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RABIES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Rabies is an acute encephalomyelitis caused by a virus of the rhabdovirus group. Humans are infected most frequently through the bite of a warm-blooded animal. The incubation period may range from 12 days to as long as 701 days, but averages 20 to 40 days. In areas excluding the United States, 25% of patients have incubation periods of less than 30 days.

Specific Substances

    1) Rabies
    2) Rabies virus
    3) Animal bites
    4) Domestic animal bite
    5) Wild animal bite

Available Forms Sources

    A) FORMS
    1) SUMMARY
    a) Two types of rabies immunizing products are available in the United States (Manning et al, 2008).
    1) RABIES VACCINE: Provides an active immune response by the production of neutralizing antibodies which occurs within 7 to 10 days and lasts for approximately 2 years (Prod Info RABAVERT(R) IM injection, 2006; Prod Info IMOVAX(R) RABIES IM injection, 2005).
    2) RABIES IMMUNE GLOBULIN (RIG): Provides rapid, passive immunity that lasts for a brief time (half-life approximately 21 days) (Prod Info IMOGAM(R) RABIES - HT intramuscular injection, 2005; Prod Info HyperRAB(R) S/D intramuscular injection solution, 2010).
    3) Both products are indicated postexposure (prophylaxis) and should be given concurrently, unless the individual has been previously immunized.
    2) HUMAN RABIES VACCINES
    a) Two formulations of inactivated rabies vaccines are licensed for pre- and postexposure prophylaxis in the United States (Manning et al, 2008):
    b) HUMAN DIPLOID CELL VACCINE (HDCV)
    1) INTRAMUSCULAR: A single-dose vial containing lyophilized vaccine reconstituted with the accompanying diluent to yield 1 mL for injection.
    2) INTRADERMAL: In the US, intradermal vaccines are NO longer available.
    3) VACCINE AVAILABLE: The following product is available from Sanofi-Pasteur at 1-800-VACCINE OR 1-800-822-2463 or www.vaccineshoppe.com
    1) Imovax(R) Rabies Vaccine (Sanofi-Pasteur) (Prod Info IMOVAX(R) RABIES IM injection, 2005)
    c) PURIFIED CHICK EMBRYO CELL VACCINE (PCECV)
    1) PCECV: This vaccine is prepared from the fixed rabies virus strain Flury LEP grown in primary cultures of chicken fibroblasts, which is inactivated with betapropiolactone. Given by IM route only and available as a single-dose vial of lyophilized vaccine that is reconstituted in the vial with the accompanying diluent to a final volume of 1 mL just prior to administration (Manning et al, 2008; Prod Info RABAVERT(R) IM injection, 2006).
    2) VACCINE AVAILABLE: The following product is available from Novartis at 877 683 4732 or 877-NV-DIRECT
    1) RabAvert(R): Rabies Vaccine for Human Use (Novartis) (Prod Info RABAVERT(R) IM injection, 2006)
    3) RABIES IMMUNE GLOBULIN (RIG)
    a) SUMMARY: These antirabies immunoglobulin preparations are developed by cold ethanol fractionation from plasma of hyperimmunized human donors (Manning et al, 2008). The antibody is available in a standardized concentration of 150 IU/mL and supplied in 2 mL (300 IU) vials for pediatric use and a 10 mL (1500 IU) vial for adult use.
    1) Imogam(R) Rabies-HT: Rabies Immune Globulin (Human) USP, Heat Treated (Sanofi-Pasteur at 1-800-VACCINE OR 1-800-822-2463 or www.vaccineshoppe.com) (Prod Info IMOGAM(R) RABIES - HT intramuscular injection, 2005)
    2) HyperRab(TM) S/D: Talecris Biotherapeutics, Research Triangle Park, USA, (800-243-4153) (Prod Info HyperRAB(R) S/D intramuscular injection solution, 2010)
    4) RABIES VACCINE ADSORBED
    a) Rabies Vaccine Adsorbed (RVA), is NO longer available in the US (Manning et al, 2008).
    5) OUTSIDE THE UNITED STATES
    a) The following postexposure prophylaxis regimens are available to patients's outside the United States. They are NOT approved for use by the US FDA (Manning et al, 2008):
    1) Purified Vero Cell Rabies Vaccine: Verorab(TM), Imovax - Rabies vero(TM), TRC Verorab(TM)
    2) Purified Duck Embryo Vaccine: Lyssavac N(TM)
    3) PCECV (Rapipur(R)) - Differs from the US formulation
    4) HDCV (Rabivac(TM)) - Differs from US formulation
    b) Purified Equine Rabies Immune Globulin (ERIG) has been used in developing countries where HRIG may not be available (Manning et al, 2008).
    B) SOURCES
    1) SUMMARY
    a) The rhabdovirus which causes rabies is endemic in some parts of the world and unknown in others. It is carried by warm-blooded animals; sources of infection include dogs, bats, skunks, monkeys, and raccoons.
    b) UNITED STATES: Carnivorous wild animals (i.e., raccoons, skunks, foxes, coyotes and bobcats) and bats continue to be the animals most commonly infected with rabies and have caused most of the indigenous cases of human rabies in the United States since 1960.
    c) Widespread immunity to the virus among these source populations may decrease the threat of human exposure. A vaccine which is placed in ingestible bait has been developed for use in wildlife extensively in Europe (Kharmachi et al, 1992).
    d) IMPORTED HUMAN RABIES
    1) RABIES ACQUIRED IN OTHER COUNTRIES: Since 2000, there have been 8 (3 from Haiti) human rabies cases associated with dog bite exposures reported in the US; all were acquired outside of the US. In Haiti, a rabies-endemic country, less than 50% of dogs and cats are vaccinated against rabies, and the 2010 earthquake further interrupted efforts to vaccinate more animals (Centers for Disease Control and Prevention, 2012a). A child from the Philippines also developed rabies after being bitten by a dog from that country. Rabies virus RNA testing was genetically consistent to Philippine dog rabies (Aramburo et al, 2011).
    a) CASE REPORT: A 73-year-old Haitian woman received a minor bite by a dog she adopted approximately 2 months prior to developing symptoms of progressive acute encephalitis when she presented to an emergency department. The patient died a few weeks later. Rabies virus RNA was detected in the biopsy and saliva by reverse transcription-polymerase chain reaction testing. Further testing revealed a rabies virus variant with an RNA sequence closest to that found in a 2004 Florida human rabies patient, that was associated with a canine rabies virus from Haiti. Thee family members and a close friend received postexposure prophylaxis (Centers for Disease Control and Prevention, 2012a).
    e) INCIDENCE
    1) Wild animals accounted for 93% of reported cases of rabies in the United States during 2000. 7369 cases of veterinary rabies were reported in the US in 2000, with raccoons accounting for nearly 38% (a decrease of 3.2% from the totals reported in 1999) of all cases, followed by skunks (30.1%), bats (16.8%), foxes (6.1%) and other wild animals, including rodents and lagomorphs (0.7%). Although reported cases of rabies decreased in raccoons in 2000, reported cases of skunks, foxes and bats increased 7.1%, 17.9%, and 25.3%, respectively from the total number of cases reported in 1999 ((CDC, 2000a)).
    2) Over this century, the number of deaths related to rabies has steadily declined and averages 1 to 2 deaths per year in the United States ((CDC, 1998)). For the years 1997 and 1998, a total of 4 deaths occurred. The decline is based on vaccination and animal control programs and the development of an effective human rabies vaccine and immune globulin.
    3) Despite the low incidence of rabies among persons in the US, approximately 18,000 individuals receive pre-exposure prophylaxis and an additional 40,000 receive postexposure prophylaxis every year ((CDC, 2000)).
    4) Outside the US, most countries such as Asia, Africa, and Latin America reported that dogs remained the major species for human exposure to rabies.
    f) INCUBATION PERIOD
    1) The incubation period may range from 12 days to as long as 701 days, but averages 20 to 40 days (Corey & Hattwick, 1975; Eng & Fishbein, 1988). Cases with suspected incubation periods of over 6 years have been reported (Bek et al, 1992). In areas excluding the United States, 25% of patients have incubation periods of less than 30 days (Dean, 1963).
    2) ROUTE OF EXPOSURE
    a) WILD CARNIVORES are the most frequent carriers of rabies. Exotic pets and domestic animals crossbred with wild animals are considered wild animals. After biting a human, these animals should either be killed and tested or observed by a veterinarian for rabies testing ((IPAC, 1999)).
    b) BATS: Bat exposures remain the most common cause for human rabies in the US. All bites by a bat require thorough evaluation (Manning et al, 2008).
    c) RODENTS and RABBITS are not considered to be transmitters of rabies virus in the US and treatment is rarely indicated following their bites.
    1) Rodents or rabbits that exhibit aggressive, unprovoked behavior culminating in a bite exposure should be caught and submitted for testing. If the animal cannot be caught, consult state public health officials for treatment recommendations (Manning et al, 2008).
    d) DOMESTIC DOGS, CATS and FERRETS: The likelihood of rabies from a domestic animal is variable and the need for postexposure treatment also varies (Manning et al, 2008). In general, exposure from dogs is sporadic (except along the US-Mexican border) and most cases have been associated with enzootic wildlife rabies, in particular among raccoons in the eastern United States. The large number of rabies-infected cats may reflect the limited regulation of vaccine among these pets, along with fewer leash laws and roaming habits of cats.
    1) Based on new information, ferrets are now considered in the category with domestic dogs and cats based on pathogenesis and viral shedding patterns among ferrets. If a healthy domestic dog, cat or ferret bites an individual, the animal should be confined and observed for 10 days; any illness should be evaluated by a veterinarian.
    e) DAIRY CATTLE: During 1990 to 1996, the CDC had received reports of approximately 150 rabid cattle, which potentially raises the concern for foodborne transmission (McGuill et al, 1999). Theoretically, the rabies virus can be transmitted by unpasteurized milk or dairy products. A total of 66 individuals required rabies postexposure prophylaxis (PEP) following exposure to unpasteurized milk from a cow that was infected with a variant of the rabies virus associated with raccoons in the eastern United States.
    f) HUMAN-TO-HUMAN TRANSMISSION: Organ and tissue transplantation (ie, cornea, solid organ, and vascular tissue) have resulted in rabies transmission in a very small number of transplant recipients (Manning et al, 2008) .

