The hemolytic uremic syndrome (HUS) is frequently caused by a bacterial gastroenteritis. The most commonly responsible organism is E. coli O157:H7.68 Other bacteria and xenobiotics cause the same findings.
Typical laboratory findings in HUS include microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury.
HUS begins with a prodrome of diarrhea 90% of the time. The diarrhea lasts for 3 to 4 days and frequently becomes bloody. Abdominal pain due to colitis is common, and vomiting, altered mental status (irritability or lethargy), pallor, and low-grade fever frequently occur. At presentation, many have oliguria or anuria, and 10% of children have a generalized seizure at HUS onset.151
HUS is frequently associated with enterohemorrhagic E. coli (EHEC) or E. coli O157:H7 with postdiarrheal HUS.25,109,124,125,137,172 Food products from cattle (ground beef, milk, yogurt, cheese) and water contaminated with fecal material are EHEC sources.48,111 Contaminated water used in gardens and unpasteurized apple cider have caused bloody diarrhea and HUS as a result of EHEC.16,44
EHEC, including E. coli O157:H7, produces a toxin similar to the toxin produced by Shigella dysenteriae type I, referred to as Shigalike toxin (SLT) or verotoxin.21 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.161 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 may 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.83,169 More than one type of SLT exists; SLT-1, SLT-2, and variants of SLT-2 structure are identified.17
Detection of E. coli O157:H7 through stool culture early in the course of disease is useful. The recovery decreases after the first week of illness.161E. 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.27
Treatment of HUS should focus on meticulous supportive care, with fluid and electrolyte balance the priority. Dialysis should be instituted early for azotemia, hyperkalemia, acidosis, and fluid overload. Red blood cells and platelet transfusions may be required. Hypertension should be treated with short-acting calcium channel blockers (nifedipine 0.25–0.5 mg/kg/dose orally) and seizures with benzodiazepines. Plasmapheresis has been used in nondiarrheal HUS and in recurrent HUS after renal transplants. Anti–SLT-2 antibodies have protected mice from SLT-2 toxicity, but intravenous immunoglobulin with SLT-2 activity has not improved 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.166
The mortality from HUS with good supportive care is approximately 5%; another 5% of victims suffer end-stage kidney disease or cerebral ischemic events and chronic neurologic impairment. Prolonged anuria (>1 week), oliguria (>2 weeks), or severe extrarenal disease may serve as markers for higher mortality and morbidity.131
There is some evidence that early treatment with antibiotics increases the risk of development HUS in children with E. coli O157:H7 infections.156 An earlier meta analysis and randomized trial did not find this association.134,140 Due to this concern, many experts recommend not treating 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.
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 insuring 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.4 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.76 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 2992 documented cases in a published review had a subjective sense of fever.76 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 have been reported. At a public event in Brazil in 1998, one-half of the 8000 people who attended had nausea, emesis, diarrhea, abdominal pain, and dizziness within hours of consuming food. Of the ill patients, 2000 overwhelmed the capacity of local emergency departments, 396 (20%) were admitted including 81 to intensive care units, and 16 young children and elderly participants died.154 In another report, 328 individuals became ill with symptoms of diarrhea, vomiting, dizziness, chills, and headache after eating cheese or milk.153 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 may exert a sudden explosive effect on the emesis center in the brain and diverse other organ systems. Discrimination of unique S. aureus isolates from those found in foodborne outbreaks can be made using restriction fragment length polymorphism analysis by pulsed-field gel electrophoresis and PCR techniques.173
Another foodborne toxin with GI symptoms 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.108 Bacillus cereus type II has a delayed onset of similar GI symptoms, including diarrhea.59
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 in food are raw or undercooked poultry products54 and unpasteurized milk.157 Birds are a common reservoir, and small outbreaks are associated with contamination of milk by birds pecking on milk-container tops.157 Contaminated water supplies are also frequent sources of Campylobacter enteritis involving large numbers of individuals.19C. jejuni is heat labile; cooking of food, pasteurization of milk, and chlorination of water will 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 may include headache, vomiting, excessive gas, and malaise. The diarrhea may contain gross blood, and leukocytes are frequently present on microscopic examination.74 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. The organism may be detected using PCR identification techniques.62 Treatment is supportive, and consists of volume resuscitation, and possibly antibiotics for the more severe cases.3
Bacterial infections not usually associated with food or food handling are nevertheless occasionally transmitted by food or food handling. Transmission of streptococcal pharyngitis in food prepared by an individual with streptococcal pharyngitis has been demonstrated.46 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.7
In the last 3 decades, a median of four cases of foodborne botulism, three cases of wound botulism, and 71 cases of infant botulism have been reported annually to the CDC.150 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 symptoms include some initial GI symptoms, followed by malaise, fatigue, diplopia, dysphagia, and rapid development of small muscle incoordination.98 In botulism, the toxin is irreversibly bound to the neuromuscular junction, where it impairs the presynaptic release of acetylcholine.92 A patient’s survival depends on rapidly diagnosing botulism and immediate initiation of aggressive respiratory therapy. Establishing the diagnosis early may make it possible to treat the “sentinel” or index patient and also others who consumed the contaminated food with antitoxin prior to their developing signs and symptoms (Chap. 41 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 41–1 and 41–2).
