Tammy Jacoby Alner

Thesis

Australian snake venoms: Immunological cross-reactivity and detection in envenomed patients

Summary

There are up to 3,000 reported snakebites in humans and an estimated 6,000 snakebites in domestic animals each year in Australia. Australian elapids venoms contain potent coagulant, myolytic, and neurotoxic components and envenomings by these snakes result in similar clinical presentations and cause serious morbidity in patients. Members of the tiger snake family are indistinguishable from each other by the commercial venom detection kit so it is unclear what proportion of bites is due to each of these closely related species (Notechis sp, H.stephensii and T.carinatus). Crude venom levels have not been reported for the closely related tiger snake family species and the quantitation of venom has not been reported in clinically envenomed domestic animals. Under the umbrella of the Australian Snakebite Project (ASP) and in collaboration with the Murdoch Emergency Pet Centre (MPEC), human and domestic animal patients were examined for this study.

My thesis describes the development of sensitive, species-specific diagnostic assays to: (i) accurately determine which species of snake (Notechis sp, T.carinatus or H.stephensii) is responsible and (ii) measure crude venom, coagulopathic and neurotoxic components of venom in serial patient samples. The ability of various commercially available (Australian) human and veterinary antivenom (AV) preparations was measured for their ability to bind and neutralise the procoagulants toxins. Results suggests that the protection offered by commercial AVs against various brown snake species may be dependent on the brown snake species it has been raised against, identifying an area for further study. In addition, work was completed to localise venom components in tissue of envenomed animals, successfully illustrating the role of developed antibodies as a novel tool for examining venom toxins in vivo.

Why my research is important

This work has focused on the coagulopathic effects of Australian snake venoms as venom-induced consumptive coagulopathy (VICC) is the most common potentially lethal clinical manifestation of envenoming. It is not known whether the features and severity of VICC vary between species of snake and whether the current antivenoms are sufficiently effective in both humans and domestic animals. This work has been successful is providing retrospective diagnostic tools to determine circulating venom levels in patients for comparison with clinical data. This will aid in an evidence- based approach to determining appropriate levels of antivenom for treatment. This work has also shed light on the efficacy of commercially available antivenom treatments with implications for antivenom manufacture techniques.

Funding

• Australian Postgraduate Award (APA)