Rabies

Though rabies has been documented since before the birth of Christ, the recent deaths from rabies of four people in the United States, who had received transplanted organs from a man infected but not actively suffering from the disease, show that the rabies continues to be a virulent and silent killer of people. Scientists speculate that rabies first appeared in Africa or Asia as five other viruses related to rabies are isolated there. As early as 2,300 B.C. there were laws in Babylonia that required the owner of a rabid dog to pay a fine if the dog bit someone. Writings have been found in Greece in the fifth and fourth centuries B.C. that described rabies in domestic animals as well as dogs. There are accounts of rabies epidemics in wolves in western Europe in 1271 and it is believed that rabies was brought to the New World in 1753 when dogs brought to the Virginia colony were found to be infected. In 1998, there were from 30,000 to 50,000 deaths worldwide from rabies, but only one in the United States, though 18,000 in the U.S. received rabies vaccine after being bitten by infected animals.1

It has been widely accepted that people who had access to the vaccine were essentially safe from the disease. However, the death of the fourth person in the U.S. in the course of a week from rabies contracted through organ transplants made national headlines on July 8, 2004 2 because no one had suspected the 20 year old male donor had been infected. This event brought the threat of rabies to the forefront again as one of the trademarks of rabies is that it shows no symptoms until it is too late for a vaccine to be effective. The reason there are no early symptoms is because of the way rabies is transmitted and the way it affects the human body. Rabies is caused by a rhabdovirus similar to those that cause encephalitis. However, the rabies virus requires the involvement of the central nervous system as part of its lifecycle. Rabies virus is usually transmitted through the saliva of a rabid animal via a bite that punctures the skin of the victim. In more infrequent cases it can be contracted via saliva entering an existing wound or through inhalation in a cave with a dense, long term population of infected bats. Once the bullet shaped virus breaks through the protective epithelium, it reaches the central nervous system via peripheral nerves by exploiting retrograde axoplasmic transport or transsynaptic transmission.3 There is an incubation period averaging three to seven weeks (minimum of 10 days, maximum of several years) during which time the virus may amplify in peripheral tissue, particularly the skeletal muscle. The incubation period is somewhat connected to the distance of the point of infection to the brain. The virus gains access to the central nervous system via motor and sensory nerves. Early symptoms include fever, headache and a sore throat. Once the virus reaches the brain, the first area to be infected is the limbic system (the portion of the brain involved in emotions). The rabies sufferer grows nervous, restless and unusually sensitive to light and sound. Abnormalities in behavior become pronounced, including delirium and biting behavior, alternating with periods of calm, widespread brain dysfunction and impairment of respiratory and autonomic nervous systems. Attempts at drinking cause laryngeal spasms which give rise to a violent reaction to even the site of water (hydrophobia). As the infection becomes widespread and often includes the brain stem, spinal cord, hippocampus, basal ganglia, cortex and related structures. The virus then migrates along efferent nerves to the salivary glands. This form is referred to as furious rabies. Less common is the paralytic or dumb form where acute ascending paralysis resembling Guillain-Barre syndrome predominates with relative staring of higher cortical functions internally. Both forms progress to coma, autonomic nervous system dysfunction and death. Once early symptoms begin to appear, treatment includes intensive care, attention to the airway, maintenance of oxygenation and control of seizures. Death is almost inevitably occurs after seven days usually due to respiratory failure (only four cases of survival are documented as of 2004).

Diagnosis of rabies is generally done postmortem by examining the brain via the fluorescent antibody technique. A fluorescent antibody of skin biopsy material is possible from the posterior neck - where hair follicles are highly inverted - but this is only 60% to 80% effective, so is not widely used. Currently, the Center for Disease Control is advocating reverse transcriptase PCR and nucleic acid sequence based amplification of the cerebrospinal fluid or saliva as a definitive diagnostic procedure. However, whenever a person is bitten by a wild animal, especially a skunk, raccoon, fox or bat when the animal cannot be located to test it for rabies, rabies vaccine is seriously considered. According to the recommendation of the United States Public Health Service Advisory Committee guidelines doctors are to consider include the circumstances of the bite (extent/location of the wound), history of prior vaccination and local prevalence of rabies. When administered, a full dose (20 mg) of rabies immune globulin is infiltrated around the wound. Remaining doses - five injections muscularly in the deltoid muscle - are administered on days 0, 3, 7, 14 and 28 after exposure. This treatment has virtually eliminated death of humans from rabies in the United States.

Unfortunately, if there is no knowledge of the possibility of infection, treatment is not started and death is virtually assured. This was the case of eleven-year-old Kelly Ahrendt of New York state who, in July of 1993, complained of a sore arm and shoulder. Her pediatrician examined her and said it was probably a sprain, but prescribed an antibiotic because he noted she had a slight ear infection and sore throat. He said she should be able to go camping with her family. While on the trip, Kelly began running a high fever and suffered from hallucinations. Shortly thereafter she developed muscle spasms, uncontrollable salivation and hysterical terror. Her parents rushed her to the emergency room, but there was nothing that could be done for her; she died a few hours later. Kelly's parents requested an autopsy and tests ultimately showed evidence of rabies, a particular strain that infects bats. The parents said that they had found bats in their attic a few times, but were not aware of Kelly having been bitten. It was surmised that the family cat may have eaten a bat and, though the cat was immunized, traces of the bat's body fluids may have remained on the cat's fur and been transmitted to Kelly. However, there was no way of knowing for sure. A similar case took place in 1992 in California. An eleven-year-old boy was given medication