Each year in the United States known foodborne pathogens are responsible for approximately 30.7 million illnesses, 228,144 hospitalizations, and 2,612 deaths.47 It is estimated that foodborne illness costs an annual burden to the American society of 36 billion dollars, which is estimated to be an average cost burden per illness of $3,630.143 Worldwide food distribution, large-scale national food preparation and distribution networks, limited food regulatory practices, and corporate greed place everyone at risk. Food poisoning causes morbidity and mortality by one or more of the following mechanisms: (bacteria, viruses and parasites) that can be transmitted in food; toxins that are produced by organisms, can be consumed in food; and xenobiotics can be inadvertently or purposefully used to contaminate food and ultimately be ingested.
This chapter is organized into four major types of food poisoning: foodborne poisoning with neurologic effects, food poisoning with gastrointestinal (GI) symptoms, foodborne poisoning with anaphylaxislike effects, and food poisoning used for bioterrorism.
In the United States, viruses are the most responsible cause of foodborne outbreaks (82%) followed by bacteria (12%), and parasites (6%). Norovirus was the most common cause of single, confirmed etiology outbreaks (54%). The bacteria that caused the largest number of food poisonings were Salmonella spp, Clostridium perfringens, Staphylococcus aureus enterotoxin, and Shigella spp. The estimated annual number of episodes of foodborne pathogen related illness, hospitalization and death in the United States is shown in Table 39–1.48
TABLE 39–1Estimated Annual Number of Episodes of Illness, Hospitalizations and Death Caused by Pathogens Transmitted Commonly by Food in the United States (2014)48 ||Download (.pdf) TABLE 39–1 Estimated Annual Number of Episodes of Illness, Hospitalizations and Death Caused by Pathogens Transmitted Commonly by Food in the United States (2014)48
|Pathogen ||Total Mean Episodes ||Total Mean Hospitalizations ||Total Mean Deaths |
|Bacillus cereus ||62,623 ||20 ||0 |
|Campylobacter spp. ||1,322,137 ||13,240 ||119 |
|Clostridium botulinum ||56 ||42 ||9 |
|Clostridium perfringens ||969,342 ||439 ||26 |
|STEC 0157 * ||96,534 ||3,268 ||31 |
|Listeria monocytogenes ||1,662 ||1,520 ||266 |
|Salmonella spp. ||1,229,007 ||23,128 ||452 |
|S. enterica ||5,752 ||623 ||0 |
|Shigella spp. ||494,908 ||5,491 ||38 |
|Staphylococcus spp. ||241,994 ||1,067 ||6 |
|Streptococcus Group A ||11,257 ||1 ||0 |
|Vibrio vulnificus ||207 ||202 ||77 |
|Vibrio parahaemolyticus ||44,950 ||129 ||5 |
|Yersinia enterocolitica ||116,706 ||637 ||34 |
|Cryptosporidium spp. ||748,123 ||210 ||46 |
|Giardia intestinalis ||1,221,564 ||225 ||34 |
|Trichinella ||162 ||6 ||0 |
|Astrovirus ||3,090,384 ||17,430 ||5 |
|Hepatitis A ||35,769 ||2,255 ||171 |
|Norovirus ||20,865,958 ||56,013 ||571 |
|Rotavirus ||3,090,384 ||69,721 ||32 |
Globally, researchers estimated foodborne pathogens were found to cause 582 million cases of illnesses annually. The leading cause of foodborne illness was norovirus (125 million cases) followed by campylobacter (96 million). Most important, around 43% of the disease burden from contaminated food occurred in children younger than 5 years of age, who make up 9% of the population.110
In the past decade, large numbers of people have also had food poisoning because of purposeful placement of chemicals in food.51
Many foodborne illnesses result in long-term sequelae to the GI, immune, nervous, respiratory, renal, cardiovascular, endocrine, and hepatic systems.14
FOODBORNE POISONING WITH NEUROLOGIC SYMPTOMS
The differential diagnosis of patients with foodborne poisoning presenting with neurologic symptoms is vast (Tables 39–2 and 39–3). The sources of many of these cases are ichthyosarcotoxic, involving toxins from the muscles, viscera, skin, gonads, and mucous surfaces of the fish; rarely, toxicity follows consumption of the fish blood or skeleton. Most episodes of poisoning are not species specific, although particular forms of toxicity from Tetraodontiformes (puffer fish), Gymnothoraces (moray eel), and newts (Taricha and other species) are recognized.
TABLE 39–2Differential Diagnosis of Possible Foodborne Poisoning Presenting with Neurologic Findingsa ||Download (.pdf) TABLE 39–2 Differential Diagnosis of Possible Foodborne Poisoning Presenting with Neurologic Findingsa
Bacterial food poisoning
Dinoflagellates (brevetoxin, saxitoxin)
Marine food poisoning (ciguatoxin, tetrodotoxin)
Metals (arsenic, lead, mercury)
Mushrooms (Amanita spp, Gyromitra spp)
Organic phosphorus compounds
TABLE 39–3Foodborne Neurologic Toxicity (Primary Presenting Symptoms) ||Download (.pdf) TABLE 39–3 Foodborne Neurologic Toxicity (Primary Presenting Symptoms)
|Disease ||Toxin ||Toxin Source and Mechanism** ||Onset ||Duration ||Findings ||Therapy ||Diagnosis |
Large reef fish: amber jack, barracuda, snapper, parrot, sea bass, moray
**Increased sodium channel permeability
|Paresthesias, nausea; vomiting, diarrhea, temperature reversal || |
Clinical, mouse bioassay, immunoassay
Puffer fish, fugu, blue-ringed octopus, newts, horseshoe crab
**Blocks sodium channel
Minutes to hours
|Paresthesias, respiratory depression, hypotension || |
Neurotoxic shellfish poisoning
Mussels, clams, scallops, oysters, Ptychodiscus brevis: “red tide”
**Increased sodium channel permeability
15 min to 18 h
|Bronchospasm, temperature reversal, nausea; vomiting, diarrhea, paresthesias ||Bronchodilators ||Clinical, mouse bioassay of food, HPLC |
Paralytic shellfish poisoning
Mussels, clams, scallops, oysters, Protogonyaulax catanella, Protogonyaulax tamarensis
**Decreases sodium channel permeability
|Respiratory depression, paresthesias, nausea, vomiting, diarrhea || |
Clinical, mouse bioassay of food, HPLC
Amnestic shellfish poisoning
Mussels, possibly other shellfish; Nitzschia pungens
15 min to 38 h
|Amnesia, nausea; vomiting, diarrhea, paresthesias, respiratory depression || |
Clinical, mouse bioassay of food, HPLC
Home-canned foods, honey, corn syrups, Clostridium botulinum
**Binds presynaptically, blocks acetylcholine release
|Vomiting, diarrhea, respiratory depression, initial cranial nerve paralysis followed by a symmetric descending paralysis of the motor and autonomic nerves || |
Antitoxin, respiratory support
Clinical, immunoassay, serologic, bacteriologic
In cases of ciguatera poisoning, the major symptoms usually are neurotoxic, and the GI symptoms are minor. Knowing where the fish was caught often helps establish a diagnosis, but refrigerated transport of foods and rapid worldwide travel can complicate the assessment. Travelers to Caribbean, Pacific, and Canary islands, as well as those traveling within the United States, have experienced ciguatera poisoning.119,155 In geographically disparate regions of Canada,161 individuals have experienced domoic acid poisoning caused by ingestion of cultivated mussels from Prince Edward Island.
In the differential diagnosis of foodborne poisons presenting with neurologic findings, activities other than eating must always be considered. In particular, sport divers often perform their activities in high-risk areas such as Florida, California, and Hawaii and often during the high-risk periods from May through August. In the process, they may sustain a sting from a stingray tail, or laceration (from a deltoid or pectoral fin spine of a lionfish or stonefish) that can cause consequential marine toxicity (Chap. 116). Scientists have found that the chance of encountering numerous bacterial pathogens harmful to both human and marine life was cut in half near seagrass meadows. Swimmers and divers can limit disease by choosing waters rich in seagrass meadows.165
Ciguatera poisoning is one of the most commonly reported forms of vertebrate fishborne poisonings in the United States, accounting for almost half of the reported cases.85 Ciguatoxins are lipid soluble, polyether compounds consisting of 13 to 14 rings fused by ether linkages into a rigid ladder-like structure (Fig. 39–1). Ciguatera poisoning is endemic to warm water, bottom-dwelling reef fish living around the globe between 35° North and 35° South latitude, which includes tropical areas such as the Indian Ocean, the South Pacific, and the Caribbean. Hawaii and Florida report 90% of all cases occurring in the United States, most commonly from May through August.125 The incidence and geographical distribution of ciguatera are increasing because of increased fish trade and consumption, international tourism, and climate changes.
The structure of Pacific and Caribbean ciguatoxins. Source: Food and Agriculture Organization of the United Nations. 2004, Marine Biotoxins; FAO Food and Nutrition Paper 80. http://www.fao.org/docrep/007/y5486e/y5486e00.htm. Reproduced with permission.
