Al Jazeera / Healthcare professionals / Researchers / Scientists

Sri Lanka’s antivenom leap forward

Colombo, Sri Lanka – In 2006, a Russell’s viper sank one fang into Sanath Weeraratne’s left hand.

Weeraratne immediately started to bleed profusely as the anticoagulant properties in the venom took effect. He knew what could come next: more bleeding from the rectum and the gums and blood-stained vomit.

The blood could seep into the brain and affect other organs, and this could be fatal. Fortunately for Weeraratne, the two people he was with were experts themselves. They identified the snake that had bitten him, applied first aid, and rushed him to a nearby hospital where he was successfully treated.

He tells Al Jazeera that the accident was a turning point in his life.

It led him to his job as a caretaker at Sri Lanka’s first national serpentarium, home to some 185 venomous snakes. Common kraits, cobras, Russell’s vipers, saw-scaled vipers and hump-nosed pit vipers lie coiled in their containers – with water bowls, foliage and coconut shells. The small three-man team at the serpentarium keeps odd hours because some of these snakes, such as the kraits, are most active at night.

Weeraratne and his team must see to the serpents’ health and extract their venom, which is collected and sent to a lab in Costa Rica. It is there that the first polyspecific freeze-dried antivenom to offer protection specifically against Sri Lankan snakes is being produced.

The serpentarium was set up and is operated by the United States-based Animal Venom Research International (AVRI). Its executive director, however, is the Sri Lankan-born Roy Malleappah, a herpetological field operations specialist. It has taken him and his team years of dedicated work to make the Sri Lankan antivenom a reality.

Sri Lanka boasts 92 different species of snakes, but most deaths are attributed to only three – the highly venomous cobra, Russell’s viper and krait [Madushan Blair/Al Jazeera]

A medical breakthrough

The antivenom was developed in close collaboration with the Instituto Clodomiro Picado (ICP) in Costa Rica, while the University of Peradeniya – partly funded by the National Research Council of Sri Lanka – is responsible for the clinical trials, which are now ongoing.

The antivenom ICP and AVRI have produced is polyspecific – covering multiple species including, for the first time, Sri Lanka’s hump-nosed pit viper. It is the most common cause of snakebite envenoming in Sri Lanka and is known to cause serious systemic toxicity and death.

Sri Lanka has one of the highest snakebite rates in the world, yet statistics are hard to come by as many cases go unreported. The island boasts 92 different species of snakes, but most deaths are attributed (PDF) to just three – the highly venomous  cobra, Russell’s viper and krait.

The national serpentarium itself is located in Dambulla in central Sri Lanka. Locals here know well what damage a snakebite can do. There is always a rash of incidents in March, when farmers go into the fields to harvest paddy and find snakes hiding amid the green stalks.

Weeraratne himself remembers a trip to a village in this area. “Every single house I visited told me that they had lost someone to a snakebite: from fathers to a 17-year-old who was sitting for her A-Level exams. The stories are enough to bring tears to your eyes.”

Even among those who survived, there were some who would struggle with chronic kidney disease for the rest of their lives.

Common kraits, cobras, Russell’s vipers, saw-scaled vipers and hump-nosed pit vipers lie coiled in their containers with water bowls, foliage and coconut shells [Madushan Blair/Al Jazeera]

An island-wide community survey in 2016 extrapolated that, over a 12-month period, there were more than 80,000 bites, 30,000 envenomings and 400 deaths from snakebites.

Today, the antivenom used in Sri Lankan hospitals is imported – typically from India, where many of the same species exist.

“However, the reaction to the antivenom has become part of the problem,” says Sarath Kotagama, a conservationist and emeritus professor of environmental science at the University of Colombo.

He explains that what is not always understood is how much variation there is between Indian and Sri Lankan snakes, even though they may belong, in theory, to the same species.

“The toxicity and composition of the venom is affected by the snakes’ diet and other regional variations,” says Kotagama, adding that “the Hypnale hypnale group [the hump-nosed pit vipers] are very specific to this country, and so you need a specific antivenom for them”.

When a person is brought into a hospital with a bite from a hump-nose pit viper, doctors are at a loss.

“The bite from this snake is not covered by the antivenom we have, even though it is one of the most common bites,” says Dr Indika Gawarammana, the lead investigator for the AVRI/ICP antivenom clinical trials at the University of Peradeniya’s teaching hospital.

He explains that symptomatic treatment, such as surgical incisions and pain relief medications, is all that is on offer.

There is another reason doctors sometimes hesitate to treat snakebite victims with the current antivenom, he says.

“The imported antivenom creates adverse effects in a big proportion of those patients who receive it,” Gawarammana tells Al Jazeera, citing a range of symptoms from relatively mild skin reactions, such as itching, to life-threatening anaphylactic reactions.

Sri Lanka’s excellent network of hospitals means that most people are within 30 minutes to an hour of getting help, but the side-effects of the antivenom can mean doctors will insist that patients be transferred to bigger, more distant hospitals where severe reactions can be managed. The delay is increased if a patient is not certain what species of snake bit them.

“This allows complications to set in,” says Gawarammana.

Currently, 2500 vials of the antivenom have been produced as part of a test batch. First freeze-dried, it can be stored at room temperature.  [Malaka Mp/Al Jazeera]

Currently, 2,500 vials of the new antivenom have been produced as part of a test batch. First freeze-dried, the antivenom can be stored at room temperature. Malleappah notes that ICP’s technology has produced a particularly pure, concentrated and effective version of the antivenom. This is why treatment can begin with only two vials instead of the 10 vials that are currently routine with imported antivenom.

The clinical trials are still ongoing, but Gawarammana says the patients have so far responded very well to the new antivenom.

The allergic reactions have been negligible, necessitating fewer days in the hospital.

“In Sri Lanka, we haven’t really calculated the cost to the government of treating the allergic reactions to the old antivenom,” he says, noting that, typically, patients would spend days, and sometimes weeks, at home recuperating, thereby adding to the economic cost.

In contrast, the new antivenom has delivered quick recoveries that allow people to return to work within days of being bitten. As part of the trial, the AVRI/ICP antivenom will also be sent to an Australian laboratory to have its efficacy tested.

Maintaining a balance

It is Malleappah’s hope that Sri Lanka will be able to begin producing its own antivenom very soon. He is currently arranging for more than 100 horses to be imported to help produce the antivenom in a new Sri Lankan facility. These will be injected with a small amount of snake venom and will generate antibodies that can then be extracted and used to create an antivenom.

Malleappah says this is typically not a lucrative business and so very few pharmaceutical giants are willing to invest money into research and development or manufacturing the product. He believes that if Sri Lanka were to start producing its own antivenom, it would be a boost to the island’s technology capacity, and serve as a model that could be exported to other countries in the region.

Gawarammana agrees. “We should have our own manufacturing capabilities. There are lots of issues in this country where the same approach can be used to produce antidotes, for example, for plant poisons. It’s important Sri Lanka has the technology.”

While people are the focus of these efforts, for the AVRI team, saving snakes is a crucial goal as well.

“I am really sad to see the indiscriminate killing of snakes in this country. It has a huge, catastrophic effect on the ecological balance,” Malleappah says.

As another unapologetic conservationist, Kotagama, too, is interested in seeing the antivenom developed.

“Today, every snake is a deadly snake,” he says. “If people were confident that they could be treated, that they would not die from this bite, then we would definitely see fewer snakes being killed out of hand.”

Published in Al Jazeera on February 18, 2017. By Smriti Daniel. Pix by Madushan Blair and Malaka Mp.