Marine Envenomation in Okinawa: Overview and Treatment Concept.

Okinawa prefecture is a popular tourist destination due to its beaches and reefs. The reefs host a large variety of animals, including a number of venomous species. Because of the popularity of the reefs and marine activities, people are frequently in close contact with dangerous venomous species and, thus, are exposed to potential envenomation. Commonly encountered venomous animals throughout Okinawa include the invertebrate cone snail, sea urchin, crown-of-thorns starfish, blue-ringed octopus, box jellyfish, and fire coral. The vertebrates include the stonefish, lionfish, sea snake, and moray eel. Treatment for marine envenomation can involve first aid, hot water immersion, antivenom, supportive care, regional anesthesia, and pharmaceutical administration. Information on venomous animals, their toxins, and treatment should be well understood by prehospital care providers and physicians practicing in the prefecture.

Associative learning: Box jellyfish learns to avoid bumps.

Operant conditioning - learning to do something for a desired outcome - has never been convincingly demonstrated in Cnidaria. A study now shows that box jellyfish, Tripedalia cystophora, can learn to avoid bumping into an obstacle based on visual cues.

Associative learning in the box jellyfish Tripedalia cystophora.

Associative learning, such as classical or operant conditioning, has never been unequivocally associated with animals outside bilatarians, e.g., vertebrates, arthropods, or mollusks. Learning modulates behavior and is imperative for survival in the vast majority of animals. Obstacle avoidance is one of several visually guided behaviors in the box jellyfish, Tripedalia cystophora Conant, 1897 (Cnidaria: Cubozoa), and it is intimately associated with foraging between prop roots in their mangrove habitat. The obstacle avoidance behavior (OAB) is a species-specific defense reaction (SSDR) for T. cystophora, so identifying such SSDR is essential for testing the learning capacity of a given animal. Using the OAB, we show that box jellyfish performed associative learning (operant conditioning). We found that the rhopalial nervous system is the learning center and that T. cystophora combines visual and mechanical stimuli during operant conditioning. Since T. cystophora has a dispersed central nervous system lacking a conventional centralized brain, our work challenges the notion that associative learning requires complex neuronal circuitry. Moreover, since Cnidaria is the sister group to Bilateria, it suggests the intriguing possibility that advanced neuronal processes, like operant conditioning, are a fundamental property of all nervous systems.

Improved patient mortality predictions in emergency departments with deep learning data-synthesis and ensemble models.

The triage process in emergency departments (EDs) relies on the subjective assessment of medical practitioners, making it unreliable in certain aspects. There is a need for a more accurate and objective algorithm to determine the urgency of patients. This paper explores the application of advanced data-synthesis algorithms, machine learning (ML) algorithms, and ensemble models to predict patient mortality. Patients predicted to be at risk of mortality are in a highly critical condition, signifying an urgent need for immediate medical intervention. This paper aims to determine the most effective method for predicting mortality by enhancing the F1 score while maintaining high area under the receiver operating characteristic curve (AUC) score. This study used a dataset of 7325 patients who visited the Yonsei Severance Hospital's ED, located in Seoul, South Korea. The patients were divided into two groups: patients who deceased in the ED and patients who didn't. Various data-synthesis techniques, such as SMOTE, ADASYN, CTGAN, TVAE, CopulaGAN, and Gaussian Copula, were deployed to generate synthetic patient data. Twenty two ML models were then utilized, including tree-based algorithms like Decision tree, AdaBoost, LightGBM, CatBoost, XGBoost, NGBoost, TabNet, which are deep neural network algorithms, and statistical algorithms such as Support Vector Machine, Logistic Regression, Random Forest, k-nearest neighbors, and Gaussian Naive Bayes, as well as Ensemble Models which use the results from the ML models. Based on 21 patient information features used in the pandemic influenza triage algorithm (PITA), the models explained previously were applied to aim for the prediction of patient mortality. In evaluating ML algorithms using an imbalanced medical dataset, conventional metrics like accuracy scores or AUC can be misleading. This paper emphasizes the importance of using the F1 score as the primary performance measure, focusing on recall and specificity in detecting patient mortality. The highest-ranked model for predicting mortality utilized the Gaussian Copula data-synthesis technique and the CatBoost classifier, achieving an AUC of 0.9731 and an F1 score of 0.7059. These findings highlight the effectiveness of machine learning algorithms and data-synthesis techniques in improving the prediction performance of mortality in EDs.

