1413

Foodborne DiseaseSAMIR V. SODHA | PATRICIA M. GRIFFIN | JAMES M. HUGHES

9999

The primary focus of this chapter is foodborne disease in the United States. Foodborne diseases result from ingestion of a wide variety of foods contaminated with pathogenic microorganisms, microbial toxins, or chemicals. From 1998 to 2002, a mean of approximately 1300 outbreaks of foodborne disease affecting more than 25,000 people in the United States were reported annually to the Centers for Disease Control and Prevention (CDC).1 These figures underestimate the magnitude of the problem. The actual incidence of foodborne disease is unknown but was estimated in 1997 to be approximately 76 million cases, with 325,000 hospitalizations and 5000 deaths each year in the United States.2 CDC’s Foodborne Diseases Active Surveillance Network (FoodNet) has conducted surveillance for nine foodborne pathogens since 1996 in several states, with 15% of the U.S. population in active surveillance catchment areas in 2007. Analysis of surveillance data from the baseline period 1996 to 1998 through 2007 has shown a decrease in the incidence of illnesses due to several pathogens: The incidence of Campylobacter isolates decreased 31%, that of Listeria decreased 42%, Yersinia decreased 49%, Shigella decreased 36%, and Salmonella decreased 8%, indicating important advances in food safety (Fig. 99-1).3 Those declines occurred mostly before 2004. Comparing 2007 with 2004 to 2006, the estimated incidence of infections caused by Campylobacter, Listeria, Salmonella, Shigella, Escherichia coli O157:H7, Vibrio, and Yersinia did not decline significantly, and the incidence of Cryptosporidium infections increased.3 Marked declines in the incidence of E. coli O157:H7 in 2003 and 2004 were not main-tained. Certain serotypes of Salmonella had important increases in 2007 compared with 2004 to 2006, such as I 4,5,12:i- and Newport, whereas others had significant decreases, such as Typhimurium and Heidelberg.3 Table 99-1 shows the incidences of illnesses associated with different foodborne pathogens in 2007. Clearly, foodborne dis-eases are common and can be severe, and food safety programs need to be intensified.

This discussion focuses mostly on foodborne disease syndromes that are acute and whose clinical features include gastrointestinal or neu-rologic symptoms and signs. The agents discussed and the frequency with which outbreaks were reported to CDC from 1998 to 2002 are indicated in Table 99-2.

The spectrum of foodborne diseases has expanded in recent decades. Noroviruses are now recognized as the most frequent cause of food-borne illness in the United States. New foodborne agents causing severe disease have emerged (e.g., E. coli O157:H7, Cyclospora cayeta-nensis)4; previously uncommon food vehicles such as fresh fruits and vegetables have become important sources5; and several pathogens have become increasingly resistant to antimicrobial drugs. Important food sources have been defined for some established pathogens, such as Vibrio cholerae O1 and Listeria monocytogenes. Clostridium difficile, a well-known cause of diarrheal illness, has been found in retail ground meat samples, but foodborne transmission has not been documented.6 Several outbreaks of enteroaggregative E. coli that were probably food-borne have been reported from outside the United States.7,8 Studies are needed to assess the possible role of C. difficile and enteroaggregative E. coli in foodborne disease in the United States. Postinfectious syn-dromes have been recognized as important sequelae of foodborne infections, including hemolytic uremic syndrome after infection with Shiga toxin–producing E. coli, such as O157:H7,9 reactive arthritis after salmonellosis,10 and Guillain-Barré syndrome after campylobacterio-sis.11 Centralization of the food supply has increased the risk for nationwide outbreaks. Globalization of the food supply has facilitated

exposure to foodborne pathogens from other parts of the world. The share of imported food in domestic consumption has increased from 11% in 1990 to 15% in 200612; both domestic and imported food sup-plies can cause foodborne illnesses. The growing population of people with immunosuppressive conditions or treatments and the increasing number of institutionalized older individuals mean that more people have elevated susceptibility to the effects of microbial contamination of food.

Pathogenesis and Clinical FeaturesFoodborne disease can appear as an isolated sporadic case or, less frequently, as an outbreak of illnesses affecting a group of people after a common food exposure. The diagnosis of foodborne disease should be considered when an acute illness, especially one with gastrointesti-nal or neurologic manifestations, affects two or more people who had shared a common meal. Important clues to the etiologic agent are provided by the signs and symptoms of affected persons and the incubation period.

FOODBORNE DISEASE SYNDROMES CAUSED BY MICROBIAL AGENTS OR THEIR TOXINS

The following divides foodborne diseases into a variety of syndromes, mostly based on signs and symptoms and time of onset after consump-tion of contaminated food, and indicates the agents most likely responsible for the illness (Table 99-3). The incubation period in an individual illness is usually unknown, but it is often apparent in the focal outbreak setting.

NauseaandVomitingwithin1to6Hours. The major etiologic con-siderations are Staphylococcus aureus and Bacillus cereus. The relatively short incubation period reflects the fact that these diseases are caused by preformed enterotoxins. Staphylococcal food poisoning is charac-terized by vomiting (82% of cases) and diarrhea (68%); fever is rela-tively uncommon (16%).13,14 Staphylococci responsible for episodes of food poisoning produce one or more enterotoxins; multiple serologi-cally distinct enterotoxins have been identified (A through U, exclud-ing F, S, and T) but not all cause vomiting.15 The staphylococcal enterotoxins are grouped with toxic shock syndrome toxin-1 (TSST-1) as pyrogenic toxin superantigens; enterotoxin B and C have been implicated in nonmenstrual toxic shock syndrome.16 Although the mechanism of action of these enterotoxins in humans has not been clarified, studies in monkeys and cats suggest that the enterotoxin produces its emetic action after interaction with abdominal viscera and that the sensory stimulus is carried to the vomiting center in the brain by the vagus and sympathetic nerves.16