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) DEFINITION: Rabies is an acute encephalomyelitis caused by a virus of the rhabdovirus group. It is transmitted to humans most commonly through the bite of an infected animal.
    B) EPIDEMIOLOGY: Rabies can occur in any mammal. Rabies is most commonly found in wild animals such as raccoons, skunks, bats and foxes, and coyotes. The domestic animals that are most frequently affected in the US are cats, cattle, and dogs. In the US, approximately 1 to 2 deaths each year are attributable to rabies (unrecognized cases are likely to occur). Although rabies is relatively rare among the US population, each year between 16,000 and 39,000 persons receive postexposure prophylaxis. Rabies is much more common in the developing world.
    C) WITH POISONING/EXPOSURE
    1) INCUBATION PERIOD: After being exposed to rabies, the incubation period may range from 12 days to as long as 6 years, but averages 20 to 40 days. Once symptoms develop, rabies is nearly always fatal.
    2) There are 3 PHASES in humans:
    a) PHASE ONE: Consists of nonspecific symptoms including malaise, anorexia, irritability, low grade fever, headache, and vomiting which may persist from 1 to 3 days to 2 weeks.
    b) PHASE TWO: This is an acute neurological phase which lasts 2 to 7 days and is characterized by restlessness, dysarthria, agitation, dysphagia, and visual or auditory hallucinations.
    c) PHASE THREE: This final phase of 7 to 10 days is characterized by painful contraction of the pharyngeal muscles which causes a fear of swallowing, seizures, prolonged apnea with generalized flaccid paralysis and coma. The final stage generally begins with coma and results in respiratory and vascular collapse.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) Fever commonly occurs in the prodromal phase. Hypothermia was reported in one case.

Laboratory Monitoring

    A) Most patients receiving rabies prophylaxis do not need any laboratory studies.
    B) In patients with rabies, findings include leukocytosis, glycosuria, proteinuria, and oliguria.
    C) Definitive diagnosis is usually made at autopsy by the fluorescent rabies antibody test on brain impression smears. The fluorescent rabies antibody test performed on living ocular impression smears and skin biopsies may be of value.

