Jellyfish Envenomation Research Articles

Protective effects of batimastat against hemorrhagic injuries in delayed jellyfish envenomation syndrome models

Previously, we established delayed jellyfish envenomation syndrome (DJES) models and proposed that the hemorrhagic toxins in jellyfish tentacle extracts (TE) play a significant role in the liver and kidney injuries of the experimental model. Further, we also demonstrated that metalloproteinases are the central toxic components of the jellyfish Cyanea capillata (C. capillata), which may be responsible for the hemorrhagic effects. Thus, metalloproteinase inhibitors appear to be a promising therapeutic alternative for the treatment of hemorrhagic injuries in DJES.In this study, we examined the metalloproteinase activity of TE from the jellyfish C. capillata using zymography analyses. Our results confirmed that TE possessed a metalloproteinase activity, which was also sensitive to heat. Then, we tested the effect of metalloproteinase inhibitor batimastat (BB-94) on TE-induced hemorrhagic injuries in DJES models. Firstly, using SR-based X-ray microangiography, we found that BB-94 significantly improved TE-induced hepatic and renal microvasculature alterations in DJES mouse model. Secondly, under synchrotron radiation micro-computed tomography (SR-μCT), we also confirmed that BB-94 reduced TE-induced hepatic and renal microvasculature changes in DJES rat model. In addition, being consistent with the imaging results, histopathological and terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL)-like staining observations also clearly corroborated this hypothesis, as BB-94 was highly effective in neutralizing TE-induced extensive hemorrhage and necrosis in DJES rat model.Although it may require further clinical studies in the near future, the current study opens up the possibilities for the use of the metalloproteinase inhibitor, BB-94, in the treatment of multiple organ hemorrhagic injuries in DJES.

Jellyfish Envenomation Presenting with Delayed Identical Cutaneous Lesions in a Mother and Child.

Jellyfish envenomation can present with local cutaneous lesions both immediate and delayed. While the immediate reaction is toxin mediated, an immune mechanism is responsible for the delayed eruptions. This is a report of a mother and child who developed identical papular lesions in a bizarre, linear distribution after coming in contact with jellyfish almost simultaneously while on holiday. Histology showed focal basal cell degeneration along with peri-vascular and peri-appendageal lympho-mononuclear infiltrate. Both patients responded well to topical tacrolimus.

Detection of microvasculature alterations by synchrotron radiation in murine with delayed jellyfish envenomation syndrome

Using the tentacle extract (TE) from the jellyfish Cyanea capillata, we have previously established a delayed jellyfish envenomation syndrome (DJES) model, which is meaningful for clinical interventions against jellyfish stings. However, the mechanism of DJES still remains unclear. Thus, this study aimed to explore its potential mechanism by detecting TE-induced microvasculature alterations in vivo and ex vivo. Using a third-generation synchrotron radiation facility, we, for the first time, directly observed the blood vessel alterations induced by jellyfish venom in vivo and ex vivo. Firstly, microvasculature imaging of whole-body mouse in vivo indicated that the small blood vessel branches in the liver and kidney in the TE-treated group, seemed much thinner than those in the control group. Secondly, 3D imaging of kidney ex vivo showed that the kidneys in the TE-treated group had incomplete vascular trees where distal vessel branches were partly missing and disorderly disturbed. Finally, histopathological analysis found that obvious morphological changes, especially hemorrhagic effects, were also present in the TE-treated kidney. Thus, TE-induced microvasculature changes might be one of the important mechanisms of multiple organ dysfunctions in DJES. In addition, the methods we employed here will probably facilitate further studies on developing effective intervention strategies against DJES.

Recurrent Dermatitis and Dermal Hypersensitivity Following a Jellyfish Sting: A Case Report and Review of Literature

Jellyfish envenomation often causes an immediate painful vesiculopapular eruption. Less commonly it can cause a type IV allergic hypersensitivity that manifests with delayed or recurrent cutaneous lesions at the primary site or distant from the primary site. These secondary reactivations may be related to high antijellyfish immunoglobulin levels, intracutaneously sequestered antigen, or cross-reacting venom. Immunomodulators such as pimecrolimus and tacrolimus and topical and intralesional corticosteroid therapy decrease this recurrent dermatitis. We report a case of a 9-year-old girl with a recurrent jellyfish dermatitis lasting more than 1 year after the initial envenomation. The dermatitis finally resolved after treatment with tacrolimus and intralesional triamcinolone acetonide therapy.

