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Sucking the venom out of the bite

- Shaun Smillie

Treating snake bite victims remains antiquated – hopefully a new way of creating antivenom can lead to a better solution.

The fight against snakebites relies on a century old method that involves horses as a source for the treatment of the toxins. And while this technology is effective, it has done little to stem the estimated 138 000 deaths a year globally, most of whom are the poor who can't afford the treatment or make the journey to medical centres where the antivenom is kept.

Besides the fatalities, hundreds of thousands of snakebite victims every year are left seriously maimed through the loss of limbs or eyes. In 2017, the World Health Organization officially recognised venomous snakebite as a neglected tropical disease, but to save more lives, health professionals believe antivenom needs to become cheaper, safer and easier to access.

The answer could be in a new generation of antivenom serum that involves isolating monoclonal antibodies. It is a process that has proven success when it was used to develop the first Covid-19 therapeutics.

Horses for courses

Here in South Africa, Dr Constantinos Kurt Wibmer is working on developing this new antivenom in his lab based at the National Institute for Communicable Diseases (NICD) in Sandringham, Johannesburg. The horses which are used in the current manufacture of antivenom, that has changed little since the late 19th Century, are kept not far away.

“We are essentially using animal blood as a medicine. We basically immunise animals with snake venom and repeat the process, so you get better and better antibodies,” says Wibmer, who holds a joint appointment as a researcher in the Wits’ Faculty of Health Sciences.

According to the African Snakebite Institute, the process takes up to nine months as only small quantities of snake venom are injected into the horse, which is not harmed, allowing the animal to build immunity. In the next step, the serum is removed from the horse’s blood and purified. In South Africa, a polyvalent antivenom is manufactured in which the venom of ten common South African venomous snakes, including the puff adder, Gaboon adder, rinkhals, green mamba, Jameson’s mamba, black mamba, cape cobra, forest cobra, snouted cobra and Mozambique spitting cobra, is used.

South Africa has a reputation for producing high quality snakebite serum, but recently there have been shortages that have been blamed on the increase in power outages.

“The problem with these antivenoms is that it is a very impure medicine. From batch to batch it is different, it is not like a drug made in a lab,” explains Wibmer.

Snake and venom | Curiosity 16: #Drugs ©

The hunt for super B cells is on

The discovery of this new antivenom still involves horses – for now. Among the horse’s blood B cells are what Wibmer refers to as “super B cells”, for which he is on the hunt.. These are the immune cells responsible for making extremely cross-reactive antibodies.

“You find individual B cells that make spectacular antibodies so essentially we take the DNA out of those cells, clone it into a lab construct, and then we can reproduce those antibodies in the lab,” says Wibmer.

The ultimate aim is to create an antivenom that is temperature stable, that will not need to be stored in a refrigerator and can be taken into the field. Aside from the storage issue, another problem with antivenom is the cost. When snake bite victims are treated, they often need several vials of antivenom, which, in South Africa, can cost as much as R100 000. Should Wibmer’s new antivenom be successful, it could be stored anywhere, and would require just a single vial.

“We are looking forward to the next generation of antivenoms that are broader, safer, and generally applicable to whole general or even whole families of snakes,” explains Wibmer.

When treatment is worse than the cause

Another disadvantage of antivenoms currently on the market is their serious side effects that for some people can be as deadly as the snakebite. Wits herpetologist Professor Graham Alexander discovered this while conducting field research a number of years ago near Heidelberg in Gauteng.

Alexander, from the School of Animal, Plant and Environment Sciences was handling a puff adder when it bit him on the leg. He was rushed to the nearby Heidelberg clinic where he was given antivenom.

“Within 30 seconds I went into complete anaphylaxis,” he recalls. Alexander’s heart stopped and he had to be resuscitated. He was fortunately able to make a full recovery. However, if Alexander, who makes a living by researching venomous snakes was bitten again, doctors would be forced to treat him symptomatically and not give him antivenom.

“It means I have to think twice when handling seriously venomous snakes like black mambas,” says Alexander.

Wibmer’s new antivenom may be heaven-sent for people like Alexander, who have adverse reactions to the serum proteins that can act as immunogens. The new antivenom treatment will not have side effects such as Alexander’s allergic reaction.

“I really think in the next couple of years we are going to see some major developments,” says Wibmer whose new technology might help save the lives of hundreds of thousands of people who for so long have been neglected.

“Snakebite is not a reportable cause of death in South Africa, so who knows how many people could be saved by a new way of treating them?” says Alexander.

  • Shaun Smillie is a freelance writer.
  • This article first appeared in Curiosity, a research magazine produced byWits Communications and the Research Office
  • Read more in the 16th issue, themed: #Drugs, where we highlight the diversity, scope, and multi-dimensional nature of drug-related research at Wits University.