1. Seafood Safety and Natural Marine Toxins
Robert J. Price
Food Science & Technology
Sea Grant Extension Program
UC Davis

2. Major Causes of Seafood-borne Illness
Live molluscan shellfish
Vibrio species
Norwalk-like viruses
Natural marine toxins
Scombroid fish poisoning
Ciguatera fish poisoning
Live molluscan shellfish continue to be a major cause of seafood-borne illness.

3. Estimated Cases Per Year
Norwalk-like virus 100,000
Scombroid fish poisoning 8,000
Ciguatera fish poisoning 1,600
Vibrio species 1,060
Hepatitis A 1,000
Salmonella 200
Shigella 200
Clostridium perfringens 200
Includes recreational and subsistence fishing (not common for other protein sources)

4. Natural Marine Toxins Scombroid fish poisoning (histamine)
Ciguatera fish poisoning
Shellfish toxins (ASP, DSP, NSP, PSP)
Tetrodotoxin
Gempylotoxin
Pfiesteria

5. Scombroid Fish Poisoning
Named for the family Scomberidae (tunas and mackerels)
Can involve any fish containing high levels of free histidine
Bacteria break down free histidine into histamine

6. Histamine Formation Histamine itself is often nontoxic
Histamine is a useful marker for fish that could cause scombroid fish poisoning.
Histamine is heat stable and not destroyed by cooking or canning

7. H2N–CH2–CH2–CH2–CH2–CH2–NH2
Diamines
Cadaverine
H2N–CH2–CH2–CH2–CH2–CH2–NH2
Putrescine
H2N–CH2–CH2–CH2–CH2–NH2
The actual mechanism of poisoning must depend on additional cofactors, possible diamines such as cadaverive and putrescene

8. Scombroid Fish Poisoning
Source: improperly handled (time/temperature abuse) mahi mahi, tuna, bluefish, sardines, mackerel
Range: worldwide
Source: improperly handled (time/temperature abuse) mahi mahi, tuna, bluefish, sardines, mackerel
Range: worldwide

9. Scombroid Fish Poisoning
Onset: immediate to 30 minutes
Initial symptoms: tingling or burning sensation in the mouth, rash on the upper body, drop in blood pressure, headache, itching of the skin
Later symptoms: nausea, vomiting, and diarrhea
Duration: 3 hours to several days
Onset: immediate to 30 minutes
Initial symptoms: tingling or burning sensation in the mouth, rash on the upper body, drop in blood pressure, headache, itching of the skin
Later symptoms: nausea, vomiting, and diarrhea
Duration: 3 hours to several days

10. Scombroid Fish Poisoning
Treatment: antihistamines
Control: proper chilling and temperature control
FDA guideline: 50 ppm
Treatment: Antihistamines
Control: proper chilling and temperature control after capture
FDA guideline: 50 ppm histamine in raw, frozen tuna and mahi mahi; Canned tuna; and related species

11. Scombrotoxin Outbreaks
: >200 cases (imported mahi mahi)
1986: 10 cases (Pacific yellowtail)
1988: 9 cases (yellowfin tuna)
1988: 8 cases (mahi mahi)
1998: 4 cases (yellowfin tuna)
2000: 21 cases in California (escolar)
: >200 cases (imported mahi mahi)
1986: Three restaurants in Alabama and Tennessee. Nine customers and one employee ate Pacific amberjack fish (yellowtail or kahala). Onset minutes. Facial rash, body rash, headache, oral paresthesias, shortness of breath, vomiting. Duration 3-36 hours (median 14 hours) mg% histamine in fish sampled by FDA
1987: Albuquerque, New Mexico. Mahi-mahi. Symptoms: nausea, vomiting, diarrhea, headache, fever, flushing, rapid pulse rate. Duration: 36 hours. Fish contained 20 mg% histamine.
1989: 9 cases, South Carolina. Yellowfin tuna. Onset 38 minutes. Symptome: flushing, dairrhea, headache, fever, nausea, rapid pulse, pruitus, dizziness, vomiting. Duration: 6 hours. Fish contained mg% histamine.
1989: Illinois. Mahi mahi. Onset: 90 minutes. Symptoms: headache, nausea, flushing, dizziness, diarrhea. Fish contained mg% histamine.
1998: Pennsylvania. 4 cases from tuna-spinach salad (yellowfin tuna). Onset 5 minutes to 2 hours
2000: 21 cases in California (Escolar)

