Jeanna Giese
Encyclopedia
The Milwaukee protocol is an experimental course of treatment of an acute infection of rabies
Rabies
Rabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms...

 in a human being. The treatment involves putting the patient into a chemically induced coma
Induced coma
A barbiturate-induced coma, or barb coma, is a temporary coma brought on by a controlled dose of a barbiturate drug, usually pentobarbital or thiopental...

 and administering antiviral drug
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

s. It was developed and named by Dr. Rodney Willoughby, Jr., M.D., following the successful treatment of Jeanna Giese. Giese, a teenager from Wisconsin
Wisconsin
Wisconsin is a U.S. state located in the north-central United States and is part of the Midwest. It is bordered by Minnesota to the west, Iowa to the southwest, Illinois to the south, Lake Michigan to the east, Michigan to the northeast, and Lake Superior to the north. Wisconsin's capital is...

, became the first of only six patients known to have survived symptomatic rabies without receiving the rabies vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

.

Initial infection

On September 12, 2004, Giese, then fifteen years old, and a student at St. Mary Springs High School
St. Mary Springs High School
St. Mary's Springs Academy is a private Catholic, coeducational, college prep high school in Fond du Lac, Wisconsin owned by the Archdiocese of Milwaukee. It was founded by the Sisters of Saint Agnes in 1909...

, picked up a bat
Bat
Bats are mammals of the order Chiroptera "hand" and pteron "wing") whose forelimbs form webbed wings, making them the only mammals naturally capable of true and sustained flight. By contrast, other mammals said to fly, such as flying squirrels, gliding possums, and colugos, glide rather than fly,...

 while attending St. Patrick's Church in her hometown of Fond du Lac, Wisconsin
Fond du Lac, Wisconsin
Fond du Lac is a city in Fond du Lac County, Wisconsin, United States. The name is French for bottom of the lake, for it is located at the bottom of Lake Winnebago. The population was 42,203 at the 2000 census...

. She sustained a small bite on her left index finger from the animal, and having treated it with hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

, the family decided not to seek medical attention. Thirty-seven days after the bite, Giese developed neurological symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...

s. She was admitted to St. Agnes Hospital with a 102 °F (38.9 °C) fever, double vision, slurred speech, and jerking in her left arm. She did not respond to treatment and tested negative for all other diseases. As her condition deteriorated, her mother mentioned that Giese had been bitten by a bat about a month before getting sick. She was then diagnosed with rabies and referred to Dr. Willoughby at Children's Hospital of Wisconsin in Wauwatosa
Wauwatosa, Wisconsin
Wauwatosa is a city in Milwaukee County, Wisconsin, United States, and was incorporated on May 27, 1897. As of the 2006 census estimate, the city's population was 44,798. Wauwatosa is located immediately west of Milwaukee, Wisconsin, and is a part of the Milwaukee metropolitan area...

. The diagnosis was later confirmed by laboratory tests at the Centers for Disease Control.

Induced coma treatment

Medical history has shown that most rabies deaths are caused by temporary brain dysfunction with little to no damage occurring to the brain itself. Using this information, Willoughby's team devised an experimental treatment for rabies. Giese’s parents agreed to the experimental treatment at Children's Hospital of Wisconsin. Dr. Willoughby's goal was to put Giese into an induced coma
Induced coma
A barbiturate-induced coma, or barb coma, is a temporary coma brought on by a controlled dose of a barbiturate drug, usually pentobarbital or thiopental...

 to essentially protect herself from her brain, with the hope that she would survive long enough for her immune system to produce the antibodies to fight off the virus. Giese was given a mixture of ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...

, midazolam
Midazolam
Midazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...

, and phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...

 to suppress brain activity
EEG
EEG commonly refers to electroencephalography, a measurement of the electrical activity of the brain.EEG may also refer to:* Emperor Entertainment Group, a Hong Kong-based entertainment company...

 and the antiviral drug
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

s ribavirin
Ribavirin
Ribavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...

 and amantadine
Amantadine
Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...

 while waiting for her immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 to produce antibodies to attack the virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

. Giese was brought out of the coma after six days once signs of the immune system's progress became apparent.

Post-infection

After thirty-one days in the hospital, Giese was declared virus-free and removed from isolation. There was some initial concern about the extent of brain damage she had suffered, but while she had suffered some, the disease (and treatment) seemed to have left her cognitive abilities largely intact. She spent several weeks undergoing rehabilitation therapy and was discharged on January 1, 2005. By early 2005 she was able to walk on her own, had returned to school, and had started driving automobiles. Mayo Clinic
Mayo Clinic
Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...

 neurologist Dr. Kenneth Mack described her condition as she entered college: she's recovered "remarkably well" and should continue to improve. Giese graduated as a biology major from Lakeland College
Lakeland College
Lakeland College is a liberal arts college located in Sheboygan County, Wisconsin west of Howards Grove; however it uses a Sheboygan postal address for all correspondence...

 in the spring of 2011, at a ceremony attended by her parents and Dr. Willoughby. Giese, a bright and diligent student both before and after her medical adventure, had written a thesis on a serious disease affecting bats, and hopes to continue her studies and work with animals in some capacity, possibly in research as a biologist or veterinarian. Although she was a very conditioned athlete in high school, because of the neurological sequelae (leftover complications) from the rabies, she still has problems with running and balance.

Theories about survival

The reasons for Giese's survival under the Milwaukee protocol remain controversial. While the treatment appears to have worked as planned, her doctors suggest Giese might have been infected with a particularly weak form of the virus, or that the fact that she was bitten in a site far from the brain provided her unusually strong immune system sufficient time to fight the virus. When admitted to the hospital no live virus, only antibodies, could be isolated from her body, and the bat was not recovered for testing.

There is no specific medication to fight rabies - the body will kill it off eventually, if it can survive long enough.

Other attempts

Giese's treatment regimen has since undergone revision (the second version omits the use of ribavirin
Ribavirin
Ribavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...

). There were 2 survivors out of 25 patients treated under the first protocol. A further 10 patients have been treated under the revised protocol and there have been a further 2 survivors.

In June 2011, yet another young child survived infection with rabies without receiving the vaccine before showing symptoms. An eight-year-old girl named Precious Reynolds, of Willow Creek, Calif., contracted the disease sometime in April 2011, but she did not receive medical care until mid-May, after her grandmother took her to the doctor because of flulike symptoms that grew so serious her grandmother said they began to resemble polio. The hospital said doctors followed the protocol first established with Giese. Precious was placed in a drug-induced coma as she received anti-viral medications. She spent two weeks in intensive care undergoing the treatments, and immediately showed that her immune system was strong. She was then moved to the hospital's general pediatric unit.

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