A small number of algal species produce potent hepatotoxins or neurotoxins that can be transferred through the food web where they may kill other life forms such as zooplankton, shellfish, fish, birds, marine mammals and even humans that feed, either directly or indirectly, on them. Scientists use the term, harmful algal bloom, HAB, to refer to such high density algal populations that contain toxins or that cause negative impacts. Most toxic marine blooms are caused by algae; toxic freshwater algal blooms are rare. Almost all toxic freshwater blooms are caused by cyanophytes; they also cause many toxic marine blooms.
The very potent toxins produced by many solitary, filamentous or colonial, primarily marine, algae are responsible for an increasing number of water-related poisonings of both wildlife and people worldwide since the 1970s. Researchers generally understand the biochemistry of these toxins once they are consumed or absorbed, but not as much about what causes the algae to produce them and how they can be prevented from flourishing. Pollution with high nutrient runoff, particularly high phosphorus levels encourages and prolongs the blooms; it also causes blooms in nearshore and estuarine areas where there is the highest chance of contact by people and the most effect on the harvesting of marine resources. However, there are significant economic and political obstacles impeding efforts to clean up polluted, high-nutrient, runoff which contributes to such algal blooms or to enforce adequate drinking water treatment and watershed protection.
There are naturally occurring toxins in some marine species that do not involve marine algae, several are mentioned briefly below but are not dealt with further in this report. They are mentioned simply for interest, and to indicate that getting sick from eating fish or shellfish is not always attributable to algal toxins. This is by no means an exhaustive list.
Fish known as Escolar, Lepidocybium flavobrunneum and Ruvettus pretiosus, contain a strong purgative oil, called gempylotoxin. The diarrhea caused by eating the oil contained in the flesh and bones of these fish develops rapidly and is pronounced but generally occurs without pain or cramping. No other untoward effects have been reported.
Puffer fish, or fugu, may contain tetrodotoxin in some portions of their flesh. Poisonings from tetrodotoxin have usually been associated with the consumption of puffer fish from waters of the Indo-Pacific ocean regions. However, several reported cases of poisonings, including fatalities, involved puffer fish from the Atlantic Ocean, Gulf of Mexico, and Gulf of California. There have been no confirmed cases of poisonings from the northern puffer, Sphoeroides maculatus, found in the Atlantic Ocean, but there is still reason for concern. Symptoms of poisoning usually begin within 10 minutes of consuming puffer fish. The victim first experiences numbness and tingling of the mouth. This is followed by weakness, paralysis, decreased blood pressure and quickened and weakened pulse. Death usually occurs within 30 minutes.
Tetramine is a toxin that is found in the salivary glands of Neptunia, a type of whelk.
Some algae produce compounds that are lethal to fish and shellfish. These include species such as Gyrodinium aureolum, Gymnodinium, Chrysochromulina polylepis, Prymnesium parvum and Heterosigma carterae. Heterosigma carterae (syn. Heterosigma akashiwo) is a chloromonad that has killed thousands of caged fish in Japan, Canada, Scotland and Ireland. Heterosigma carterae kills fish with peroxides which cause copious amounts of mucus to occur on the gills. In some cases hyperplasia of the gill epithelial surfaces is noted, however in most cases, no obvious histological problems are observed. Prymnesium parvum, a small golden-brown flagellate, secretes its toxin into the surrounding water and is the case of large recurrent fish mortalities in Europe and the Middle East. These toxins affect cell permeability, leading to osmotic imbalances. The toxicity of Prymnesium parvum is promoted by phosphorus deficiency.
Some algae and diatoms impart off-flavours or bitter taints to shellfish, rendering them unpalatable and unmarketable. In 1987 in Port Phillip Bay, Melbourne, Australia, a bloom of the diatom Rhizosolenia chunii occurred and 3 species of shellfish within the bay, mussels, oysters and scallops, developed a powerful bitter taint. The taint was so persistent and unpleasant that the mussels from the bay were unmarketable for 7 months, causing a revenue loss of approximately $1 million. A similar effect was reported in 1987 in Alaska where bitter crab disease was described in Alaskan tanner crabs. This was attributed to an infection with a dinoflagellate of the genus Hematodinium.
Heterosigma carterae is a poor food source for mussels, clams and oysters and under bloom conditions, when it is the only food available, the shellfish do not get adequate nutrition even though the volume of food taken in may increase.
Another way that algae kill without toxins is exemplified by the diatoms Chaetoceros concavicornis and Chaetoceros convolutum which are lethal to salmonids at 5 cells per mL and cause chronic damage at 2 cells per mL. These alga have barbed spines which break off, irritate the gills and penetrate the gill membranes. This causes the fish to produce an overabundant supply of mucous which clogs the gills and causes suffocation by reducing oxygen uptake. The fish die of oxygen starvation and their blood goes anaerobic. There is also capillary hemorrhage and secondary infections. The setae can also induce multiple granulomas in more chronic cases. One prymnesiophyte, Phaeocystis pouchetii, as well as producing mucus that can foul fishing nets, also produces acrylic acid that is highly irritant to fish gills.
Certain species of algae can seriously harm fish and shellfish by producing mucus which can clog the gills and cause suffocation, or mechanically obstruct and damage the gills. Several species of diatoms within the genus Thalassiosira form gelatinous masses that have been noted as clogging the gills of farmed oysters in Japan and gelatinous Thalassiosira blooms have been seen in Australia, in New South Wales and the Gulf of Carpentaria.
Thus, blooms that occur in areas where fish and shellfish are commercially farmed or harvested can cause serious economic losses in several ways.
The direct economic importance of the algae is considerable and is likely to increase rapidly as the human population of the world expands faster than the conventional sources of protein foodstuffs. It is certain that man's contact with these organisms will increase, and it is probable that their role in human disease either as opportunistic pathogens or as cutaneous irritants or sensitizers has been underestimated and unsuspected. While most are never toxic and some species are not toxic most of the time, some algal species, particularly the diatoms and dinoflagellates, have strains or varieties which are sometimes lethally toxic. This usually occurs under heavy bloom conditions when there are high nutrients, lots of sunshine and warm temperatures in poorly flushed waters.
Only a few dozen of the many thousands of species of microscopic and macroscopic algae are repeatedly associated with toxic or harmful blooms. Some species, such as the dinoflagellate Alexandrium tamarense and the diatom Pseudo-nitzschia australis produce potent toxins which are liberated when the algae are eaten. Others like Pfiesteria piscicida use exotoxins to kill their prey. Other species kill without toxins, such as Chaetoceros which has spines with serrated edges which can lodge in fish gill tissues, causing irritation, over production of mucous and eventual death. A natural part of the marine environment, dinoflagellates are microscopic, free-swimming, single-celled organisms, usually classified as a type of alga. The vast majority of dinoflagellates are not toxic. Although many dinoflagellates are plant-like and obtain energy by photosynthesis, others, including Pfiesteria, are more animal-like and acquire some or all of their energy by eating other organisms.
Many species produce novel compounds that exhibit potent biological activities. These are generally considered to be secondary metabolites, that is, compounds which are not essential to the basic metabolism and growth of the organism, which are present in restricted taxonomic groups. The biosynthesis of secondary metabolites is common in bacteria, as well as in eukaryotic microbes and plants. The roles played by secondary metabolites in the life history of the producing organism are much debated. Many are considered to be chemical defenses, which confer competitive advantage over other species or discourage predation by higher trophic level organisms. Others may serve roles in chemical signaling and communication, and yet others have been proposed to be evolutionary relics. The elaborate biosynthetic pathways required to synthesize these compounds, and the observation that genes involved in biosynthesis of a given secondary metabolite are often clustered within the genome, are consistent with the notion that these metabolites serve a specific function for the organism.
Among the many secondary metabolites that have been identified, a number are potent toxins responsible for a wide array of human illnesses, marine mammal and bird morbidity and mortality and extensive fish kills. Toxins of human health significance occur primarily in three groups, dinoflagellates, diatoms and cyanobacteria. Dinoflagellates are responsible for the widest array. However, only a few dozen species, of the several thousand species of dinoflagellates known, appear to be toxic. Among the diatoms Pseudo-nitzschia is the best known species that produces a toxin impacting human health.
About 75% of the known toxic marine algal species are dinoflagellates which are microscopic, single-celled algae with flagella that enable them to travel through the water. Some dinoflagellate species are photosynthetic, some eat other organisms and some do both. There are around 2,000 species of dinoflagellates in the world. While most species are not harmful, about 30 dinoflagellates produce potent neurotoxins that are capable of producing poisoning in human consumers of contaminated seafood. Some species can grow rapidly, accumulating near the sea surface and discoloring the water in a phenomenon called a red tide. While red tides usually have benign effects, some species produce toxins as they redden the sea. Other algal species produce toxins but do not discolor the sea at all.
Diatoms are single-celled, microscopic algae that secrete and are enclosed by cell walls which form an often intricate, round-to-elongated shell consisting of almost identical halves, which fit together much as a box fits into its lid. The walls contain some cellulose but are primarily composed of silica, which gives them rigidity and also produces elaborately sculpted patterns of grooves that often serve as identifying features. The cytoplasm contains the green pigment chlorophyll, but other pigments, especially the yellowish xanthophyll, give the organisms a golden-brown appearance. Reproduction is usually by cell division. The shells separate and each half secretes a slightly smaller shell that fits inside the old one. Successive cell divisions result in ever smaller daughter cells until a minimum size is reached. Periodically, sexual reproduction by means of fertilization of haploid gametes produces cells the original size for the species. More than 8000 species exist, mostly in freshwater lakes and ponds or on the surface of the oceans, where they are a major component of the plankton on which aquatic life depends.
Diatoms are found in fresh and salt water, in moist soil, and on the moist surfaces of other plants; they are the principal constituent of plankton, an important food source for aquatic animals. Most exist singly, but some form stalked or branched colonies. When the aquatic forms die, their shells collect in on the bottom, eventually forming diatomaceous earth, kieselguhr, or the more compact, chalky, light-weight rock called diatomite, used in sound and heat insulation, in making explosives and for filters and abrasives. Most limestone and much petroleum is of diatom origin.