More than 500 fish species have caused human cases of ciguatera poisoning, with the barracuda, sea bass, parrot fish, red snapper, grouper, amber jack, kingfish, and sturgeon the most common sources. The common factor is the comparably large size of the fish involved.
Large fish (1.5–3.0 kg or more) become vectors of ciguatera poisoning in accordance with complex feeding patterns inherent in aquatic life. This traditional teaching is challenged by a recent study. The lack of relationship between toxicity and size observed for most of the species and families from the six islands in French Polynesia suggests that fish size cannot be used as an efficient predictor of fish toxicity.75 Ciguatoxin is found in blue-green algae, protozoa, and the free algae dinoflagellates. These plankton members of the phylum Protozoa are single-celled, motile, flagellated, pigmented organisms thriving through photosynthesis. Photosynthetic dinoflagellates such as Gambierdiscus toxicus and bacteria within the dinoflagellates are the origins of ciguatoxin.66,97,130 Dinoflagellates are the main nutritional source for small herbivorous fish, which, in turn, are the major food source for larger carnivorous fish, thereby increasing the ciguatoxin concentrations in the flesh, adipose tissue, and viscera of larger and larger fish.12
Ciguatoxin is heat stable, lipid soluble, acid stable, odorless, and tasteless. When purified, the toxin is a large (molecular weight, 1,100 Da) complex ester that does not harm the fish but is stored in its tissues.125,131 The molecule binds to voltage-sensitive sodium channels in diverse tissues and increases the sodium permeability of the channel.191 The ciguatoxins cause hyperpolarization and a shift in the voltage dependence of channel activation, which opens the sodium channels. Ciguatoxins bind selectively to a particular binding site on the neuron’s voltage-sensitive sodium channel protein.129
Multiple ciguatoxins are identified in the same fish, perhaps explaining the variability of symptoms and differing severity.130 People can be affected after eating fresh or frozen fish that was prepared by all common methods: boiling, baking, frying, stewing, or broiling. The appearance, taste, and smell of the ciguatoxic fish are usually unremarkable. The majority of symptomatic episodes begin 2 to 6 hours after ingestion, 75% within 12 hours, and 96% within 24 hours.12 Symptoms include acute onset of diaphoresis; headaches, abdominal pain with cramps, nausea, or vomiting; profuse watery diarrhea; and a constellation of dramatic neurologic symptoms.209 A sensation of loose or painful teeth is reported. Typically, peripheral dysesthesias and paresthesias predominate. Watery eyes, tingling, and numbness of the tongue, lips, throat, and perioral area occur. A strange metallic taste is frequently reported as is a reversal of temperature discrimination, the pathophysiology of which remains to be elucidated.34 Myalgias, most often in the lower extremities; arthralgias; ataxia; and weakness are commonly experienced.12
Dysuria81 and symptoms of dyspareunia and vaginal and pelvic discomfort are reported to occur in some women after sexual intercourse with men who are ciguatoxic and whose semen contains the toxin.118 Vertigo, seizures, and visual disturbances (eg, blurred vision, scotomata, and transient blindness) are reported.
Bradycardia and orthostatic hypotension are described.77 The GI symptoms usually subside within 24 to 48 hours; however, cardiovascular and neurologic symptoms typically persist for several days to weeks, depending on the amount of toxin ingested. Delayed effects include protracted itching and hiccoughs. Ciguatoxin is transmitted in breast milk23 and can cross the placenta.159
Although deaths are reported, internationally, none have been documented in the United States.85 When it occurs, death is a result of respiratory paralysis and seizures not managed with adequate life support. One study showed that the main contributory factors associated with death were the consumption of ciguatoxin-rich fish parts (viscera and head) in larger amounts, ingestion of the ciguatoxic fish species (eg, barracuda, sea bass, red snapper, grouper), ingestion of reef fish collected after storms, and ultimately individual susceptibility.52
The Food and Drug Administration’ (FDA’s) and Ciguatoxin (CTX) fish testing procedure is performed in an analytical laboratory setting and uses a two-tiered protocol involving: (1) in vitro mouse neuroblastoma (N2a) cell assay as a semiquantitative screen for toxicity consistent with CTX mode of action and (2) liquid chromatography tandem–mass spectrometry (LC-MS/MS) for molecular confirmation of CTX. To date, there is no commercially available, rapid, cost-effective, fish-testing product that has been demonstrated by independent investigations to provide CTX detection in seafood with adequate reliability or accuracy.
Laboratory testing is not readily available, and it often takes days to weeks to receive the result. A useful approach to diagnosis and management includes laboratory testing to exclude other possible etiologies and determine the need for, or extent of, specific therapeutic interventions.
Initial treatment for victims of ciguatoxin poisoning includes standard supportive care for a toxic ingestion.209 In most patients, elimination of the toxin is accelerated if vomiting (40%) and diarrhea (70%) have occurred. Administration of activated charcoal has benefit for patients who are not vomiting. In patients with significant GI fluid loss through vomiting, diarrhea, or both, intravenous (IV) fluid and electrolyte repletion are essential. The orthostatic hypotension responds to IV fluids and α-adrenergic agonists. Symptomatic bradycardia is treated with atropine.73
Intravenous mannitol is reported to alleviate neurologic and muscular dysfunctional symptoms associated with ciguatera; however, GI symptoms are not ameliorated.158,160 An in vivo study showed that there was no change in neuronal swelling when ciguatera-poisoned cells were treated with mannitol but did show some prevention of the membrane depolarization and repetitive firing of action potentials induced by ciguatera.19 Despite these findings, one prospective randomized control trial, mannitol failed to produce any greater improvement in symptoms than did IV normal saline solution. This study is a randomized double-blinded control trial to answer this question. Most of the previous data on the use of mannitol in ciguatera poisoning was either obtained in an uncontrolled or randomized but nonblinded fashion or is the result of case reports.179 Mannitol should be used with caution because it causes hypotension. Vascular reexpansion and cardiovascular stability should be initial treatment priorities. Mannitol works by inhibiting the ciguatoxin-induced opening of sodium channels on the neuron membranes or reducing the neural edema via an osmotic gradient and is recommended in the hemodynamically stable patient. The search for a treatment for ciguatera poisoning that has minimal side effects and is easily accessible is ongoing. Two cases were reported of symptomatic patients exposed to ciguatera who were successfully treated with pregabalin.30
There is limited evidence for the efficacy of pregabalin.30
Admission to the hospital for cautious supportive care is essential when the diagnosis is uncertain or when volume depletion or any consequential manifestations are present (Tables 39–2 and 39–3). The etiology of the symptoms must be rapidly identified to provide specific therapy, if available. Diaphoresis is a common clinical finding and an important factor in the differential diagnosis. Late in the course of ciguatera poisoning, amitriptyline 25 mg orally twice daily helps alleviate symptoms,27 which have been reported to persist up to 1 year. Patients recovering from ciguatera should avoid alcohol and nuts for 3 to 6 months if their consumption exacerbates symptoms.
Moray, conger, and anguillid eels carry a ciguatoxinlike neurotoxin in their viscera, muscles, and gonads that does not affect the eel itself. The toxin is a complex ester that is structurally very similar to ciguatoxin and is heat stable.154 Individuals who eat these eels can infrequently manifest neurotoxic symptoms similar to ciguatoxin or show signs of cholinergic toxicity, such as hypersalivation, nausea, vomiting, and diarrhea. Shortness of breath, mucosal erythema, and cutaneous eruptions also occur. These findings are present in addition to the neurotoxic symptoms.90 Management is supportive. Death is related to the complications of neurotoxicity, such as seizures and respiratory paralysis.
Healthy mollusks living between 30° North and 30° South latitude ingest and filter large quantities of dinoflagellates. These dinoflagellates are the major source of available ocean food during the “non-R” months (May through August) in the northern hemisphere. During this time, these dinoflagellates are responsible for the “red tides” that occur from California to Alaska, from New England to the St. Lawrence, and across the west coast of Europe.137 The number of toxic dinoflagellates in these “red tides” is often so overwhelming that birds and fish die, and humans who walk along the beach experience respiratory symptoms caused by aerosolized toxin.140
Ingestion of shellfish, including oysters, clams, mussels, and scallops, contaminated by dinoflagellates or algae causes neurotoxic, paralytic, and amnestic syndromes. The dinoflagellates most frequently implicated are Karenia brevis (originally named Gymnodinium breve in 1948, renamed Ptychodiscus brevis in 1979, and reclassified again to the current nomenclature in 2000). The diatoms causing neurotoxic shellfish poisoning (NSP) include Protogonyaulax catanella and Protogonyaulax tamarensis, which cause paralytic shellfish poisoning, and Nitzschia pungens, the diatom implicated in amnestic shellfish poisoning. Proliferation of these diatoms cause a red tide, but shellfish poisoning occurs even in the absence of this extreme proliferation.
