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Milwaukee Protocol: Scientists learn from rabies treatment failure

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Rabies virus, one of twelve viruses in the Lyssavirus genus and the Rhabdoviridae family, is nearly always fatal once symptoms appear. It is spread through the saliva of infected animals, including domestic animals such as cats, dogs, and horses; and wild animals, such as bats, skunks, and woodchucks. Most people who survive a bite from a rabid animal receive post-exposure prophylaxis, including rabies immunoglobulin to help them fight the infection and four rabies vaccine injections over 14 days.

However, in 2004, a pediatrician in Milwaukee, Wisconsin, successfully treated a symptomatic individual with a set of treatments that came to be known as the "Milwaukee Protocol." The Milwaukee Protocol includes placing the patient in a medically induced coma while the patient's body mounts a natural immune response to the virus, along with administering antiexcitatory and antiviral drugs. Since this first successful treatment of a 15-year-old girl, five of 43 Milwaukee Protocol attempts have succeeded in saving the lives of potential rabies victims.

Unfortunately, a British citizen of South Asian descent who contracted rabies while visiting her extended family, was not one of those saved. The woman did not seek -- or was unable to obtain -- post-exposure prophylaxis after her infection abroad, and manifested symptoms including paraesthesia, vomiting, confusion, and aversion to water (the reason that rabies is commonly called "hydrophobia"). She was treated with the Milwaukee Protocol; her condition stabilized, but she subsequently developed heart block and acidosis, and died on her eighth day of treatment (her tenth day in the hospital).

Scientists studying this patient's case emphasize the danger of allowing wild and feral animal populations to serve as rabies virus reservoirs, as well as the importance of receiving prompt post-exposure treatment that includes immunoglobulin and rabies vaccine. (A recent survey finds that only two-thirds of travelers to Asia bitten by wild dogs receive post-exposure prophylaxis against rabies.) However, they also hope that this patient's treatment and death will yield some clues as to why the Milwaukee Protocol works for some patients and not for others. Some factors that may be relevant include:

Scientists are also investigating biomarkers that can help guide treatment decisions. Although the best course of action is to seek immediate treatment advice from a doctor when bitten by any animal that can be a carrier of rabies, medical researchers are hopeful that advances can be made in treating those who do not receive appropriate treatment right away, and become symptomatic.