snake bites

OPOSSUM-BASED ANTIDOTE TO VENOM FROM SNAKE BITES COULD SAVE THOUSANDS OF LIVES

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Scientists will report in a presentation today that they have turned to the opossum to develop a promising new and inexpensive antidote for poisonous snake bites. They predict it could save thousands of lives worldwide without the side effects of current treatments.

The presentation will take place here at the 249th National Meeting & Exposition of the American Chemical Society (ACS), the world’s largest scientific society. The meeting features nearly 11,000 reports on new advances in science and other topics. It is being held through Thursday.

Worldwide, an estimated 421,000 cases of poisonous snake bites and 20,000 deaths from these bites occur yearly, according to the International Society on Toxicology.

Intriguingly, opossums shrug off snake bite venom with no ill effects. Claire F. Komives, Ph.D., who is at San Jose State University, explains that initial studies showing the opossum’s immunity to snake venom were done in the 1940s. In the early 1990s, a group of researchers identified a serum protein from the opossum that was able to neutralize snake venoms. One researcher, B. V. Lipps, Ph.D., found that a smaller chain of amino acids from the opossum protein, called a peptide, was also able to neutralize the venom.

But Komives says it appears that no one has followed up on those studies to develop an antivenom therapy –– at least not until she and her team came along. Armed with this information, they had the peptide chemically synthesized. When they tested it in venom-exposed mice, they found that it protected them from the poisonous effects of bites from U.S. Western Diamondback rattlesnakes and Russell’s Viper venom from Pakistan.

The exact mechanism is not known, but recently published computer models have shown that the peptide interacts with proteins in the snake venom that are toxic to humans, she says. “It appears that the venom protein may bind to the peptide, rendering it no longer toxic.”

Komives’ team showed that they could program the bacteria E. coli to make the peptide. Producing the peptide in bacteria should enable the group to inexpensively make large quantities of it. The peptide should also be easy to purify from E. coli.

“Our approach is different because most antivenoms are made by injecting the venom into a horse and then processing the serum,” says Komives. “The serum has additional components, however, so the patient often has some kind of adverse reaction, such as a rash, itching, wheezing, rapid heart rate, fever or body aches. The peptide we are using does not have those negative effects on mice.”

Because the process is inexpensive, the antivenom has a good chance of being distributed to underserved areas across the globe, according to Komives. That includes India, Southeast Asia, Africa and South America, where poisonous snakes bite thousands of people every year.

Komives says that based on the original publications, the antivenom would probably work against venoms from other poisonous snakes, as well as against scorpion, plant and bacterial toxins.

The new antivenom has another potential advantage: It likely could be delivered in just one injectable dose. “Since when a snake bites, it injects venom into the victim in different ways, depending on which part of the body is bitten and the angle of the bite, it is likely that each snake bite would need to be treated differently,” says Komives. “It is common that additional antivenom needs to be injected if the patient continues to show the effects of the venom.” But because the new antidote appears to have no side effects, at least in mice, it probably could be given in one large dose to attack all of the venom, making additional injections unnecessary, she explains. The team plans to test this theory soon. They also will make large quantities of the antivenom and test it on mice, using a wide variety of venoms and toxins.

New blood test could help treat snake bites .

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Working out whether a snake has delivered venom with its bite may one day be determined by a simple blood test, new Australian research suggests.

The discovery could dramatically improve snakebite treatment in tropical rural areas, particularly in the developing world, where snakebite is a major health issue.

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The work, previously published in Nature Scientific Reports, was presented this week at the Australian Society for Medical Research Annual Scientific Meeting in Sydney.

Senior author Dr Geoffrey Isbister, at the University of Newcastle‘s School of Medicine and Public Health, says the delivery of snakebite antivenom is often delayed until symptoms appear. This can sometimes be too late.

“The important thing is to be able to give the right patients antivenom early,” says Isbister. “We need to identify in the first few hours if we’ve got envenomation.”

“At the moment that is based on whether the patient feels a bit sick; but you also feel like that when you’ve just been confronted by a snake.”

Isbister says once signs of paralysis and muscle damage begin to appear, it cannot be reversed by antivenom.

“Everyone thinks [antivenom] is this magic thing, but it doesn’t reverse most things that have happened,” he says.

“You’ve got to get the antivenom into the circulation early to bind to the snake toxins before they get to the muscles, before they get to the nerves and do the damage.”

The scale of the snakebite problem is large with the World Health Organisation recognising it about four years ago as a tropical disease.

Isbister says there are one to two million cases of snake envenomation, with a potential fatality rate of 100,000 deaths worldwide.

Snakebite treatment is hampered by the availability of antivenom; high reaction rates to antivenom; and difficulties in diagnosing envenomation to allow early antivenom treatment.

Isbister says the development of a cheap diagnostic test for envenomation that can be done at the bedside is critical in addressing these issues.

Cheap detection tool

For this latest study his team, including Dr Margaret O’Leary at the University of Newcastle and Dr Kalana Maduwage from University of Peradeniya, Sri Lanka, focused on a common enzyme in snake venoms – phospholipase A2 (PLA2).

Using samples from confirmed snakebite patients in Sri Lanka and Australia they checked to see if PLA2 could be detected in the blood.

Pre-antivenom samples were collected from venomous bites from samples collected from Russell’s viper, hump-nosed pit viper, Indian cobra, Indian krait and five red-bellied black snake were included in the study. These were compared with PLA2 levels in a group of un-envenomated patients.

Isbister says the levels of PLA2 were elevated in all those who had been bitten and injected with venom.

He says confirmation of envenomation means only patients who require antivenom will receive it.

“Even in a health clinic in Africa if you have antivenom then this test would help guide whether to give it rather than travelling eight hours to a hospital where it would be too late,” he says.

Bringing it to the bedside

This can also have major financial implications even in developed countries such as Australia where antivenom is available at more than 90 per cent of hospitals, Isbister adds.

He says while thousands of cases of “snakebites” would appear at hospitals, only about five to 10 per cent would have envenomation.

“What comes into hospital is a suspected snakebite,” he says adding this can range from being “attacked” by a stick, a bite by a non-venomous snake, to an attack from a venomous snake that didn’t cause any effects.

Isbister warns against too much excitement as the analysis for this study involved expensive laboratory testing.

However, he says the “proof of concept” findings make it now feasible to begin research on development of a cheap testing kit.

“The actual test itself is not too complicated,” he says, “it’s working out a way you can do that simply at the bedside.”