The Snake Study: Survey of National Attitudes and Knowledge in Envenomation.

Despite recent reviews of best practice for the treatment of Australian venomous bites and stings, there is controversy about some aspects of care, particularly the use of antivenom. Our aim was to understand current attitudes and practice in the management of suspected snake envenoming. A single-stage, cross-sectional survey of Australian emergency care physicians who had treated snake envenomation in the previous 36 months was conducted. Hospital pharmacists were also invited to complete a survey about antivenom availability, usage, and wastage in Australian hospitals. The survey was available between 5 March and 16 June 2019. A total of 121 snake envenoming cases were reported, and more than a third (44.6%) of patients were not treated with antivenom. For those treated with antivenom (n = 67), 29 patients (43%) received more than one ampoule. Nearly a quarter of respondents (21%) identified that antivenom availability was, or could be, a barrier to manage snake envenoming, while cost was identified as the least important factor. Adverse reactions following antivenom use were described in 11.9% of cases (n = 8). The majority of patients with suspected envenoming did not receive antivenom. We noted variation in dosage, sources of information, beliefs, and approaches to the care of the envenomed patient.

Incidence of fatal snake bite in Australia: A coronial based retrospective study (2000-2016).

INTRODUCTION: It has been over 20 years since a national review of recorded deaths from snake envenoming. The present study aimed to provide an updated review of the epidemiology of deaths from snake bites in Australia. METHODS: Deaths were identified from January 2000 to December 2016 from the National Coronial Information System. Cases identified due to snakes were extracted with data on coronial findings, autopsy and police records. RESULTS: Thirty five deaths (2.2 per year) were ascribed or antecedent to a snake bite. Sixteen cases were attributed to snake bite/envenoming as leading directly to death, with other direct causes of death being multiple organ failure (n = 3), intracerebral haemorrhage (n = 2), cerebral hypoxia or anoxia (n = 3), cardiac arrest (n = 1), complications of snake bite (n = 3) or brain stem death (n = 1). Four cases did not have a snake bite indicated in the case history, with an initial diagnosis of either hyperthermia, stroke, gastroenteritis and a horse accident. The median age was 46.5 years (range 1.5-70 years), and 74% were males (n = 25). The time from bite to death varied from 1 h to 19 days. Fifty four percent of bites occurred at the person's residence (n = 1), with 17 being in an urban environment. CONCLUSIONS: Death from snake bite remains rare in Australia, and has maintained a steady rate for over 20 years. Usually considered a 'rural issue', and with varying recorded causes of death, a nationally co-ordinated effort to further review the national picture of envenoming in Australia can inform education and resource needs within state and local contexts.

Proteomics and antivenomics of Papuan black snake (Pseudechis papuanus) venom with analysis of its toxicological profile and the preclinical efficacy of Australian antivenoms.

The Papuan black snake (Pseudechis papuanus Serpentes: Elapidae) is endemic to Papua New Guinea, Indonesian Papua and Australia's Torres Strait Islands. We have investigated the biological activity and proteomic composition of its venom. The P. papuanus venom proteome is dominated by a variety (n≥18) of PLA2s, which together account for ~90% of the venom proteins, and a set of low relative abundance proteins, including a short-neurotoxic 3FTx (3.1%), 3-4 PIII-SVMPs (2.8%), 3 cysteine-rich secretory proteins (CRISP; 2.3%) 1-3 l-amino acid oxidase (LAAO) molecules (1.6%). Probing of a P. papuanus cDNA library with specific primers resulted in the elucidation of the full-length nucleotide sequences of six new toxins, including vespryn and NGF not found in the venom proteome, and a calglandulin protein involved in toxin expression with the venom glands. Intravenous injection of P. papuanus venom in mice induced lethality, intravascular haemolysis, pulmonary congestion and oedema, and anticoagulation after intravenous injection, and these effects are mainly due to the action of PLA2s. This study also evaluated the in vivo preclinical efficacy of Australian black snake and polyvalent Seqirus antivenoms. These antivenoms were effective in neutralising the lethal, PLA2 and anticoagulant activities of P. papuanus venom in mice. On the other hand, all of the Seqirus antivenoms tested using an antivenomic approach exhibited strong immunorecognition of all the venom components. These preclinical results suggest that Australian Seqirus1 antivenoms may provide paraspecific protection against P. papuanus venom in humans. SIGNIFICANCE PARAGRAPH: The toxicological profile and proteomic composition of the venom of the Papuan black snake, Pseudechis papuanus, a large diurnal snake endemic to the southern coast of New Guinea and a handful of close offshore islands, were investigated. Intravenous injection of P. papuanus venom in mice induced intravascular hemolysis, pulmonary congestion and edema, anticoagulation, and death. These activities could be assigned to the set of PLA2 molecules, which dominate the P. papuanus venom proteome. This study also showed that Australian Seqirus black snake or polyvalent antivenoms were effective in neutralising the lethal, PLA2 and anticoagulant activities of the venom. These preclinical results support the continued recommendation of these Seqirus antivenoms in the clinical management of P. papuanus envenoming in Australia, Papua New Guinea or Indonesian Papua Province.

Full length nucleotide sequence of a factor V-like subunit of oscutarin from Oxyuranus scutellatus scutellatus (coastal Taipan).

An Oxyuranus scutellatus scutellatus venom gland cDNA expression library was screened with antivenom. Positive clones were isolated and their nucleotide sequences determined. The complete sequence for a Factor V-like component from the Taipan venom prothrombin activator, oscutarin (EC 3.4.21.60) (Walker, F.J., Owen, W.G., Esmon, C.T., 1980. Characterization of the prothrombin activator from the venom of Oxyuranus scutellatus scutellatus (Taipan venom). Biochemistry, 19(5), 1020-1023; Speijer, H.G.R., Zwall, J., Robert, F.A., Rosing, J., 1986. Prothrombin acitvation by an activator from the venom of Oxyuranus Scutellatus (Taipan Snake). J. Biol. Chem. 261, 13258-13267) was determined from the sequencing of antigenic cDNA clones. The cDNA sequence encoded a protein of 1460 amino acid residues, including a 30-residue signal peptide. This sequence shared 95% sequence similarity with the non-enzymic subunit of the prothrombin activator (pseutarin C) from brown snake (Pseudonaja textilis) venom. This sequence in turn has been reported to share high similarity with mammalian Factor V. Sequence comparisons indicated the size, charge and cleavage sites were conserved across the two species. This is the first nucleotide sequence of a Factor V-like component from Oxyuranus venom and the second sequence within Elapidae to be reported.