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Jellyfish envenoming syndromes: unknown toxic mechanisms and unproven therapies.

Interest in envenoming syndromes caused by Australian jellyfish has been intense since the deaths in early 2002 of two tourists in Queensland, attributed to the Irukandji syndrome. We review current knowledge of these envenoming syndromes, mechanisms of venom action and therapy, focusing on the deadly box jellyfish, Chironex fleckeri, and the array of jellyfish thought to cause the Irukandji syndrome. Current understanding of jellyfish venom activity is very limited, and many treatments are unproven and based on anecdote.

Animals↗

Prospective study of Chironex fleckeri and other box jellyfish stings in the "Top End" of Australia's Northern Territory.

OBJECTIVE: To describe the epidemiology and clinical features of box jellyfish envenoming in the Top End of the Northern Territory and, in particular, confirmed stings from the major Australian box jellyfish, Chironex fleckeri. DESIGN: Prospective collection of clinical data and skin scrapings or sticky-tape tests for nematocyst identification from patients presenting to Royal Darwin Hospital and remote coastal community health clinics in the Northern Territory, spanning 10 950 km of coastline; analysis of tidal, weather and seasonal data. PATIENTS: All patients with jellyfish sting details recorded between 1 April 1991 and 30 May 2004. MAIN OUTCOME MEASURES: Demographic and clinical features, use of C. fleckeri antivenom, and associations between weather, seasonal and tidal factors and confirmed C. fleckeri stings. RESULTS: Of 606 jellyfish stings documented, 225 were confirmed to have been caused by C. fleckeri. 37% of C. fleckeri stings were in children, 92% occurred during the "stinger season" (1 October to 1 June), 83% occurred in water 1 m or less deep, and 17% occurred while victims were entering the water. Stings were least common on outgoing tides (P < 0.001) and commonest between 15:00 and 18:00 (P < 0.001) and on days with wind speed less than that month's average (P < 0.001). Nearly all victims experienced immediate pain, but this could often be controlled with ice; only 30% required parenteral narcotics and 8% required hospital admission. Cardiorespiratory arrest occurred within several minutes of the sting in the one fatal case, involving a 3-year-old girl with only 1.2 m of visible tentacle contact. C. fleckeri antivenom was given to another 21 patients, none of whom had life-threatening features at the time they were given antivenom. CONCLUSIONS: Most C. fleckeri stings are not life-threatening; patients who die usually have cardiopulmonary arrest within minutes of the sting. The potential benefit of antivenom and magnesium under these circumstances remains to be shown, but a protocol with their rapid use is recommended if cardiopulmonary arrest has occurred. Unfortunately, this is unrealistic for many rural coastal locations, and the priority remains prevention of stings by keeping people, especially children, out of the sea during the stinger season.

Acetic Acid↗

Marine envenomations. Part 1--Jellyfish.

BACKGROUND: Many venomous marine creatures inhabit Australian waters, causing significant morbidity and occasional fatalities. Part 1 of this article looks at jellyfish envenomations, an important overall cause of marine injuries. OBJECTIVE: To discuss the features of envenomation by some of the more commonly encountered jellyfish of medical significance, and the recommended first aid and medical management of such envenomations. DISCUSSION: It is intended that the information contained in this article will be informative to general practitioners dealing with jellyfish stings throughout Australia. Much of what we know has come from the astute observations of GPs in tropical Australia. However, there remains a lot to be learnt about jellyfish envenomation.

Antivenins↗

Cold packs: effective topical analgesia in the treatment of painful stings by Physalia and other jellyfish.

A study has shown that, when applied to Physalia ("bluebottle") jellyfish stings, cold packs are effective as topical analgesia in the relief of mild-to-moderate skin pain. The application of ice also has been shown to be effective for topical analgesia in a number of other jellyfish stings, including by Cyanea ("hair jellyfish"), Tamoya sp. ("Moreton Bay stinger" or "fire jelly") and Carybdea rastoni ("jimble") as well as by Physalia. In the current state of knowledge, cold packs or ice are recommended as the first-aid treatment for jellyfish stings with local skin pain.

Animals↗

Bilaterally symmetrical rhopalial nervous system of the box jellyfish Tripedalia cystophora.

