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Regimen That Saved a Teen Infected With Rabies May Help Rescue Others

Doctors induce a coma and use antiviral drugs to treat a Wisconsin girl in the early stages.

June 16, 2005|Thomas H. Maugh II | Times Staff Writer

Confronted with a teenager developing the early symptoms of rabies after a bat bite, a group of Wisconsin physicians with no experience dealing with the disease have developed what may be the first effective treatment for what has been a uniformly fatal infection.

The team put 15-year-old Jeanna Giese into a deep coma to prevent her virus-infected brain from destroying internal organs while her own immune system -- combined with a healthy dose of antiviral drugs -- fought off the virus.

Eight months later, the teen is well along the road to recovery and the technique is being tested in other rabies victims with at least one other tentative success so far.

Giese, now 16, is believed to be the first unvaccinated person to survive a rabies infection, but the team hopes others will recover as their protocol, published today in the New England Journal of Medicine, becomes widely distributed.

Several physicians have contacted the researchers seeking the protocol, said Dr. Rodney E. Willoughby Jr. of the Medical College of Wisconsin, who led the team. "But by the time they find out how to reach us and we respond, we have typically lost two or three days" and the patient is beyond help.

"People can now read the article and be prepared," he said, "and that will make a big difference."

Rabies is rare in the United States. Although humans frequently encounter one of the estimated 7,500 wild animals typically confirmed to have the disease each year, the development of the disease can almost always be prevented by immediate administration of five doses of the rabies vaccine, as well as human rabies immune globulin.

As a result, there are generally one or two cases a year of human rabies in the U.S. Five people were previously known to have survived rabies after showing symptoms. All of them had received the vaccine either before or after exposure, according to the Centers for Disease Control and Prevention.

The problem is more severe in the developing world. Worldwide, about 55,000 people die of the disease each year, mostly in Asia and Africa -- both locations where rabies is endemic in dogs.

Physicians have a limited understanding of how the virus kills, said Dr. Alan C. Jackson of Queens University in Kingston, Canada. Although the virus infects primarily brain and nerve cells, post-mortem examinations show little physical damage to those tissues.

But the cells do become hyper-excited by environmental stimuli, producing disproportionate reactions to light, sound and other external cues. Because of the stimulation, the brain sends dysfunctional signals to other organs in the body, causing them to malfunction or fail. The heart can stop beating or the lungs can cease breathing, for example.

"Victims die 100 different ways," Willoughby said.

One common treatment for victims is to sedate them and put them in a dark room to minimize stimulation, he said, but that has proved to be more palliative than therapeutic.

Giese, then 15, was bitten on the finger Sept. 12 after she picked up a bat that had flown into a window pane inside her church in Fond du Lac, Wis. The bite was small, however, and she and her parents dismissed it.

A month later, she developed numbness in her finger, nausea, blurred vision and a general fatigue. Physicians initially diagnosed encephalitis, but a blood sample sent to the CDC confirmed the presence of rabies antibodies.

The team at the Medical College of Wisconsin and Children's Hospital in Milwaukee consulted with her parents and offered them two options: Doctors could provide supportive care while she died, or they could initiate an aggressive treatment, albeit with little likelihood of success.

The parents opted for the latter course.

The team treated her with two drugs, ketamine and amantadine, that are known to help protect the brain, and two other types of drugs, benzodiazepines and barbiturates, that placed her in a deep coma.

They did not administer anti-rabies gamma globulin because the teen was manufacturing her own antibodies and they feared too many antibodies would overexcite brain cells. They did give her the antiviral drug ribavirin, which they hoped would help protect her heart from the disease.

After a week in the coma, "nothing bad had happened, and we were starting to pay a bit of a price in terms of toxicity, so we tapered off the medicines," Willoughby said.

Giese woke from the coma, but her nerves remained largely deadened, and she did not respond to environmental stimuli, he said.

Over a week or two, however, her senses began coming back rapidly. "It was like Hanukkah, a gift every day," Willoughby said. "It was a delight to watch her come back."

Giese spent two months in intensive care before returning home on New Year's Day. This month, she celebrated her 16th birthday with a cake that read "Jeanna 1, Rabies 0."

This year, German physicians used the protocol on four transplant recipients who developed rabies from infected organs. But the patients all died because the transplant drugs they were receiving suppressed their immune battle against the virus.

"One man died at 56 days, which is easily double the survival of anyone who has gotten rabies through transplants," Willoughby said. "We all thought he was going to make it, but ultimately his immune system wasn't kicking in."

Willoughby noted that "there is another patient active at the moment [in India] that we have high hopes for."

Willoughby and Jackson cautioned that Giese might have been infected with a weak strain of the virus, and both agreed that her youth and prior good health were important contributors to her survival.

But in an editorial accompanying the paper, Jackson also said that the drug regimen they used was clearly beneficial.

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