Rapid and permanent cytotoxic effects of venom from Chiropsella bronzie and Malo maxima on human skeletal and cardiac muscle cells.

Jellyfish envenomation is a global public health risk; Cubozoans (box jellyfish) are a prevalent jellyfish class with some species causing potent and potentially fatal envenomation in tropical Australian waters. Previous studies have explored the mechanism of action of venom from the lethal Cubozoan Chironex fleckeri and from Carukia barnesi (which causes "Irukandji syndrome"), but mechanistic knowledge to develop effective treatment is still limited. This study performed an in-vitro cytotoxic examination of the venoms of Chiropsella bronzie and Malo maxima, two understudied species that are closely related to Chironex fleckeri and Carukia barnesi respectively. Venom was applied to human skeletal muscle cells and human cardiomyocytes while monitoring with the xCELLigence system. Chiropsella bronzie caused rapid cytotoxicity at concentrations as low as 58.8 µg/mL. Malo maxima venom caused a notable increase in cell index, a measure of cell viability, followed by cytotoxicity after 24-h venom exposure at ≥11.2 µg/mL on skeletal muscle cells. In contrast, the cardiomyocytes mostly showed significant increased cell index at the higher M. maxima concentrations tested. These findings show that these venoms can exert cytotoxic effects and Malo maxima venom mainly caused a sustained increase in cell index across both human cell lines, suggesting a different mode of action to Chiropsella bronzie. As these venoms show different real-world envenomation symptoms, the different cellular toxicity profiles provide a first step towards developing improved understanding of mechanistic pathways and novel envenomation treatment.

The Dermatological Effects of Box Jellyfish Envenomation in Stinging Victims in Thailand: Underestimated Severity.

INTRODUCTION: The dermatological effects of box jellyfish envenomation among stinging victims in Thailand are not well reported, particularly concerning chronic effects. For first aid, different recommendations indicate the necessity for the removal of tentacles in life-threatening situations. This study aimed to describe the dermatological effects of box jellyfish envenomation and propose recommendations regarding first aid for victims in urgent care or life-threatening situations. METHODS: Surveillance systems and Toxic Jellyfish Networks were established to improve detection and investigation. The networks investigated all severe victims of jellyfish envenomation. A retrospective study was conducted, and victims of stinging by box jellyfish investigated from 1999 to 2021 were included. RESULTS: One hundred and twenty-four victims were recorded. The majority of victims were males (55%), tourists (69%), and Thai nationals (49%). Direct contact had more severe consequences than indirect contact. Dermatological effects included edema, erythematous caterpillar track-like rash, blistering, bullae, papular eruption, necrosis, digital gangrene, recurrent dermatitis, dermal hypersensitivity, numbness, lichenification, hyperpigmentation, keloids, and scarring. Suffering and healing continued from several weeks to many years. Victims with multiple-tentacle box jellyfish stings had papular eruptions and greater severity of skin issues. All fatally envenomed victims collapsed within a few minutes and received incorrect/no first aid. The proposed first aid for life-threatening box jellyfish stings is continuous irrigation of the wound with vinegar for at least 30 s and initiation of cardiopulmonary resuscitation if there is no respiration or heartbeat. Tentacles often detach spontaneously, and removal is not always necessary, thus saving time. CONCLUSIONS: The findings provide input for improving diagnosis and treatment guidelines.

Apoptotic gene loss in Cnidaria is associated with transition to parasitism.

The phylum Cnidaria consists of several morphologically diverse classes including Anthozoa, Cubozoa, Hydrozoa, Polypodiozoa, Scyphozoa, Staurozoa, and Myxozoa. Myxozoa comprises two subclasses of obligate parasites-Myxosporea and Malacosporea, which demonstrate various degrees of simplification. Myxosporea were previously reported to lack the majority of core protein domains of apoptotic proteins including caspases, Bcl-2, and APAF-1 homologs. Other sequenced Cnidaria, including the parasite Polypodium hydriforme from Polypodiozoa do not share this genetic feature. Whether this loss of core apoptotic proteins is unique to Myxosporea or also present in its sister subclass Malacosporea was not previously investigated. We show that the presence of core apoptotic proteins gradually diminishes from free-living Cnidaria to Polypodium to Malacosporea to Myxosporea. This observation does not favor the hypothesis of catastrophic simplification of Myxosporea at the genetic level, but rather supports a stepwise adaptation to parasitism that likely started from early parasitic ancestors that gave rise to Myxozoa.