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.8,160,171 Other associated symptoms include nausea, vomiting, anorexia, and weight loss. The incubation period may be 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.22,70,99 The diagnosis may be 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 may be identified by PCR.84 Patients receiving the chelator deferoxamine (Antidotes in Depth: A7) may acquire yersinia infections due to the patients’ increased susceptibility. 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 intravenous antibiotics. Fluoroquinolones and third-generation cephalosporins are highly bacteriocidal against Yersinia spp.
Listeriosis transmitted by food usually occurs in pregnant women and their fetuses, the elderly, and immunocompromised individuals using corticosteroids or with malignancies, diabetes mellitus, kidney disease, or HIV infection.15,34,36,146 Typical food sources include unpasteurized milk, soft cheeses such as feta, and undercooked chicken. Individuals at risk should avoid the usual sources and should be evaluated for listeriosis if typical symptoms of fever, severe headache, muscle ache, and pharyngitis develop. Treatment with intravenous ampicillin and aminoglycoside, or trimethoprim/sulfamethoxazole is indicated for systemic Listeria infections.
In addition to the aforementioned saxitoxin TTX, 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.67 Eating malathion-contaminated chapatti and wheat flour resulted in 60 poisonings including a death in one outbreak42 (Chap. 113). 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 considered. 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 may be 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 (Chap. 120).
Intestinal Parasitic Infections
The popularity of eating raw fish, or sushi, has led to an increase in reported intestinal parasitic infections. Etiologic agents are roundworms (Eustrongyloides anisakis) and fish tapeworms (Diphyllobothrium spp). Symptoms of anisakiasis may be 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 may be 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.31,89,106,138,144,176
Diphyllobothriasis (fish tapeworm disease) is caused by eating uncooked fish that harbor the parasite, including herring, salmon, pike, and whitefish. The symptoms are less acute than with intestinal roundworm ingestions and usually begin 1–2 weeks after ingestion.30 Signs and symptoms include nausea, vomiting, abdominal cramping, flatulence, abdominal distension, diarrhea, and megaloblastic anemia. 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.35
This clinical presentation is misnamed “Chinese restaurant syndrome” since it results from the ingestion of monosodium glutamate (MSG), which has multicultural use in the preparation of many foods. Affected individuals present with a burning sensation of the upper torso, facial pressure, headache, flushing, chest pain, nausea and vomiting, and, infrequently, life-threatening bronchospasm,3 and angioedema.1,58 Intensity and duration of symptoms are generally dose related but with significant variation in individual responses to the amount ingested.145,178 MSG causes “shudder attacks” or a seizurelike syndrome in young children. Absorption is more rapid following fasting, and the typical burning symptoms rapidly spread over the back, neck, shoulders, abdomen, and occasionally the thighs. GI symptoms are rarely prominent and symptoms can usually be prevented by prior ingestion of food. When symptoms do occur, they tend to last approximately one hour. The syndrome is a reaction to MSG, which had been commonly used in Chinese and many other restaurants. MSG is also marketed as an effective flavor enhancer.13 Many sausages and canned soups contain large doses of MSG.
MSG (regarded as “safe” by the FDA) can cause other acute and bizarre neurologic symptoms. There is evidence that humans have a unique taste receptor for glutamate.91 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 may be the explanation for some of the neurologic symptoms described with ingestion.179
Anaphylaxis and Anaphylactoid Presentations
Some foods and foodborne toxins may cause allergic or anaphylacticlike manifestations,85 also sometimes referred to as “restaurant syndromes”149 (Table 44–6). 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.141,180 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 may still be processed in equipment used for dairy products or contain flavor enhancers of a dairy origin (eg, partially hydrolyzed sodium caseinate), both of which can cause morbidity and death in allergic individuals.61 Individuals with known food allergies do not always carry prescribed autoinjectable spring-injected epinephrine syringes, in some cases from a belief that the allergen is easily identifiable and avoidable.85 Food additives that can cause anaphylaxis include antibiotics, aspartame, butylated hydroxyanisole, butylated hydroxytoluene, nitrates or nitrites, sulfites, and paraben esters.102 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 agents may be impossible.