Virtually all freshwater blooms are caused by cyanophyta and all the toxic freshwater species are cyanophyta. Freshwater algae rarely cause more than oxygen depletion problems due to high density blooms. In a healthy and balanced aquatic ecosystem, algae are an important component of the natural plankton population. Unfortunately, human impact can stimulate massive growth of algae and in the worst cases the resulting bloom can turn a lake or river green. The severity of the blooms varies from year to year depending on the climate, blooms tend to be worst in particularly dry summers or during droughts and least severe in wetter summers. Although blooms occur naturally, water bodies which have been enriched with plant nutrients from municipal, industrial or agricultural sources, particularly phosphorus, are susceptible to these growths. Water inflow from fertile agricultural land and from sewage or certain industrial wastes encourages algal growth. Blooms usually occur during summer and the ponds or lakes involved have been found to be enriched in some way by the inflow of water from arable land or by animal excreta. Algal blooms are most common in warm, calm, shallow bodies of water, ponds, reservoirs sloughs, roadside ditches and other man-made impoundments, where the water is rich in nitrogen, phosphates and organic matter. They do not normally occur in flowing waters, rivers, streams, springs, irrigation canals or wells.
There are two main types of human activity that stimulate algal blooms.
Marine outbreaks occur worldwide but usually only cause concern in near-coastal waters when they affect shellfish or fin fish. Ocean warming has combined with nutrient enrichment to create larger, more frequent algal blooms around the world. Satellite images have confirmed increases in the size and scope of algal growth during the 1980s and early 1990s. El Niño-precipitated events that bring heavier rainfall and regional warming have been associated with the emergence or resurgence of harmful blooms, especially at higher latitudes. Other environmental stresses that encourage blooms include over-harvesting of fish that feed on plankton and destruction of wetlands that filter nitrogen and phosphorus.
Marine algal blooms affect commercial and recreational shellfish and fish harvesting, recreational swimming and diving and the fish and wildlife food chain. The toxins produced are among the most potent and fast acting known and there are no antidotes only or treatments, other than life support, after ingestion has occurred. Human fatalities are common when ingestion occurs, fortunately such occurrences are quite rare; animal fatalities can be enormous when major marine blooms occur, especially in nearshore waters.
Scientists and environmentalists seeking answers to the Pfiesteria problem in North Carolina believe much of the blame lies with the industrial-scale hog farming that has mushroomed in the eastern part of the state. More than 16 million hogs were raised between Interstate 95 and the Outer Banks in one recent year. Hundreds of millions of gallons of untreated, nutrient-rich hog feces and urine produced at these loosely regulated factory farms are stored in earthen lagoons that sometimes leak or collapse. In 1995, 25 million gallons of liquid swine manure, more than twice the volume of the Exxon Valdez oil spill , flowed into the New River after a lagoon was breached. Plankton feed on these nutrients and Pfiesteria, which feeds on the plankton, thrives.
A harmful algal bloom occurs when one of several related species of dinoflagellates in the genus Alexandrium grows rapidly and contaminates shellfish. Paralytic shellfish poisoning, PSP, which can be life-threatening, occurs when people eat the contaminated shellfish. Alexandrium species can also kill fish, birds, and marine mammals. PSP occurs along more coastline in the United States than any other harmful algal problem. On the East Coast, PSP recurs frequently from Maine to Massachusetts, and occasionally farther south to New Jersey. Since 1991, PSP has recurred on the West Coast each year from northern California to Alaska. Researchers do not believe that nutrients from human sources are driving these blooms since Alexandrium can grow in relatively pristine waters and it is difficult to argue that anthropogenic nutrient inputs are stimulating the blooms. The reported appearance of PSP since 1991 on the West Coast is probably due to improved detection methods and to communication among scientists.
The notorious alga, Chrysochromulina polylepis, was debated in the Norwegian Parliament. It built up a bad reputation in Norway after it knocked out all life in the upper layers of the waters along much of the coast of Southern Norway in the summer of 1988. The N/P ratio of the sea, which is usually fairly constant, was much higher than normal that spring and summer and absolute concentrations were high. This was caused by the addition of nitrates and other sources of nitrogen from rivers in regions surrounding the North Sea, in Germany and The Netherlands. A very wet spring leached large quantities of such compounds out of the soil and washed them down the rivers to the North Sea. Then the Jylland Current carried them northwards to the Skagerrak.
The relationship between nitrogen and phosphates in the sea is expressed as a ratio, N/P, which is normally about 15. The algae were exposed to N/P ratios ranging from 2.5 to 100. The Chrysochromulina polylepis growth rate was not very sensitive to the N/P ratio, while other algae tested in the same way obviously grew more slowly when the N/P ratio was high. This means that Chrysochromulina polylepis is at a competitive advantage when the nutrient content of the ocean is dominated by N-salts. This is one factor that helps to explain the huge algal bloom of 1988. It killed practically all other life-forms in the upper layers of the water.
The oldest known toxic species in North America is the dinoflagellate Gymnodinium breve that causes neurotoxic shellfish poisoning, NSP. In blooms, this dinoflagellate's toxins also kill fish, invertebrates, birds and marine mammals. NSP blooms may also become aerosolized in surf, and can cause respiratory problems in people who breathe them. NSP is the best-documented illness caused by a harmful algal species. Centuries ago, Tampa Bay Indians and Spanish explorers noticed fish kills in certain seasons when coastal waters turned red. In 1880, shellfish poisonings were reported along the west coast of Florida, and in 1916 the first complaints about respiratory problems in association with algal blooms were recorded. In 1946, Gymnodinium breve was discovered to be the cause of NSP.
Gymnodinium breve grows naturally offshore on the continental shelf consuming low levels of nutrients. But Gymnodinium breve blooms are also transported inshore by currents. In coastal bays the blooms may last longer if provided with additional nutrients from man-made sources. Evidence suggests that dense blooms inshore cannot be sustained without inputs of new nutrients. If so, human inputs of nutrients could be responsible for extending the duration, severity and impacts of red tides once blooms enter the nearshore zone, including bays and canals.
Researchers once believed that Gymnodinium breve stayed almost exclusively in the Gulf of Mexico from Yucatan to the Texas coast, sightings have also occurred in Alabama, Mississippi and Louisiana waters. However, in recent years scientists have documented the transport of Gymnodinium breve from the Gulf. In 1987-1988, the Gulf Stream carried the algae to the east coast of Florida and pushed it further north. Eventually, toxic blooms reached North Carolina for the first time and shellfish beds were subsequently closed to harvesting for months. There was a public health crisis with 48 documented cases of illness from shellfish poisoning. The regional economic impact of the shellfish bed closing was estimated to be $25 million. In January 1998 Gymnodinium breve was once again transported from the Gulf of Mexico to Palm Beach County on Florida's east coast. In the surf, the toxins aerosolized and wafted inland with the breezes and caused breathing problems for people living near the ocean.
syn. Pfiesteria piscimorte
syn. Pfiesteria piscimortius
Pfiesteria piscicida is a toxic dinoflagellate that has been associated with fish lesions and fish kills in coastal waters from Delaware to North Carolina. Discovered in 1988, Pfiesteria piscicida is now known to have a highly complex life-cycle with 24 reported life stages, a few of which can produce toxins. A few other toxic dinoflagellate species with characteristics similar to Pfiesteria have been identified but not yet named. These are referred to as Pfiesteria-like organisms, and they occur from Delaware to the Gulf of Mexico.
Pfiesteria normally exists in non-toxic forms, feeding on algae and bacteria in the water and in sediments of tidal rivers and estuaries. It is an estuarine species that forms ephemeral toxic blooms, the causative agent of at least 30% of the recent major fish kills within three annual cycles in estuaries of the southeastern USA. This small species is heterotrophic and the flagellated stages have large food vacuoles. Chloroplasts or photosynthetic prey, whole diatom cells, are phagocytized. Most of the known stages in its complex life cycle consist of amoebae that can transform from flagellated forms, vegetative cells, planozygotes and gametes. One amoeboid stage is uninucleate and has a typical eukaryotic nucleus. The flagellated stage can turn into a naked, amoeboid, star-like stage within minutes.
Pfiesteria only becomes toxic in the presence of fish, particularly schooling fish like Atlantic menhaden, triggered by their secretions or excrement in the water. At that point Pfiesteria cells change morphology and begin emitting a powerful toxin that stuns the fish making them lethargic. Other toxins break down fish skin tissue causing bleeding sores or lesions. The toxins or subsequent lesions are frequently fatal to the fish. Fish may also die without developing lesions. As fish are incapacitated the Pfiesteria cells feed on their tissues and blood. Fish may also be killed by secondary infections once the toxins have caused lesions to develop. Live fish or their fresh tissues stimulate toxicity and gamete production and fusion which usually occurs within a benthic or floating gelatinous mass. After the fish die the remaining gametes revert to asexual, nontoxic, zoospores that thrive in the nutrient-enriched waters. In the absence of fish transformations among nontoxic flagellated, amoeboid and encysted stages in the dinoflagellate's complex life cycle are influenced by the availability of microbial prey, bacteria, algae and microfauna including protozoan ciliates and rotifers.
Toxic outbreaks of Pfiesteria are typically very short, not more than a few hours. After such an event Pfiesteria cells change back into non-toxic forms very quickly and the Pfiesteria toxins in the water break down within a few hours. However, once fish are weakened by the toxins Pfiesteria-related fish lesions or fish kills may persist for days or possibly weeks. Pfiesteria piscicida is known to occur in brackish coastal waters from the Delaware Bay to North Carolina. Other Pfiesteria-like organisms occur along the southeast coast from Delaware to the Gulf of Mexico.