Cubomedusae, or box jellyfish, have the most elaborate visual system of all cnidarians. They have 24 eyes of four morphological types, distributed on four sensory structures called rhopalia. Box jellyfish also display complex, probably visually guided behaviors such as obstacle avoidance and fast directional swimming. Here we describe the strikingly complex and partially bilaterally symmetrical nervous system found in each rhopalium of the box jellyfish, Tripedalia cystophora, and present the rhopalial neuroanatomy in an atlas-like series of drawings. Discrete populations of neurons and commissures connecting the left and the right side along with two populations of nonneuronal cells were visualized using several different histochemical staining techniques and electron microscopy. The number of rhopalial nerve cells and their overall arrangement indicates that visual processing and integration at least partly happen within the rhopalia. The larger of the two nonneuronal cell populations comprises approximately 2,000 likely undifferentiated cells and may support a rapid cell turnover in the rhopalial nervous system.

Animals↗

Autonomic neurotoxicity of jellyfish and marine animal venoms.

Venoms and poisons of jellyfish and other marine animals can induce damage to the human nervous and circulatory systems. Clues to the pathogenesis and clinical manifestations of these lesions can be obtained from data of human envenomations and animal experimentation. Because many investigators are unaware that marine animal venoms have autonomic actions, this paper aims to elucidate the broad antagonistic or toxic effects these compounds have on the autonomic nervous system. Marine venoms can affect ion transport of particularly sodium and calcium, induce channels or pores in neural and muscular cellular membranes, alter intracellular membranes of organelles and release mediators of inflammation. The box jellyfish, particularly Chironex fleckeri, in the Indo-Pacific region, is the world's most venomous marine animal and is responsible for autonomic disorders in patients. The symptoms induced by these venoms are vasospasm, cardiac irregularities, peripheral neuropathy, aphonia, ophthalmic abnormalities and parasympathetic dysautonomia. Cases of Irukandji syndrome, caused by the jellyfish Carukia barnesi, have symptoms that mimic excessive catecholamine release. Coelenterate venoms can also target the myocardium, Purkinje fiber, A-V node or aortic ring. Actions on nerves, as well as skeletal, smooth or cardiac muscle occur. Recent studies indicate that the hepatic P-450 enzyme family may be injured by these compounds. The multiplicity of these venom activities means that a thorough understanding of the sting pathogenesis will be essential in devising effective therapies.

Animals↗

A guinea-pig model of corneal jellyfish envenomations.

Corneal jellyfish stings are painful, self-limited injuries which usually produce conjunctival hyperemia and chemosis, corneal edema, and mild iridocyclitis with resolution in 48 hr. We have developed a guinea-pig model of corneal jellyfish stings in order to study pathogenesis of human injury. Guinea-pig eyes were exposed to sea nettle (Chrysaora quinquecirrha) venom in vivo in the following ways: contact with live tentacles, intracameral injection of crude venom, and intracorneal injection of crude jellyfish venom. Slit lamp examination and histologic sections of the eye performed at intervals up to 8 days after exposure to the venom demonstrated conjunctival hyperemia and chemosis, corneal stromal inflammatory edema, anterior chamber inflammation, and opacities on the anterior capsule of the lens. Nematocysts adherent to the corneal epithelium were noted in eyes exposed to live tentacles.

Animals↗

Development studies of Aurelia (jellyfish) ephyrae which developed during the SLS-1 mission.