Treatment Overview

    0.4.7) BITES/STINGS
    A) SUPPORT
    1) Once clinical manifestations develop, rabies is nearly always fatal. The focus of treatment is on prevention of rabies in patients with potential exposure.
    B) RISK ASSESSMENT
    1) SUMMARY: Rabies prophylaxis must be considered when a patient has been potentially exposed via an animal bite, laboratory accident, contaminated organ transplant, or other known source. Domestic animals (especially vaccinated), rodents, and rabbits are unlikely to be sources; wild animals and wild/domestic animal hybrids are less likely to be vaccinated and more likely to be infected.
    2) DOG AND CAT BITES: The probability that a biting domestic dog or cat is infected with rabies varies from region to region but is usually small. Rabid cats represent the majority (62.2%) of reported domestic animal cases in the US, especially in States where raccoon rabies is enzootic. An apparently healthy dog or cat that bites a person should be confined, and observed for 10 days and evaluated by a veterinarian to see if the animal becomes ill during the observation period. If the dog or cat exhibits disease signs suggestive of rabies, the animal should be humanely killed and its head removed and shipped, under refrigeration, to a qualified laboratory for fluorescent antibody testing. Dogs or cats that appear normal at 10 days may be released without qualification, unless other issues or health or public safety exist. Observation of even vaccinated dogs or cats is prudent. If the dog or cat cannot be caught for observation, consult public health officials. PROPHYLAXIS THERAPY: In the event of a POSITIVE RABIES TEST or a SYMPTOMATIC ANIMAL, prophylaxis should be initiated immediately.
    3) RODENTS OR LAGOMORPHS BITES: Bites from rodents (such as squirrels, groundhogs, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) and lagomorphs (including rabbits and hares) are rarely found to be infected with rabies and have not been known to cause human rabies in the United States, though in certain species outside the US this is well reported. However, check with your local health department if outbreaks have occurred; outbreaks in rodents and lagomorphs have occurred most often in areas where raccoon rabies is enzootic.
    4) WILD ANIMAL BITES: The identity of the biting animal must be determined when possible. Carnivorous wild animals (i.e., raccoons, skunks, foxes, coyotes and bobcats) and bats continue to be the animals most commonly infected with rabies and have caused most of the indigenous cases of human rabies in the US. UNPROVOKED ATTACK: BEGIN POSTEXPOSURE TREATMENT IMMEDIATELY following an unprovoked attack by an animal including a bat. In most cases, an unprovoked attack by an animal rabies host is more likely than a provoked attack to indicate the animal is rabid. PROVOKED ATTACK: Bites inflicted on a person attempting to feed or handle an animal should generally be regarded as provoked. However, the virus may be present in saliva of affected animals several days before signs of disease occur. The virus could also be transmitted through saliva or other excretion without any bite. Unless such an animal is captured and has a negative fluorescent antibody test for rabies, postexposure treatment should be initiated immediately, upon a bite exposure. If treatment has been initiated and subsequent testing by a competent laboratory shows the biting animal is not rabid, treatment can be discontinued. Holding such an animal for observation is not recommended.
    5) REPORTING: HUMAN EXPOSURE: A case of suspected or confirmed rabies in a human should be reported to the state health department. Requirements vary by State. ANIMAL EXPOSURE: A case of suspected or confirmed rabies in an animal should be reported by the veterinarian to State livestock officials. Requirements vary by State.
    C) WOUND CARE
    1) Bite wounds should be carefully cleaned with soap and water to decrease the possibility of viral and bacterial infection. If available, a virucidal agent such as povidone-iodine solution should be used to irrigate the wounds. Prophylactic antibiotics tetanus toxoid, and surgical wound treatment may be necessary in some cases.
    D) AIRWAY MANAGEMENT
    1) Endotracheal intubation may be necessary in patients who develop respiratory failure and require mechanical ventilation; it may also be necessary in patients with pharyngeal spasms or decreased CNS function.
    E) RABIES IMMUNE GLOBULIN
    1) Administer human rabies immune globulin (HRIG) once, at the beginning of anti-rabies prophylaxis, to previously unvaccinated persons.
    2) DOSE: 20 units/kg (both adults and children). Infiltrate as much of the dose as possible into the area around and into the wound(s). Any remaining volume should be injected intramuscularly at a site distant from vaccine administration.
    3) HRIG should never be administered in the same syringe or in the same anatomical site as the first vaccine dose. However, subsequent doses of vaccine in the 4-dose series can be administered in the same anatomic location where the HRIG dose was administered.
    4) If HRIG was not administered when vaccination was begun, it can be administered up to 7 days after the administration of the first dose of vaccine.
    F) RABIES VACCINE
    1) A regimen of 4 1-mL doses of HDCV or PCEC vaccines should be administered intramuscularly to previously unvaccinated persons. The first dose of the 4-dose course should be administered as soon as possible after exposure. Additional doses should be administered on days 3, 7, and 14 after the first vaccination.
    2) For adults, the vaccination should always be administered IM in the deltoid area. For children, the anterolateral aspect of the thigh is also acceptable. The gluteal area should never be used for rabies vaccine injection.
    3) PREVIOUSLY VACCINATED: If exposed to rabies, previously vaccinated persons should receive 2 IM doses (1 mL each) of vaccine, one immediately and one 3 days later. Previously vaccinated persons are those who have received one of the recommended preexposure or postexposure regimens of HDCV, RVA, or PCECV, or those who received another vaccine and had a documented rabies antibody titer.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: All patients with potential rabies exposure should be referred to a healthcare facility.
    2) OBSERVATION CRITERIA: All patients with potential rabies exposure should be referred to a healthcare facility for wound care, evaluation and rabies prophylaxis.
    a) SUMMARY: Rabies prophylaxis must be considered when a patient has been potentially exposed via an animal bite, laboratory accident, contaminated organ transplant, or other known source. Domestic animals (especially vaccinated), rodents, and rabbits are unlikely to be sources; wild animals and wild/domestic animal hybrids are less likely to be vaccinated and more likely to be infected.
    b) DOG AND CAT BITES: The probability that a biting domestic dog or cat is infected with rabies varies from region to region but is usually small. Rabid cats represent the majority (62.2%) of reported domestic animal cases in the US, especially in States where raccoon rabies is enzootic. An apparently healthy dog or cat that bites a person should be confined, and observed for 10 days and evaluated by a veterinarian to see if the animal becomes ill during the observation period. If the dog or cat exhibits disease signs suggestive of rabies, the animal should be humanely killed and its head removed and shipped, under refrigeration, to a qualified laboratory for fluorescent antibody testing. Dogs or cats that appear normal at 10 days may be released without qualification, unless other issues or health or public safety exist. Observation of even vaccinated dogs or cats is prudent. If the dog or cat cannot be caught for observation, consult public health officials. PROPHYLAXIS THERAPY: In the event of a POSITIVE RABIES TEST or a SYMPTOMATIC ANIMAL, prophylaxis should be initiated immediately.
    c) RODENTS OR LAGOMORPHS BITES: Bites from rodents (such as squirrels, groundhogs, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) and lagomorphs (including rabbits and hares) are rarely found to be infected with rabies and have not been known to cause human rabies in the United States, though in certain species outside the US this is well reported. However, check with your local health department if outbreaks have occurred; outbreaks in rodents and lagomorphs have occurred most often in areas where raccoon rabies is enzootic.
    d) WILD ANIMAL BITES: The identity of the biting animal must be determined when possible. Carnivorous wild animals (i.e., raccoons, skunks, foxes, coyotes and bobcats) and bats continue to be the animals most commonly infected with rabies and have caused most of the indigenous cases of human rabies in the US. UNPROVOKED ATTACK: BEGIN POSTEXPOSURE TREATMENT IMMEDIATELY following an unprovoked attack by an animal including a bat. In most cases, an unprovoked attack by an animal rabies host is more likely than a provoked attack to indicate the animal is rabid. PROVOKED ATTACK: Bites inflicted on a person attempting to feed or handle an animal should generally be regarded as provoked. However, the virus may be present in saliva of affected animals several days before signs of disease occur. The virus could also be transmitted through saliva or other excretion without any bite. Unless such an animal is captured and has a negative fluorescent antibody test for rabies, postexposure treatment should be initiated immediately, upon a bite exposure. If treatment has been initiated and subsequent testing by a competent laboratory shows the biting animal is not rabid, treatment can be discontinued. Holding such an animal for observation is not recommended.
    e) REPORTING: HUMAN EXPOSURE: A case of suspected or confirmed rabies in a human should be reported to the state health department. Requirements vary by State. ANIMAL EXPOSURE: A case of suspected or confirmed rabies in an animal should be reported by the veterinarian to State livestock officials. Requirements vary by State.
    3) ADMISSION CRITERIA: Any patient with symptoms of rabies should be admitted.
    4) CONSULT CRITERIA: Consult animal control authorities to catch and quarantine the animal in question. Consult the local health department for information on the current incidence of rabies in the area.

