Aflatoxins

Aflatoxicosis
Aflatoxicosis is poisoning that results from ingestion of aflatoxins in contaminated food or feed. The aflatoxins are a group of structurally related toxic compounds produced by certain strains of the fungi Aspergillus flavus and A. parasiticus. Under favorable conditions of temperature and humidity, these fungi grow on certain foods and feeds, resulting in the production of aflatoxins. The most pronounced contamination has been encountered in tree nuts, peanuts, and other oilseeds, including corn and cottonseed. The major aflatoxins of concern are designated B1, B2, G1, and G2. These toxins are usually found together in various foods and feeds in various proportions; however, aflatoxin B1 is usually predominant and is the most toxic. When a commodity is analyzed by thin-layer chromatography, the aflatoxins separate into the individual components in the order given above; however, the first two fluoresce blue when viewed under ultraviolet light and the second two fluoresce green. Aflatoxin M a major metabolic product of aflatoxin B1 in animals and is usually excreted in the milk and urine of dairy cattle and other mammalian species that have consumed aflatoxin-contaminated food or feed.

Aflatoxins produce acute necrosis, cirrhosis, and carcinoma of the liver in a number of animal species; no animal species is resistant to the acute toxic effects of aflatoxins; hence it is logical to assume that humans may be similarly affected. A wide variation in LD50 values has been obtained in animal species tested with single doses of aflatoxins. For most species, the LD50 value ranges from 0.5 to 10 mg/kg body weight. Animal species respond differently in their susceptibility to the chronic and acute toxicity of aflatoxins. The toxicity can be influenced by environmental factors, exposure level, and duration of exposure, age, health, and nutritional status of diet. Aflatoxin B1 is a very potent carcinogen in many species, including nonhuman primates, birds, fish, and rodents. In each species, the liver is the primary target organ of acute injury. Metabolism plays a major role in determining the toxicity of aflatoxin B1; studies show that this aflatoxion requires metabolic activation to exert its carcinogenic effect, and these effects can be modified by induction or inhibition of the mixed function oxidase system.

Aflatoxicosis in humans has rarely been reported; however, such cases are not always recognized. Aflatoxicosis may be suspected when a disease outbreak exhibits the following characteristics:
· the cause is not readily identifiable
· the condition is not transmissible
· syndromes may be associated with certain batches of food
· treatment with antibiotics or other drugs has little effect
· the outbreak may be seasonal, i.e., weather conditions may affect mold growth.
The adverse effects of aflatoxins in animals (and presumably in humans) have been categorized in two general forms.
A. (Primary) Acute aflatoxicosis is produced when moderate to high levels of aflatoxins are consumed. Specific, acute episodes of disease ensue may include hemorrhage, acute liver damage, edema, alteration in digestion, absorption and/or metabolism of nutrients, and possibly death.
B. (Primary) Chronic aflatoxicosis results from ingestion of low to moderate levels of aflatoxins. The effects are usually subclinical and difficult to recognize. Some of the common symptoms are impaired food conversion and slower rates of growth with or without the production of an overt aflatoxin syndrome.

In the United States, aflatoxins have been identified in corn and corn products, peanuts and peanut products, cottonseed, milk, and tree nuts such as Brazil nuts, pecans, pistachio nuts, and walnuts. Other grains and nuts are susceptible but less prone to contamination.

The relative frequency of aflatoxicosis in humans in the United States is not known. No outbreaks have been reported in humans. Sporadic cases have been reported in animals.

In well-developed countries, aflatoxin contamination rarely occurs in foods at levels that cause acute aflatoxicosis in humans. In view of this, studies on human toxicity from ingestion of aflatoxins have focused on their carcinogenic potential. The relative susceptibility of humans to aflatoxins is not known, even though epidemiological studies in Africa and Southeast Asia, where there is a high incidence of hepatoma, have revealed an association between cancer incidence and the aflatoxin content of the diet. These studies have not proved a cause-effect relationship, but the evidence suggests an association.
One of the most important accounts of aflatoxicosis in humans occurred in more than 150 villages in adjacent districts of two neighboring states in northwest India in the fall of 1974. According to one report of this outbreak, 397 persons were affected and 108 persons died. In this outbreak, contaminated corn was the major dietary constituent, and aflatoxin levels of 0.25 to 15 mg/kg were found. The daily aflatoxin B1 intake was estimated to have been at least 55 ug/kg body weight for an undetermined number of days. The patients experienced high fever, rapid progressive jaundice, edema of the limbs, pain, vomiting, and swollen livers. One investigator reported a peculiar and very notable feature of the outbreak: the appearance of signs of disease in one village population was preceded by a similar disease in domestic dogs, which was usually fatal. Histopathological examination of humans showed extensive bile duct proliferation and periportal fibrosis of the liver together with gastrointestinal hemorrhages. A 10-year follow-up of the Indian outbreak found the survivors fully recovered with no ill effects from the experience.
A second outbreak of aflatoxicosis was reported from Kenya in 1982. There were 20 hospital admissions with a 60% mortality; daily aflatoxin intake was estimated to be at least 38 ug/kg body weight for an undetermined number of days.
In a deliberate suicide attempt, a laboratory worker ingested 12 ug/kg body weight of aflatoxin B1 per day over a 2-day period and 6 months later, 11 ug/kg body weight per day over a 14-day period. Except for transient rash, nausea and headache, there were no ill effects; hence, these levels may serve as possible no-effect levels for aflatoxin B1 in humans. In a 14-year follow-up, a physical examination and blood chemistry, including tests for liver function, were normal.

Although humans and animals are susceptible to the effects of acute aflatoxicosis, the chances of human exposure to acute levels of aflatoxin is remote in well-developed countries. In undeveloped countries, human susceptibility can vary with age, health, and level and duration of exposure.

Many chemical procedures have been developed to identify and measure aflatoxins in various commodities. The basic steps include extraction, lipid removal, cleanup, separation and quantification. Depending on the nature of the commodity, methods can sometimes be simplified by omitting unnecessary steps. Chemical methods have been developed for peanuts, corn, cottonseed, various tree nuts, and animal feeds. Chemical methods for aflatoxin in milk and dairy products are far more sensitive than for the above commodities because the aflatoxin M animal metabolite is usually found at much lower levels (ppb and ppt). All collaboratively studied methods for aflatoxin analysis are described in Chapter 26 of the AOAC Official Methods of Analysis.

Literature references can be found at the links below.
Very little information is available on outbreaks of aflatoxicosis in humans because medical services are less developed in the areas of the world where high levels of contamination of aflatoxins occur in foods, and, therefore, many cases go unnoticed.
For more information on recent outbreaks see the Morbidity and Mortality Weekly Reports from CDC.

Literature references can be found at the links below.
Available from the GenBank Taxonomy database, which contains the names of all organisms that are represented in the genetic databases with at least one nucleotide or protein sequence.

These structures were created by Fred Frye of the FDA.

Aflatoxin G1
Toxin produced by certain strains of the fungi Aspergillus flavus and A. parasiticus.


Aflatoxin B1 and M1
Toxin produced by certain strains of the fungi Aspergillus flavus and A. parasiticus.

Pyrrolizidine Alkaloids

Pyrrolizidine Alkaloids Poisoning
Pyrrolizidine alkaloid intoxication is caused by consumption of plant material containing these alkaloids. The plants may be consumed as food, for medicinal purposes, or as contaminants of other agricultural crops. Cereal crops and forage crops are sometimes contaminated with pyrrolizidine-producing weeds, and the alkaloids find their way into flour and other foods, including milk from cows feeding on these plants. Many plants from the Boraginaceae, Compositae, and Leguminosae families contain well over 100 hepatotoxic pyrrolizidine alkaloids.

Most cases of pyrrolizidine alkaloid toxicity result in moderate to severe liver damage. Gastrointestinal symptoms are usually the first sign of intoxication, and consist predominantly of abdominal pain with vomiting and the development of ascites. Death may ensue from 2 weeks to more than 2 years after poisoning, but patients may recover almost completely if the alkaloid intake is discontinued and the liver damage has not been too severe.

Evidence of toxicity may not become apparent until sometime after the alkaloid is ingested. The acute illness has been compared to the Budd-Chiari syndrome (thrombosis of hepatic veins, leading to liver enlargement, portal hypertension, and ascites). Early clinical signs include nausea and acute upper gastric pain, acute abdominal distension with prominent dilated veins on the abdominal wall, fever, and biochemical evidence of liver disfunction. Fever and jaundice may be present. In some cases the lungs are affected; pulmonary edema and pleural effusions have been observed. Lung damage may be prominent and has been fatal. Chronic illness from ingestion of small amounts of the alkaloids over a long period proceeds through fibrosis of the liver to cirrhosis, which is indistinguishable from cirrhosis of other etiology.