Paralytic shellfish poisoning is caused by saxitoxin. Saxitoxin blocks the voltage-sensitive sodium channel in a manner identical to tetrodotoxin (TTX; see later). The shellfish implicated usually are clams, oysters, mussels, and scallops, but poisoning has occurred through consumption of crustaceans, gastropods, and fish. In the summer of 2013, a saxitoxin outbreak was identified among 31 individuals in the who consumed green mussels in the Philippines. The symptoms in these individuals ranged from circumoral and extremity numbness to dizziness and lightheadedness. One adult and one child died secondary to cardiorespiratory arrest.56
The higher the number of affected shellfish consumed, the more severe the symptoms. Symptoms usually occur within 30 minutes of ingestion. Neurologic effects predominate and include paresthesias and numbness of the mouth and extremities, a sensation of floating, headache, ataxia, vertigo, muscle weakness, paralysis, and cranial nerve dysfunction manifested by dysphagia, dysarthria, dysphonia, and transient blindness. Gastrointestinal symptoms are less common and include nausea, vomiting, abdominal pain, and diarrhea. Fatalities occur as a result of respiratory failure, usually within the first 12 hours after symptom onset. Muscle weakness often persists for weeks.
Treatment is supportive. Early intervention for respiratory failure is indicated. Orogastric lavage and cathartics were used to remove unabsorbed toxin from the GI tract and were not efficacious and thus are not recommended.31,127,145,183 Activated charcoal is reasonable if vomiting has not occurred. Antibodies against saxitoxin have reversed cardiorespiratory failure in animals,16 but this therapy is not yet available for humans. Assays for saxitoxin include a mouse bioassay, enzyme-linked immunosorbent assay (ELISA), and high-performance liquid chromatography (HPLC). High-performance liquid chromatography is demonstrated to result in good interlaboratory accuracy,203 but the differences in saxitoxin derivatives make standardization of an analytic test difficult.11,121
Neurotoxic shellfish poisoning is caused by brevetoxin. Brevetoxin, which is produced by K. brevis (previously Gymnodium brevis, and subsequently P. brevis), is a lipid-soluble, heat-stable polyether toxin similar to ciguatoxin. It acts by stimulating sodium flux through the sodium channels of both nerve and muscle.8,35 Similar to paralytic shellfish poisoning, the shellfish implicated usually are clams, oysters, mussels, and other filter feeders. Neurotoxic shellfish poisoning is characterized by gastroenteric manifestations with associated neurologic symptoms. Gastrointestinal symptoms include abdominal pain, nausea, vomiting, diarrhea, and rectal burning. Neurologic features include paresthesias, reversal of hot and cold temperature sensation, myalgias, vertigo, and ataxia. Other effects include headache, malaise, tremor, dysphagia, bradycardia, decreased reflexes, and mydriasis. Paralysis does not occur. Bradycardia and mydriasis are not commonly present in an individual patent. The incubation period is 3 hours (range, 15 minutes–18 hours). Gastrointestinal and neurologic symptoms appear simultaneously. Other manifestations of brevetoxin poisoning include mucosal irritation, cough, and bronchospasm, which occur when P. brevis is aerosolized by wave action during red tides. The duration of effects averages 17 hours (range, 1–72 hours).145
Brevetoxins are identified by mouse bioassay; ELISA; and, more recently, antibody radioimmunoassay and reconstituted sodium channels. (Reconstitution is when a purified membrane protein is incorporated into a membrane bilayer and the reconstituted channel is then used as a tool for the measurement of specific toxin binding.163,200) Treatment is supportive, and severe respiratory depression is very uncommon. Therapy includes removal of the patient from the environment and the administration of bronchodilators. An antagonist to brevetoxin named brevenal has been discovered and is in the early research phase as a potential therapy.82 Neurotoxic shellfish poisoning is not fatal.
Amnestic shellfish poisoning is caused by domoic acid, which is produced by the diatom a N. pungens. Domoic acid is structurally similar to glutamic acid, kainic acid, and aspartic acid (Fig. 39–2). Because of this structural similarity, domoic acid interacts with the glutamate receptors on nerve cell terminals. Glutamate is the principal neuroexcitatory transmitter in the brain and is necessary for synaptic transmission (Chap. 13). However, excessive glutamate is associated with neurodegeneration, seizures, and apoptosis.124
Comparison of the chemical structures of domoic acid, kainic acid, glutamic acid, and aspartic acid.121
The most extensively documented human outbreak occurred in Canada in 1987, when 107 individuals who had consumed mussels harvested from cultivated river estuaries on Prince Edward Island were affected.161 Other human outbreaks have occurred due to a similar diatom—Pseudonitzschia australis—which has been isolated in shellfish from other areas.74 Pelican deaths caused by domoic acid–laden anchovies were reported in 1991 and Canada instituted monitoring for domoic acid after this outbreak.197 The death of 400 sea lions in California in 1998 was linked to domoic acid from the same diatom.180
Amnestic shellfish poisoning is characterized by GI symptoms of nausea, vomiting, abdominal cramps, diarrhea, and neurologic symptoms of memory loss and, less frequently, coma, seizures, hemiparesis, ophthalmoplegia, purposeless chewing, and grimacing. Other signs and symptoms include hemodynamic instability and cardiac dysrhythmias. Symptoms typically begin 5 hours (range, 15 minutes–38 hours) after ingestion of mussels. The mortality rate is 2%, with death most frequently occurring in older patients, who experience more severe neurologic symptoms. Ten percent of victims have long-term antegrade memory deficits, as well as motor and sensory neuropathy. Postmortem examinations revealed neuronal damage in the hippocampus and amygdala.195 Animal studies show that domoic acid can cross the placenta.138
This type of fish poisoning involves only the order Tetraodontiformes. Although this order of fish is not restricted geographically, it is eaten most frequently in Japan, California, Africa, South America, and Australia.90 Cases also occurred in Florida and New Jersey, as well as Europe, the Mediterranean, and Bangladesh. Approximately 100 freshwater and saltwater species exist in this order, including a number of pufferlike fish such as the globe fish, balloon fish, blowfish, and toad fish.147 Tetrodotoxin (TTX) found in these fish is also isolated from the blue-ringed octopus71 and the gastropod mollusk211 and are responsible for fatalities from ingestion of horseshoe crab eggs.102 Certain TTX-containing newts (Taricha, notophthalmus, triturus, and cynops), particularly Taricha granulosa, found in Oregon, California, and southern Alaska, are reportedly fatal when ingested. Most newts and salamanders with bright colors and rough skins contain toxins.28 In Japan, fugu (a local variety of puffer fish) is considered a delicacy, but special licensing is required to prepare this exceedingly toxic fish. In 1989, the US FDA legalized the importation of puffer fish. However, before exportation from Japan, the fish must be laboratory tested and certified by two Japanese organizations to be free of TTX.49
Tetrodotoxin is a heat-stable, water-soluble nonprotein found mainly in the fish skin, liver, ovary, intestine, and possibly muscle.90,175 The ovary has a high concentration of the toxin and is most poisonous if eaten during the spawning season. Tetrodotoxin is detected by mouse bioassay. It is unstable when heated to 212°F (100°C) in acid, distinguishing it from saxitoxin. Tetrodotoxin from fish is detected using fluorescent spectrometry11 or from the urine of poisoned patients using a combination of immunoaffinity chromatography and fluorometric HPLC.105
Similar to saxitoxin, TTX is produced by marine bacteria and likely accumulate in animals higher on the food chain that consume these bacteria.151 Accumulation of toxins, primarily in the skin, of two species of Asian puffer fish is documented. Whether this accumulation of toxin is simply an evolutionary adaptation, to remove a toxic substance, or one that has evolutionary advantages of protection is unclear.150
Neurotoxicity is produced by inhibition of sodium channels and blockade of neuromuscular transmission. The sodium channel is blocked from the external surface of the neuron by the TTX molecule, which contains a guanidinium group that fits into the external orifice of the sodium channel. This causes external “plugging” of the sodium channel, although the gating mechanism remains functional.148,149
Effects of TTX poisoning typically occur within minutes of ingestion. Headache, diaphoresis, dysesthesias, and paresthesias of the lips, tongue, mouth, face, fingers, and toes evolve rapidly. Buccal bullae and salivation develop. Dysphagia, dysarthria, nausea, vomiting, and abdominal pain ensue. Generalized malaise, loss of coordination, weakness, fasciculations, and an ascending paralysis (with risk of respiratory paralysis) occur in 4 to 24 hours. Other cranial nerves are involved. In more severe toxicity, hypotension is present. In some studies, the mortality rate approaches 50%.186
Therapy is supportive. Removal of the toxin and prevention of absorption are the essential measures. Supportive respiratory care emphasizing airway protection, including intubation, if necessary, is extremely important. Neostigmine, a cholinesterase inhibitor, is proposed as a therapy for tetrodotoxicity. The theory is that increasing acetylcholine at the neuromuscular junction combats TTX effects at the motor end plate and motor axon. Although this sounds promising, a recent literature review found the data insufficient to make an evidence-based recommendation.132
In 2015, the CDC reported 39 cases of laboratory-confirmed foodborne botulism and 141 cases of infant botulism.50 Home-canned fruits and vegetables, as well as commercial fish products, are among the common foods causing botulism. The incubation period usually is 12 to 36 hours; typical signs and symptoms include some initial GI symptoms followed by malaise, fatigue, diplopia, dysphagia, and rapid development of small muscle incoordination.122 In botulism, the toxin is irreversibly bound to the structures within the nerve terminal, where it impairs the presynaptic release of acetylcholine.115 A patient’s survival depends on rapidly diagnosing botulism and immediate initiation of aggressive respiratory therapy. Establishing the diagnosis early makes it possible to treat the “sentinel” or index patient and also others who consumed the contaminated food with antitoxin before their developing signs and symptoms (Chap. 38 and Antidotes in Depth: A6). The differential diagnosis of botulism includes myasthenia gravis, atypical Guillain-Barré syndrome, tick-induced paralysis, and certain chemical ingestions (Tables 39–1 and 39–2).
