Rabies in Dogs

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Dog Picture 79Mad Dogs and Friendly Skunks

One of humanity's oldest and most feared diseases is a form of viral encephalitis transmitted by the saliva of infected animals. First described in a Mesopotamian tract dating from 1800 B.C., the illness was known to the ancient Greeks as lyssa, meaning "frenzy." But the Romans, adapting the Latin word that means "to rage," gave us the name by which the disease is known today: rabies.

For at least 38 centuries, and probably much longer, the threat of rabies has terrified people throughout the world. The cry "mad dog" has long been a warning literally to run for your life, because mad dog meant rabies, and rabies meant death.

A combination of innovative research and determined public health measures has all but eradicated human rabies in the United States and many other countries. On average, one case a year was reported to the U.S. Centers for Disease Control in the 1980s, down from an average of 11 cases a year in the
1950s.

Rabies is a "reportable" disease, which means state health authorities must notify CDC of every case in humans or animals. And where rabies is concerned, "case" is virtually synonymous with death. Only three people who showed clear evidence of rabies are known to have survived the illness, and all three suffered permanent nervous system damage resulting in physical or psychological aftereffects.

Dogs Not Only Villains

Rabies is a disease primarily of mammals, including both wild and domestic animals and human beings. Although people usually associate rabies with dogs, among domesticated animals in the United States, rabies today is more likely to be found in cats.

Cats, dogs and cattle account for nearly 90 percent of rabies cases in domestic animals, with horses, mules, sheep, goats, swine, and ferrets making up the remaining cases. Among wild animals, the disease is most often reported in skunks and raccoons. Other wild species in this country in which rabies is commonly found include bats, foxes, mongooses (only in Puerto Rico), groundhogs, and rodents.

The rabies virus, present in the saliva of an infected animal, is usually spread by a bite or scratch that punctures the victim's skin. The virus has a strong affinity for cells of the nervous system. It enters nerve cells at the site of the wound, travels to the brain, and then follows other nerve pathways to muscles and organs that are especially affected by rabies.

There are at least two other ways in which humans are known to have contracted rabies, both extremely rare. Two people were exposed by breathing the air in caves inhabited by rabid bats. And six people contracted rabies following implants of corneas from donors who had undiagnosed rabies.

The virus concentrates in the salivary glands, which explains why it is usually spread by bites. It also invades and damages the muscles involved in drinking and swallowing. Most human victims, and apparently lower animals as well, suffer excruciating pain on swallowing liquids. Though they suffer from thirst, animal and human rabies victims can be terrified by the sight of water--hence another name for the disease: hydrophobia.

Symptoms usually develop between 20 and 60 days after exposure. Rabid animals may become aggressive, combative, and highly sensitive to touch and other kinds of stimulation. And they can be vicious. This is the "furious" form of rabies, the kind traditionally associated with mad dogs.

But there is also a "dumb" form of the disease in which the animal is lethargic, weak in one or more limbs, and unable to raise its head or make sounds because its throat and neck muscles are paralyzed. In both kinds of animal rabies, death occurs a few days after symptoms appear, usually from
respiratory failure.

In humans the course is similar. After a symptom-free incubation period that ranges from 10 days to a year or longer (the average is 30 to 50 days), the patient complains of malaise, loss of appetite, fatigue, headache, and fever. Over half of all patients have pain (sometimes itching) or numbness at the site of exposure. Patients become excited, anxious, and irritable. They may complain of insomnia or depression. Two to 10 days later, signs of nervous system damage appear--hyperactivity and hypersensitivity, disorientation, hallucinations, seizures, and paralysis. Death may be sudden--due to cardiac or respiratory arrest--or follow a period of coma that can last for months with the aid of life-support
measures.

Aristotle Got It Wrong

The ancients were certainly familiar with rabies; Homer refers to "canine madness" in the Iliad. But they had some major misconceptions about it.  Aristotle, for example, said that lyssa (rabies) would afflict any animal bitten by a mad dog, except humans.

A Roman scholar, Celsus, apparently more perceptive than Aristotle, recognized that people were susceptible to the disease. But, like others before and after him, Celsus thought human rabies could be cured, and he offered advice on how to treat it. Among other things, Celsus advocated holding victims under water both to relieve thirst and overcome hydrophobia. Chances are the hapless beneficiaries of this treatment who didn't drown died of rabies.

In the 16th century, an Italian physician and scientist, Fracastorius, called rabies "the incurable wound," and said it was invariably fatal. His great reputation ensured that his opinion was well received by scholars of the day. But within a generation the misguided, if more hopeful, view of rabies treatment resurfaced, and dangerous, ineffective "cures" were again widely employed, among them the water treatment, in use as late as the 18th
century.

Prevention Is Key

The advent of scientific medicine made rabies control possible--not by cure, but by prevention. A series of observations and experiments led to Pasteur's development of a rabies vaccine in 1885. (See accompanying article, page 26.) Within a few years, the Pasteur treatment was being administered to thousands of potential rabies victims.