Box jellyfish envenomation: case report of effective lemon and oil emulsion treatment

Box jellyfish are highly venomous and numerous possible treatments for envenomation have already been reported in the published literature. The hand of a 55-year-old scuba diver was stung in the Gulf of Guinea resulting in two crops of coalescing vesicles with intense pain and lymphadenopathy. Traditional therapies such as hot water, cold packs and acetic acid were ineffective. Symptoms were rapidly relieved after the application of a lemon-oil emulsion balm. Treatments for jellyfish envenomation generally aim to either denature the jellyfish venom or prevent the discharge of the venom. Lemon-oil emulsion therapy has not yet been reported in the published literature but may be an economical and novel treatment for box jellyfish envenomation.

Interventions for the symptoms and signs resulting from jellyfish stings.

Jellyfish envenomations are common amongst temperate coastal regions and vary in severity depending on the species. Stings result in a variety of symptoms and signs, including pain, dermatological reactions and, in some species, Irukandji syndrome (including abdominal/back/chest pain, tachycardia, hypertension, sweating, piloerection, agitation and sometimes cardiac complications). Many treatments have been suggested for the symptoms and signs of jellyfish stings. However, it is unclear which interventions are most effective. To determine the benefits and harms associated with the use of any intervention, in both adults and children, for the treatment of jellyfish stings, as assessed from randomised trials. We searched the following electronic databases in October 2012 and again in October 2013: the Cochrane Central Register of Controlled Trials (CENTRAL;The Cochrane Library, Issue 9, 2013); MEDLINE via Ovid SP (1948 to 22 October 2013); EMBASE via Ovid SP (1980 to 21 October 2013); and Web of Science (all databases; 1899 to 21 October 2013). We also searched reference lists from eligible studies and guidelines, conference proceedings and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and contacted content experts to identify trials. We included randomised controlled trials that compared any intervention(s) to active and/or non-active controls for the treatment of symptoms and signs of jellyfish sting envenomation. No language, publication date or publication status restrictions were applied. Two review authors independently conducted study selection and data extraction and assessed risk of bias using a standardised form. Disagreements were resolved by consensus with a third review author when necessary. We included seven trials with a total of 435 participants. Three trials focused on Physalia (Bluebottle) jellyfish, one trial on Carukia jellyfish and three on Carybdea alata (Hawaiian box) jellyfish. Two ongoing trials were identified.Six of the seven trials were judged as having high risk of bias. Blinding was not feasible in four of the included trials because of the nature of the interventions. A wide range of interventions were assessed across trials, and a wide range of outcomes were measured. We reported results from the two trials for which data were available and reported the effects of interventions according to our definition of primary or secondary outcomes.Hot water immersion was superior to ice packs in achieving clinically significant (at least 50%) pain relief at 10 minutes (one trial, 96 participants, risk ratio (RR) 1.66, 95% confidence interval (CI) 1.01 to 2.72; low-quality evidence) and 20 minutes (one trial, 88 participants, RR 2.66, 95% CI 1.71 to 4.15; low-quality evidence). No statistically significant differences between hot water immersion and ice packs were demonstrated for dermatological outcomes.Treatment with vinegar or Adolph's meat tenderizer compared with hot water made skin appear worse (one trial, 25 participants, RR 0.31, 95% CI 0.14 to 0.72; low-quality evidence).Adverse events due to treatment were not reported in any trial. This review located a small number of trials that assessed a variety of different interventions applied in different ways and in different settings. Although heat appears to be an effective treatment for Physalia (Bluebottle) stings, this evidence is based on a single trial of low-quality evidence. It is still unclear what type of application, temperature, duration of treatment and type of water (salt or fresh) constitute the most effective treatment. In addition, these results may not apply to other species of jellyfish with different envenomation characteristics. Future research should further assess the most effective interventions using standardised research methodology.

