The pathology of Chironex fleckeri venom and known biological mechanisms.

Melissa Piontek,Jamie E Seymour,Alan Nimmo,Ernest Jennings,Yide Wong,John J Miles,Tyler Gilstrom,Jeremy Potriquet

doi:10.1016/j.toxcx.2020.100026

Melissa Piontek, Jamie E Seymour + Show 6 more

Open Access

https://doi.org/10.1016/j.toxcx.2020.100026

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Abstract

The large box jellyfish Chironex fleckeri is found in northern Australian waters. A sting from this cubozoan species can kill within minutes. From clinical and animal studies, symptoms comprise severe pain, welts, scarring, hypotension, vasospasms, cardiac irregularities and cardiac arrest. At present, there is no cure and opioids are used to manage pain. Antivenom is available but controversy exists over its effectiveness. Experimental and combination therapies performed in vitro and in vivo have shown varied efficacy. These inconsistent results are likely a consequence of the different methods used to extract venom. Recent omics analysis has shed light on the systems of C. fleckeri venom action, including new toxin classes that use pore formation, cell membrane collapse and ion channel modulation. This review covers what is known on C. fleckeri pathomechanisms and highlights current gaps in knowledge. A more complete understanding of the mechanisms of C. fleckeri venom-induced pathology may lead to novel treatments and possibly, the discovery of novel cell pathways, novel drug scaffolds and novel drug targets for human disease.

Highlights

Chironex fleckeri is a large box jellyfish commonly found in Australia waters, and suspected through out the Indo Pacific region (Fenner and Williamson, 1996; Gershwin et al, 2010; Lippmann et al, 2011; Tib balls, 2006)
Clinical reports of non-fatal C. fleckeri envenomation have contributed to the understanding of systemic venom effects including severe pain, urticaria and scarring from nematocyst contact, hypotension, vasospasms, car diac irregularities and acute onset of cardiac arrest (Burnett et al, 1998; Cegolon et al, 2013; Nimorakiotakis and Winkel, 2003)
59% of the animals administered antivenom died within 3 min, 68% of the animals administered Verapamil died within 24 min, and 26% of mice given a mixture of antivenom and Verapamil died within 34 min (Burnett et al, 1990)

Summary

Introduction

Chironex fleckeri is a large box jellyfish commonly found in Australia waters, and suspected through out the Indo Pacific region (Fenner and Williamson, 1996; Gershwin et al, 2010; Lippmann et al, 2011; Tib balls, 2006). A separate study showed that while prophylactic administration of antivenom did not have any effect on blood pressure after envenomation, the antivenom did prevent cardiovascular collapse in 40% of test animals (Ramasamy et al, 2004) Another prophylactic study reported improved arterial pressure post low dose administration (Hughes et al, 2012; Ramasamy et al, 2004; Winter et al, 2007). A related study attempted a rescue experiment post envenomation using a combination of antivenom and Verapamil (Bloom et al, 1999) This treatment nearly doubled the survival time. The results of C. fleckeri venom treatment have been inconsistent both in vitro and in vivo

Consistencies and variabilities in animal testing

Findings

10. Future directions and conclusion