Venoms and Poisons from Marine Organisms

Venoms and Poisons from Marine Organisms

CHAPTER 114  VENOMS AND POISONS FROM MARINE ORGANISMS   697 posterior and ventral to the maxillary bone. The relatively short length of the fangs pr...

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CHAPTER 114  VENOMS AND POISONS FROM MARINE ORGANISMS  

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posterior and ventral to the maxillary bone. The relatively short length of the fangs prevents effective envenomation through most protective clothing such as dive suits. If the subject reacts to envenomation by forceful retraction, the fangs are often dislodged from the maxillary bone of the snake and may remain in the site—a condition that imposes an additional risk for infection. Because of the nature of the venom and the size of the fangs, the sea snake bite itself is not generally painful. One or two small prick marks are present at the envenomation site, occasionally with additional marks from the other teeth in the snake’s mouth. The primary toxin in sea snake venom is a postsynaptic peptide neurotoxin that functions by blocking the acetylcholine receptor at neuromuscular junctions (Fig. 114-1). Ptosis, dysphagia, and nonrigid paralysis, which are the most common symptoms of sea snake envenomation, typically appear within 30 minutes to 2 hours after the bite. In severe cases, respiratory failure may develop, and respiratory support may be necessary. Antivenom is available.

Weeverfish, Lionfish, Scorpionfish, and Stonefish

114  VENOMS AND POISONS FROM MARINE ORGANISMS JAY W. FOX The term envenomation implies penetration of a target by an organism for delivery of venom containing one or more toxins. In contrast, poisons are toxins acquired from the environment by mechanisms such as absorption, inhalation, and ingestion. In the marine environment, both forms of intoxication cause effects ranging from mild irritation and discomfort to death (Table 114-1). Severe outbreaks of poisoning can result from the ingestion of marine organisms that contain toxins, and such outbreaks have become more frequent as microorganisms in coastal waters increase, owing to a combination of global sea warming, eutrophication, aquaculture, and discharge of organisms from ship ballasts. Encroachment on the marine environment for recreation, living space, and food sources increases the frequency of adverse encounters with venomous and poisonous marine organisms.

VENOMOUS MARINE ORGANISMS

Venomous marine organisms deliver their venom by bites and stings. Envenomation involves penetration of the skin and may be complicated by secondary bacterial infections, especially after deep puncture wounds and bites.

Chordata

Sea Snakes

Sea snakes, which are members of the family Hydrophiidae, are generally found in tropical and subtropical waters, especially the coastal waters of Thailand, Indonesia, the Persian Gulf, Australia, and India. One species, the yellow-bellied sea snake (Pelaramis platurus), is found in the Pacific coastal waters of Central America. Sea snakes, which are very capable swimmers and are relatively immobile on land, inject their venom with two small maxillary fangs (2 to 4 mm long) that contain ducts connected to venom glands located

Weeverfish belong to the Trachinidae family, whereas scorpionfish, stonefish, and lionfish all belong to the family Scorpaenidae. Members of the Scorpaenidae family are found mostly in tropical and subtropical waters, but weeverfish are in European and African waters. All of these fish sting by using dorsal spines. The anal spines of Scorpaenidae fish and the opercular spines of Trachinidae fish can also deliver venom. The spines are encased in an integumentary sheath that is torn when the spine punctures the victim’s skin. Venom glands are located at the base of the spine. Few details are known regarding the biochemistry and pharmacology of the toxins in weeverfish venom. The sting of the weeverfish is extremely painful and may produce systemic effects such as aphonia, fever, chills, dyspnea, cyanosis, nausea, syncope, hypotension, and arrhythmias. The wound is edematous, erythematous, and ecchymotic. Bacterial infection is typical, and gangrene has developed in severe cases of infection. The venom may be somewhat heat labile, and soaking in tolerably hot water may reduce pain and attenuate the effects of the venom. Death from an untreated weeverfish sting is rare. Scorpaenidae envenomation symptoms are generally less severe for lionfish (Pterois), more severe for scorpionfish (Scorpaena), and most severe for stonefish (Synanceia). Lionfish (turkey fish, dragon fish, butterfly cod), which are found worldwide, have long thin spines. Scorpionfish have shorter, thicker spines and are primarily found in tropical and subtropical waters and the Mediterranean. The local consequences of edema and erythema from stings of these fish are very similar to those of the weeverfish. Immersion in hot water is generally effective to alleviate pain associated with envenomation. The stonefish (Synanceja) group has short strong spines and is found throughout the Indo-Pacific area, China, Australia, and the Indian Ocean. Their toxins are high-molecular-weight, multimeric, heat-labile proteins. Symptoms of envenomation are similar to those from the stings of members of the other groups. A lethal toxin, stonustoxin, from the venom of Synanceja horrida causes muscle relaxation by producing nitric oxide and also causes hemolysis, platelet aggregation, and inhibition of neuromuscular function. Trachynilysin, a pore-forming neurotoxin from Synanceja trachynis, causes massive presynaptic release of acetylcholine. Soaking of the wound site in hot water (45° C) is recommended. In cases of severe blistering, the blisters should be excised to flush residual active venom from the blister fluid to ameliorate dermal necrosis. As with all fish stings, care should be taken to ensure that no broken portions of the spines remain in the wound; vigilance against bacterial infections is imperative. Antivenom should be used only if it is clear that envenomation has occurred.

