On January 10th, the first reports of a Florida child, infected with rabies and undergoing an experimental treatment protocol, began making the rounds. 6-year-old Ryker Roque, according to the news coverage, had come into contact with an injured bat that his father had placed in a bucket outside the family’s home. At some point over the next few days, Ryker had unsupervised access to the bat and, despite his father’s warnings, let curiosity get the better of him. This proved fatal on January 14th when Ryker was declared brain dead, the last ditch therapy having failed to save him.

But first…

Before I delve into this tragic cautionary tale, I wanted to give a brief primer on rabies. Most of you likely knows the basics of rabies, such as the potential for aggression, the hydrophobia, and the high mortality, but the finer details are really interesting. I learned a lot reading up for this post. For instance, I did not realize that rabies is caused by several different viruses in the Rhabdoviridae Family, genus Lyssavirus. I had thought there was just the one rabies virus. And all mammals can potentially become infected but some, like the opossum, are extremely resistant.

Each virus in this genus can cause a disease that we know clinically as rabies, but which particular one can actually make a difference in the clinical course. Using genetic sequencing of the particular virus, we can tell if a patient is infected with bat rabies as opposed to dog or raccoon rabies. Bat rabies virus tends to have a less aggressive course, though still nearly always fatal, than dog rabies virus. The virus specific to canines was officially eliminated from the United States in 2007, but dogs can still become infected with bat rabies or raccoon rabies, for example, and imported dogs can be infected. So still vaccinate your pooch.

The viruses that cause rabies love neural tissue. Once they have entered the body, almost always via the bite of an infected animal, they infect peripheral nerves and travel along them towards the spinal cord at a clip of 50 to 100 mm each day. Once there, their migration speed picks up and they quickly reach the brain, resulting in widespread inflammation. Symptoms start around this time, signaling the point of no return for nearly 100% of patients. The virus then travels back out of the brain and throughout the body, but the salivary glands in particular are supportive of viral replication.

From a global perspective, dogs are the leading source of human rabies infections, accounting for more than 90% of cases. And rabies is seen throughout the world with few exceptions, such as Antarctica, New Zealand, Japan, Sweden, and Spain. Of note, Hawaii is the only state spared. Roughly 60,000 people die every year from rabies, even though there is an extremely effective vaccine. As would be expected, however, most deaths occur in resource-poor regions with limited access to vaccines and medical care, and endemic infection among domesticated animals.

The United States, like most of the developed world, rarely sees rabies deaths anymore. There were less than 100 cases between 1980 and 2015, with a third of these being acquired abroad. When cases do occur in the United States, it’s almost always after exposure to a bat, although raccoons, skunks, and foxes are also considered high risk. Wild small mammals, such as gerbils, squirrels, and rabbits, rarely transmit rabies to us because they are typically killed and eaten by the animal that infects them.

Speaking of bats…

According to his father, Ryker was scratched on a finger by the bat. When reading the early reports, this was the first claim that struck me as odd. It’s incredibly unlikely to get rabies from a scratch. You really need saliva from the bite of an infected mammal with extremely rare non-bite exception. There have, for example, been cases where rabies has been transmitted from person to person via the transplantation of infected tissue, most infamously involving corneal transplants. There have also been reports of infection being acquired by lab personal working with a rabies virus, and even one case linked to aerosolized virus from millions of cave bats, although it is impossible to fully rule out a bite with that kind of exposure.

Poor Ryker was almost certainly bitten. But considering how small bat teeth are, and the fact that he was only 6-years-old, it’s easy to see how he might have been confused. Bat bites often go unrecognized, and in many cases they do not even leave a mark. This, and the difficulty in immunizing one-fifth of the mammal population, is why bats are the most common source for human rabies infections in the United States.

A decision with deadly consequences…

What happened next will undoubtedly haunt Ryker’s parents for the rest of their lives. Reports of the parents’ thought process, and their understanding of the implications of Ryker’s injury, are a bit confusing. It isn’t clear that they knew how dangerous bats can be, but they were at the very least worried enough to consult the internet, just not enough to call Ryker’s pediatrician or family doctor.