PREVENTION OF MARINE FOODBORNE DISEASE
Careful evaluation of the symptoms and meticulous reporting to local and state health departments, as well as to the US Centers for Disease Control and Prevention (CDC), will allow for more precise analysis of epidemics of poisoning from contaminated or poisonous food or fish. Many states and countries have developed rigorous health codes with regard to harvesting certain species of fish in certain areas at certain times.
Some examples of actions taken by state, federal, and foreign health agencies in controlling epidemics of seafood-borne food poisoning are the following: The health code of Miami, Florida, prohibits the sale of barracuda and warns against eating fillets from large and potentially toxic fish containing ciguatoxin. A 3,230-km stretch of the Massachusetts coastline was noted to be unsafe for shellfish harvesting because of a red tide bloom. The National Oceanic and Atmospheric Administration’s Fisheries Service along with the FDA declared a health emergency and confiscated shellfish harvested in this area and prohibited the marketing, export, and serving of shellfish.33 The Japanese closely regulate preparation and selling of the puffer fish (fugu), requiring that preparers receive special training and licensing. The sale of fugu is now also permitted under strict control in the United States as well. The Canadian government identifies and registers the location and time of harvesting of mussels, and mussels are tested for the presence of domoic acid.74,161
The sea urchin usually causes toxicity by contact with its spinous processes, but this Caribbean delicacy is also toxic upon ingestion. When the sea urchin is prepared as food, the venom-containing gonads should be removed because they contain an acetylcholine-like substance that causes the cholinergic syndrome of profuse salivation, abdominal pain, nausea, vomiting, and diarrhea.
The consumption of cooked seafood can potentially lead to a syndrome of myalgias and rhabdomyolysis. This syndrome is termed Haff disease, after an outbreak occurred in the 1920s in approximately 1,000 persons living along the Koenigsberg Haff, an inlet of the Baltic Sea. The actual etiology of Haff disease is unknown, but it is suspected that the causative agent is similar to a palytoxin (potent vasoconstrictor). Treatment is hydration with intravenous fluids.63
FOOD POISONING ASSOCIATED WITH DIARRHEA
The initial differential diagnosis for acute diarrhea involves several etiologies: infectious (bacterial, viral, parasitic, and fungal), structural (including surgical), metabolic, functional, inflammatory, toxin induced, and food induced. The differential diagnosis is described in greater detail in Chap. 18.
An elevated temperature is caused by invasive organisms, including Salmonella spp, Shigella spp, Campylobacter spp, invasive E. coli, Vibrio parahaemolyticus, and Yersinia spp, as well as some viruses. Episodes of acute gastroenteritis not typically associated with fever are caused by organisms producing toxins, including S. aureus, Bacillus cereus, Clostridium perfringens, enterotoxigenic E. coli, and viruses.4
Fecal leukocytes typically are found in patients with invasive shigellosis, salmonellosis, Campylobacter enteritis, typhoid fever, invasive E. coli colitis, V. parahaemolyticus, Yersinia enterocolitica, and inflammatory bowel disease. In all of these conditions, except typhoid fever, the leukocytes are primarily polymorphonuclear; in typhoid fever, they are mononuclear. No stool leukocytes are noted in cholera, viral diarrheas, noninvasive E. coli diarrhea, or nonspecific diarrhea.95
The timing of diarrheal onset after exposure or the incubation period is useful in differentiating the cause. Extremely short incubation periods of less than 6 hours are typical for Staphylococcus spp, B. cereus (type I), enterotoxigenic E. coli,4,134,194 and preformed enterotoxins, as well as roundworm larval ingestions. Intermediate incubation periods of 8 to 24 hours are found with C. perfringens, B. cereus (type II enterotoxin), enteroinvasive E. coli,64,142 and Salmonella. Longer incubation periods occur in other bacterial causes of acute gastroenteritis (Table 39–4).
TABLE 39–4Foodborne Infections: Gastrointestinal (Time of Onset and Primary Presenting Symptom) ||Download (.pdf) TABLE 39–4 Foodborne Infections: Gastrointestinal (Time of Onset and Primary Presenting Symptom)
| ||Symptoms || || || |
|Etiology ||Onset ||A ||V ||Di ||Dy ||F ||Source ||Pathogenesis ||Therapy |
|Staphylococcus spp ||2–6 h ||+ ||+ ||+ ||– ||– ||Prepared foods: meats, pastries, salads ||Heat-stable enterotoxin ||Fluid and electrolyte resuscitation |
|Bacillus cereus || || || || || || || || || |
| Type I ||1–6 h ||+ ||+ ||+ ||– ||– ||Fried rice ||Heat-labile toxin ||Fluid and electrolyte resuscitation |
| Type II ||12 h ||+ ||– ||+ ||– ||– ||Meats, vegetables ||Heat-labile toxin || |
|Anisakiasis ||1–12 h ||+ ||+ ||– ||– ||– ||Raw fish, sushi, (Eustrongyloides), minnows, salmon, cod, herring, squid, tuna ||Intestinal larvae ||Endoscopy, laparotomy removal |
|Clostridium perfringens ||8–24 h ||+ ||± ||+ ||± ||– ||Poultry, heat-processed meats ||Heat-labile enterotoxin ||Fluid and electrolyte resuscitation |
|Salmonella spp ||8–24 h ||± ||± ||+ ||± ||+ ||Poultry, egg ||Bacteria, endotoxin (bacteremia) ||Antibiotics |
|Escherichia coli || || || || || || || || || |
| Enterotoxigenic ||<6 h ||+ ||± ||+ ||– ||+ ||Enteric contact || ||Fluid and electrolyte resuscitation |
| Invasive ||24–72 h ||+ ||– ||+ ||+ ||+ ||Raw produce ||Bacteria (invasive) ||Antibiotics |
| Hemorrhagic ||24–72 h ||+ ||+ ||+ ||+ ||± ||Under cooked beef, unpasteurized milk ||Shiga toxin heat stable ||Fluid and electrolyte resuscitation and hematologic (blood transfusion) support |
|Vibrio cholerae ||24–72 h ||± ||± ||+ ||– ||± ||Water, food enteric contact ||Heat labile enterotoxin ||Fluid and electrolyte resuscitation, antibiotics |
|Shigella spp ||24–72 h ||+ ||± ||+ ||+ ||± ||Institutional food handler, household, preschool, enteric contact || |
|Campylobacter jejuni ||1–7 d ||+ ||+ ||+ ||± ||+ ||Milk, poultry, unchlorinated water ||Bacteria, heat labile enterotoxin ||Antibiotics |
|Yersinia spp ||1–7 d ||+ ||+ ||+ ||± ||+ ||Pork, milk, pets ||Bacteria, enterotoxin ||Antibiotics |
The three most likely etiologies of diarrhea are infectious, xenobiotics (chemicals found in an organism, not normally present, frequently a pollutant or contaminant), and foodborne. These three etiologies are not mutually exclusive. The differential diagnosis must be established among these groups. When the time from exposure to onset of symptoms is brief, all of the nonbacterial infectious etiologies (viral, parasitic, fungal, and algal), except for upper GI invasion by roundworm larvae, can be eliminated and the possibility of a bacterial etiology with enterotoxin production becomes more likely (Table 39–4).4,24
Epidemiologic analysis is of immediate importance, particularly when GI diseases strike more than one person in a group. The questions raised in Table 39–5 should be answered.174 If available, an infectious disease consultant or infection control officer should be called for assistance. Alternatively, assistance from state and local health departments should be sought. Often, only the CDC or state health department has the resources to investigate and confirm a presumptive diagnosis in an outbreak. Sophisticated techniques such as toxin detection, matching the organism in the food by phage type with a food handler, matching an organism by phage type with other persons, isolating 10 or more organisms per gram of implicated food,64,68 or polymerase chain reaction (PCR) identification of bacterial or plasmid DNA are potentially useful, although generally not possible using the laboratory and personnel available in most hospitals.32,39,83 Structural, metabolic, and functional causes often can be eliminated. As in these diseases, neither a significant grouping of cases nor a limited clinical history is characteristic. Foodborne parasites such as Trichinella spiralis (trichinosis), Toxoplasma gondii (toxoplasmosis), and G. lamblia (giardiasis) must be considered, although acute GI symptoms are not usually prominent.
