By Rose Hoban
Nothing like spending the day with a group of medical experts on snakebite to make you paranoid when you walk your dog later that evening.
But if I had managed to be bitten by a copperhead on a Triangle street on a cool March evening (highly unlikely), I’d have been in luck, because last week was one of the largest gatherings of experts on every kind of venomous bites.
They were in Greenville, at East Carolina University’s Brody School of Medicine, where dozens of medical toxicologists, doctors, veterinarians and others are gathered for Venom Week, an annual meeting sponsored by the North American Society of Toxinology.
Once the experts dispersed, I’m still in luck if a copperhead manages to bite me while I roam the woods near our house, as happened to a visiting friend in 2014. ECU emergency physician Sean Bush is one of the nation’s experts on snakebite, and he presented data on a new form of anti-venom at the meeting this week, showing that it’s effective as well as safe.
“There’s been a controversy going on for the past decade and a half as to whether or not copperhead bites were severe enough to warrant anti-venom at all,” Bush explained.
“Before the currently available anti-venom was being used, we had a medicine that caused real bad allergic reactions,” he said. “So sometimes the treatment was worse than the injury.”
Bush studied CroFab®, along with researchers at Duke, UNC-Chapel Hill and 15 other medical centers around the country. He said he relocated to Greenville from Southern California in order to participate in the study.
“And then it was my loose plan to host Venom Week at the end of this clinical trial, but it really, actually, cut really close,” Bush said. “We didn’t find out the results until last week. Then it was announced here.”
‘Why did it have to be snakes?’
According to the Centers for Disease Control and Prevention, between 7,000 and 8,000 people are bitten annually by snakes, but only a handful die, as medical care has become better.
The last time data was compiled, in 2010, North Carolina had the distinction of having the most copperhead bites of any state in the nation. They’re well distributed throughout all of the state’s 100 counties, where they hang out, well camouflaged by leaf litter, usually minding their own business.
“In North Carolina, you get quite a few kids bitten in their yards because they run around with no protective footwear, and the copperheads first line of defense is to freeze. But if you step on them, they’ll bite you,” said Bush, who noted even his own kids don’t always wear shoes out in the yard.
He said that for smaller snakes, shoes, or even denim, will help defer a bite.
“For adults, they might get a little ‘over-beveraged’ … and they may think I need to handle or manage the snake with my hands, and that’s how they get bit,” Bush said. “Those are our demographics.”
[pullquote_right]According to the Carolinas Poison Center, there were 614 snakebites reported to them in North Carolina in 2015, including 344 copperhead bites, 11 cottonmouths and 11 rattlesnakes. [/pullquote_right]Indeed, a 10-year review of snakebite in Southern California found that males under 30 were most commonly bit; the majority of those bites were to people who were handling the snakes, and 28 percent of the victims “appeared intoxicated.”“Beer and snakes don’t mix,” Bush said.
He also said people get bitten as they’re gardening and clearing brush, commonly around dusk, when the snakes are most active.
Complex molecule
The reason venomous snakebites can be so painful is because the proteins in the venom are actually starting the process of digestion, explained Fred Boyce, a herpatologist from the N.C. Aquarium at Pine Knoll Shoals, who was attending the conference. That dose of venom begins, in essence, to digest the cells surrounding the bite.
“That’s what makes vipers able to eat much larger meals,” Boyce said. “It’s a great advantage.”
A rattlesnake can actually eat a rabbit or a squirrel because of the venom that starts the digestive process.
“Other snakes, like [non-venomous] rat snakes or king snakes, would have to pass up that meal,” Boyce said. “It doesn’t give them as many options on the menu.”
Those proteins in the venom have also, traditionally, made it more difficult to come up with an anti-venom to treat snakebite, Bush explained. And it’s not just one kind of poison in the venom; it can be dozens of poisons, another reason why effective anti-venoms have been slow to develop.
A logistical problem is that the venom is a protein, and in the past anti-venom was also a protein. The body can have strong allergic reactions to those introduced proteins.
“That used to be so,” Bush said. “But now all these new anti-venoms don’t have the part [of the molecule] that causes the allergic reaction. So allergic reactions are relatively rare now, not like they used to be.”
“Fifteen, 16 years ago, it was like Russian roulette; you could kill your patient with anti-venom” if the patient had a severe allergic reaction, he said. “Those days are gone. Snakebite anti-venoms in the U.S. are much safer now.”
Bush disclosed that he has done work for BTG International, which makes CroFab®. In the past, he did lectures for the company, and a video featuring him is on the company’s website.
“These are all funded studies,” he said.
He did note that BTG’s main competitor, Anavip, was also present at the conference, and both companies had sponsorships.
Pricey cure
But even with positive data, like from the CroFab® study Bush worked on, there’s still controversy over the use of anti-venom, and that’s because of the tremendous cost.
“That’s a lot of the topic of this conference,” Boyce said.
Bush admitted that CroFab® costs are high.
“Last I heard, CroFab® is $2,400 a vial, and a starting dose is four to six vials,” he said. “And it’s common to get 10, 12 or 14 vials. There are a lot of factors that weigh into that.”
But Bush said the cost was worth it to him when his 2-year-old was bitten by a rattlesnake several years ago.
“I think [cost] is a consideration,” he said. “But when you’re there, you want to get the best medicine.”
A recent commentary in the American Journal of Medicine noted the costs of treatment for snakebite and anti-venom are skewed by high hospital costs, costs of litigation, regulatory constraints and the fact that anti-venoms will always comprise a small, “orphan-drug” market, making development expensive.
Others at the conference held that the best medicine, when it comes to copperheads, can be supportive care like intravenous fluids, pain relievers and rest.
“If one of those little fellas bit me, if it was a canebrake or a diamondback [rattlesnake], I would go for anti-venom, because they can do a whole lot of damage fast,” said Dorcas O’Rourke, a veterinarian who manages the animals used in research at ECU.
But O’Rourke said supportive care is often enough for copperhead bites, even though the recent study showed the use of anti-venom shortened the time to recovery for patients bitten by one.
Supportive care was enough for my friend who was bitten near my house and it’s enough for many of the copperhead-bite victims around North Carolina. And in a health care system where patients often have hefty co-pays, the cost question becomes salient.
A lot of it depends.
“[Snakes] control exactly how much they deliver, so they can dump their venom glands or they may not give you anything,” O’Rourke said. “So it really is variable, based on what gets put into your body, where it’s put into your body and then your reaction. Different people and animals react differently.”
O’Rourke did know one thing though. If she got bitten, she said she’d want Bush providing her care.
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