No Rabies Treatment After All: Failure of the Milwaukee Protocol

By Chris Healey

Doctors are abandoning the only treatment for rabies.

The Milwaukee protocol, a procedure reported to prevent death after the onset of rabies symptoms, has been performed over 26 times since its inception in 2004 but has only saved one life. Overwhelming failure has lead health officials to label the protocol a red herring.

Rabies is caused by the rabies virus, an RNA-based virus in the genus Lyssavirus. Transmission typically occurs when virus-laden saliva from a rabid animal enters a wound or mucous membrane. Infection typically occurs from a rabid animal bite. The virus travels along peripheral nerves until it reaches the brain and salivary glands. A characteristic rabies symptom is aversive behavior toward water or water consumption called hydrophobia. Individuals demonstrating hydrophobia will generally avoid water and resist drinking it. Other symptoms include anxiety, nerve pain, itching, impaired sensation of touch, convulsions, paralysis, and coma. Cases among unvaccinated individuals almost always result in death.

The Milwaukee protocol was conceived in 2004 by a team of medical professionals, led by Dr. Rodney Willoughby, after a 15-year-old girl was admitted to a Milwaukee hospital after a rabies diagnosis.

After consulting with researchers at the Centers for Disease Control and Prevention in Atlanta, the team formulated and implemented a novel procedure. The patient was placed in a drug-induced coma and given an antiviral cocktail composed of ketamine, ribavirin, and amantadine. Considering the theory that rabies pathology stems from central nervous system neurotransmitter dysfunction, doctors hypothesized suppressed brain activity would minimize damage while the patient’s immune system developed an adequate response.

The patient was discharged from the hospital 76 days after admission. She demonstrated speech impediment and difficulty walking during a clinic visit 131 days after discharge. It is unclear how long those conditions persisted. In subsequent years, the patient attended college. She remains the only Milwaukee protocol success.

There has been confusion regarding the efficacy of the Milwaukee protocol. A 2009 report published by Dr. Willoughby in the journal Future Virology described the efficacy and promise of the procedure. In that article, Dr. Willoughby cited two new instances of rabies patient survival following Milwaukee protocol implementation. Those two cases brought the total number of rabies patients saved by Milwaukee protocol procedure to three. However, those survivor reports were rebuked by a 2013 article published in the journal Antiviral Research. That article explicitly states Dr. Willoughby’s claims in Future Virology are misleading because the two patients mentioned actually succumbed to rabies.

Overwhelming Milwaukee protocol failure has been attributed to anomaly in the initial patient. For example, she was bitten by a bat, but that bat was not recovered. Without the bat, it is impossible to test the causative rabies agent to rule out a less virulent variant. A mild version could be fought off more easily and could help explain her survival. Additionally, researchers cannot rule out the possibility the patient possessed extraordinary physiology that somehow impaired the rabies progression.

Health officials claim Milwaukee protocol repetition impedes efforts to find new treatments. Instead of exploring new techniques, doctors fall back on the Milwaukee protocol because it was once successful. Crushing failure has prompted the health community to place a taboo on the protocol, encouraging experimentation that may lead to different treatment options.


Image Credit: CDC