Development of an Irukandji Jellyfish Antivenom
A project undertaken at the Australian Venom Research Unit, University of Melbourne, and supervised by K D Winkel
The Irukandji syndrome is a potentially catastrophic complex of clinical signs and symptoms that has been attributed to the stings of various species of jellyfish. The term ‘Irukandji’ refers to an Australian Aboriginal tribe that inhabited the Palm Cove region of northern Queensland where this illness occurs most frequently. The syndrome has also been described throughout the Pacific basin and recently from waters off Florida. In 1999, the research team described the first case from temperate Australian waters. Two fatalities, both affecting overseas tourists holidaying in north Queensland, occurred in early 2002. Both cases were attributed to intracranial haemorrhage associated with severe hypertension.
The initial sting is typically mild and is followed, minutes to hours later, by vomiting, profuse sweating, headache, agitation, rapid heart rate and very high blood pressure. The increase in blood pressure may be life-threatening and can be associated with abnormal heart beat and heart failure. The symptoms may last from hours to several days, and victims usually require hospitalisation. Though the syndrome was first described almost fifty years ago, its pharmacological basis and a specific treatment have eluded investigators.
To date, only one species of jellyfish, Carukia barnesi, has been confirmed as capable of causing the syndrome, but others are suspected.
In this project, the Australian Venom Research Unit, in collaboration with Surf Life Saving Australia (Queensland), studied the venom of C. barnesi jellyfish, with a view to developing a specific therapy for the syndrome.
Initially, small numbers of C. barnesi jellyfish were obtained from northern Queensland in order to optimise the venom preparation method. A quick and simple way of extracting venom from the thumb-sized jellyfish was developed and the extract proved to be lethal to mice injected with it. More recently, large numbers of specimens were obtained, allowing the extraction of sufficient venom for detailed study of its mode of action. It was concluded from this study that the Irukandji syndrome was caused by the release of endogenous adrenaline and noradrenaline (‘fight or flight’ hormones) stimulated by the jellyfish toxin acting on the nervous system (i.e. the venom is a ‘neurotoxin’). These hormones were detected at high levels and caused a significant increase in the heart rate and blood pressure in experimental animals injected with venom. We recently confirmed the mechanism of Carukia barnesii venom action by examining its effect on human heart tissue in collaboration with colleagues at the Prince Charles Hospital in Brisbane.
The research team also studied the venom of the ‘jimble’ (Carybdea rastonii), a closely-related species of jellyfish that is suspected of causing an Irukandji-like illness. In preliminary studies, the venom of Carybdea rastonii was found to exert a similar toxicity to C. barnesi, but its mechanism of action appeared to be more complex. The collection of other potential ‘Irukandji’ species, from the Great Barrier Reef, southern Western Australia and the Northern Territory is continuing. The world’s only commercially available jellyfish antivenom is that made by CSL Limited (in Victoria) to combat the venom of the box jellyfish, Chironex fleckeri. The plan is to test the effectiveness of this antivenom against C. barnesi and all closely-related jellyfish. So far its efficacy has been assessed against only jimble venom. It has proved ineffective at neutralising the effects of C. barnesi and C. rastoni venoms in vitro.
The results of the project have been presented at several international conferences.
In addition to a grant from the Hermon Slade Foundation, the project has received support from the University of Melbourne Collaborative Research Grant Scheme, the Cooperative Research Centre for Reef Research, the Lions Foundation, the Royal Children’s Hospital (Melbourne) and the Baker Institute of Medical Research.
Cheng, A, Winkel, K, Hawdon, GM and McDonald, M (1999). Irukandji-like syndrome in Victoria. Aust NZ J Med, 29, 835.
Nevalainen, TJ, Peuravuori, HJ, Quinn, RJ, Llewellyn, LE, Benzie, JAH, Fenner, PJ and Winkel, KD (2004). Phospholipase A2 in Cnidaria. Comparative Biochemistry and Physiology, Part B, 139, 731-735. (View PDF)
Tibballs, J, Hawdon, G, Winkel, KD, Wiltshire, C, Lambert G, Gershwin LA, Fenner PJ and Angus JA (2000). The in vivo cardiovascular effects of Irukandji (Carukia barnesi) venom. International Society of Toxinology XIIIth World Congress on Animal, Plant and Microbial Toxins Abstract p.276, September 2000, Paris France.
Wiltshire CJ, Sutherland SK, Fenner PJ and Young AR (2000). Optimisation and preliminary characterisation of venom isolated from medically important jellyfish: the box jellyfish (Chironex fleckeri), the Irukandji (Carukia barnesi) and the blubber (Catostylus mosaicus). Wilderness and Environmental Medicine, 11, 241–250.
Wiltshire, CJ, Sutherland, SK, Winkel, KD and Fenner, PJ (1998). Comparative studies on venom extracts from three jellyfish: the Irukandji (Carukia barnesi), the box jellyfish (Chironex fleckeri southcott) and the blubber (Catostylus mosaicus). Toxicon, 36, 1239.
Winkel, KD, Tibballs, J, Molenaar, P, Lambert, G, Coles, P, Ross-Smith, M, Wiltshire, C, Fenner, PJ, Gershwin, L-A, Hawdon, GM, Wright, CE and Angus, JA. Cardiovascular actions of the venom from the Irukandji (Carukia barnesi) jellyfish: effects in human, rat and guinea-pig tissues in vitro and in pigs in vivo. Clinical and Experimental Pharmacology and Physiology (2005) 32, 777-788. (View PDF)
Winkel KD, Christopoulos A, Coles P, Wiltshire C, Gershwin LA, Fenner PJ and Angus JA. (2000). Irukandji (Carukia barnesi) venom contains a potent neuronal sodium channel agonist. International Society of Toxinology XIIIth World Congress on Animal, Plant and Microbial Toxins Abstract p.83, September 2000, Paris France.