Cone Snail Toxicity


Article Author:
Sasha Kapil


Article Editor:
Jeffrey Cooper


Editors In Chief:
Heather Murphy-Lavoie
Jeffrey Cooper
Stephen Hendriksen


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Komal Shaheen
Sandeep Sekhon


Updated:
11/15/2018 10:29:10 PM

Introduction

Both experienced and novice scuba divers are drawn to warm, tropical seas, but when traveling to these areas, divers must practice additional cautionary measures to avoid predators specific to these environments. One example is the Conus genus, which includes over 500 different species of predatory snails. While humans are not the intended prey for these mollusks, naive divers may inadvertently pick up cones with the intention of keeping them as souvenirs. The handful of humans that are stung by a cone snail are often subject to a venom potent enough to immediately paralyze and eventually kill its prey. The venom from one cone snail has a hypothesized potential of killing up to 700 people.[1][2]

The Conus genus, within the Conidae family, is a group of predatory gastropod mollusks. The spiral shells of the snail are the life-long habitat for the indwelling predator. As the snail continues to grow, it builds upon its patterned shell. All members of the genus appear similar, but many different Conus species fall under this umbrella, some of which pose a greater threat to humans than others. Cone snails range in size from a few centimeters up to nine inches long. These snails sense prey within their environment using an appendage called a siphon. While some species do have eyestalks, the siphon provides a more sensitive method of locating prey, as well as performing additional respiratory functions.  There is variability in the prey each Conus species tends to hunt. Some feed on worms (vermivores), others on mollusks (molluscivores), and those most toxic to humans feed on fish (piscivores). Knowing these specific feeding patterns make differentiation of deadly Conus species easier; though all cone snails are capable of envenomation. The geographic cone is the most toxic of the known species, and several human deaths have resulted from envenomation. Humans are not typical cone snail prey and envenomation is most likely to occur during handling. Unsurprisingly, envenomation occurs most often on the palms and fingers.[3]

Within piscivorous snails, two primary methods of hunting have been documented: hook and line versus net hunting. The species that utilize the hook and line method use an additional appendage called a proboscis. Within the proboscis is a tooth or harpoon, coated with species-specific venom. This proboscis can extend to all parts of the shell and handling. Only a certain part of the cone does not protect from envenomation. The second method of hunting also involves a venom-covered harpoon, but instead, the snail opens its mouth to catch fish and the harpoon is released within the mouth. Once a harpoon is engaged, it is discarded. At any time, a cone snail has about twenty harpoons in various stages of growth and development.

Etiology

Conus venom is a complex mixture of compounds that cause paralysis through multiple neuromuscular blocking steps. The combinations of peptides that comprise venom vary between species, and it has been estimated that each cone snail harbors over 100,000 different bioactive compounds within their venom. The complexity of this poison and the variation in target pathways has prevented the production of effective anti-venom.[4]

Epidemiology

Cone snail habitats include mainly tropical waters, such as the Red Sea, the Caribbean, the Indian Ocean, and the Pacific. Despite the preference for tropical environments, cone snails do live in warm deep seas off the coast of Florida. They tend to live in the deep seas near reefs and hunt primarily at night. During the day, they bury in the sand and primarily encounter humans only when provoked. While different sources report fatality rates ranging from 15% to 75%, the point remains that cone snail envenomation is a preventable cause of death of which all deep-sea divers should be aware.[5]

Pathophysiology

Based on the rarity of cone snail envenomation and the lack of data, it is uncertain whether death is the result of respiratory toxicity, cardiovascular toxicity, or a combination of the two. The effects of envenomation vary based on the specific peptides within the venom and as a result, the effects are largely unpredictable. These toxins have a variety of neuromuscular effects through glutamate, adrenergic (chi conotoxin), serotonin, and cholinergic pathways.[6]

Histopathology

Case reports at autopsy have described injection site swelling, petechial hemorrhages, cardiac dilation, and cerebral edema. 