Application of wastewater-based surveillance and copula time-series model for COVID-19 forecasts.

The objective of this study was to develop a novel copula-based time series (CTS) model to forecast COVID-19 cases and trends based on wastewater SARS-CoV-2 viral load and clinical variables. Wastewater samples were collected from wastewater pumping stations in five sewersheds in the City of Chesapeake VA. Wastewater SARS-CoV-2 viral load was measured using reverse transcription droplet digital PCR (RT-ddPCR). The clinical dataset included daily COVID-19 reported cases, hospitalization cases, and death cases. The CTS model development included two steps: an autoregressive moving average (ARMA) model for time series analysis (step I), and an integration of ARMA and a copula function for marginal regression analysis (step II). Poisson and negative binomial marginal probability densities for copula functions were used to determine the forecasting capacity of the CTS model for COVID-19 forecasts in the same geographical area. The dynamic trends predicted by the CTS model were well suited to the trend of the reported cases as the forecasted cases from the CTS model fell within the 99 % confidence interval of the reported cases. Wastewater SARS CoV-2 viral load served as a reliable predictor for forecasting COVID-19 cases. The CTS model provided robust modeling to predict COVID-19 cases.

Investigating the mechanism of photoisomerization in jellyfish rhodopsin with the counterion at an atypical position.

The position of the counterion in animal rhodopsins plays a crucial role in maintaining visible light sensitivity and facilitating the photoisomerization of their retinal chromophore. The counterion displacement is thought to be closely related to the evolution of rhodopsins, with different positions found in invertebrates and vertebrates. Interestingly, box jellyfish rhodopsin (JelRh) acquired the counterion in transmembrane 2 independently. This is a unique feature, as in most animal rhodopsins, the counterion is found in a different location. In this study, we used Fourier Transform Infrared spectroscopy to examine the structural changes that occur in the early photointermediate state of JelRh. We aimed to determine whether the photochemistry of JelRh is similar to that of other animal rhodopsins by comparing its spectra to those of vertebrate bovine rhodopsin (BovRh) and invertebrate squid rhodopsin (SquRh). We observed that the N-D stretching band of the retinal Schiff base was similar to that of BovRh, indicating the interaction between the Schiff base and the counterion is similar in both rhodopsins, despite their different counterion positions. Furthermore, we found that the chemical structure of the retinal in JelRh is similar to that in BovRh, including the changes in the hydrogen-out-of-plane band that indicates a retinal distortion. Overall, the protein conformational changes induced by the photoisomerization of JelRh yielded spectra that resemble an intermediate between BovRh and SquRh, suggesting a unique spectral property of JelRh, and making it the only animal rhodopsin with a counterion in TM2 and an ability to activate Gs protein.

A visual opsin from jellyfish enables precise temporal control of G protein signalling.

Phototransduction is mediated by distinct types of G protein cascades in different animal taxa: bilateral invertebrates typically utilise the Gαq pathway whereas vertebrates typically utilise the Gαt(i/o) pathway. By contrast, photoreceptors in jellyfish (Cnidaria) utilise the Gαs intracellular pathway, similar to olfactory transduction in mammals1. How this habitually slow pathway has adapted to support dynamic vision in jellyfish remains unknown. Here we study a light-sensing protein (rhodopsin) from the box jellyfish Carybdea rastonii and uncover a mechanism that dramatically speeds up phototransduction: an uninterrupted G protein-coupled receptor - G protein complex. Unlike known G protein-coupled receptors (GPCRs), this rhodopsin constitutively binds a single downstream Gαs partner to enable G-protein activation and inactivation within tens of milliseconds. We use this GPCR in a viral gene therapy to restore light responses in blind mice.

Managing an Unidentified Jellyfish Sting with Mixed Envenomation Syndrome at a Noncoastal Hospital: Is This a New Form of Jellyfish Envenomation?

