or the USDA for dRIT testing. • Apply and manage quarantine for pets when appropriate.

Local veterinary clinics and hospitals (can also be a first responder): • Communicate with local animal control agencies, ADHS or ADA to coordinate the investigation of animal bites/saliva exposures involving humans, pets or livestock. • Fill-out and submit lab form to ADHS. • As needed: impound, euthanasia, decapitation, and shipping of animal heads (wild or domestic) to ASPHL, or to the AVDL for decapitation and brain removal. • Apply and manage quarantine for vaccinated and unvaccinated pets when appropriate.

Arizona Game and Fish Department/AGFD (can also be a first responder): • Communicate with ADHS to coordinate the investigation of wild animal bites/saliva exposures involving humans, pets or livestock. • Fill-out and submit lab form to ADHS. • As needed: impound, euthanasia, decapitation, and shipping of wild animal heads to ASPHL.

Arizona Department of Agriculture-Office of the State Veterinarian/ADA (can also be a first responder): • Communicate with ADHS to coordinate the investigation of wild animal bites/saliva exposures involving livestock and subsequent exposures to owners, family members and attending veterinarian and staff.

Rabies Protocol Last Revised: 3/25/2020 • Fill-out and submit lab form to ADHS. • Impound suspect rabid livestock and apply and manage quarantine when appropriate. • When required, euthanize and prepare suspect rabid livestock for shipment to ASPHL.

University of Arizona Veterinary Diagnostic Laboratory/AVDL: • Remove and ship the brains of large animals to the ASPHL to coordinate the investigation of wild animal bites/saliva exposures involving livestock and subsequent exposures to owners, family members and attending veterinarian and staff. • Fill-out and submit lab form to ADHS.

Local health department: • Communicate with ADHS or local animal control agencies to coordinate the investigation of animal bites/saliva exposures to humans based on available information. • Advise bite victims on medical treatment for bites including PEP when required. • Work with ADHS and other partners to implement control measures or provide educational information, as needed.

Arizona Department of Health Service/ADHS: • Communicate with local health department and/or animal control investigators, ASPHL, AGFD, ADA, AVDL and, if need be, CDC to coordinate the investigation of human/animal rabies bites, and determining the need for animal testing or PEP. • Assist the local health department in gathering case information, as needed. • Assist local animal control agencies, AGFD, ADA and zoos in the recovery of biting animals for rabies testing, and facilitate their preparation and shipment to ASPHL or USDA. • Work with ASPHL and USDA to ensure proper recording and reporting of test results.

Rabies Protocol Last Revised: 3/25/2020 References

1. Centers for Disease Control and Prevention. The Rabies Virus. https://www.cdc.gov/rabies/transmission/virus.html

2. Heyman DL, ed. Control of Communicable Diseases Manual (19th edition). Washington DC: American Public Health Association, 2008; pp. 498-508.

3. Centers for Disease Control and Prevention. How is Rabies Transmitted? https://www.cdc.gov/rabies/transmissiom/index.html

4. Dyer JL, Yager P, Orciari L, et al. Rabies Surveillance in the United States during 2013. JAVAM, 2014; 245(10): 1111-1123.

5. Centers for Disease Control and Prevention. What are the Signs and Symptoms of Rabies? http://www.cdc.gov/rabies/symptoms/index.html

6. Brown, CM, Slavinski, S. Ettestad, P. Sidwa, TL and Sorhage FE. Compendium of Animal Rabies Prevention and Control, 2016. JAVMA 2016; 248(5): 505-717.

7. Centers for Disease Control and Prevention. Rabies: Public Health Importance of Rabies. http://www.cdc.gov/rabies/location/usa/index.html

8. Centers for Disease Control and Prevention. Rabies: Wildlife Reservoirs for Rabies. http://www.cdc.gov/rabies/exposure/animals/widlife_reservoirs.html

9. Centers for Disease Control and Prevention. Rabies: Bats. http://www.cdc.gov/rabies/exposure/animals/bats.html

10. Centers for Disease Control and Prevention. Rabies: Other Wild Animals. http://www.cdc.gov/rabies/exposure/animals/other.html

11. Manual for Rabies Control and Bite Management. Phoenix, Arizona Department of Health Services, 2017. http://azdhs.gov/documents/preparedness/epidemiology-disease- control/rabies/az-rabies-manual.pdf

12. Historic Rabies Data, 1944 - Present, Vector-Borne and Zoonotic Diseases Program, Arizona Department of Health Service.

13. Fitzpatrick JL, Dyer JL, Blanton JD Kuzman IV and Rupprecht CE. Rabies in Rodents and Lagomorphs in the United State, 1995-2010, JAVAM 2014; 245(3): 333-337.

