eMedicine Specialties > Emergency Medicine > Infectious Diseases

Rabies

Author: Mark A Merlin, DO, EMT-P, FACEP, Assistant Professor, EMS Medical Director, Department of Emergency Medicine, University of Medicine and Dentistry-Robert Wood Johnson Medical School; Medical Director, New Jersey EMS/Disaster Medicine Fellowship, New Jersey EMS Physician Response Program, New Jersey EMS Task Force; Chair of New Jersey Mobile Intensive Care Unit Advisory Council, New Jersey Department of Health and Senior Services
Coauthor(s): Peter W Pryor II, MD, MPH, Fellow in Emergency Medical Services/Disaster Medicine, Attending Physician, Department of Emergency Medicine, Robert Wood Johnson University Hospital, University of Medicine and Dentistry of New Jersey; John Bertolini, MD, Chair, Department of Emergency Medicine, Union Hospital; Raffi Kapitanyan, MD, Assistant Professor, Assistant Professor of Emergency Medicine, Emergency Medicine, Robert Wood Johnson University Hospital/UMDNJ
Contributor Information and Disclosures

Updated: May 11, 2009

Introduction

Background

Rabies is a viral disease of the central nervous system (CNS); it is one of the oldest and most feared diseases reported in medical literature. Incidence of rabies is widespread throughout the world.

Human rabies cases have been documented on all continents except Australia and the Antarctic. Many cases are unreported (or greatly underreported) in developing countries.

Since control of canine rabies in the 1940s and 1950s, human rabies in the United States has become very rare. However, with recent raccoon rabies epizootic in the United States and high transmissibility of the rabies virus by bats, a fear of reemergence of rabies in humans continues to exist. Practicing physicians must understand the biology, pathogenesis, and epidemiology of the disease. Physicians also must have detailed knowledge regarding postexposure prophylaxis for patients who may have been exposed to the disease through animal contact.

Pathophysiology

Most rabies viruses belong to the genus Lyssavirus and the family Rhabdoviridae. They are bullet-shaped RNA viruses with an incubation period of 5 days to 1 year, with an average of 20-90 days. In some cases, the incubation period has been thought to be significantly longer than 1 year.

Susceptibility to infection appears to be related to several factors, including size of inoculum, size and depth of bite, and proximity to the CNS.

Since 1980, most patients with human rabies in the United States have not had definite exposure through a bite wound, making total understanding of the mechanism of transmission somewhat elusive.

After inoculation, viral glycoprotein attaches to the nicotinic acetylcholine receptor of skeletal muscle. Initial replication occurs in myocytes. The virus then enters the nervous system via unmyelinated sensory and motor terminals. At this point, the virus is sequestered from the immune system, and vaccination can no longer be effective. The exact time course of these events is unknown because incubation may take years.

Rabies spreads via retrograde axoplasmic flow at 8-20 mm/d until it reaches the spinal cord. Paresthesias then may begin at the wound site. Rabies continues to spread throughout the CNS, subsequently undergoing centrifugal spread along peripheral nerves to the skin, intestine, and into salivary glands, where it is shed in saliva.

Transmission

The risk of contracting rabies from a bite wound is 5-80%, depending on incidence of rabies in endemic species or other terrestrial animals in the region. Cases from nonbite exposures now are more common in the United States than bite exposures. Unfortunately, most patients with rabies are interviewed after encephalitis symptoms have begun, which complicates ascertaining history. Nonbite exposures include being scratched, being licked over an open wound or mucus membrane, or exposure to brain tissue or cerebrospinal fluid (CSF) of a rabid animal. Nonbite exposures from bats are the exception, and respiratory exposure from bats is a growing concern.

Rabies prophylaxis is now recommended for any routine contact with at-risk animals. Intact skin contact with urine, blood, or feces of an animal has not been shown to constitute exposure, except in bats.

Rodents and lagomorphs (eg, hares) seldom carry rabies, and their bites generally do not require postexposure prophylaxis. Woodchucks are an exception and have been shown to carry rabies. Contacting local or state health departments may be helpful when risk of rabies from a species in a specific geographic region is unknown. The 24-hour/7-day Centers for Disease Control and Prevention (CDC) clinician phone number is (877) 554-4625.

Direct human-to-human transmission of rabies has not been documented. However, 8 cases have been reported in which people died of rabies after transplantation of corneas from people who were diagnosed with the disease. All 8 occurred in transplanted corneas in 5 countries. Only one case was within the United States. Strict corneal transplant regulations are in place to prevent this occurrence.

Frequency

United States

In 2007, 49 states and Puerto Rico reported 7,258 cases of rabies in animals and 1 case in a human (Minnesota) to the CDC, which represents a 4.6% increase from the 6,940 cases in animals and 3 cases in humans reported in 2006. Approximately 93% of the cases were in wildlife and 7% were in domestic animals. To date, raccoons, followed by bats, are the most frequent primary vectors in the eastern United States, with 2659 (36.6%) cases of rabid raccoons and 1,973 (27.2%) cases of bats reported in 2007.¹  However, only one case of documented human rabies in the United States is associated with the raccoon rabies variant. Lack of spread of raccoon rabies variant to humans is attributed to domestic animal immunization programs and rapid postexposure prophylaxis of bites to humans. On the other hand, during 2000-2007, 72% of human rabies cases were associated with suspected exposure to rabid bats or infection with bat rabies virus variants.²  Skunk epizootics appear to be widespread in north-central and south-central United States and California.