These organisms are believed to be native species and are probably common inhabitants of estuarine waters within their range. The ubiquitous occurrence of flagellated and amoeboid stages in the water column and sediments of warm temperate and subtropical waters, and their voracious phagotrophy on bacterial, algal and microfaunal prey, point to a major role of toxic ambush-predator dinoflagellates in the structure and function of estuarine microbial food webs. It seems clear that Pfiesteria growth is exacerbated by large increases of nutrients in coastal waters. Recently, scientists have learned more about the complexity of the Pfiesteria phenomenon. The attention on Pfiesteria has stimulated research on other small dinoflagellates that resemble Pfiesteria in general appearance. Some of these 6 to 8 so-called Pfiesteria look-alikes are also toxic, but otherwise have different behavior patterns and life cycles.
Any human health problems associated with Pfiesteria stem from the release of toxins into river and estuarine waters. Preliminary evidence suggests that exposure to waters where toxic forms of Pfiesteria are active may cause memory loss, confusion and a variety of other symptoms including respiratory, skin and gastro-intestinal problems. It has been shown that similar human health effects can be caused by exposure to Pfiesteria toxins in a laboratory setting. To date, other Pfiesteria-like organisms have not been shown to cause human illness.
syn. Nitzschia pseudoseriata
Diatoms in the genus Pseudo-nitzschia produce a neurotoxin, domoic acid. It is the cause of amnesic shellfish poisoning, ASP, which can be life-threatening. In severe cases, neurological symptoms occur within 48 hours of eating toxic shellfish. Toxic Pseudo-nitzschia species are also found on the West Coast of the United States. Most Pseudo-nitzschia blooms have not been linked to nutrient pollution but instead to natural events including spring and summer changes in currents, temperature, and salinity.
Table of Algal Species and the Toxins Produced
|Marine Dinoglagellate||Toxin Type|
|Alexandrium acatenella||PSP-Paralytic Shellfish Poisoning|
|Alexandrium catenella||PSP-Paralytic Shellfish Poisoning|
|Alexandrium excavatum||PSP-Paralytic Shellfish Poisoning|
|Alexandrium fundyense||PSP-Paralytic Shellfish Poisoning|
|Alexandrium minutum||PSP-Paralytic Shellfish Poisoning|
|Alexandrium monilata||PSP-Paralytic Shellfish Poisoning|
|Alexandrium tamarense||PSP-Paralytic Shellfish Poisoning|
|Chatonella antiqua||NSP-Neurotoxic Shellfish Poisoning|
|Chatonella marina||NSP-Neurotoxic Shellfish Poisoning|
|Fibrocapsa japonica||NSP-Neurotoxic Shellfish Poisoning|
|Gambierdiscus toxicus||CFP-Ciguatara Fishfood Poisoning|
|Gymnodinium breve||NSP-Neurotoxic Shellfish Poisoning|
|Gymnodinium catenatum||NSP-Neurotoxic Shellfish Poisoning|
|Gymnodinium nagasakiense||NSP-Neurotoxic Shellfish Poisoning|
|Pfiesteria piscicida||NSP-Neurotoxic Shellfish Poisoning|
|Marine Diatoms||Toxin Type|
|Chaetoceros concavicornis||non-toxic gill irritant|
|Chaetoceros convolutum||non-toxic gill irritant|
|Pseudo-nitzschia australis||ASP-Amnesic Shellfish Poisoning, Domoic Acid|
|Pseudo-nitzschia pseudodelicatissima||ASP-Amnesic Shellfish Poisoning, Domoic Acid|
|Pseudo-nitzschia pungens||ASP-Amnesic Shellfish Poisoning, Domoic Acid|
|Rhizosolenia chunii||Taste Impairment|
|Thalasssiosira||non-toxic, gill irritant|
|Other Algae||Toxin Type|
|Amphidinium carterae||CFP-Ciguatara Fishfood Poisoning|
|Cochlodinium citron||PSP-Paralytic Shellfish Poisoning|
|Coolia monotis||CFP-Ciguatara Fishfood Poisoning|
|Dinophysis acuminata||DSP-Diarrhetic Shellfish Poisoning|
|Dinophysis acuta||DSP-Diarrhetic Shellfish Poisoning|
|Dinophysis fortii||DSP-Diarrhetic Shellfish Poisoning|
|Dinophysis norvegica||DSP-Diarrhetic Shellfish Poisoning|
|Gyrodinium aureolum||PSP-Paralytic Shellfish Poisoning|
|Heterosigma carterae||Peroxide Radicals|
|Ostreopsis lenticularis||CFP-Ciguatara Fishfood Poisoning|
|Ostreopsis siamensis||CFP-Ciguatara Fishfood Poisoning|
|Phaeocystis pauchetii||non-toxic gill irritant|
|Prorocentrum concavum||CFP-Ciguatara Fishfood Poisoning|
|Prorocentrum hoffmannianum||CFP-Ciguatara Fishfood Poisoning|
|Prorocentrum lima||CFP-Ciguatara Fishfood Poisoning|
|Prorocentrum maculosum||CFP-Ciguatara Fishfood Poisoning|
|Prorocentrum micans||DSP-Diarrhetic Shellfish Poisoning|
|Prorocentrum minimum||DSP-Diarrhetic Shellfish Poisoning|
|Pyrodinium bahamense||PSP-Paralytic Shellfish Poisoning|
|Thecadinium||CFP-Ciguatara Fishfood Poisoning|
The presumptive role of many of these complex toxins, which require a significant investment in cellular machinery and energy expenditure, is as feeding deterrents to prevent or reduce the predation by other organisms. This is not the case for Pfiesteria which uses the toxins offensively to acquire food as opposed to defensively to avoid being eaten. Copepods and other macro-zooplankton reduce their grazing rates when they encounter dense blooms of some toxic dinoflagellates, perhaps as a result of impaired motor control and elevated heart rates. Heterosigma carterae is avoided by zooplankton predators including rotifers, copepods, pilchard larvae and juvenile menhaden due to peroxide production. The tintinnid Favella taraikaensis avoids Heterosigma even when starved and reverses the beat of its adoral membranelle to reject the cells. Chrysochromulina polylepis causes reduced feeding and growth rates of the tintinnid Favella ehrenbergii. These are but a few examples of how zooplankton avoid or reject certain toxic algal species and how they can be physiologically impaired once they have consumed the toxic algae.
There is no way to tell for sure if water is toxic unless some of it is actually injected into an experimental laboratory animal. Harmless strains of potential toxin-producing algae look the same as deadly strains under a microscope. A toxin will not give a distinguishing odor or color to the water in which it is dissolved. There are two basic kinds of algae toxins, the milder peptide type is rarely fatal but may produce chronic liver damage and general long term debility while the more potent alkaloid type is usually fatal within a short time. The toxins are complex organic compounds. While the chemical structures of some have been known for many years new ones are still being determined. There is no antidote known to be effective at counteracting the effects of the toxins once they have been ingested.
The extent to which marine mammals and birds react to algal toxins in their natural setting is not known. However, sea otters do alter their diet since they are able to detect, reject and avoid ingesting shellfish with lethal levels of PSP toxin. Little is known about other harmful algae bloom-related toxins and marine mammals, although many sea lions have died as a result of domoic acid poisoning from blooms of toxic diatoms that are consumed by anchovies and then eaten by the sea lions. Man is normally exposed to the naturally-occurring toxins produced by harmful algae through the consumption of contaminated seafood products.
The alkaloid neurotoxins cause convulsions, staggering, spasms, respiratory distress or arrest and death. A very rigid neck is characteristic at death which is caused by respiratory arrest. CPR is the required supportive treatment. There may be tingling or numbness of fingers and toes, dizziness, fainting and hay-fever-like symptoms. Neurotoxic effects are quite rapid. The peptide hepatotoxins cause abdominal pain, diarrhea, vomiting, cramps, lethargy, liver damage and death. Liver tumors and cancers may be promoted by the hepatotoxins. These effects may occur relatively slowly.
Paralytic shellfish poisoning, PSP, toxins and domoic acid are naturally occurring marine toxins and marine organisms that filter their food from seawater may accumulate these toxins in their tissues. The toxins do not appear to directly harm the filter feeders but humans and some predatory animals eating contaminated sea foods may become poisoned. PSP toxins and domoic acid have no taste or odor. There is no visible, taste or odour difference between toxic and safe sea foods. Cleaning sea foods in many cases will not remove the toxins and cooking does not destroy the toxins.
The common classification of human health problems caused by harmful marine algae consists of the following syndromes.
Each of these syndromes are caused by different species of toxic algae which occur in various coastal waters of North America and the world. With the increase in internal and international transport of seafood, as well as international travel by seafood consumers, there are virtually no human populations that are free of risk. Since 1978 illnesses in the US due to natural algal toxins have included PSP, NSP, CFP and ASP. No incidents of DSP have yet been verified in the US. However, records are incomplete because reporting to the Centers for Disease Control, CDC, is voluntary. Evidence indicates that ciguatera was responsible for about half of all seafood intoxications. A growing body of evidence indicates that incidents of ASP are on the increase and that DSP may shortly make its debut in the United States since the causative organisms occur throughout the temperate coastal waters of the US.
Amnesic Shellfish Poisoning (ASP)
causative organisms: Pseudo-nitzschia australis, Pseudo-nitzschia pungens
toxin produced: Domoic Acid
Diatoms produce domoic acid. Bivalve shellfish and some fin fish filter these diatoms from the water. In most cases domoic acid accumulates in the viscera of these animals. In razor clams domoic acid also accumulates in the meat. Unsafe levels of domoic acid have been found in anchovies, mussels, razor clams and crab viscera but not crab meat. Many other species have not yet been investigated.
Amnesic shellfish poisoning is generally associated with the consumption of molluscan shellfish from the northeast and northwest coasts of North America. It has not yet been a problem in the Gulf of Mexico although the algae that produces the toxin has been found there. ASP toxins have recently been identified as a problem in the viscera of Dungeness crab, tanner crab, red rock crab and anchovies along the west coast of the United States.
ASP can be a life-threatening syndrome. It is characterized by both gastrointestinal and neurological disorders. Gastroenteritis usually develops within 24 hours of the consumption of toxic shellfish and symptoms include nausea, vomiting, abdominal cramps and diarrhea. In severe cases neurological symptoms also appear, usually within 48 hours of toxic shellfish consumption. These symptoms include dizziness, headache, seizures, disorientation, short-term memory loss, respiratory difficulty and coma.