Public Library of Science

Worldwide there are more than 10,000 reported jellyfish stings annually that can potentially cause local dermatonecrosis and systemic symptoms including cardiovascular instability, respiratory distress, and anaphylaxis. When dermal tissue is exposed to jellyfish venom, there is a significant inflammatory reaction and upregulation of matrix metalloproteinase (MMP) activity. Other than its use as an antibiotic, tetracycline is also an effective metalloproteinase inhibitor but has never been studied as a topical treatment for jellyfish stings. This study investigated the role of MMP activity in dermal toxicity after a sting from the Nemopilema nomurai Scyphozoan jellyfish and the ability of tetracycline to inhibit the clinical sequelae after envenomation. After treating human keratinocyte and mouse fibroblast models with isolated N nomurai jellyfish venom and different concentrations of tetracycline, the investigators measured MMP activity with gelatin zymography, electrophoresis, and Western blot analysis. Additionally, the investigators performed in vivo experiments using envenomated rabbit models treated with lanolin cream alone or containing tetracycline. Finally, the authors analyzed the histological effects of envenomated rabbit skin after treatment with tetracycline. After venom exposure, MMP activity significantly increased but was suppressed in the presence of tetracycline. In the in vivo rabbit models, the maximal skin lesion size was noted after 24 hours and steadily decreased over a period of 48 hours. Topical application of lanolin cream with tetracycline to envenomated areas of skin significantly reduced maximal lesion size at 24 hours. Additionally, histological analysis showed a decreased level of hemorrhage and neutrophilic infiltration for skin treated with tetracycline. This study suggested that tetracycline is able to downregulate MMP activity induced by N nomurai jellyfish venom and can also decrease maximal lesion size when applied topically. The authors conclude that tetracycline creams may be beneficial as a first-aid dermal treatment after jellyfish envenomation. Limitations of the study include applicability to human skin and accessibility to tetracycline cream shortly after jellyfish envenomation. (PLoS One. 2013;8:e57658) C Kang, YB Jin, J Kwak, et al.

Jellyfish envenomation in an ocean swimmer

A healthy 28-year-old man presented to the Emergency Department (ED) one hour after the sudden onset of sharp, right-sided leg pain that occurred while swimming in the North Atlantic Ocean. He also reported shooting pains radiating toward the groin, worsened by weight-bearing and walking. On examination, he was afebrile with a mild tachycardia and hypertension. Several curvilinear, urticarial lesions, surrounded by a 3 cm by 15 cm region of erythema, were seen on the right lower extremity (Fig. 1). The clinical picture was consistent with a jellyfish sting. Cnidariae, which include jellyfish, possess specialized stinging apparatus called nematocysts, which are concentrated on the tentacles, and which rapidly deliver venom. Cnidarian envenomation should be suspected and treated in patients with painful pruritus after sea-bathing, even if the organism is not directly observed. When left untreated, jellyfish stings may result in scarring, anaphylaxis, or even death in some cases due to a syndrome of systemic pain, hypertension, cardiotoxicity, and pulmonary edema [1]. Species with the most potent venoms largely inhabit IndoPacific waters, but this potentially fatal reaction has been reported on the US coast [2]. Current evidence supports treating jellyfish stings by mechanically scraping the lesions to remove embedded nematocysts, and irrigating the area involved with hot water to deactivate heat-labile venoms [3, 4]. Acetic acid is thought to inactivate the nematocysts of diverse species, and to inhibit the discharge of venom, but its clinical effectiveness has been contested [5]. Because most jellyfish envenomation cases occur in remote locations, emergency personnel should recognize local marine fauna, and direct empiric treatment to these species after suspected stings. The patient did not recall seeing the organism. Scrapings of the wound contained numerous visible nematocysts. The wound was irrigated with an 8 % acetic acid solution, and a topical steroid was applied for symptomatic relief. At 10-day follow-up, the lesions had resolved with moderate post-inflammatory hyperpigmentation, and the radiating pain had subsided.

