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Snakebites are a neglected health problem, despite causing up to 84,000 deaths a year worldwide. A new cheap and easy-to-use nasal spray could help reduce the toll, according to researchers.
Antivenoms, traditionally designed to treat the most common deadly snakebites, are often expensive and can be ineffective if not used shortly after an attack. They do not work against the bites of all venomous snake species, something that may be hard to overcome because of the different ways they produce venom.
But a new approach to treating snakebites soon after they occur has been tested, and its creators believe it holds hope. A team of researchers, led by Matthew Lewin from the California Academy of Sciences, in the US, and Stephen Samuel, from Trinity College Dublin, Ireland, says a simple nasal spray containing neostigmine can reduce fatalities.
"It would be one ingredient primarily directed against rapid onset paralysis – one of the causes of fast death following snakebite," Lewin said. "It is inexpensive and available everywhere in the world." If combined with atropine, a substance that is absorbed through the nose, neostigmine would have few ill effects, according to Lewin.
The team tested the spray on mice injected with fatal doses of Indian cobra venom. Mice treated with the spray outlived those that were not, and, in many cases, survived, according to a study published in May in the Journal of Tropical Medicine.
More than three-quarters of snakebite victims who die in India, the country with the highest number of venomous bites and deaths, do so before they reach hospital, according to the Million Death Study, one of the world's largest databases of premature mortality.
Traditional treatments are injected, but this happens too late for most victims. Many of them die from respiratory failure, after being paralysed by neurotoxins.
Despite 5 million people being bitten by snakes every year, public health bodies generally ignore the issue, Lewin said. "It's ironic that virtually every medical organisation has a snake on its flag or badge, but no ability to treat it in the field," he said.
Sakthivel Vaiyapuri, co-author of the study from the University of Reading, UK, recently surveyed snakebite victims in Tamil Nadu, India. "It mainly affects poor farmers living in remote rural villages," he said.
According to the World Health Organisation, which recognised snakebites as a neglected tropical condition in 2009, the problem is greatest in south and south-east Asia and sub-Saharan Africa.
The nasally administrated drug is an alternative to antivenoms, Lewin said. He argues that, besides being expensive, antivenoms can vary in effectiveness depending on factors including the snake's diet, the time of year and the geographic location.
A paper published in the Proceedings of the National Academy of Sciences last month says it may be harder than originally thought to develop an antivenom that works against many snakebites. "We discovered that the genetics of the animals can be very similar, yet their venoms very different," the lead author, Nicholas Casewell, from Liverpool School of Tropical Medicine, said.
Using six related snakes – the Saharan horned viper, the puff adder and four species of saw-scaled vipers – Casewell and colleagues discovered that various genetic regulatory processes act at different stages of toxin production.
"These processes result in major differences in toxin composition, and these different toxins cause different pathologies or levels of toxicity when they are injected, and they also undermine antivenom treatment," Casewell said. According to Casewell, there are about 500 species of venomous snakes worldwide.
"Antivenom is necessary, but not sufficient to manage this problem," Lewin said. "Its limitations are fairly well known at this point and we need a better bridge to survival." The nasal spray could be a cheap, fast and easy method to treat the paralysis caused by snakebites, he added.
In 2013, to see if neostigmine could be absorbed through the nose, Lewin tried the spray on himself, after being infused with a drug to induce awake paralysis in a manner similar to cobra venom. He made a complete recovery in a little over two hours, as described in Clinical Case Reports. Clinical trials of the spray are being planned in India.
Developing inexpensive, heat-stable and easy-to-administer antiparalytics could facilitate early treatment of snakebites and save lives, Lewin and his colleagues argue in the paper. "Doing so would make a profound difference in the health of millions," Lewin said.
For Casewell, the new approach looks promising. "Any treatment that provides the patient with more time before symptoms occur, would be beneficial," he says. "However, it remains to be seen how many different species this would be useful for."
