Toxicology Letters 187 (2009) 94–98 Contents lists available at ScienceDirect Toxicology Letters journal homepage: www.elsevier.com/locate/toxlet An in vivo comparison of the efficacy of CSL box jellyfish antivenom with antibodies raised against nematocyst-derived Chironex fleckeri venom Kelly L. Winter a , Geoffrey K. Isbister a,b , Tamara Jacoby c , Jamie E. Seymour d , Wayne C. Hodgson a,∗ a Monash Venom Group, Department of Pharmacology, Monash University, Victoria, Australia b Tropical Toxicology Unit, Menzies School of Health Research, Northern Territory, Australia c Monoclonal Antibody Facility, Western Australian Institute for Medical Research, UWA, Western Australia, Australia d School of Marine and Tropical Biology, James Cook University, Queensland, Australia article info Article history: Received 11 December 2008 Received in revised form 21 January 2009 Accepted 9 February 2009 Available online 20 February 2009 Keywords: Venom Jellyfish Antivenom Antibodies Cardiovascular Envenoming abstract Although CSL box jellyfish antivenom (AV) remains the primary treatment for Chironex fleckeri envenom- ing, there has been considerable debate regarding its clinical effectiveness. Animal studies have shown that AV is largely ineffective in preventing C. fleckeri-induced cardiovascular collapse. This study examined the effectiveness of CSL box jellyfish AV (ovine IgG), raised against ‘milked’ venom, and polyclonal rab- bit IgG antibodies (Ab) raised against nematocyst-derived venom. A venom dose of 30 g/kg, i.v., which causes an initial presser response (34 ± 5 mmHg; n = 7) followed by cardiovascular collapse, was used in all experiments. A bolus dose of AV (3000U/kg, i.v.) or Ab (12mg; i.e. an equivalent protein ‘load’ to 3000 U/kg AV), administered 15 min prior to a bolus dose of venom, did not significantly attenuate the effects of venom. The venom response was also not significantly attenuated when AV (3000U/kg) was given as a bolus dose 10–60 min prior to venom infusion. However, when the venom was incubated with either AV (3000 U/kg) or Ab (12 mg) for 3 h prior to infusion, the effect of the venom was almost abolished. The results of this study demonstrate that antibodies raised against both ‘milked’ and nematocyst-derived venom are able to neutralise the cardiovascular collapse produced by the venom. However, large amounts of AV are required and must be preincubated with the venom to be protective. This indicates a very rapid action of the toxin(s) and that AV is unlikely to be clinically effective because it cannot be administered early enough. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Jellyfish stings occur in most coastal waters around the world, and include thousands of minor stings due to Physalia sp. and less common life-threatening stings by box jellyfish (Cubozoa) (Bengston et al., 1991; Williamson et al., 1996). The Australian box jellyfish Chironex fleckeri is the most venomous jellyfish and, arguably, the most venomous creature in the world. This is a rep- utation earned by the rapid onset of life-threatening envenoming, including hypotension and cardiac arrest (Williamson et al., 1996). Clinical and experimental observations support the lethal toxins having a cardiovascular action (Ramasamy et al., 2004, 2005; Turner and Freeman, 1969; Winter et al., 2007a,b) although the mechanism of this effect remains to be elucidated. Antivenom therapy is the major therapeutic option for enven- oming and despite the large number of antivenoms available for terrestrial venomous creatures, the only commercial antivenom ∗ Corresponding author. Tel.: +61 3 99054861; fax: +61 3 99055851. E-mail address: wayne.hodgson@med.monash.edu.au (W.C. Hodgson). available worldwide for the treatment of box jellyfish envenom- ing is CSL box jellyfish antivenom. This ovine IgG antivenom has been available since 1970 and is raised against C. fleckeri venom (Currie, 2003). Deaths, mainly in children in isolated parts of north- ern Australia, have lead to large amounts of antivenom being kept through-out the region, including antivenom being kept by the Queensland ambulance service for intramuscular use. However, the effectiveness of the antivenom has been the subject of much debate (Currie, 2003). No controlled trials or observational studies exist to support its effectiveness and because of the uncommon and isolated nature of life-threatening stings its administration is often delayed and not optimal. There are increasing numbers of cases where death has occurred despite the use of antivenom (Currie, 2003). Clearly this raises questions about the efficacy of the antivenom and whether the antibodies are in fact able to bind and neutralise the lethal components of the venom. Animal studies have produced conflicting results, possibly due to the different venom preparations used and the clinical relevance of the bioassays. Baxter and Marr (1974) showed that CSL box jel- lyfish antivenom neutralized the haemolytic, dermatonecrotic and lethal effects of tentacle extract and ‘milked’ venom, in vivo. How- 0378-4274/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.toxlet.2009.02.008