Mitochondrial dysfunction contributes to the cytotoxicity induced by tentacle extract from the jellyfish Cyanea capillata in rat renal tubular epithelial NRK-52E cells

Our previous studies have shown that tentacle extract (TE) from the jellyfish Cyanea capillata could induce a delayed jellyfish envenomation syndrome with severe multiple organ dysfunctions, among which renal injury with tubular necrosis seemed to be most serious. So, in this study, we aimed to explore the toxic effect of TE on rat renal tubular epithelial NRK-52E cells. Based on the previous findings that TE could cause oxidative damage in erythrocytes, the effects of TE on cell oxidative stress conditions, including ROS production and lipid peroxidation, and mitochondrial dysfunction associated with cell death were investigated in NRK-52E cells. The results showed that TE caused cell morphological change and decreased cell viability through induction of apoptosis and necrosis in NRK-52E cells. Meanwhile, ROS overproduction and mitochondrial membrane potential decrease were found before the cell death occurred. It was concluded that TE could induce cytotoxicity, especially apoptosis and necrosis, in NRK-52E cells, and mitochondrial dysfunction and ROS overproduction might play important roles in the process of cell injury and death.

Jellyfish Stings and Their Management: A Review

Jellyfish (cnidarians) have a worldwide distribution. Despite most being harmless, some species may cause local and also systemic reactions. Treatment of jellyfish envenomation is directed at: alleviating the local effects of venom, preventing further nematocyst discharges and controlling systemic reactions, including shock. In severe cases, the most important step is stabilizing and maintaining vital functions. With some differences between species, there seems to be evidence and consensus on oral/topical analgesics, hot water and ice packs as effective painkillers and on 30 s application of domestic vinegar (4%–6% acetic acid) to prevent further discharge of unfired nematocysts remaining on the skin. Conversely, alcohol, methylated spirits and fresh water should be carefully avoided, since they could massively discharge nematocysts; pressure immobilization bandaging should also be avoided, as laboratory studies show that it stimulates additional venom discharge from nematocysts. Most treatment approaches are presently founded on relatively weak evidence; therefore, further research (especially randomized clinical trials) is strongly recommended. Dissemination of appropriate treatment modalities should be deployed to better inform and educate those at risk. Adequate signage should be placed at beaches to notify tourists of the jellyfish risk. Swimmers in risky areas should wear protective equipment.

A case of immediate and delayed reactions after contact with a venomous mauve-stinger jellyfish in a diabetic patient

A contact with the venoms produced by a pelagic jellyfish type, known as Pelagia noctiluca, can induce both local and general symptoms. We report here a case of jellyfish envenomation with a mauve-stinger in a diabetic patient who developed localized skin involvement, delayed systemic reaction and hyperglycemia. To our knowledge this is the first report of this kind in literature. The patient, an adult male tourist with type I diabetes, was stung on the forehead by a mauve-stinger jellyfish while swimming on the Maltese coast in summer 2012. Local symptoms were initially of an erythematous, edematous and a vesicular topical lesion in the forehead region, followed by massive eye swelling 72 hours after the incident. In addition, his normally well-controlled diabetes was affected, with an unusual severe episode of hyperglycemia that did not respond readily to alterations in his insulin regime. <i>Pelagia noctiluca</i> is a jellyfish known for its strong cytotoxic properties. We hypothesize that the stress response, following the jellyfish attack could have triggered a metabolic response and the consequences seen in this person with diabetes. The reaction described suggests that people with diabetes stung by <i>P. noctiluca</i> should monitor their glucose levels closely and in some cases seek treatment with more specialized endocrinology services.

Multiple organ dysfunction: A delayed envenomation syndrome caused by tentacle extract from the jellyfish Cyanea capillata

The delayed jellyfish envenomation syndrome (DJES) with serious multiple organ dysfunction or systemic damages, generally developed 2 h after jellyfish stings, deserves special attention for it is very meaningful to the clinical interventions. To set up a DJES model as well as to obtain more details about its process, an integrative approach, including clinical chemistry, pathology and immunohistochemistry, was conducted to simultaneously monitor the effects of tentacle extract (TE) from the jellyfish Cyanea capillata on the vital target organs (heart, lung, liver and kidney). Our results showed that the TE from C. capillata could induce diverse toxic effects on these organs, among which the liver and kidney injuries seemed to be more serious than cardiopulmonary injuries and might be the leading causes of death in rats with DJES. In summary, we have established a DJES model with multiple organ dysfunction, which could facilitate the research on its underlying mechanism as well as the development of specific prevention or therapy strategies against jellyfish envenomation. The application of this model suggested that the possible mechanism of DJES might be attributed to the synergy of cytotoxicity, vasoconstriction effect and other specific target organ toxicities of jellyfish venom.