The plants most frequently implicated in pyrrolizidine poisoning are members of the Borginaceae, Compositae, and Leguminosae families. Consumption of the alkaloid-containing plants as food, contaminants of food, or as medicinals has occurred.

Reports of acute poisoning in the United States among humans are relatively rare. Most result from the use of medicinal preparations as home remedies. However, intoxications of range animals sometimes occur in areas under drought stress, where plants containing alkaloids are common. Milk from dairy animals can become contaminated with the alkaloids, and alkaloids have been found in the honey collected by bees foraging on toxic plants. Mass human poisonings have occurred in other countries when cereal crops used to prepare food were contaminated with seeds containing pyrrolizidine alkaloid.

No information currently available.

All humans are believed to be susceptible to the hepatotoxic pyrrolizidine alkaloids. Home remedies and consumption of herbal teas in large quantities can be a risk factor and are the most likely causes of alkaloid poisonings in the United States.

The pyrrolizidine alkaloids can be isolated from the suspect commodity by any of several standard alkaloid extraction procedures. The toxins are identified by thin layer chromatography. The pyrrolizidine ring is first oxidized to a pyrrole followed by spraying with Ehrlich reagent, which gives a characteristic purple spot. Gas-liquid chromatographic and mass spectral methods also are available for identifying the alkaloids.

There have been relatively few reports of human poisonings in the United States. Worldwide, however, a number of cases have been documented. Most of the intoxications in the USA involved the consumption of herbal preparations either as a tea or as a medicine. The first patient diagnosed in the USA was a female who had used a medicinal tea for 6 months while in Ecuador. She developed typical hepatic veno-occlusive disease, with voluminous ascites, centrilobular congestion of the liver, and increased portal vein pressure. Interestingly, the patient completely recovered within one year after ceasing to consume the tea. Another herbal tea poisoning occurred when Senecio longilobus was mistaken for a harmless plant (called "gordolobo yerba" by Mexican Americans) and used to make herbal cough medicine. Two infants were given this medication for several days. The 2-month-old boy was ill for 2 weeks before being admitted to the hospital and died 6 days later. His condition was first diagnosed as Reye's syndrome, but was changed when jaundice, ascites, and liver necrosis were observed. The second child, a 6-month-old female, had acute hepatocellular disease, ascites, portal hypertension, and a right pleural effusion. The patient improved with treatment; however, after 6 months, a liver biopsy revealed extensive hepatic fibrosis, progressing to cirrhosis over 6 months. Another case of hepatic veno-occlusive disease was described in a 47-year-old nonalcoholic woman who had consumed large quantities of comfrey (Symphytum species) tea and pills for more than one year. Liver damage was still present 20 months after the comfrey consumption ceased.
For more information on recent outbreaks see the Morbidity and Mortality Weekly Reports from CDC.

Literature references can be found at the links below.
Pyrrolizidine Alkaloids of Symphytum spp.
Toxin produced by plants from the Boraginaceae, Compositae, and Leguminosae families.

Pyrrolizidine Alkaloids of Senecio longilobus Benth.
Toxin produced by plants from the Boraginaceae, Compositae, and Leguminosae families.


This compound, a lectin or hemagglutinin, has been used by immunologists for years to trigger DNA synthesis in T lymphocytes, and more recently, to activate latent human immunodeficiency virus type 1 (HIV-1, AIDS virus) from human peripheral lymphocytes. Besides inducing mitosis, lectins are known for their ability to agglutinate many mammalian red blood cell types, alter cell membrane transport systems, alter cell permeability to proteins, and generally interfere with cellular metabolism.

Red Kidney Bean (Phaseolus vulgaris) Poisoning, Kinkoti Bean Poisoning, and possibly other names.

The onset time from consumption of raw or undercooked kidney beans to symptoms varies from between 1 to 3 hours. Onset is usually marked by extreme nausea, followed by vomiting, which may be very severe. Diarrhea develops somewhat later (from one to a few hours), and some persons report abdominal pain. Some persons have been hospitalized, but recovery is usually rapid (3 - 4 h after onset of symptoms) and spontaneous.

Diagnosis is made on the basis of symptoms, food history, and the exclusion of other rapid onset food poisoning agents (e.g., Bacillus cereus, Staphylococcus aureus, arsenic, mercury, lead, and cyanide).

Phytohaemagglutinin, the presumed toxic agent, is found in many species of beans, but it is in highest concentration in red kidney beans (Phaseolus vulgaris). The unit of toxin measure is the hemagglutinating unit (hau). Raw kidney beans contain from 20,000 to 70,000 hau, while fully cooked beans contain from 200 to 400 hau. White kidney beans, another variety of Phaseolus vulgaris, contain about one-third the amount of toxin as the red variety; broad beans (Vicia faba) contain 5 to 10% the amount that red kidney beans contain.
The syndrome is usually caused by the ingestion of raw, soaked kidney beans, either alone or in salads or casseroles. As few as four or five raw beans can trigger symptoms. Several outbreaks have been associated with "slow cookers" or crock pots, or in casseroles which had not reached a high enough internal temperature to destroy the glycoprotein lectin. It has been shown that heating to 80°C may potentiate the toxicity five-fold, so that these beans are more toxic than if eaten raw. In studies of casseroles cooked in slow cookers, internal temperatures often did not exceed 75°C.

This syndrome has occurred in the United Kingdom with some regularity. Seven outbreaks occurred in the U.K. between 1976 and 1979 and were reviewed (Noah et al. 1980. Br. Med. J. 19 July, 236-7). Two more incidents were reported by Public Health Laboratory Services (PHLS), Colindale, U.K. in the summer of 1988. Reports of this syndrome in the United States are anecdotal and have not been formally published.

The disease course is rapid. All symptoms usually resolve within several hours of onset. Vomiting is usually described as profuse, and the severity of symptoms is directly related to the dose of toxin (number of raw beans ingested). Hospitalization has occasionally resulted, and intravenous fluids may have to be administered. Although of short duration, the symptoms are extremely debilitating.

All persons, regardless of age or gender, appear to be equally susceptible; the severity is related only to the dose ingested. In the seven outbreaks mentioned above, the attack rate was 100%.

The difficulty in food analysis is that this syndrome is not well known in the medical community. Other possible causes must be eliminated, such as Bacillus cereus, staphylococcal food poisoning, or chemical toxicity. If beans are a component of the suspected meal, analysis is quite simple, and based on hemagglutination of red blood cells (hau).

Literature references can be found at the links below.
As previously stated, no major outbreaks have occurred in the U.S. Outbreaks in the U.K. are far more common. The syndrome is probably sporadic, affecting small numbers of persons or individuals, and is easily misdiagnosed or never reported due to the short duration of symptoms. Differences in reporting between the U.S. and U.K. may be attributed to greater use of dried kidney beans in the U.K., or better physician awareness. The U.K. has established a reference laboratory for the quantitation of hemagglutinins from suspected foods.
For more information on recent outbreaks see the Morbidity and Mortality Weekly Reports from CDC.

Literature references can be found at the links below.
Available from the GenBank Taxonomy database, which contains the names of all organisms that are represented in the genetic databases with at least one nucleotide or protein sequence.
NOTE: The following procedure has been recommended by the PHLS to render kidney, and other, beans safe for consumption:
Soak in water for at least 5 hours. Pour away the water. Boil briskly in fresh water, with occasional stirring, for at least 10 minutes. Undercooked beans may be more toxic than raw beans.
Grayanotoxin (formerly known as andromedotoxin, acetylandromedol, and rhodotoxin)

Honey Intoxication
Honey intoxication is caused by the consumption of honey produced from the nectar of rhododendrons. The grayanotoxins cause the intoxication. The specific grayanotoxins vary with the plant species. These compounds are diterpenes, polyhydroxylated cyclic hydrocarbons that do not contain nitrogen. Other names associated with the disease is rhododendron poisoning, mad honey intoxication or grayanotoxin poisoning.

The intoxication is rarely fatal and generally lasts for no more than 24 hours. Generally the disease induces dizziness, weakness, excessive perspiration, nausea, and vomiting shortly after the toxic honey is ingested. Other symptoms that can occur are low blood pressure or shock, bradyarrhythima (slowness of the heart beat associated with an irregularity in the heart rhythm), sinus bradycardia (a slow sinus rhythm, with a heart rate less than 60), nodal rhythm (pertaining to a node, particularly the atrioventricular node), Wolff-Parkinson-White syndrome (anomalous atrioventricular excitation) and complete atrioventricular block.

