Marine Envenomation

With global warming and an increasing frequency of human interaction with venomous marine organisms, physicians are likely to encounter more cases of marine envenomation in clinical practice in Japan and around the world. Few review articles regarding the clinical characteristics of marine envenomation have been published and there has been no comprehensive review of available antivenoms, which are the definitive treatment. We discuss the epidemiology, venom activity, clinical symptoms, diagnosis, and treatment of marine envenomation by the Okinawan box jellyfish, stonefish, Portuguese man-of-war, geography cone, and blue-ringed octopus. A comprehensive review of available antivenom treatments is also presented.


Background
The annual incidence of marine envenomation in Florida and eastern Australia is approximately 100,000 [1]. Previous clinical reports of marine envenomation include an outbreak of Portuguese man-of-war envenomation in southeastern Brazil [2] and a compilation of human injuries and fatalities due to envenomation by the geography cone, which is the most dangerous species to humans [3]. Currently, it appears that the incidence of marine envenomation in Japan and around the world is likely to increase due to global warming and increasing frequency of human interactions with venomous marine organisms [4][5][6]. However, few clinical reviews of marine envenomation have been published [7][8][9], and there has been no comprehensive review of available antivenoms, which are the definitive treatment. In this review, we discuss the epidemiology, venom activity, clinical symptoms, diagnosis, and treatment of marine envenomation by the box jellyfish, stonefish, Portuguese man-of-war, geography cone, and blueringed octopus and also provide a comprehensive review of available antivenoms.

Box Jellyfish
Scientific name: Chironex yamaguchii Appearance: The diameter of the hood is approximately 10-14 cm, and the body length can reach approximately 1.5 m with tentacles extended. This jellyfish possesses seven tentacles attached to four arms (Fig. 1).
Epidemiology: Jellyfish appear in large numbers in swimming areas, particularly inlets and beaches where waves are subdued. Several jellyfish sting cases have been reported in the literature [10][11][12] and recently, Hifumi et al. comprehensively described the clinical characteristics of jellyfish stings in Japan [13]. One urban emergency department in Hawaii experiences approximately 20 jellyfish sting cases annually [14]. The annual number of cases in Japan is relatively small compared with the annual incidence of approximately 100,000 in Florida and eastern Australia [1].
Venom activity and clinical symptoms: Box jellyfish venom has hemolytic and neurotoxic effects and causes skin necrosis and hypotension.

Diagnosis:
No definite diagnostic criteria exist. Diagnosis of jellyfish stings is based on either the patient's history or positive identification of the responsible jellyfish presented by the patient [13]. Severe stings result in systemic envenomation, which may result in Irukandji syndrome and/or anaphylaxis, and most often require hospital admission [15].
Treatment: Applying vinegar to any tentacles remaining on the skin prior to removal can deactivate unfired nematocysts. After vinegar application, the tentacles may be gently removed. Cardiac arrest and cardiogenic shock are appropriate indications for antivenom administration [16]; earlier administration of antivenom may neutralize the venom.
Prevention: Box jellyfish are a common hazard, as they are translucent and difficult to see through the water's surface. Swimming within an area protected by anti-jellyfish barrier netting is recommended.

Stonefish
Scientific name: Synanceia verrucosa Appearance: Reef stonefish have an overall body length of approximately 40 cm and are difficult to see, as they blend in with rocks on the seabed. Their spines are tough and able to penetrate rubber-soled boots and wetsuits (Fig. 2).
Epidemiology: Stonefish stings, including those from reef stonefish, are a common injury seen in the emergency room. They are primarily found in the coastal waters of the Indo-Pacific region, including the USA, Australia, Malaysia, Hong Kong, and Singapore [17][18][19][20][21]. Few Japanese studies of stonefish envenomation have been reported [22,23]; however, Hifumi et al. recently reported 15 cases over a 5-year observation period [24] and two deaths related to stonefish envenomation have been reported in Japan [25].
Venom activity and clinical symptoms: Fatalities resulting from reef stonefish stings have been reported in Okinawa prefecture. These injuries may have been sustained by individuals fishing for food, since stonefish are eaten in some regions. Venom from the genus Synanceia has hyaluronidase activity and causes hemolysis, hypotension, and nerve paralysis.
Diagnosis: Currently, there are no definitive diagnostic criteria for stonefish envenomation. The diagnosis of stonefish envenomation is based on the patient's history or the positive identification of the stonefish presented by the patient [24].
Treatment: It is important to warm the site of stonefish stings as this helps to relieve pain. Warming the affected area to approximately 43°C is recommended. Antivenom is available and consists of the purified F(ab)2 fragment of equine IgG antibodies raised against the venom of Synanceia trachynis [26]. In a study conducted in Hong Kong, 25% of patients received treatment with antivenom [21].
Prevention: Use thick rubber-soled footwear to prevent spine penetration.

