1. MILWAUKEE PROTOCOL Jane Harrington, Ph.D. Course Director and Assistant Professor of Microbiology University of Medicine and Health Sciences, St Kitts

2. http://www.nejm.org/doi/full/10.1056/NEJMoa050382

3. PATIENT HISTORY Sunday, September 12, 2004 15-year-old Jeanna Giese attended church in Fond du Lac, WI Jeanna is bitten by a Silver Haired bat.

6. PATIENT PRESENTATION October 13, 2004 Jeanna starts noticing generalized flu-like symptoms (nausea, myalgia, extreme fatigue, double vision). October 16-18, 2004 Symptoms progressed to left sided-weakness, abnormal gait, and vomiting, fever, slurred speech, eye twitching, dilated pupils, tremors of left arm, spontaneous salivating with uncoordinated swallowing.

7. PATIENT DIAGNOSIS MRI results were normal and CSF was clear of any bacterial pathogen. Rabies-specific IgM antibodies were detected in CSF, serum and skin biopsy by CDC. No rabies virion particles or nucleic acid were detected in CSF, skin or saliva samples.

8. RABIES PATHOBIOLOGY Rabies viral protein are homologous to glutamate (NMDA) neurotransmitter. Activation of glutamate-NMDA receptor leads to excitation state. Excessive excitation triggers Ca 2+ influx and superoxide production. “Glutamate poisoning” aka cytotoxicity results in cellular apoptosis and eventual systemic neurological dysfunction.

9. PATIENT COURSE OF THERAPY Therapeutic Goal Reduce damage from neurotoxicity and target virus with antivirals, to allow patient to illicit naturally acquired immuno-protective anti-rabies IgG. GABA = inhibitory neurotransmitter. Glutamate/NMDA = activating neurotransmitter.

10. PATIENT COURSE OF THERAPY Jeanna was admitted to intensive care and induced into a medical coma. Ketamine (NMDA/glutamate receptor antagonist) Phenobarbital (GABA receptor agonist) Benzodiazepine (GABA receptor agonist) Additionally antiviral therapy was administered. Ribavirin (nucleoside analogue) Amantadine (un-coating inhibitor and anti-excitotoxic)

11. PATIENT COURSE OF THERAPY Onset of fever corresponding to increase in Anti-Rabies IgG Reduction of fever and high levels of Anti-Rabies IgG

12. PATIENT OUTCOME http://www.nejm.org/doi/full/10.1056/NEJMoa050382 Jeanna experienced a successful recovery with physical therapy, though has lasting minor balance and memory issues.

13. DR. RODNEY WILLOUGHBY WAS NOT READY TO LET ME DIE

14. PATIENT FOLLOW UP Jeanna got married on September 20, 2014!