Featured Poison

Brevetoxin: Weaponized Neurotoxic Shellfish Poisoning

Saltwater algal blooms can give rise to harmful toxins that accumulate in filter-feeding mollusks, like mussels, clams, and oyster. While these toxins may be harmless to our shellfish friends, they can be particularly harmful, even deadly, to the humans that eat them. It’s taken a while, but we’re finally at the last installment of shellfish poisoning. To recap, here are the four shellfish poisoning syndromes, with links to the previous posts:

  • Amnesic shellfish poisoning (ASP)
    • One of the best! Domoic acid not only causes anterograde amnesia – the ability to form new memories after exposure, but can be lethal. Alfred Hitchcock observed the bizarre behavior of a flock of domoic acid poisoned birds and used it as inspiration for his classic movie “The Birds.”
  • Diarrheal shellfish poisoning (DSP)
    • Okadaic acid: spend 3 days on the toilet after ingesting algae bloom affected oysters. As little as 0.048 milligrams of okadaic acid is all that is needed to bring about nausea, vomiting, GI distress, and all day toilet marathons.
  • Paralytic shellfish poisoning (PSP)
    • I grew up with red tides in the Pacific Northwest and its accompanying PSP caused by saxitoxin. Symptoms start with a tingling of the lips but can progress to total paralysis and even death…from one clam. Saxitoxin is one of the more potent, and lethal toxins known.
  • Neurotoxic shellfish poisoning (NSP)
    • You’re on this page, so if you want to read about how Mother Nature has weaponized toxins, keep reading.

Not all red tides are created equal. In the Pacific Northwest, red tides are primarily due to the explosive growth of the dinoflagellate genus Alexandrium, which produce saxitoxin, the toxin responsible for paralytic shellfish poisoning (PSP). On the kitty-corner side of the country, red tides in the Gulf of Mexico and up the southeastern coast of the United States are chiefly due to the dinoflagellate Karenia brevis.

Blooms of K. brevis occur every year off the west coast of Florida in the late summer and early fall months. These noxious blooms kill off large numbers of fish and birds, and appear to be more extreme and occurring more frequently. Whether climate and ocean temperature change are responsible is debatable, as are human interventions and pollution, but it is important to note that red tides in Florida have been recorded as early as 1844, long before notable human development and pollutions. Regardless of the cause, K. brevis blooms pose a significant human health risk in the form of neurotoxic shellfish poisoning (NSP). (1)

Karenia brevis by Florida Fish and Wildlife Conservation Commission (public domain)

Karenia brevis by Florida Fish and Wildlife Conservation Commission (public domain)

Most dinoflagellates have a thecal plate made of cellulose that is essentially armor plating. Those dinoflagellates are hardcore. K. brevis? They swim around naked. They’re fragile. As the waves break upon the shores, our delicate dinoflagellates rupture, spewing their toxin. These toxins are harmful to fish, leading to massive fish die-offs, but are inert to shellfish. Filter-feeding mollusks like clams and oysters continuously take up these toxins and store them within their tissues. When they are harvested and eaten by humans and other animals, they become intoxicated and feel its effects. Neither freezing or cooking has any effect on the toxin.

But ingestion is only a small part of the problem. Of particular risk to humans is the aerosolization of toxins. As K. brevis breaks up on the shore, its toxin is taken up by the salt air and winds, spreading it throughout. In this way, Mother Nature has weaponized a toxin in her arsenal and subjected it to unsuspecting humans. And the toxin? Brevetoxin.*

*The total synthesis of brevetoxin was seen as the “Holy Grail” of natural product synthesis, and the success by K.C. Nicolaou – or rather dozens of graduate students and postdocs – was widely celebrated. It’s cool and all I guess, but at over 100 steps with a total yield of about 0.0005%, it’s certainly not practical. (2)BrevetoxinBrevetoxins bind to voltage-gated sodium channels – membrane proteins that allow the flow of sodium ions through the cell’s plasma membrane, generating an action potential, which is essentially an electrical current across the cell – and keeps them activated. The constantly open sodium channel allows sodium ions to flow freely through the cell membrane, allowing nerves and muscles to spontaneously fire, as if in a constantly excited state. This is in contrast to saxitoxin, of PSP fame, in which saxitoxin blocks sodium channels, keeping them in a persistently closed state, leading to paralysis.

Signs of brevetoxin intoxication include a range of both neurological and gastrointestinal symptoms. Neurologically, victims report the loss of body control (ataxia), slurred speech, and disorientation. On the gastrointestinal side, there is the trifecta of nausea, vomiting, and diarrhea. Symptoms usually occur within hours after the consumption of contaminated shellfish and may last several days. On the plus side, no one is known to have died from brevetoxin exposure, and people recover completely in a few days. Treatment is general supportive care, including fluid repacement and sedatives as necessary. Exposure due to aerosolized brevetoxin presents a little differently, with symptoms primarily consisting of eye and throat irritation, nasal congestion, and headaches. But these too, like with ingestions, will go away on their own without any lingering effects. (3, 4)

Aerosolized brevetoxin is what I find to be so cool about NSP, it’s like Mother Nature is using chemical warfare against us. Imagine taking a vacation to Florida and walking along the sandy beach, only to start having itchy, watery eyes and a massive headache! Mother Nature is certainly out to get us, so be on you guard.

