Snakebite!

Saw-scaled viper

2 March 2012 by Nick Casewell

Two million people are bitten by venomous snakes every year. Nick Casewell's team are working to find a solution.

Astonishingly, in some regions snakebite victims occupy over 70 per cent of all hospital beds, and as many as 95,000 people die each year, even though effective treatments exist.

Snakes are often viewed in a negative way. Let's face it, this isn't particularly surprising, considering the social stigma attached ever since their time in the Garden of Eden or living on Medusa's head. Yet in some cultures snakes are actually worshipped, and they appear in positive contexts on the emblems of medical and pharmacy associations, which may well have been an early and appropriate masterstroke - more on this later.

Snake venoms usually differ between different species, but all are toxic mixes of proteins that are injected (usually by fangs) to incapacitate the snake's prey. Although most snakes are technically venomous, relatively few species are dangerous to man.

I noticed a barefoot farmer, knocking stones aside to till the earth not ten yards away from where we'd recently found a saw-scaled viper.

Snakes will try to avoid encounters with people or display a warning signal, such as a rattlesnake's rattle, before they bite. Unfortunately, when one feels threatened or is surprised by a person, it will often bite in self-defence, resulting in a medical emergency.

Sadly this is extremely common across the tropics. In the UK we only have one potentially dangerous snake species, which is rarely encountered. In sub-Saharan Africa and south Asia, where most snakebite deaths occur, there are many dangerous snakes, including cobras, mambas and vipers. In rural tropical regions, people's lifestyle is dictated by poverty, so interacting with snakes is a daily occupational hazard when farming, walking or even sleeping. These encounters are often made worse because people cannot afford appropriate footwear and often work in flip-flops or even barefoot.

I recently had the opportunity to go to Senegal to collect venomous snakes for our antivenom research project - our target species were the saw-scaled vipers, a group of very small dangerous snakes which are extremely well camouflaged. We often found them hiding under rocks during the day - by the side of roads, around agricultural fields and even in school playgrounds. On one occasion I noticed a barefoot farmer knocking stones aside to allow him to till the earth not ten yards away from where we'd recently found a saw-scaled viper beneath a similar rock. It is not hard to imagine how people stand on these snakes and are bitten.

Local farmers ploughing just yards from where the snakes live

Local farmers wear poor or non-existent footwear while ploughing just yards from where the snakes live

So what happens if you're bitten by a venomous snake? If you live in the developed world, you go to hospital and, if you need it, the doctors give you antivenom, which will usually save your life. Antivenoms are made by immunising animals with tiny (non-harmful) amounts of venom collected from snakes. After a while, the immune system of the animal produces 'antibodies' against the snake venom.

These immune proteins are collected and purified into antivenom. When this is injected into a patient, the antibodies work by finding the venom proteins and sticking to them, preventing them from causing harm. However, these antibodies work only on the venom that was used to produce them, so rattlesnake antivenom won't work against a cobra bite.

In the tropics, the situation is less favourable for the victim - antivenom is expensive, often costing up to six months' salary. It may not be available, and even if it is, it may have taken the victim many hours, or even days, to reach a hospital - by this time the antivenom is less effective because the venom has already had a chance to damage the body. Together these problems mean snakebite is very much a disease of poor people in the rural tropics.

At the Alistair Reid Venom Research Unit at the Liverpool School of Tropical Medicine we are passionate about helping, by improving existing antivenoms and developing new treatments for snakebite. For example, in collaboration with two antivenom-manufacturing companies, UK's MicroPharm and ICP in Costa Rica, we have co-ordinated the development of two new, highly-effective and safe antivenoms that the Nigerian Ministry of Health is now buying for use in hospitals in parts of the country.

So far, this work has resulted in 32,000 antivenom treatments and saved around 16,000 lives. However, these collaborations are rare because the financial incentives for antivenom manufacturers are low - their antivenoms are specific to certain snakes in certain regions and many governments and people simply can't afford to buy them, which results in low demand.

As part of the antivenom research we are carrying out with scientists from Bangor University, we wanted to investigate how effective antivenom made for one species was at preventing damage caused by different snakes' venom. Saw-scaled vipers, comprising at least nine different species, kill more people worldwide than any other group, so we used them as the targets for our investigation.

A juvenile saw-scaled viper

A juvenile saw-scaled viper (with finger for scale) found underneath a rock

After collecting venom from different varieties of saw-scaled viper living in various parts of Africa and Asia, we tested each venom in the laboratory against a single antivenom made from the venom of the West African lineage. We were delighted to find that this antivenom was just as effective against all African saw-scaled vipers, not just those from West Africa.

This is really important because it means we can now use the existing antivenom to treat saw-scaled viper bites in parts of Africa where antivenom is not currently used - this expanded geographical market will lead to economies of scale, where an increase in manufacturing means antivenom costs governments and people less, which in turn increases demand still further and improves the delivery of antivenom to the patients.

This model is also being used by the Global Snakebite Initiative, a recently established consortium of physicians, scientists and antivenom manufacturers designed to improve medical care of, and delivery of life-saving antivenoms to, snakebite victims throughout the world.

Although the venoms of snakes and other animals can cause very serious harm to people, they are also a valuable natural biological resource. Venom proteins have been a fantastic starting point for the development of new pharmaceutical drugs and diagnostic tools. For example, the blood pressure medication captopril was developed from the venom of a South American viper and has been used to treat about 16 million people in the UK.

Because of these early successes there is now a lot of interest in developing new drugs from the venoms of a variety of animals, including snakes, lizards, fish and spiders. We are really interested in discovering how proteins found in the venoms of these animals work and whether they can be used in the treatment of human diseases. This exciting new line of research means that it's starting to look like the medical and pharmacy associations may have been right to put the snake on their emblems all those years ago.


Dr Nick Casewell is a postdoctoral research associate at the Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine.

The antivenom research project is headed by Dr Robert Harrison at the Liverpool School of Tropical Medicine in collaboration with Dr Wolfgang Wüster at Bangor University.