12. Ciguatera Fish Poisoning
Four toxins: structure not determined
Source: certain species of fish feeding on several algae species including Gambierdiscus
Range:
Tropical and subtropical waters worldwide
U.S.: East coast, Puerto Rico, Hawaii, Virgin Islands
Toxins: heat stable
Four toxins: structure not determined
Source: certain species of tropical and subtropical fish feeding on several algae species including Gambierdiscus
Range: Tropical and subtropical waters worldwide
U.S.: East coast, Puerto Rico, Hawaii, Virgin Islands
Toxins: heat stable

13. Ciguatera Fish Poisoning
Onset: <6 hours
Symptoms:
Gastrointestinal: nausea, vomiting, diarrhea
Neurological: numbness and tingling around mouth, joint pain, muscle ache, headache, temperature sensory reversal
Cardiovascular: arrhythmia, bradycardia, tachycardia, reduced blood pressure
Onset: <6 hours
Symptoms:
Gastrointestinal: nausea, vomiting, diarrhea
Neurological: perioral (around the mouth) numbness and tingling, arthralgia (joint pain), myalgia (muscle ache), headache, temperature sensory reversal, acute sensitivity to temperature extremes, vertigo (dizziness), and muscular weakness to the point of prostration
Cardiovascular: arrhythmia (irregular heart reat), bradycardia (slow heart rate), tachycardia (rapid heart rate), reduced blood pressure

14. Ciguatera Fish Poisoning
Duration:
Usually self-limiting within several days
Rarely some neurological symptoms may persist for months or years
Treatment:
Treat symptoms
Duration:
Usually self-limiting within several days
Rarely some neurological symptoms may persist for months or years
Treatment:
Treat symptoms

15. Ciguatera Fish Poisoning
Control:
Mouse bioassay
“Cigua-check” test kit available
Enzyme immunoassay under evaluation
Obtain fish from safe harvest areas
Commonly implicated species:
Groupers, barracudas, snappers, jacks, mackerel, and triggerfish
FDA guideline: no guideline
Control:
Mouse bioassay
“Cigua-check” test kit available
Enzyme immunoassay under evaluation
Obtain fish from safe harvest areas
Commonly implicated species:
Groupers, barracudas, snappers, jacks, mackerel, and triggerfish
FDA guideline: no guideline

16. Ciguatera Outbreaks
1981: Puerto Rico, 49 cases, 2 deaths (barracuda, amberjack, blackjack)
1987: Caribbean, 57 cases (fish casserole)
1988: Florida, >100 cases (hogfish)
1992: California, 25 cases (flag cabrilla)
1994: California, several cases (yellowtail)
1995: Guam (sea weed?)
1981: Puerto Rico, 49 cases, 2 deaths (barracuda, amberjack, blackjack)
1987: Caribbean, 57 cases (fish casserole)
1988: Florida, >100 cases (hogfish)
1992: California, 25 cases (flag cabrilla)
1994: California, several cases (yellowtail)
1995: Guam (sea weed?)

17. Shellfish Toxins Amnesic shellfish poisoning
Diarrheic shellfish poisoning
Neurotoxic shellfish poisoning
Paralytic shellfish poisoning

18. Amnesic Shellfish Poisoning
Heterocyclic nitrogen compound, similar in structure to kainic acid and glutamate (exicitatory neurotransmitter)
Identified in 1959
Heat stable

