Milwaukee protocol

The Milwaukee protocol is an experimental course of treatment of an infection of rabies in a human being. The treatment involves putting the patient into a chemically induced coma and administering antiviral drugs. It was developed and named by Rodney Willoughby, Jr., M.D., following the successful treatment of Jeanna Giese.^[1]

Giese, a teenager from Wisconsin, became the first patient known to have survived symptomatic rabies without receiving the rabies vaccine.^[2] The Milwaukee protocol is sometimes referred to as the Wisconsin protocol.^[3][4]

Case history

Initial infection

On September 4, 2004,^[5] Jeanna Giese, a 15-year-old student at St. Mary Springs High School, picked up a bat while attending St. Patrick's Church in her hometown of Fond du Lac, Wisconsin.^[6] She sustained a small bite on her left index finger from the animal, and having treated it with hydrogen peroxide, the family decided not to seek medical attention.^[1][6] Thirty-seven days after the bite, Giese developed neurological symptoms. She was admitted to St. Agnes Hospital with a fever of 102 °F (39 °C), double vision, slurred speech, and jerking in her left arm.^[6]

She did not respond to treatment and tested negative for all other diseases. As her condition deteriorated, her mother mentioned 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. The diagnosis was later confirmed by laboratory tests at the Centers for Disease Control and Prevention.^[7][8]

Induced coma treatment

Medical history has shown 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.^[6] Giese's parents agreed to the experimental treatment.^[6]

Willoughby's goal was to put Giese into an induced coma to essentially protect her from her brain, with the hope 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 and midazolam to suppress brain activity, and the antiviral drugs ribavirin and amantadine, while waiting for her immune system to produce antibodies to attack the virus.^[6] Giese was brought out of the coma after six days, once signs of the immune system's progress became apparent.

After infection

After 31 days in the hospital, Giese was declared virus-free and removed from isolation. The extent of brain damage she had suffered was of initial concern, 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.^[9] By early 2005, she was able to walk on her own, had returned to school, and started driver's education, indicating a successful recovery.^[10]

Mayo Clinic neurologist Dr. Kenneth Mack described her condition as she entered college: "She's recovered 'remarkably well' and should continue to improve."^[10] Giese graduated as a biology major from Lakeland College 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 illness, 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 (complications) from the rabies, she still has problems with running and balance.^[11]

Survival hypotheses

The reasons for Giese's survival under the Milwaukee protocol remain controversial. While the treatment appears to have worked as planned, her doctors have suggested that Giese might have been infected with a particularly weak form of the virus,^[6] or that being bitten in a site far from the brain provided her immune system sufficient time to fight the virus. When admitted to the hospital, no live virus, only antibodies, could be isolated from her body,^[12] and the bat was not recovered for testing.^[6]

Medical experts disagree about the effectiveness of the Milwaukee treatment, pointing out that a certain antibody type appears in all survivors.^[13] This suggests that it is perhaps genetics, not the Milwaukee protocol, that was key to the survival of Giese and others.

Other attempts

Giese's treatment regimen has since undergone revision (the second version omits the use of ribavirin). Two of 25 patients treated under the first protocol survived. A further 10 patients have been treated under the revised protocol, with a further two survivors.^[14]

In June 2011, another child survived infection with rabies without receiving the vaccine before showing symptoms. Precious Reynolds, an eight-year-old girl from Willow Creek, California, contracted the disease in April 2011, but did not receive medical care until mid-May, after her grandmother took her to the doctor because of influenza-like symptoms that grew so serious, her grandmother said they resembled polio. The hospital said doctors followed the protocol established for Giese. Reynolds was placed in a drug-induced coma and received antiviral medications. She spent two weeks in intensive care undergoing the treatments.^[15] Some critics say those survivors (5 out of 36 survival rate) are due to the patients having a genetic rabies immunity and that the Milwaukee protocol has nothing to do with the survival rate;^[16] however this would imply the five patients all happened to coincidentally survive rabies while receiving the Milwaukee protocol - despite no documented survivors before them. Ketamine has been shown to have a direct effect against the rabies virus.^[17]

References

External links

• Rabies Registry
• Description of the Protocol

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