The grayanotoxins bind to sodium channels in cell membranes. The binding unit is the group II receptor site, localized on a region of the sodium channel that is involved in the voltage-dependent activation and inactivation. These compounds prevent inactivation; thus, excitable cells (nerve and muscle) are maintained in a state of depolarization, during which entry of calcium into the cells may be facilitated. This action is similar to that exerted by the alkaloids of veratrum and aconite. All of the observed responses of skeletal and heart muscles, nerves, and the central nervous system are related to the membrane effects.
Because the intoxication is rarely fatal and recovery generally occurs within 24 hours, intervention may not be required. Severe low blood pressure usually responds to the administration of fluids and correction of bradycardia; therapy with vasopressors (agents that stimulate contraction of the muscular tissue of the capillaries and arteries) is only rarely required. Sinus bradycardia and conduction defects usually respond to atropine therapy; however, in at least one instance the use of a temporary pacemaker was required.

In humans, symptoms of poisoning occur after a dose-dependent latent period of a few minutes to two or more hours and include salivation, vomiting, and both circumoral (around or near the mouth) and extremity paresthesia (abnormal sensations). Pronounced low blood pressure and sinus bradycardia develop. In severe intoxication, loss of coordination and progressive muscular weakness result. Extrasystoles (a premature contraction of the heart that is independent of the normal rhythm and arises in response to an impulse in some part of the heart other than the sinoatrial node; called also premature beat) and ventricular tachycardia (an abnormally rapid ventricular rhythm with aberrant ventricular excitation, usually in excess of 150 per minute) with both atrioventricular and intraventricular conduction disturbances also may occur. Convulsions are reported occasionally.

Grayanotoxin poisoning most commonly results from the ingestion of grayanotoxin-contaminated honey, although it may result from the ingestion of the leaves, flowers, and nectar of rhododendrons. Not all rhododendrons produce grayanotoxins. Rhododendron ponticum grows extensively on the mountains of the eastern Black Sea area of Turkey. This species has been associated with honey poisoning since 401 BC. A number of toxin species are native to the United States. Of particular importance are the western azalea (Rhododendron occidentale) found from Oregon to southern California, the California rosebay (Rhododendron macrophyllum) found from British Columbia to central California, and Rhododendron albiflorum found from British Columbia to Oregon and in Colorado. In the eastern half of the United States grayanotoxin-contaminated honey may be derived from other members of the botanical family Ericaceae, to which rhododendrons belong. Mountain laurel (Kalmia latifolia) and sheep laurel (Kalmia angustifolia) are probably the most important sources of the toxin.

Grayanotoxin poisoning in humans is rare. However, cases of honey intoxication should be anticipated everywhere. Some may be ascribed to a increase consumption of imported honey. Others may result from the ingestion of unprocessed honey with the increased desire of natural foods in the American diet.

All people are believed to be susceptible to honey intoxication. The increased desire of the American public for natural (unprocessed) foods, may result in more cases of grayanotoxin poisoning. Individuals who obtain honey from farmers who may have only a few hives are at increased risk. The pooling of massive quantities of honey during commercial processing generally dilutes any toxic substance.

The grayanotoxins can be isolated from the suspect commodity by typical extraction procedures for naturally occurring terpenes. The toxins are identified by thin layer chromatography.

Literature references can be found at the links below.
Several cases of grayanotoxin poisonings in humans have been documented in the 1980s. These reports come from Turkey and Austria. The Austrian case resulted from the consumption of honey that was brought back from a visit to Turkey. From 1984 to 1986, 16 patients were treated for honey intoxication in Turkey. The symptoms started approximately 1 h after 50 g of honey was consumed. In an average of 24 h, all of the patients recovered. The case in Austria resulted in cardiac arrhythmia, which required a temporal pacemaker to prevent further decrease in heart rate. After a few hours, pacemaker simulation was no longer needed. The Austrian case shows that with increased travel throughout the world, the risk of grayanotoxin poisoning is possible outside the areas of Ericaceae-dominated vegetation, namely, Turkey, Japan, Brazil, United States, Nepal, and British Columbia. In 1983 several British veterinarians reported a incident of grayanotoxin poisoning in goats. One of the four animals died. Post-mortem examination showed grayanotoxin in the rumen contents.
For more information on recent outbreaks see the Morbidity and Mortality Weekly Reports from CDC.

Literature references can be found at the links below.
Available from the GenBank Taxonomy database, which contains the names of all organisms that are represented in the genetic databases with at least one nucleotide or protein sequence.

Grayanotoxin (andromedotoxin, acetylandromedol, rhodotoxin)
Toxin produced from the nectar of rhododendrons, occassionally found in honey.

Ciguatera

Ciguatera Fish Poisoning
Ciguatera is a form of human poisoning caused by the consumption of subtropical and tropical marine finfish which have accumulated naturally occurring toxins through their diet. The toxins are known to originate from several dinoflagellate (algae) species that are common to ciguatera endemic regions in the lower latitudes.

Manifestations of ciguatera in humans usually involves a combination of gastrointestinal, neurological, and cardiovascular disorders. Symptoms defined within these general categories vary with the geographic origin of toxic fish.

Clinical testing procedures are not presently available for the diagnosis of ciguatera in humans. Diagnosis is based entirely on symptomology and recent dietary history. An enzyme immunoassay (EIA) designed to detect toxic fish in field situations is under evaluation by the Association of Official Analytical Chemists (AOAC) and may provide some measure of protection to the public in the future.

Marine finfish most commonly implicated in ciguatera fish poisoning include the groupers, barracudas, snappers, jacks, mackerel, and triggerfish. Many other species of warm-water fishes harbor ciguatera toxins. The occurrence of toxic fish is sporadic, and not all fish of a given species or from a given locality will be toxic.

The relative frequency of ciguatera fish poisoning in the United States is not known. The disease has only recently become known to the general medical community, and there is a concern that incidence is largely under-reported because of the generally non-fatal nature and short duration of the disease.

Initial signs of poisoning occur within six hours after consumption of toxic fish and include perioral numbness and tingling (paresthesia), which may spread to the extremities, nausea, vomiting, and diarrhea. Neurological signs include intensified paresthesia, arthralgia, myalgia, headache, temperature sensory reversal and acute sensitivity to temperature extremes, vertigo, and muscular weakness to the point of prostration. Cardiovascular signs include arrhythmia, bradycardia or tachycardia, and reduced blood pressure. Ciguatera poisoning is usually self-limiting, and signs of poisoning often subside within several days from onset. However, in severe cases the neurological symptoms are known to persist from weeks to months. In a few isolated cases neurological symptoms have persisted for several years, and in other cases recovered patients have experienced recurrence of neurological symptoms months to years after recovery. Such relapses are most often associated with changes in dietary habits or with consumption of alcohol. There is a low incidence of death resulting from respiratory and cardiovascular failure.

All humans are believed to be susceptible to ciguatera toxins. Populations in tropical/subtropical regions are most likely to be affected because of the frequency of exposure to toxic fishes. However, the increasing per capita consumption of fishery products coupled with an increase in interregional transportation of seafood products has expanded the geographic range of human poisonings.

The ciguatera toxins can be recovered from toxic fish through tedious extraction and purification procedures. The mouse bioassay is a generally accepted method of establishing toxicity of suspect fish. A much simplified EIA method intended to supplant the mouse bioassay for identifying ciguatera toxins is under evaluation.

Literature references can be found at the links below.
This report summarizes an investigation of this outbreak by the Texas Department of Health (TDH), which indicated that 17 crew members experienced ciguatera fish poisoning resulting from eating a contaminated barracuda.
Twenty cases of ciguatera fish poisoning from consumption of amberjack were reported to the Florida Department of Health and Rehabilitative Services (HRS) in August and September 1991. This report summarizes the investigation of these cases by the Florida HRS.
On October 29, 1985, the Epidemiology Division, Vermont Department of Health, learned of two persons with symptoms consistent with ciguatera fish poisoning. Both had eaten barracuda at a local restaurant on October 19.
On March 6, 1982, the U.S. Coast Guard in Miami, Florida, received a request for medical assistance from an Italian freighter located in waters off Freeport, Bahamas. Numerous crew members were ill with nausea, vomiting, and muscle weakness and required medical evacuation for hospitalization and treatment. There findings were consistent with ciguatera fish poisoning.
For more information on recent outbreaks see the Morbidity and Mortality Weekly Reports from CDC.