19. Amnesic Shellfish Poisoning
Source: Molluscan shellfish (mussels) feeding on algae (Pseudo-nitzschia spp.), viscera of Dungeness crab and anchovies
Range: Northeast and northwest North America
First reported in 1987 off Prince Edward Island, Canada
Northeast and Gulf of Mexico
Toxic Pseudo-nitzschia are present. Low levels have been detected in shellfish
West Coast
3 species of Pseudo-nitzschia (not all produce toxin)
First noticed in Pelicans and comorants dying in Monterey Bay with neurological symptoms. Tons of anchovy catches recalled or diverted. Identified in razor clams, Dungeness crab viscera, anchovies, blue mussels, viscera of tanner and red rock crab
May and June 1998: sea lions along the southern and central California coast with strange and unusual behavior. July 1998: domoic acid in razor clams in both Oregon and Washington state. Clams ~300 ppm, may retain toxin at high levels for 6-12 months.
Blooms are common in late summer and fall. Monitored along entire coast

20. Amnesic Shellfish Poisoning
Onset:
Gastrointestinal symptoms within 24 hours
Neurological symptoms within 48 hours
Symptoms:
Gastrointestinal: vomiting, diarrhea, vomiting
Neurological: confusion, memory loss, disorientation, seizure coma
Onset:
Gastrointestinal symptoms within 24 hours
Neurological symptoms within 48 hours
Symptoms:
Gastrointestinal: vomiting, diarrhea, vomiting
Neurological: confusion, memory loss, disorientation, seizure coma

21. Amnesic Shellfish Poisoning
Duration:
Self-limiting within several days
Short-term memory loss can be permanent
Control:
HPLC laboratory procedure
Obtain shellfish from approved waters
Monitoring of coastal water and shellfish
Duration:
Self-limiting within several days
Short-term memory loss can be permanent
Control:
HPLC laboratory procedure
Obtain shellfish from approved waters
Monitoring of coastal water and shellfish

22. Amnesic Shellfish Poisoning
FDA guideline:
20 ppm domoic acid in all fish
30 ppm domoic acid in viscera of Dungeness crab
Outbreaks:
1987: Prince Edward Island, Canada
156 cases, 3 deaths, 12 with permanent short-term memory loss (mussels)
1991: Washington state
24 cases (razor clams)
FDA guideline:
20 ppm domoic acid in all fish
30 ppm domoic acid in viscera of Dungeness crab
Outbreaks:
1987: 156 cases, 3 deaths (mussels)
156 cases from cultured blue mussels (Mytilus edulis) harvested off Prince Edward Island. 22 people hospitalized; 3 elderly patients died. Some short-term memory loss
1991: 24 cases, not severe (razor clams)
Annual problem on the west coast

23. Diarrheic Shellfish Poisoning
Okadaic acid and its derivatives
Presumably caused by a group of high molecular weight polyethers, including okadaic acid, the dinophysis toxins, the pectenotoxins, and yessotoxin.

24. Diarrheic Shellfish Poisoning
Source: molluscan shellfish feeding on algae (Dinophysis and Prorocentrum spp.)
Range: Japan, southeast Asia, Scandinavia, western Europe, Chile, New Zealand, eastern Canada
Toxins: heat stable
Source: molluscan shellfish feeding on algae (Dinophysis and Prorocentrum spp.)
Range: Japan, southeast Asia, Scandinavia, western Europe, Chile, New Zealand, eastern Canada
No cases reported in the U.S., but the organisms are present in U.S. waters
May be widespread and under reported

25. Diarrheic Shellfish Poisoning
Onset: 30 minutes to 3 hours
Symptoms: mild diarrhea, nausea, vomiting, abdominal pain, chills, headache, fever
Duration: 2-3 days with or without treatment
Onset: 30 minutes to 3 hours
Symptoms: mild diarrhea, nausea, vomiting, abdominal pain, chills, headache, fever
Duration: 2-3 days with or without treatment

26. Diarrheic Shellfish Poisoning
Control:
Mouse bioassay
HPLC procedure
Molluscan shellfish from approved waters
FDA guideline:
0.2 ppm okadaic acid plus 35-methyl okadaic acid (DXT 1) in all fish
Control:
Mouse bioassay
HPLC procedure
Molluscan shellfish from approved waters
FDA guideline:
0.2 ppm okadaic acid plus 35-methyl okadaic acid (DXT 1) in all fish

27. Neurotoxic Shellfish Poisoning
Polyether brevetoxins (6 toxins + 2 phosphorus containing toxins)
Group of polyethers called brevetoxins.

