In the Fall of 2004, 15 year old Jeanna Giese checks into the Children's Hospital of Wisconsin with a set of puzzling symptoms. Jeanne has arm tingling, double vision and flu-like symptoms. Each day she becomes more exhausted and eventually her body stiffens up and begins to spasm. Her neurologist runs test after test and they all come back negative. Finally, Jeanna is hospitalized as her symptoms continue to worsen. Finally, Jeanna's mother thinks to tell her pediatrician about the bat...
Four weeks earlier, while in church, Jeanna had been carrying an injured bat outside and was bitten on her index finger. Upon hearing this, the pediatrician's face turns white and he leaves the room. Why? Because Jeanna has rabies. And if you are diagnosed with rabies, you die 100% of the time (Paoli, 2013). (Fun fact: Not a single other documented virus has a 100% fatality rate in humans)
The way a typical virus travels is as follows: it replicates locally at the point of entry, makes its way into the bloodstream circulating widely until it travels to target tissue to replicate there. This is not how rabies behaves. Rabies enters the body at the bite wound site, binds to a nerve right there via a specific receptor (p75NTR) and "crawls" its way up the nervous system at a pace of 1-2 cm per day to reach and attack the brain (Gluska et al., 2014). Creepy. While the rabies virus is slowly crawling up her peripheral nervous system, Jeanna's body is cultivating an immune response. If she is given a vaccine before the virus reaches her brain then it can help boost her immune response. But once Jeanna has an onset of flu-like symptoms, the vaccine can no longer help her body fight the virus and she will die.
Jeanna's doctor, Dr. Rodney Willoughby, won't accept this answer; he is hesitant but he thinks he may have come up with a new treatment! It turns out that the way the rabies virus effects the brain may be via excitotoxicity. This means that instead of physically destroying the brain, the rabies virus causes the neurons to become overstimulated (via excessive amounts of neurotransmitters) which disrupts the parts of the brain responsible for controlling life-sustaining functions such as breathing and heart rate, leaving them overwhelmed and unable to function. We can think of the rabies virus as a software problem, not a hardware problem, with the brain itself spared from injury (Radiolab, 2013).
Dr. Willoughby knew that Jeanna's immune system had the tools to fight rabies but that the virus would kill her due to a faster attack than her immune response could ward off. So, he wondered, how could he buy Jeanna more time? What if he administered sedatives and antivirals and induced a coma to wait 7-10 days for an immune response hefty enough to kill off the rabies virus? With trepidation, this is what he did.
After 7 days, Dr. Willoughby checks Jeanna's cerebrospinal fluid for antibody levels indicative of an immune response. The treatment has worked, antibody levels are high! They slowly bring Jeanna out of her coma and wait with bated breath. At first she is responsive just to light (pupillary response), by day two she regains her leg reflexes, and within a week she is ambulatory. Jeanna goes on to regain all regular function. Lasting side effects are only occasional trouble with balance and speaking more slowly than before infection. Jeanna becomes the first person to survive rabies without the vaccine!
Dr. Willoughby's treatment becomes known as the Milwaukee Protocol and is the only known means to possibly save unvaccinated rabies patients. As of 2013, it had been tried 41 times and was successful in only 6 cases (Paoli, 2013). The reasons for this low success rate are for another blog post, however, this is a 14.5% efficacy rate. Definitely something to consider when a patient is battling the previously-100% deadly rabies virus.
Abumrad, J. (Writer). (2013, August 13). Rodney Versus Death [Radio series episode]. In Radiolab. New York, New York: WNYC.
Gluska S, Zahavi EE, Chein M, Gradus T, Bauer A, et al. (2014) Rabies Virus Hijacks and Accelerates the p75NTR Retrograde Axonal Transport
Machinery. PLoS Pathog 10(8): e1004348. doi:10.1371/journal.ppat.1004348
Paoli, J. (2013, August 21). Is Rabies Really 100% Fatal? Retrieved November 26, 2017, from https://www.nature.com/scitable/blog/viruses101/is_rabies_really_100_fatal
You had me hanging on the edge of my seat, and I would LOVE to see The Milwaukee Protocol: Chapter 2. It is amazing that a disease like rabies, which has existed for so long, is still a mystery in its pathology. I hadn't even thought about rabies still being an issue in this day and age, but clearly it is, and as far as I know, not much research is being done on it because it's not a "trendy" topic.
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