Tetrodotoxin Toxicity

What is Tetrodotoxin Toxicity?

Tetrodotoxin is a harmful substance or poison found in sea creatures, specifically the pufferfish, but it’s also in some land animals. The pufferfish takes the lead as the animal with the most tetrodotoxin – over 20 types of pufferfish can make it, and there are 26 known natural types of this substance.

While tetrodotoxin is poisonous for most, those animals that make it have special changes in their DNA that make them immune to the harmful effects. In humans, this toxin is known to cause a feeling of numbness around the mouth in those who consume sushi made from pufferfish, a dish popular in Japan called fugu. Interestingly, cooking doesn’t get rid of the poison because it’s not affected by heat. If people consume it, the toxin can block certain pathways in their body called sodium channels, causing paralysis. This can lead to immediate serious health problems if it’s not quickly identified.

Areas where animals carrying tetrodotoxin are found are more prone to occurrences of poisoning, particularly in seafood-related cases. Though less common, improperly prepared food can cause poisoning even in areas where this toxin isn’t typically found. Regrettably, there’s no known cure for such a poison, and there isn’t a definitive treatment. Therefore, it’s very important to understand the symptoms and signs to ensure the condition doesn’t lead to fatal outcomes.

What Causes Tetrodotoxin Toxicity?

Tetrodotoxin is a natural toxin found in various animals including newts, toads, pufferfish, angelfish, blue-ringed octopus, moon snails, starfish, xanthid crabs, arrow worms, ribbon worms, some flatworms, and planarians. Interestingly, these animals don’t produce the toxin themselves. It’s created by bacteria and builds up in creatures that are higher up in the food chain.

An experiment found this by measuring the levels of tetrodotoxin in pufferfish raised in captivity, particularly in their organs like the liver. All captive pufferfish had unnoticeable levels of tetrodotoxin. When they were fed the livers of wild pufferfish, the levels increased, showing that the toxin accumulates in them.

The bacteria guilty of producing this toxin belong to several groups, including Pseudoalteromonas, Pseudomonas, Vibrio, Aeromonas, Alteromonas, Shewanella, Roseobacter, Raoultella, Actinomycetes, Microbacterium, and Serratia. Some creatures have these toxin-producing bacteria naturally present, contributing to the toxin accumulation. The situation with newts is a bit unclear – we’re not sure yet if the tetrodotoxin is naturally produced inside them or comes from outside.

Interestingly, the creatures containing this toxin are immune to its ill effects. Usually, sodium channels have a chain of aromatic amino acids, and the toxin affects them. But the creatures with the toxin in their bodies have a different amino acid, which reduces the affinity of the sodium channels for tetrodotoxin – making them effectively immune.

Poisoning can occur in humans if they ingest organisms containing tetrodotoxin. In the U.S., common sources of poisoning include imported pufferfish, mislabeled pufferfish, Pacific and Eastern newts. Of the 4 Pacific newt species containing the toxin, the deadliest are found in Oregon. The Eastern newt contains the toxin too, but it’s only 1/100th as potent as the Pacific newts.

While pufferfish are usually the culprits in the U.S., Bangladesh, Japan, Australia, and India, locally found wildlife can also be the source worldwide. For instance, toadfish cause poisoning in Australia, marine gastropods and thread-sail fish in Japan, and the eggs of horseshoe crabs in Thailand. In New Zealand, a number of dogs were poisoned after eating grey side-grilled sea slugs.

Risk Factors and Frequency for Tetrodotoxin Toxicity

Tetrodotoxin poisoning isn’t very common, but its frequency can vary depending on where you live and what kind of animals live there. This type of poisoning is mostly caused by pufferfish. Countries such as Japan, Taiwan, and some places in Southeast Asia have a higher rate of tetrodotoxin poisoning because pufferfish is a regular part of their diet.

Between 2002 and 2006, 223 people in Japan were affected by this poisoning, and 13 of them died.
From 2001 to 2006, 53 people in Singapore were diagnosed with tetrodotoxin poisoning, and 8 died.
In 2008, the sale of cheap pufferfish in Bangladesh fish markets led to three outbreaks of the poisoning, affecting 141 people, 17 of whom died from respiratory failure.
Another outbreak happened when people ate the eggs of a type of pufferfish called Takifugu oblongus. This outbreak led to 5 deaths.
In 2018, there was a case in Oman where 5 people got tetrodotoxin poisoning from eating some locally caught pufferfish.

