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Neurologic Illness Associated with Eating Florida Pufferfish, 2002

Since January 1, 2002, human illness after eating pufferfish caught in waters near Titusville, Florida, has been reported (Figure 1). The illnesses were manifested by neurologic symptoms consistent with exposure to paralytic shellfish toxins. Laboratory analysis in early April confirmed the presence of saxitoxin in uneaten pufferfish. This report presents selected case examples and summarizes all cases reported to the Toxic Exposure Surveillance System of the American Association of Poison Control Centers (TESS).

Case Reports

Florida. On January 2, the poison control center in Tampa, Florida, received a call from an emergency department (ED) physician about a man aged 34 years who had numbness and tingling of his hands. On January 1, he had experienced vomiting and diarrhea after eating approximately eight mouthfuls of pufferfish recreationally caught in waters near Titusville. The man was admitted to the hospital for observation and was administered intravenous fluids. His symptoms gradually resolved, and he was released 2 days after admission.

Virginia. On March 12, a man aged 50 years and his son aged 24 years returned from a fishing trip to Titusville, where they had caught several pufferfish. Approximately 3 hours after they had cooked and eaten the fish, they contacted the Richmond poison control center complaining of numbness and tingling of the lips and tongue. The two men decided to monitor their symptoms at home. The younger man's symptoms were limited to oral numbness and resolved in 3--4 days. The older man's symptoms progressed during the evening to include numbness and tingling in the face, neck, and shoulders; the next day, he still had numbness in his mouth. The symptoms reportedly resolved over 2 weeks.

New Jersey. On March 18, a woman aged 65 years was brought to the hospital ED by her husband. Hours earlier, they had eaten a meal of pufferfish that a family member had caught in Titusville. Several minutes after eating the fish, both persons experienced tingling around their lips. During the next 2 hours, the woman's symptoms worsened, and she developed vomiting. They contacted the New Jersey Poison Information and Education System and were advised to go to the hospital ED. The woman developed increasing chest pain and had mild tachycardia and blood pressure of 160/70 mmHg; she was treated with topical nitroglycerine. During the next 4--6 hours, she developed an ascending muscular paralysis. A test of her respiratory function indicated carbon dioxide retention and a rapid decrease to <20% of normal vital capacity for a woman her age. She was electively intubated and placed on a ventilator. Over the next day, she regained her reflexes and voluntary movement. She was extubated at approximately 72 hours and discharged.

Laboratory Findings

Uneaten fish samples recovered in New Jersey were submitted for toxin analysis to the Institute for Marine Biosciences, National Research Council, Canada. Liquid chromatographic-tandem mass spectrometric analysis of uneaten fish samples did not detect tetrodotoxin in any of the pufferfish samples (1). However, the analysis confirmed that the fish contained the paralytic shellfish toxin, saxitoxin, and two analogs, N-sulfocarbamoylsaxitoxin and decarbamoylsaxitoxin. Liquid chromatography with postcolumn oxidation and fluorescence detection confirmed these analytical results (2).

A split specimen also was submitted to the regional Food and Drug Administration (FDA) laboratory in Queens, New York. Presence of a sodium channel-blocking toxin was confirmed by cell bioassay (3). These results are consistent with the presence of saxitoxin or tetrodotoxin.

Toxic Exposure Surveillance System

Since January 1, TESS has identified 10 illnesses of presumed pufferfish poisoning (five from Florida, three from New Jersey, and two from Virgnia). All ill persons reported eating pufferfish originating from the Titusville area (Indian and Banana rivers). All reported at least one of the following symptoms: tingling in the mouth and lips or fingertips, numbness, or peripheral neuropathy. All cases eventually resolved. Efforts are ongoing to identify additional cases.

Reported by: S Marcus, MD, MY Wong, B Ruck, PharmD, New Jersey Poison Information and Education System, Univ of Medicine and Dentistry of New Jersey/New Jersey Medical School, Newark; E Bresnitz, MD, State Epidemiologist, New Jersey Dept of Health and Senior Svcs. R Hammond, PhD, Florida Dept of Health. H Rogers, PhD, M McGeehin, PhD, Div of Environmental Hazards and Health Effects, National Center for Environmental Health, CDC.

Editorial Note:

Neurologic illnesses associated with eating pufferfish (i.e., blowfish, sea squab, and Fugu [Terodontidae and Diodontidae families]) are not common in the United States. Pufferfish are harvested recreationally and commercially in the United States and internationally. Fish harvested in the United States are often transported to different states for sale. Several of the approximately 100 species of pufferfish contain neurotoxins (i.e., tetrodotoxin and/or saxitoxin); most pufferfish caught in U.S. waters are not known to be toxic, although there have been reports of toxic pufferfish.

The cases in this report occurred after eating pufferfish but are consistent with paralytic shellfish poisoning (PSP). In the United States, PSP is associated with eating filter-feeding shellfish or mollusks. Approximately 10 outbreak-associated PSP cases are reported to CDC each year. Ingestion of paralytic shellfish toxins produces neurologic symptoms that are sensory, cerebellar, and motor. The most common symptoms are tingling and burning of the mouth and tongue, numbness, drowsiness, and incoherent speech. These symptoms occur 30 minutes to 2 hours after ingestion of the fish, depending on the amount of toxin ingested. In severe cases, ataxia, muscle weakness, respiratory paralysis, and death can occur (4).