Aurelia polyps (scyphistomae) and ephyrae were exposed to microgravity for nine days aboard the space shuttle during the SLS-1 mission. During strobilation, polyps segment transversely and each segment develops into an ephyra. Polyps were induced to strobilate at 28 degrees C, using iodine or thyroxine, at L(Launch)-48h, L-24h, and L+8h. Ephyrae developed in the groups tested in space and on Earth. The number of ephyrae formed per polyp was slightly higher in the L+8h groups as compared with those induced at L-24h and L-48h. On Earth, iodine is used by jellyfish to synthesize jellyfish-thyroxine (Jf T4), needed for ephyra production. Since iodine-treated polyps strobilated and formed ephyrae in space, it appears that jellyfish can synthesize Jf-T4 in space. Indeed, two groups of polyps not given inducer formed ephyrae [correction of ephryae] in space, presumably due to enhanced Jf-T4 synthesis, utilization or accumulation. Some ephyrae that formed in space were also fixed in space on Mission Day (MD) 8; others were fixed post-flight. Examination of living ephyrae with the light microscope and fixed ones with the Scanning and Transmission Electron Microscopes revealed that those which developed in space were morphologically very similar to those which developed on Earth. Quantitation of arm numbers determined that there were no significant differences between space and Earth-developed ephyrae. Pulsing abnormalities, however, were found in greater numbers (18.3%) in space-developed ephyrae than in Earth-developed controls (2.9%). These abnormalities suggest abnormal development of the graviceptors, the neuromuscular system, or a defect in the integration between these systems in apparently microgravity-sensitive animals.

Animals↗

The in vivo cardiovascular effects of an Australasian box jellyfish (Chiropsalmus sp.) venom in rats.

Using a new technique to extract venom from the nematocysts of jellyfish, the in vivo cardiovascular effects of Chiropsalmus sp. venom were investigated in anaesthetized rats. Chiropsalmus sp. venom (150 microg/kg, i.v.) produced a transient hypertensive response (44+/-4 mmHg; n=6) followed by hypotension and cardiovascular collapse. Concurrent artificial respiration or pretreatment with Chironex fleckeri antivenom (AV, 3000 U/kg, i.v.) did not have any effect on the venom-induced hypertensive response nor the subsequent cardiovascular collapse. The cardiovascular response of animals receiving venom after the infusion of MgSO4 (50-70 mM @ 0.25 ml/min, i.v.; n=5) alone, or in combination with AV (n=5), was not significantly different from rats receiving venom alone. Prior administration of prazosin (50 microg/kg, i.v.; n=4) or ketanserin (1 mg/kg, i.v.; n=4) did not significantly attenuate the hypertensive response nor prevent the cardiovascular collapse induced by venom (50 microg/kg, i.v.). In contrast to previous work examining C. fleckeri venom, administration of AV alone, or in combination with MgSO4, was not effective in preventing cardiovascular collapse following the administration of Chiropsalmus sp. venom. This indicates that the venom of the two related box jellyfish contain different lethal components and highlights the importance of species identification prior to initiating treatment regimes following jellyfish envenoming.

Animals↗

Stings of edible jellyfish (Rhopilema hispidum, Rhopilema esculentum and Nemopilema nomurai) in Japanese waters.

Three edible jellyfish Rhopilema hispidum, R. esculentum and Nemopilema nomurai are virulent to humans. We monitored one patient that was stung sequentially by these three species of jellyfish. The first species caused a persistent eruption, the second produced significant pruritus and the last induced only cutaneous symptoms rather than severe systemic disorders reported for its Chinese counterpart. The lesions of these jellyfish species are characteristic and common in workers harvesting medusae. There is no significant incidence of symptoms by ingesting these animals.

Animals↗

Australian venomous jellyfish, envenomation syndromes, toxins and therapy.

The seas and oceans around Australia harbour numerous venomous jellyfish. Chironex fleckeri, the box jellyfish, is the most lethal causing rapid cardiorespiratory depression and although its venom has been characterised, its toxins remain to be identified. A moderately effective antivenom exists which is also partially effective against another chirodropid, Chiropsalmus sp. Numerous carybdeids, some unidentified, cause less severe illness, including Carybdea rastoni whose toxins CrTX-A and CrTX-B are large proteins. Carukia barnesi, another small carybdeid is one cause of the 'Irukandji' syndrome which includes delayed pain from severe muscle cramping, vomiting, anxiety, restlessness, sweating and prostration, and occasionally severe hypertension and acute cardiac failure. The syndrome is in part caused by release of catecholamines but the cause of heart failure is undefined. The venom contains a sodium channel modulator. Two species of Physalia are present and although one is potentially lethal, has not caused death in Australian waters. Other significant genera of jellyfish include Tamoya, Pelagia, Cyanea, Aurelia and Chyrosaora.