In 1987, four victims died after consuming toxic mussels from Prince Edward Island, Canada. Since that time, Canadian authorities have monitored both the water column for the presence of the causative diatom and shellfish for the presence of the toxin, domoic acid. Shellfish beds are closed to harvesting when the domoic acid concentration reaches 20 µg/g in shellfish meat. Fish and crab viscera can also contain domoic acid so the risk to human consumers and animals in the marine food chain is more significant than previously believed.
Ciguatara Fishfood Poisoning (CSP)
causative organisms: Gambierdiscus toxicus, Prorocentrum concavum, Prorocentrum hoffmannianum, Prorocentrum lima, Ostreopsis lenticularis, Ostreopsis siamensis, Coolia monotis, Thecadinium and Amphidinium carterae
toxins produced: Ciguatoxin, Maitotoxin
Ciguatera poisoning in humans and domestic animals is caused by potent neurotoxins produced by benthic dinoflagellates including Gambierdiscus toxicu. In the tropics and subtropics toxic dinoflagellates living on coral reefs are eaten by small herbivorous fish grazing on coral which in turn are eaten by larger carnivores. The poisons move up the food chain into the organs of larger top-order predators such as coral trout, red bass, chinaman fish, mackerels and moray eels and cause ciguatera fish poisoning, CFP, in people who eat these fish. Over 400 non-lethal cases of ciguatera food poisoning have been recorded in Australia and tropical countries such as French Polynesia report thousands of cases every year.
More than 400 different fish species are involved in CFP including grouper, barracuda, snapper, jack, mackerel and triggerfish. The toxic algae that cause CFP are a natural phenomenon, with no known link to excess nutrients. The alga species most often associated with CFP is Gambierdiscus toxicus, but others are occasionally involved. There are at least four known toxins that concentrate in the viscera, head or central nervous system of affected fish.
In the south Florida, Bahamian and Caribbean regions barracuda, amberjack, horse-eye jack, black jack, other large species of jack, king mackerel, large groupers and snappers are particularly likely to contain ciguatoxin. These species are not generally associated with ciguatera in the northern Gulf of Mexico. Many other species of large fish-eating fishes may be suspect. In Hawaii and throughout the central Pacific barracuda, amberjack and snapper are frequently ciguatoxic and many other species both large and small are suspect. Mackerel and barracuda are frequently ciguatoxic from mid to northeastern Australian waters.
CFP produces gastrointestinal, neurological and cardiovascular symptoms. Generally, diarrhea, vomiting and abdominal pain occur initially, followed by neurological dysfunction including reversal of temperature sensation, muscular aches and lack of co-ordination, dizziness, itching, anxiety, chills, sweating and a numbness and tingling of the mouth and digits. Paralysis and death have been documented but symptoms are usually less severe although debilitating. Recovery time is variable and may take weeks, months or years. Rapid treatment, within 24 hours, with manitol is reported to relieve some symptoms. There is no antidote, supportive therapy is the rule, and survivors recover completely. Absolute prevention of intoxication depends upon complete abstinence from eating any tropical reef fish since there is currently no easy way to routinely measure ciguatoxin or maitotoxin in any seafood product prior to consumption.
This form of seafood poisoning is probably the most serious human health threat from harmful algae in the US and its territories. Only a few dozen cases are reported each year in the US, with isolated poisonings from south Florida to Vermont and more regular ones in Hawaii, the US Virgin Islands and Puerto Rico. But the great majority of ciguatera poisonings are likely unreported. An estimated 100 cases of poisonings are unreported for every reported case in Puerto Rico and the Virgin Islands where many people are so poor they don't go to the hospital and three of every four cases are unreported in Florida.
Diarrhetic Shellfish Poisoning (DSP)
causative organisms: Dinophysis, Prorocentrum, Dinophysis fortii, Dinophysis acuminata, Dinophysis norvegica, Dinophysis acuta
toxin produced: Okadaic Acid
Diarrhetic shellfish poisoning was first recognised in 1976 in Japan. Between 1976 and 1982 there were more than 1,300 diagnosed cases in Japan with the armoured dinoflagellates Dinophysis fortii and Dinophysis acuminata being the algae responsible. Ingestion of shellfish contaminated with the diarrhetic shellfish toxins, okadaic acid, dinophysistoxins and pectenotoxins, causes severe gastrointestinal disturbances in humans. Although no mortalities have been reported the symptoms can last for 2-3 days.
Diarrhetic shellfish poisoning is generally associated with the consumption of molluscan shellfish. The occurrence of DSP in Europe is sporadic, continuous and presumably widespread. DSP poisoning has not been confirmed in US seafood but the organisms that produce DSP are present in US waters. However, instances have been documented in Japan, southeast Asia, Scandinavia, western Europe, Chile, New Zealand and eastern Canada. A number of algae species in the genera Dinophysis and Prorocentrum have been associated with DSP.
DSP produces gastrointestinal symptoms usually beginning within 30 minutes to a few hours after consumption of toxic shellfish. The illness, which is not fatal is characterized by incapacitating diarrhea, nausea, vomiting, abdominal cramps and chills. Recovery occurs within three days with or without medical treatment.
Neurotoxic Shellfish Poisoning (NSP)
causative organism: Gymnodinium breve
toxins produced: Brevetoxins
Neurotoxic shellfish poisoning in the US is generally associated with the consumption of molluscan shellfish harvested along the coast of the Gulf of Mexico and, sporadically, along the southern Atlantic coast. There has been a significant occurrence of toxins similar to NSP in New Zealand and some suggestions of occurrence elsewhere. NSP is caused by Gymnodinium breve. Blooms of this algae usually result in fish kills and can make shellfish toxic to humans. The blooms generally begin offshore and move inshore. Gymnodinium breve produces three known brevetoxins.
NSP produces an intoxication syndrome nearly identical to that of ciguatera. In this case gastrointestinal and neurological symptoms predominate. After people eat contaminated shellfish, they can suffer numbness, tingling, cramps, nausea, vomiting, diarrhea, chills and sweats. Less commonly victims may experience prolonged diarrhea, nausea, poor coordination and burning pain in the rectum. In addition, formation of toxic aerosols by wave action can produce respiratory asthma-like symptoms. No deaths have been reported and the syndrome is less severe than ciguatera, but nevertheless debilitating. Unlike ciguatera, recovery is generally complete in a few days. Monitoring programs, based on Gymnodinium breve cell counts, are generally sufficient to prevent human intoxication except when officials are caught off-guard in previously unaffected areas.
Paralytic Shellfish Poisoning (PSP)
causative organisms: Alexandrium excavatum, Alexandrium monilata, Alexandrium tamarense, Gymnodinium catenatum, Pyrodinium bahamense
toxins produced Saxitoxins
Dinoflagellates produce PSP toxins. Bivalve shellfish filter these organisms from the water. PSP toxins accumulate in the dark digestive organs or viscera of most shellfish. In clams PSP toxins also accumulate in the siphons or necks. Mussels, oysters, clams and scallops have caused PSP outbreaks but abalone, crab, shrimp and fish have never been implicated as a source of PSP.
Paralytic shellfish poisoning is probably the best known of all the shellfish poisonings with one of the first reported cases occurring in 1793 in British Columbia, Canada and over 100 reported deaths and several thousand illnesses being attributed to PSP around the world. Around 20 species of dinoflagellates have been implicated as producing the causative alkyloids, saxitoxins, that accumulates in shellfish. Saxitoxins, a group of 18 toxins, are potent neuromuscular blocking agents that finds their way through shellfish to consumers including man. A few of the dinoflagellate species that are known to produce these toxins are Gymnodinium catenatum, Alexandrium catenella, Alexandrium minutum and Alexandrium tamarense; most of these dinoflagellates have not been shown to be directly toxic to fish or shellfish.
Paralytic shellfish poisoning in the US is generally associated with the consumption of molluscan shellfish from the northeast and northwest coastal regions. PSP in other parts of the world has been associated with molluscan shellfish from environments ranging from tropical to temperate waters. In the US PSP toxin has recently been reported from the viscera of mackerel, lobster, dungeness crabs, tanner crabs and red rock crabs. PSP is caused by many species of toxic algae. These include Alexandrium, Pyrodinium and Gymnodinium. PSP can be caused by a combination of any of 18 saxitoxins, depending on the species of algae, geographic area and type of shellfish involved.
PSP, like ASP, is a life threatening syndrome. Symptoms are purely neurological and their onset is rapid. Duration of effects is a few days in non-lethal cases. Symptoms include tingling, numbness and burning of the lips and tongue, ataxia, giddiness, drowsiness, fever, rash, a general lack of muscle coordination in the arms, legs and neck and staggering. The most severe cases result in respiratory arrest within 24 hours of consumption of the toxic shellfish. If the patient is not breathing or if a pulse is not detected CPR may be needed as first aid. There is no antidote, supportive therapy is the only treatment and survivors recover fully. PSP is prevented by large-scale proactive monitoring programs, assessing toxin levels in mussels, oysters, scallops and clams and by rapid closure-to-harvest of suspected or demonstrated toxic areas. PSP toxins and domoic acid are powerful nerve poisons.
List of Toxins
The chemical structures of some of these toxins are bewilderingly complex and there is no purpose in giving extensive details of formulae or structural diagrams in this report. Some have proven to be exercises in structural elucidation and subsequent synthesis that have occupied chemists for many years. Many have not yet been characterized. There is a brief synopsis of some chemistry and biosynthesis in the appendix.
These are neurotoxins but are not fatal.
This and other DSP's are phosphatase inhibitors and interfere with the essential process of phosphorylation. These are eukaryotic poisons and do not affect prokaryotes or the plastids in eukaryotic cells. They cause non-fatal gastrointestinal effects.
This is a gastrointestinal and neurotoxic compound and rarely fatal.