Range Of Toxicity

    A) TOXICITY: Human rabies is almost always fatal. There have been a few reports in the literature of patients recovering from rabies, one patient was left with severe neurologic impairment.
    B) Approximately 1 to 2 deaths each year are recognized as attributable to rabies in the United States, but it is likely that unrecognized cases occur. Although rabies is relatively rare among the US population, each year between 16,000 and 39,000 persons receive postexposure prophylaxis.

Clinical Effects

Summary Of Exposure

    A) DEFINITION: Rabies is an acute encephalomyelitis caused by a virus of the rhabdovirus group. It is transmitted to humans most commonly through the bite of an infected animal.
    B) EPIDEMIOLOGY: Rabies can occur in any mammal. Rabies is most commonly found in wild animals such as raccoons, skunks, bats and foxes, and coyotes. The domestic animals that are most frequently affected in the US are cats, cattle, and dogs. In the US, approximately 1 to 2 deaths each year are attributable to rabies (unrecognized cases are likely to occur). Although rabies is relatively rare among the US population, each year between 16,000 and 39,000 persons receive postexposure prophylaxis. Rabies is much more common in the developing world.
    C) WITH POISONING/EXPOSURE
    1) INCUBATION PERIOD: After being exposed to rabies, the incubation period may range from 12 days to as long as 6 years, but averages 20 to 40 days. Once symptoms develop, rabies is nearly always fatal.
    2) There are 3 PHASES in humans:
    a) PHASE ONE: Consists of nonspecific symptoms including malaise, anorexia, irritability, low grade fever, headache, and vomiting which may persist from 1 to 3 days to 2 weeks.
    b) PHASE TWO: This is an acute neurological phase which lasts 2 to 7 days and is characterized by restlessness, dysarthria, agitation, dysphagia, and visual or auditory hallucinations.
    c) PHASE THREE: This final phase of 7 to 10 days is characterized by painful contraction of the pharyngeal muscles which causes a fear of swallowing, seizures, prolonged apnea with generalized flaccid paralysis and coma. The final stage generally begins with coma and results in respiratory and vascular collapse.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Fever commonly occurs in the prodromal phase. Hypothermia was reported in one case.
    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) HYPERTHERMIA: Fever is commonly noted in the prodromal phase (Centers for Disease Control and Prevention, 2012; Willoughby et al, 2005; Udwadia et al, 1989).
    2) RARE EFFECTS: Hypothermia was reported in one case 10 days after onset of symptoms (Udwadia et al, 1989).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) RARE EFFECTS: Choroiditis, focal nongranulomatous cyclitis, and inner retinal necrosis was described in a fatal case (Haltia et al, 1989).
    2) Diplopia and nystagmus were reported in a 15-year-old girl who developed rabies (Willoughby et al, 2005).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CONDUCTION DISORDER OF THE HEART
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT (RARE EFFECTS): Hypotension, dysrhythmias, and ST-segment depression were reported during the terminal phase in one case (Udwadia et al, 1989).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) WITH POISONING/EXPOSURE
    a) Apnea, succeeded by eventual respiratory collapse may occur (Srinivasan et al, 2005; Anon, 2004; CDC, 1977).
    B) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT (RARE EFFECTS): Adult respiratory distress syndrome was reported in one case, 7 days after onset of symptoms (Udwadia et al, 1989).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) TOXIC ENCEPHALOPATHY
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Restlessness, visual or auditory hallucinations, manic behavior alternating with lethargy, vertigo, nystagmus, polyneuritis, diplopia, strabismus; hyperactive deep tendon reflexes, plantar extension, and nuchal rigidity may occur in the second stage of the clinical course. Coma may occur in the third stage (CDC, 1977).
    1) Duration of second stage: 2 to 7 days
    2) Duration of third stage: 7 to 10 days
    b) CASE REPORT: A 29-year-old man from Virginia, died from rabies encephalitis associated with a presumed (a definitive animal bite could not be confirmed) bat exposure (MMWR , 1999). Initial symptoms were malaise, back and abdominal pain, and vomiting followed by muscle tremors and difficulty walking. Three days later, a fever (39.4 degrees Celsius) and periods of hallucination, agitation and disorientation occurred. The patient died approximately 15 days after the initial onset of symptoms.
    c) CASE REPORTS: Lethargy, deterioration in mental status, and cerebral edema were reported in three transplant recipients who received their organs from a donor, who was subsequently found to have serologic evidence of rabies infection. All three patients died within 2 months after receiving their organs (Srinivasan et al, 2005; Anon, 2004).
    d) CASE REPORT/SURVIVAL: An 8-year-old girl from a rural area developed rabies (positive detection of rabies virus specific antibodies in serum and CSF was diagnosed on hospital day 3) after having contact with unvaccinated cats found at her local school. She was initially admitted with a 1-week history of sore throat, difficulty swallowing, and bilateral lower extremity weakness. Symptoms progressed to include ascending flaccid paralysis, decreased mentation, and fever. Treatment included intubation and ventilation, therapeutic coma (ketamine and midazolam), amantadine and nimodipine (to prevent cerebral artery vasospasm). She did not receive human rabies immunoglobulin nor rabies vaccine. About 7 days after admission, the patient moved her head spontaneously and began to move her arms and legs over the next few days. She was extubated after 2 weeks and transferred to a medical floor. The patient was discharged after 4 weeks to a rehabilitation center for further care due to residual foot drop. Within 3 weeks she was ambulating and tolerating daily activities with no residual cognitive impairment (Centers for Disease Control and Prevention, 2012).
    e) CASE REPORT/FATALITY: An 11-year-old boy from the Philippines presented to an emergency department with evidence of clinical rabies. The child had been bitten 2 years earlier by a dog in the Philippines and had not received any treatment (ie, rabies vaccine, postexposure prophylaxis). Symptoms included progressive dysphagia, shortness of breath, and alternating extreme agitation and obtundation. The child was placed in a coma using ketamine and midazolam for presumed rabies. Ongoing aggressive supportive care was provided. By day 15, pupils were fixed and dilated and by day 24 a head CT showed severe cerebral edema. Secondary complications were severe and included ventilator-induced pneumonia, pancreatitis, heart block requiring transvenous pacing and thrombophlebitis. Treatment was withdrawn on day 27. Overall, autopsy findings were consistent with severe lymphocytic encephalitis with superimposed secondary hypoxic ischemic encephalopathy; rabies was confirmed in brain tissue (Aramburo et al, 2011).
    f) CASE REPORT/FATALITY: A 73-year-old man died 9 weeks after intensive care of encephalitis caused by a rabies virus variant associated with silver-haired bats. His past medical history include a bite by a bat on his shoulder that was not treated 6 months prior to admission (6th day of clinical illness). Initial symptoms included general weakness, anorexia and dysphagia. He developed respiratory compromise and required intubation (9th day of clinical illness). Rabies immune globulin (1200 units IM) was given once the family recalled the bite after approximately 2 weeks of clinical illness. Additional intensive care was provided. Despite improvement in hemodynamic function with low-dose pressor support and ventilation and gradual withdrawal of sedation, the patient did not regain neurologic function. His clinical course was also complicated by arrhythmias, SIADH, ventilator-induced pneumonia and ribavirin-associated hemolysis. Approximately 8 weeks after the initiation of therapy, diagnostic studies concluded that brain death had occurred and care was withdrawn. At autopsy, direct fluorescent antibody staining showed an abundance of the rabies virus in the brain stem and cerebral cortex and confirmed by reverse-transcription polymerase chain reaction (Centers for Disease Control and Prevention (CDC), 2008).
    g) CASE REPORT/SURVIVAL: A 15-year-old girl, who was bitten on her left index finger by a bat, experienced generalized fatigue and paresthesia of the left hand one month later. Over the next several days, her condition deteriorated with development of fever, diplopia, nausea and vomiting, partial bilateral sixth-nerve palsy, dysarthria, ataxia, slurred speech, nystagmus, and tremors of her left arm. The patient began salivating with uncoordinated swallowing, necessitating intubation for airway protection. Laboratory analysis, confirmed by the Centers for Disease Control, revealed the presence of rabies virus-specific antibody in her serum and cerebrospinal fluid. Treatment included induction of coma, using ketamine (2 mg/kg/hour) with midazolam (1 to 3.5 mg/kg/hr), administration of ribavirin and amantadine, and intensive supportive care. Approximately 6 days after induction of coma, a lumbar puncture revealed an increased level of rabies-virus antibody in the serum and cerebrospinal fluid. Ketamine was tapered over 24 hours, and midazolam was replaced by diazepam. The patient's condition improved and she was discharged hospital day 76; however, 5 months post-hospitalization, she continued to experience choreoathetosis, dysarthria, and an unsteady gait (Willoughby et al, 2005).
    B) SECONDARY PERIPHERAL NEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) PERIPHERAL NERVOUS SYSTEM: Dysphagia, polyneuritis, hyperactive tendon reflexes, plantar extension, and generalized flaccid paralysis or Guillian-Barre syndrome, leading to coma and respiratory and vascular collapse may occur (Baer, 1975; Libby & Meislin, 1983; Bhatt et al, 1974; CDC, 1977).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Nausea and vomiting occurred in a 15-year-old girl approximately 1 month after being bitten by a bat. Subsequent laboratory analysis revealed the presence of rabies virus-specific antibody in her serum and cerebrospinal fluid (Willoughby et al, 2005).
    B) EXCESSIVE SALIVATION
    1) WITH POISONING/EXPOSURE
    a) Hypersalivation with uncoordinated swallowing may occur (Willoughby et al, 2005).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) EDEMA
    1) WITH POISONING/EXPOSURE
    a) MYOEDEMA was present in 4 paralytic rabies cases. This finding is not commonly associated with Guillain-Barre syndrome, and may aid in differential diagnosis (Hemachudha et al, 1987).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Most patients receiving rabies prophylaxis do not need any laboratory studies.
    B) In patients with rabies, findings include leukocytosis, glycosuria, proteinuria, and oliguria.
    C) Definitive diagnosis is usually made at autopsy by the fluorescent rabies antibody test on brain impression smears. The fluorescent rabies antibody test performed on living ocular impression smears and skin biopsies may be of value.
    4.1.2) SERUM/BLOOD
    A) HEMATOLOGIC
    1) Findings can include leukocytosis.
    4.1.3) URINE
    A) URINALYSIS
    1) Glycosuria, proteinuria, and oliguria may occur.
    4.1.4) OTHER
    A) OTHER
    1) CEREBROSPINAL FLUID
    a) CSF may contain slightly increased protein and mononuclear cells.

