The mysteries of rabies

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One day, towards the end of summer, I walked into my living room and found my cats playing "Secret CIA Prison" with a bat. He was alive, but just barely. He lay on my floor twitching, his wings torn to Swiss cheese. The cats looked up at me as if to say, "We do good work, yes?" I locked them in the bedroom and called the vet. Fortunately, the cats were all up on their shots. Unfortunately, I couldn't tell the vet how the bat had gotten into the house, nor how long he'd been there.

"You should maybe call your doctor," she said.

On average, 55,000 people worldwide die from rabies every year, but only two or three of those cases happen in the United States, thanks to widespread vaccination of domestic animals and availability of post-bite treatment for humans. Today, when Americans die of rabies, it's usually because they didn't realize they'd been bitten until it was too late—which is to say, when they first noticed symptoms.

See, we know how to prevent rabies, but we have absolutely no idea how to cure it. In fact, we don't even really know how it kills people. Despite (and, perhaps, because of) its status as one of the first viruses to be tamed by a vaccine, rabies remains a little-understood disease.

It's a mystery that makes doctors understandably nervous. Just a week before I found my bat, some friends of mine in St. Paul had woken up to find a bat in their bedroom. Being asleep is one of those times when tiny bat teeth could bite you without you being aware of it. My friends had to get post-exposure prophylaxis, a treatment designed to neutralize any rabies virus in your system before it has a chance to reach your brain and develop into a full-blown infection.

"You think about flu, that's a very quick virus. You develop symptoms in a couple of days. In a week, it's passed. But rabies incubation is very long," said Zhen Fu, DVM Ph.D., professor of pathology in the College of Veterinary Medicine at the University of Georgia. "It may be weeks or even months before you develop an active infection. So we have enough time after a bite to immunize with normal vaccine and bring up the immune system."

That means five doses of vaccine, over the course of 28 days, according the Centers for Disease Control and Prevention. If there's also an obvious bite, doctors will clean the wound and apply rabies antibody serum to the site. The antibodies are basically the key part of a lock-and-key system that tells your immune system to destroy anything the key fits. The idea is that antibodies will help destroy most of the virus at the site of entry, while the vaccine will train your body to knock out any strays it finds elsewhere. The CDC also recommends a shot of antibodies, separate from the vaccine, even if there is no obvious bite.

This one-two punch is almost 100% effective, provided you get it in time. How fast is "in time"? Nobody really knows. The CDC says that, as long as a bite victim isn't yet symptomatic, they should get the prophylaxis. Dr. Fu said that the window of opportunity can vary in length, depending on how close the bite is to the person's central nervous system. Without post-exposure prophylaxis, rabies is fatal. By the time symptoms--fever, confusion, partial paralysis, difficulty swallowing--appear, it's too late. There's not much doctors can do after that, because they aren't even sure what the virus is doing to you.

"We don't know how rabies kills people. There are some unproven hypotheses, but that's it," Dr. Fu said. "One idea is that, once the infection reaches the neurons in the brain, it blocks the transmission of messages from the brain to the rest of the body. If that's the case, it could explain many of the phenomenon we see in humans and animals, such as end-stage paralysis. That could even be why humans die, because of paralysis of muscles in the heart and lungs."

Given the lack of information and the risk of death, it's not surprising that even a situation like mine, where a bite was extremely unlikely, ended with a referral to a nearby hospital for post-exposure prophylaxis. But, after several conversations between the emergency room doctor and the Minnesota state rabies hotline, I ended up not getting it. Turns out, sneak-attack bites don't really happen to wide-awake, sober, cognitively normal adults in the middle of the day. The chance that I or my husband were actually bitten by the bat before the cats set upon it was so small that, on the advice of medical professionals, we decided that it wasn't worth the pain, potential side-effects, or cost of treatment.

That's right. I am my own death panel.

But on the off-chance that I do come down with symptoms—there've been cases of rabies incubating for up to a year—is there really no hope? Well, sort of. Maybe. Ish. Researchers have been experimenting with a treatment that they think could save the lives of people with full-blown rabies. Called the Milwaukee Protocol, it involves putting the patient into a coma and also giving them antiviral medication. The idea is that the human immune system—with some help from antivirals—can fight off a rabies infection, while the coma limits damage to the brain that seems to be a common cause of rabies death. In 2004, a teenage girl who received this treatment became the first person—ever—to survive symptomatic rabies without having received the vaccine either before being bitten, or before symptoms appeared.

The problem: We still don't know whether the Milwaukee Protocol actually works. It's been tried—and failed—at least 13 times since 2004, according to a 2009 paper published in the journal Current Infectious Disease Reports. There are two reported successes, but in one of those the patient received the vaccine before her she became symptomatic. The other success is very recent and there aren't many details available yet.

So why did the first girl survive? Again, nobody knows. It's possible that either she had a particularly hardcore immune system, or the variant of the virus she contracted was particularly weak, or both. When she was diagnosed, she had rabies antibodies in her cerebral spinal fluid—something that would indicate the presence of rabies in her brain—but doctors weren't able to isolate any actual virus—suggesting that her body was already on its way to winning the fight before the Milwaukee Protocol was used.

Unfortunately, any effort to really conquer rabies may be hampered by the fact that the vaccine works so well, Dr. Fu said.

"Treatments haven't been successful because we don't know what it's doing in the brain," he said. "We need more research but, usually, once you have a good vaccine the funding for the research goes away."

New England Journal of Medicine: Survival After Treatment of Rabies With Induction of Coma
Current Infectious Disease Reports: Update on Rabies Diagnosis and Treatment

Image courtesy Flickr user WilsonB, via CC