In 1970, when David Warrell was a young hospital clinician in northern Nigeria, he faced three horrifying snakebite cases in quick succession that would change the course of his career. One man had stepped on a puff adder while getting out of bed. He arrived with a gangrenous leg and died of sepsis before Warrell could amputate. Another man was bitten by a saw-scaled viper while farming sorghum. He arrived bleeding from his mouth and urinary tract, and he soon died from massive internal bleeding. A third victim, a boy, was struck by a snake charmer’s Egyptian cobra. He was dead on arrival, after the snake’s venom progressively paralyzed his body, starting with his eyelids and ending with his breathing muscles. In no cases did Warrell have antivenom to administer as he helplessly observed deaths that he soon realized were common.
“I got a missionarylike attitude toward snakebite as a neglected public health problem,” says Warrell, an emeritus professor of tropical medicine at the University of Oxford in the United Kingdom and director of the Global Snakebite Initiative in Brisbane, Australia.
Snakebites kill as many as 138,000 people a year, mostly among the rural poor in sub-Saharan Africa and South Asia. Another 400,000 victims suffer major disabilities such as amputation. The health burden is greater than that of any of the 20 neglected tropical diseases tracked by the World Health Organization (WHO) and equal to that of prostate or cervical cancer. Yet funders, more interested in infectious diseases that can be prevented and eradicated, have largely stayed away.
That is now changing. Today, the Wellcome Trust charity in London announced an £80 million, 7-year research program to improve antivenoms and search for new treatments—a major influx of money in a small field. The announcement comes ahead of the first-ever WHO snakebite strategy, set to be unveiled on 23 May, that seeks to halve death and disability from snakebites by 2030. “The tide really does seem to have turned,” Warrell says.
The Wellcome money could invigorate a small research field that, by Wellcome’s estimate, has received only £30 million over the past decade. “It’s transformational,” says David Lalloo, director of the Liverpool School of Tropical Medicine in the United Kingdom. “It will make an enormous difference,” Lalloo says the money could help refine the scale of the problem by shoring up spotty data on incidents around the world. “It builds the economic argument for manufacturers to invest in antivenom,” he says.
Each of the world’s 250 species of venomous snakes produces a unique cocktail of toxins that must be counteracted by a specific antivenom. But the antivenoms are plagued by problems. Even when such antidotes are available—and they often aren’t in the rural areas where most snakebites occur—they can be expensive, beyond the reach of poor people. Clinical data on their effectiveness are lacking. And they are often unsafe, triggering allergic reactions. That is because of the way that antivenoms are produced: Venoms, milked from snakes, are injected at low doses into animals, typically horses, to trigger an immune response. Antibodies from the animals’ blood are harvested, purified, and then used as antivenoms. But people’s immune systems can react to the animal product.
Phil Price, Wellcome’s science lead for its snakebite priority area, says a first goal for the new program will be to improve existing antivenoms. Wellcome funding could help manufacturers follow protocols and avoid bad practices, such as using a single animal to produce a mix of antivenoms. The process could also be simplified. For example, some manufacturers use enzymes to split harvested antibodies into pieces and eliminate the stalk of the Y-shaped molecules, which is believed to trigger allergic reactions. “We don’t necessarily know that’s true,” Price says. Instead, he says, it may be that other bits of animal proteins cause most side effects, and splitting the antibodies is unnecessary. By helping establish a clinical trial network, he says, scientists can begin to evaluate the safety and effectiveness of antivenoms in a more rigorous way.
A second prong of the Wellcome program will look for new treatments. One approach would look for traditional small-molecule drugs—developed for other medical uses—that could neutralize the toxic effects of snakebites. Warrell says the drug varespladib, for instance, used to combat inflammation, appears to stop bleeding caused by snakebites.
Another approach would identify the proteins in a snake’s venom that are the most toxic, Lalloo says. Then, scientists could genetically engineer cells to produce human antibodies for those toxins. Price points out that treatment research should also include efforts to improve the long-term care of victims, who suffer from trauma and other persistent disabilities.
The forthcoming WHO strategy could also nudge snakebite up the global health agenda. “The real significance is that this is the first time WHO has ever done this,” Lalloo says. Bernadette Abela-Ridder, head of WHO’s neglected zoonotic diseases department in Geneva, Switzerland, says the strategy will include outreach, focusing on prevention by encouraging people who work among snakes to wear shoes and gloves.
For Warrell, the Wellcome money and the support of WHO are signs that 50 years after his first encounters with snakebites, the field is changing. “Neither of these developments would have been thinkable to me a few years ago,” he says.
Source: Science Mag