This is a neural toxin and ties up the synapses interfering with nerve impulse transmission. It is also a glutamate antagonist and causes gastrointestinal problems. It may be fatal.
This is a gastrointestinal and neurotoxic compound and rarely fatal.
This is a neurotoxin that results in respiratory arrest and death.
This and other DSP's are phosphatase inhibitors and interfere with the essential process of phosphorylation. These are eukaryotic poisons and do not affect prokaryotes or the plastids in eukaryotic cells. They cause non-fatal gastrointestinal effects.
This and other DSP's are phosphatase inhibitors and interfere with the essential process of phosphorylation. These are eukaryotic poisons and do not affect prokaryotes or the plastids in eukaryotic cells. They cause non-fatal gastrointestinal effects.
These are neurotoxins that result in respiratory arrest and death.
These are peroxides formed by Heterosigma. They are chemically very reactive and interfere with metabolic pathways quite non-specifically.
In June 1990 after collecting shellfish from a beach, an Alaskan fisherman carried butter clams to a fishing boat where he steamed and ate 25-30 of them. Within an hour of the meal he complained of numbness around his face and fingers. In two hours he died. The fisherman had eaten shellfish contaminated with the toxic algae Alexandrium and suffered a condition, PSP, in which nerve impulses do not reach the muscles. Without the nerve impulses, the diaphragm and lungs did not work, which lead to respiratory failure and death. In Guatemala an outbreak of 187 cases of PSP with 26 deaths occurred in 1987 from ingestion of clam soup. The outbreak led to the establishment of a control program over shellfish harvested in Guatemala. An outbreak of DSP was recently confirmed in Eastern Canada. Outbreaks of NSP are sporadic and continuous along the Gulf coast of Florida and were recently reported in North Carolina and Texas.
Two drunken (blood alcohol levels measured 12 hours after they stopped drinking still measured about 0.31) clam harvesters near Port McNeill, on Northeastern Vancouver Island ate PSP contaminated clams. One of them spat out the one clam he tried because it tasted bad; the other swallowed several clams but vomited them up shortly. Both 'died' on the beach in 10 minutes when their breathing stopped. However, CPR kept them alive until they were airlifted to a hospital and maintained for several days on artificial life support until they detoxified and made a full recovery.
In 1991 toxins concentrated to dangerous levels in razor clams and dungeness crabs on the Oregon and Washington coasts. In western Washington alone, the economic impact of the 1991 toxic bloom was estimated at $15-20 million. A few people became ill in Washington State after consuming razor clams with mild, short-lived symptoms including gastrointestinal disorders and memory loss. At some point each year between 1992 and 1995 toxin levels in razor clams which are harvested recreationally have been above regulatory limits in Washington. To protect human health the state has temporarily closed some shellfish beds. Some harvesters have complained that regulators exaggerate the toxicity. In a few instances regulators have had to put up roadblocks to prevent harvesters from reaching contaminated shellfish beds.
The first recorded fatal cases of shellfish poisoning occurred in 1793 after Captain George Vancouver and his crew landed along the northwestern coast of North America. Some of his sailors ate shellfish from an area in British Columbia known today as Poison Cove. Later, Captain Vancouver learned that local Indians would not eat shellfish during dinoflagellate blooms which reddened the waters. ASP first came to the attention of public health authorities in 1987 when 156 cases of acute intoxication occurred as a result of ingestion of cultured blue mussels, Mytilus edulis, harvested off Prince Edward Island in eastern Canada. Twenty two individuals were hospitalized, 105 suffered permanent short-term memory loss and four elderly patients eventually died. The mussels were contaminated with domoic acid from the toxic diatom, Pseudo-nitzschia.
In May 1998 a major invasion of toxic algae killed at least three-hundred tonnes of farmed fish, mostly salmon, along the southern coast of Norway. The algae included a species that was previously unknown in the country, one which kills the fish by blocking their gills. Algae invasions occur regularly off the Norwegian coast and fish farms suffered losses of up to ten million dollars after a major invasion ten years ago. Along the west coast of North America up to Alaska hundreds of miles of coastline are closed to shellfish harvesting due to toxic algae. In New England harmful blooms over the past 20 years have killed shellfish, lobsters, fish and marine mammals. In 1988 alone algae blooms killed vast numbers of scallops in New York State waters causing a $2 million loss to the shell fishing industry.
In September 1991 more than 100 brown pelicans and cormorants died in Monterey Bay, California, after eating anchovies containing domoic acid. The dominant diatom in the area at the time was Pseudo-nitzschia australis. In 1998 over 400 California sea lions were killed by domoic acid, a neurotoxin generated by various marine algae. Domoic acid also affects birds, sea otters and humans. The sea lions ate large quantities of anchovies and sardines that had fed on the algae. Using a DNA probe to identify the genetic signature of the toxin, the researchers were quickly able to process the samples and track the toxin through the food chain while the evidence was still available. There are many similar reports of toxic algal blooms from all over the world reported in the scientific literature, newspapers, internet and other sources every year.
There is another category of harmful algae that kills farmed and wild fish, but does not directly affect human health. In recent years New York and Texas coastlines have been the sites of brown tides caused by marine plankton called chrysophytes. Brown tide cells grow to extraordinary densities and shade the plant life in shallow bays. In 1985 the first known brown tide appeared off Long Island and ruined the local $20 million bay scallop industry. In 1989 a brown tide bloomed off the Corpus Christi area of the Texas coast and remained for eight years. It killed the eelgrass and other underwater vegetation. With their habitat destroyed the fish have disappeared and with them many of the tourists.
Researchers hypothesize that a brown tide toxin influences nerve transmission in shellfish. Brown tide algae could have evolved their toxins to ward off shellfish, one of their main predators. In large concentrations the toxin may prevent shellfish gills from functioning so the shellfish can't feed and thus starve. Brown tide species are probably stimulated, at least in part, by excess nutrients from human sources.
In 1991 Pfiesteria was implicated in numerous fish kills in North Carolina. In 1995 officials closed a section of the lower Neuse River after Pfiesteria outbreaks apparently caused huge fish kills equaling millions of menhaden, a commercially important fish in the herring family. In 1997 officials closed sections of Maryland's Pocomoke River and two other waterways that flow into Chesapeake Bay after similar fish kills and human health effects were reported. Pfiesteria has killed hundreds of millions of fish in North Carolina. State workers have used bulldozers to clear piles of dead menhaden from the beaches. A 1995 outbreak wiped out 14 million fish, temporarily closed parts of the Neuse River and put 364,000 acres of shellfish beds off limits. Since then the problem has been spreading. Around the country, outbreaks of Pfiesteria and other harmful algal blooms known as red or brown tides are devastating marine life and posing risks for fishermen in bays and estuaries. Earlier, 20,000 rockfish in a Maryland fish farm on the Chesapeake Bay were killed by this organism.
Pfiesteria piscicida has been implicated as a cause of major fish kills at many sites along the North Carolina coast, particularly the New River and the Albemarle-Pamlico estuarine system which includes the Neuse and Tar-Pamlico Rivers. Millions of fish have died from Pfiesteria in North Carolina. In 1997 Pfiesteria or Pfiesteria-like organisms killed thousands of fish in several Eastern Shore tributaries of the Chesapeake Bay, including the Chicamacomico and Manokin Rivers and King's Creek. Pfiesteria piscicida is known to occur in brackish coastal waters from the Maryland and the lower Pocomoke River in Maryland and Virginia. Pfiesteria piscicida is the probable cause for a 1987 fish kill in Delaware's Indian River. Fish kills in coastal aquaculture operations in Maryland and North Carolina have also been linked to Pfiesteria and Pfiesteria-like organisms. Lesioned fish found in association with Pfiesteria or Pfiesteria-like organisms have been documented in several Maryland and Virginia tributaries of the Chesapeake Bay, in many coastal areas of North Carolina, and in the St. John's River in Florida.
People heavily exposed to Pfiesteria-infested waters in rivers draining into Chesapeake Bay suffered skin disorders, respiratory irritation, learning disorders, memory loss and confusion. Burkholder and her research assistant both suffered memory loss and other effects from working with this toxic dinoflagellate in the lab. Pfiesteria has not, however, been linked to any known poisonings due to eating seafood.
This estuarine dinoflagellate produces exotoxins that can be absorbed from water or fine aerosols. Culture filtrate, 0.22 microns porosity filters, and more than 250 toxic flagellated cells/ml, induces formation of open ulcerative sores, hemorrhaging and death of fin fish and shellfish. Human exposure to aerosols from cultures toxic to fish, greater than 2000 cells/ml, has been associated with health problems, narcosis, respiratory distress with asthma-like symptoms, severe stomach cramping, nausea, vomiting and eye irritation with reddening and blurred vision for hours or days, autonomic nervous system dysfunction including localized sweating, erratic heart beat for weeks, central nervous system dysfunction such as sudden rages and personality change for hours or days, reversible cognitive impairment and short-term memory loss for weeks, chronic effects including asthma-like symptoms, exercise fatigue and sensory symptoms such as tingling or numbness in lips, hands and feet for months or years.
Elevated hepatic enzyme levels and high phosphorus excretion suggested hepatic and renal dysfunction for weeks and susceptibility to infection and low counts of several T-cell types may indicate immune system suppression for months or years. A North Carolina fisherman, David Jones, struggles with symptoms similar to those of several chronic afflictions: the mental confusion of Alzheimer's, the physical crippling of multiple sclerosis and the wasting of AIDS. However, Jones has none of these, all the evidence points to the Pfiesteria neurotoxin. Jones is one of about 100 North Carolina victims, fishermen, commercial divers and marine construction workers, who appear to have been poisoned by Pfiesteria found in the state's eastern rivers and estuaries. The symptoms include open sores, nausea, memory loss, fatigue, disorientation and in severe cases the near-total incapacitation suffered by Jones.