Literature references can be found at the links below
Ciguatoxin (CTx-1)
Toxin produced by the Dinoflagellate Gambierdiscus toxicus and isolated from the flesh and viscera of ciguatoxic fish.
Shellfish poisoning is caused by a group of toxins elaborated by planktonic algae (dinoflagellates, in most cases) upon which the shellfish feed. The toxins are accumulated and sometimes metabolized by the shellfish. The 20 toxins responsible for paralytic shellfish poisonings (PSP) are all derivatives of saxitoxin. Diarrheic shellfish poisoning (DSP) is presumably caused by a group of high molecular weight polyethers, including okadaic acid, the dinophysis toxins, the pectenotoxins, and yessotoxin. Neurotoxic shellfish poisoning (NSP) is the result of exposure to a group of polyethers called brevetoxins. Amnesic shellfish poisoning (ASP) is caused by the unusual amino acid, domoic acid, as the contaminant of shellfish.

Types of Shellfish Poisoning.
Paralytic Shellfish Poisoning (PSP)
Diarrheic Shellfish Poisoning (DSP)
Neurotoxic Shellfish Poisoning (NSP)
Amnesic Shellfish Poisoning (ASP)

Ingestion of contaminated shellfish results in a wide variety of symptoms, depending upon the toxins(s) present, their concentrations in the shellfish and the amount of contaminated shellfish consumed. In the case of PSP, the effects are predominantly neurological and include tingling, burning, numbness, drowsiness, incoherent speech, and respiratory paralysis. Less well characterized are the symptoms associated with DSP, NSP, and ASP. DSP is primarily observed as a generally mild gastrointestinal disorder, i.e., nausea, vomiting, diarrhea, and abdominal pain accompanied by chills, headache, and fever. Both gastrointestinal and neurological symptoms characterize NSP, including tingling and numbness of lips, tongue, and throat, muscular aches, dizziness, reversal of the sensations of hot and cold, diarrhea, and vomiting. ASP is characterized by gastrointestinal disorders (vomiting, diarrhea, abdominal pain) and neurological problems (confusion, memory loss, disorientation, seizure, coma).

Diagnosis of shellfish poisoning is based entirely on observed symptomatology and recent dietary history.

All shellfish (filter-feeding molluscs) are potentially toxic. However, PSP is generally associated with mussels, clams, cockles, and scallops; NSP with shellfish harvested along the Florida coast and the Gulf of Mexico; DSP with mussels, oysters, and scallops, and ASP with mussels.

Good statistical data on the occurrence and severity of shellfish poisoning are largely unavailable, which undoubtedly reflects the inability to measure the true incidence of the disease. Cases are frequently misdiagnosed and, in general, infrequently reported. Of these toxicoses, the most serious from a public health perspective appears to be PSP. The extreme potency of the PSP toxins has, in the past, resulted in an unusually high mortality rate.

PSP: Symptoms of the disease develop fairly rapidly, within 0.5 to 2 hours after ingestion of the shellfish, depending on the amount of toxin consumed. In severe cases respiratory paralysis is common, and death may occur if respiratory support is not provided. When such support is applied within 12 hours of exposure, recovery usually is complete, with no lasting side effects. In unusual cases, because of the weak hypotensive action of the toxin, death may occur from cardiovascular collapse despite respiratory support.
NSP: Onset of this disease occurs within a few minutes to a few hours; duration is fairly short, from a few hours to several days. Recovery is complete with few after effects; no fatalities have been reported.
DSP: Onset of the disease, depending on the dose of toxin ingested, may be as little as 30 minutes to 2 to 3 hours, with symptoms of the illness lasting as long as 2 to 3 days. Recovery is complete with no after effects; the disease is generally not life threatening.
ASP: The toxicosis is characterized by the onset of gastrointestinal symptoms within 24 hours; neurological symptoms occur within 48 hours. The toxicosis is particularly serious in elderly patients, and includes symptoms reminiscent of Alzheimer's disease. All fatalities to date have involved elderly patients.

All humans are susceptible to shellfish poisoning. Elderly people are apparently predisposed to the severe neurological effects of the ASP toxin. A disproportionate number of PSP cases occur among tourists or others who are not native to the location where the toxic shellfish are harvested. This may be due to disregard for either official quarantines or traditions of safe consumption, both of which tend to protect the local population.

The mouse bioassay has historically been the most universally applied technique for examining shellfish (especially for PSP); other bioassay procedures have been developed but not generally applied. Unfortunately, the dose-survival times for the DSP toxins in the mouse assay fluctuate considerably and fatty acids interfere with the assay, giving false-positive results; consequently, a suckling mouse assay that has been developed and used for control of DSP measures fluid accumulation after injection of the shellfish extract. In recent years considerable effort has been applied to development of chemical assays to replace these bioassays. As a result a good high performance liquid chromatography (HPLC) procedure has been developed to identify individual PSP toxins (detection limit for saxitoxin = 20 fg/100 g of meats; 0.2 ppm), an excellent HPLC procedure (detection limit for okadaic acid = 400 ng/g; 0.4 ppm), a commercially available immunoassay (detection limit for okadaic acid = 1 fg/100 g of meats; 0.01 ppm) for DSP and a totally satisfactory HPLC procedure for ASP (detection limit for domoic acid = 750 ng/g; 0.75 ppm).

Literature references can be found at the links below.
Paralytic shellfish poisoning (PSP) is a foodborne illness caused by consumption of shellfish or broth from cooked shellfish that contain either concentrated saxitoxin, an alkaloid neurotoxin, or related compounds. This report summarizes outbreaks of PSP that occurred in Massachusetts and Alaska in June 1990.
PSP is associated with relatively few outbreaks, most likely because of the strong control programs in the United States that prevent human exposure to toxic shellfish. That PSP can be a serious public health problem, however, was demonstrated in Guatemala, where an outbreak of 187 cases with 26 deaths, recorded in 1987, resulted from ingestion of a clam soup. The outbreak led to the establishment of a control program over shellfish harvested in Guatemala.
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; 22 individuals were hospitalized and three elderly patients eventually died.
The occurrence of DSP in Europe is sporadic, continuous and presumably widespread (anecdotal). DSP poisoning has not been confirmed in U.S. seafood, but the organisms that produce DSP are present in U.S. waters. 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.
For more information on recent outbreaks see the Morbidity and Mortality Weekly Reports from CDC.

Dinophysis Toxin
Toxin produced or elaborated by planktonic algae(dinoflagellates, in most cases) upon whichthe shellfish feed.
Brevetoxin
Toxin produced or elaborated by planktonic algae(dinoflagellates, in most cases) upon whichthe shellfish feed.


Saxitoxin
Paralytic shellfish toxin produced or elaborated by planktonic algae(dinoflagellates, in most cases) upon which the shellfish feed.

Okadaic Acid
Toxin produced by planktonic algae (dinoflagellates, in most cases) upon which the shellfish feed.
Domoic Acid
Toxin produced by planktonic algae(dinoflagellates, in most cases)upon which the shellfish feed.
Yessotoxin
Toxin produced by planktonic algae(dinoflagellates, in most cases) uponwhich the shellfish feed.
Pectenotoxin
Toxin produced or elaborated by planktonic algae(dinoflagellates, in most cases) upon whichthe shellfish feed.
Scombrotoxin

Scombroid Poisoning (also called Histamine Poisoning)
Scombroid poisoning is caused by the ingestion of foods that contain high levels of histamine and possibly other vasoactive amines and compounds. Histamine and other amines are formed by the growth of certain bacteria and the subsequent action of their decarboxylase enzymes on histidine and other amino acids in food, either during the production of a product such as Swiss cheese or by spoilage of foods such as fishery products, particularly tuna or mahi mahi. However, any food that contains the appropriate amino acids and is subjected to certain bacterial contamination and growth may lead to scombroid poisoning when ingested.

Initial symptoms may include a tingling or burning sensation in the mouth, a rash on the upper body and a drop in blood pressure. Frequently, headaches and itching of the skin are encountered. The symptoms may progress to nausea, vomiting, and diarrhea and may require hospitalization, particularly in the case of elderly or impaired patients.

Diagnosis of the illness is usually based on the patient's symptoms, time of onset, and the effect of treatment with antihistamine medication. The suspected food must be analyzed within a few hours for elevated levels of histamine to confirm a diagnosis.

