Milwaukee protocol

The Milwaukee protocol is an experimental course of treatment of an acute 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 Dr. Rodney Willoughby, Jr., M.D., following the successful treatment of Jeanna Giese.^[1] Giese, a teenager from Wisconsin, became the first of only six patients known to have survived symptomatic rabies without receiving the rabies vaccine.^[2]

Case history

Initial infection

On September 12, 2004, Giese, then fifteen years old, and a 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.^[3] 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][3] Thirty-seven days after the bite, Giese developed neurological symptoms. She was admitted to St. Agnes Hospital with a 102 °F (39 °C) fever, double vision, slurred speech, and jerking in her left arm.^[3] 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. 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.^[3] Giese’s parents agreed to the experimental treatment at Children's Hospital of Wisconsin.^[3] Dr. Willoughby's goal was to put Giese into an induced coma 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, midazolam, and phenobarbital to suppress brain activity and the antiviral drugs ribavirin and amantadine while waiting for her immune system to produce antibodies to attack the virus.^[3] Giese was brought out of the coma after six days once signs of the immune system's progress became apparent.^[3]

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.^[4] Mayo Clinic neurologist Dr. Kenneth Mack described her condition as she entered college: she's recovered "remarkably well" and should continue to improve.^[4] 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 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.^[5]

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,^[3] 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,^[6] and the bat was not recovered for testing.^[3]

There is no specific medication to fight rabies - the body will kill it off eventually, if it can survive long enough.^[7]

Other attempts

Giese's treatment regimen has since undergone revision (the second version omits the use of ribavirin). 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.^[8]

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.^[9] 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.

References

1. ^ ^{a b} Rodney E. Willoughby, Jr., "A Cure for Rabies?" Scientific American, V. 256, No. 4, April 2007, p. 95 (online link)
2. ^ Jordan Lite (2008-10-08). "Medical Mystery: Only One Person Has Survived Rabies without Vaccine--But How?". Scientific American. pp. 4. http://www.sciam.com/article.cfm?id=jeanna-giese-rabies-survivor&sc=WR_20081014. Retrieved 2008-10-16. 
3. ^ ^{a b c d e f g h i} Johnson, Mark; Kawanza Newson (2006-05-11). "Hoping again for a miracle". Milwaukee Journal Sentinel. Archived from the original on July 28, 2006. http://web.archive.org/web/20060728015454/http://www.jsonline.com/story/index.aspx?id=423103. Retrieved 2008-07-16. 
4. ^ ^{a b} "Giese Overcomes Rabies, Heads to College", WEAU, August 30, 2007, Retrieved September 4, 2007
5. ^ "Rabies survivor Jeanna Giese graduates from college", May 8, 2011 Retrieved June 13, 2011
6. ^ Rodney E. Willoughby, Jr., et. al. "Survival after Treatment of Rabies with Induction of Coma", The New England Journal of Medicine, June 16, 2005 352:2508-2514, accessed February 12, 2011.
7. ^ Allday, Erin (2011-06-13). "Rabies: Humboldt girl beats virus against odds – Page 2 of 2". The San Francisco Chronicle. http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2011/06/11/MN241JRH8J.DTL&ao=2#ixzz1PD6PKerw. 
8. ^ Willoughby RE (2009). "Are we getting closer to the treatment of rabies?: medical benchmarks". Future Virology (MedScape) 4 (6): 563–570. doi:10.2217/fvl.09.52. http://www.medscape.com/viewarticle/712839_7. 
9. ^ http://news.yahoo.com/s/ap/20110613/ap_on_he_me/us_rabies_survivor;_ylt=AkIisX0PcA.mIznMaXBYRP3QbbUC;_ylu=X3oDMTNja29jMHViBGFzc2V0A2FwLzIwMTEwNjEzL3VzX3JhYmllc19zdXJ2aXZvcgRjY29kZQN0b3BnbXB0b3AyMDBwb29sBGNwb3MDNARwb3MDNARzZWMDeW5fdG9wX3N0b3JpZXMEc2xrA2hvc3BpdGFsZ2lybA--

External links

• "Rabies survivor leaves hospital". jsonline.com. Milwaukee Journal Sentinel. 2005-01-02. http://www.jsonline.com/story/index.aspx?id=289357. ^{[dead link]}
• "Jeanna Giese struggles to be... just your normal rabies survivor". jsonline.com. Milwaukee Journal Sentinel. 2005-11-26. http://www.jsonline.com/story/index.aspx?id=373532. ^{[dead link]}
• "First Person in Recorded History to Survive Advanced Rabies Without Vaccination or Postexposure". Purple Medical Blog. 2005-12-05. http://purplemedicalblog.blogspot.com/2005/12/first-person-in-recorded-history.html. 
• "First Unvaccinated Rabies Survivor Goes Home". Daily News Central. 2005-01-03. http://health.dailynewscentral.com/content/view/258/. 
• Rodney E. Willoughby, Jr., M.D.; et al. (2005-06-16). "Survival after Treatment of Rabies with Induction of Coma". New England Journal of Medicine 352 (24): 2508–2514. doi:10.1056/NEJMoa050382. PMID 15958806. http://content.nejm.org/cgi/content/short/352/24/2508. 
• "Jeanna Giese Learns to Drive". WBAY. 2006-04-08. http://www.wbay.com/Global/story.asp?S=4147294. ^{[dead link]}
• "Surviving Rabies : A Medical First Takes Place at Children's Hospital". Healthlink. Medical College of Wisconsin. 2005-05-26. http://healthlink.mcw.edu/article/1031002506.html. 
• "Down to a Prayer". jsonline.com. Milwaukee Journal Sentinel. 2005-06-18. http://www.jsonline.com/features/health/47465427.html.