Toxicokinetics

Within the snail venom, there are various “conotoxins” in combinations specific to the species. These toxins have a variety of neuromuscular effects through glutamate, adrenergic (chi conotoxin), serotonin, and cholinergic pathways. Some conotoxins exert their effects on sodium (delta conotoxin), potassium, and calcium ion channels. Additional, more obscure targets exist, such as toxins that act on hormonal receptors, simulating the effects of oxytocin and vasopressin (conopressins). Another integral part of cone snail venom is various alpha-conotoxins. These toxins specifically act on nicotinic receptors, which are responsible for skeletal muscle contraction. This mechanism is similar to botulinum toxin in that they act on the same pathway. Alpha-conotoxins block nicotinic receptors, which results in paralysis that may eventually involve the diaphragm. Due to the wide range of molecular targets and the variation in the venom of each Conus species, it is virtually impossible to create effective anti-venom.

History and Physical

The initial symptoms of envenomation vary depending on the species of cone snail and the victim. When stung by a piscivorous cone snail, one may feel anything from a sharp pricking sensation to unbearable pain.  At the envenomation site, local numbness, ischemia, cyanosis, and necrosis may occur and sometimes involves entire regions of the body. Given that the affected neurotransmitter pathways exist throughout the body, systemic symptoms may develop. These progress from initial weakness, sweating, and visual changes to generalized muscle paralysis, respiratory failure, cardiovascular collapse, and coma. If a patient is untreated, death is rapid and often occurs within one to five hours. Less severe envenomations, resulting from contact with a molluscivore and vermivorous species, are milder in their toxic effects. These effects are also variable and may include numbness, paresthesias, and limb immobility.

Evaluation

Based on the variability of presentation, ordering of the appropriate laboratory tests is largely guided by the patient presentation and the acute issues that arise during hospitalization. Based on the nature of the systemic symptoms, serum metabolic parameters, chest radiography, and electrocardiography are all reasonable initial diagnostic tests to order upon hospitalization.[7]

Treatment / Management

The most important intervention after cone snail envenomation is to seek urgent hospital-based therapy and to ensure that the patient’s airway, breathing, and circulation remains intact. Once the patient arrives at the hospital, mechanical ventilation and supportive therapies are enacted. While in transport, some additional methods can be utilized to prevent venom spread. Pressure immobilization involves bandaging the limb starting at the distal end (fingers or toes) and moving towards the axial joints. This technique has been suggested to prevent further injury following envenomation. The wrapping should be tight but not to the point that circulation is affected. There should be a frequent examination to ensure that the most distal parts (i.e., fingers, toes) remain pink. It is suggested that these bandages should be removed for 90 seconds and reapplied every 10 minutes, but this should in no way impact the speed of transport to a hospital.[8][9][7]

Additional reports have suggested that hot water (40 C to 50 C) may be effective for pain relief after cone snail envenomation. More reports are needed before this becomes standard of care, but at this time it is primarily based on anecdotal data.

Differential Diagnosis

  • Allergic reaction
  • Cnidaria envenomation
  • Sea snake envenomation
  • Shellfish envenomation

Prognosis

Even in cases where the patient receives appropriate therapy, death may still result. Rapid transport to a hospital for intubation and supportive therapy are paramount to patient survival.

Pearls and Other Issues

In the past, conotoxins and affected ion channels have been studied to understand the toxic effects that envenomation can have on the body. In recent years, research has focused on how conotoxins can be used as medicinal therapies. The primarily explored pharmaceutical potential has been in cases of intractable pain. At this time, a conotoxin from C. magus has been FDA-approved for pain management under the trade name Prialt. Other toxins have been considered as management of Parkinson’s disease and to provide cardioprotective effects. Given the large variety of neuromodulatory targets, conotoxins could potentially serve as therapy for a wide range of disease. 

