7.1. Envenomation
Humans face a variety of dangers from jellyfish species across European waters. The threat encountered upon a jellyfish sting depends on the species, the anatomical penetration, and geographic location. The sting results in a cutaneous reaction in most cases, and systemic symptoms from a larger envenomation due to a toxic effect of the venom. Cross-reactivity can lead to a severe allergic reaction of angioedema or anaphylaxis. It is recommended that an individual is evaluated for the development of allergies after a severe jellyfish sting, as it may be necessary to carry an epinephrine pen and antihistamines when returning to the sea [
10,
54]. The prevention of envenomation should be a priority through wearing protective equipment such as wet suits when entering the water and avoidance of areas with jellyfish blooms.
Further research into the life cycles and life histories of all envenoming species would be advantageous to establish what factors are important in the development of nematocysts, toxins and where jellyfish polyps are likely to develop. There is a considerable knowledge deficiency relating to jellyfish life histories. Specific research may lead to better understanding of the development of venomous species and how this can be avoided and treated [
6]. The monitoring of biotic and abiotic factors, such as how prey availability and temperature affect the development of nematocysts and the venom. This may lead to an understanding of how to tackle blooms and envenomations as well as recognizing why certain areas have more dangerous species [
6,
43].
The study of Wiebring et al. [
6] has identified how relative frequencies of nematocysts correlate with the available prey species; thus, the nematocysts reflect the diet of the jellyfish [
70]. Accordingly nematocysts treatment can be more specifically analyzed in a given area if prey populations are monitored and subsequently lead to nematocyst or toxin-specific treatments for envenomation. Nematocyst type can have a great effect on the envenomation severity due to the tubule length and thus this research would be beneficial.
There is confusion on species causing different sting severities in various locations. DNA sequencing of jellyfish species may explain why reactions vary between areas. Identification of DNA similarities may lead to better understanding of how envenomation treatment is beneficial in a genus or species specific manner, with certain species closely related perhaps sharing favorable methods of first aid treatment. This research established speciation occurred between the “New World” and “Old World”
Aurelia aurita and thus why in some areas the species is venomous, and innocuous in others [
71].
The effect of a changing climate may alter the distribution of species and envenomation ability, therefore, the monitoring of these factors is highly recommended. Variations in nematocyst length and venom potency have been identified outside of European waters in
A. aurita and
Cassiopea sp. dependent on location, habitat and environmental conditions. This emphasizes the threat of climate change altering which species threaten human safety.
Cassiopea sp. have been reported to be venomous or not, depending on the habitat. The individual jellyfish that were discovered all have identical cnidoms thus, the venom composition must be the variation.
Cassiopea sp. has been found to possess dinoflagellates in their venoms, which may be another factor that alters toxicity between geographic locations [
43]. Further research is necessary to identify the factors that lead to the variation between geographic localities, as this vital piece of information is necessary in order to develop the most effective therapy.
The threat of climate change could also facilitate a change in the geographic distribution of species, as well as their physiology and toxicity. The El Niño effect in Florida, which increases the water temperature, led to an increased length of tentacles in
A. aurita and subsequently increased the ability of envenomation [
43,
62]. Events such as the findings from the El Niño portray how environmental factors may play a large role in the toxicity of species and why species can vary due to localities they inhabit. This climate change effect could be mirrored in European species, thus, environmental factors should be further investigated as these changes may lead to mild species becoming an increased threat to the public.
The identification of human-mediated activities on jellyfish blooms will enable blooms to be monitored and controlled in relation to overfishing, eutrophication, and construction [
72]. Many jellyfish species polyps have been found to favor artificial materials and man-made developments. The development of a protocol to monitor materials used in coastal development will aid in the surveying and avoidance of jellyfish blooms arising in popular areas. Factors such as heavy metals have been proven to affect nematocysts discharge response and the biological activity of crude venom [
73]. Therefore, if such factors are polluting certain areas it may explain why there is variability in the severity of the sting.
7.2. Treatment
First aid treatment is the primary concern when dealing with jellyfish stings. The process that is carried out to remove tentacles and treatment of the stung area can be crucial to avoid the further release of nematocysts and heightened symptoms through a change in osmotic pressure or mechanical stimulation [
25]. Anecdotal treatments are more common than EBM for jellyfish stings due to a lack of understanding of jellyfish venom and patient variability playing a large role in the efficacy of the therapeutic agents. Many treatments that have previously been advised are a counteractant or a placebo. Ultimately much of what is considered a beneficial therapy is unavailable for immediate first aid response such as IV channel blockers. Topical therapy is unable to catch up with the initial severe envenomation as the toxin is injected into the dermis directly, whilst topical treatment takes thirty minutes to reach the same area as the initial sting [
16,
18].