There have been a few instances of tetrodotoxin poisoning from other animals that contain the toxin, but these are rare because these animals are usually not eaten. Some of these cases involve exposure to poisonous types of newts kept as unusual pets and certain kinds of crabs.

Signs and Symptoms of Tetrodotoxin Toxicity

If someone eats something containing tetrodotoxin, like a pufferfish, newt, or sea snail, they can get poisoned. The time it takes for symptoms to appear and how severe they are can vary based on how much was eaten and when it was consumed. Usually, symptoms appear within half an hour after eating. But, in rare cases, it might take up to 20 hours for them to show up.

If the poisoning isn’t too severe, symptoms could start anywhere from half an hour to six hours after eating. These will generally get better after 24 hours. If the poisoning is more serious, symptoms can come on quickly and lead to difficulty breathing in just 15 to 20 minutes.

The severity of tetrodotoxin poisoning is usually categorized into four grades based on a scale developed by Fukuda and Tani in 1941:

Grade 1: Tingling feelings and numbness around the mouth, along with possible gastrointestinal symptoms (like nausea, vomiting, abdominal pain, and diarrhea)
Grade 2: Numbness in the face, slurred speech, early stage paralysis and a loss in coordination, but reflexes remain normal
Grade 3: Full-body limpness, loss of voice, difficulty breathing, and enlarged pupils (while still conscious)
Grade 4: Difficulty breathing leading to low oxygen levels, slow heartbeat, low blood pressure, abnormal heart rhythms, and a lack of consciousness

Testing for Tetrodotoxin Toxicity

Your doctor might run various tests to understand the cause of your symptoms. For instance, an electrocardiogram could be used to check your heart’s activity if you’re experiencing chest pain or a rapid heart rate. A brain scan (CT scan) might be performed to check for potential strokes or other issues within your brain. Additionally, they might do blood tests to check your electrolyte levels, how well your kidneys are working, and your blood counts.

Unfortunately, there aren’t any specific lab tests that can confirm tetrodotoxin poisoning, which is often diagnosed based on your medical history and symptoms. That being said, in the research setting, tests like mouse bioassays and a technology called liquid chromatography coupled with mass spectrometry can be used to find evidence of tetrodotoxin. There are also specialized labs, like at the CDC, that can measure levels of tetrodotoxin in your urine or blood, using a testing method known as LC-MS/MS. However, it’s important to note that the results from these types of tests can take some time and should not delay any necessary treatment decisions.

Treatment Options for Tetrodotoxin Toxicity

Tetrodotoxin poisoning doesn’t have a known antidote or specific cure. Instead, doctors primarily focus on supportive care. This includes helping the patient breathe and providing other necessary treatments until the body naturally eliminates the tetrodotoxin.

If the poison was eaten less than an hour ago and the patient isn’t confused or actively throwing up, medical professionals might use activated charcoal to soak up the toxin or perform gastric lavage. This is a procedure where they clean out the stomach.

Hemodialysis, a process where a machine filters waste and water from your blood, might potentially help patients with kidney disease. However, it’s unclear whether this treatment can actually remove the toxin. Tetrodotoxin doesn’t dissolve in water well enough to be effectively removed by hemodialysis. There are instances where some patients showed improvement after multiple sessions of hemodialysis. However, reports regarding the effectiveness of this treatment are conflicting and inconclusive.

An antitoxin (anti-tetrodotoxin) that binds and neutralizes tetrodotoxin has been created and it worked in mice. However, we don’t have any information on whether it would work in humans.

Neostigmine, a type of drug, has been used in treating acute respiratory failure – a condition in which fluid leaks into the lungs making breathing difficult – caused by tetrodotoxin poisoning. However, a recent review found that there’s insufficient evidence to conclude whether it’s an effective treatment for tetrodotoxin poisoning.

In cases of suspected tetrodotoxin poisoning, the patient should be closely observed in the intensive care unit. This is because the symptoms can sometimes occur up to 20 hours after exposure to the toxin.