TABLE 39–5Epidemiologic Analysis of Gastrointestinal Disease ||Download (.pdf) TABLE 39–5 Epidemiologic Analysis of Gastrointestinal Disease
Is the occurrence of the disease in a large group significant enough to be consistent with foodborne disease (two or more cases)?
Is the symptomatology in affected individuals well defined and similar?
Are the onset, time, and duration of illness similar among affected group members (incubation)?
What are the possible modes of transmission (eg, contact, food, water)?
Is there a relationship between the time of exposure of the group and the mode of transmission?
Do attack rates differ for age, gender, or occupation?
Can it be determined which foods were served and to whom? Can the items that were not eaten by those who did not become ill be identified?
What is the food-specific attack rate?
How was the food procured? How was it stored?
Was cooking technique adequate?
Was personal hygiene acceptable?
Was there animal contamination?
Salmonella enterica infections are of great concern in the United States. Two particular outbreaks define very special problems. In the 1980s, recurrent outbreaks associated with grade A eggs or food containing such eggs occurred. In the past, such outbreaks of Salmonella enteritis were attributed to infection of the egg with Salmonella (from the GI tract of the chicken) through cracks in the shell. More recently, outbreaks involved noncracked, nonsoiled eggs.144 In these cases, presumably, the Salmonella has infected the eggs before the shell was formed. In either case, people who consume raw or undercooked eggs are at most risk for Salmonella enteritis. Raw eggs are standard ingredients of chocolate mousse, hollandaise sauce, eggnog, Caesar salads, and homemade ice cream. Whole, partially cooked eggs are problematic when eaten sunny side up or poached.45 The second group of outbreaks was associated with raw milk,164 which has become very popular in certain communities. Inadequate microwave cooking also causes small outbreaks.68 These outbreaks are of great concern because they frequently involve multiple drug-resistant Salmonella infections.58 Drinking pasteurized milk is not absolutely protective. An outbreak of salmonellosis resulting in more than 16,000 culture-proven cases was traced to one Illinois dairy. The probable cause of the outbreak was a transfer line connecting raw and pasteurized milk containment tanks.171
The contamination of food that is widely distributed places thousands at risk. An outbreak of Salmonella food poisoning from peanut butter caused 529 confirmed illnesses in 48 states and Canada, 116 hospitalizations, and possibly 8 deaths.44 The CDC estimates that the proportion of Salmonella infections that are confirmed by laboratory testing is 3% of the total, so that the estimated magnitude of infected people affected by this type of contamination incident is more than 15,000 individuals annually. News reports state that the peanut butter contamination with Salmonella was suspected; however, the peanut butter was then nationally distributed before confirmatory testing resulted.93,94 The ethical and public health implications of maintaining meticulous standards are highlighted by this epidemic.
Additional concern developed over the widespread use of antibiotics in animal feed, responsible for meats, poultry, and manure-fertilized vegetables now frequently containing resistant bacterial strains to which virtually the entire population is exposed.58,171
The diagnosis of Salmonella infection is made through culture of the stool. The treatment of Salmonella is fluid and, electrolyte resuscitation, and antibiotics (ciprofloxacin or alternatively azithromycin).112
FOODBORNE POISONING ASSOCIATED WITH MULTIORGAN SYSTEM DYSFUNCTION
The hemolytic uremic syndrome (HUS) is frequently caused by a bacterial gastroenteritis. The most commonly responsible organism is E. coli O157:H7.87 Other bacteria and xenobiotics cause the same findings. Typical laboratory findings in HUS include microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI).
Hemolytic uremic syndrome begins with a prodrome of diarrhea 90% of the time. The diarrhea lasts for 3 to 4 days and frequently becomes bloody. Abdominal pain caused by colitis is common, and vomiting, altered mental status (irritability or lethargy), pallor, and low-grade fever frequently occur. At presentation, many patients have oliguria or anuria, and 10% of children have a generalized seizure at HUS onset.182
Hemolytic uremic syndrome is frequently associated with enterohemorrhagic E. coli (EHEC) or E. coli O157:H7 with postdiarrheal HUS.29,136,156,157,169,206 Food products from cattle (ground beef, milk, yogurt, cheese) and water contaminated with fecal material are EHEC sources.62,139 Contaminated water used in gardens and unpasteurized apple cider have caused bloody diarrhea and HUS as a result of EHEC.18,57
Enterohemorrhagic E. coli, including E. coli O157:H7, produces a toxin similar to that produced by Shigella dysenteriae type I, referred to as Shigalike toxin (SLT) or verotoxin.24 The proposed mechanism for SLT damage is intestinal absorption, bloodstream access to renal glomerular endothelium, intracellular adsorption via glycolipid receptors, ribosomal inactivation, and cell death.193 In animal models, organ damage is more severe if endothelial cells have high concentrations of globotriaosylceramide receptors, which have a high binding affinity for Shiga toxin. Other organs with these receptors include the kidney, GI, and central nervous systems, which explain the pattern of organ damage in children with HUS. Endothelial cell damage and other pathologic processes, including platelet and leukocyte activation, triggering of the coagulation cascade, and the production of cytokines, occur.104,202 Types of SLT exist as SLT-1, SLT-2, and additional variants of SLT-2 structure are identified.20
Detection of E. coli O157:H7 through stool culture early in the course of disease is useful. The recovery of organisms decreases after the first week of illness.193 Escherichia coli O157:H7 almost always produces SLT; therefore, if stool cultures are negative, enzyme immunoassay (EIA) and PCR tests can be used to detect SLT in the stool when E. coli can no longer be identified by culture.32
Treatment of HUS should focus on meticulous supportive care, with fluid and electrolyte balance the priority. Dialysis should be instituted early for azotemia, hyperkalemia, acidemia, and fluid overload. Red blood cells and platelet transfusions are required. It is reasonable to treat hypertension with short-acting calcium channel blockers (nifedipine 0.25–0.5 mg/kg/dose orally) and seizures with benzodiazepines. Plasmapheresis was in nondiarrheal HUS and in recurrent HUS after renal transplantation. Anti–SLT-2 antibodies protected mice from SLT-2 toxicity, but IV immunoglobulin with SLT-2 activity did not improve outcome in children with HUS. A double-blind, placebo-controlled study on the use of synthetic SLT receptors attached to an oral carrier found that mortality or serious morbidity of HUS syndrome did not change as a result.199
The mortality rate from HUS with good supportive care is approximately 5%; another 5% of victims have end-stage kidney disease or cerebral ischemic events and chronic neurologic impairment. Prolonged anuria (longer than 1 week), oliguria (longer than 2 weeks), or severe extrarenal disease serve as markers for higher mortality and morbidity.162
There is some evidence that early treatment with antibiotics increases the risk of development HUS in children with E. coli O157:H7 infections.187 An earlier meta-analysis and randomized trial did not find this association.166,172 Because of this concern, it is not typically recommended to treat patients with clinical or epidemiologic presentations consistent with E. coli O157:H7 infections (crampy abdominal pain, bloody diarrhea, regional outbreak) until a definitive pathogen can be identified.196
Approximately 10% of the cases of HUS are not caused by SLT-producing bacteria or streptococci and are classified as atypical. Atypical HUS has a poor prognosis, with death rates as high as 25% and progression to end-stage kidney disease in half of the patients.153
Strategies to prevent the spread of E. coli O157:H7 and subsequent HUS include public education on the importance of thorough cooking of beef to a “well-done” temperature of 170°F (77°C), pasteurization of milk and apple cider, and thorough cleaning of vegetables. Public health measures include education of clinicians to consider E. coli O157:H7 in patients with bloody diarrhea and ensuring the routine capability of microbiology laboratories to culture E. coli O157:H7 and provide for EIA or PCR determination of SLT. Public health departments should provide active surveillance systems to identify early outbreaks of E. coli O157:H7 infection.
In cases of suspected food poisoning with a short incubation period, the physician should first assess the risk for staphylococcal causes. The usual foods associated with staphylococcal toxin production include milk products and other proteinaceous foods, cream-filled baked goods, potato and chicken salads, sausages, ham, tongue, and gravy. Pie crust can act as an insulator, maintaining the temperature of the cream filling and occasionally permitting toxin production even during refrigeration.6 A routine assessment must be made for the presence of lesions on the hands or nose of any food handlers involved. Unfortunately, carriers of enterotoxigenic staphylococci are difficult to recognize because they usually lack lesions and appear healthy.96 A fixed association between a particular food and an illness would be most helpful epidemiologically but rarely occurs clinically. Factors such as environment, host resistance, nature of the agent, and dose make the results surprisingly variable.