Fishery products that have been implicated in scombroid poisoning include the tunas (e.g., skipjack and yellowfin), mahi mahi, bluefish, sardines, mackerel, amberjack, and abalone. Many other products also have caused the toxic effects. The primary cheese involved in intoxications has been Swiss cheese. The toxin forms in a food when certain bacteria are present and time and temperature permit their growth. Distribution of the toxin within an individual fish fillet or between cans in a case lot can be uneven, with some sections of a product causing illnesses and others not. Neither cooking, canning, or freezing reduces the toxic effect. Common sensory examination by the consumer cannot ensure the absence or presence of the toxin. Chemical testing is the only reliable test for evaluation of a product.

Scombroid poisoning remains one of the most common forms of fish poisoning in the United States. Even so, incidents of poisoning often go unreported because of the lack of required reporting, a lack of information by some medical personnel, and confusion with the symptoms of other illnesses. Difficulties with underreporting are a worldwide problem. In the United States from 1968 to 1980, 103 incidents of intoxication involving 827 people were reported. For the same period in Japan, where the quality of fish is a national priority, 42 incidents involving 4,122 people were recorded. Since 1978, 2 actions by FDA have reduced the frequency of intoxications caused by specific products. A defect action level for histamine in canned tuna resulted in increased industry quality control. Secondly, blocklisting of mahi mahi reduced the level of fish imported to the United States.

The onset of intoxication symptoms is rapid, ranging from immediate to 30 minutes. The duration of the illness is usually 3 hours, but may last several days.

All humans are susceptible to scombroid poisoning; however, the symptoms can be severe for the elderly and for those taking medications such as isoniazid. Because of the worldwide network for harvesting, processing, and distributing fishery products, the impact of the problem is not limited to specific geographical areas of the United States or consumption pattern. These foods are sold for use in homes, schools, hospitals, and restaurants as fresh, frozen, or processed products.

An official method was developed at FDA to determine histamine, using a simple alcoholic extraction and quantitation by fluorescence spectroscopy. There are other untested procedures in the literature.

Literature references can be found at the links below.
Scombroid fish poisoning is an acute syndrome resulting from consumption of fish containing high levels of histamine. This report summarizes investigations of two outbreaks of scombroid fish poisoning in Illinois and South Carolina in 1988.
In July 1987, state and local public health officials in New Mexico investigated two cases of scombroid fish poisoning (histamine poisoning) in persons living in Albuquerque. A husband and wife had become ill within 45 minutes after eating dinner. Their symptoms included nausea, vomiting, diarrhea, headache, fever, flushing, and rapid pulse rate. An investigation by the Albuquerque Environmental Health Department found that the couple had shared a meal of grilled mahi mahi, pasta, salad, water, and wine. Their dog had eaten some of the fish and had vomited. Both of the patients had been treated with Benadryl, activated charcoal, and ipecac in a hospital emergency room. Their symptoms resolved within 36 hours of onset of illness.
Between December 31, 1985, and January 4, 1986, three restaurants in Alabama and Tennessee received complaints of illness from nine customers and one employee who ate Pacific amberjack fish (also called yellowtail or kahala). One restaurant cook, who did not eat the fish, reported a transient red rash on the hands shortly after handling the fish. Ill persons reported no other menu items in common. The fish meals were prepared by grilling or frying. Three people sought medical evaluation. One had diastolic hypotension, and one had bronchospasm. All three were diagnosed as having food or fish allergy and were treated with an antihistamine. The symptoms of scombroid fish poisoning resemble those of a histamine reaction. Scombroid poisoning is a response to toxic by-products--not an allergic reaction to fish.
Several large outbreaks of scombroid poisoning have been reported. In 1970, some 40 children in a school lunch program became ill from imported canned tuna. In 1973, more than 200 consumers across the United States were affected by domestic canned tuna. In 1979-1980 more than 200 individuals became ill after consuming imported frozen mahi mahi. Symptoms varied with each incident. In the 1973 situation, of the interviewed patients, 86% experienced nausea, 55% diarrhea, 44% headaches and 32% rashes.
Other incidents of intoxication have resulted from the consumption of canned abalone-like products, canned anchovies, and fresh and frozen amberjack, bluefish sole, and scallops. In particular, shipments of unfrozen fish packed in refrigerated containers have posed a significant problem because of inadequate temperature control.
For more information on recent outbreaks see the Morbidity and Mortality Weekly Reports from CDC.

Literature references can be found at the links below.
Scombrotoxin
Toxin produced by the growth of certain bacteria and thesubsequent action of their decarboxylase enzymes onhistidine and other amino acids in food.
Tetrodotoxin (anhydrotetrodotoxin 4-epitetrodotoxin, tetrodonic acid)

Pufferfish Poisoning, Tetradon Poisoning, Fugu Poisoning

Fish poisoning by consumption of members of the order Tetraodontiformes is one of the most violent intoxications from marine species. The gonads, liver, intestines, and skin of pufferfish can contain levels of tetrodotoxin sufficient to produce rapid and violent death. The flesh of many pufferfish may not usually be dangerously toxic. Tetrodotoxin has also been isolated from widely differing animal species, including the California newt, parrotfish, frogs of the genus Atelopus, the blue-ringed octopus, starfish, angelfish, and xanthid crabs. The metabolic source of tetrodotoxin is uncertain. No algal source has been identified, and until recently tetrodotoxin was assumed to be a metabolic product of the host. However, recent reports of the production of tetrodotoxin/anhydrotetrodotoxin by several bacterial species, including strains of the family Vibrionaceae, Pseudomonas sp., and Photobacterium phosphoreum, point toward a bacterial origin of this family of toxins. These are relatively common marine bacteria that are often associated with marine animals. If confirmed, these findings may have some significance in toxicoses that have been more directly related to these bacterial species.

The diagnosis of pufferfish poisoning is based on the observed symptomology and recent dietary history.

Poisonings from tetrodotoxin have been almost exclusively associated with the consumption of pufferfish from waters of the Indo-Pacific ocean regions. Several reported cases of poisonings, including fatalities, involved pufferfish from the Atlantic Ocean, Gulf of Mexico, and Gulf of California. There have been no confirmed cases of poisoning from the Atlantic pufferfish, Spheroides maculatus. However, in one study, extracts from fish of this species were highly toxic in mice. The trumpet shell Charonia sauliae has been implicated in food poisonings, and evidence suggests that it contains a tetrodotoxin derivative. There have been several reported poisonings from mislabelled pufferfish and at least one report of a fatal episode when an individual swallowed a California newt.

From 1974 through 1983 there were 646 reported cases of pufferfish poisoning in Japan, with 179 fatalities. Estimates as high as 200 cases per year with mortality approaching 50% have been reported. Only a few cases have been reported in the United States, and outbreaks in countries outside the Indo-Pacific area are rare.

The first symptom of intoxication is a slight numbness of the lips and tongue, appearing between 20 minutes to three hours after eating poisonous pufferfish. The next symptom is increasing paraesthesia in the face and extremities, which may be followed by sensations of lightness or floating. Headache, epigastric pain, nausea, diarrhea, and/or vomiting may occur. Occasionally, some reeling or difficulty in walking may occur. The second stage of the intoxication is increasing paralysis. Many victims are unable to move; even sitting may be difficult. There is increasing respiratory distress. Speech is affected, and the victim usually exhibits dyspnea, cyanosis, and hypotension. Paralysis increases and convulsions, mental impairment, and cardiac arrhythmia may occur. The victim, although completely paralyzed, may be conscious and in some cases completely lucid until shortly before death. Death usually occurs within 4 to 6 hours, with a known range of about 20 minutes to 8 hours.

All humans are susceptible to tetrodotoxin poisoning. This toxicosis may be avoided by not consuming pufferfish or other animal species containing tetrodotoxin. Most other animal species known to contain tetrodotoxin are not usually consumed by humans. Poisoning from tetrodotoxin is of major public health concern primarily in Japan, where "fugu" is a traditional delicacy. It is prepared and sold in special restaurants where trained and licensed individuals carefully remove the viscera to reduce the danger of poisoning. Importation of pufferfish into the United States is not generally permitted, although special exceptions may be granted. There is potential for misidentification and/or mislabelling, particularly of prepared, frozen fish products.

The mouse bioassay developed for paralytic shellfish poisoning (PSP) can be used to monitor tetrodotoxin in pufferfish and is the current method of choice. An HPLC method with post-column reaction with alkali and fluorescence has been developed to determine tetrodotoxin and its associated toxins. The alkali degradation products can be confirmed as their trimethylsilyl derivatives by gas chromatography/mass spectrometry. These chromatographic methods have not yet been validated.

