Rabies Raves On

Before treatment became available, rabies was one of the most uniformly fatal viral infections. It still kills too many.

By Claire Panosian DunavanMar 1, 2003 6:00 AM


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In a darkened room, a 9-year-old boy lay on a mattress, loosely bound with a cloth rope. Occasionally, he jerked or twitched. Mostly he stared. His breathing was irregular. He was dying.

One week earlier, the boy had arrived fighting and gagging. For several days, his family grieved at his side as he writhed and choked at the mere sight of water. Now that he was so close to death, his parents had left to arrange the funeral.

I witnessed this case of rabies in 1987, when I was a visiting professor of infectious disease at the Aga Khan Medical School in Karachi, Pakistan. The main hospital, with its brick buildings and leafy courtyards, was surprisingly like my own in Los Angeles. But on this day I had traveled to a public hospital on Karachi's outskirts. The facility housed patients with diseases that American doctors had only read about. My host, Dr. Mohammed, had told me the boy's story and invited me to see him.

At first, the child's condition so unnerved me that I had to look away. Still, a voice inside me said, "Look and remember." While I gazed at him, my thoughts turned to a colleague who had visited Mexico a few years earlier. During his stay in a remote village, Matt had noticed a dog behaving oddly. One evening, from out of the darkness, the dog snarled and lunged at his leg. When he undressed, my friend found bloody marks where teeth had punctured his calf.

"I instantly knew I had three options," he later told me. "In my halting Spanish, I could try to find the dog's owner and inquire if the dog had ever been vaccinated. Or I could ask to have the dog killed and his brain examined. Or I could get a series of shots." Two days later, Matt was in San Diego receiving rabies antiserum and the first of five rabies vaccinations. Fortunately for him, a new vaccine for rabies had just been approved in the United States. For Americans, the days of painful injections of rabies vaccine in the stomach following unprovoked animal bites were over.

Halfway around the globe, of course, pain was not the issue. For many poor people in India and Pakistan—where thousands of rabies exposures occur every year—treatment was either unaffordable or unavailable. By contrast, improved treatments have helped bring deaths from rabies in the United States down from more than 100 a year a century ago to about one or two every year.

When someone is treated for rabies infection, the goal is to arrest the deadly virus before it reaches the spinal cord or the brain. The pathogen, which commonly gains entry via saliva from a rabies-infected animal, breeds first in local muscle, then advances through long, lanky nerve cells. An initial injection of rabies antiserum (a highly specific antibody culled from rabies-immune humans) can be thought of as a stun gun that slows the virus. Meanwhile, five doses of rabies vaccine given over four weeks are the bullets that complete the counterattack. They do so by kindling enough native antibody to wipe out the remaining invaders.

Before treatment became available, rabies was one of the most uniformly fatal viral infections. As early as the 23rd century B.C., the legal code of the Babylonian city of Eshnunna refers to a disease that was probably rabies. In 500 B.C., the Greek philosopher Democritus recorded an unmistakable description of canine rabies. The word rabies itself comes from the Latin verb rabere, "to rave," as well as a Sanskrit word for doing violence, underscoring a frequent but not universal feature of the virus's deadly assault.

The two common forms of rabies are "furious" and paralytic, or "dumb." Furious symptoms, such as hydrophobia, delirium, and agitation, reflect invasion of the brain by rabies virus. But in one out of five cases, the disease seems to target only the spinal cord and brain stem. These victims experience confusion and weakness but not the wild, explosive behavior that still prompts straitjackets and padlocked cells for victims in some parts of the world.

In 1892 the renowned physician William Osler described hydrophobia in his medical textbook. "Any attempt to take water," he observed, "is followed by an intensely painful spasm of the muscles of the larynx and the elevators of the hyoid bone [a horseshoe-shaped bone situated at the base of the tongue]. It is this which makes the patient come to dread the very sight of water. . . . These spasmodic attacks may be associated with maniacal symptoms. In the intervals between them the patient is quiet and the mind unclouded."

Osler's text goes on to state that rabies victims rarely injure attendants during their violent episodes, although they may "give utterance to odd sounds." Mercifully, hydrophobia usually gives way to deeper unconsciousness within three or four days. Soon after, organs fail and the heart stops.

Leaving the ward, Dr. Mohammed and I headed for a nearby lounge where we could talk and drink tea. "The boy liked dogs," Dr. Mohammed said quietly as we walked. "It's almost certain he was infected by a dog." I had seen many street dogs in the slums of Karachi, including a few that were sick and whimpering. How easy it would have been, in an impulsive gesture, to reach out to one of them.

Of course, many other animals contract and transmit rabies. Since the 1980s, the silver-haired bat and its kin, the eastern pipistrelle, have been the source of roughly two-thirds of all human rabies cases in the United States. Other susceptible mammals include wolves, foxes, coyotes, cats, skunks, raccoons, and even horses and livestock.

Most human victims sicken within three months of exposure to rabies, but sometimes infections remain dormant for a year or more. Once symptoms begin, however, the die is cast. Over the next one to three weeks, the condemned patient sinks as the virus relentlessly moves from muscle to nerve to spinal cord or brain.

Ancient healers espoused an array of immediate postexposure antidotes, from caustics and cupping to applying a poultice of goose grease and honey. In the first century A.D., Celsus, a Roman physician-naturalist, recognized that saliva transmitted rabies and recommended sucking or burning suspect wounds. Eighteen hundred years later, William Osler's suggestions were surprisingly similar: careful washing, chemical cauterization, and keeping the wound open for several weeks.

Osler did not know of Louis Pasteur's landmark research, conducted just a few years earlier. Pasteur had reported experiments leading to the world's first animal rabies vaccine. He wasn't planning to use the vaccine on a human until he learned of a desperate case: a 9-year-old boy from Alsace bitten 14 times by a rabid dog. Of his next action, Pasteur wrote: "The death of this child seemed inevitable, and I decided, not without lively and cruel doubts . . . to try in Joseph Meister the method which has been successful in dogs. Consequently, on July 6 at 8 in the evening, 60 hours after the bites, in the presence of Doctors Vulpian and Grancher, we inoculated under a skin fold in the right hypochondrium [upper abdomen] of the little Meister a half syringe of the [spinal] cord of a rabid rabbit preserved in a flask of dry air for 15 days." After 12 more injections, it was time to watch and wait. Joseph Meister never developed rabies.

Two 9-year-olds—one in modern Pakistan, one in 19th-century France. One was a rabies victim, the other a rabies survivor. Today an updated form of Pasteur's remedy saves countless lives, yet every year 40,000 to 70,000 people die for the lack of it. If the 19th century's greatest microbiologist knew of these ongoing 21st-century tragedies, what would he say?

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