An additional, but concerning, potential use of conotoxins is the capability of creating bioterrorism agents. Most toxins are relatively simple combinations of peptides, so as they are studied, these combinations are relatively easy to recreate within a laboratory setting. Potential bioterrorism concerns include utilization of conotoxins in food source contamination and aerosolization of conotoxins for wide dispersal.

Enhancing Healthcare Team Outcomes

With many people favoring water-based activities, it is inevitable that cone snail toxicity will occur in some individuals. The majority of patients with cone snail toxicity first present to the emergency department and hence, the triage nurse must be aware of its potential morbidity and mortality. Quick triage and prompt notification of the emergency department team is key to survival. Over the years, fatalities have been reported to several species of cones, with death occurring within 5-8 hours after envenomation. The vast majority of patients will develop a chronic wound with ulceration that often requires meticulous care. The key to cone snail toxicity is patient education. Anyone who is into water sports should have some idea what cone snails look like and should only handle them with proper gloves. Swimmers should be urged not to carry a live cone on them close to the skin. Finally, when going to the beach, it is important for the public to wear appropriate footwear and avoid reaching blindly under rocks or crevices.

 


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Cone Snail Toxicity - Questions

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Envenomation with which of the following is least likely to result in respiratory arrest?



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When is cone snail envenomation most likely to occur?



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A 48-year-old novice diver arrives at the emergency department after suspected cone snail envenomation in his right forearm. The patient is alert but appears in distress. His mucous membranes are dry and he has a blue tinge to his lips. Admission vitals are temperature 38C, pulse 120 bpm, blood pressure 146/86 mmHg, and respiratory rate 6/minute. What is the next appropriate step in management?



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Cone Snail Toxicity - References

References

Abdel-Wahab M,Miyashita M,Ota Y,Juichi H,Okabe R,Sarhan M,Fouda M,Abdel-Rahman M,Saber S,Nakagawa Y, Isolation, structural identification and biological characterization of two conopeptides from the Conus pennaceus venom. Bioscience, biotechnology, and biochemistry. 2017 Nov     [PubMed]
Gao B,Peng C,Lin B,Chen Q,Zhang J,Shi Q, Screening and Validation of Highly-Efficient Insecticidal Conotoxins from a Transcriptome-Based Dataset of Chinese Tubular Cone Snail. Toxins. 2017 Jul 6     [PubMed]
Safavi-Hemami H,Lu A,Li Q,Fedosov AE,Biggs J,Showers Corneli P,Seger J,Yandell M,Olivera BM, Venom Insulins of Cone Snails Diversify Rapidly and Track Prey Taxa. Molecular biology and evolution. 2016 Nov     [PubMed]
Wang F,Yan Z,Liu Z,Wang S,Wu Q,Yu S,Ding J,Dai Q, Molecular basis of toxicity of N-type calcium channel inhibitor MVIIA. Neuropharmacology. 2016 Feb     [PubMed]
Yoshiba S, [An estimation of the most dangerous species of cone shell, Conus (Gastridium) geographus Linne, 1758, venom's lethal dose in humans]. Nihon eiseigaku zasshi. Japanese journal of hygiene. 1984 Jun     [PubMed]
Reimers C,Lee CH,Kalbacher H,Tian Y,Hung CH,Schmidt A,Prokop L,Kauferstein S,Mebs D,Chen CC,Gründer S, Identification of a cono-RFamide from the venom of {i}Conus textile{/i} that targets ASIC3 and enhances muscle pain. Proceedings of the National Academy of Sciences of the United States of America. 2017 Apr 25     [PubMed]
Norton RS,Olivera BM, Conotoxins down under. Toxicon : official journal of the International Society on Toxinology. 2006 Dec 1     [PubMed]
András CD,Albert C,Salamon S,Gálicza J,András R,András E, Conus magus vs. Irukandji syndrome: a computational approach of a possible new therapy. Brain research bulletin. 2011 Oct 10     [PubMed]
Lewis RJ, Ion channel toxins and therapeutics: from cone snail venoms to ciguatera. Therapeutic drug monitoring. 2000 Feb     [PubMed]

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