Stingrays

Stingrays (family Dasyatidae) are found in most seas but are predominant in the Indo-Pacific area. Some members of the family are also found in fresh water. Venom containing serotonin is delivered by stings from spines (one or more) on the tail of the stingray. Stingray spines are retroserrated on the margins and are covered by an integumentary sheath. Venomous glandular tissue is located at the base of the spines. On puncture of the skin, the sheath is torn by the serrated spine, and venom flows along the two ventrolateral grooves of the spine into the surrounding tissue. The spines are often deeply embedded in the tissue and difficult to extract because of the retroserration. Care must be taken to remove all spine and sheath fragments. Depending on the location of the spine and the depth of penetration, specialized care may

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CHAPTER 114  VENOMS AND POISONS FROM MARINE ORGANISMS  

TABLE 114-1 SIGNIFICANT VENOMOUS AND POISONOUS MARINE ORGANISMS ORGANISM Sea snakes (Hydrophiidae)

MECHANISM OF INTOXICATION (EVENOMING/POISONING) Bite

PRIMARY TOXINS Postsynaptic neurotoxins

ANTIVENOM AVAILABLE (SOURCE) Yes (CSL, Ltd.)

Blue-ringed octopus (Octopodidae)

Bite

Tetrodotoxin (neurotoxin)

No

Cone shell (Conidae)

Sting

Presynaptic and postsynaptic neurotoxins

No

Box jellyfish (Chironex fleckeri, Chiropsalmus quadrigatus)

Sting

Hemolysins, proteinases, cardiotoxin, necrotoxins

Yes (CSL, Ltd.)

Portuguese man-of-war (Physalia physalis)

Sting

Hemolysins, proteinases, cardiotoxin, necrotoxins

No

Sea nettles (Chrysaora quinquecirrha, Cyanea capillata)

Sting

Hemolysins, proteinases, cardiotoxin, necrotoxins

No; generally no need

Sea anemone (Anemonia sulcata)

Sting

Neurotoxins

No; generally no need

Scorpionfish (Scorpaenidae)

Sting puncture

Hemolysins, necrotoxins?

Yes (CSL, Ltd.)

Lionfish (Scorpaenidae)

Sting puncture

Hemolysins, necrotoxins?

No

Stonefish (Scorpaenidae)

Sting puncture

Hemolysins, necrotoxins?

Yes (CSL, Ltd)

Weeverfish (Trachinidae)

Sting puncture

Hemolysins, necrotoxins?

No

Stingrays (Rajiformes)

Sting puncture

Uncertain

No

Dinoflagellates   Gambierdiscus toxicus   Ptychodiscus brevis   Gonyaulax species   Pyrodinium species   Jania species

Ingestion (found in seafood) Ingestion (found in fish) Ingestion (found in shellfish) Ingestion (found in shellfish) Ingestion (found in shellfish) Ingestion (found in shellfish)

Ciguatera poisoning Ciguatoxins, maitotoxin (neurotoxins) Neurotoxic shellfish poisoning, neurotoxins Paralytic shellfish poisoning Saxitoxin, neosaxitoxin, and gonyautoxin Okadaic acid (phosphatase inhibitors)

No No No No No No

Pufferfish (Tetraodontiformes)

Ingestion

Tetrodotoxin (neurotoxin)

No

Porcupinefish (Tetraodontiformes)

