Rabies is Still Here

When you think about the world's deadliest illnesses, your mind may conjure up frightening media images of Anthrax, Ebola or even Smallpox. However, the world's actual most deadly virus may be off your radar these days: Rabies. With its near 100% fatality rate, rabies has been with humans for thousands of years. Tales of people writhing in ecstatic pain, climbing up the walls with hydrophobia, experiencing non-stop spontaneous ejaculations and dying a hideously painful death are deeply entrenched in historical documents and folklore. Rabies, also historically referred to as a kind of Lyssa, Latin for beast-like madness, has miffed doctors throughout the ages. It was blamed on everything from demonic possession to bad air. Historians believe that it inspired belief in werewolves and vampires (both of whom exhibit rabid human behavior). The timeless search for a cure has often resulted in ridiculous, even torturously futile attempts. For example, “Doctors” once believed that tying a dead chicken's anus against the wound and leaving it there for days was a step in the right direction. Other cures included attempting to drown the victim in a well, or rubbing some pepper into the wound which had been stirred in a magical bowl beforehand. Long story short, Rabies has been a fatal, torturous burden on humanity for as far back as we can see in the records (Waisik, 2012). However, no one has been able to understand it - or cure it - until recently.

The historical accounts of the disease may sound far out and far away. The truth is that Rabies is still thriving today. There have been only a handful of cured cases, so the fatality rate still lies near 100% (Mayo Clinic). How does this effect us? While rabies is uncommon in most Westernized nations, over 55,000 people die each year of the disease. Millions more need post-exposure vaccination treatments which, if they are received immediately after exposure, can prevent infection (Huang, 2014). Fortunately, if you are able to identify a rabies bite and you receive immediate post-vac care, you have a good shot at survival. However, many people are not aware of their exposure or do not realize the danger of getting bitten or scratched by a local stray animal or a bat (Mayo Clinic).

We need better rabies education across the globe, particularly in high risk areas. Since there is an effective immediate post-vac, one of the biggest threats is ignorance. If you are scratched or bitten by an animal, you must to seek preventative treatment immediately, and people need to know this. We also need to continue supporting the search for a cure. The good news is that we have never been closer to finding one.

"Basically, the best way to deal with rabies right now is simple: Don't get rabies,"

-Biao He, professor of infectious diseases in the UGA College of Veterinary Medicine.

The last decade or so has shown vast improvement in the treatment of rabies. This is despite the fact that we still do not know how to cure it and most victims still die unless they receive immediate post exposure vaccination. These statements may not sound particularly hopeful, but it goes to show you how little we have come to understand this disease over the last thousands of years. Never the less, we are finally making some progress. Let's take a look at some of the cases where humans have actually survived, and examine the possible mechanisms behind that survival.

The most notable treatment is what is known as the Milwaukee Protocol. Of the 35 people treated, only 5 have survived. This is hardly a promising figure, but it does suggest that there is some key to overriding rabies; maybe something we haven't really understood yet. Its not what we want, but its obviously wonderful at the same time.

Here's how the story goes. In 2004 Jeanna Giese became the first person in the world to survive symptomatic rabies. The 15-year-old girl was bitten by a bat (which was fluttering around in the daytime) while she was attending church with her parents. The family dressed the wound and went on with their lives; forgetting about it. Bats are infamous rabies vectors so it is amazing that a child living in a supposedly educated and industrialized nation could be bitten by one (that's flying around in the daytime no less), and that adults would not know to seek medical care as a potential rabies precaution. Like many cases, Jeanna's subsequent rabies infection could have been entirely avoided if there had been better rabies education in her community. However, history tells a different story and Jeanna did go on to have full blown rabies. When she showed up at the hospital and the tests were conclusive, her doctor was unfamiliar with any treatment. However, after reading medical literature and doing some creative thinking, Dr. Rodney Willoughby concluded that it may be possible to essentially override the deadly virus by putting the girl into a deep coma. In a case that would otherwise have zero options, his line of thought was brilliant and certainly worth a shot.

Rabies ultimately kills the body, because it infects the brain and the brain then causes all of the body's functions to misfire; essentially causing complete havoc and destruction which results in death. Since rabies usually kills its victims within a few weeks after symptoms occur, the theory was that if the victim was kept alive long enough, and the brain was kept in deep coma; unable to communicate to most of the body's systems, then the immune system may have a chance to overcome the virus while the brain was sleeping.

Basically, since the brain kills the body, if you shut down the brain, then the body has a chance to fight back.

