Nobody survives rabies. Sure, the disease can be prevented by administrating a vaccine after exposure to the virus. But if this window of opportunity is missed, if the virus makes it to the brain, if the classic symptoms – delirium, agitation, loss of motor control, hydrophobia – emerge, then it’s too late and the results are fatal. Always. Or so we used to think. That’s why it was big news when, in 2004, an unvaccinated 15-year-old girl recovered from full-blown symptomatic rabies after receiving an experimental treatment later dubbed the Milwaukee Protocol.
But the idea that this experimental intervention – which involves placing the patient into a medically induced coma to allow their immune system time to fight off the virus – is responsible for her remarkable recovery is not universally accepted. Since its advent, the Milwaukee Protocol has been attempted on dozens of additional rabies cases, but has yielded only five successes. Critics suspect these survivors owe their lives not to the treatment, but to some other factor. A particularly strong immune system? An especially weak form of the virus? Is it possible that rabies isn’t as unilaterally lethal as we’ve been told? A new study of two rural populations in the Peruvian Amazon suggests that non-fatal encounters with rabies virus may not be such rarities.
The study, led by scientists from the U.S. Centers for Disease control, examined two remote communities in a region of Peru where rabies outbreaks are common. Rabies virus in Latin America is spread primarily by common vampire bats (Desmodus rotundus), a species whose sustenance consists entirely of blood. While these bats are more prone to feeding on the blood of livestock, they also prey on humans when cattle and such aren’t available.
Researchers interviewed 92 residents (the combined size of both communities is estimated at just over 300) about their history of bat encounters and rabies vaccination, and also managed to collect blood samples from 63 people. Eleven percent of samples (7 of 63) were positive for rabies virus neutralizing antibodies (rVNAs), indicating that they’d somehow come into contact with the rabies virus and yet were, impressively, not dead. Prior vaccination for rabies could also explain the presence of antibodies, but of those that tested positive, only one individual reported ever having received the rabies vaccine. All seven, however, (along with many folks who tested negative for rVNA) did report at least one run-in with bats – most commonly a bite, but sometime also a scratch or just a bat bumping into them (as their name implies, the bats are quite common in the region).*
So what does this mean? Well, it doesn’t mean that we can add six more cases of unvaccinated recovery from full-blown rabies to the medical literature. The study could not assess whether individuals with antibodies ever developed symptoms as a result of the virus. The authors think it more likely that those who tested positive for rVNA received low doses of the virus from multiple bat encounters – enough for their immune systems to produce antibodies, but not so much as to cause illness. Think of it as a quasi vaccination program run by vampire bats. The observation that older residents (i.e., those who had potentially accumulated more bat exposures) were more likely to test positive than younger ones provides some support for this explanation.
However, we also can’t assume that the antibody-producing Peruvians are fully immune to rabies virus. Testing that would require exposing them to the virus and waiting to see if they developed the disease, probably not something either scientists or subjects would be especially eager to try. Because of rabies’ grim prognosis, even those who have been previously vaccinated against the virus are advised to get a two-shot booster dose (as opposed to the four shot regimen given to the unvaccinated) of the vaccine if they think they’ve been exposed to the virus.
For those skeptical of the legitimacy of the Milwaukee Protocol, this study does provide further examples of the variability of the rabies virus. One case against crediting the Milwaukee Protocol with patients’ survival is that not all strains of the rabies virus are equal. The strength of the virus varies with its animal host. While rabies kills over 55,000 humans yearly (primarily in Asia and Africa), most of the victims acquire the virus from dogs, and canine rabies is thus thought to be the deadliest strain. The original Milwaukee Protocol patient had been bitten by a bat, and additional success stories involved bites from either bats or cats. The location of the bite is also an important factor. Bites closer to the central nervous system are more dangerous because the virus has a shorter route to the brain (it must travel through a labyrinth of nerve cells to get there). It is in the brain that the virus multiplies and generally runs amok, so prolonging its journey could potentially result in the immune system actually having a chance at fighting off the virus before it proves fatal. Here too, the first Milwaukee Protocol patient matches those circumstances, having been bitten on her index finger. Is it possible that patients who survived after receiving the Milwaukee Protocol just got “lucky” in the source and severity of their virus, picking up comparatively meek bat rabies rather than ferociously unstoppable canine rabies?
One wonders if people outside of Peru are also unknowingly walking around with potentially protective rabies antibodies, albeit perhaps in less substantial numbers. After all, bat bites are more subtle than dog bites. Sometimes people don’t even realize they’ve been bitten. In addition to the study in Peru, smaller studies of longtime hunters of animals known to carry rabies (raccoons and foxes) have found some evidence of rabies antibodies. It would be interesting to see a large scale sampling of blood from residents in other parts of the world, especially in areas with varied bat populations.
What the Peru study really highlights is how much about the rabies virus remains to be learned. Over at Wired, Monica Murphy and Bill Wasik have an article exploring the controversy surrounding the Milwaukee Protocol (they literally wrote the book on rabies, or at least a book). One striking observation they make is that we still aren’t even sure how rabies kills its victims once reaching the brain. Dr. Rodney Willoughby, who created the Milwaukee Protocol, believes the disease destroys the brain by over-stimulating brain cells until they burn out – thus the induced coma idea, to slow down brain activity. Others think rabies kills brain cells directly, in which case slowing brain function would offer no benefits.
For now preventative strategies, namely rabies vaccine for both humans and other animals†, are the best bet for reducing rabies fatalities. Yet increasing evidence that the virus may be a diverse pathogen with varied outcomes, rather than an all or nothing killer, creates hope that we might someday find a treatment for the disease that is less physically and financially costly (and preferably also has a better success rate) than the only currently available option.
* On a side note, they also found that “individuals reporting eating or cooking a bat as food” was a reassuring zero percent in both communities.
† It’s worth noting that rabies doesn’t kill 100 percent of non-human animals infected with it. Another reason to suspect our species too may not always succumb to the pathogen.