Commercially available antivenoms in India can be ineffective in treating bites from certain medically important yet neglected snakes, a study conducted by the Evolutionary Venomics Lab (www.venomicslab.com), has shown. These so called the ‘neglected many’, are snakes whose bites are harmful to humans, yet remain poorly studied.
Each year, about 46,000 people die and 140,000 people are disabled in the country because of snakebites. The only scientifically validated treatment for snakebites is the use of antivenom, for which manufacturing protocols have remained unchanged for over a century. In India, a polyvalent antivenom is produced against the so-called ‘big four’ snakes: the spectacled cobra, the common krait, Russell’s viper, and the saw-scaled viper. However, in addition to these snakes, India is home to many other species of venomous snakes that have the potential to inflict deadly, even fatal bites – about 60 of the 300 species of Indian snakes are considered medically important. But specific antivenoms are not produced against these species; instead, the ‘big four’ antivenom is routinely used to treat bites from all snakes.
To better understand the consequences of using the polyvalent antivenom to treat all snakebites, the researchers conducted a two-fold study. In the first part, they characterised the venoms of major neglected, yet medically important, Indian snakes: their composition, biochemical and pharmacological activities, and potencies. These snakes included the Sochurek’s viper, the Sind krait, the banded krait, and two populations of monocled cobras, as well as their closest ‘big four’ relatives (saw-scaled viper, common krait and spectacled cobra). Owing to the underlying differences in the feeding ecology of these snakes, dramatic differences in venom compositions were observed. For example, the banded krait and the Sochurek’s viper, which are known to specialize on non-mammalian prey (reptilian and arthropod, respectively), exhibited reduced toxicities towards mammalian targets. This study also found stark intraspecific variations in the venoms of two populations of monocled cobra (N. kaouthia) from West Bengal and Arunachal Pradesh. The former was found to be highly neurotoxic (targeting the nervous system), while the latter was rich in cytotoxins (targeting cells and tissues).
In the second part of the study, the research team evaluated how effective commercially marketed Indian antivenoms are in treating snakebites from these neglected species. Again, the results were startling. The researchers found that the antivenoms were completely ineffective in overcoming the effects of envenomations by many of these neglected snakes, with one of the antivenoms being completely ineffective against the Arunachal Pradesh population of monocled cobra in the mouse model. Surprisingly, this widely marketed commercial antivenom even failed to neutralise the venom of one of the ‘big four’ snakes from North India – the common krait.
This study also found that the venom of the Sind krait from western India is over 40 times more potent than that of the spectacled cobra, making it the most toxic Indian snake. Unfortunately, the polyvalent antivenom was found to be ineffective against the venom of this species as well.
The main takeaway from the study for antivenom manufacturers, public health officials and policy makers, is a pressing need to develop region-specific snakebite therapies for the many neglected species. The paper also provides future directions for Indian antivenom manufacturers to improve the pan-India effectiveness of their commercially marketed antivenoms. As a step forward, the Evolutionary Venomics Lab has now initiated collaborations with the Indian antivenom manufacturers to produce these region-specific antivenoms.
Senji Laxme RR, Khochare S, de Souza HF, Ahuja B, Suranse V, Martin G, Whitaker R, and Sunagar K. 2019. Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies. PLoS Neglected Tropical Diseases. 13(12): e0007899.