Although patients with staphylococcal food poisoning rarely have significant temperature elevations, 16% of 2,992 documented cases in a published review had a subjective sense of fever.96 Abdominal pain, nausea followed by vomiting, and diarrhea dominate the clinical findings. Diarrhea does not occur in the absence of nausea and vomiting. The mean incubation period is 4.4 hours with a mean duration of illness of 20 hours. Two staphylococcal enterotoxin food poisoning incidents involving large numbers of people are reported. At a public event in Brazil in 1998, half of the 8,000 people who attended had nausea, emesis, diarrhea, abdominal pain, and dizziness within hours of consuming food. Of the ill patients, 2,000 overwhelmed the capacity of local emergency departments; 396 (20%) were admitted, including 81 to intensive care units; and 16 young children and older adults died.185 In another report, 328 individuals became ill with symptoms of diarrhea, vomiting, dizziness, chills, and headache after eating cheese or milk.182 In both reports, staphylococcus enterotoxin was found in the food consumed.
Most enterotoxins are produced by S. aureus coagulase–positive species. The enterotoxins initiate an inflammatory response in GI mucosal cells and lead to cell destruction. The enterotoxins also result in sudden effects on the emesis center in the brain and diverse other organ systems. Discrimination of unique S. aureus isolates from those found in foodborne outbreaks is established using restriction fragment length polymorphism analysis by pulsed-field gel electrophoresis and PCR techniques.207 The illness usually lasts for 24 to 48 hours. The treatment is supportive care with hydration and electrolyte repletion.188
Another foodborne toxin that produces GI effects is associated with eating reheated fried rice. Bacillus cereus type I is the causative organism, and bacterial overgrowth and toxin production causes consequential early onset nausea and vomiting.2 Infrequently, this toxin causes liver failure.135 Bacillus cereus type II has a delayed onset of similar GI effects including diarrhea.76 The diagnosis of B. cereus infection is made through culture of the stool. The treatment of B. cereus is fluid and electrolyte resuscitation, and antibiotics (including ciprofloxacin or vancomycin).25
Campylobacter jejuni is a major cause of bacterial enteritis. The organism is most commonly isolated in children younger than 5 years and in adults 20 to 40 years of age. Campylobacter enteritis outbreaks are more common in the summer months in temperate climates. Although most cases of Campylobacter enteritis are sporadic, outbreaks are associated with contaminated food and water. The most frequent sources of Campylobacter spp in food are raw or undercooked poultry products70 and unpasteurized milk.189 Birds are a common reservoir, and small outbreaks are associated with contamination of milk by birds pecking on milk-container tops.189 Contaminated water supplies are also frequent sources of Campylobacter enteritis involving large numbers of individuals.22 Campylobacter jejuni is heat labile; cooking of food, pasteurization of milk, and chlorination of water prevent human transmission.
The incubation period for Campylobacter enteritis varies from 1 to 7 days (mean, 3 days). Typical symptoms include diarrhea, abdominal cramps, and fever. Other symptoms include headache, vomiting, excessive gas, and malaise. The diarrhea contains gross blood, and leukocytes are frequently present on microscopic examination.95 Illness usually lasts 5 to 6 days (range, 1–8 days). Rarely, symptoms last for several weeks. Severely affected individuals present with lower GI hemorrhage, abdominal pain mimicking appendicitis, a typhoidlike syndrome, reactive polyarthritis (Reiter syndrome), or meningitis. Guillain-Barré is associated with the disease with an incidence of less than 1 in 1,000 cases.3 The organism is detected using PCR identification techniques.79 Treatment is supportive and consists of volume resuscitation and antibiotics for the more severe cases.4
Bacterial infections not usually associated with food or food handling are nevertheless occasionally transmitted by food or food handling. Transmission of streptococci in food prepared by an individual with streptococcal pharyngitis is demonstrated.60 A Swedish food handler caused 153 people to become ill with streptococcal pharyngitis when his infected finger wound contaminated a layer cake served at a birthday party.9
Yersinia enterocolitica causes enteritis most frequently in children and young adults. Typical clinical features include fever, abdominal pain, and diarrhea, which usually contains mucus and blood.10,192,204 Other associated findings include nausea, vomiting, anorexia, and weight loss. The incubation period is 1 to 7 days or more. Less common features include prolonged enteritis, reactive polyarthritis, pharyngeal and hepatic involvement, and rash. Yersinia is a common pathogen in many animals, including dogs and pigs. Sources of human infection include milk products, raw pork products, infected household pets, and person-to-person transmission.26,89,123 The diagnosis is based on cultures of food, stool, blood, and, less frequently, skin abscesses, pharyngeal cultures, or cultures from other organ tissues (mesenteric lymph nodes, liver). Yersinia is identified by PCR.103 Patients receiving the chelator deferoxamine (Antidotes in Depth: A7) frequently acquire Yersinia infections because the deferoxamine–iron complex acts as a siderophore for organism growth. Therapy is usually supportive, but patients with invasive disease (eg, bacteremia, bacterial arthritis) should be treated with IV antibiotics. Fluoroquinolones and third-generation cephalosporins are highly bacteriocidal against Yersinia spp.
Listeriosis transmitted by food usually occurs in pregnant women and their fetuses, older adults, and immunocompromised individuals using corticosteroids or with malignancies, diabetes mellitus, kidney disease, or HIV infection.17,41,43,178 Typical food sources include undercooked chicken and unpasteurized milk as well as soft cheeses such as feta, queso fresco, queso blanco, queso panela, blue cheese, and brie. Individuals at risk should avoid the usual sources and should be evaluated for listeriosis if typical symptoms of fever, severe headache, muscle aches, and pharyngitis develop. Treatment with IV ampicillin and aminoglycoside, or trimethoprim–sulfamethoxazole is indicated for systemic Listeria infections.
In addition to the aforementioned saxitoxin, tetrodotoxin, domoic acid, and ciguatoxin, many other xenobiotics contaminate our food sources. Careful assessment for possible foodborne pesticide poisoning is essential. For example, aldicarb contamination has occurred in hydroponically grown vegetables and watermelons contaminated with pesticides.86 Eating malathion-contaminated chapatti and wheat flour resulted in 60 poisonings, including a death in one outbreak54 (Chap. 110). Insecticides, rodenticides, arsenic, lead, or fluoride preparations can be mistaken for a food ingredient. These poisonings usually have a rapid onset of signs and symptoms after exposure.
The possibility of unintentional acute metal salt ingestion must also be evaluated. This type of poisoning most typically occurs when very acidic fruit punch is served in metal-lined containers. Antimony, zinc, copper, tin, or cadmium in a container are dissolved in an acidic food or juice medium.
Some species produce major GI effects. Amanita phalloides, the most poisonous mushroom, usually causes GI symptoms as well as hepatotoxic effects with a delay to clinical manifestations. The rapid onset of symptoms suggests some of the gastroenterotoxic mushrooms, but this is not always true as in the case of Amanita smithiana, which has an early GI phase followed later by acute kidney injury (Chap. 117).
Intestinal Parasitic Infections
The popularity of eating raw fish, or sushi, led to an increase in reported intestinal parasitic infections. Etiologic agents are roundworms (Eustrongyloides anisakis) and fish tapeworms (Diphyllobothrium spp). Symptoms of anisakiasis are either upper intestinal (occur 1–12 hours after eating) or lower intestinal (delayed for days or weeks). Typical symptoms include nausea, vomiting, and severe crampy abdominal pain; with intestinal perforation, severe pain, rebound, and guarding occur. A dietary history of eating raw fish is needed to establish diagnosis and therapy. Visual inspection of the larvae (on endoscopy, laparotomy, or pathologic examination) is useful. Treatment of intestinal infection involves surgical or laparoscopic removal. Anisakis simplex and Pseudoterranova decipiens are Anisakidae that are found in several types of consumed raw fish, including mackerel, cod, herring, rockfish, salmon, yellow fin tuna, and squid. Reliable methods of preventing ingestion of live anisakid larvae are freezing at –4°F (–20°C) for 60 hours or cooking at 140°F (60°C) for 5 minutes.38,111,133,170,176,210
Diphyllobothriasis (fish tapeworm disease) is caused by eating uncooked fish such as herring, salmon, pike, and whitefish that harbor the parasite. The symptoms are less acute than with intestinal roundworm ingestions and usually begin 1 to 2 weeks after ingestion.37 Signs and symptoms include nausea, vomiting, abdominal cramping, flatulence, abdominal distension, diarrhea, and megaloblastic anemia due to vitamin B12 deficiency. The diagnosis is based on a history of ingesting raw fish and on identification of the tapeworm proglottids in stool. Treatment with niclosamide, praziquantel, or paromomycin usually is effective.42
This clinical presentation is misnamed “Chinese restaurant syndrome” because it results from the ingestion of monosodium glutamate (MSG), which has multicultural use in the preparation of many foods. Monosodium glutamate (regarded as “safe” by the FDA) can cause other acute and bizarre neurologic symptoms. Affected individuals present with a burning sensation of the upper torso, facial pressure, headache, flushing, chest pain, nausea and vomiting, and, infrequently, life-threatening bronchospasm4 and angioedema.190 The intensity and duration of symptoms are generally dose related but with significant variation in individual responses to the amount ingested.177,212 Monosodium glutamate causes “shudder attacks” or a seizurelike syndrome in young children. Absorption is more rapid after fasting, and the typical burning symptoms rapidly spread over the back, neck, shoulders, abdomen, and occasionally the thighs. Gastrointestinal symptoms are rarely prominent and symptoms can usually be prevented by prior ingestion of food. When symptoms do occur, they tend to last approximately 1 hour. Monosodium glutamate is also marketed as an effective flavor enhancer.15 Many sausages and canned soups contain large doses of MSG.