Jellyfish stings are the most common cause of marine envenomation in humans. Various species of box jellyfish have been identified around Penang Island, Malaysia, and these include multitentacled and four-tentacled box jellyfish (class Cubozoa). The typical syndrome following envenomation from these jellyfish has been poorly documented, posing a greater challenge when managing an unidentified jellyfish sting from Penang Island. We report a case of a 32-y-old man from Penang Island who was stung by an unidentified jellyfish while walking into the sea. The patient reported that he felt an immediate and severe electric current‒like pain over both thighs, left flank, and left forearm, followed by chest discomfort and breathlessness. Vinegar was applied over the affected areas, and he was rushed to a hospital, where he was treated with analgesia, steroids, and antihistamine. He refused hospitalization and was discharged against medical advice. He then presented to a noncoastal hospital 377 km away in Kuala Lumpur on the following day with severe pain over the affected sites as well as chest discomfort, shortness of breath, and abdominal cramps. The electrocardiograph demonstrated features of Wolff-Parkinson-White. Serial blood test results showed elevated creatine kinase but normal troponin I levels. The patient was managed symptomatically over a period of 4 d and was discharged with cardiology follow-up. Appropriate health-seeking behavior needs to be emphasized. This case report provides an opportunity to document the signs and symptoms of envenomation from possibly an undescribed jellyfish species near the coastal waters of Penang Island.

Investigation of Best Practices for Venom Toxin Purification in Jellyfish towards Functional Characterisation.

The relative lack of marine venom pharmaceuticals can be anecdotally attributed to difficulties in working with venomous marine animals, including how to maintain venom bioactivity during extraction and purification. The primary aim of this systematic literature review was to examine the key factors for consideration when extracting and purifying jellyfish venom toxins to maximise their effectiveness in bioassays towards the characterisation of a single toxin.An up-to-date database of 119 peer-reviewed research articles was established for all purified and semi-purified venoms across all jellyfish, including their level of purification, LD50, and the types of experimental toxicity bioassay used (e.g., whole animal and cell lines). We report that, of the toxins successfully purified across all jellyfish, the class Cubozoa (i.e., Chironex fleckeri and Carybdea rastoni) was most highly represented, followed by Scyphozoa and Hydrozoa. We outline the best practices for maintaining jellyfish venom bioactivity, including strict thermal management, using the "autolysis" extraction method and two-step liquid chromatography purification involving size exclusion chromatography. To date, the box jellyfish C. fleckeri has been the most effective jellyfish venom model with the most referenced extraction methods and the most isolated toxins, including CfTX-A/B. In summary, this review can be used as a resource for the efficient extraction, purification, and identification of jellyfish venom toxins.

Localization of Multiple Jellyfish Toxins Shows Specificity for Functionally Distinct Polyps and Nematocyst Types in a Colonial Hydrozoan.

Hydractinia symbiolongicarpus is a colonial hydrozoan that displays a division of labor through morphologically distinct and functionally specialized polyp types. As with all cnidarians, their venoms are housed in nematocysts, which are scattered across an individual. Here, we investigate the spatial distribution of a specific protein family, jellyfish toxins, in which multiple paralogs are differentially expressed across the functionally specialized polyps. Jellyfish toxins (JFTs) are known pore-forming toxins in the venoms of medically relevant species such as box jellyfish (class Cubozoa), but their role in other medusozoan venoms is less clear. Utilizing a publicly available single-cell dataset, we confirmed that four distinct H. symbiolongicarpus JFT paralogs are expressed in nematocyst-associated clusters, supporting these as true venom components in H. symbiolongicarpus. In situ hybridization and immunohistochemistry were used to localize the expression of these JFTs across the colony. These expression patterns, in conjunction with known nematocyst type distributions, suggest that two of these JFTs, HsymJFT1c-I and HsymJFT1c-II, are localized to specific types of nematocysts. We further interpret JFT expression patterns in the context of known regions of nematogenesis and differential rates of nematocyst turnover. Overall, we show that JFT expression patterns in H. symbiolongicarpus are consistent with the subfunctionalization of JFT paralogs across a partitioned venom system within the colony, such that each JFT is expressed within a specific set of functionally distinct polyp types and, in some cases, specific nematocyst types.

Unique horizontal gaze control in the box jellyfish, Tripedalia cystophora.

All known cubozoans, box jellyfish, have a similar visual system. They possess four sensory structures called rhopalia, which carry-six eyes each. Two of these six eyes are true image-forming camera type eyes in several ways similar to vertebrate eyes. The rhopalia hang by a thin flexible stalk and in the distal end, there is a high-density crystal. In an earlier study of the Caribbean species Tripedalia cystophora, we showed that the crystals act as weights ensuring that the rhopalia are always upright no matter the orientation of the medusa and the vertical part of the visual field of the eyes thus kept relatively constant. Here we have examined the horizontal part of the visual field under different experimental conditions including different visual environments. We find that the horizontal gaze direction is largely controlled by the anatomy of the rhopalium and rhopalial stalk, similar to what has previously been shown for the vertical gaze direction. In a vertically oriented medusa, the rhopalia are kept with a 90° angle between them with the lower lens eyes (LLE) pointing inwards. This 90° shift is kept in horizontally swimming medusa, resulting in the left LLE gazing right, the right gazing left, the bottom gazing orally (backwards compared to swimming direction), and the top LLE gazing aborally (forwards compared to swimming direction). The light environment was manipulated to test if the visual input influences this seemingly strict horizontal gaze direction but even in complete darkness there is tight mechanistic control.

