Animal Rabies Epidemiology A. Agent: The rabies virus 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 bat 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 bats.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, raccoons, and skunks.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 raccoon 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 skunk 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 cat, javelina, mountain lion, badger, bear 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% cats. 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.