Acetic Acid↗

An in vivo examination of the stability of venom from the Australian box jellyfish Chironex fleckeri.

We have previously characterised the pharmacological activity of a number of jellyfish venoms with a particular emphasis on the profound cardiovascular effects. It has been suggested that jellyfish venoms are difficult to work with and are sensitive to pH, temperature and chemical changes. The current study aimed to examine the working parameters of the venom of the Australian box jellyfish Chironex fleckeri to enable fractionation and isolation of the toxins with cardiovascular activity. C. fleckeri venom was made up fresh each day and subjected to a number of different environments (i.e. a pH range of 5-9 and a temperature range of 4-30 degrees C). In addition, the effect of freeze drying and reconstituting the venom was investigated. Venom (50 microg/kg, i.v.) produced a transient hypertensive response followed by cardiovascular collapse in anaesthetised rats. This biphasic response was not significantly effected by preparation of the venom at a pH of 5, 7 or 9. Similarly, venom (50 microg/kg, i.v.) did not display a loss of activity when exposed to temperatures of 4, 20 or 30 degrees C for 1.5h. However, the cardiovascular activity was abolished by boiling the venom. Freeze drying, and then reconstituting, the venom did not significantly affect its cardiovascular activity. However, repeated freeze drying and reconstituting of extracted venom resulted in a significantly loss of activity. This study provides a more detailed knowledge of the parameters in which C. fleckeri venom can be used and, while supporting some previous studies, contradicts some of the perceived problems of working with the venom.

Animals↗

The Sine oculis/Six class family of homeobox genes in jellyfish with and without eyes: development and eye regeneration.

The development of visual organs is regulated in Bilateria by a network of genes where members of the Six and Pax gene families play a central role. To investigate the molecular aspects of eye evolution, we analyzed the structure and expression patterns of cognate members of the Six family genes in jellyfish (Cnidaria, Hydrozoa), representatives of a basal, non-bilaterian phylum where complex lens eyes with spherical lens, an epidermal cornea, and a retina appear for the first time in evolution. In the jellyfish Cladonema radiatum, a species with well-developed lens eyes in the tentacle bulbs, Six1/2-Cr and Six3/6-Cr, are expressed in the eye cup. Six4/5-Cr is mainly expressed in the manubrium, the feeding, and sex organ. All three Six genes are expressed in different subsets of epidermal nerve cells, possibly of the RFamide type which are part of a net connecting the different eyes with each other and the effector organs. Furthermore, expression is found in other tissues, notably in the striated muscle. During eye regeneration, expression of Six1/2-Cr and Six3/6-Cr is upregulated, but not of Six4/5-Cr. In Podocoryne carnea, a jellyfish without eyes, Six1/2-Pc and Six3/6-Pc are also expressed in the tentacle bulbs, Six1/2-Pc additionally in the manubrium and striated muscle, and Six3/6-Pc in the mechanosensory nematocytes of the tentacle. The conserved gene structure and expression patterns of all Cladonema Six genes suggest broad conservation of upstream regulatory mechanisms in eye development.

Animals↗

Evolution of striated muscle: jellyfish and the origin of triploblasty.

The larval and polyp stages of extant Cnidaria are bi-layered with an absence of mesoderm and its differentiation products. This anatomy originally prompted the diploblast classification of the cnidarian phylum. The medusa stage, or jellyfish, however, has a more complex anatomy characterized by a swimming bell with a well-developed striated muscle layer. Based on developmental histology of the hydrozoan medusa this muscle derives from the entocodon, a mesoderm-like third cell layer established at the onset of medusa formation. According to recent molecular studies cnidarian homologs to bilaterian mesoderm and myogenic regulators are expressed in the larval and polyp stages as well as in the entocodon and derived striated muscle. Moreover striated and smooth muscle cells may have evolved directly and independently from non-muscle cells as indicated by phylogenetic analysis of myosin heavy chain genes (MHC class II). To accommodate all evidences we propose that striated muscle-based locomotion coevolved with the nervous and digestive systems in a basic metazoan Bauplan from which the ancestors of the Ctenophora (comb jellyfish), Cnidaria (jellyfish and polyps), as well as the Bilateria are derived. We argue for a motile tri-layered cnidarian ancestor and a monophyletic descent of striated muscle in Cnidaria and Bilateria. As a consequence, diploblasty evolved secondarily in cnidarian larvae and polyps.