The earliest news articles, which quoted Ryker’s father, give the impression that his parents knew that the bat posed some risk to their son. Ryker was warned to stay clear after all, and when the injury was discovered his father “frantically googled it real quick“. Of course, I don’t know what search terms were used, or what website(s) were accessed, but Mr. Roque claims to have found a recommendation to wash the area with soap and water for five minutes, which they did.

As readers of SBM are likely to know all too well, the internet is full of all manner of bad medical advice. But when it comes to rabies, you aren’t going to find much nonsense, although it is there if you dig deep, because we aren’t talking about a condition that has subjective symptoms and a high rate of spontaneous recovery. There is some nuance to the discussion, but rabies remains, even with advanced critical care, an essentially 100% fatal disease.

So it is hard to imagine, unless there was some next level bad luck, that Mr. Roque stumbled onto a source that wouldn’t recommend immediate medical attention. And even using search terms that would otherwise be likely to bring up untrustworthy sources, it is challenging to find much that says anything other than to seek proper care, which involves prophylaxis with rabies immune globulin and vaccine injections. This, and only this, has been proven to prevent the deadly disease, and it is considered to be virtually 100% effective.

So if their search in any way involved the words “bat” and “scratch”, they almost certainly knew at that point that the potential for rabies was very real, and that appropriate medical intervention to prevent rabies was critically important. Based on an interview of the father, early news coverage implied, or outright claimed, that the parents were aware. But they didn’t seek medical attention and Ryker’s fate was sealed.

Ryker’s parents apparently knew the risk but chose to forego medical evaluation for their son because, and this is the part that really made for some angry online comments, he was emotionally upset by the possibility of needing shots. That was the only reason given. It is possible that other factors, such as distrust of the medical system or fear of the vaccine outweighed their concern for possible rabies infection, but I don’t think that’s the case this time. And it would probably have been reported if they chose an alternative therapy of some kind over science-based medicine.

But I digress…

Not that some people don’t seek out alternative care for the non-specific symptoms experienced at the onset of rabies infections, which often includes fever, headache, muscle pain, nausea, and malaise. Sounds a lot like a common viral illness known as influenza, doesn’t it? The chiropractor in this case report failed to recognize early rabies in an adult patient over numerous visits during a six day period. The patient, who had awoken with a bat on his left arm 9 months previously, had presented to the chiropractor with rapidly worsening numbness and weakness of the same extremity.

As is the norm, the patient died. He would have died anyway, so the chiropractor didn’t increase the patients risk of death. But they did waste precious time that could have been spent settling affairs and establishing palliative care, and they likely gave false hope of recovery. More importantly, there are treatable conditions that are much more common than rabies which can present in a similar fashion. For some, time is of the essence.

The story changes…maybe…

Most of the news coverage came out as Ryker was about to undergo an experimental therapy, which I’ll address shortly, and then was simply updated when he died. They all repeated the same initial quotes from the father. In an interesting twist, the events as described in an Orlando Sentinel article, which was the only source to speak directly to the family after Ryker’s death, didn’t quite match up with the earlier account.

In the Sentinel piece, Ryker’s mother relates how she didn’t want the bat kept in the house, but said that they didn’t know of any connection between bats and rabies at the time. When Ryker notified them of his injury, which they initially believed to be a scratch, she Googled it and followed a recommendation to cleanse the area with hot water. There is no mention of the fear of needles, or of any awareness that urgent medical attention was warranted. It reads like they just did what they thought was appropriate and were completely caught off guard when the symptoms began. It’s implied that if they had only known at the time that it was a bite, rather than just a scratch, things might have been different.

Now of course it is possible that the reporter simply chose to leave out certain details, to not kick this poor family while they are down. I get that. It isn’t going to bring back their child and they have suffered enough. And they are trying to raise awareness to help prevent future tragedies. But I also know how the human mind tends to work when facing a situation sure to create the kind of cognitive dissonance that would keep most people from having a good night’s sleep for a long time. These types of life changing events often result in broken marriages and significant mental health repercussions.

