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Emergency Medicine News:
ID Rounds

Lions and Tigers and … Puppies? Oh, My!

Saks, Mark MD

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Dr. Saks is a clinical instructor of emergency medicine at Drexel University College of Medicine and an attending emergency physician at Hahnemann University Hospital in Philadelphia.

An 8-week-old puppy was adopted from a Philadelphia branch of the American Society for the Prevention of Cruelty to Animals (ASPCA), but subsequently developed paralysis and was returned. Testing revealed rabies, making it the first rabid dog detected in the city in more than 55 years, and post-exposure prophylaxis was initiated on four family members who had potential exposure to the puppy's saliva.

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Despite being considered in every animal bite that presents to the ED, rabies is actually an uncommon cause of human illness in developed countries. Worldwide, however, more than 50,000 annual deaths are attributed to rabies. This high disease burden is primarily due to deficiencies in wild animal control, few pet vaccination programs, and a lack of human post-exposure prophylaxis in developing countries.

Rabies is one of the oldest recognized zoonotic diseases. Prior to 1960, the majority of rabies cases reported to the Centers for Disease Control and Prevention were in domestic animals. Due to improvements in veterinary care and pet vaccination programs, however, this has changed. Of the 7,170 cases of rabies reported to the CDC in 2003, more than 90 percent were among wild animals. (J Am Vet Med Assoc 2004;225[12]:1837.) Although all mammals are susceptible to rabies virus infection, only a few North American species are considered an important natural reservoir for the disease including raccoons, bats, skunks, foxes, and coyotes. Rabies is seldom reported in lagomorphs (rabbits and hares) or small rodents because they rarely survive an attack by a rabid animal. Since 1980, more than half of U.S. cases of human rabies have been associated with bats.

Transmission typically occurs through direct contact. Viral accumulation in the salivary glands and virus-induced aggressive biting in the host animal maximize chances of transmitting the infection to a new host. Although passage of infectious saliva during a bite is the most common means of transmission, any contact between infected tissue or fluids with an uninfected animal can lead to transmission. At least two incidents of potential mass exposures to rabies from drinking the unpasteurized milk of rabid cows have been reported. (MMWR 1999;48;228.) There are also several reports of transmission through solid-organ donation. (MMWR 2004;53;586.)

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Process and Symptoms

Following primary infection, the rabies virus enters an incubation phase that lasts for several days or months, during which it cannot be detected easily and does not cause any apparent symptoms. After uptake into peripheral nerves, rabies virus is transported to the CNS via sensory and motor nerves from the initial site of infection. Dissemination of the virus within the CNS is rapid, and it spreads centrifugally to other highly innervated sites. In an infected animal, the virus is widely distributed, and is found in the central and peripheral nervous systems, kidney, prostate, pancreas, saliva, and other body fluids. (MMWR 1999;48;228.)

Rabies is rapidly progressive and nearly always fatal. Early symptoms are nonspecific, and consist of fever, headache, and general malaise. Patients also may complain of discomfort, itching, or paresthesias at the site of the bite. As the disease progresses, patients may develop hydrophobia, become hyperexcitable, or exhibit autonomic dysfunction such as hypersalivation, piloerection, and priapism. Focal neurologic deficits, cranial nerve palsies, or flaccid paralysis also may develop. A generalized encephalomyelitis rapidly degrades to a coma, and death usually occurs within days from the onset of symptoms. A Wisconsin teenager recently made headlines by becoming the first person to survive clinical rabies without receiving pre- or post-exposure prophylaxis, although she has significant residual neurologic deficits. (N Engl J Med 2005;352[24]:2549.)

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Diagnosis and Prevention

In animals, the gold standard and the most frequently used diagnostic test is a direct fluorescent antibody test (DFA). Because it requires brain tissue from suspected animals, however, it can only be performed post-mortem. In humans, no single test is sufficient to diagnosis ante-mortem rabies. Saliva can be tested by viral isolation or reverse transcription polymerase chain reaction (RT-PCR), and serum and spinal fluid can be tested for antibodies to the rabies virus. Skin biopsy may reveal rabies antigen in cutaneous nerves at the base of hair follicles.

Rabies is almost always fatal, and is 100 percent preventable. Emergency physicians must maintain an appropriately low threshold for treating animal bites. Additionally, any patient who presents with encephalopathy of unknown cause should be considered potentially to have rabies, even in the absence of known exposure. (Ann Intern Med 1998;128[11]:922.) Although there are no documented cases of transmission of the rabies virus from patients to health care providers or family members, post-exposure prophylaxis is recommended for providers who have been exposed to a patient's saliva, nerve tissues, or cerebrospinal fluid two weeks before, or any time after, the onset of rabies in a patient. Prophylaxis also is recommended for those exposed to bats if there was a chance of contact, even if it was not recognized. (MMWR 1999;48:1.)

Human rabies is uncommon in developed countries, but causes more than 50,000 deaths a year in developing ones

The mainstay of preventing human rabies focuses on pre-exposure and post-exposure prophylaxis with human rabies immune globulin (HRIG) and a cell-culture-derived vaccine. Pre-exposure prophylaxis is recommended for certain high-risk people such as veterinarians, animal handlers, and laboratory workers. This does not eliminate the need for post-exposure treatment, but it negates the need for post-exposure HRIG, decreases the number of additional vaccine doses needed, and enhances immunity in unapparent exposures or if therapy is delayed.

Post-exposure prophylaxis should be initiated after copious wound irrigation with soap and water. It is currently recommended to give one dose of HRIG (20 IU/kg) at the initial presentation with as much volume as anatomically possible locally injected into the wound and immediate surrounding area. Any remaining HRIG should be given IM at a distant site. HRIG should never be administered in the same syringe or in the same anatomical site as the vaccine. The rabies vaccine is given as a course of five doses on days 0, 3, 7, 14, and 28. When initiated promptly, there have been no reported failures of this regimen. (MMWR 1999;48:1.)

© 2006 Lippincott Williams & Wilkins, Inc.

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