Animals↗

A randomized paired comparison trial of cutaneous treatments for acute jellyfish (Carybdea alata) stings.

The objective of the study was to compare cutaneous treatments (heat, papain and vinegar) for acute jellyfish (Carybdea alata) stings. Healthy adult volunteer subjects received a single-tentacle jellyfish sting on each forearm. One forearm was treated with hot-water immersion (40-41 degrees C). This was compared with the other forearm, which was randomized to a comparison treatment of papain meat tenderizer or vinegar. Pain was measured at 0, 2, 4, 6, 8, 10, 15, and 20 minutes using a 10-cm visual analog scale (VAS). For 25 subject runs, the average VAS scores at t = 0 were 3.6 cm (hot water) and 3.7 cm (comparison treatment). At t = 4 minutes (2 minutes after treatment had started), the differences between hot-water and comparison group VAS scores were 2.1 cm versus 3.2 cm, respectively. The mean difference between hot-water and comparison treatments was 1.1 cm (95% confidence interval, 0.6 to 1.6). At t = 20 minutes (the end of the study period), the differences between hot-water and comparison group VAS scores were 0.2 cm versus 1.8 cm, respectively. The mean difference between hot-water and comparison treatments was 1.6 cm (95% confidence interval, 0.9 to 2.3). This study suggests that the most efficacious initial treatment for C alata jellyfish envenomation is hot-water immersion to the afflicted site.

Acetic Acid↗

In vitro and in vivo evaluation of a jellyfish valve for practical use.

A practical model (Model-1) of a jellyfish valve was developed, which was composed of a valve seat and a flexible membrane. The valve seat has 12 spokes to hold the membrane, and is made of solution-cast polyurethane coated with segmented polyurethane or Cardiothane. The flexible membrane is 200 microns thick, and made of segmented polyurethane or Cardiothane by a casting method. The valves were built into a sac type blood pump. In mock circulation tests, this jellyfish valve revealed performance superior to Bjork-Shiley (B-S) valves. No stagnation point was observed in the flow visualization study, and durability testing is ongoing beyond 7.5 months. The valves were used in animal artificial heart experiments for up to 112 days with good performance. No thrombi were formed on the valve membrane or around the spokes. Although a ring thrombus was observed behind the valve, it would be prevented by perfect adhesion of the valve seat to the blood pump. The plasma free hemoglobin level was less than 2 mg/dl during these experiments. These results suggest that a jellyfish valve (Model-1) is useful in ventricular assist devices, and in short-term bridge use of a total artificial heart.

Animals↗

Fabrication of a jellyfish valve for use in an artificial heart.

For a valve to be fabricated seamlessly into an artificial heart (AH) blood pump, a jellyfish valve has been developed, in which a thin membrane is fixed at the center of a valve seat having several spokes to protect against prolapse of the membrane. The valve is superior in performances to a Björk-Shiley valve, and reveals good blood compatibility. The valve would be very useful not only for AH animal study, but for future clinical use in infants to adults. Several institutions are already trying the valve. In this paper, the fabrication of the jellyfish valve is introduced, and in vitro and in vivo results summarized. A computer aided design (CAD) system was developed to cut a male wax mold of the valve seat. The input parameters to the CAD are diameter, height, thickness of rim, number of spokes, width and thickness of spokes, etc. Jellyfish valves with diameters of 4 to 27 mm have already been fabricated for many types of AHs and assist pumps.

Animals↗

Severe delayed cutaneous reaction due to Mediterranean jellyfish (Rhopilema nomadica) envenomation.

During summer, Mediterranean Sea waters are invaded by a species of jellyfish designated as Rhopilema nomadica. Their tentacles contain numerous nematocysts loaded with a toxin that causes envenomation, usually expressed as immediate appearance of redness, burning sensation and papulovesicular eruption in the affected skin. We report a lady with a severe delayed reaction due to jellyfish envenomation that developed 2 days after contact with jellyfish tentacles.

Adult↗