Literature references can be found at the links below.
On April 29, 1996, three cases of tetrodotoxin poisoning occurred among chefs in California who shared contaminated fugu (puffer fish) brought from Japan by a co-worker as a prepackaged, ready-to-eat product. The quantity eaten by each person was minimal, ranging from approximately 1/4 to 1 1/2 oz. Onset of symptoms began approximately 3-20 minutes after ingestion, and all three persons were transported by ambulance to a local emergency department.
Pufferfish poisoning is a continuing problem in Japan, affecting 30 - 100 persons/year. Most of these poisoning episodes occur from home preparation and consumption and not from commercial sources of the pufferfish. Three deaths were reported in Italy in 1977 following the consumption of frozen pufferfish imported from Taiwan and mislabelled as angler fish.
For more information on recent outbreaks see the Morbidity and Mortality Weekly Reports from CDC.

Literature references can be found at the links below.

Tetrodotoxin
Toxin produced by members of the order Tetraodontiformes. Themetabolic source of tetrodotoxin is uncertain.
Amanitin, Gyromitrin, Orellanine, Muscarine, Ibotenic Acid, Muscimol, Psilocybin, Coprine

Mushroom Poisoning, Toadstool Poisoning
Types of Poisons.
Mushroom poisoning is caused by the consumption of raw or cooked fruiting bodies (mushrooms, toadstools) of a number of species of higher fungi. The term toadstool (from the German Todesstuhl, death's stool) is commonly given to poisonous mushrooms, but for individuals who are not experts in mushroom identification there are generally no easily recognizable differences between poisonous and nonpoisonous species. Old wives' tales notwithstanding, there is no general rule of thumb for distinguishing edible mushrooms and poisonous toadstools. The toxins involved in mushroom poisoning are produced naturally by the fungi themselves, and each individual specimen of a toxic species should be considered equally poisonous. Most mushrooms that cause human poisoning cannot be made nontoxic by cooking, canning, freezing, or any other means of processing. Thus, the only way to avoid poisoning is to avoid consumption of the toxic species. Poisonings in the United States occur most commonly when hunters of wild mushrooms (especially novices) misidentify and consume a toxic species, when recent immigrants collect and consume a poisonous American species that closely resembles an edible wild mushroom from their native land, or when mushrooms that contain psychoactive compounds are intentionally consumed by persons who desire these effects.

Mushroom poisonings are generally acute and are manifested by a variety of symptoms and prognoses, depending on the amount and species consumed. Because the chemistry of many of the mushroom toxins (especially the less deadly ones) is still unknown and positive identification of the mushrooms is often difficult or impossible, mushroom poisonings are generally categorized by their physiological effects. There are four categories of mushroom toxins: protoplasmic poisons (poisons that result in generalized destruction of cells, followed by organ failure); neurotoxins (compounds that cause neurological symptoms such as profuse sweating, coma, convulsions, hallucinations, excitement, depression, spastic colon); gastrointestinal irritants (compounds that produce rapid, transient nausea, vomiting, abdominal cramping, and diarrhea); and disulfiram-like toxins. Mushrooms in this last category are generally nontoxic and produce no symptoms unless alcohol is consumed within 72 hours after eating them, in which case a short-lived acute toxic syndrome is produced.

A clinical testing procedure is currently available only for the most serious types of mushroom toxins, the amanitins. The commercially available method uses a 3H-radioimmunoassay (RIA) test kit and can detect sub-nanogram levels of toxin in urine and plasma. Unfortunately, it requires a 2-hour incubation period, and this is an excruciating delay in a type of poisoning which the clinician generally does not see until a day or two has passed. A 125I-based kit which overcomes this problem has recently been reported, but has not yet reached the clinic. A sensitive and rapid HPLC technique has been reported in the literature even more recently, but it has not yet seen clinical application. Since most clinical laboratories in this country do not use even the older RIA technique, diagnosis is based entirely on symptomology and recent dietary history. Despite the fact that cases of mushroom poisoning may be broken down into a relatively small number of categories based on symptomatology, positive botanical identification of the mushroom species consumed remains the only means of unequivocally determining the particular type of intoxication involved, and it is still vitally important to obtain such accurate identification as quickly as possible. Cases involving ingestion of more than one toxic species in which one set of symptoms masks or mimics another set are among many reasons for needing this information. Unfortunately, a number of factors (not discussed here) often make identification of the causative mushroom impossible. In such cases, diagnosis must be based on symptoms alone. In order to rule out other types of food poisoning and to conclude that the mushrooms eaten were the cause of the poisoning, it must be established that everyone who ate the suspect mushrooms became ill and that no one who did not eat the mushrooms became ill. Wild mushrooms eaten raw, cooked, or processed should always be regarded as prime suspects. After ruling out other sources of food poisoning and positively implicating mushrooms as the cause of the illness, diagnosis may proceed in two steps. The first step, outlined in Table 1, provides an early indication of the seriousness of the disease and its prognosis.
As described above, the protoplasmic poisons are the most likely to be fatal or to cause irreversible organ damage. In the case of poisoning by the deadly Amanitas, important laboratory indicators of liver (elevated LDH, SGOT, and bilirubin levels) and kidney (elevated uric acid, creatinine, and BUN levels) damage will be present. Unfortunately, in the absence of dietary history, these signs could be mistaken for symptoms of liver or kidney impairment as the result of other causes (e.g., viral hepatitis). It is important that this distinction be made as quickly as possible, because the delayed onset of symptoms will generally mean that the organ has already been damaged. The importance of rapid diagnosis is obvious: victims who are hospitalized and given aggressive support therapy almost immediately after ingestion have a mortality rate of only 10%, whereas those admitted 60 or more hours after ingestion have a 50-90% mortality rate. Table 2 provides more accurate diagnoses and appropriate therapeutic measures. A recent report indicates that amanitins are observable in urine well before the onset of any symptoms, but that laboratory tests for liver dysfunction do not appear until well after the organ has been damaged.

Mushroom poisonings are almost always caused by ingestion of wild mushrooms that have been collected by nonspecialists (although specialists have also been poisoned). Most cases occur when toxic species are confused with edible species, and a useful question to ask of the victims or their mushroom-picking benefactors is the identity of the mushroom they thought they were picking. In the absence of a well- preserved specimen, the answer to this question could narrow the possible suspects considerably. Intoxication has also occurred when reliance was placed on some folk method of distinguishing poisonous and safe species. Outbreaks have occurred after ingestion of fresh, raw mushrooms, stir-fried mushrooms, home-canned mushrooms, mushrooms cooked in tomato sauce (which rendered the sauce itself toxic, even when no mushrooms were consumed), and mushrooms that were blanched and frozen at home. Cases of poisoning by home-canned and frozen mushrooms are especially insidious because a single outbreak may easily become a multiple outbreak when the preserved toadstools are carried to another location and consumed at another time.
Specific cases of mistaken mushroom identity appears frequently. The Early False Morel Gyromitra esculenta is easily confused with the true Morel Morchella esculenta, and poisonings have occurred after consumption of fresh or cooked Gyromitra. Gyromitra poisonings have also occurred after ingestion of commercially available "morels" contaminated with G. esculenta. The commercial sources for these fungi (which have not yet been successfully cultivated on a large scale) are field collection of wild morels by semiprofessionals. Cultivated commercial mushrooms of whatever species are almost never implicated in poisoning outbreaks unless there are associated problems such as improper canning (which lead to bacterial food poisoning). A short list of the mushrooms responsible for serious poisonings and the edible mushrooms with which they are confused is presented in Table 3. Producers of mild gastroenteritis are too numerous to list here, but include members of many of the most abundant genera, including Agaricus, Boletus, Lactarius, Russula, Tricholoma, Coprinus, Pluteus, and others. The Inky Cap Mushroom (Coprinus atrimentarius) is considered both edible and delicious, and only the unwary who consume alcohol after eating this mushroom need be concerned. Some other members of the genus Coprinus (Shaggy Mane, C. comatus; Glistening Inky Cap, C. micaceus, and others) and some of the larger members of the Lepiota family such as the Parasol Mushroom (Leucocoprinus procera) do not contain coprine and do not cause this effect. The potentially deadly Sorrel Webcap Mushroom (Cortinarius orellanus) is not easily distinguished from nonpoisonous webcaps belonging to the same distinctive genus, and all should be avoided.
Most of the psychotropic mushrooms (Inocybe spp., Conocybe spp., Paneolus spp., Pluteus spp.) are in general appearance small, brown, and leathery (the so-called "Little Brown Mushrooms" or LBMs) and relatively unattractive from a culinary standpoint. The Sweat Mushroom (Clitocybe dealbata) and the Smoothcap Mushroom (Psilocybe cubensis) are small, white, and leathery. These small, unattractive mushrooms are distinctive, fairly unappetizing, and not easily confused with the fleshier fungi normally considered edible. Intoxications associated with them are less likely to be accidental, although both C. dealbata and Paneolus foenisicii have been found growing in the same fairy ring area as the edible (and choice) Fairy Ring Mushroom (Marasmius oreades) and the Honey Mushroom (Armillariella mellea), and have been consumed when the picker has not carefully examined every mushroom picked from the ring. Psychotropic mushrooms, which are larger and therefore more easily confused with edible mushrooms, include the Showy Flamecap or Big Laughing Mushroom (Gymnopilus spectabilis), which has been mistaken for Chanterelles (Cantharellus spp.) and for Gymnopilus ventricosus found growing on wood of conifers in western North America. The Fly Agaric (Amanita muscaria) and Panthercap (Amanita pantherina) mushrooms are large, fleshy, and colorful. Yellowish cap colors on some varieties of the Fly Agaric and the Panthercap are similar to the edible Caesar's Mushroom (Amanita caesarea), which is considered a delicacy in Italy. Another edible yellow capped mushroom occasionally confused with yellow A. muscaria and A. pantherina varieties are the Yellow Blusher (Amanita flavorubens). Orange to yellow-orange A. muscaria and A. pantherina may also be confused with the Blusher (Amanita rubescens) and the Honey Mushroom (Armillariella mellea). White to pale forms of A. muscaria may be confused with edible field mushrooms (Agaricus spp.). Young (button stage) specimens of A. muscaria have also been confused with puffballs.