Unlike other immunizations, the rabies vaccine is administered after exposure to the virus. This unusual technique is successful because, as Pasteur showed, the rabies virus takes a comparatively long time to induce disease--a minimum of 10 days, and in rare cases up to a year. The length of the incubation period apparently depends on both the location of the wound--the farther from the brain, the longer the incubation--and the dose of virus received. Thus, without treatment, severe bites on the head or upper body might lead to the appearance of symptoms earlier than would a superficial bite or scratch on the ankle.

No matter where the wound, however, authorities emphasize that the first and most valuable preventive measure is thorough cleaning of the site with soap and water and immediate medical attention. If rabies vaccine treatment is called for, it should be started as soon as possible after exposure. Counting the first day of vaccine treatment as day 0, injections are administered on days 0, 3, 7, 14, and 28.

Two rabies vaccines are currently licensed for use in the United States, and both are markedly different from the crude, rabbit brain material Pasteur used more than 100 years ago. The Michigan Department of Public Health produces a vaccine in rhesus monkey cells that is used primarily in Michigan. The more widely used product, human diploid cell vaccine (HDCV), Imovax, is produced in cultures of human cells. Both vaccines are dramatically safer and more effective than Pasteur's material, but the principle at work is the same--make the patient's immune system produce antibodies to neutralize the virus before it causes disease.

In addition to vaccine, patients who have not previously been vaccinated for rabies also receive an injection of rabies immune globulin (RIG) on the day they first get the vaccine (day 0). RIG is prepared from the blood of persons who have been immunized against rabies and contains antibodies to the rabies virus. This "passive" immunity helps protect patients during the period before rabies vaccine causes their own immune systems to produce antibodies to counter the virus--so-called "active" immunity.

Certain people have a comparatively high risk of exposure to rabies. These include: veterinarians, animal handlers, cave explorers, laboratory workers who come in contact with tissue from rabid animals, and anyone who spends extended periods in areas where rabies is prevalent, such as parts of Africa, India, and Latin America. Such persons are encouraged to have preexposure immunization consisting of three vaccine injections over three to four weeks. Two years ago, FDA approved a low-dose version of HDCV for preexposure use. Booster injections are given when previously immunized persons are known to have been exposed to rabies.

Controlling Rabies in Animals

Medical and public health authorities agree that rabies prevention depends on controlling the disease in animals. That strategy became a realistic one in the 1920s with the development of a successful rabies vaccine for dogs. Vaccines for other domestic animals followed, and there are now rabies vaccines for dogs, cats, sheep, cattle, and horses. The most recent addition to this list, a vaccine for ferrets, was approved earlier this year by the U.S. Department of Agriculture, which regulates animal vaccines. Experimental vaccines for other wild animal species are under investigation.

Control of rabies in domestic animals in recent years has been remarkably successful, thanks to large-scale vaccination of pets and vigorous control of stray animals. Some 2,700 cases of rabies in dogs were reported to CDC in 1955. By 1988, the number had fallen to 128. In that year, cats, with 192 reported cases, became the major victims of rabies among domestic animals. As a result, public health authorities are concentrating efforts to make sure pet cats are properly vaccinated.

Wild animals account for nearly 9 out of 10 cases of animal rabies. While skunks are the most commonly reported rabid animal, the disease is increasing among raccoons, especially in Delaware, Maryland, Pennsylvania, Virginia, West Virginia, and the District of Columbia. Nationwide, 1,465 cases of rabies in raccoons were reported in 1988, all but 1 percent of them from the Mid- and South-Atlantic regions.

Because there is as yet no practical way to eliminate rabies in susceptible wild animal populations, public health agencies advise people to stay clear of wild animals, especially those acting in a bizarre or unusual manner. Signs that could mean rabies include: extreme aggressiveness; apparent loss of the fear of people; daytime activity in animals normally active only at night, such as bats and skunks; and lethargy in an animal that would otherwise move quickly away from other animals or people.

When such animals are sighted, they should be reported to local health authorities. Anyone who comes in direct contact with a possibly rabid animal needs immediate medical attention. Details about the potential exposure, together with information from health authorities who monitor animal rabies, allow a physician to decide whether rabies treatment is necessary.