First record of fossil psocodeans in copula from mid-Cretaceous Burmese amber.

We report the first discovery of barklice preserved in copula from amber dating back to the mid-Cretaceous, thus documenting the oldest preserved reproductive behaviour of Psocodea. The new finding provides new insight into the evolution of copulatory behaviour in Trogiomorpha. Moreover, we describe and illustrate the new fossil material of Burmempheria densuschaetae (= Latempheria kachinensis) in the extinct family Empheriidae and Longiantennum fashengi in the extinct family Archaeatropidae, two diverse and widely distributed groups during the Cretaceous. No significant sexual dimorphism is recorded, apart from variation in size where males are larger. The taxonomy of Cretaceous empheriids from Burmese amber is revised and discussed.

Comparative Study of Toxic Effects and Pathophysiology of Envenomations Induced by Carybdea brevipedalia (Cnidaria: Cubozoa) and Nemopilema nomurai (Cnidaria: Scyphozoa) Jellyfish Venoms.

Jellyfish stings can result in local tissue damage and systemic pathophysiological sequelae. Despite constant occurrences of jellyfish stings in oceans throughout the world, the toxinological assessment of these jellyfish envenomations has not been adequately reported in quantitative as well as in qualitative measurements. Herein, we have examined and compared the in vivo toxic effects and pathophysiologic alterations using experimental animal models for two representative stinging jellyfish classes, i.e., Cubozoa and Scyphozoa. For this study, mice were administered with venom extracts of either Carybdea brevipedalia (Cnidaria: Cubozoa) or Nemopilema nomurai (Cnidaria: Scyphozoa). From the intraperitoneal (IP) administration study, the median lethal doses leading to the deaths of mice 24 h post-treatment after (LD50) for C. brevipedalia venom (CbV) and N. nomurai venom (NnV) were 0.905 and 4.4697 mg/kg, respectively. The acute toxicity (i.e., lethality) of CbV was much higher with a significantly accelerated time to death value compared with those of NnV. The edematogenic activity induced by CbV was considerably (83.57/25 = 3.343-fold) greater than NnV. For the evaluation of their dermal toxicities, the epidermis, dermis, subcutaneous tissues, and skeletal muscles were evaluated toxinologically/histopathologically following the intradermal administration of the venoms. The minimal hemorrhagic doses (MHD) of the venoms were found to be 55.6 and 83.4 µg/mouse for CbV and NnV, respectively. Furthermore, the CbV injection resulted in extensive alterations of mouse dermal tissues, including severe edema, and hemorrhagic/necrotic lesions, with the minimum necrotizing dose (MND) of 95.42 µg/kg body weight. The skin damaging effects of CbV appeared to be considerably greater, compared with those of NnV (MND = 177.99 µg/kg). The present results indicate that the toxicities and pathophysiologic effects of jellyfish venom extracts may vary from species to species. As predicted from the previous reports on these jellyfish envenomations, the crude venom extracts of C. brevipedalia exhibit much more potent toxicity than that of N. nomurai in the present study. These observations may contribute to our understanding of the toxicities of jellyfish venoms, as well as their mode of toxinological actions, which might be helpful for establishing the therapeutic strategies of jellyfish stings.

There's something in the water: an overview of jellyfish, their stings, and treatment.

An increasing presence on many beaches worldwide, jellyfish are a diverse group of Cnidarians equipped with stinging cells termed cnidocytes. Though few of the over 10,000 species are dangerous to humans, and most that are produce no more than a painful sting, some jellyfish can produce systemic symptoms and even death. Chironex fleckeri, the Australian box jellyfish, has a venom potent enough to kill in less than 10 minutes, and for which there is an antivenom of debatable efficacy. Stings from Carukia barnesi can cause Irukandji syndrome, characterised by severe pain and hypertension. Jellyfish stings have also been associated with Guillain-Barre syndrome and anaphylaxis. Though optimal treatment of stings remains controversial, after removal from the water and addressing any immediate life threats, the tentacles should be removed and the area washed, with seawater being the best choice due to its low likelihood of inducing further cnidocyte discharge. Hot water immersion may be beneficial for pain control for non-tropical jellyfish stings, and cold packs for tropical stings. In general, there is no consensus for the optimal treatment of jellyfish stings, and so further research is needed into species-specific guidelines and whether there are any overarching rules.

