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A Cure for Rabies

From: The Hospitalist, September 2007

Teen’s unlikely recovery created new standard for patient care

by John James Ross, MD

In September 2004, animal-loving Wisconsin teenager Jeanna Giese picked up a bat trapped inside her church and took it outside. As she tried to set it free, the bat sank its teeth into her left index finger for an instant before she shook it loose.

Back at home, her mother rinsed the tiny wound with hydrogen peroxide and thought no more about it. A month later, the girl, a star student and athlete, developed fatigue, double vision from bilateral sixth nerve palsies, and paresthesias in her left arm. She deteriorated rapidly over the next few days, with high fever, ataxia, confusion, tremor, drooling, and spasm with swallowing, and was intubated for airway protection. Rabies antibody was found in her spinal fluid and serum.

The Fond du Lac girl’s doctors at Children’s Hospital of Wisconsin (Milwaukee) offered the family a dismal choice. She could receive hospice care for the gruesome and invariably fatal consequences of rabies in unvaccinated patients. Or, the doctors could embark on experimental treatment, with no guarantee she would have any meaningful neurological function or quality of life should she survive.

Parents Chose Treatment

On the basis of data indicating rabies patients are capable of clearing the virus, but die largely of secondary complications (e.g., autonomic dysfunction and excitatory neurotoxicity), the team administered massive doses of ketamine, midazolam, and phenobarbital, the antivirals ribavirin and amantadine, and supplementation with coenzyme Q to counter the possible mitochondrial toxicity of ribavirin. Ketamine blocks the neuroexcitatory NMDA receptor, possibly a receptor for rabies virus.

After a stormy, four-week intensive-care course characterized by autonomic instability and other complications, Giese was extubated and went home on New Year’s Day 2005. She made a remarkable recovery, eventually returning to school full time— although she was unable to participate in athletics. At 17, she has been accepted to college to study biology starting this fall.1-3

While the Wisconsin protocol has achieved the previously impossible, it is not yet a surefire cure for rabies. Two U.S. children treated last year with the Wisconsin protocol and meticulous supportive care died—one with cerebral edema, the other with cerebral and cerebellar herniation.4 Additional clinical experience and further tinkering with the protocol are likely required to optimize outcomes.

Jeanna Giese, 15, leaves Milwaukee’s Childrens Hospital with her mother, Ann, and father, John, on Jan. 1, 2005. Giese was released from the hospital after being treated for rabies with an experimental combination of drugs. Rabies specialist Charles Rupprecht, MD, from the Centers for Disease Control and Prevention in Atlanta says Giese is the first person known to have survived the disease without receiving the rabies vaccine.

What To Know

While rabies is rare is the U.S., it retains a disproportionate importance because of its historic 100% fatality rate. Hospitalists should know this about rabies:

Suspect rabies in all patients with undiagnosed neurological disease. Making the diagnosis of rabies as early as possible is more critical than ever, now that a potential treatment exists. Unfortunately, in the United States rabies is rarely considered when patients first present for medical attention.

During the prodromal phase of rabies, which lasts about four days, patients have non-specific symptoms of fever, malaise, and nausea. This is quickly followed by paresthesias at the bite or wound site, personality change and hallucinations, and the classic manifestations of “furious rabies”: agitation, delirium, hydrophobia, aerophobia, aggression, and spasms affecting swallowing and respiration.

In up to 20% of patients, the disease may present in atypical form as “dumb rabies,” an ascending paralysis that may mimic Guillain-Barré syndrome. Tests for rabies include polymerase chain reaction of cerebrospinal fluid or saliva, antibody testing of serum and CSF, and direct fluorescent antibody of biopsy from the nape of the neck, where the virus congregates in hair follicles.

Ask all patients about bat and animal exposure when rabies is in the differential. Worldwide, there are 55,000 cases of human rabies a year. The vast majority of these occur in developing countries as a result of dog bites. In the United States, there is only a handful of human cases of rabies each year, almost always associated with bat exposure. It is not necessary to get a bat bite or scratch to be at risk for rabies. Some U.S. patients seem to have contracted rabies after exposure to bat saliva or vapors, sometimes having been bitten while asleep. Any patient who wakes up in a room or cabin and finds a bat should be considered at risk for rabies.

Other animals commonly infected with rabies in the U.S. include raccoons, skunks, and foxes. Unvaccinated dogs and cats also are at risk of rabies.

Consider prevention the best treatment. Wash bite wounds with 20% soap and irrigate with povidone-iodine to reduce the risk of rabies by up to 90%. If the biting animal is available for observation, the rabies vaccine may be deferred or not administered at all if the animal is well after 10 days. Many state laboratories will also perform rabies testing on euthanized animals. If the biting animal is unavailable for observation, promptly give the rabies vaccine and immune globulin. Current rabies vaccines are safe and highly effective in preventing infection after exposure, provided they are given in a timely fashion. Vaccine and immune globulin have no role in treatment once rabies symptoms have developed. TH

Dr. Ross is an associate physician and hospitalist at Brigham and Women’s Hospital, Boston, and a fellow of the Infectious Diseases Society of America. Contact him at jross4@partners.org.

References

  1. Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med. 2005;352(24):2508-2514.
  2. Johnson M, Nelson K. Down to a prayer. Milwaukee Journal Sentinel. June 18, 2005.
  3. Nelson K. Potential cure for rabies fails in others. Milwaukee Journal Sentinel. April 22, 2007.
  4. Centers for Disease Control and Prevention. Human rabies Indiana and California, 2006. MMWR. 2007;56(15):361-365.

This copy is for your personal, noncommercial use only. No part of this article can be reproduced without the written permission of the publisher. Order presentation-ready copies for distribution to your colleagues, clients, or customers by contacting our reprints department at reprints@wiley.com. Copyright © 2009 Society of Hospital Medicine, administered by John Wiley & Sons Inc.

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