Accurate figures on the relative frequency of mushroom poisonings are difficult to obtain. For the 5-year period between 1976 and 1981, 16 outbreaks involving 44 cases were reported to the Centers for Disease Control in Atlanta (Rattanvilay et al. MMWR 31(21): 287-288, 1982). The number of unreported cases is, of course, unknown. Cases are sporadic and large outbreaks are rare. Poisonings tend to be grouped in the spring and fall when most mushroom species are at the height of their fruiting stage. While the actual incidence appears to be very low, the potential exists for grave problems. Poisonous mushrooms are not limited in distribution as are other poisonous organisms (such as dinoflagellates). Intoxications may occur at any time and place, with dangerous species occurring in habitats ranging from urban lawns to deep woods. As Americans become more adventurous in their mushroom collection and consumption, poisonings are likely to increase.

The normal course of the disease varies with the dose and the mushroom species eaten. Each poisonous species contains one or more toxic compounds which are unique to few other species. Therefore, cases of mushroom poisonings generally do not resembles each other unless they are caused by the same or very closely related mushroom species. Almost all mushroom poisonings may be grouped in one of the categories outlined above.
PROTOPLASMIC POISONS
Amatoxins:
Several mushroom species, including the Death Cap or Destroying Angel (Amanita phalloides, A. virosa), the Fool's Mushroom (A. verna) and several of their relatives, along with the Autumn Skullcap (Galerina autumnalis) and some of its relatives, produce a family of cyclic octapeptides called amanitins. Poisoning by the amanitins is characterized by a long latent period (range 6-48 hours, average 6-15 hours) during which the patient shows no symptoms. Symptoms appear at the end of the latent period in the form of sudden, severe seizures of abdominal pain, persistent vomiting and watery diarrhea, extreme thirst, and lack of urine production. If this early phase is survived, the patient may appear to recover for a short time, but this period will generally be followed by a rapid and severe loss of strength, prostration, and pain-caused restlessness. Death in 50-90% of the cases from progressive and irreversible liver, kidney, cardiac, and skeletal muscle damage may follow within 48 hours (large dose), but the disease more typically lasts 6 to 8 days in adults and 4 to 6 days in children. Two or three days after the onset of the later phase, jaundice, cyanosis, and coldness of the skin occur. Death usually follows a period of coma and occasionally convulsions. If recovery occurs, it generally requires at least a month and is accompanied by enlargement of the liver. Autopsy will usually reveal fatty degeneration and necrosis of the liver and kidney.
Hydrazines:
Certain species of False Morel (Gyromitra esculenta and G. gigas) contain the protoplasmic poison gyromitrin, a volatile hydrazine derivative. Poisoning by this toxin superficially resembles Amanita poisoning but is less severe. There is generally a latent period of 6 - 10 hours after ingestion during which no symptoms are evident, followed by sudden onset of abdominal discomfort (a feeling of fullness), severe headache, vomiting, and sometimes diarrhea. The toxin affects primarily the liver, but there are additional disturbances to blood cells and the central nervous system. The mortality rate is relatively low (2-4%). Poisonings with symptoms almost identical to those produced by Gyromitra have also been reported after ingestion of the Early False Morel (Verpa bohemica). The toxin is presumed to be related to gyromitrin but has not yet been identified.
Orellanine:
The final type of protoplasmic poisoning is caused by the Sorrel Webcap mushroom (Cortinarius orellanus) and some of its relatives. This mushroom produces orellanine, which causes a type of poisoning characterized by an extremely long asymptomatic latent period of 3 to 14 days. An intense, burning thirst (polydipsia) and excessive urination (polyuria) are the first symptoms. This may be followed by nausea, headache, muscular pains, chills, spasms, and loss of consciousness. In severe cases, severe renal tubular necrosis and kidney failure may result in death (15%) several weeks after the poisoning. Fatty degeneration of the liver and severe inflammatory changes in the intestine accompany the renal damage, and recovery in less severe cases may require several months.
NEUROTOXINS
Poisonings by mushrooms that cause neurological problems may be divided into three groups, based on the type of symptoms produced, and named for the substances responsible for these symptoms.
Muscarine Poisoning:
Ingestion of any number of Inocybe or Clitocybe species (e.g., Inocybe geophylla, Clitocybe dealbata) results in an illness characterized primarily by profuse sweating. This effect is caused by the presence in these mushrooms of high levels (3- 4%) of muscarine. Muscarine poisoning is characterized by increased salivation, perspiration, and lacrimation within 15 to 30 minutes after ingestion of the mushroom. With large doses, these symptoms may be followed by abdominal pain, severe nausea, diarrhea, blurred vision, and labored breathing. Intoxication generally subsides within 2 hours. Deaths are rare, but may result from cardiac or respiratory failure in severe cases.
Ibotenic acid/Muscimol Poisoning:
The Fly Agaric (Amanita muscaria) and Panthercap (Amanita pantherina) mushrooms both produce ibotenic acid and muscimol. Both substances produce the same effects, but muscimol is approximately 5 times more potent than ibotenic acid. Symptoms of poisoning generally occur within 1 - 2 hours after ingestion of the mushrooms. An initial abdominal discomfort may be present or absent, but the chief symptoms are drowsiness and dizziness (sometimes accompanied by sleep), followed by a period of hyperactivity, excitability, illusions, and delirium. Periods of drowsiness may alternate with periods of excitement, but symptoms generally fade within a few hours. Fatalities rarely occur in adults, but in children, accidental consumption of large quantities of these mushrooms may cause convulsions, coma, and other neurologic problems for up to 12 hours.
Psilocybin Poisoning:
A number of mushrooms belonging to the genera Psilocybe, Panaeolus, Copelandia, Gymnopilus, Conocybe, and Pluteus, when ingested, produce a syndrome similar to alcohol intoxication (sometimes accompanied by hallucinations). Several of these mushrooms (e.g., Psilocybe cubensis, P. mexicana, Conocybe cyanopus) are eaten for their psychotropic effects in religious ceremonies of certain native American tribes, a practice which dates to the pre- Columbian era. The toxic effects are caused by psilocin and psilocybin. Onset of symptoms is usually rapid and the effects generally subside within 2 hours. Poisonings by these mushrooms are rarely fatal in adults and may be distinguished from ibotenic acid poisoning by the absence of drowsiness or coma. The most severe cases of psilocybin poisoning occur in small children, where large doses may cause the hallucinations accompanied by fever, convulsions, coma, and death. These mushrooms are generally small, brown, nondescript, and not particularly fleshy; they are seldom mistaken for food fungi by innocent hunters of wild mushrooms. Poisonings caused by intentional ingestion of these mushrooms by people with no legitimate religious justification must be handled with care, since the only cases likely to be seen by the physician are overdoses or intoxications caused by a combination of the mushroom and some added psychotropic substance (such as PCP).
GASTROINTESTINAL IRRITANTS
Numerous mushrooms, including the Green Gill (Chlorophyllum molybdites), Gray Pinkgill (Entoloma lividum), Tigertop (Tricholoma pardinum), Jack O'Lantern (Omphalotus illudens), Naked Brimcap (Paxillus involutus), Sickener (Russula emetica), Early False Morel (Verpa bohemica), Horse mushroom (Agaricus arvensis) and Pepper bolete (Boletus piperatus), contain toxins that can cause gastrointestinal distress, including but not limited to nausea, vomiting, diarrhea, and abdominal cramps. In many ways these symptoms are similar to those caused by the deadly protoplasmic poisons. The chief and diagnostic difference is that poisonings caused by these mushrooms have a rapid onset, rather than the delayed onset seen in protoplasmic poisonings. Some mushrooms (including the first five species mentioned above) may cause vomiting and/or diarrhea which lasts for several days. Fatalities caused by these mushrooms are relatively rare and are associated with dehydration and electrolyte imbalances caused by diarrhea and vomiting, especially in debilitated, very young, or very old patients. Replacement of fluids and other appropriate supportive therapy will prevent death in these cases. The chemistry of the toxins responsible for this type of poisoning is virtually unknown, but may be related to the presence in some mushrooms of unusual sugars, amino acids, peptides, resins, and other compounds.
DISULFIRAM-LIKE POISONING
The Inky Cap Mushroom (Coprinus atramentarius) is most commonly responsible for this poisoning, although a few other species have also been implicated. A complicating factor in this type of intoxication is that this species is generally considered edible (i.e., no illness results when eaten in the absence of alcoholic beverages). The mushroom produces an unusual amino acid, coprine, which is converted to cyclopropanone hydrate in the human body. This compound interferes with the breakdown of alcohol, and consumption of alcoholic beverages within 72 hours after eating it will cause headache, nausea and vomiting, flushing, and cardiovascular disturbances that last for 2 - 3 hours.
MISCELLANEOUS POISONINGS
Young fruiting bodies of the sulfur shelf fungus Laetiporus sulphureus are considered edible. However, ingestion of this shelf fungus has caused digestive upset and other symptoms in adults and visual hallucinations and ataxia in a child.