Review of Fatal and Severe Cases of Box Jellyfish Envenomation in Thailand

The study aimed to describe severe and fatal cases of box jellyfish stings in Thailand. Medical records were reviewed and patients, relatives, health staffs, and witnesses were interviewed. The pictures of suspected box jellyfish were sent via e-mail to experts in the toxic jellyfish network for further identification. There were at least 8 cases of box jellyfish envenomation, with 4 fatal and 4 near-fatal cases. There were an equal number of male and female patients from 4 to 26 years of age. In each case, there was immediate severe pain followed by systemic reactions. Immediately after exposure to the sting, 7 victims collapsed experiencing severe pain at the tentacle marks, respiratory failure, and cardiac arrest. All patients had tentacle marks on their bodies. In none of the fatal cases was vinegar applied to the tentacle marks as first aid, but 3 out of the 4 near-fatal cases were treated with a vinegar application.

Target organ identification of jellyfish envenomation using systemic and integrative analyses in anesthetized dogs

Proper treatment of jellyfish envenomed patients can be successfully achieved only from an understanding of the overall functional changes and alterations in physiological parameters under its envenomation. The majority of previous investigations on jellyfish venoms have covered only a couple of parameters at a time. Unlike most other fragmentary jellyfish studies, we employed an integrative toxicological approach, including hemodynamics, clinical chemistry and hematology analyses, using N. nomurai jellyfish venom (NnV) in dogs. After the baseline measurements for mean arterial pressure (MAP), cardiac output (CO) and heart rate (HR), NnV was intravenously administered to the dogs at doses of 0.1 or 0.3 mg/kg body weight. The dogs showed significant decreases in MAP (− 27.4 ± 3.7 and − 48.1 ± 9.9 mm Hg), CO (− 1.1 ± 0.1 L/min and − 1.0 ± 0.2 L/min), and HR (− 4.5 ± 0.3 and − 9.9 ± 3.1 beats/min) comparing with the respective baseline controls. The onset of systemic hypotension and bradycardia occurred within 1 min of NnV injection and they lasted for 1–35 min, depending on the NnV doses. Interestingly, serum biochemical analyses of envenomed dogs exhibited dramatic increases of alkaline phosphatase (ALP), creatine phosphokinase (CPK), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indicating its possible target organs. In conclusion, we have demonstrated simultaneously, for the first time, the multiple organ toxicities (cardiotoxic, myotoxic and hepatotoxic) of a scyphozoan jellyfish venom. Based on these results, an integrative toxinological approach using dogs appears to be effective in predicting jellyfish venom toxicities and designing their therapeutic strategies. We expect this method can be applied to other jellyfish venom research as well.