Environmental drivers of the occurrence and abundance of the Irukandji jellyfish (Carukia barnesi).

Understanding the links between species and their environment is critical for species management. This is particularly true for organisms of medical and/or economic significance. The 'Irukandji' jellyfish (Carukia barnesi) is well known for its small size, cryptic nature, and highly venomous sting. Being the namesake of the Irukandji syndrome, contact with this marine stinger often leads to hospitalization and can be fatal. Consequently, the annual occurrence of this organism is believed to cost the Australian government an estimated $AUD3 billion annually in medical costs and losses for tourism. Despite its economic importance the logistical difficulties related to surveying C.barnesi in situ has led to a paucity of knowledge regarding its ecology and significantly impeded management strategies to date. In this study, we use six years of direct C. barnesi capture data to explore patterns pertaining to the annual occurrence and abundance of this species in the nearshore waters of the Cairns coast. We provide novel insights into trends in medusae aggregations and size distribution and primarily focus on the potential role of environmental drivers for annual C. barnesi occurrence patterns. Using a two-part hurdle model, eight environmental parameters were investigated over four time periods for associations with records of medusa presence and abundance. Final models showed a small amount of variation in medusa presence and abundance patterns could be accounted for by long-term trends pertaining to rainfall and wind direction. However, the assessed environmental parameters could not explain high annual variation or site location effects. Ultimately best-fit models had very low statistical inference power explaining between 16 and 20% of the variance in the data, leaving approximately 80% of all variation in medusa presence and abundance unexplained.

Research on the insurance of swimming crab temperature and salinity index insurance based on Copula function.

Under climate change, the sea surface temperature and salinity change greatly, which poses a considerable threat to sustainable food security. Sea surface temperature and salinity (SST/SSS) are selected to examine the annual output of swimming crab in 24 cities along the eastern China. The Copula-based function was used to construct the probability distribution model of the swimming crab yield with SST and SSS. The pure premium rate of the swimming crab production in these 24 cities are also examined. The results show that 1) There is significant positive correlations between the yield of swimming crab with temperature and salinity over the study area. The only exception is that the correlation between yield of swimming crab and salinity is not significant in the south of study area. 2) The span of the pure insurance premium rate of swimming crab in 24 cities increases rapidly with the increase of the protection level, the maximum span up to 2.04%, and the minimum span is only 1.6%. 3) The distribution of the swimming crab insurance premium rate is various in space. The insurance premium rate of 8 cities in the south of Taizhou is low with the highest premium rate at 5.6%. The insurance premium rate of 16 cities in north of Taizhou is relatively high with the rate between 6%-22%. The research can provide a theoretical basis for the pricing of insurance products for swimming crab in 24 cities in the typical aquaculture areas in eastern China.

Raising Awareness on the Clinical and Forensic Aspects of Jellyfish Stings: A Worldwide Increasing Threat.

Jellyfish are ubiquitous animals registering a high and increasing number of contacts with humans in coastal areas. These encounters result in a multitude of symptoms, ranging from mild erythema to death. This work aims to review the state-of-the-art regarding pathophysiology, diagnosis, treatment, and relevant clinical and forensic aspects of jellyfish stings. There are three major classes of jellyfish, causing various clinical scenarios. Most envenomations result in an erythematous lesion with morphological characteristics that may help identify the class of jellyfish responsible. In rare cases, the sting may result in delayed, persistent, or systemic symptoms. Lethal encounters have been described, but most of those cases happened in the Indo-Pacific region, where cubozoans, the deadliest jellyfish class, can be found. The diagnosis is mostly clinical but can be aided by dermoscopy, skin scrapings/sticky tape, confocal reflectance microscopy, immunological essays, among others. Treatment is currently based on preventing further envenomation, inactivating the venom, and alleviating local and systemic symptoms. However, the strategy used to achieve these effects remains under debate. Only one antivenom is currently used and covers merely one species (Chironex fleckeri). Other antivenoms have been produced experimentally but were not tested on human envenomation settings. The increased number of cases, especially due to climate changes, justifies further research in the study of clinical aspects of jellyfish envenoming.