Methods

    A) IMMUNOASSAY
    1) FLUORESCENT ANTIBODY TEST: Definitive diagnosis is usually made at autopsy by the fluorescent rabies antibody (FRA) test on brain impression smears. The FRA test can also be performed on living ocular impression smears and skin biopsies.
    2) SEROLOGY: The Rapid Fluorescent Focus Inhibition Test (RFFIT) is done by the laboratories listed below for a fee. Sample needed: 2 mL serum, shipped frozen. For optimum titer, the blood serum should be taken 2 to 3 weeks after completion of the vaccination series. Send samples to 
    Attn:  Dr. Deborah J. Briggs, Director/RFFIT
Mosier Hall
Department of Veterinary Diagnosis
Veterinary Medical Center
Kansas State University
1800 Denison Avenue
Manhattan, KS 66506-5600
For additional information
contact the rabies lab - 
Tel. (785) 532-4483
http://www.vet.ksu.edu/depts/rabies/index.htm

    Laboratory Corporation of America
http://www.labcorp.com

    a) The Immunization Practices Advisory Committee (ACIP) has determined that virtually all persons treated with RIG and 1.0 mL IM doses of HDCV since June 1980 have developed adequate antibody levels (Anon, 1984).
    1) Therefore, serologic confirmation of antibody production is no longer considered necessary except in immunocompromised patients.
    3) POSTVACCINATION SEROLOGY TESTING: Testing is NOT indicated in healthy patients who have completed prophylaxis treatment to document seroconversion, unless the patient is immunosuppressed. If titers are collected, specimens obtained 1 to 2 weeks after prophylaxis should be able to completely neutralize challenge virus at a 1:5 serum dilution by the rapid fluorescent focus inhibition test (Centers for Disease Control and Prevention, 2009).
    B) OTHER
    1) VIRUS TYPING may be used to trace an infecting virus to its source. Differences between strains of wild rabies virus and their origins can be detected (Anon, 1991; Anon, 1992a; Smith et al, 1991).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.6) DISPOSITION/BITE-STING EXPOSURE
    6.3.6.1) ADMISSION CRITERIA/BITE-STING
    A) Any patient with symptoms of rabies should be admitted.
    6.3.6.2) HOME CRITERIA/BITE-STING
    A) All patients with potential rabies exposure should be referred to a healthcare facility.
    6.3.6.3) CONSULT CRITERIA/BITE-STING
    A) Consult animal control authorities to catch and quarantine the animal in question. Consult the local health department for information on the current incidence of rabies in the area.
    6.3.6.5) OBSERVATION CRITERIA/BITE-STING
    A) All patients with potential rabies exposure should be referred to a healthcare facility for wound care, evaluation and rabies prophylaxis.
    1) SUMMARY: Rabies prophylaxis must be considered when a patient has been potentially exposed via an animal bite, laboratory accident, contaminated organ transplant, or other known source. Domestic animals (especially vaccinated), rodents, and rabbits are unlikely to be sources; wild animals and wild/domestic animal hybrids are less likely to be vaccinated and more likely to be infected.
    2) DOG AND CAT BITES: The probability that a biting domestic dog or cat is infected with rabies varies from region to region but is usually small. Rabid cats represent the majority (62.2%) of reported domestic animal cases in the US, especially in States where raccoon rabies is enzootic. An apparently healthy dog or cat that bites a person should be confined, and observed for 10 days and evaluated by a veterinarian to see if the animal becomes ill during the observation period. If the dog or cat exhibits disease signs suggestive of rabies, the animal should be humanely killed and its head removed and shipped, under refrigeration, to a qualified laboratory for fluorescent antibody testing. Dogs or cats that appear normal at 10 days may be released without qualification, unless other issues or health or public safety exist. Observation of even vaccinated dogs or cats is prudent. If the dog or cat cannot be caught for observation, consult public health officials. PROPHYLAXIS THERAPY: In the event of a POSITIVE RABIES TEST or a SYMPTOMATIC ANIMAL, prophylaxis should be initiated immediately.
    3) RODENTS OR LAGOMORPHS BITES: Bites from rodents (such as squirrels, groundhogs, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) and lagomorphs (including rabbits and hares) are rarely found to be infected with rabies and have not been known to cause human rabies in the United States, though in certain species outside the US this is well reported. However, check with your local health department if outbreaks have occurred; outbreaks in rodents and lagomorphs have occurred most often in areas where raccoon rabies is enzootic.
    4) WILD ANIMAL BITES: The identity of the biting animal must be determined when possible. Carnivorous wild animals (i.e., raccoons, skunks, foxes, coyotes and bobcats) and bats continue to be the animals most commonly infected with rabies and have caused most of the indigenous cases of human rabies in the US. UNPROVOKED ATTACK: BEGIN POSTEXPOSURE TREATMENT IMMEDIATELY following an unprovoked attack by an animal including a bat. In most cases, an unprovoked attack by an animal rabies host is more likely than a provoked attack to indicate the animal is rabid. PROVOKED ATTACK: Bites inflicted on a person attempting to feed or handle an animal should generally be regarded as provoked. However, the virus may be present in saliva of affected animals several days before signs of disease occur. The virus could also be transmitted through saliva or other excretion without any bite. Unless such an animal is captured and has a negative fluorescent antibody test for rabies, postexposure treatment should be initiated immediately, upon a bite exposure. If treatment has been initiated and subsequent testing by a competent laboratory shows the biting animal is not rabid, treatment can be discontinued. Holding such an animal for observation is not recommended.

Monitoring

    A) Most patients receiving rabies prophylaxis do not need any laboratory studies.
    B) In patients with rabies, findings include leukocytosis, glycosuria, proteinuria, and oliguria.
    C) Definitive diagnosis is usually made at autopsy by the fluorescent rabies antibody test on brain impression smears. The fluorescent rabies antibody test performed on living ocular impression smears and skin biopsies may be of value.