The risk of exposure to rabies from the bite or scratch of a rabid animal--or from the contaminated air of a cave occupied by rabid bats--is difficult to quantify. But experts recognize that the risk is far from 100 percent. Yet, given the nature of rabies, few people would choose to forgo treatment and take their chances. On the other hand, no one should undergo rabies immunization needlessly. Here are the chief criteria doctors use to decide whether to begin rabies immunization:

1. Was the patient's skin broken or mucous membranes contaminated? If not, no exposure occurred.
2. If the bite was by a dog or cat, is domestic animal rabies found in the area? In many cities, even stray animals are extremely unlikely to be rabid.
3. Has the dog or cat been vaccinated against rabies?
4. Is the biting animal a healthy dog or cat and available for confinement and observation? In that case, vaccination can begin, but then be stopped if
the animal shows no sign of rabies after 10 days. If the animal can be killed and its tissue examined, a highly accurate fluorescent antibody test
can detect rabies in only about four hours.
5. If the bite was inflicted by a wild animal that can't be tested because it got away, is it a species likely to be rabid?
6. Was the bite provoked or unprovoked? Rabid animals are more likely to
attack without provocation.

Human rabies is extremely rare in the United States, and rabies in domestic animals is far less common than it was a few decades ago. In wild animals, however, rabies is still a serious concern because it poses a threat to humans and unvaccinated domestic animals. Until science devises an effective way to eliminate the disease in wild animal populations, the price of rabiescontrol will continue to be eternal vigilance.

Ken Flieger is a free-lance writer in Washington, D.C.

First Vaccine from Rabid Rabbits
A small dog raced wildly along the sidewalk, a black and white blur among children on their way to school. It stopped only for an instant--just long enough to bite a boy on the ankle--and then was gone.

Hours later the boy couldn't be sure that the dead dog he was shown at the county health department was the one that had bitten him. Rabid dogs had been reported in the county, and they were known to attack without provocation. Tests would show later that the dog did indeed have rabies. But even before they knew the test results, county health authorities and the boy's parents agreed he had to start the Pasteur treatment, a course of injections to protect against a disease that would otherwise almost certainly be fatal.

That all happened more than 40 years ago. Back then--and, in fact, since 1885, when French scientist Louis Pasteur successfully used his rabies treatment in a human patient--postexposure rabies immunization consisted of 23 or more doses of a vaccine made from spinal cords of rabbits injected with the rabies virus. Pasteur and his co-workers had discovered that rabid rabbit tissue lost infectivity after exposure to room air for 15 days. Yet injection of this rabbit brain material protected animals challenged with lethal doses of rabies virus. They had in effect produced the first rabies vaccine.

In one of history's most celebrated clinical trials, Pasteur treated a 9-year-old boy who had been savagely bitten by a dog judged to be rabid on the basis of erratic and unusual behavior before its death. One piece of "evidence" for the diagnosis of rabies: The dog's stomach was full of "hay, straw, and fragments of wood." Today that would hardly be accepted as proof that the animal had rabies, but it was enough to convince Pasteur that, without treatment, the boy would certainly die.

Young Joseph Meister didn't die of rabies, and we will never know whether he was even exposed to the disease. But we do know that the Pasteur treatment Meister and thousands of others received was a risky procedure justified only by the knowledge that untreated rabies was invariably fatal.

The old Pasteur vaccine and others like it contained "fixed virus"--live rabies virus that had been stabilized by injecting and recovering it from a series of laboratory animals--and animal brain tissue. Injected into humans, this type of vaccine could cause serious, even fatal, reactions, including a form of paralysis that advanced from the legs and arms to the muscles of the face and throat. Paralytic vaccine accidents occurred in about 1 in every 1,600 patients receiving the Pasteur treatment, 30 percent of whom died.

Over the decades, scientists improved both the safety and effectiveness of rabies vaccines. A vaccine produced from duck embryos, approved for marketing in the United States in 1956 and used over the following 16 years, cut the paralytic accident rate to 1 in 32,000. A substantially different vaccine licensed in 1980 and in use today has been associated with so few cases of paralytic disease--only 3 in the first 500,000 patients--that it is not certain the vaccine actually caused the paralysis. Sore arm, malaise, headache, and other mild symptoms occur fairly often, however. In one study, 21 percent of patients had local reactions. Allergic symptoms are far less common, about 1 in 10,000 cases, and none has been fatal.

Today's rabies vaccines are the product of advances in virology and immunology, and in the science of tissue culture--growing cells in the laboratory. One product is made by allowing the rabies virus to multiply in cultures of human diploid cells, cells that contain two complete sets of human chromosomes. The other licensed vaccine is made using fetal rhesus monkey cells. The viruses harvested from these human or monkey cell cultures are chemically killed, but the vaccines produced are nonetheless immunologically very potent. Instead of 23, 28, and sometimes as many as 40 injections of the old Pasteur-type vaccine, only five injections of modern rabies vaccines administered over 28 days afford full protection. (Booster
shots are administered if a person is suspected of having had another exposure to rabies.)

Although he didn't have the benefit of modern vaccine technology, the boy bitten on his way to school 40-odd years ago suffered nothing more serious than a bad scare and sore arms. Much the same awaits anyone treated today for exposure to rabies. But today, for the first time since Pasteur, the treatment is no longer a calculated risk.

Article by Ken Flieger. (FDA) http://www.fda.gov