14. Centers for Disease Control and Prevention. Rabies: Exposure to the Virus. http://www.cdc.gov/rabies/transmission/exposure.html

15. Centers for Disease Control and Prevention. Rabies: What Materials can spread rabies? http://www.cdc.gov/rabies/transmission/exposure.html

Rabies Protocol Last Revised: 3/25/2020

16. Centers for Disease Control and Prevention. Rabies: What Care Will I Receive? http://www.cdc.gov/rabies/medical_care/index/other.html

17. Centers for Disease Control and Prevention. Rabies: Rabies Vaccine. http://www.cdc.gov/rabies/medical_care/vaccine.html

18. Rupprecht, CE, Briggs, DB, CM Brown, et al. Use of a Reduced (4-Dose) Vaccine Schedule for Postexposure Prophylaxis to Prevent Human Rabies: Recommendations of the Advisory Committee on Immunization Practices. MMWR 2010: 59 (RR02); 1-9. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5902a1.htm

19. Centers for Disease Control and Prevention. Rabies: Human Rabies Immune Globulin. http://www.cdc.gov/rabies/medical_care/hrig.html

20. Centers for Disease Control and Prevention. Rabies: Preexposure Vaccinations. http://www.cdc.gov/rabies/specific_groups/travelers/pre-exposure_vaccinations.html

21. Centers for Disease Control and Prevention. Rabies: Direct Fluorescent Antibody Test. http://www.cdc.gov/rabies/diagnosis/direct_fluorescent_antibody.html

22. Centers for Disease Control and Prevention. Rabies: Diagnosis in Animals and Human. http://www.cdc.gov/rabies/diagnosis/animals-humans.html

Rabies Protocol Last Revised: 3/25/2020 Table 3. Rabies Vaccines and Immunoglobulin Available in the United States16 Type Name Route Indications Human Diploid Cell Imovax® Pre-exposure or Intramuscular Vaccine (HDCV) Rabies Post-exposure Purified Chick Pre-exposure or Embryo Cell Vaccine RabAvert® Intramuscular Post-exposure (PCEC) Local infusion at wound site, with Human Rabies Imogam® additional amount intramuscularly Post-exposure Immune Globulin Rabies-HT in the upper thigh Local infusion at wound site, with Human Rabies HyperRab TM additional amount intramuscularly Post-exposure Immune Globulin S/D in the upper thigh

Post-exposure Prophylaxis for Non-immunized Individuals Treatment Regimen All post-exposure prophylaxis should begin with immediate thorough cleansing of Wound all wounds with soap and water. If available, a virucidal agent such as povidine- cleansing iodine solution should be used to irrigate the wounds. If possible, the full dose should be infiltrated around any wound(s) and any remaining volume should be administered IM at an anatomical site distant from RIG vaccine administration. Also, RIG should not be administered in the same syringe as vaccine. Because RIG might partially suppress active production of antibody, no more than the recommended dose should be given. Vaccine HDCV or PCECV 1.0 mL, IM (deltoid area), one each on days 0, 3, 7, and 14. Post-exposure Prophylaxis for Previously Immunized Individuals Treatment Regimen All post-exposure prophylaxis should begin with immediate thorough cleansing Wound of all wounds with soap and water. If available, a virucidal agent such as cleansing povidine-iodine solution should be used to irrigate the wounds. RIG RIG should not be administered. Vaccine HDCV or PCECV 1.0 mL, IM (deltoid area), one each on days 0 and 3.

Rabies Protocol Last Revised: 3/25/2020 Table 4. Rabies Pre-exposure Prophylaxis Guide20 Risk Pre-exposure Nature of Risk Typical Population Category Recommendations Continuous Virus present Rabies research laboratory Primary course. Serologic continuously, often in workers; rabies biologics testing every 6 months; high concentrations. production workers. booster vaccination if Specific exposures likely antibody titer is below to go unrecognized. acceptable level. Bite, non-bite, or aerosol exposure. Frequent Exposure usually Rabies diagnostic lab Primary course. Serologic episodic, with source workers, spelunkers, testing every 2 years; recognized, but veterinarians and staff, and booster vaccination if exposure also might be animal-control and wildlife antibody titer is below unrecognized. Bite, workers in rabies-enzootic acceptable level. non-bite, or aerosol areas. All persons who exposure. frequently handle bats. Infrequent Exposure nearly always Veterinarians and terrestrial Primary course. No episodic with source animal-control workers in serologic testing or recognized. Bite or non- areas where rabies is booster vaccination. bite exposure. uncommon to rare. Veterinary students. Travelers visiting areas where rabies is enzootic and immediate access to appropriate medical care including biologics is limited. Rare Exposure always U.S. population at large, No vaccination necessary (population episodic with source including persons in rabies- at large) recognized. Bite or non- epizootic areas. bite exposure.

Rabies Protocol Last Revised: 3/25/2020 Protocol Reviewed/Approved by:

_____Heather Venkat______Program Manager______3/25/2020______Signature Title Date

Last Revised:

Date Revised by Epi Manager Signature 1/26/15 Mike Fink 11/15/15 Laura Adams 4/2017 Mike Fink Joli Weiss

Rabies Protocol Last Revised: 3/25/2020