Ingestion

Tetrodotoxin (neurotoxin)

No

Sunfish (Mola species)

Ingestion

Tetrodotoxin (neurotoxin)

No

Motor axon N-type Ca2+ channel Blocked by ω-conotoxin Voltage-gated Na + channel Opening blocked by: • µ-conotoxin • tetrodotoxin • saxitoxin Channel closing slowed by: • sea anemone toxin • brevetoxins • ciguatoxin

Ca

Acetylcholine synaptic vesicles

2+

Ca2+ channel Maitotoxin increases Ca2+ flux L-type

Ca + Na

2+

+ Na

Muscle cell

2+

Ca K+ Acetylcholine Receptor Na+–K+ channel Blocked by sea snake neurotoxins, α-conotoxin

be necessary to extract the spine and cleanse the wound. A sting produces severe pain and edema, which in extreme cases is accompanied by hemorrhage, syncope, vomiting, hypotension, and cardiac arrhythmias. In rare cases, death can occur, especially if the pericardial, peritoneal, or pleural cavities are penetrated. Soaking the wound in hot water inactivates some of the heat-labile toxins in the venom.

FIGURE 114-1.  Schematic representation of a motor axon synapse and the sites of action  of various marine neurotoxins.

Mollusca

Cone Snails

Cone snail (Conidae) venom is injected into victims through a hollow, harpoon-like tooth. The venom, which is primarily neurotoxic, causes paresthesias, hypotension, and respiratory impairment or failure. Fourteen superfamilies of conopeptide toxins have been identified in cone snail venom:

CHAPTER 114  VENOMS AND POISONS FROM MARINE ORGANISMS  

A, I, M, O, P, S, T, I2, J, L, O2, O3, V, and Y. All of the conopeptides are short polypeptides that demonstrate a variety of neurotoxic actions by targeting specific subtypes of ion channels, neurotransmitter receptors, or transporters (see Fig. 114-1). The bite is very painful and may be followed by systemic symptoms such as dysphagia, aphonia, pruritus, blurred vision, syncope, muscular paralysis, and respiratory and cardiac failure. Treatment is supportive; in cases of severe envenomation, preparation for cardiovascular and respiratory support should be made. Rare cases of coagulopathy have been reported, and fatal envenomation has occurred.

Octopuses

The two species of blue-ringed octopuses (Hapalochlaena maculosa and Hapalochlaena lunulata), found in Australian waters, inject their venom by a relatively painless bite that produces two small puncture wounds. Hemorrhage at the site may occur. The major toxic component in the venom is tetrodotoxin, a neurotoxin that blocks action potentials of voltage-activated sodium channels and causes perioral and intraoral paresthesias, dysphagia, nausea, ataxia, aphonia, flaccid muscular paralysis, and respiratory distress or failure. Fatal envenomation has occurred, and urgent respiratory support may be required in severe cases.

Cnidaria

Jellyfish and Anemones

Jellyfish and anemones belong to the Cnidaria phylum, so named because of their venomous organelles called cnidae. The cnidae found in jellyfish and anemones (called nematocysts and spirocysts, respectively) are located on exposed tentacles. On tactile stimulation, the tentacles send forth a tethered projectile to deliver venom through the dermis. As the victim’s surrounding musculature contracts, the venom is disseminated. Hemolysins, DNAase, and histamine releasers have been identified in some venoms. A number of peptide toxins of sea anemones mostly function by binding to sodium channel receptor site 3 to delay the inactivation phase of the channel. Other peptide toxins from anemones target the Kv3 potassium channel. Stings by jellyfish and anemones typically produce immediate pain at the site of envenomation, followed by erythematous and urticarial lesions. Anaphylaxis is not common unless the patient has previously been sensitized. Depending on the severity of the sting, wheals and whiplike patterns may appear at the sites of envenomation within a few minutes or be delayed by several hours, followed in some cases by dermal necrosis. Eruptions sometimes recur days after the envenomation. Systemic reactions may include muscle spasms and cramps, vomiting, nausea, diarrhea, diaphoresis, and, in rare cases, cardiorespiratory failure. Unfired nematocysts on tentacles adhering to the skin may be neutralized by vinegar or baking soda, depending on the species of jellyfish. Vinegar appears to be most useful for Australian blue bottle (Physalia utriculus) stings, whereas baking soda appears more efficacious for sea nettle (Chrysaora quinquecirrha) stings. The box jellyfish (Chironex fleckeri) found in Australian waters is perhaps the most venomous jellyfish; it produces very severe stings that may cause death from hypotension, muscular and respiratory paralysis, and ultimately, cardiac arrest. Treatment of box jellyfish stings may require respiratory support and administration of antivenom. The Portuguese man of war (Physalia physalis) is not a true jellyfish, and its venom differs from true jellyfish. It stings through nematocysts that cause intense pain and, occasionally, an allergic reaction. Flushing with salt water (sea water) followed by application of heat may ease the pain.