TABLE 44–6.Common Foodborne Disease Symptoms: Flushing, Bronchospasm, and Headache (Primary Presenting Symptoms) ||Download (.pdf) TABLE 44–6. Common Foodborne Disease Symptoms: Flushing, Bronchospasm, and Headache (Primary Presenting Symptoms)
| ||Onset ||Symptoms/Signs ||Cause ||Therapy |
|Anaphylaxis (anaphylactoid) ||Minutes to hours ||Urticaria, angioedema, bronchospasm, hypotension ||Allergens—nuts, eggs, milk, fish, shellfish, peanuts, soy ||Oxygen, epinephrine, β2-adrenergic agonist, corticosteroids, volume expansion, H1, H2 histamine blockers, avoidance |
|Monosodium glutamate (MSG) ||Minutes ||Flushing, hypotension, palpitations, facial pressure, headaches, rhinitis, bronchospasm, shivering ||Flavor enhancer of foods ||Oxygen, β2-adrenergic agonists, volume expansion, 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, pruritis, gastrointestinal symptoms ||Large fish—poorly refrigerated; tuna, bonito, albacore, mackerel, mahi mahi (histamine) ||H1, H2 blockers, supportive care, avoidance |
|Tyramine ||Minutes to hours ||Headache, hypertension (INH or MAOI) increases risk ||Wines, aged cheeses ||Avoidance for those with hypertension, migraines |
|Tartrazine ||Hours ||Urticaria, angioedema, brochospasm ||Yellow coloring food additive ||See Anaphylaxis, avoidance |
Scombroid poisoning originally was described with the Scombroidae 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.33 All of the implicated fish species live in temperate or tropical waters. Ingestion of bluefish in New Hampshire was the probable cause of scombroid poisoning in five people,52 and in a large outbreak, tuna was the offender in 71 cases reported from a military outpost.47 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 following removal from the water.
Scombroid poisoning results 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 has been suggested as the causative toxin, chromatographic analysis demonstrates that histamine is found as histamine phosphate and saurine is merely histamine hydrochloride.56,117 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.5 Rarely, the skin has an abnormal “honeycombing” character or a pungent, peppery taste that may be 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.86 Rarely, pruritus, urticaria, angioedema, or bronchospasm ensues. Nausea, vomiting, dizziness, palpitations, abdominal pain, diarrhea, and prostration may develop.43,63,86,113
The prognosis is good with appropriate supportive care and parenteral antihistamines such as diphenhydramine. H2-receptor antagonists such as cimetidine or ranitidine may also be useful in alleviating gastrointestinal symptoms.18 The toxic substance should be removed or absorbed from the gut. Inhaled β2-adrenergic agonists and epinephrine may be necessary if bronchospasm is prominent. Patients usually show significant improvement within a few hours.
Elevated serum or urine histamine concentrations can confirm the diagnosis, but are usually 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.79 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.79 Isoniazid may increase the severity of the reaction to scombroid fish by inhibiting enzymes that break down histamine.78,168
Patients may be reassured that they are not allergic to fish if other individuals experience a similar reaction to 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 must be considered. Table 44–6 lists the differential diagnosis of flushing, bronchospasm, and headache. Because many people often consume alcohol with fish, alcohol must be considered an independent variable.
The differential diagnosis of the scombrotoxic flush apart from a disulfiramlike reaction includes ingestion of niacin or nicotinic acid, and pheochromocytoma. The history and clinical evolution usually establish the diagnosis quickly.
Global Food Distribution, Illegal Food Additives
Xenobiotics are given to animals to increase their health and growth. Clenbuterol, a β2 agonist, has been administered to cattle raised for human consumption. The substance can cause 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 and leukocytosis.136 No deaths have been 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, as melamine has been found in candy, chocolate, cookies, and biscuits sold in the United States, likely due to 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 had previously been 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.69 Both melamine and cyanuric acid appear necessary to cause kidney stones in animals. The combination alone caused renal crystals in cats.135 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 six deaths.41,80
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.
Plants, vegetables, and their diverse presentations often are involved in food poisonings.72,87,88,93,94 Edible plants and plant products may be poorly cooked or prepared, or they may be contaminated. Extensive discussion of this may be found in Chap. 121.