When you have certain symptoms, a doctor will consider many possible causes. Those can include:

Poisoning from a specific fish (ciguatera toxicity)
A minor heart condition called first-degree AV block
A rare condition that affects the nerves and weakens muscles, known as Guillain-Barré syndrome
Low calcium levels in the blood (hypocalcemia)
A condition that impacts the communication between nerves and muscles, known as Lambert-Eaton myasthenia syndrome
Poisoning from an octopus sting
A condition causing irregular heartbeat, known as second-degree AV block
Poisoning from eating certain types of shellfish
A serious heart condition that can cause your heart to beat irregularly or stop beating, known as third-degree AV block

Your doctor will consider all these possibilities based on your symptoms and will conduct the necessary tests to arrive at the correct diagnosis.

What to expect with Tetrodotoxin Toxicity

If severe toxicity isn’t treated, it could lead to serious heart complications or paralysis of the respiratory system, which are life-threatening. However, with the right supportive care, most patients are likely to recover completely without any lasting damage to the nervous system.

Possible Complications When Diagnosed with Tetrodotoxin Toxicity

Eating pufferfish or other similar marine animals can cause Tetrodotoxin poisoning, leading to dangerous and potentially deadly problems.

Problems related to Tetrodotoxin poisoning may include:

Neurological Symptoms: Tetrodotoxin poisoning affects the nerves first. You might feel numb or have a tingling sensation around your mouth and in your hands and feet. People can also experience paralysis that starts with the face and spreads to other parts of the body. Muscle strength may decrease and difficulties with talking or swallowing may be noticed.
Respiratory Distress: It can also harm your breathing muscles leading to difficulties with breathing. In serious cases, this can result in a complete failure to breathe, which necessitates immediate medical help such as a ventilator.
Cardiovascular Effects: The poison can decrease your blood pressure significantly. There may also be a slow heart rate or an irregular heartbeat, which could lead to instability in the circulatory system.
Gastrointestinal Symptoms: You may feel nauseous, vomit or have stomach pain soon after eating seafood containing tetrodotoxin.
Seizures: Tetrodotoxin poisoning can sometimes cause seizures along with neurological problems.
Coma: In serious instances, poisoning can lead to unconsciousness or even coma.
Death: Tetrodotoxin poisoning can be fatal, primarily due to respiratory failure or cardiovascular collapse.
Delayed Onset: Symptoms may not appear for several hours after eating contaminated seafood, making diagnosis and treatment complicated.
No Antidote: Unfortunately, there’s no concrete solution for tetrodotoxin poisoning. Treatment mainly involves care and managing symptoms.

Preventing Tetrodotoxin Toxicity

Tetrodotoxin poisoning mainly happens from eating improperly cooked pufferfish, a popular dish in Japan and other East and South Asian countries. The best way to avoid this type of poisoning is to not eat pufferfish.

If you start to feel numbness around your mouth that then spreads to your face, slurred speech, and a lack of coordination, these could be signs of poisoning. You might also feel sick to your stomach, vomit, have diarrhea or stomach pain. More serious indications of severe poisoning could include symptoms like chest pain, feeling less mentally alert, or having trouble breathing. If you experience any of these symptoms, it’s crucial that you go to the hospital immediately. Although there’s no specific cure for this poisoning, the right supportive care and monitoring should help you recover fully.

You can also get tetrodotoxin poisoning from eating animals that are not usually consumed as food. Some examples include the blue-ringed octopus and the rough-skinned newt. Additionally, you could get poisoned from a bite, like the one from a blue-ringed octopus. Be careful while handling animals that could potentially have this toxin.

Frequently asked questions

Tetrodotoxin toxicity is the harmful effect caused by the ingestion of tetrodotoxin, a poisonous substance found in certain sea creatures such as pufferfish. It can lead to symptoms such as numbness, paralysis, and serious health problems if not quickly identified and treated.

