Death Adder Envenoming Causes Neurotoxicity Not Reversed by Antivenom - Australian Snakebite Project (ASP-16)

Abstract

BackgroundDeath adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment.Methodology/Principal FindingsDefinite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5–74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5–15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5–168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4–245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom.Conclusions/SignificanceDeath adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The persistent neurological effects despite antivenom, suggests that neurotoxicity is not reversed by antivenom.

Antivenom for Neuromuscular Paralysis Resulting From Snake Envenoming

“…This is well supported by clinical observations that neurotoxic snake envenoming almost exclusively results in flaccid paralysis [4,5,6,7,8,9,10,11,12] which is due to the blockade of neurotransmission at the neuromuscular junction by venom neurotoxins [13,14,15,16]. Neuromuscular paralysis in snake envenoming varies from mild to life threatening, depending on the degree of envenoming (i.e., quantity of injected venom reaching the circulation), the composition of the venom and potentially early therapeutic interventions.…”

“…[12], Papuan black snake ( Pseudechis papuanus ) [102], and viperids such as Sri Lankan Russell’s viper ( Daboia russelii ) [5,103,104,105], Balken adder ( Viper berus bosniensis ) [17], southern tropical rattlesnake ( Crotalus durissus terrificus ) [106,107] and Mojave rattlesnake ( C. scutulatus scutulatus ) [108] and North American crotalids [109]. In addition, there was a large number of case reports on snake bite induced paralysis and the effect of antivenom.…”

Snakebite Envenoming – A Combined Density Equalizing Mapping and Scientometric Analysis of the Publication History

“…They range, for example, from neurotoxicological aspects [39], immune responses [37], phylogeny, venom composition of diverse species [38], the analysis of geographical information [40] to basic science issues [41–43] and public health [44]. Despite the burden of disease caused by snakebite envenoming and the need for increased transnational and national funding, there has been no in-depth scientometric analysis of this topic so far.…”

Cross-Neutralisation of In Vitro Neurotoxicity of Asian and Australian Snake Neurotoxins and Venoms by Different Antivenoms

“…Although the effectiveness of antivenoms in treating established neurotoxic envenoming in humans has been questioned for many snakes, these antivenoms are clearly efficacious in preventing in vitro neurotoxicity and have been shown to bind with circulating venom [22,23,24,25]. Snake antivenoms contain polyclonal antibodies—Fab or F(ab’) 2 fragments—purified from serum of animals immunised against snake venoms [26].…”