Portuguese Man-of-War
Scientific name: Physalia physalis utriculus Appearance: A lovely blue hue. Also called "blue bottles," they have a bluish-white floating hood from which tentacles extend to reach a length of 10-20 m [27]. The Portuguese man-of-war is also called the "electric jellyfish" because its tentacles contain many nematocysts that induce a strong sensation akin to an electric shock (Fig. 3).
Epidemiology: An outbreak of Portuguese man-of-war envenomation in southeastern Brazil was reported in 2013 [2]. In addition, a massive outbreak at Yuigahama Beach, Japan, occurred in 2018.
Venom activity and clinical symptoms: Portuguese manof-war venom induces hemolysis, swelling, and necrosis and can be lethal. Extreme pain is experienced immediately following the sting. Areas of skin that contact the man-of-war's  Treatment: Use sea or tap water to wash away any tentacles that remain wrapped around the body. If tentacles cannot be rinsed off, gently remove them with the fingertips. Do not use vinegar as you would for box jellyfish stings because this promotes nematocyst firing in the Portuguese man-of-war. Use strong topical steroids if inflammation at the site of the sting is severe.
Prevention: Do not enter the ocean when alerted to the presence of jellyfish. Swim in areas protected by an antijellyfish barrier net. Minimize exposure of unprotected skin as much as possible.

Geography Cone
Scientific name: Gastridium geographus Appearance: The shell of the geography cone grows to a size of 10-13 cm and it beautifully intertwines clouds of crimson with a fine mesh pattern (Fig. 4).
Venom activity and clinical symptoms: G. geographus is the most dangerous species known to humans [3]. Conotoxins target receptors and channels that mediate neuromuscular blockade [29]. Paralysis at the site of injury, dizziness, double vision, numbness of the mouth, and other symptoms may occur. In severe cases, ventilatory support may be required.
Diagnosis: Currently, there are no definitive diagnostic criteria for geography cone envenomation. The diagnosis is based on the patient's history or the positive identification of the geography cone presented by the patient.

Treatment:
The wound should be soaked in hot water (maximum 45°C) for 30-90 min [7]. Standard medical care should be provided. Mechanical ventilation may be required in severe cases. There is no antivenom for a geography cone sting. Treatment is supportive until the toxins become inactive.
Prevention: Do not pick up seashells carelessly.

Blue-Ringed Octopus
Scientific name: Hapalochlaena fasciata Appearance: A small octopus approximately 10 cm in length. The skin is yellow and spotted with blue circles [30] (Fig. 5).
Epidemiology: H. fasciata is most commonly found around intertidal rocky shores and coastal waters between Australia and through the Pacific Ocean north to Japan.   Venom activity and clinical symptoms: Blue-ringed octopus venom includes tetrodotoxin and can cause respiratory muscle paralysis [30].
Treatment: Standard medical care should be provided. Mechanical ventilation may be required in severe cases.
Prevention: The blue-ringed octopus may be found during clam digging when large rocks are overturned. They should not be touched with bare hands.

Antivenom
Clinical availability of antivenoms and indications for their use are summarized in Table 1 [31]. Only antivenoms for jellyfish and stonefish stings are available. Both are manufactured by immunizing horses against unbound venom; therefore, adverse reactions, including anaphylaxis, should be anticipated and prepared for. The incidence of adverse reactions to snake antivenom produced from horse serum is 2.4-11% [32]. The establishment of airway, breathing, and circulation is required before using antivenom. This section may be divided by subheadings. It should provide a concise and precise description of the experimental results, their interpretation, and the experimental conclusions that can be drawn.

Conclusions
This review provides a comprehensive summary of the available information regarding marine envenomation in humans. Data continue to be collected on a case-by-case basis as no large-scale epidemiological studies have been conducted to date. Clinical marine envenomation research is severely lacking. Since more cases of marine envenomation will undoubtedly occur in the future, emergency physicians need to be aware of their diagnosis and management.

Compliance with Ethical Standards
Ethical Approval and Consent to Participate Not applicable.

Consent for Publication Not applicable.
Competing Interests The authors declare that they have no competing interests.
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