Pfiesteria piscicida kills marine fish directly with an exotoxin. Most of the time the cells remain in a hard cyst-like condition in the sediment of bays and estuaries. But when fish swim by the organisms transform into predators and using twin flagella they swim toward their prey. They then release a toxin that is, even in minute quantities, deadly to fish, killing a guppy in 10 minutes and a 20-pound striped bass in four hours. Poisoned fish gasp for oxygen and swim upside down or in circles. The toxin also causes the distinctive oozing red sores found both on fish and on humans who have been in direct contact with the organism. The Pfiesteria feed on the dying fish, reproduce, then change shape and return to dormancy in the sediment.
Although attacks on humans are much rarer than attacks on fish, Pfiesteria does pose significant risks to fishermen or people in prolonged contact with the organism or the toxins. Laboratory tests show that the neurotoxin is powerful enough to harm humans. Clams, mussels, scallops, oysters and other shellfish filter toxic algae from the water and the toxins accumulate in their tissues, frequently without much effect on shellfish health. But people who eat algae-contaminated seafood can suffer gastrointestinal disorders, respiratory problems, confusion, memory loss and death. In some cases one clam or mussel can contain enough poison to kill a human being. What makes such toxins especially dangerous is that they are tasteless, odourless and colorless and cooking the shellfish will not destroy the toxins. Moreover, one type of algal toxin can be aerosolized by surf and then carried inland by breezes, and cause respiratory problems in people who breathe it in.
Dermatitis and Allergies
In addition to toxins many algae are allergenic or cause dermatitis in some people. The genera of algae which have so far proved to be of interest to the dermatologist are listed below.
An atopic sensitivity to algae has been reported. Many green algae are airborne in significant numbers at certain seasons. Carrying out algal skin tests on children with respiratory allergic disorders produced some positive reactions. Six strains of green algae commonly encountered in air, water and soil samples in the United States were used to skin-test 79 atopic patients. There were positive results with 47 of them. Species of Chlorella, Chlorococcum and Scenedesmu were chiefly involved. Further investigations showed a high incidence of positive skin tests to a Chlorella species found in house dust, in patients with perennial rhinitis. Urticaria may accompany the rhinitis. Sensitization to the algal component of lichens has also been reported.
Tables of US Finfish, Shellfish and Wildlife Affected by Toxic Algal Species
ASP-Amnesic Shellfish Poisoning
|Diatom Species||Geographic Area||Affected Organisms|
|Pseudo-nitzschia pungen||Gulf of Maine; Puget Sound, Washington; Massachusetts; Maine||mussels, bay scallops, sea scallops|
|Pseudo-nitzschia australis||California||anchovies, sea birds|
|Pseudo-nitzschia australis||Washington, Oregon||razor clams , dungeness crabs|
CFP-Ciguatara Fishfood Poisoning
|Algal Species||Geographic Area||Affected Organisms|
|South Florida, Florida Keys, Puerto Rico, US Virgin Islands, Hawaii, Guam||grouper, snapper, mackerel, jack, barracuda, parrot fish, tang, goat fish, and other fin fish, gastropods|
NSP-Neurotoxic Shellfish Poisoning
|Algal Species||Geographic Area||Affected Organisms|
|Gymnodinium breve||Gulf of Mexico, South Atlantic Bight||bay scallops, surf clams, oysters, southern quahogs, coquinas, tunicates, many commercial and recreational species of fish, sea birds, sea turtles, manatees, dolphins|
PSP-Paralytic Shellfish Poisoning
|Dinoflagellate Species||Geographic Area||Affected Organisms|
|Northern Atlantic and Pacific Coast of North America||mussels, surf clams, softshell clams, sea scallops, butter clams, ocean quahogs, oysters, gastropods, lobsters, crabs, herring, salmon, menhaden, sandlance, mackerel and possibly other fish species, whales, sea lions, sea otters, sea birds, squid, zooplankton, and other benthic invertebrates|
|Algal Species||Geographic Area||Affected Organisms|
|Alexandrium monilata||Gulf of Mexico||oysters, coquinas, mussels, gastropods, fish|
|Pfiesteria-like dinoflagellates||North Carolina estuaries and adjacent coastal waters||atlantic menhaden, blue crab, catfish, mullet, spot, white perch, american eel, croaker, hogchoker, southern flounder, sheepshead|
|Prorocentrum||Long Island Sound||northern quahogs, bay scallops|
|Gyrodinium aureolum||Northern New England||mussels, softshell clams|
|Aureococcus anophagefferens||New York, Rhode Island, New Jersey||bay scallops, mussels Anchoa, cladocerans|
|Chaetoceros||Pacific northwest||salmon aquaculture|
|Heterosigma carterae||Pacific northwest, Narragansett Bay||salmon aquaculture, wild fish, zooplankton|
In the estuaries and oceans the natural food chain consists of primary producers, mostly algae, zooplankton, small fish and large fish. Algae are consumed by the zooplankton, which in turn are consumed by the small fish, which themselves are eaten by larger fish. In addition there are filter-feeding animals such as mussels, clams and oysters that may consume the algae directly, and many animals that eat the shellfish. Bacteria and protozoa also play an important role in the functioning of a healthy aquatic food chain.
Zooplankton and mussels can accumulate algal toxins. We do not know how much toxin is accumulated under natural conditions and what effects these toxins have on the organisms along the food chain. The potential effects may be subtle, perhaps only a small reduction in growth rate, brood size or body weight. However, in a complex and dynamic natural ecosystem even small changes can be sufficient to cause a major decline in the survival of sensitive species. Studies have shown that the feeding rate and vigour of shellfish is reduced when they are fed exclusively on a diet of toxic algae or only certain species of algae. The same deleterious effects could occur in the natural environment, for instance, during an algal bloom a single species of algae can represent more than 90% of the total biomass.
Shifts in aquatic community structure caused by toxins may already be occurring. We have simply lacked the means or resources to identify them or their impacts on the health of our aquatic environment. It is even possible that toxic algae have impacted sufficiently on our marine habitats to have stimulated or assisted in the decline of native fish.
Mussels are very dangerous because people eat the entire mussel including the viscera. In razor clams the toxin, domoic acid, is present in the meat. In clams the toxin is also present in the siphons. Following an outbreak of PSP the siphons of clams may retain toxins for a year or more. In fish and crabs domoic acid is confined to the internal organs. The USFDA has established guidance levels for all of the natural marine algal toxin groups except for CFP.
|Toxin Type||Guideline Levels|
|ASP||20 ppm domoic acid, except in the viscera of dungeness crab, where 30 ppm is permitted|
|DSP||0.2 ppm okadaic acid plus 35-methyl okadaic acid|
|NSP||0.8 ppm (20 mouse units/100g) brevetoxin-2 equivalent|
|PSP||0.8 ppm (80µg/100g) saxitoxin equivalent|
Dermatitis and Allergies
Dermatitis and Allergies
Algal toxins that impact human health may be functionally categorized as neurotoxins or hepatotoxins. Neurotoxicity of algal toxins is mediated by diverse, highly specific interactions with ion channels involved in neurotransmission. Such specificity may reflect their role in anti-predation; alternatively, it may suggest the presence of conserved structures on primitive targets present in eukaryotic microbes, or may support the hypothesis of primitive regulatory roles for these compounds. Okadaic acid and microcystins are examples of structurally unrelated compounds which are elaborated by phylogenetically unrelated groups. The dinoflagellates produce okadaic acid and cyanophytes produce microcystins to inhibit a common target, the serine/threonine protein phosphatases.
Dinoflagellate and diatom toxins impact human health primarily through the consumption of seafood. Filter-feeding shellfish, zooplankton and herbivorous fish serve as vectors either directly or through further food web transfer of sequestered toxin to higher trophic levels. Five major human marine, primarily algal, poisoning syndromes are known. Paralytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), amnesic shellfish poisoning (ASP), diarrhetic shellfish poisoning (DSP) and ciguateric fish poisoning (CFP).
Paralytic Shellfish Toxins
Paralytic shellfish poisoning, PSP, is the most widespread algal derived shellfish poisoning on a worldwide basis. The toxins responsible for PSP are a suite of heterocyclic guanidines collectively called saxitoxins of which there are currently over 21 known congeners. The structures of saxitoxin congeners vary by differing combinations of hydroxyl and sulfate substitutions at four sites on the molecule. Based on substitutions the saxitoxins can be sub-divided into four groups, the carbamate toxins, sulfo-carbamoyl toxins and decarbamoyl and deoxydecarbamoyl toxins. Substitutions result in substantial changes in toxicity, with the carbamate toxins being the most, the decarbamoyl toxins being of intermediate in potency and the sulfo-carbamoyl toxins generally being the least potent.
Paralytic shellfish toxins are produced by a number of genera of gonyaulacoid or gymnodinioid dinoflagellates, including Alexandrium, Gymnodinium and Pyrodinium, and have also been found in freshwater cyanophytes. Several studies suggest that saxitoxins can be produced autonomously by bacteria isolated from cultures of PSP producing dinoflagellates, although chemical identity of the toxic activity present in these bacteria has not been unambiguously confirmed. In addition, endosymbiotic or cell-associated bacteria may play a role in the production of paralytic shellfish toxins by dinoflagellates. Paralytic shellfish toxins are produced in varying proportions by different dinoflagellate species, and even by different isolates within a species. All congeners are not found in any one species. Metabolic pathways responsible for biosynthesis have been identified by radio tracer studies, which indicate that positions 1-12 of the molecule are formed by the condensation of acetate and arginine. The most prevalent congeners in dinoflagellates on a molar basis are the sulfocarbamoyl derivatives. This is of particular interest because the occurrence of N-sulfated groups is rare among natural products and may represent another novel dinoflagellate biosynthetic mechanism. N-sulfotransferase and N-oxidase activities have been identified in saxitoxin-producing dinoflagellates.
The toxin composition in bivalve tissues can differ markedly from that found in the dinoflagellates ingested. The capacity to metabolize PSP toxins varies substantially between shellfish species. In most shellfish, PSP toxins with a hydroxysulfate at the C11 position undergo epimerization. Of human health significance, the N-sulfocarbamoyl derivatives which account for the majority of toxin in some dinoflagellates may be metabolically converted to the more potent decarbamoyl congeners when metabolized in some shellfish species.