Abstracts

Case Reports

    A) ADULT
    1) A 45-year-old man was bitten by a dog and began treatment with human diploid vaccine 3 days later after the dog had died. He had an allergic reaction to the test dose of rabies immune globulin and was advised not to proceed with therapy. He presented 15 days after the bite with fever, nausea, vomiting, and headache. On the 4th day dysphagia developed. On the 5th day, bilateral facial weakness and glossopharyngeal and vagal paralysis were noted. A tracheostomy was performed and intense supportive care and monitoring initiated. On the 7th day, a rapidly ascending paralysis began, complicated by ARDS. On the 10th day hypothermia was noted. Subsequent complications included diabetes insipidus, stress gastrointestinal bleeding, paralytic ileus, and myocarditis. Death occurred secondary to ventricular fibrillation 25 days after onset of symptoms (Udwadia et al, 1989).
    2) Three transplant recipients (1 liver recipient and 2 kidney recipients) received their organs from a man who had presented to two hospitals, with severe mental status changes and low grade fever. Neurologic imaging of the patient showed a subarachnoid hemorrhage which rapidly progressed to cerebral herniation and death. His liver and kidneys were recovered and were subsequently transplanted after donor eligibility screening and testing did not reveal any contraindications to transplantation.
    a) The liver recipient developed tremors, lethargy, anorexia, and rapid deterioration of mental status approximately 22 days post transplantation. An MRI indicated diffuse encephalitis and the patient subsequently died. The female kidney transplant recipient experienced increasing lethargy and twitching 25 days post transplantation. She developed progressive mental status changes, seizures, hypotension, and respiratory failure requiring mechanical ventilation, with subsequent death. An MRI, performed 2 weeks after admission, showed severe cerebral edema. The male kidney transplant recipient experienced progressively deteriorating mental status and myoclonic jerks 27 days post transplantation. He developed respiratory failure and subsequently died. An MRI, performed 10 days after admission, showed diffuse cerebral edema.
    b) Histopathologic examination of the CNS of all 3 patients showed encephalitis with viral inclusions suggestive of Negri bodies. A diagnosis of rabies was confirmed via immunohistochemical testing and by the detection of the rabies virus antigen in fixed brain tissue via direct fluorescent antibody tests. It is believed that transmission of the rabies virus from the organ donor to the solid organ transplant recipients occurred via neuronal tissue contained in the transplanted organs (Srinivasan et al, 2005; Anon, 2004).

Range Of Toxicity

Summary

    A) TOXICITY: Human rabies is almost always fatal. There have been a few reports in the literature of patients recovering from rabies, one patient was left with severe neurologic impairment.
    B) Approximately 1 to 2 deaths each year are recognized as attributable to rabies in the United States, but it is likely that unrecognized cases occur. Although rabies is relatively rare among the US population, each year between 16,000 and 39,000 persons receive postexposure prophylaxis.

Minimum Lethal Exposure

    A) SUMMARY
    1) The actual numbers of viral particles necessary for infection are unknown. Any bite from an infected animal may cause the disease, but it is unknown if every such bite will result in infection.
    2) Human rabies is almost always a fatal viral encephalitis transmitted by the bite of a rabid animal. Most cases in the United States and Canada have been due to exposure to bats (Webster et al, 1987). An average of 1 to 2 deaths are reported annually due to rabies in the United States ((CDC, 1998)).
    B) CASE REPORTS
    1) CASE REPORTS: Lethargy, deterioration in mental status, and cerebral edema were reported in three transplant recipients who received their organs from a donor, who was subsequently found to have serologic evidence of rabies infection. All three patients died within 2 months after receiving their organs (Srinivasan et al, 2005; Anon, 2004).
    2) CASE REPORT: An 11-year-old boy from the Philippines presented to an emergency department with evidence of clinical rabies. The child had been bitten 2 years earlier by a dog in the Philippines and had not received any treatment (ie, rabies vaccine, postexposure prophylaxis). Symptoms included progressive dysphagia, shortness of breath, and alternating extreme agitation and obtundation. The child was placed in a coma using ketamine and midazolam for presumed rabies. Ongoing aggressive supportive care was provided. By day 15, pupils were fixed and dilated and by day 24 a head CT showed severe cerebral edema. Secondary complications were severe and included ventilator-induced pneumonia, pancreatitis, heart block requiring transvenous pacing and thrombophlebitis. Treatment was withdrawn on day 27. Overall, autopsy findings were consistent with severe lymphocytic encephalitis with superimposed secondary hypoxic ischemic encephalopathy; rabies was confirmed in brain tissue (Aramburo et al, 2011).
    3) CASE REPORT: A 73-year-old man died 9 weeks after intensive care of encephalitis caused by a rabies virus variant associated with silver-haired bats. His past medical history include a bite by a bat on his shoulder that was not treated 6 months prior to admission (6th day of clinical illness). Initial symptoms included general weakness, anorexia and dysphagia. He developed respiratory compromise and required intubation (9th day of clinical illness). Rabies immune globulin (1200 units IM) was given once the family recalled the bite after approximately 2 weeks of clinical illness. His clinical course was also complicated by arrhythmias, SIADH, ventilator-induced pneumonia and ribavirin-associated hemolysis. Approximately 8 weeks after the initiation of therapy, diagnostic studies concluded that brain death had occurred and care was withdrawn. At autopsy, direct fluorescent antibody staining showed an abundance of the rabies virus in the brain stem and cerebral cortex and confirmed by reverse-transcription polymerase chain reaction (Centers for Disease Control and Prevention (CDC), 2008).