IV therapy is unavailable at the scene directly after the envenomation unless IV first aid protocol has been set up in the most dangerous areas. Although IV channel blockers are shown to be beneficial for nematocyst inhibition and pain relief with 100% (11 papers) efficacy, there is the threat of disguising a medium to severe sting, and hence, leading to systemic complications remaining undetected and resulting in the danger of life. Complications of delayed kidney and liver failure have been reported after medium envenomation, referred to as delayed jellyfish envenomation syndrome (DJES) [
12,
29,
35]. Deaths within two hours of envenomation are typically resultant from cardiotoxicity due to large doses of venom generating cardiovascular collapse. Cardiotoxicity results from the ionic disturbances with the loss of potassium and increase in sodium and calcium ions leading to the ultimate loss of action potentials, with the venom influencing calcium binding [
40,
74,
75]. Moderate envenomation depresses respiration through the central nervous system minutes to hours after the sting. The deaths that occur between 2 h and 48 h after a lower dose of venom may be due to DJES through cellular or tubular necrosis. The proteolytic enzymes in the venom are believed to cause a hemorrhage through the breakdown of connective tissue around blood vessels and extracellular matrix, injuring the organs. The vascular system seems to be one of the main targets of the venom, similar to snake venom, containing metalloproteins, caseinolytic, and fibrinolytic activities [
12,
32,
33,
45]. Understanding aspects of the venom and the microvascular network is important to establish the mechanism that leads to DJES to create appropriate intervention therapies, with further research required to understand if calcium and sodium channel blockers aid cardiotoxicity but mask DJES.
The rate of venom uptake is dose dependent and relative to the peripheral circulation, thus, the victim must be kept calm and immobile to prevent increased blood flow. Peripheral circulation of the venom is mainly governed by muscular contraction of the surrounding envenomed tissue as well as the total injected dose of venom, however PIB is no longer recommended to reduce blood flow as the pressure may discharge remaining nematocysts [
10,
12,
17,
27,
76].
Freshwater should never be used as a treatment for jellyfish stings as a change in osmotic concentration can trigger nematocyst release further intensifying the initial sting. Sea water has been established to be an effective painkiller and should be used in aqueous treatments, such as baking soda slurry, as an immediate therapy and to wash off tentacles [
6,
8,
10].
A great deal of dispute over the efficacy of treatment is due to the different methods of venom extraction displaying a variation in results. Several studies have identified differences between the biological activities of nematocysts venom compared to tentacle-only extract (TOE) [
33,
75,
77]. These investigations using TOE produce false positive results and highlight problems with research into the testing of treatments.
A new research method, published by Yanagihara et al. assessing the efficacy of topical first aid treatment on cubozoan tentacle firing and venom toxicity presents a new in vitro method of testing. This involves a living sting model composed of human red blood cells suspended in agarose gel, covered by lanolin-rubber sterile porcine intestine as a mock skin and live stinging tentacles to test first aid measures. This avoids ethical issues of experimenting on humans while allowing the measurement of first aid with live tentacle applicant using an artificial and cost-effective model that could be utilized to test other jellyfish species [
17].
The research of Cuypers et al. [
65] identified TRPV1 receptors to be associated with cnidarian envenomation, which is pH and heat sensitive. Further to this, scyphozoan venoms have been identified to have heightened hemolytic activity at low temperatures and are dramatically reduced upon an increase in pH and temperature [
78]. Many anecdotal treatments are light acids in an attempt to relieve pain; however, further investigation into blocking these receptors without the further release of nematocysts would produce an effective pain relief treatment. The investigation into infrequent therapies that have been identified as showing a beneficial response could prove favorable for first aid treatment of pain and deactivation of venom, such as palm oil and lemon juice emulsion which is a common anecdotal therapy in the tropics [
79]. Jellyfish envenomation studies should concentrate on genus based or individual species treatment as opposed to a general protocol for a better therapeutic impact, using large sample sizes, double blind tests and species from various areas, as well as the use of a dolorimeter to assess the intensity of pain if focus is on a case by case level.
The presence of first aid stations and response teams along the coastlines of highly affected areas in Europe is recommended, for instance along the Mediterranean coast. Hot showers erected on beaches that distribute water at a continuous temperature of between 42 °C and 45 °C are recommended to suppress pain and to deactivate venom. Baking soda and Stingose should be available along high-risk areas as an immediate response. These three therapies have displayed beneficial outcomes of first aid response for a variety of jellyfish species envenomations and are available at a low cost with no necessary training in the administration of these treatments. Cold packs are another treatment that has displayed a highly beneficial outcome across a number of species. Cold packs in mild envenomation cases are beneficial as there has been no adverse effect reported with this treatment due to the cold resulting in a slow diffusion rate of venom around the body, unlike heat mediated treatments. Despite this, extreme heat has proven more favorable across a number of marine envenomations and is effective on TRPV1 receptors, unlike extreme cold [
34,
36,
80,
81,
82,
83].
The training of lifeguards and education on jellyfish envenomation is recommended, in addition to the distribution of signage to warn public and tourists of how to avoid the dangers of jellyfish, what species are most hazardous and a recommended first aid protocol with post-sting infographics to help establish the best form of species-specific treatment. A forecast of jellyfish sightings is recommended on popular beaches on the coasts of Europe that have a high frequency of jellyfish. At peak times with the presence of blooms, it may be advisable to cordon off beaches or implement the use of anti-jellyfish nets, as well as develop monitoring protocols to detect when and where a bloom may arise. The promotion of citizen science tools will enable jellyfish blooms to be monitored to a better degree, prepared for, and identify the best intervention techniques through the tracking of environmental factors during their occurrence.