These are loving parents, at least I have no evidence to think otherwise, and probably reasonably intelligent people. But they did something that most folks, even when taking into account the risk of making a fundamental attribution error, would ascribe to mind-boggling bad judgement that might raise questions about their ability to make appropriate medical decisions in general. I certainly would understand it if their personal narrative shifted a bit to provide some degree of psychological stress reduction.

Ryker’s diagnosis and likely discussion of management

The timing of Ryker’s bat exposure and the development of symptoms is somewhat hard to tease out. Reports differed, ranging from “a week or so” to “a few weeks later”, but Ryker eventually began to show concerning signs of illness. A week would be extremely unlikely, even with a high risk exposure, but I can’t say it’s impossible.

The incubation period, the time between exposure and the onset of symptoms, tends to be much longer than a week. It often takes months, rarely even years, although in cases of apparent extreme incubation periods it can be difficult to rule out additional exposures that happened closer to the onset of symptoms. The incubation period varies depending on factors such as location and severity of the wound, genetics, host specific immune response, adequacy of prophylaxis, and which virus is involved. Ryker, with a small bat bite about as far from the brain as you can get in a young child, would be more likely to have had a longer incubation period, but it is difficult to predict these things with any certainty.

Regardless, what we know is that at some point Ryker complained of numbness in the same hand as the bite, a huge red flag for rabies, and headache. One report mentions that he began to have unusual jerking movements of the arm, which has been reported with bat rabies virus infection, confusion, and difficulty walking. At this point, apparently concerned about the possibility of a head injury, his parents sought medical care at Arnold Palmer Hospital for Children.

Ryker’s exposure to a bat was naturally very worrisome to the treating physicians and he was admitted to the hospital for an extensive work-up, which included testing for rabies. This typically, although I’m not privy to his specific medical information, involves looking for evidence of the virus and/or an immune response to the virus in the patient’s blood, spinal fluid, saliva, and skin. After consultation with experts, a family meeting was held to discuss their concerns, and the parents were informed of the low likelihood of survival should rabies be the cause of his symptoms. After a few days, laboratory results confirmed the diagnosis.

The treatment of rabies remains primarily palliative in most cases, which is largely dictated by the fact that most rabies cases occur in regions without access to advanced critical care. Aggressive management, which Ryker did receive, is more likely to occur in developed regions, particularly in younger and healthier patients. But even with the full, kitchen sink approach there have only been 15 well-documented cases of survival, and a smattering of anecdotal reports, once symptoms have started. All were young and healthy, and all but one had at least one dose of rabies vaccine prior to developing symptoms. We actually have no idea if any aspect of aggressive treatment beyond supportive cardiac and respiratory care in an ICU improves survival, and there are factors other than specific therapies that likely play a larger role.

The palliative approach, at least when modern critical care is available, is typically undertaken in cases where survival is less likely, such as older patients with more medical problems, when disease is already severe, when dog rabies virus is involved, or when there is no lab evidence of an immune response against the virus. Almost all survivors have had significant neurologic problems after recovery, something that should also be discussed with patients, if possible, and family prior to deciding a course of action.

The goal of palliative care is to reduce suffering. This involves the use of medications to sedate patients and to treat pain because agitation and discomfort can be severe. Patients can become confused, delirious, even aggressive. So a quiet and calm environment is also key. When this course is chosen, complications that can result in death, such as cardiac arrhythmia or respiratory failure are not treated. Palliative care can also take place at home, depending on the desires of the patient and family.

In contrast, aggressive management requires admission to an intensive care unit where cardiac and respiratory support is available, as well as various experts in critical care and infectious disease. Complications are managed with intent to cure and patients are provided intravenous nutrition if needed. It is probably safe to say that ICU care is the main reason we have seen a handful of survivors over the past few decades.

Various other therapies have been tried over the years in addition to supportive ICU management. This has been based on the notion that some serious infections, as well as many cancers, require a combination of therapies with different goals to improve rates of survival. In this effort, drugs that modulate the immune system, antiviral medications, and therapies aimed at protecting the brain from injury and improving access of medications to the central nervous system have been tried in various combinations. None have been proven to work, and each has potential for severe side effects.

