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.

Enzymatic Activity And Brine Shrimp Lethality Of Venom From The Large Brown Spitting Cobra (Naja Ashei) And Its Neutralization By Antivenom

“…B. arietans venom was non-toxic after 24 hours but toxic after 48 and 72 hours. Table 2.Discussion svPLA 2 make up to 30% of viperid and elapid venoms[28,29], and the local effects of venomous snakebite in sub-Saharan Africa have been linked to svPLA 2 's[12,[30][31][32][33]. Our results suggest that the Eastern forest cobra had the highest svPLA 2 activity while mamba venoms had the least activity.This observation seems to corroborate clinical reports on venomous snakebite in Sub-Saharan Africa where cobra bites are associated with severe muscle and tissue damage, and painful progressive swelling which are generally absent in mamba bites[30,[34][35][36][37][38][39].…”

“…Both antivenoms had poor neutralization capacity against the svPLA 2 activity of N. ashei venom. It is no surprise therefore that research into compounds like varespladib, methylvarespladib, and medicinal plant extracts continue to be pursued as possible adjuncts in the management of svPLA 2 -induced effects of viper and elapid venoms[20,28,31,40,41].To the best of our knowledge, this is the first report to establish that the non-spitting Eastern forest cobra (N. subfulva) is more potent than the red spitting cobra (N. pallida) and the large brown spitting cobra (N. ashei) in as far as svPLA 2 activity is concerned. However, considering that both the Eastern forest cobra (N. subfulva) and the Egyptian cobra (N. haje) are non-spitting cobras, it is not clear why they have varying svPLA 2 activity.…”

Identifying the snake: First scoping review on practices of communities and healthcare providers confronted with snakebite across the world

“…Atractaspis bibronii (22) Afrotyphlops schlegelii (1) Causus defilippi (8) Bitis arietans (8) Boaedon capensis (2) Causus rhombeatus (9) Bitis atropos (1) Crotaphopeltis hotamboeia (3) Daboia mauritanica (3) Dasypeltis scabra (1) Dendroaspis polylepis (12) Philothamnus spp. (2) Echis romani (103) Hemachatus haemachatus (1) Naja annulifera (3) Naja melanoleuca (1) Naja mossambica (18) Asia Bitis arietans (1) Acrochordus javanicus (NR) Bungarus caeruleus (623) Ahaetulla nasuta (10) Bungarus candidus (17) Ahaetulla prasina (NR) Bungarus fasciatus (6) Argyrogena fasciolata (1) Bungarus lividus (3) Atreitum schistosum (1) Bungarus multicinctus (6) Boiga ceylonensis (10) Bungarus niger (1) Boiga cyanea (NR) Bungarus spp.…”

“…Australo-papua Acanthophis sp. (13) Antaresia childreni (12) Boiga irregularis (3) Notechis scutatus (NR) Dendrelaphis punctulatus (2) Cryptophis pallidiceps (4) Oxyuranus microlepidotus (1) Fordonia leucobalia (1) Demansia olivacea (5) Oxyuranus scutellatus (1) Liasis fuscus (9) Demansia spp. (17) Pseudechis australis (30) Liasis olivaceus (4) Denisonia maculata (1) Pseudechis guttatus (1) Morelia spilota (8) Furina ornata (3) Pseudonaja nuchalis (13) Pseudoferania polylepis (1) Hemiaspis signata (2) Pseudonaja spp.…”

“…At the clinical level, the identity of the biting snake (BSN) can help healthcare providers anticipate victims' syndromes and support decision making when treating the patient (i.e. whether or not to administer antivenom or which type of antivenom) [8,9]. This decision is important because not only are antivenoms effective against a limited number of venomous snakes but they have potentially lethal side effects such as fatal allergic reactions and should not be used to treat bites from non-venomous snakes.…”