It worked. Jeanna was severely affected and spent over a year in therapy after her recovery. She had to learn to walk and talk again. However, she ultimately went on to graduate high school and to be a normal kid again. While the theory behind the Milwaukee treatment is promising, the sad news is that most people treated subsequently with the protocol did not make it. The cases are sordid and inconsistent. Eight year old Precious Reynolds survived thanks to the protocol in 2011. The protocol also takes credit for curing Nelsy Gomez in Columbia. However, she died of pneumonia whilst in the coma. Her doctor's were still certain that the protocol had been effective in curbing her rabies, but the verdict is still out on a case like this (Juncosa 2008). As you see, the follow up stories for the protocol usually ended in tragedy, but undoubtedly saved some human lives. There obviously is some value to the protocol, but due to its poor success rate most doctors and scientists see it as a fluke and don't consider it a valid treatment. If you try and learn about the treatment, you will see that articles are scattered over the last 10 years or so, and that no one is actively perusing it today in any real scientific sense. But you have to ask yourself if the treatment somehow did hold a key that we were simply unable to identify. If the disease claims 100% of human lives, how did that lucky 15% survive?

It is possible that throughout history some people did survive rabies. As with any virus, it has numerous strains. Some scientists believe that survivors of the protocol may actually have caught weakened strains of the virus. In 1970, a boy survived rabies for the first time in recorded history. In his case, he received the immediate post-vac treatment (which was less successful at the time), but the virus still took a hold of him. After an uphill battle he did go on to survive and live a life basically free of neurological complications. Most doctors and scientists agree that his unsuccessful post-vac shots had somehow weakened the virus which enabled him to live (Juncosa 2008). This suggests that if the virus is weakened, the patient has a small chance. Maybe that is all that the Milwaukee protocol survivors represent; a strain that is naturally weakened for some reason and thus a deep coma is enough to override the virus. This treatment provided the world with a strange combination of hope, disappointment, miracle and mystery. The good news is that a recent scientific study is bringing us closer to a viable solution by shattering the old conception that there is no cure.

2015 was a breakthrough year for rabies, because scientists at the University of Georgia successfully were able to cure mice that were infected with the disease. They did not receive the immediate post-vac, and they were already showing symptoms. Typically, this ensures near-certain death. The following excerpt comes directly from the study report, and the findings are pretty exciting compared to anything we have seen before.

“In their mouse experiments, the animals were exposed to a strain of the rabies virus that generally reaches the brain of infected mice within three days. By day six, mice begin to exhibit the telltale physical symptoms that indicate the infection has become fatal. However, 50 percent of mice treated with the new vaccine were saved, even after the onset of physical symptoms on day six (Huang, 2014).”

How did they do it? The team inserted proteins from the rabies virus into another virus called parainfluenza virus 5, or PIV5. Interestingly, PIV5 is what most of us know as Kennel Cough; a common respiratory infection that dogs can get. The good thing about Kennel Cough is that it acts as a carrier to the immune system for the rabies virus, so that the immune system is able to deal with it directly and fight the virus (Hataway, 2015).

This particular treatment is still in its infancy. 50% is far better than anything we have seen before, but the treatment will need to see better numbers and it will have to be rigorously tested before it could be potentially available to humans. It's too early to say what will happen, but it is fair to say that the breakthrough is very promising.

One thing that has rung true in both the case of the Milwaukee Protocol and the Georgia study, is that the key to beating rabies was in discovering a loophole that gives the immune system a chance to actually fight the virus. Whether it is through a coma or by letting rabies face the immune system with a little help from a famous (albeit unsuspecting) K9 pathogen, all of the information shows that we need to find a way to let the body's natural defenses fight rabies.

There has been progress here and there, but we still do not know how to cure the world's deadliest virus. Thanks to an effective immediate post-vac, people can be spared if they seek medical attention immediately after a bite. Less than 10 people die in US every year due to Rabies, but about 30,000 require immediate post-vac care due to exposure. Unfortunately, there are countries in Asia and Africa that do not have access to rabies education and adequate health care, and these places attribute the almost 60,000 rabies deaths that occur every year.

We need to remember that rabies is still with us, and that so many people are affected. With better campaigns to raise awareness, many lives could be saved. If we continue to support research, it is clear that we are closer than ever to finding a cure, and there is a good chance that sometime in the next years, we can be reading articles about “How the World's Deadliest Virus was Finally Cured.”

Sources:

Huang, Y., & Chen, Z. (2014). Parainfluenza virus 5 expressing the G protein of rabies virus protected mice after rabies virus infection.Journal of Virology. Retrieved from http://jvi.asm.org/content/early/2014/12/26/JVI.03656-14.full.pdf

Juncosa, B. (2008, November 21). Hope for Rabies Victims: Unorthodox Coma Therapy Shows Promise. Scientific American.

Rabies. http://www.mayoclinic.org/diseases-conditions/rabies/basics/preparing-for-your-appointment/con-20019900

Hataway, J. (2015, January 26). Beating the clock: UGA researchers develop new treatment for rabies. Retrieved from http://news.uga.edu/releases/article/beating-the-clock-researchers-develop-new-rabies-treatment-0115/

University of Georgia

UC Davis Children's Hospital patient becomes third person in U.S. to survive rabies. (2011, June 15). Retrieved from https://www.ucdmc.ucdavis.edu/medicalcenter/features/2010-2011/06/20110616_rabies-survivor.html

UCDavis Children's Hospital

Wasik, B., & Murphy, M. (2012). Rabid: A cultural history of the world's most diabolical virus. Viking.