There is evidence that humans have a unique taste receptor for glutamate.114 This explains its ability to act as a flavor enhancer for foods. Glutamate is also an excitatory neurotransmitter that can stimulate central nervous system neurons through activation of glutamate receptors and be the explanation for some of the neurologic symptoms described with ingestion.213
Animal studies in which MSG was administered perorally in doses similar to average human intake or intake of extreme users showed that MSG led to disturbances in metabolism affecting insulin, fatty acids, and triglycerides in serum. Monosodium glutamate also affected several genes implicated in adipocytes differentiation. It elevated aminotransferase concentrations and bile synthesis and led to oxidative stress in the liver and to pathological changes in ovaries and fallopian tubes. These more recent findings will lead to further understanding of MSG and its safety in long-term use.100
Anaphylaxis and Anaphylactoid Presentations
Some foods and foodborne toxins cause allergic or anaphylacticlike manifestations,106 also sometimes referred to as “restaurant syndromes”181 (Table 39–6). The similarity of these syndromes complicates a patient’s future approach to safe eating. Isolating the precipitant is essential so that the risk can be effectively assessed. Manufacturers of processed foods should provide an unambiguous listing of ingredients on package labels. Sensitive individuals (or in the cases of children, their parents) must be rigorously attentive.173,215 Those who experience severe reactions should make sure that epinephrine and antihistamines are always available immediately. Attempts to prevent allergic reactions to dairy products by avoiding dairy-containing foods may fail. Nondairy foods are still periodically processed in equipment used for dairy products or contain flavor enhancers of a dairy origin (eg, partially hydrolyzed sodium caseinate), both of which cause morbidity and mortality in allergic individuals.78 Individuals with known food allergies do not always carry prescribed autoinjectable epinephrine syringes, in some cases from a belief that the allergen is easily identifiable and avoidable.106 Food additives that cause anaphylactic or anaphylactoid reactions include antibiotics, aspartame, butylated hydroxyanisole, butylated hydroxytoluene, nitrates or nitrites, sulfites, and paraben esters.128 Regulation of these preservatives is limited, and xenobiotics such as sulfites are so ubiquitous that predicting which guacamole, cider, vinegar, fresh or dried fruits, wines, or beers contain these sensitizing xenobiotics may be impossible.
TABLE 39–6Symptoms of Foodborne Toxicity ||Download (.pdf) TABLE 39–6 Symptoms of Foodborne Toxicity
| ||Onset ||Symptoms or Signs ||Cause ||Therapy |
|Anaphylaxis (anaphylactoid) ||Minutes to hours ||Urticaria, angioedema, bronchospasm, hypotension, cardiorespiratory arrest ||Allergens—nuts, eggs, milk, fish, shellfish, peanuts, soy ||Oxygen, epinephrine, β2-adrenergic agonist, corticosteroids, fluid and electrolyte resuscitation, H1, H2 histamine antagonists, avoidance |
|Monosodium glutamate (MSG) ||Minutes ||Flushing, hypotension, palpitations, facial pressure, headaches, rhinitis, bronchospasm, shivering ||Flavor enhancer of foods ||Oxygen, β2-adrenergic agonists, fluid and electrolyte resuscitation, avoidance |
|Metabisulfites ||Minutes ||Flushing, hypotension, bronchospasm ||Preservative in wines, salad (bars), fruit juice, shrimp ||See Anaphylaxis; avoidance |
|Scombroid ||Minutes to hours ||Flushing, hypotension, urticaria, headache, pruritus, gastrointestinal symptoms ||Large fish—poorly refrigerated; tuna, bonito, albacore, mackerel, mahi mahi (histamine) ||Histamine (H1, H2) antagonists |
|Tyramine ||Minutes to hours ||Headache, hypertension ||Wines, aged cheeses that contain tyramine (INH or MAOI) increases risk ||Avoidance |
|Tartrazine ||Hours ||Urticaria, angioedema, bronchospasm ||Yellow coloring food additive ||See Anaphylaxis; avoidance |
Scombroid poisoning originally was described with the Scombridae fish (including the large dark-meat marine tuna, albacore, bonito, mackerel, and skipjack). However, the most commonly ingested vectors identified by the CDC are nonscombroid fish, such as mahi mahi and amber jack. All of the implicated fish species live in temperate or tropical waters. Ingestion of bluefish and tilapia is associated with scombroid poisoning.67,152 The incidence of this disease is probably far greater than was originally perceived. This type of poisoning differs from other fishborne causes of illness in that it is entirely preventable if the fish is properly stored after removal from the water.
Scombroid poisoning can result from eating cooked, smoked, canned, or raw fish. The implicated fish all have a high concentration of histidine in their dark meat. Morganella morganii, E. coli, and Klebsiella pneumoniae, commonly found on the surface of the fish, contain a histidine decarboxylase enzyme that acts on a warm (not refrigerated), freshly killed fish, converting histidine to histamine, saurine, and other heat-stable substances. Although saurine was suggested as the causative toxin, chromatographic analysis demonstrates that histamine is found as histamine phosphate and saurine is merely histamine hydrochloride.72,146 The term saurine originated from saury, a Japanese dried fish delicacy often associated with scombroid poisoning. The extent of spoilage usually correlates with histamine concentrations. Histamine concentrations in healthy fish are less than 0.1 mg/100 g fish meat. In fish left at room temperature, the concentration rapidly increases, reaching toxic concentrations of 100 mg/100 g fish within 12 hours.
The appearance, taste, and smell of the fish are usually unremarkable.7 Rarely, the skin has an abnormal “honeycombing” character or a pungent, peppery taste that is a clue to its toxicity. Within minutes to hours after eating the fish, the individual experiences numbness, tingling, or a burning sensation of the mouth; dysphagia; headache; and, of particular significance for scombroid poisoning, a unique flush characterized by an intense diffuse erythema of the face, neck, and upper torso.107 Rarely, pruritus, urticaria, angioedema, or bronchospasm ensues. Nausea, vomiting, dizziness, palpitations, abdominal pain, diarrhea, and prostration may develop.55,61,80,107,141
The prognosis is good with appropriate supportive care and parenteral antihistamines such as diphenhydramine. Histamine (H2)-receptor antagonists such as cimetidine or ranitidine are also reasonable to administer because they can also be useful in alleviating GI symptoms.21 Toxic substance removal using orogastric suctioning or adsorption from the gut by activated charcoal are reportedly used, but no randomized trials demonstrate benefit over treatment with antihistamines. Inhaled β2-adrenergic agonists and epinephrine are necessary if bronchospasm is prominent. Although rare, another concern with scombroid toxicity is coronary vasospasm.5,59 Patients usually show significant improvement within a few hours.
Elevated serum or urine histamine concentrations can confirm the diagnosis but are clinically unnecessary. If any uncooked fish remains, isolation of causative bacteria from the flesh is suggestive but not diagnostic. A capillary electrophoretic assay makes rapid histamine detection possible.96 Histamine concentrations greater than 50 mg/100 g fish meat are considered hazardous by the FDA; in Europe, the concentrations are 100 to 200 mg/100 g.99 Research demonstrates that human subjects can tolerate up to 180 mg of pure histamine orally without noticeable effects.5 Isoniazidincreases the severity of the reaction to scombroid fish by inhibiting enzymes that metabolize histamine.99,201
Patients should be reassured that they are not allergic to fish if other individuals experience a similar reaction while eating the same fish at the same time or if any remaining fish can be preserved and tested for elevated histamine concentrations. If this information is not available, then an anaphylactic reaction to the fish cannot be excluded. Table 39–6 represents the differential diagnosis of flushing, bronchospasm, and headache. Because many people often consume alcohol with fish, alcohol is an independent variable.
The differential diagnosis of the scombrotoxic flush apart from a disulfiramlike reaction includes ingestion of niacin or nicotinic acid, pheochromocytoma and carcinoid syndrome. The history and clinical evolution usually establish the diagnosis quickly.