** Featured image of Dead Fish after Red Tide by Judy Baxter (CC BY-NC-SA 2.0) **

References:

  1. Kirkpatrick, Barbara, et al. “Literature Review of Florida Red Tide: Implications for Human Health Effects.” Harmful Algae 3.2 (2004): 99-115.
  2. Nicolaou, K. C., et al. “Total Synthesis of Brevetoxin A.” Nature 392.6673 (1998): 264-69.
  3. Watkins, Sharon M. “Neurotoxic Shellfish Poisoning.” Marine Drugs 6.3 (2008): 430-55.
  4. Backer, Lorraine C., et al. “Occupational Exposure to Aerosolized Brevetoxins during Florida Red Tide Events: Effects on a Healthy Worker Population.” Environmental Health Perspectives 113.5 (2005): 644-49.

 

8 thoughts on “Brevetoxin: Weaponized Neurotoxic Shellfish Poisoning

  1. I seem to recall that the toxin ( not sure of its nature) from another dinoflagellate, Pfiesteria piscicida, also may aerosolize.

    Also, some entertaining toxic dinoflagellate sci-fi out there: Powlik’s Sea Change and Schatzing’s The Swarm.

  2. Does palytoxin also aerosolize? On the subject of massive dinoflagellate-produced toxins requiring an excess of postdocs to synthesise…
    Also your PSP link leads to your post on tetrodotoxin, not saxitoxin.
    Also, LOVE your work.

    • Palytoxin does aerosolize – I’m not sure about in nature, though I doubt it. The poisonings I’m familiar with are typically from people cleaning out aquariums that have zoanthid corals. Thanks for the tip on the bad link and thank you very much for reading and the kind words.

  3. Nice read! I was just at a conference on the west coast of Florida a couple of weeks ago. The hotel was about 3/4 of a mile from the beach, which was closed due to a red tide. I’d go out on my balcony, cough, and hear everyone else out on their balconies coughing, all due to the aerosolized brevetoxin. One of the speakers (an expert on algal toxins) mentioned during his presentation that as soon as he got into town he took a shuttle down to the beach. He got there and immediately started coughing and thought “This is awesome!! Well, it’s not really a good thing, but it was awesome!”. I have to say that I kinda thought the same thing. (f course, it’s still a terrible thing for the people in Florida to have to deal with.)

  4. Your series on shellfish poisoning is outstanding. Just a vey minor criticism. I understand that your interests and professional experience is obviously North American-centric, but I am sure you have also some audience in Asia and Europe. Neurotoxic shellfish poisoning is indeed a “private” American problem (US Atlantic coast and Gulf of Mexico; other reports as far as I know only from New Zealand — Walkins SM et al. Drugs 2008; 6: 431-55), but amnesic shellfish
    poisoning (ASP) has been widely reported all over the Mediteanean area—although likely through different ecological mechanisms, as reported by the Harmful Algal Bloom Programme of the Intergovernamental Oceonographic Commission of Unesco). Much the same is true for paralytic shellfish poisoning.

  5. Another comment, if I can. It is true that Ciguatera fish poisoning is not, strictly speaking, a shellfish-derived problem, since ciguatoxins (ciguatoxin and maitotoxin) strike humans after accumulating (serially in the alimentary chain) in dinoflagellates (genus Gambierdiscus) associated with microalgae in coral reefs. Yet there were 24,000 cases of Ciguatera in French Polynesia alone between 1960 and 1984 (Ferrante M et al, 2013. doi:10.4172/scientificreports.5
    87), and dinoflagellate toxicity is quite similar to the topics you discussed so fascinatingly in your series: only the ecological mechanism is a bit different. Moreover, shellfishs can filter and accumulate ciguatoxins, although this has not been so far the dominant toxic mechanism.

  6. Desperate for relief! I cannot move away right now school starts. What do i do?
    Here is the recent situation.
    I am going to start in Mid july. I started having extreme scalp itching. I think Lice, NO LICE. This is on going still. By July 27th, I am having severe sore throat, itchy eyes, and burning ears. This was so bad that I green secretions from nose and eyes. No biggie I figured my daughter brought this home. She is 13 and was at a local summer camp and was complaining of sore throat. During this time I am following the Wahl’s protocol an (AIP paleo diet) and other than the above complaints I am feeling very good, more energy and enthusiastic.

    Now we start to hear about Red Tide fish kills.

    I wake up on August 7th this past Tuesday- the whole left side of m body is numb, from my shoulder to the tip of my toes. Let’s just say it is very comfortable. I go to my primary care and she looks through my chart and sends me to the ER for a CAT scan. Dr. in ER looks at CAT scan and says it’s perfect. My labs are normal. I go home. PCP calls and says I want you to have an MRI to rule out MS. Again I am not shocked, having CFS for 13 years, it could be.
    Wednesday 8/8 my right arm is now numb. I call my accupuncturist get an appointment but no real relief. Thinking about a pinched nerve.
    Thursday 8/9- I am still whole left side numb, with right arm numb. About 9:30 am my tongue get’s numb more on the left side. Oh I forgot to say that I am having problems distortions in distinguishing cold and wet. It is hard to explain. If I lie on the bed the cold sheet feels wet, warm water does not feel wet but cold.
    I am really frustrated so I take to Facebook and the Wahl’s protocol page and explain what I am explaining to you. There are loads of very intelligent and immuno-compromised people there. I got so much information on a wide range off things. Top of the list was MS, CIRS, and BREVATOXIN poisoning! With the help of these wonderful people we tracked down an article from the CDC that explains my weird symptoms to a T. I went to my PCP with a copy of the article, I was dismssed and told to take an antianxiety pill. Is there anything that can relieve my distress.
    But the ER Dr. diagnosed me with Paresthesias. Parathesias is listed as a symptom of brevatoxin poisoning. I am very uncomfortable and frightened because it also mentions liver damage.

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