28. Neurotoxic Shellfish Poisoning
Source: molluscan shellfish feeding on algae (Gymnodinium breve)
Range: gulf of Mexico and southern Atlantic coast in U.S.; New Zealand
Toxins: heat stable

29. Neurotoxic Shellfish Poisoning
Onset: a few minutes to a few hours
Symptoms: tingling and numbness of the lips, tongue, and throat, muscular aches, dizziness, cold hot sensation reversal, diarrhea, vomiting
Duration: a few hours to several days
Resembles mild ciguatera fish poisoning or PSP
Blooms usually cause fish kills

30. Neurotoxic Shellfish Poisoning
Control:
Mouse bioassay
HPLC
Commercial immunoassay
Obtain molluscan shellfish from approved waters
FDA guideline:
0.8 ppm brevetoxin-2 equivalent (20 mouse units/100g) in clams, mussels and oysters
Bioassay
Probably not many cases in the U.S. per year

31. Neurotoxic Shellfish Poisoning
Outbreaks:
Sporadic and continuous along the gulf coast of Florida, North Carolina, and Texas

32. Paralytic Shellfish Poisoning
Saxitoxins (12-20 analogs)
Heterocyclic multi-ring nitrogen containing compounds
Production by bacteria? (Vibrio, Pseudomonas, Moraxella spp.)

33. Paralytic Shellfish Poisoning
Source: contaminated molluscan shellfish feeding on algae (Alexandrium, Pyrodinium, Gymnodinium spp.)
Range: tropical to temperate waters worldwide
Worldwide in temperate areas
Can cause death
California quarantine from May 1 to October 31
Found in viscera of mackerel, lobster, Dungeness crab, tanner crab, red rock crab; eggs of horseshoe crab (Thailand)

34. Paralytic Shellfish Poisoning
Onset: ½ to 2 hours
Symptoms: tingling, burning, numbness, drowsiness, incoherent speech, respiratory paralysis
Duration: respiratory support within 12 hours of exposure results in complete recovery
Controls in California

35. Paralytic Shellfish Poisoning
Control:
Mouse bioassay
Monitoring of coastal waters and shellfish
Obtain molluscan shellfish from approved waters
FDA guideline:
0.8 ppm saxitoxin equivalent (80μg/100g) in all fish

36. PSP Outbreaks 1976-89: 42 outbreaks in Alaska
1980: California, 98 cases, 2 deaths (oysters)
1990: Massachusetts, 6 cases (mussels)
1990: Alaska, 11 cases
1980: California, 98 cases, 2 deaths
1990: Massachusetts, 6 cases (blue mussels)
1990: Alaska, 11 cases, butter clams and mussels ( , 42 outbreaks in Alaska)
Mean outbreak size = 8 persons

37. October 1999
Alexandrium catenella 1-10%
Pseudo-nitzschia 1 = <10%, 3 = 10-50%

38. October 1999
Alert level = 80 ug/100g (0.8 ppm)
360 ug Kehoe Beach
390 ug Drakes Estero
440 ug Limantour Beach

39. Tetrodotoxin
Produced by bacteria (Vibrio, Altermonas, Pseudomonas)

40. Tetrodotoxin
Source:
Gonads, liver, intestines, and skin of about 80 species of puffer fish, blowfish or fugu
Also found in the California newt, parrotfish, frogs (Atelopus genus), blue-ringed octopus, starfish, octopus, and xanthid crabs