Sponges

Some sponges colonized by coelenterates produce toxins that can cause a pruritic, allergic dermatitis or an irritant dermatitis. These toxins are delivered by the sharp spicules, which penetrate the dermis. The toxins can cause the typical sponge diver’s disease, which is characterized by local burning and itching and may be accompanied by soft tissue edema and purulent vesiculation. Serious illness is rare.

Corals

Fire coral (Millepora alcicornis) is found in shallow tropical waters. Stings are a common consequence of brushing or rubbing against the coral. Envenomation produces a burning or stinging sensation, followed by severe pruritus. Edematous wheals may develop but generally dissipate over the course of several days. The site of envenomation should be soaked in vinegar (5% acetic acid) or 70% isopropanol to relieve pain.

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Annelida

Bristle worms

Bristle worms are segmented invertebrates found in tropical Pacific waters and the Gulf of Mexico. The bristles can penetrate the skin and produce severely painful envenomation, with pruritus and burning that may persist for several days. Local paresthesia is typical and may linger for weeks. Treatment is symptomatic, with consideration of possible tetanus infection (Chapter 304). Little is known regarding the chemistry of bristle worm venom.

Echinodermata Sea Urchins

Of the echinoderms, sea urchins and sea stars are responsible for most stings in humans. The venom is delivered by the long spines and pedicellaria protruding from the sea urchin body. The spines are covered at the tips with a venom sac that is broken when it penetrates the skin. The pedicellaria, present on some species of sea urchins, are pincer-like appendages carrying venom glands. The toxins of sea urchin venom are not well characterized. Stings can produce pain, hemorrhage, aphonia, paresthesias, paralysis, hypotension, nausea, syncope, and respiratory distress. Immersion in hot water helps inactivate heat-labile toxins in the venom. Attached pedicellaria and embedded spines must be removed to prevent additional envenomation and infection.

POISONOUS MARINE ORGANISMS

Unlike envenomation, marine poisoning nearly always results from consumption of fish or shellfish that have accumulated various toxins from dinoflagellates. Most marine poisonings cause neurologic and gastrointestinal effects associated with the specific toxins found in the food source. Diagnosis is clinical, based on the type of fish ingested and the clinical symptoms presented. Neurotoxic marine poisoning is generally caused by one of six different toxins.

Neurotoxic Marine Toxins Ciguatoxins

Ciguatoxins are occasionally found in reef fish of the Caribbean and Pacific. These toxins are cyclic polyethers that act as excitatory agents by binding to sodium channels. Maitotoxin, from the same dinoflagellate, is a water-soluble polyether that acts by enhancing calcium entry through L-type calcium channels. Symptoms of ciguatera poisoning generally appear within 2 to 12 hours after the ingestion of contaminated fish. Gastrointestinal symptoms, including diarrhea, abdominal pain, nausea, and vomiting, appear first, followed by neurologic and cardiovascular symptoms. Neurologic symptoms include aphonia, dental dysesthesias, fatigue, tremor, ataxia, pruritus, extremity and perioral dysesthesia, vertigo, headache, myalgia, arthralgia, temperature reversal, and hyporeflexia. Cardiovascular symptoms, such as bradycardia and hypotension, are less common. Treatment of ciguatera poisoning is supportive, with symptom-based therapy as indicated. Death from ciguatera poisoning is rare.