The signs and symptoms of Tetrodotoxin Toxicity can vary based on the severity of the poisoning. Here are the possible signs and symptoms: - Grade 1: Tingling feelings and numbness around the mouth, along with possible gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and diarrhea. - Grade 2: Numbness in the face, slurred speech, early stage paralysis, and a loss of coordination. However, reflexes remain normal. - Grade 3: Full-body limpness, loss of voice, difficulty breathing, and enlarged pupils while still conscious. - Grade 4: Difficulty breathing leading to low oxygen levels, slow heartbeat, low blood pressure, abnormal heart rhythms, and a lack of consciousness. In general, symptoms usually appear within half an hour to six hours after eating something containing tetrodotoxin. However, in rare cases, it might take up to 20 hours for symptoms to show up. If the poisoning is not too severe, symptoms generally improve after 24 hours. But if the poisoning is more serious, symptoms can come on quickly and lead to difficulty breathing in just 15 to 20 minutes.

You can get Tetrodotoxin Toxicity by ingesting organisms that contain tetrodotoxin, such as pufferfish, newts, or sea snails.

The doctor needs to rule out the following conditions when diagnosing Tetrodotoxin Toxicity: 1. Poisoning from a specific fish (ciguatera toxicity) 2. A minor heart condition called first-degree AV block 3. A rare condition that affects the nerves and weakens muscles, known as Guillain-Barré syndrome 4. Low calcium levels in the blood (hypocalcemia) 5. A condition that impacts the communication between nerves and muscles, known as Lambert-Eaton myasthenia syndrome 6. Poisoning from an octopus sting 7. A condition causing irregular heartbeat, known as second-degree AV block 8. Poisoning from eating certain types of shellfish 9. A serious heart condition that can cause your heart to beat irregularly or stop beating, known as third-degree AV block

There are no specific lab tests that can confirm tetrodotoxin poisoning. However, in a research setting, tests like mouse bioassays and liquid chromatography coupled with mass spectrometry can be used to find evidence of tetrodotoxin. Specialized labs, such as those at the CDC, can measure levels of tetrodotoxin in urine or blood using a testing method known as LC-MS/MS. It's important to note that these tests can take some time for results and should not delay necessary treatment decisions.

Tetrodotoxin poisoning is primarily treated with supportive care. This includes assisting the patient with breathing and providing necessary treatments until the body naturally eliminates the toxin. If the poisoning occurred less than an hour ago and the patient is not confused or actively vomiting, medical professionals may use activated charcoal or perform gastric lavage to remove the toxin from the stomach. Hemodialysis may potentially help patients with kidney disease, but its effectiveness in removing the toxin is uncertain. An antitoxin that neutralizes tetrodotoxin has been developed and shown to work in mice, but its effectiveness in humans is unknown. Neostigmine, a drug used to treat acute respiratory failure caused by tetrodotoxin poisoning, has insufficient evidence to support its effectiveness. Patients suspected of tetrodotoxin poisoning should be closely observed in the intensive care unit due to the delayed onset of symptoms.

The side effects when treating Tetrodotoxin Toxicity may include: - Neurological Symptoms: Numbness or tingling sensation around the mouth, hands, and feet. Paralysis starting from the face and spreading to other parts of the body. Decreased muscle strength and difficulties with talking or swallowing. - Respiratory Distress: Difficulty breathing, which can progress to complete failure to breathe, requiring immediate medical assistance such as a ventilator. - Cardiovascular Effects: Decreased blood pressure, slow heart rate, and irregular heartbeat, leading to circulatory system instability. - Gastrointestinal Symptoms: Nausea, vomiting, and stomach pain. - Seizures: Tetrodotoxin poisoning can sometimes cause seizures along with neurological problems. - Coma: In serious cases, unconsciousness or coma can occur. - Death: Tetrodotoxin poisoning can be fatal, primarily due to respiratory failure or cardiovascular collapse. - Delayed Onset: Symptoms may not appear for several hours after exposure, making diagnosis and treatment challenging. - No Antidote: There is no known antidote or specific cure for tetrodotoxin poisoning. Treatment mainly involves supportive care and managing symptoms.

With the right supportive care, most patients are likely to recover completely without any lasting damage to the nervous system. However, if severe toxicity isn't treated, it could lead to serious heart complications or paralysis of the respiratory system, which are life-threatening.

A medical professional or doctor should be consulted for Tetrodotoxin Toxicity.