The role toxicity plays in the life history of the dinoflagellate species which produce them is not clear. It has been suggested that saxitoxins may play a role in nitrogen metabolism since some strains accumulate toxin up to 60 pg/cell or about 0.2% of total wet weight. However, the occurrence of healthy non-toxic strains would suggest that the saxitoxins are secondary metabolites which are not essential for dinoflagellate growth.
Saxitoxin binds with high affinity to site 1 on the voltage dependent sodium channel inhibiting channel opening. The binding affinity of saxitoxin congeners to site 1 varies proportionally with their toxicity in mice. The voltage dependent sodium channel plays a critical role in neurotransmission at both the neuronal synapses and neuromuscular junctions. The polarity of the molecule largely excludes it from traversing the blood brain barrier therefore, the primary site of action in humans is most likely at the neuromuscular junction. This is consistent with the rapid onset, less than one hour, of symptoms which are classical for paralytic shellfish poisoning, including: tingling and numbness of the peri-oral area and extremities, loss of motor control, drowsiness, incoherence and in the case of high doses, respiratory paralysis. The lethal dose in humans is 1-4 mg. Clinical symptoms of PSP in humans occurs when approximately 0.72 mg are ingested and serious cases generally involve ingestion of 0.9-3.6 mg. In a study of clinical samples from a PSP outbreak in Alaska in 1994 the clearance of saxitoxins from the blood in humans was found to be less than 24 hours even in patients who had experienced respiratory paralysis and were maintained on life support. Clearance was largely via the urine.
Currently, there is no widely available antidote for PSP. Monoclonal antibodies tested in vitro and in situ show some protection against binding and induced reduction of peripheral nerve action potential in rat tibial nerve, suggesting that antibodies may potentially provide useful reagents for protection against toxicity in vivo. In addition, the potassium channel blocker, 4-aminopurine, has recently been shown to significantly reverse the effects of toxicosis in rats suggesting that it may be useful as an antidote for PSP.
Neurotoxic Shellfish Toxins
The occurrence of neurotoxic shellfish poisoning, NSP, has historically been limited to the west coast of Florida where blooms of the dinoflagellate Gymnodinium breve initiate offshore and are subsequently carried inshore by wind and current conditions. Gulf of Mexico Gymnodinium breve blooms are occasionally carried around the base of Florida by the Loop Current and northward by the Gulf Stream resulting in red tides on the east coast of Florida and, in a single incident in 1987, as far north as North Carolina. In 1993 an unprecedented outbreak of shellfish toxicity in New Zealand resulted in the identification of additional Gymnodinium species, referred to as Gymnodinium cf. breve, which produce NSP-like toxins. Recently other fish killing flagellate species, Chatonella marina,Chatonella antiqua, Fibrocapsa japonica and Heterosigma akashiwo have also been reported to produce this class of polyether toxins.
The toxins responsible for NSP are a suite of ladder-like polycyclic ether toxins collectively called brevetoxins produced by Gymnodinium breve (syn. Ptychodiscus brevis). Brevetoxin congeners fall into two types based on backbone structure, the brevetoxin B backbone, type 1 and brevetoxin A backbone, type 2. The type 1 congeners are the most abundant in nature and the most prevalent in Gymnodinium breve. Although the ring systems in the middle of the molecules differ somewhat type 1 and type 2 toxins share a lactone in the A ring and a conserved structure on the ring both of which are required for their toxicity. Type 2 congeners are more flexible with 38 rotatable bonds, than those with the type 1 backbone which has only 31 rotatable bonds. This structure may play a role in their generally greater potency.
Brevetoxins bind with high affinity to site 5 on the voltage dependent sodium channel. Binding to this site alters both the voltage sensitivity of the channel, resulting in inappropriate opening of the channel under conditions in which it is normally closed, and inhibits channel inactivation, resulting in persistent activation or prolonged channel opening. The toxic potency of brevetoxin congeners correlates well with their relative binding to the sodium channel. Backbone flexibility may determine the relative ease with which the toxin can intercalate between trans-membrane domains of the sodium channel to interact with both the voltage sensor near the outside of the channel and the inactivation gate on the intracellular side. The symptoms of NSP include nausea, tingling and numbness of the peri-oral area, loss of motor control and severe muscular ache. Unlike PSP, NSP has not been known to be fatal and symptoms generally clear within a few days. Like PSP, there is presently no antidote for NSP.
Unlike most other dinoflagellates responsible for seafood poisonings, Gymnodinium breve is an unarmored dinoflagellate which is easily lysed in turbulent water. Gymnodinium breve red tides are frequently associated with massive fish kills. The extreme sensitivity of fish to the Florida red tide may result from lysis of cells passing through the gills. One route of human intoxication results from the consumption of shellfish that have accumulated brevetoxins by filter feeding. Recent studies in the greenshell mussel demonstrate that brevetoxins can be metabolized by shellfish to yield novel derivatives.
An additional route of human exposure to brevetoxins is through respiration of aerosolized toxin which is the result of cells breaking due to wave action. A common symptom associated with exposure to aerosolized brevetoxin is irritation and burning of the throat and upper respiratory tract. In 1996 at least 149 manatees died during an outbreak in Florida concurrent with a persistent red tide. Immuno-histochemical staining of tissues from affected animals revealed brevetoxin immuno-reactivity in lymphocytes and macrophages associated with inflammatory lesions of the respiratory tract and with lymphoid tissues. Molecular modeling studies have implicated brevetoxin as an inhibitor of a class of lysosomal proteases, the cysteine cathepsins, which are important in antigen presentation. The demonstration of brevetoxin immuno-reactivity in lymphoid tissue of the manatees raises the possibility of immuno-suppression as a second mode by which brevetoxin exposure may affect human health, particularly in individuals with chronic exposure to aerosolized toxin during prolonged red tide incidents.
Another seafood intoxication caused by ladder-like polyether toxins is ciguatera fish poisoning. Ciguatera occurs circum-globally in tropical coral reef regions and results from the consumption of fish which have accumulated toxins through the food web. It is estimated to affect over 50,000 people annually and is no longer a disease limited to the tropics due both to travel to the tropics and to shipping of tropical fish species to markets elsewhere in the world. Large carnivorous fishes associated with coral reefs are the most frequent source of ciguatera. Baracuda, snapper, grouper, jacks and moray eels are particularly notorious for their potential to carry high toxin loads. However, smaller herbivorous fishes may also be ciguatoxic particularly when viscera are consumed. The symptoms of ciguatera vary somewhat geographically as well as between individuals and incidents and may also vary temporally within an area, but generally include early onset, 2-6 hour, gastrointestinal disturbance, including nausea, vomiting and diarrhea which may be followed by a variety of later onset, 18 hour, neurological effects including numbness of the peri-oral area and extremities, reversal of temperature sensation, muscle and joint aches, headache, itching, tachycardia, hypertension, blurred vision and paralysis. Ciguatera is very rarely fatal. Ciguatera symptoms in the Caribbean differ somewhat from those in the Pacific in that gastrointestinal symptoms dominate, whereas in the Pacific neurological symptoms tend to dominate. This may reflect geographic differences in the toxins involved.
The origin of ciguatera toxins has been identified as the benthic coral reef associated dinoflagellate Gambierdiscus toxicus which grows as an epiphyte on filamentous macro-algae associated with coral reefs and reef lagoons. Its toxins enter the food web when these algae are grazed upon by herbivorous fishes and probably also invertebrates. Gambierdiscus toxicus produces two classes of polyether toxins, the ciguatoxins and maitotoxins. Ciguatoxins are lipophilic and are accumulated in fish through food web transfer. More than 20 ciguatoxin congeners have been isolated but only a few have been fully characterized structurally. Three classes of ciguatoxins are currently recognized based on polyether backbone structure. The first to be purified is the parent compound for the group which possess 60 carbons in 13 fused ether rings and is believed to be responsible for 90% of the toxicity associated with the Pacific intoxications. Several other type 1 toxins are found in fish flesh. The toxins found in fish flesh are more highly oxygenated than the congeners isolated from Gambierdiscus toxicus suggesting that they are metabolites of the dinoflagellate toxins of the same backbone structure. Type 2 congeners possess 57 carbons in 13 fused ether rings. Type 2 ciguatoxins lack the C1-C4 side chain present in type 1 and have an 8-membered rather than a 7-membered ring E. Like the type 1 toxins there is evidence that the congeners present in fish, represent an oxygenated metabolite of a dinoflagellate precursor. Several Caribbean congeners have been isolated chromatographically of which the most abundant is the first to be fully structurally characterized. There is a third class of ciguatoxin that lacks the spiroketal at C52 which is replaced by an additional fused 6-membered cyclic ether.
The ciguatoxins are structurally related to the brevetoxins and compete with brevetoxin for binding to site 5 on the voltage dependent sodium channel with a high affinity. Various estimates of human toxic potency have been made. Concentrations of less than 1.0 to 0.1 ppb of ciguatoxins are estimated to be toxic to humans. In a study of fish implicated in ciguatera cases in French Polynesia a minimum toxicity level to humans was estimated at 0.5 ng/g. Among the ciguatoxin congeners binding affinity correlates well with toxic potency in mice. However, the toxic potency of ciguatoxins in mice is several orders of magnitude greater than that of the brevetoxins relative to their binding affinities at the sodium channel. This may be related to differences in the bio-availability of the toxins or to undefined toxic effects of ciguatoxin.
The maitotoxins are transfused ladder-like polyether toxins but are somewhat more polar due to the presence of multiple sulfate groups. Maitotoxin was originally identified as a water soluble toxin in the viscera of surgeonfishes and later found to be the principal toxin produced by Gambierdiscus toxicus. The structure of three maitotoxin congeners have been identified in Pacific isolates of Gambierdiscus toxicus, They have not been demonstrated to bio-accumulate in fish tissues possibly due to their more polar structure. Thus, if maitotoxin is involved in ciguatera poisoning it may be implicated only in ciguatera poisonings derived from herbivorous fishes. Early hypotheses that maitotoxin may be a metabolic precursor to ciguatoxin have not proven to be true.