Maximum Tolerated Exposure

    A) SUMMARY
    1) Although rabies is relatively rare among the US population, each year between 16,000 and 39,000 persons receive postexposure prophylaxis (Manning et al, 2008; (CDC, 2000); (IPAC, 1999)).
    B) CASE REPORTS
    1) CASE REPORT: An 8-year-old girl from a rural area developed rabies (positive detection of rabies virus specific antibodies in serum and CSF was diagnosed on hospital day 3) after having contact with unvaccinated cats found at her local school. She was initially admitted with a 1-week history of sore throat, difficulty swallowing, and bilateral lower extremity weakness. Symptoms progressed to include ascending flaccid paralysis, decreased mentation, and fever. Treatment included intubation and ventilation, therapeutic coma (ketamine and midazolam), amantadine and nimodipine (to prevent cerebral artery vasospasm). She did not receive human rabies immunoglobulin nor rabies vaccine. About 7 days after admission, the patient moved her head spontaneously and began to move her arms and legs over the next few days. She was extubated after 2 weeks and transferred to a medical floor. The patient was discharged after 4 weeks to a rehabilitation center for further care due to residual foot drop. Within 3 weeks she was ambulating and tolerating daily activities with no residual cognitive impairment (Centers for Disease Control and Prevention, 2012).
    2) CASE REPORT: A 15-year-old girl, who was bitten on her left index finger by a bat, experienced generalized fatigue and paresthesia of the left hand one month later. Over the next several days, her condition deteriorated with development of fever, diplopia, nausea and vomiting, partial bilateral sixth-nerve palsy, dysarthria, ataxia, slurred speech, nystagmus, and tremors of her left arm. The patient began salivating with uncoordinated swallowing, necessitating intubation for airway protection. Laboratory analysis, confirmed by the Centers for Disease Control, revealed the presence of rabies virus-specific antibody in her serum and cerebrospinal fluid. Treatment included induction of coma, using ketamine (2 mg/kg/hour) with midazolam (1 to 3.5 mg/kg/hr), administration of ribavirin and amantadine, and intensive supportive care. Approximately 6 days after induction of coma, a lumbar puncture revealed an increased level of rabies-virus antibody in the serum and cerebrospinal fluid. Ketamine was tapered over 24 hours, and midazolam was replaced by diazepam. The patient's condition improved and she was discharged hospital day 76; however, 5 months post-hospitalization, she continued to experience choreoathetosis, dysarthria, and an unsteady gait (Willoughby et al, 2005).

Pharmacology Toxicology

Toxicologic Mechanism

    A) Human rabies is almost always a fatal viral encephalitis transmitted by the bite of a rabid animal. The rabies virus, contained in the saliva, is neurotropic and spreads from the site of inoculation along nerve pathways to the posterior columns of the spinal cord and then to the brain. From facial or head wounds it spreads to the brain via the cranial nerves.
    B) Once the virus enters through a wound, it proliferates in muscle cells near the bite. It then moves to the neuromuscular spindles, peripheral nervous system, and finally the central nervous system (Frenia et al, 1992).

Animal Toxicology

Clinical Effects

    11.1.3) CANINE/DOG
    A) Clinical signs occur in 3 stages: (1) the prodromal stage, which usually lasts 2 to 3 days, includes a slight rise in temperature and a subtle behavior change. (2) Excitative phase: dogs will show aggression, irritability and restlessness. They may exhibit pica, or snap at anything that moves. Dogs may exhibit the "dumb" form of rabies, characterized by extreme lethargy. (3) Paralytic phase, which leads to death (Kirk, 1986).
    B) There are reports of dogs surviving for at least a month with active rabies (Anon, 1991).
    11.1.5) EQUINE/HORSE
    A) In a study of 21 horses with confirmed rabies, the most commonly reported clinical signs were: ataxia and paresis of the hindquarters, lameness, recumbency, loss of tail and anal sphincter tone, fever, and hyperesthesia. Mean survival time after onset of clinical signs was 4.47 days (Green et al, 1992).
    11.1.6) FELINE/CAT
    A) Clinical signs occur in 3 stages: (1) the prodromal stage, which usually lasts 2 to 3 days, includes a slight rise in temperature and a subtle behavior change. (2) Excitative phase: cats will show aggression, irritability and restlessness. Cats less often exhibit the "dumb" form of rabies. (3) Paralytic phase, which leads to death (Kirk, 1986).
    11.1.13) OTHER
    A) OTHER
    1) POST-VACCINE RABIES - Rabies has been reported in several species after they were vaccinated with a modified-live rabies virus vaccine (Kirk, 1986).
    2) SUSCEPTIBLE SPECIES - All mammals are susceptible to rabies. Wild species that have been implicated or in which diagnosis of rabies has occurred include skunks, raccoons, foxes, bobcats, badgers, weasels, coyotes, ocelots, oppossums, mountain lions, and bats (Kirk, 1989).