41. Tetrodotoxin Range: Primarily the Indo-Pacific Ocean
Other cases and deaths have occurred from puffer fish from the Atlantic Ocean, Gulf of Mexico, and Gulf of California
Range: Pacific, Atlantic and Indian oceans
Onset: 20 minutes to 3 hours
Initial symptoms: numbness of the lips and tongue
Secondary symptoms: prickling of the face and extremities, a sensation of lightness or floating, headache, epigastric pain, nausea, diarrhea and/or vomiting
Tertiary symptoms: increasing paralysis and death within 4-6 hours

42. Tetrodotoxin Onset: 20 minutes to 3 hours
Initial symptoms: numbness of the lips and tongue
Secondary symptoms: prickling of the face and extremities, a sensation of lightness or floating, headache, epigastric pain, nausea, diarrhea and/or vomiting
Tertiary symptoms: increasing paralysis and death within 4-6 hours
Onset: 20 minutes to 3 hours
Initial symptoms: numbness of the lips and tongue
Secondary symptoms: prickling of the face and extremities, a sensation of lightness or floating, headache, epigastric pain, nausea, diarrhea and/or vomiting
Tertiary symptoms: increasing paralysis and death within 4-6 hours (range 20 min. to 8 hours)

43. Tetrodotoxin Control: FDA guideline: Mouse bioassay HPLC method
Do not eat puffer fish or avoid improperly prepared pufferfish
FDA guideline:
Puffer fish may not be imported except under specific authorization from FDA
Control:
Mouse bioassay
HPLC method
Do not eat puffer fish or avoid improperly prepared pufferfish
FDA guideline:
Puffer fish may not be imported except under specific authorization from FDA
One importer in New York City certified to import puffer fish (1999)

44. Tetrodotoxin Outbreaks
Japan:
, 646 cases, 179 deaths
persons per year mostly from home preparation and consumption
Mortality about 50%
California:
1996, 3 cases, no deaths
Japan:
, 646 cases, 179 deaths
persons per year mostly from home preparation and consumption
Mortality about 50%
California:
1996, 3 cases, no deaths
Illegally brought into country from Japan. Chef who brought fish didn’t eat any

45. Gempylotoxin
Toxin: oil contained in the flesh and bones of specific species
Source: Gemplids, escolars or pelagic mackerels (escolar; oilfish, castor oil fish or purgative fish; snek)
Range: almost worldwide

46. Gempylotoxin Symptoms: diarrhea, generally without pain or cramping
Control: avoid specific fish species
FDA guideline: escolar should not be imported
Outbreaks: California, 8+ cases, March 2000
Symptoms: diarrhea, generally without pain or cramping
Control: avoid specific fish species
FDA guideline: escolar should not be imported (no longer enforced)

47. Pfiesteria
planetENN, September 30, 1996

48. Pfiesteria piscicida Discovered in 1988 Phytoplankton (dinoflagellate)
Up to 24 life stages (4 may be toxic)
Eats other organisms, usually algae
Discovered in 1988
Phytoplankton (dinoflagellate)
Up to 24 life stages (4 may be toxic)
Eats other organisms, usually algae

49. Pfiesteria Blooms
Pfiesteria may produce toxins that numb fish, allowing the microbes to feed on the fish
High concentrations of Pfiesteria can cause deep lesions on fish and may kill them
Blooms usually exist for only a few hours
Several massive fish kills in estuaries along coastal North Carolina
Pfiesteria may produce toxins that numb fish, allowing the microbes to feed on the fish
High concentrations of Pfiesteria can cause deep lesions on fish and may kill them
Blooms usually exist for only a few hours
Several massive fish kills in estuaries along coastal North Carolina

50. Pfiesteria No cases of seafood-borne illness have been reported
Human health effects have occurred in laboratories where researchers were working in close proximity to high concentrations of the microorganism
Anglers, water skiers, fish-kill monitors have complained of skin lesions, headaches, lightheadedness, short-term memory loss
No cases of seafood-borne illness have been reported
Human health effects have occurred in laboratories where researchers were working in close proximity to high concentrations of the microorganism
Anglers, water skiers, fish-kill monitors have complained of skin lesions, headaches, lightheadedness, short-term memory loss

51. Information Sources FDA’s Bad Bug Book
Seafood Network Information Center