Protocol used to treat the first known survivor of rabies without prior vaccination published

Jun 15 2005

The protocol used to treat the first known survivor of rabies without prior vaccination is published in the June 16, 2005, issue of the New England Journal of Medicine. It is hoped that this approach can be replicated, tested, and provide a guide for treating this fatal condition, especially in parts of the world where the incidence of rabies is rampant.

Experts at the Medical College of Wisconsin and Children’s Hospital of Wisconsin treated 16-year-old Jeanna Giese from Fond du Lac, Wis., who was bitten by a bat on September 12, 2004. She did not seek treatment until after symptoms appeared a month later. She was hospitalized and treated with an intense regime to minimize the ravages of the rabies virus on her nervous system while allowing her native immune response to take hold. Her heroic story made international headlines. She continues her ongoing recovery and rehabilitation at her home and is progressing well.

“For over 3000 years, no one who developed rabies, without being previously vaccinated following a bite from a rabid animal, has survived,” points out Giese’s health care team leader, Rodney E. Willoughby, Jr. M.D., associate professor of pediatrics at the Medical College and infectious disease specialist at Children’s Hospital.

Rabies is an infectious viral disease that affects the nervous system of humans and other mammals. People typically get rabies from the bite of an animal with rabies (a rabid animal) such as a raccoon, skunk, fox, coyote, or bat. Most of the recent human rabies cases in the United States have been caused by rabies virus from bats.

Thousands of people in the US are successfully treated each year after exposures to an animal that may have rabies. A few people die of rabies each year in the United States, usually because they do not recognize the exposure or risk of rabies from the bite of a wild animal and do not seek medical advice.

If untreated, the rabies virus affects the nervous system giving rise to dysfunction of the brain and nerves. The patient becomes alternately lethargic and agitated. Swallowing becomes difficult and the patient avoids food and water, hence the term hydrophobia describes this condition. Incoordination is followed by paralysis. The autonomic nervous system is also affected resulting in failure of internal organs such as the heart. Death may occur from coma, heart failure, or many other complications.

According to Dr. Willoughby, in Giese’s case, no symptoms occurred for a month after exposure when she sought medical help. On day five of the onset and progression of symptoms, she was transferred to Children’s Hospital. She was put on ventilatory support in the ICU and fed through a gastrointestinal tube to maintain nutrition.

On the second day, the presence of rabies virus-specific antibody was confirmed in the spinal fluid, although the rabies virus could not be isolated from skin biopsies or saliva. She continued to make more rabies antibodies as the days progressed. Along with supportive care in the intensive unit, the doctors instituted a combined anti-excitatory and anti-viral strategy. Neither rabies vaccine, considered clinically ineffective once rabies develops, nor anti rabies-immune globulin were used. The diagnosis had been made because of her natural immune response to the rabies infection, so the need for vaccination or infusion of additional antibodies was low and might have contributed to an adverse reaction.

The strategy consisted of a multi-drug cocktail. Ketamine and amantadine, members of one class of drug that protects brains against damage, with additional specific activity against rabies in animal models, were used. A second class of brain protectors, benzodiazepines with supplemental barbiturates, were also used at levels that suppress brain activity and metabolism and induce a coma-like sedation. Her brain activity was monitored with the help of an electroencephalogram or EEG.

Even though recent literature had confirmed the futility of antiviral therapy, it was thought, in consultation with the U.S. Centers for Disease Control and Prevention, that ribavirin could prove beneficial. Ribavirin was administered in the hope that it could protect the heart from the virus.

Although Giese survived and continues to improve five months since her hospitalization, Dr. Willoughby cautions against over-interpreting survival from rabies by a single individual. Jeanna is young, athletic, with a clinical syndrome more consistent with the milder paralytic form than “furious” rabies. “Since the bat was not recovered to isolate and detect rabies virus, we cannot rule out an unusual, more temperate or mutated rabies virus and not the classical variety,” he said.

“While the literature was helpful in knowing the milestones when various symptoms presented, we were essentially flying blindly once these had passed,” explains Dr. Willoughby. “We hope that the recipe that we developed will have some use in treating future cases which heretofore have been fatal.”

Co-authors from the Medical College and Children’s Hospital include Kelly S. Tieves, D.O., assistant professor and pediatric critical care specialist; George Hoffman, M.D., associate professor of anesthesiology in clinical pediatrics; Nancy S. Ghanayem, M.D., assistant professor and critical care specialist; Catherine M. Amlie-Lefond, M.D., and Michael J. Schwabe, M. D., assistant professors of neurology in clinical pediatrics; Michael J. Chusid, M.D., professor and chief of pediatric infectious disease; and Charles E. Rupprecht, V.M.D., Ph.D., at Centers for Disease Control and Prevention, Atlanta, Ga.