Global Food Distribution: Illegal Food Additives
The United States imports food from all over the world, year round. Approximately 19% of the food consumed in the United States is imported. An analysis of outbreak data from 1996 to 2014 shows 195 outbreak investigations implicated an imported food, resulting in about 11,000 illnesses, about 1,000 hospitalizations, and 19 deaths. The number of outbreaks associated with an imported food has increased from an average of 3 per year (1996–2000) to an average of 18 per year (2009–2014).84 Xenobiotics are given to animals to increase their health and growth. Clenbuterol, a β2 agonist, was administered to cattle raised for human consumption. Clenbuterol causes toxicity in humans who eat contaminated animal meat. Tachycardia, tremors, nausea, epigastric pain, headache, muscle pain, and diarrhea were present in 50 poisoned patients. Other findings included hypertension, hypokalemia, and leukocytosis.168 No deaths are reported. The use of antibiotics, β2 agonists, and other growth enhancers continues, despite safety concerns and laws against their use, because these practices increase yield and profit.
The globalization of food supplies and international agricultural trade has created a new global threat—the apparent purposeful contamination of food for profit. In 2008, almost 300,000 children in China were affected by melamine contamination of milk. Of these, 50,000 were hospitalized, and 6 reported deaths occurred.
The melamine-contaminated milk was sold in China as powdered infant formula, with more than 22 brands containing melamine. The contamination was not limited to China because melamine has been found in candy, chocolate, cookies, and biscuits sold in the United States, likely because of the adulteration of milk used in preparation of these products.
Melamine is a non-nutritious, nitrogen-containing compound, usually used in glues, plastics, and fertilizers. To increase profits, milk sold in China was previously diluted, causing protein malnutrition in children. Because the nitrogen content of milk (a surrogate measure for protein content) is now carefully monitored to detect dilution and to prevent another episode of malnutrition, melamine was added to increase the measured nitrogen content and hide the dilution. This purposeful addition of melamine is suspected to be the cause of the melamine contamination of powdered milk in China.
Melamine and its metabolite cyanuric acid are excreted in the kidneys. Kidney stones containing melamine and uric acid were found in 13 children with acute kidney injury who had consumed melamine containing milk formula.88,205 Both melamine and cyanuric acid appear necessary to cause kidney stones in animals. The combination alone caused renal crystals in cats.164 Melamine found in wheat gluten was added to pet food in 2007 resulted in thousands of complaints and dozens of suspected animal deaths in the United States.
The melamine milk contamination is one of the largest reported deliberate food adulteration incidents. It affected about 300,000 Chinese infants and young children and caused 6 deaths.51,101
In India, 22 children were killed after becoming poisoned when eating their school lunch. It was discovered that the cooking oil was being kept in a container previously used for monocrotophos, a water-soluble organophosphate.92,126
Food products from all over the world find their way into our foods. Increased vigilance by the agencies responsible for food safety, both in countries where the food originates and in countries that import the food, is needed to prevent other events such as the melamine contaminations. Chapter 2 discusses numerous other foodborne toxicologic outbreaks.
Plants and vegetables produce clinical signs and symptoms that are associated with diverse presentations often are involved in food poisoning.91,108,109,115,117 Edible plants and plant products that are poorly cooked or prepared or contaminated result in poisoning. Extensive discussion of this is found in Chap. 118. The development of genetically modified plants has led many to be concerned about both the long- and short-term health effects. Currently, animal data are being collected, and no definitive conclusions about health effects have been made.
FOOD POISONING AND BIOTERRORISM
The threat of terrorist assaults is discussed in Chaps. 126 and 127. The use of food as a vehicle for intentional contamination with the intent of causing mass suffering or death has already occurred in the United States.46,113,198 In the first report, 12 laboratory workers had GI signs and symptoms, primarily severe diarrhea, after consuming food purposefully contaminated with Shigella dysenteriae type II served in a staff break room.113 Four workers were hospitalized; none had reported long-term sequelae. This Shigella strain rarely causes endemic disease. Nevertheless an identical strain, identified by pulsed-field gel electrophoresis, was found in eight of the 12 symptomatic workers, as well as in the pastries served in the break room and in the laboratory stock culture of S. dysenteriae. This finding suggests purposeful poisoning of food eaten by laboratory personnel. The person responsible and the motive remain unknown.
The second case series describes a large community outbreak of food poisoning caused by Salmonella typhimurium.198 The outbreak occurred in the Dalles, Oregon, area during the fall of 1984; a total of 751 people developed Salmonella gastroenteritis. The outbreak was traced to the intentional contamination of restaurant salad bars and coffee creamer by members of a religious commune using a culture of S. typhimurium purchased before the outbreak of food poisoning. A criminal investigation found a Salmonella culture on the religious commune grounds that contained S. typhimurium identical to the Salmonella strain found in the food poisoning victims. It was identified by using antibiotic sensitivity, biochemical testing, and DNA restriction endonuclease digestion of plasmid DNA. Only after more than 1 year of investigation was this Salmonella outbreak linked to terrorist activity. Reasons for the delay in identifying the outbreak as a purposeful food poisoning included (1) no apparent motive; (2) no claim of responsibility; (3) no pattern of unusual behavior in the restaurants; (4) no disgruntled restaurant employees identified; (5) multiple time points for contamination indicated by epidemic exposure curves, suggesting a sustained source of contamination and not a single act; (6) no previous event of similar nature as a reference; (7) the likeliness of other possibilities (eg, repeated unintentional contamination by restaurant workers); and (8) fear that the publicity necessary to aid the investigation might generate copycat criminal activity.
Publication of the event was delayed by almost 10 years out of fear of unintentionally encouraging copycat activity. On the other hand, use of biological weapons by the Japanese cult Aum Shinrikyo appears to have motivated authorities to release this publication in the hopes of quickly identifying similar deliberate food poisoning patterns in the future.
A third report describes a disgruntled employee who contaminated 200 lb of meat at a supermarket with a nicotine-containing insecticide.46 Ninety-two people became ill, and four sought medical care. Signs and symptoms included vomiting, abdominal pain, rectal bleeding, and one case of atrial tachycardia.
There are multiple reports of deliberate food poisoning with tetramine.53,214 In one particular case of human greed, a Chinese restaurant owner poisoned the food in his neighbor’s restaurant with tetramine. Tetramine or tetramethylenedisulfotetramine is a highly lethal neurotoxic rodenticide, once used worldwide, now illegal in the United States. The snack shop owner caused hundreds to become ill and 38 deaths by spiking his competitor’s breakfast offerings (fried dough sticks, sesame cakes, and sticky rice balls). Tetramethylenedisulfotetramine is an odorless and tasteless white crystal that is water soluble. The mechanism of action is noncompetitive irreversible binding to the chloride channel on the γ-aminobutyric acid receptor complex, which blocks the influx of chloride and alters the neurons potential. It is referred to as a “cage convulsant” because of its globular structure. Severe toxicity presents with tachycardia, dysrhythmias, agitation, status epilepticus, and coma. Immediate or early treatment with sodium-(RS)-2,3-dimercaptopropane-1-sulfonate (DMPS) and pyridoxine (vitamin B6) (A15) appears to be effective in a mouse model.13,65,208
The capacity of foodborne xenobiotics that are easy to obtain and disburse to infect large numbers of people is clearly exemplified by two specific outbreaks: (1) the purposeful Salmonella outbreak in Oregon and (2) the apparently unintentional Salmonella outbreak that resulted in more than 16,000 culture-proven cases traced to contamination in an Illinois dairy. The probable cause of the outbreak was a contaminated transfer pipe connecting the raw and pasteurized milk containment tanks.171 These events emphasize the vulnerability of our food supply and the importance of ensuring its safety and security.
PREVENTION OF FOODBORNE ILLNESS
The incidence of foodborne disease has increased over the years and has resulted in a major public health problem on the global level. The current methods for detecting foodborne pathogens are inefficient. This has led to the research and development of rapid detection methods.
The three major types of rapid detection methods are biosensor-based, nucleic acid–based, and immunological-based methods. Biosensor detection methods use an analytical device that contains a bioreceptor and transducer. The transducer converts the biological interactions into a measurable electrical signal. Examples of biosensor based methods are optical, electrochemical, and mass-based biosensors. Nucleic acid–based detection methods work by detecting specific DNA or RNA in the pathogen. An example of this test is the PCR, immunological-based methods detect foodborne pathogens based on antibody–antigen interactions, whereby a particular antibody binds to the specific antigen. An example of an immunological based detection method is ELISA.
In general, the rapid detection methods are more efficient and sensitive than the conventional detection methods. Rapid detection methods may be a very useful way of preventing foodborne disease in the future. Currently, implementing special equipment and training personnel along with high costs have thwarted comprehensive application of rapid detection methods at this time.120
The diverse etiologies of food poisoning involve almost all aspects of toxicology.
Our concerns center around the natural toxicity of plants or animals, the contamination of which can occur in the field, during factory processing, subsequent transport and distribution, or during home preparation or storage.
Whether these events are intentional or unintentional, they alter our approaches to general nutrition and society.
Issues in food safety include the governmental role in food preparation and protection, bacteria such as Salmonella and E. coli 0157:H7, prions in Creutzfeldt-Jacob disease (bovine encephalopathy), and genetically altered materials such as corn.
Future discussions of food poisonings and interpretations of the importance of these problems may dramatically alter our food sources and their preparation and monitoring.
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