Tetrodotoxin

Pufferfish (i.e., blowfish, balloonfish, and toadfish), porcupinefish, and sunfish (Mola species) have a very potent toxin, tetrodotoxin, in their livers, gonads, intestines, and skin. The flesh of the fish (fugu) is a delicacy in Japan, where it is prepared by specially trained chefs to avoid serving significant amounts of toxins. Tetrodotoxin is a heterocyclic compound that binds at voltage-sensitive sodium channels to block sodium-channel conduction, thereby preventing nerve and muscle action potentials and resulting in paralysis. Symptoms occur rapidly (several minutes to several hours), beginning with circumoral paresthesias and progressing to descending widespread paresthesias. After the initial paresthesias, additional symptoms soon follow, including ataxia, weakness, aphonia, diaphoresis, excess salivation, dyspnea, dysphagia, weakness, and respiratory distress or failure. Gastrointestinal symptoms include nausea, vomiting, and diarrhea. Coagulopathies also may develop. Respiratory intervention is crucial because of the potential for complete flaccid paralysis. Without respiratory assistance, death is not unusual with severe intoxication.

Palytoxin

Palytoxin is an extremely potent toxin produced in sea anemones (Palythoa species) and accumulated in sharks, crabs, and marine turtles. The toxin functions by targeting sodium-potassium ion pumps, thereby disrupting ion

gradients. Symptoms include tachycardia, hemolysis, and angina-like chest pain. Treatment is generally symptomatic and supportive.

Saxitoxin and Gonyautoxin

Paralytic shellfish poisoning is typically associated with the ingestion of mussels, clams, and oysters. The two toxins associated with this poisoning, saxitoxin and gonyautoxin, are produced by marine microalgae dinoflagellates that are associated with harmful algal blooms, such as “red tides,” and are then accumulated in bivalve shellfish to give rise to “paralytic” shellfish poisoning. The primary paralytic shellfish poisoning toxins are heterocyclic compounds that block nerve and muscle action potentials by binding to sodium channels at the same site as tetrodotoxin, thereby resulting in paralysis. Paralytic shellfish poisoning, which is significantly more severe than neurotoxic shellfish poisoning, predominantly involves neurologic symptoms with less pronounced nausea, vomiting, or diarrhea. Symptoms appear soon after the consumption of contaminated shellfish (minutes to hours), beginning with circumoral and extremity paresthesias. Additional neurologic symptoms such as ataxia, arthralgia, dysphagia, dysmetria, diaphoresis, and tachycardia soon follow the initial paresthesias. Respiratory depression or failure can result in death, usually within 12 hours of the onset of symptoms. As with other shellfish poisoning, therapy is supportive, with close attention to potential respiratory distress or failure.

Brevetoxins

Neurotoxic shellfish poisoning is caused by eating shellfish that contain brevetoxins, which are produced by the annual blooms of the red tides that are associated with the dinoflagellate Karenia brevis. Brevetoxins are cyclic polyethers that function similarly to ciguatoxins. Gastrointestinal and neurologic symptoms of intoxication appear within 3 hours after toxic shellfish is eaten and are similar to those of ciguatera poisoning. Treatment is supportive. No deaths have been reported after neurotoxic shellfish poisoning.

Domoic Acid

Domoic acid is a neurotoxin produced by the algae Nitzschia during harmful algae blooms and causes amnesic shellfish poisoning following ingestion of contaminated shellfish. The toxin disrupts neuron function by altering calcium influx into cells. Symptoms include headaches, dizziness, loss of short-term memory, confusion, seizures, and coma. After about 24 hours, gastrointestinal symptoms may include diarrhea, vomiting, and abdominal cramping. Death is rare.

Non-neurotoxic Poisoning Histamine

Scrombroid fishes, such as mackerel, bonito, and tuna, can contain an inordinate amount of histamines in their tissues as a result of bacterial destruction of fish proteins associated with spoilage. Ingestion of spoiled fish with high histamine concentrations can result in pseudoallergic symptoms such as diarrhea, flushing, headache, rash, and vomiting. A metallic taste in the mouth may be reported by some patients. Treatment usually is not necessary for scombrotoxic fish poisoning, and the symptoms usually resolve in several hours. For more severe cases, antihistamines or epinephrine have been reported to be effective. SUGGESTED READINGS James KJ, Carey B, O’Halloran J, et al. Shellfish toxicity: human health implications of marine algal toxins. Epidemiol Infect. 2010;138:927-940. Review. Shiomi K. Novel peptide toxins recently isolated from sea anemones. Toxicon. 2009;54:1112-1118. A review of peptide toxins found in sea anemones and their structures. Stewart I, Lewis RJ, Eaglesham GK, et al. Emerging tropical diseases in Australia. Part 2. Ciguatera fish poisoning. Ann Trop Med Parasitol. 2010;104:557-571. Review.