The toxic potency of maitotoxin exceeds that of ciguatoxin in mice. Its mode of action has not been fully determined. Its biological activity is strictly calcium dependent and causes both membrane depolarization and calcium influx in many different cell types. It was originally believed to be an activator of voltage dependent calcium channels. However, voltage-dependent calcium channel antagonists can block maitotoxin-stimulated calcium influx but not maitotoxin-induced membrane depolarization. Therefore, it appears that maitotoxin-induced activation of voltage dependent calcium channels is a secondary effect of membrane depolarization. Despite numerous studies the primary target of maitotoxin has not yet been fully determined although non-selective cation channels and calcium activated chloride channels have received recent attention. Calcium-release activated calcium channels, another proposed target, do not appear to be involved based on the failure of channel antagonists to inhibit maitotoxin activity. Removal of the sulfate esters causes a significant drop in toxicity.
The definition of ciguatera is complicated by the fact that Gambierdiscus toxicu is only one member of an assemblage of benthic dinoflagellates all of which produce toxins. Unlike the planktonic dinoflagellates toxicity in the benthic coral reef dinoflagellate assemblage appears to be quite common. Among the dinoflagellates which co-occur with Gambierdiscus toxicus are Ostreopsis, Prorocentrum, Coolia and Amphidinium. Each of these genera produces toxins which target different pharmacological receptors. However, with the exception of toxins derived from Ostreopsis the accumulation of most of these toxins in upper trophic levels of the coral reef community to concentrations which may impact human health has not been confirmed and therefore their contribution to ciguatera remains equivocal. However, Ostroepsis has been proposed to be the primary dinoflagellate responsible for ciguatera in Puerto Rico based on seasonal abundance of Ostreopsis and Gambierdiscus toxicus in Puerto Rican waters.Ostreopsis produces ostreocin, an analog of palytoxin.
Palytoxin has been confirmed as the causative agent in ciguatera-like poisonings from crab in the Pacific, mackerel, triggerfish and sardine clupeotoxism. Palytoxin is a macrocyclic polyether toxin characterized by a number of novel features including a C115 straight chain incorporating many functional groups; a terminal primary amine that is important for bio-activity; an unsaturated amide, two conjugated diene systems and a hemiketal. Palytoxin poisoning may be distinguishable from ciguatera by its severity, high fatality rate and unusual taste associated with the contaminated fish. The pharmacological target of palytoxin is Na+K+-ATPase, which pumps Na+ and K+ across the cell membrane against their electrochemical gradients, such that three Na+ ions are pumped out of the cell and two K+ ions are pumped into the cell for each ATP hydrolysed. In the presence of palytoxin, the pump is converted into an open channel that permits K+ efflux and influx of monovalent cations, Na+, NH4+, Cs+, Li+, along their electrochemical gradients. The palytoxin-induced pore appears to reside within the protein, possibly by stabilizing a channel made up of trans-membrane segments of the protein when the pump is in its open state.
Diarrhetic Shellfish Toxins
The diarrhetic shellfish toxins are a class of acidic polyether toxins produced by dinoflagellates and responsible for diarrhetic shellfish poisoning, DSP, associated with seafood consumption. This toxin class consists of at least eight congeners including the parent compound okadaic acid which was first isolated from the black sponge, Halichondria fortii. There are two primary congeners involved in shellfish poisoning with the other congeners believed to be either precursors or shellfish metabolites of the active toxins. DSP is widespread in its distribution with essentially seasonal occurrences in Europe and Japan. The first incidence of human shellfish-related illness identified as DSP occurred in Japan in the late 1970's where the dinoflagellate Dinophysis fortii was identified as the causative organism and the toxin responsible was termed dinophysistoxin. Retrospective analysis of similar disease outbreaks in the Netherlands and Scandinavia confirmed that these were also associated with Dinophysis. The major toxins involved in European outbreaks are okadaic acid and the primary diarrhetic toxin. However, incidents in Ireland and Portugal were found to include an additional toxin. The first confirmed incident of DSP in North America occurred in 1990 in the maritime provinces of Canada, but was associated with the benthic dinoflagellate Prorocentrum lima and two toxins including okadaic acid. Okadaic acid and related diarrhetic toxins are also produced by a number of other Prorocentrum species, including Prorocentrum maculosum, Prorocentrum concavum and Prorocentrum hoffmanianum but do not appear to be produced by Prorocentrum micans, Prorocentrum minimum or Prorocentrum mexicanum.
The diarrhetic toxins are inhibitors of serine/threonine protein phosphatases. The binding site for okadaic acid resides on the catalytic sub-unit of the protein phosphatase at the active site of the enzyme as determined by x-ray crystal structures, molecular modeling and mutational analyses. Binding to this site requires the carboxylic acid moiety which accounts for the inactive state of the diol esters and one of the diarrhetic toxin congeners.
Serine/threonine protein phosphatases are critical components of signaling cascades in eukaryotic cells which regulate a diverse array of cellular processes involved in metabolism, ion balance, neurotransmission and cell cycle regulation. Diarrhea associated with DSP is most likely due to the hyperphosphorylation of proteins, including ion channels, in the intestinal epithelia resulting in impaired water balance and loss of fluids. In addition, okadaic acid-like polyether toxins have been identified as tumor promotors. The toxic potency of okadaic acid is much lower than that of the neurotoxin polyethers.
The biosynthesis of the diarrhetic toxins and the mechanisms by which the dinoflagellate protects itself from its toxins have received much attention. Okadaic acid is localized to the chloroplast. Most of the intracellular toxin in Prorocentrum lima is present in the form of one of the diarrhetic toxin congeners which has been shown in metabolic labeling studies to be a biosynthetic precursor to okadaic acid. Thus, it is proposed that okadaic acid is released by Prorocentrum lima as an inactive pro-toxin, which is reduced extracellularly to the diol ester in the medium of Prorocentrum lima. The diol ester may then be cleaved at the ester linkage to yield the active toxin, okadaic acid. Okadaic acid can inhibit growth of diatoms. However, the observed growth inhibition of other dinoflagellates byProrocentrum lima was not attributable to okadaic acid. Dinoflagellates do possess okadaic acid-sensitive proteins whereas the protein phosphatases in Prorocentrum lima appear to be insensitive.
Amnesic Shellfish Toxin-Domoic Acid
Amnesic shellfish poisoning, ASP, is the only shellfish poison produced by a diatom and is currently limited in its distribution to North America. The first recorded occurrence of ASP was in Prince Edward Island, Canada in 1987, when approximately 100 people became ill after consuming contaminated mussels. None of the known shellfish toxins was found to be involved in the outbreak, but rather the toxic agent was identified as domoic acid. The source of domoic acid was found to be the diatom Pseudo-nitzschia multiseries, formerly known as Nitzschia pungens f. multiseries. Domoic acid is a water soluble tricarboxylic amino acid which acts an analog of the neurotransmitter glutamate and is a potent glutamate receptor agonist. Domoic acid was previously identified in the red alga Chondria armata but had not previously been linked to human illness. It is related both structurally and functionally to the excitatory neurotoxin kainic acid isolated from the red macro-alga Digenea simplex. Seven congeners of domoic acid have been identified. Of these, three geometrical isomers, isodomoic acids D, E, and F and the C5' diasteriomer are found, in addition to domoic acid, in small amounts in both the diatom and in shellfish tissue.
The symptoms of ASP include gastrointestinal effects, nausea, vomiting, diarrhea and neurological effects including dizziness, disorientation, lethargy, seizures and permanent loss of short term memory. Domoic acid binds with high affinity to glutamate receptors. Persistent activation of the kainate glutamate receptor results in greatly elevated intracellular Ca2+through cooperative interactions with NMDA and non-NMDA glutamate receptor subtypes and voltage dependent calcium channels. Neurotoxicity due to domoic acid results in high intracellular calcium and subsequent lesions in areas of the brain where glutaminergic pathways are heavily concentrated, particularly in the CA1 and CA3 regions of the hippocampus an area responsible for learning and memory processing. However, memory deficits occur at doses below those causing structural damage. In the 1987 outbreak, human toxicity occurred at 1-5 mg/kg. Individuals found most susceptible were elderly individuals and those with impaired renal function resulting in poor toxin clearance. Increased susceptibility of elderly individuals appears to be due to impaired toxin clearance as studies in experimental animals and neonates indicate.
Since the 1987 outbreak domoic acid has been identified as the causative agent in the mass mortality of pelicans and cormorants in Monterey Bay, California in 1991 and for the extensive die-off of California sea lions in the same region in 1998. The causative organism in both the 1991 and 1998 mortality events was identified as another member of the same diatom genus, Pseudo-nitzschia australis. At least seven species of Pseudo-nitzschia are now recognized as domoic acid producers and these toxin producing Pseudo-nitzschia species have since been identified in widely diverse geographic areas around the world. However, none have been implicated in intoxication events.
As with the other algal toxins the role of domoic acid in the life history of Pseudo-nitzschia is not clear. The production of domoic acid by Pseudo-nitzschia correlates with physiological stress, including silicon or phosphorus limitation or nitrogen excess. This pattern of synthesis is consistent with classical secondary metabolite biosynthesis by bacteria and other protists and differs from the constitutive pattern observed in synthesis of polyether toxins by dinoflagellates and PSP toxins. In culture domoic acid is produced primarily in stationary phase which corresponds with the depletion of silicon from the medium. The 1987 bloom of Pseudo-nitzschia in Canada was associated with pulses of nitrate from riverine input or re-suspended sediments. The biosynthesis of domoic acid involves the condensation of acetates via two intermediates, a glutamate derivative from the Krebs cycle and an isoprenoid structure likely derived from geranyl pyrophosphate. The precise enzymatic pathways responsible for biosynthesis have not been elucidated.
There is an extensive bibliography on this topic at the following website. http://www.chbr.noaa.gov/CoastalResearch/DiversityEssay.htm.