Global antivenom crisis.
The world produces less than half of the antivenom it needs, and this only covers 57% of the world’s species of venomous snake. Barriers to snakebite treatment are driven by challenges plaguing antivenom production and use, characterized by a 19th-century technology, first developed in 1894, which continues to have high manufacturing costs and remains unaffordable and inaccessible to the poorest people who are most in need. Moreover, multi-venom treatments commonly used in Africa and India have weak, unreliable effectiveness against the venom of any single snake species and may even have harmful side effects, such as anaphylactic shock.
The challenges of antivenom technology.
Current antivenom technology repeatedly exposes large domesticated animals, such as horses, to small amounts of snake venom to produce toxin specific antibodies capable of binding and neutralizing the same toxins within the snake venom. These antibodies are then collected from the immunised animals blood and purified to form antivenom. Monovalent antivenoms are specific to the venom of a single species of snake. Polyvalent antivenoms are generated against a number of different snake venoms. While some antibodies are cross-neutralising, meaning they provide protection against venoms not included within the immunisation mix, most are not.
Snake venom is highly variable, even within snakes of the same species from different regions, let alone among the approximately 600 venomous snakes across the globe. The need for regionally specific antivenom increases the complexity and cost of antivenom production. Moreover, antivenoms pose serious and potentially life-threatening adverse effects, such as anaphylactic shock and serum sickness.
Accessible and effective snakebite therapies are urgently needed, with several different strategies currently being explored.
One approach considers whether antivenom needs to neutralize every toxin within the venom. Generating a targeted antivenom to the most medically important toxins could allow treatment of the most severe effects while potentially reducing the amount required.
Another approach seeks to generate recombinant antibodies using laboratory techniques, removing the dependency on live animals in antivenom production.
Further, small molecules such as varespledib, marimastat, and DMPS, are being investigated as replacements or complements to antivenom, allowing the targeting of families of toxins from multiple snake species.