Too sympathetic? Role of sympathoexcitation in Takotsubo cardiomyopathy

Takotsubo cardiomyopathy is classically described as sudden and transient left ventricular apical ballooning in the absence of significant coronary artery disease. First described by Dote et al, 1 Dote K. Sato H. Tateishi H. Uchida T. Ishihara M. Myocardial stunning due to simultaneous multivessel coronary spasms: a review of 5 cases. J Cardiol. 1991; 21: 203-214 PubMed Google Scholar the cardiomyopathy was named “Takotsubo” because the narrow neck and round-bottomed left ventricle resemble a traditional Japanese octopus trap. Since the initial description of the condition, patients with transient left ventricular dysfunction have been identified with both the typical apical ballooning (AB) pattern and an alternative mid-left ventricular ballooning (MB) pattern, the “inverted Takotsubo.” 2 Kurowski V. Kaiser A. von H.K. et al. Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis. Chest. 2007; 132: 809-816 Crossref PubMed Scopus (432) Google Scholar Patients present with symptoms resembling those of acute myocardial infarction, including chest pain, ST-segment elevation, and elevated cardiac enzymes. A high proportion of patients are women who develop symptoms after episodes of high emotion (after receiving bad news or being in a severe argument), and the disorder has captured the public's imagination with names such as “broken heart syndrome.” The interest of the medical profession also has been piqued, with almost 400 hits in PubMed for a search of “Takotsubo AND 2009.” Differential heart rate dynamics in transient left ventricular apical and midventricular ballooningHeart RhythmVol. 7Issue 12PreviewThe aim of the present study was to assess potential differences in cardiac autonomic nervous modulation in patients with transient left ventricular apical ballooning syndrome (AB) and the midventricular variant (MB) of this syndrome. Full-Text PDF To the Editor—Takotsubo Cardiomyopathy: A Role for Magnesium?Heart RhythmVol. 7Issue 12PreviewI read with interest the original research article on the role of sympathoexcitation in Takotsubo cardiomyopathy by Raj.1 Both classic and inverted patterns of stress cardiomyopathy have been reported in association with disorders associated with catecholamine excess, including pheochromocytoma, high-dose epinephrine infusion, and Irukandji syndrome following jellyfish envenomation.2,3 Full-Text PDF

To the Editor—Takotsubo Cardiomyopathy: A Role for Magnesium?

I read with interest the original research article on the role of sympathoexcitation in Takotsubo cardiomyopathy by Raj.1 Both classic and inverted patterns of stress cardiomyopathy have been reported in association with disorders associated with catecholamine excess, including pheochromocytoma, high-dose epinephrine infusion, and Irukandji syndrome following jellyfish envenomation.2,3

Irukandji Syndrome: A critique of current nursing management at The Townsville Hospital Emergency Department

Summary Background Irukandji Syndrome is caused by a potentially lethal jellyfish envenomation. Despite the low incidence, the condition is associated with possible life-threatening cardiovascular complications that make it difficult to manage in emergency departments. Managing Irukandji Syndrome is important for many emergency departments across Australia, particularly in North Queensland, the Northern Territory, and Western Australia. Methods The aim of this quality project was to identify current management, practices and nursing knowledge in the only emergency department in the regional city of Townsville, Queensland. This was undertaken via chart audit of all presentations over a 2-year period and a survey of nursing staff. Results Fifteen cases of Irukandji Syndrome were identified. Medical treatment options included use of opioids and magnesium for symptom control. Magnesium as a treatment option was used in 80% of cases. Chart audit indicated that in 20% of cases nursing management did not follow approved clinical guidelines for treatment and monitoring. The survey of nursing staff indicated a knowledge deficit with respect to the signs and symptoms of Irukandji Syndrome, standards of clinical monitoring, clinical assessment, and overall care provided. Conclusions To improve care of Irukandji Syndrome in the emergency department, in-service education, implementation of tendon reflex assessment for patients receiving magnesium therapy, and the development of a specific clinical documentation are recommended.

Jellyfish Envenomation Events in Selected Coastal Provinces of Thailand 1998-2008

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Cutaneous granulomatous reaction caused by Atlantic jellyfish envenomation treated with etanercept

Cutaneous granulomatous reaction caused by Atlantic jellyfish envenomation treated with etanercept

Jellyfish and other cnidarian envenomations cause pain by affecting TRPV1 channels

Cnidarian envenomations cause a burning-pain sensation of which the underlying mechanisms are unknown. Activation of TRPV1, a non-selective cation channel expressed in nociceptive neurons, leads to cell depolarisation and pain. Here, we show in vitro and in vivo evidence for desensitization-dependent TRPV1 activation in cnidarian envenomations. Cnidarian venom induced a nociceptive reactivity, comparable to capsaicin, in laboratory rats, which could be reduced by the selective TRPV1 antagonist, BCTC. These findings are the first to explain at least part of the symptomology of cnidarian envenomations and provide insights into the design of more effective treatments for this global public health problem.