Jellyfish Sting Newsletters: Number 31 - July 2004
Significant Papers Published
Ramasamy S, Isbister GK, Seymour JE, Hodgson WC. The in vivo cardiovascular effects of box jellyfish Chironex fleckeri venom in rats: efficacy of pre-treatment with antivenom, verapamil and magnesium sulphate. Toxicon 43;685-690 2004.
Using a new technique to extract venom from the nematocysts, the efficacy of CSL box jellyfish antivenom (AV) and adjunct therapies, verapamil and magnesium sulfate (MgSO4), were investigated against the in vivo cardiovascular effects of Chironex fleckeri venom in anesthetized rats. C. fleckeri venom (30μg/kg; i.v.) produced a transient hypertensive response followed by hypotension and cardiovascular collapse within 4 minutes of administration. Prophylactic treatment of anesthetized rats with CSL box jellyfish AV (3000 U/kg; i.v.) did not have any effect on the venom-induced pressor response, but prevented cardiovascular collapse in four out of 10 animals. Administration of verapamil (20 mM@0.25 ml/min; i.v.) either alone or in combination with AV, did not have any effect on the C. fleckeri venom-induced pressor response nor the consequent hypotension or cardiovascular collapse of animals. However, the administration of verapamil negated the partially protective effects of AV. Concurrent artificial respiration of animals with the above treatments did not attenuate the C. fleckeri venom-induced cardiovascular effects. MgSO4 (0.05-0.07 M@0.25 ml/min; i.v.) alone did not have any effect on the venom-induced pressor response nor the consequent cardiovascular collapse of animals. However, although combined AV and MgSO4 administration could not inhibit the transient pressor effect following the administration of C. fleckeri venom, it prevented cardiovascular collapse in all animals. For the first time, the cardiovascular effects of a C. fleckeri venom sample free of tentacular contamination and the potential of MgSO4 as an adjunct therapy for the treatment of potentially fatal C. fleckeri envenomings.
Dr. Burnett has several problems with this paper and has forwarded a letter to the Toxicon editor which has been accepted, will be published next winter and be reviewed here in a year. Their “new” method uses glass beads which can absorb active toxin (unpublished data, our laboratory) and thus the authors do not know what venom principles were deleted or altered. Their dose of verapamil was too small to achieve an effect and they cited papers as supporting data which used the same venom preparatory technique they criticized others for using.
Our group has published extensively for over 20 years on the efficacy of verapamil in animals to counteract only the cardiotoxic action of jellyfish venoms. Yet three groups have criticized this conclusion. One used the wrong verapamil isomer and the other two-employed doses to small to be effective. The effectivity of L-verapamil isomer was confirmed by Dr. Lyndon Llewelyn, (now of the Australia Institute of Marine Sciences, Townsville), myself and Dr. R. Endean in the latter’s laboratory in the late 70’s or early 80’s. Thus, positive results have been seen by more than one research team.
In one of the other two papers, which used suboptimal verapamil doses, a toxic inhalant anesthetic, which the manufacturer said was contraindicated in the face of verapamil, was also in the protocol. As a result when the researchers tried to establish a dose schedule, arrythmias appeared before the verapamil dose matched the one we had employed. Those current authors hadn’t cited the reference in which we established our dose schedule. Thus, none of these investigations reported a positive effect because they did not have sufficient verapamil in their animals.
Additionally, my bias would be that careful bag respiration would overcome the initial venom induced collapse but only for a short time. Other agents besides verapamil will be needed to correct the noncardiac defects of the venom.
I cannot be sure of the antivenom’s efficacy because it is produced heterogeneously. After working in this field for a long time, I still meet people who think our problems here are easy. Wrong! They are incredibly complicated.
Two more cases of recurrent eruptions following a single sting have appeared on the American South Atlantic coast. Both patients were female and had a linear, pruritic eruption (no pain) exactly where the earlier one was and where the sting occurred.
Another 7-year-old female stung on the left foot in the Maldives on June 10, 2004. She developed a painful, edematous, inflamed local reaction. She received an ibuprofen derivative and topical anesthetic for three days. A second local eruption followed several days later.
A South African male experienced a recurrent pruritic eruption on the foot where tentacle contact occurred.
Dr. Melissa Strogatz reports a 6-year old Bermuda girl who developed a low fever and a recurrent thigh eruption at the site of a sting by a clear jellyfish in late August 2004. Her recurrent thigh lesion typically was only pruritic.
We now add 1 male and 4 female patients with this disorder which corroborates the female prominence.
A newspaper reporter in Asbury Park, NJ noted a lot of sychomedusans presumably Chrysaora or Cyanea this summer.
The Chesapeake Bay has had a dearth of jellies for the third straight year-most unusual! Our water in August was clarified presumably by a mussel, Mytilopsis leucophaeata, which appeared in millions. The presence of this filter feeder plus a dimunition of phosphates from restriction of fertilizer has resulted in more sea grass and crabs. The water clarification could be due to removal of plankton including jellyfish larvae as well as detritus.
We saw a case of transient (45 min) dysphonia in a male swimmer who went through a swarm of small Physalia off Ft. Lauderdale, Fla. last December. His mouth was stung, a small blue-black tentacle adhered to his shoulder and his tongue swelled.
John Walker of Westmead, New South Wales, Australia says that schistosome dermatitis occurs off their rocky shores where the molluscum host is a pulmonatic limpet, Siphonarea dentculator. He also thinks that Seabathers’ eruption appears in coastal pools on the eastern beaches of Sydney. He sees the disorder in the winter and most, not all, lesions are covered by clothing. He plans to pursue the exact cause next year.
Dr. Junaid Alam of Karachi writes that their beaches had had a multitude of Physalia stings. In May 2003, 60 stings per day; mid June to mid July = 250 daily; third week of July 90; last week of July 55 and 15 for early August. An oil spill later in 2003 resulted in a low population of medusae arriving in mid July 2004. They disappeared within a month. Quite a difference!
A young male stung on the finger in British Columbia by Chrysaora developed headache and a horizontal double vision which persisted for several days. He thought he rubbed his eyes with a nematocyst laden finger.
Another 35-year old male developed a conjunctival scarring, which resulted in occasional tearing lasting more than 15 years.
A 6-year old girl developed persistent (over 3 years) telangiectasia over an arm and a shoulder-the site of tentacle contact at Myrtle Beach.
There were multiple P. utriculus stings near Goukamma Beach, Knysona District, Union of South Africa, in mid February.
Angel Yanagihara put on the Internet that “we have made significant progress in elucidating the composition and the mechanism of action of the Hawaiian box jellyfish (Carybdea alata) venom. We have isolated and partially characterized a novel hemolytic lectin like glycoprotein and discovered a venom component accelerating the appearance of acetylcholine receptors on developing cultured frog skeletal muscle cells.” Other factors in the venom include proteolytic and neurotoxic agents. Finally, she also has a rapid purification protocol specifically optimized for separation of one of several hemolytic compounds.