The Urgent Need to Develop Novel Strategies for the Diagnosis and Treatment of Snakebites

Abstract

Snakebite envenoming (SBE) is a priority neglected tropical disease, which kills in excess of 100,000 people per year. Additionally, many millions of survivors also suffer through disabilities and long-term health consequences. The only treatment for SBE, antivenom, has a number of major associated problems, not least, adverse reactions and limited availability. This emphasises the necessity for urgent improvements to the management of this disease. Administration of antivenom is too frequently based on symptomatology, which results in wasting crucial time. The majority of SBE-affected regions rely on broad-spectrum polyvalent antivenoms that have a low content of case-specific efficacious immunoglobulins. Research into small molecular therapeutics such as varespladib/methyl-varespladib (PLA₂ inhibitors) and batimastat/marimastat (metalloprotease inhibitors) suggest that such adjunctive treatments could be hugely beneficial to victims. Progress into toxin-specific monoclonal antibodies as well as alternative binding scaffolds such as aptamers hold much promise for future treatment strategies. SBE is not implicit during snakebite, due to venom metering. Thus, the delay between bite and symptom presentation is critical and when symptoms appear it may often already be too late to effectively treat SBE. The development of reliable diagnostical tools could therefore initiate a paradigm shift in the treatment of SBE. While the complete eradication of SBE is an impossibility, mitigation is in the pipeline, with new treatments and diagnostics rapidly emerging. Here we critically review the urgent necessity for the development of diagnostic tools and improved therapeutics to mitigate the deaths and disabilities caused by SBE.

Keywords: diagnostics; neglected tropical disease; snakebite envenoming (SBE); therapeutics; toxin neutralisation; venom.

Figure 1

Phylogenetic tree adapted from Reyes-Velasco et al. (2014) [44]. Shows the Caenophidia, a clade including all venomous snakes. The skull diagrams were adapted from published images [45,46]. Number of species and genera were taken from the reptile database [47].

Figure 2

Generalised effects of viper and elapid snakebite envenomation and toxins causing these effects. Inspired by Gutiérrez et al. (2017) [16]. Abbreviations: PLA₂—Phospholipase A₂, SVMP—Snake venom metalloprotease, G2PLA₂—Group 2 PLA₂, SVSP—Snake venom serine protease, CRiSPs—Cysteine rich secretory proteins, Snaclecs—Snake c-type lectins, 3FTXs—Three finger toxins, SBE—snakebite envenoming, BM—basement membrane.

Figure 3

Comparison of current and future events involved in the diagnosis and treatment of snakebite envenoming.