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) Isolate the animal immediately.
    2) ANIMAL POISON CONTROL CENTERS
    a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.
    3) TAGS - Vaccinated animals may be wearing standard tags. Shape and color of the tag indicates the year vaccinated (CDC, 1992).
    4) A case of suspected or confirmed rabies in an animal should be reported by the veterinarian to state livestock officials. Requirements vary by State.
    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.5) TREATMENT
    A) DOGS/CATS
    1) Any animal bitten or scratched by a bat or wild, carnivorous mammal not available for testing should be regarded as having been exposed to rabies (CDC, 1992).
    a) PETS CURRENT ON RABIES PROPHYLAXIS may be revaccinated immediately, leashed, and confined for 90 days following suspected exposure to rabies.
    b) UNVACCINATED DOGS AND CATS bitten by or exposed to a rabid animal should be destroyed immediately. If the owner is unwilling to do this, the animal may be placed in veterinary-supervised isolation for 6 months and vaccinated 1 month prior to release (Kirk, 1986; CDC, 1992).
    2) PRODUCTS FOR VACCINATION - Several prophylactic products are available. Recommendations for products can be found in the Compendium of Animal Rabies Control. Dogs and cats should be vaccinated at 3 months of age and yearly or triennially (dependent upon the product) thereafter (Kirk, 1989).
    3) A healthy cat or dog that bites a person must be confined and observed for ten days. A veterinarian must be consulted at any sign of illness. If signs of rabies develop, the animal must be euthanized and its head must be submitted for testing to a health department approved laboratory. Any unwanted or stray animal that bites a person may be euthanized and tested (Kirk, 1989).
    B) HORSE
    1) Vaccines approved for horses include Rabguard-TC (Norden), dosed at 1 milliliter intramuscularly; Rabvac 3 (Salsbury), dosed at 2 milliliters intramuscularly; and Imrab (Rhone Merieux), dosed at 2 milliliters intramuscularly. All recommend annual boosters (Kirk, 1989).
    a) An unvaccinated horse known to have been bitten by a rabid animal should either be euthanized or quarantined and observed for 6 months, then vaccinated if still healthy. A vaccinated horse should be observed (Robinson, 1987).
    C) SHEEP
    1) Vaccines approved for sheep include Rabguard-TC (Norden), dosed at 1 milliliter intramuscularly annually; and Imrab (Rhone Merieux), dosed at 2 milliliters intramuscularly triennially (Kirk, 1989).
    D) CATTLE
    1) Vaccines approved for cattle include Rabguard-TC (Norden), dosed at 1 milliliter intramuscularly; and Imrab (Rhone Merieux), dosed at 2 milliliters intramuscularly. All recommend annual boosters. It is often not feasible to vaccinate livestock, even though cattle are very susceptible to rabies. Livestock that are valuable and/or have high contact with humans probably should be vaccinated (Kirk, 1989).
    2) Livestock bitten by rabid animals should be destroyed immediately. If the owner is unwilling to do this, the animal may be quarantined for 6 months. If the bitten animal was currently vaccinated with a vaccine approved by USDA for that species, it may be revaccinated immediately and placed under observation for 90 days (CDC, 1992).
    3) Neither tissues nor milk from a rabid animal should be consumed; however, the rabies virus is inactivated at pasteurization and cooking temperatures so ingestion of cooked food from such animals does not constitute an exposure.
    4) Herbivore/herbivore transmission is extremely rare, so the herd usually will not have to be quarantined if one animal is affected (CDC, 1992; Howard, 1986).
    E) EXOTIC/WILD PETS/ZOO ANIMALS
    1) No rabies prophylaxis is approved for use in these animals. Wild animals captured for zoos must be quarantined for 180 days. Use of even inactivated vaccine is NOT recommended. Animal handlers should be immunized against rabies (Kirk, 1989).
    2) Wild or exotic animals bitten by a rabid animal should be euthanized immediately. If the bitten animal was currently vaccinated with a vaccine approved by USDA for that species, it may be revaccinated immediately and placed in strict isolation for at least 90 days (CDC, 1992).

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) Isolate the animal immediately.
    2) ANIMAL POISON CONTROL CENTERS
    a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.
    3) TAGS - Vaccinated animals may be wearing standard tags. Shape and color of the tag indicates the year vaccinated (CDC, 1992).
    4) A case of suspected or confirmed rabies in an animal should be reported by the veterinarian to state livestock officials. Requirements vary by State.
    11.4.3) TREATMENT
    11.4.3.5) SUPPORTIVE CARE
    A) GENERAL
    1) Ongoing treatment is symptomatic and supportive.
    11.4.3.6) OTHER
    A) OTHER
    1) SPECIFIC TOXIN
    a) LABORATORY TESTS - The best test available for rapid diagnosis is the fluorescent rabies antibody test (FRA). Tissues needed for examination include brain, salivary gland, or frozen section skin biopsies of the lateral sensory papillae which surround the sensory whiskers on the cheek of the dog. Possible laboratories to consult include the Veterinary Diagnostic Laboratory at Kansas State University, which has been conducting rabies examinations of skin tissue for several years (Kirk, 1986).

Other

    A) OTHER
    1) GENERAL
    a) IMMUNIZATION OF HUMANS -
    1) All animal handlers, veterinarians, and other staff that have frequent contact with animals should be immunized against rabies. Human exposure to inoculation with animal rabies vaccines constitutes no rabies hazard. There are no reported cases of human rabies resulting from such exposure (Kirk, 1986).
    b) PREEXPOSURE VACCINATION OF WILD AND EXOTIC ANIMALS -
    1) The Compendium of Animal Rabies Control recommends that rabies-susceptible wild or exotic animals, including cross-breeds of wild and domestic animals, not be kept as pets and vaccination of such animals against rabies is not recommended (Kirk, 1989).
    2) FERRETS are considered wild animals, and are susceptible to and could transmit rabies. Therefore, some regulatory agencies recommend that ferrets not be kept as pets and some authorities do not recommend vaccinating them for rabies. Possibly, the only time ferrets may be vaccinated would be during a rabies epizootic inside an established zoologic park. Even then, only a killed vaccine, preferably of murine origin, should be used (Kirk, 1989).
    a) An inactivated rabies vaccine was licensed in 1990 (IMRAB, by Pitman-Moore) for use in ferrets. Ferrets are given 1 milliliter of vaccine intramuscularly at ages 3 months and one year, and annually thereafter (NASPHV, 1991).

References

General Bibliography

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    3) Anon: Bat to skunk transmission of rabies. Colorado Disease Bulletin 1992a; 19:2.
    4) Anon: Human rabies case in Arkansas. Vet Hum Toxicol 1992c; 34:260.
    5) Anon: Human rabies: strain identification reveals lengthy incubation. Lancet 1991; 337:822-823.
    6) Anon: Investigation of rabies infections in organ donor and transplant recipients - Alabama, Arkansas, Oklahoma, and Texas, 2004. MMWR 2004; 53:586-589.
    7) Anon: Rabies prevention-United States. MMWR 1984; 33:393-402.
    8) Anon: Rabies risk from bats 'extremely small'. Vet Rec 1989; 125:97.
    9) Anon: Recommendations for ferrets regarding vaccination, bite follow-up and exposure to rabies. Colorado Disease Bulletin 1992; 19:1.
    10) Anon: Supplementary statement on rabies vaccine and serologic testing. MMWR 1981; 30:535-536.
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    12) Baer GM, Shaddock JH, & Houff SA: Human rabies transmitted by corneal transplant. Arch Neurol 1982; 39:103-107.
    13) Baer GM: The Natural History of Rabies, II, Academic Press, New York, NY, 1975, pp 281-304.
    14) Bek MD, Smith WT, & Levy MH: Rabies case in new south Wales, 1990: public health aspects. Med J Aust 1992; 156:596-598.
    15) Bhatt DR, Hattwick MAW, & Gerdsen R: Human rabies: diagnosis, complications, and management. Am J Dis Child 1974; 127:862-869.
    16) Blanton JD , Palmer D , Dyer J , et al: Rabies surveillance in the United States during 2010. J Am Vet Med Assoc 2011; 239(6):773-783.
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