All humans are susceptible to mushroom toxins. The poisonous species are ubiquitous, and geographical restrictions on types of poisoning that may occur in one location do not exist (except for some of the hallucinogenic LBMs, which occur primarily in the American southwest and southeast). Individual specimens of poisonous mushrooms are also characterized by individual variations in toxin content based on genetics, geographic location, and growing conditions. Intoxications may thus be more or less serious, depending not on the number of mushrooms consumed, but on the dose of toxin delivered. In addition, although most cases of poisoning by higher plants occur in children, toxic mushrooms are consumed most often by adults. Occasional accidental mushroom poisonings of children and pets have been reported, but adults are more likely to actively search for and consume wild mushrooms for culinary purposes. Children are more seriously affected by the normally nonlethal toxins than are adults and are more likely to suffer very serious consequences from ingestion of relatively smaller doses. Adults who consume mushrooms are also more likely to recall what was eaten and when, and are able to describe their symptoms more accurately than are children. Very old, very young, and debilitated persons of both sexes are more likely to become seriously ill from all types of mushroom poisoning, even those types which are generally considered to be mild.
Many idiosyncratic adverse reactions to mushrooms have been reported. Some mushrooms cause certain people to become violently ill, while not affecting others who consumed part of the same mushroom cap. Factors such as age, sex, and general health of the consumer do not seem to be reliable predictors of these reactions, and they have been attributed to allergic or hypersensitivity reactions and to inherited inability of the unfortunate victim to metabolize certain unusual fungal constituents (such as the uncommon sugar, trehalose). These reactions are probably not true poisonings as the general population does not seem to be affected.

The mushroom toxins can with difficulty be recovered from poisonous fungi, cooking water, stomach contents, serum, and urine. Procedures for extraction and quantitation are generally elaborate and time-consuming, and the patient will in most cases have recovered by the time an analysis is made on the basis of toxin chemistry. The exact chemical natures of most of the toxins that produce milder symptoms are unknown. Chromatographic techniques (TLC, GLC, HPLC) exist for the amanitins, orellanine, muscimol/ibotenic acid, psilocybin, muscarine, and the gyromitrins. The amanitins may also be determined by commercially available 3H-RIA kits. The most reliable means of diagnosing a mushroom poisoning remains botanical identification of the fungus that was eaten. An accurate pre-ingestion determination of species will also prevent accidental poisoning in 100% of cases. Accurate post-ingestion analyses for specific toxins when no botanical identification is possible may be essential only in cases of suspected poisoning by the deadly Amanitas, since prompt and aggressive therapy (including lavage, activated charcoal, and plasmapheresis) can greatly reduce the mortality rate.

Literature references can be found at the links below.
Isolated cases of mushroom poisoning have occurred throughout the continental United States.
The popular interest in gathering and eating uncultivated mushrooms has been associated with an increase in incidents of serious mushroom-related poisonings. From December 28, 1996, through January 6, 1997, nine persons in northern California required hospitalization after eating Amanita phalloides (i.e., "death cap") mushrooms; two of these persons died. Risks associated with eating these mushrooms result from a potent hepatotoxin. This report describes four cases of A. phalloides poisoning in patients admitted to a regional referral hospital in northern California during January 1997 and underscores that wild mushrooms should not be eaten unless identified as nonpoisonous by a mushroom expert.
Another one occurred in Oregon in October,1988, and involved the intoxication of five people who consumed stir-fried Amanita phalloides. The poisonings were severe, and at this writing three of the five people had undergone liver transplants for treatment of amanitin-induced liver failure.
Other cases have included the July, 1986, poisoning of a family in Philadelphia, by Chlorophyllum molybdites; the September, 1987, intoxication of seven men in Bucks County, PA, by spaghetti sauce which contained Jack O'Lantern mushroom (Omphalotus illudens); and of 14 teenage campers in Maryland by the same species (July, 1987). A report of a North Carolina outbreak of poisoning by False Morel (Gyromitra spp.) appeared in 1986. A 1985 report details a case of Chlorophyllum molybdites which occurred in Arkansas; a fatal poisoning case caused by an amanitin containing Lepiota was described in 1986.
In 1981, two Berks County, PA, people were poisoned (one fatally) after ingesting Amanita phalloides, while in the same year, seven Laotian refugees living in California were poisoned by Russula spp.
In separate 1981 incidents, several people from New York State were poisoned by Omphalotus illudens, Amanita muscaria, Entoloma lividum, and Amanita virosa.
An outbreak of gastroenterititis during a banquet for 482 people in Vancouver, British Columbia, was reported by the Vancouver Health Department in June, 1991. Seventy-seven of the guests reported symptoms consisting of early onset nausea (15-30 min), diarrhea (20 min-13 h), vomiting (20-60 min), cramps and bloated feeling. Other symptoms included feeling warm, clamminess, numbness of the tongue and extreme thirst along with two cases of hive-like rash with onset of 3-7 days. Bacteriological tests were negative. This intoxication merits special attention because it involved consumption of species normally considered not only edible but choice. The fungi involved were the morels Morchella esculenta and M. elata (M. angusticeps), which were prepared in a marinade and consumed raw. The symptoms were severe but not life threatening. Scattered reports of intoxications by these species and M. conica have appeared in anecodotal reports for many years.
Numerous other cases exist; however, the cases that appear in the literature tend to be the serious poisonings such as those causing more severe gastrointestinal symptoms, psychotropic reactions, and severe organ damage (deadly Amanita). Mild intoxications are probably grossly underreported, because of the lack of severity of symptoms and the unlikeliness of a hospital admission.
For more information on recent outbreaks see the Morbidity and Mortality Weekly Reports from CDC.

Literature references can be found at the links below.


Amatoxin
Toxin produced by several mushroom species, including the Death Capor Destroying Angel (Amanita phalloides, A. virosa),the Fool's Mushroom (A. verna) and several of their relatives,along with the Autumn Skullcap (Galerina autumnalis) andsome of its relatives.Orellanine
Toxin produced by the Sorrel Webcap mushroom (Cortinarius orellanus) and some of its relatives.
Muscarine
Toxin produced by any number of Inocybe or Clitocybe species (e.g., Inocybe geophylla, Clitocybe dealbata).

Ibotenic Acid
Toxin produced by Fly Agaric (Amanita muscaria) and Panthercap (Amanita pantherina) mushrooms.
Muscimol
Toxin produced by Fly Agaric (Amanita muscaria) and Panthercap (Amanita pantherina) mushrooms. Gyromitrin
Toxin produced by certain species of False Morel (Gyromitra esculenta and G. gigas). Coprine
Toxin produced by the Inky Cap Mushroom (Coprinus atramentarius).