In an attempt to control animal rabies, rabies vaccine–laden baits have been used in trials in the wild. A Florida trial published in 2000 showed that 57% of raccoons, 85% of opossums, and 50% of gray foxes trapped in a baited area had ingested the bait.³ Recent studies have demonstrated the efficacy of a square presentation of the vaccinia vectored glycoprotein vaccine baits (V-RG) on the red fox, domestic dogs, and raccoon dogs.⁴

From 1980-2003, 40 cases of human rabies have been documented in the United States by the CDC, although this number is controversial based on questionable cases from other agencies. The animal sources in these cases have included predominantly bats and nondomestic dogs. Other animals rarely include skunks, foxes, and raccoon (one case). 

In the 12 cases associated with dogs, actual exposure occurred outside of the United States, most commonly in Mexico. A total of 19 of the 34 reported cases (1997) have been associated with bats. The silver-haired bat (Lasionycteris noctivagans) accounted for 13 (68%) of 19 bat-related rabies cases. This bat is found throughout the United States, except in the southern coastal regions; it lives in trees and shrubs and can migrate overseas. In a study of 7047 bats in New YorkState, only 25 (0.4%) were silver-haired, and only 2 of these were rabid. These low figures are difficult to reconcile with the high incidence of the silver-haired bat rabies variant in documented human cases. History of a bite wound has only been documented in 1 of the 19 cases of bat-related human rabies. Eight of the remaining cases reported physical contact. No history of bat contact could be found for the remaining 10 cases.

The method of virus transmission in cases with no history of bat contact is unclear. Aerosolization of viral particles, unrecognized scratches or bites, and transmission through another animal species (eg, skunk, raccoon) of the bat rabies variant are possibilities.

From January to August 1997, 2 rabies cases were identified in the United States. Both cases were bat-related, with one occurring in Washington and the other in Montana. In neither case was a bite or definite contact with a bat reported. One case involved a viral strain found in the silver-haired bat, and the other was a variant associated with the big brown bat species; this was the first human rabies fatality involving the big brown bat. In 1996, 4 cases of human rabies were reported. Two cases involved nonbite exposure to the silver-haired bat, and 2 cases involved dog bites that occurred outside the United States.

A total of 18 cases were reported from 1980-1993, 6 cases were reported in 1994, 4 cases were reported in 1995, 4 cases were reported in 1996, and 3 cases were reported in 1997.

A total of 15 cases of human rabies have occurred in the time frame of 2003-2008. Three of these were recipients of solid organ transplants from a single individual. In 2004, 4 recipients of solid organ transplants from a common individual died from encephalitis of unknown source. It was later concluded that the recipients were infected with rabies virus from the donor. Since the successful treatment in 2004 of an unvaccinated infected patient with the Wisconsin rabies treatment protocol, which involved a drug-induced coma and antiviral drugs, no further successes have been reported.⁵ Two cases in 2006 attempted this treatment protocol in the United States but were unsuccessful.⁶ The most recent human rabies exposure was in Minnesota in 2007 (no human exposures in 2008), where investigators determined that the likely source was a bat.⁷  

International

Worldwide, canine rabies variants are still epidemic and a major source of human rabies. The World Health Organization (WHO) in 2004 estimates that as many as 55,000 deaths occur from rabies annually, with 56% in Asia and 44% in Africa.⁸

Mortality/Morbidity

Although rabies is considered to be a uniformly fatal disease, 3 cases of survival were reported in the 1970s. No additional survival cases have been reported in the 1980s and 1990s. These 3 cases involved patients who were given duck embryo vaccine or suckling mouse brain vaccine before onset of clinical symptoms. Three additional cases of survival, which were not clearly documented, were reported in the 1940s, 1950s, and 1960s.

An additional case in Wisconsin was reported in 2004; a 15-year-old adolescent girl survived rabies without preexposure or postexposure prophylaxis. The girl was bitten by a bat 1 month prior and was given intravenous ribavirin and kept comatose for 7 days. She has partially recovered. As stated above, this is the sixth known case of human recovery from rabies; however, this is the first patient who did not receive rabies prophylaxis either before or after the onset of symptoms.⁵

Sex

No sex predilection for rabies exists.

Age

No age predilection for rabies exists.

Clinical

History

Suspicion of rabies is clear when a history of an animal bite is given; however, because a history of an animal bite is obtained in less than one half of US cases, diagnosis is problematic. Presentation of a patient in the rabies prodromal stage without a clear exposure history is so nonspecific and rare that making the diagnosis in the ED is essentially impossible. Rabies progresses over 7-14 days, and the mean time between initial presentation and death is 16.2 days.

• Prodrome
  • Patients have presented to EDs with nonspecific fevers and pharyngitis.
  • Most prodromes last from 2-10 days.
  • Initial symptoms of pain or paresthesias at the site of bite or scratch begin during the prodrome. These are the only symptoms that specifically may raise the red flag of a rabies diagnosis.
  • Fever, headache, and anorexia also may be present.
• Neurologic stage (2-7 d)
  • Aphasia
  • Incoordination
  • Paresis
  • Paralysis
  • Mental status changes
  • Hyperactivity
• Late symptoms
  • Hypotension
  • Coma
  • Disseminated intravascular coagulation (DIC)
  • Cardiac arrhythmias
  • Cardiac arrest
  • Fatality

Physical

• High fevers with rapidly progressive encephalitis
• Myoclonus
• Increased lacrimation
• Hypersalivation
• Agitation
• Anxiety

Causes

Rabies is transmitted by contact with the rabies virus, although the method of virus transmission may be unclear in cases with no history of contact with the source animal.

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