NAIROBI — Earlier this year, in Gombe state, Nigeria, health workers injected 35 vials of anti-venom into a patient who was bitten by a snake. It didn’t work.
This is because the government imported and distributed an ineffective product, providing it to patients at no cost, according to Dr. Abdulrazaq Habib, head of the Nigeria Snakebite Research & Intervention Centre and professor of infectious and tropical diseases at Bayero University, Kano.
The patient was only saved after his relatives bought an $80 vial of a more reliable anti-venom — a practice that often pushes families to sell off livestock or other assets so they can afford to save a relative’s life.
For health care workers, treating snakebites has been a complicated and often unsuccessful process, involving many different anti-venoms that vary in effectiveness. Currently, a person needs to receive the correct anti-venom to match the type of snake that bit them, but many health clinics are not able to stock a collection of different types.
Now, a global team of researchers is trying a new approach: working to create a more effective and safer treatment through monoclonal antibodies — a form of medicine that is based on the body’s antibody response but replicated in labs and mass-produced — that they hope will combat the toxic impacts of a broad range of snake venoms, all in one treatment.
The limitations of anti-venoms
Some hospitals in Nigeria see thousands of snakebite patients per year, Habib said. But government investment does not match the burden. According to a recent study, in 2017 the government released only enough funding to treat 4% of patients.
"The only real barrier to [solving the problem of] snakebite is money, to be perfectly honest," said World Health Organization expert David Williams, as the agency launched its snakebite strategy.
“A health facility may not necessarily store anti-venom until they have a patient with a snakebite. Then they start running helter-skelter, sending the relatives of the patients to go and buy it from cities and come back with it,” Habib said.
Because of this, health clinics are not seen as trusted places to get treated for snakebites, and a sizable number of people in sub-Saharan Africa opt to visit traditional healers instead, he said.
Globally, snakebites leave an estimated 81,000 to 138,000 people dead every year and cause three times as many amputations and other permanent disabilities. These occur mostly in Africa, Asia, and Latin America and particularly impact people living in low-income, rural communities.
“It’s during farming that most people get bitten in Africa,” Habib said. “It’s a rural menace.”
Across sub-Saharan Africa, there have been significant challenges around ensuring adequate supplies of effective anti-venoms. Even if an anti-venom does save a person’s life, poor quality doses can cause other side effects, including anaphylactic shock — a potentially life-threatening allergic reaction.
The traditional way to make anti-venom includes milking the venom from a snake and then immunizing animals, typically horses, with a diluted version of the poison. The antibodies are then extracted from the blood of these animals to create a serum.
There is also variability in how well the anti-venoms work, depending on the quality and geographic areas, said Devin Sok, director of antibody discovery and development at the International AIDS Vaccine Initiative, or IAVI. For example, anti-venom created using snake venom from southern India might not be effective for snakebites in northern India, he said.
“If we produce monoclonal antibodies that work — that's a great scientific achievement. But if we can't make it affordable to the people who need it most, then it's not really much of a success.”— Devin Sok, director of antibody discovery and development, IAVI
Can antibodies tackle multiple venoms?
The Scientific Research Partnership for Neglected Tropical Snakebite consortium was launched in 2018. The consortium received nearly £10 million in funding from the United Kingdom's former Department for International Development last year to try to find a next-generation solution to snakebites through monoclonal antibodies.
As first steps, consortium researchers produced replicas of venom from a variety of snakes in labs and then immunized cows, camels, and baboons. Next, research partners expect to identify which antibodies are the most effective against a variety of snake venom toxins, Sok said. In the future, clinical trials will be held in a high-incidence area like Nigeria to test the effectiveness of the monoclonal antibodies in that setting.
A key challenge in this research is the enormous amount of diversity among toxins within snake venom regionally and across species, Sok said. But promising research in the HIV field shows that monoclonal antibodies can be effective even when high levels of diversity are present.
In the 1990s, HIV research looked into whether antibodies formed in response to an infection could effectively fight against other strains of the virus in circulation — an issue because HIV mutates rapidly. Researchers discovered that there are a few people whose own bodies developed broadly neutralizing antibodies to fight against HIV infection. Research is ongoing to explore whether the antibodies could be introduced before exposure to prevent HIV infection.
Now, countries around the world have licensed more than 100 monoclonal antibodies, and this type of treatment is “transforming the way doctors treat, prevent and even cure serious non-communicable diseases, including many cancers and autoimmune disorders,” according to a recent report by IAVI and Wellcome Trust. Currently, there are only eight antibody-based products licensed to combat infectious diseases.
Researchers are also currently evaluating the use of monoclonal antibodies in treating and preventing COVID-19, and the U.S. Food and Drug Administration just approved the world’s first Ebola treatment, which is made up of three monoclonal antibodies.
Monoclonal antibody-based treatments are among the therapies being studied to fight COVID-19. What are they, how do they work, and why the interest in them?
In the case of snakebites, it is expected that a combination of antibodies would be used as a therapy after a bite.
While serum-based anti-venoms can cause anaphylactic shock, monoclonal antibodies are primarily produced and purified in a way that ensures they are generally safe, Sok said.
“We think that with these monoclonals we'll be able to have a more consistent product … and have a product that's going to be safer in terms of toxicity,” he added.
There are hopes that a safer, more effective product could improve trust in local health systems to treat snakebites, Habib said.
Success comes with affordability
Even if researchers develop this product, affordability is still a challenge. According to the report published by IAVI and Wellcome Trust, there are few, if any, monoclonal antibodies registered in low-income countries, and those that are available in middle-income countries are “prohibitively expensive.”
The report recommends the application of new technologies to lower the cost of developing these medicines. Costs can also be cut by changing the ways in which monoclonal antibodies are packaged, stored, and delivered to patients, as well as through local production and new business models.
Experts also suggest that funding from Gavi, the Vaccine Alliance and philanthropic foundations could subsidize treatments with an initial investment followed by a “self-sustaining revolving fund model” for sub-Saharan African countries as a way of making treatments affordable.
“If we produce monoclonal antibodies that work — that's a great scientific achievement. But if we can't make it affordable to the people who need it most, then it's not really much of a success,” Sok said.
Oct. 20, 2020: This piece has been updated to clarify the funding for the Scientific Research Partnership for Neglected Tropical Snakebite consortium and to reflect the limited number of monoclonal antibody solutions for infectious diseases.