The Milwaukee protocol

I’ve mentioned an experimental treatment that Ryker underwent a few times already in this post. Virtually all of the news reports described it as having worked in the past, and implied that it was a patient’s only hope. The treatment, known as the Milwaukee Protocol [PDF, initiates automatic download] (sometimes the Wisconsin Protocol) was developed by Dr. Rodney Willoughby, a pediatric infectious disease doctor at Children’s Hospital of Wisconsin, to treat a now famous 15-year-old girl diagnosed with rabies in 2004. She was the 6th well-documented case of survival since the first in 1970, and the first ever to survive rabies without having at least received one dose of vaccine prior to developing symptoms.

The protocol involves placing the patient into a medically induced “therapeutic coma” using ketamine and a benzodiazepine for a week with the intent of protecting the brain from theorized “excitotoxic” effects of the virus on neural tissue. Patients also receive a cocktail of an antiviral medication, vitamin C, and a drug used to theoretically prevent vasospasm of cerebral blood vessels. In 2004, the first time this combination of therapies was used, the patient lived, shocking the world and forever changing rabies management.

Unfortunately, it is very likely all smoke and mirrors. From a basic science standpoint, solid evidence supporting the efficacy of any component of the Milwaukee protocol is lacking. And therapeutic coma is extremely risky. Since that seemingly miraculous case in 2004, the protocol has been put into use many more times and has failed rather spectacularly.

When studied by experts other than Willoughby, the results have been dismal. According to Willoughby, there have been 18 survivors so far, but he can’t reveal details about their cases. Two prior “success stories” where documentation was available were found to have actually died. Sometimes credit is given because a patient lives a little longer than expected. But even if a few patients have survived on the protocol, the success rate is still incredibly low, and their recovery likely should be credited more to modern supportive critical care and luck (genetics, the particular virus, robust immune response) than any specific therapy.

Despite the lack of non-anecdotal evidence for the Milwaukee protocol, and more plausible explanations for the few survivors, it has become commonplace in the treatment of rabies in the United States. There is concern that this is distracting from appropriate palliative care efforts and research into novel approaches. I can’t say if the jury is completely out, but it doesn’t look good.

Conclusion: Prevention, prevention, prevention

The take-home point from the tragic case of Ryker Roque is, I hope, obvious. Don’t mess around with bats and supervise young children when a bat is anywhere close by. Call a professional to have it removed. And if you do come into contact with a bat, or if you find a bat in the room of a sleeping child or someone unable to know if they had been bitten (drunk, cognitively impaired), essentially if there is even the slightest chance that a bat might have bitten someone, seek appropriate medical care and get the post-exposure prophylaxis when recommended.

If you are bitten by an unknown animal, especially if it is an unprovoked attack, don’t mess around. There are protocols for this. You can often avoid the need for shots if the animal can be observed or if it is low risk beast. But if recommended, do it.

People used to be terrified of the rabies vaccine. This is because it used to hurt…a lot. It was a large volume of medicine that they injected into your abdominal muscles and you needed like 500 doses. Okay, I’m exaggerating, but it was a lot. After decades of advancement in vaccine science, you can prevent a horrible death with 4 fairly painless 1 ml immunizations and a dose of rabies immune globulin. Again, do it if recommended.

Posted by Clay Jones

Clay Jones, M.D. is a pediatrician practicing at Newton-Wellesley Hospital in Newton, MA, and a regular contributor to the Science-Based Medicine blog. He primarily cares for healthy newborns and hospitalized children, and devotes his full time to educating pediatric residents and medical students. Dr. Jones first became aware of and interested in the incursion of pseudoscience into his chosen profession while completing his pediatric residency at Vanderbilt Children’s Hospital a decade ago. He has since focused his efforts on teaching the application of critical thinking and scientific skepticism to the practice of pediatric medicine. Dr. Jones has no conflicts of interest to disclose and no ties to the pharmaceutical industry. He can be found on Twitter as @skepticpedi and is the co-host of The Prism Podcast with fellow SBM contributor Grant Ritchey.