Saxitoxin and tetrodotoxin together and saxitoxin alone in freshwater pufferfish have been reported in waters near Thailand (5) and Bangladesh (6). Saxitoxin and its analogs are produced by dinoflagellates of the Gonyaulacoid family and by some freshwater cyanobacteria (7). Shellfish are contaminated when toxin-producing organisms multiply in the water and form a bloom, and water-siphoning shellfish---principally clams, mussels, and scallops---filter out organisms to feed and absorb any toxins produced. Generally, nonfilter feeders such as fish, lobsters, crabs, and shrimp are considered safe to eat, even if caught in contaminated waters. However, pufferfish eat molluscs and might accumulate or even magnify the toxin (8).

Saxitoxin is heat- and acid-stable and does not alter the odor or taste of food. This toxin cannot be destroyed by cooking or freezing. It is rapidly absorbed through the human gastrointestinal tract and excreted in urine. The molecule is complex and contains a guanidinium moiety. This portion of the molecule is believed to block the opening of the voltage-sensitive Na+ channel, preventing the rapid entrance of sodium into the cell at depolarization. The rapid movement of sodium is necessary for propagation of neural impulses and mediation of cellular function. The outcome of blockage at this site is motor paralysis.

Tetrodotoxin is a powerful neurotoxin that has been detected in many pufferfish species; its presence is usually associated with season, geographic location, sex, and organ tissue. Tetrodotoxin might be produced by Vibrio species or other bacteria that bioaccumulate in the pufferfish (9). Tetrodotoxin has been detected in pufferfish throughout the Pacific Ocean and the Baja California coastal region. This is the first report to CDC of neurotoxic pufferfish in the Atlantic Ocean.

Health-care providers should be aware that rapid onset of neurologic symptoms after a meal of pufferfish could be caused by saxitoxin. Ill persons should be advised to proceed to a hospital ED and contact their local poison control center.

On April 11, the New Jersey Department of Health and Senior Services (NJDHSS) issued a report describing two of the New Jersey cases. On April 12, NJDHSS issued a warning about eating pufferfish originating from the Titusville area. On April 15, FDA also issued a health advisory on pufferfish caught from this area. The Florida Department of Health, in collaboration with the Florida Department of Agriculture and Consumer Services and the Florida Fish and Wildlife Conservation Commission, is assessing the extent of the presence of saxitoxin in pufferfish and other marine species. New Jersey, Florida, FDA, and CDC are continuing to investigate this situation.

Acknowledgments

This report is based on data contributed by G Wolf, J Blumenstock, New Jersey Dept of Health and Senior Svcs. SR Rose, PharmD, Virginia Poison Center. JL Schauben, PharmD, V Speranza, Pharm D, Florida Poison Information Center. T Litovitz, MD, American Association of Poison Control Centers, Washington, DC. Office of Regulatory Affairs and Center for Food Safety and Applied Nutrition, Food and Drug Administration. M Quilliam, PhD, D Wechsler, Institute for Marine Biosciences, National Research Council, Canada, Halifax.

References

  1. Quilliam M, Hess P, Dell'Aversano C. Recent developments in the analysis of phycotoxins by liquid chromatography-mass spectrometry. In: deKoe WJ, Samson RA, Van Egmond HP, Gilbert J, Sabino M, eds. Mycotoxins and Phycotoxins in Perspective at the Turn of the Century. Wageningen, The Netherlands: W.J.deKoe, 2001:383--91.
  2. Oshima Y. Postcolumn derivatization liquid chromatographic method for paralytic shellfish toxins. JAOAC Int 1995;78:528--32.
  3. Manger R, Leja LS, Lee SY, Hungerford JM, Wekell MM. Tetrazolium-based cell bioassay for neurotoxins active on voltage-sensitive sodium channels: semi-automated assay for saxitoxins, brevetoxins, and ciguatoxins. Anal Biochem 1993;214:190--4.
  4. Rodrigue D, Etzel R, Hall S, et al. Lethal paralytic shellfish poisoning in Guatemala. Am J Trop Med Hyg 1990;42:267--71.
  5. Sato S, Kodama M, Ogata T, et al. Saxitoxin as a toxic principle of a freshwater puffer, Tetraodon fangi, in Thailand. Toxicon 1997;35:137--40.
  6. Zaman L, Arakawa O, Shimosu A, Onoue Y. Occurrence of paralytic shellfish poison in Bangladeshi freshwater puffers. Toxicon 1997; 35:423--31.
  7. Hall S, Strichartz GR, Moczydlowski E, Ravindran A, Reichardt PB. The saxitoxins: sources, chemistry, and pharmacology. In: Hall S, Strichartz GR, eds. Marine Toxins. ACS Symposium Series 418, Washington, DC: American Chemical Society 1990:29--65.
  8. Nakamura M, Oshima Y, Yasumoto T. Occurrence of saxitoxin in puffer fish. Toxicon 1984;22:381--5.
  9. Lee M, Jeong D, Kim W, et al. A tetrodotoxin-producing vibrio strain, LM-1, from the puffer fish Fugu vermicularis radiatus. Appl Environ Microbiol 2000;66:1698--701.


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