More than 99% of enterotoxigenic staphylococci associated with food poisoning are coagulase positive; however, an outbreak caused by enterotoxigenic Staphylococcus epidermidis has been reported.17 Strains producing type A enterotoxin alone account for most of the reported outbreaks of staphylococcal food poisoning in the United States.13,14

B. cereus strains can cause two types of food poisoning syndromes, one characterized primarily by nausea and vomiting with an incuba-tion period of 1 to 6 hours (short-incubation “emetic” syndrome) and a second manifested primarily by abdominal cramps and diarrhea with an incubation period of 8 to 16 hours (long-incubation “diarrhea” syndrome).18 The short-incubation syndrome, characterized by vomit-

1414 PART II Major Clinical Syndromes

ing (100% of cases), abdominal cramps (100%), and, less frequently, diarrhea (33%),19 is caused by a toxin named cereulide. Cereulide is resistant to heat, pH, and proteolysis. The complete mechanism of action remains to be determined, but it binds to the 5- hydroxytryptamine-3 (5-HT3) receptor of the vagus afferent nerve.18

Another clue to the cause of staphylococcal and short-incubation B. cereus illnesses is provided by the fact that they are of short duration, usually lasting less than 12 hours.13,14,19

AbdominalCrampsandDiarrheawithin8to16Hours. The major etiologic considerations for this syndrome, which is also enterotoxin mediated, are Clostridium perfringens and B. cereus. In contrast to staphylococcal food poisoning and the short-incubation B. cereus

% change estimate95% confidence interval

Campylobacter Listeria Salmonella Shigella Vibrio Yersinia

Pathogen

80

60

40

20

0

-20

-40

-60

-80

% c

hang

e*D

ecre

ase

I

ncre

ase

NoChange

*No significant change = 95% confidence interval is both above and below the no change line; significant increase = estimate and entire 95% confidence interval are above the no change line; significant decrease = estimate and entire 95% confidence interval are below the no change line.

†Shiga toxin–producing Escherichia coli.

*Shiga toxin–producing Escherichia coli.† The position of each line indicates the relative change in the incidence of that

pathogen compared with that in 1996–1998. The actual incidences of these infections can differ.

A

B

1996

1999 2000 2001 2002 2003 2004 2005 2006 2007 1998

2.0

1.00.9

0.8

0.7

0.6

0.5

0.4

Year

Rel

ativ

e ra

te (

log

scal

e)

CampylobacterListeriaSalmonellaSTEC* OH157Vibrio

STEC† OH157

Figure 99-1 Foodborne Diseases Active Surveillance Network, United States, 1996-2007. A, Percentage change in incidence of laboratory-confirmed bacterial infections in 2007 compared with 2004-2006, by pathogen. B, Relative rates (compared with 1996-1998 rates) of laboratory-confirmed infections of Campylobacter, Shiga toxin–producing E. coli O157, Listeria, Salmonella, and Vibrio, by year.

Pathogen Incidence per 100,000 Population

Campylobacter 12.79

E. coli O157:H7 1.20

Listeria 0.27

Salmonella 14.92

Shigella 6.26

Vibrio 0.24

Yersinia 0.36

Cryptosporidium 2.67

Cyclospora 0.03

Hemolytic uremic syndrome* 2.01

*Incidence per 100,000 children aged less than 5 years.

TABLE 99-1

Annual Incidence of Diagnosed Infections Identified through Active Surveillance in the Foodborne Diseases Active Surveillance Network—United States, 2007

Etiologic Agent

OutbreaksOutbreak-

Associated Illnesses

Number % Number %

BacterialBacillus cereus 37 1.7 571 0.8

Brucella 1 0.0 4 0.0

Campylobacter 61 2.8 1,440 2.1

Clostridium botulinum 12 0.6 52 0.1

Clostridium perfringens 130 6.0 6,724 9.7

Escherichia coli 140 6.5 4,854 7.0

Listeria monocytogenes 11 0.5 256 0.4

Salmonella 585 27.0 16,821 24.4

Shigella 67 3.1 3,677 5.3

Staphylococcus aureus 101 4.7 2,766 4.0

Streptococcus 1 0.0 4 0.0

Vibrio cholerae 3 0.1 12 0.0

Vibrio parahaemolyticus 25 1.1 613 0.9

Vibrio, other 1 0.0 2 0.0

Yersinia enterocolitica 8 0.4 87 0.1

Other bacteria 1 0.0 4 0.0

ChemicalCiguatoxin 84 3.9 315 0.5

Heavy metals 2 0.1 23 0.0

Mushroom toxin 2 0.1 6 0.0

Scombrotoxin 118 5.4 463 0.7

Shellfish toxin 5 0.2 36 0.0

Other chemical 10 0.5 297 0.4

ParasiticAnisakis 1 0.0 14 0.0

Cryptosporidium parvum 4 0.2 139 0.2

Cyclospora cayetanensis 9 0.4 325 0.5

Giardia intestinalis 3 0.1 119 0.2

Trichinella spiralis 6 0.3 33 0.0

ViralAstrovirus 1 0.0 14 0.0

Hepatitis A 50 2.3 981 1.4

Norovirus 657 30.3 27,171 39.4

Rotavirus 1 0.0 108 0.2

Total 2,167 100 68,981 100

CDC, Centers for Disease Control and Prevention.

TABLE 99-2

Foodborne Disease Outbreaks and Outbreak-Associated Illnesses of Known Cause Reported to the CDC, 1998-2002

99 Foodborne Disease 1415

erae non-O1, and, in endemic areas, V. cholerae O1 and O139; C. jejuni, Salmonella, and Shigella may also cause this syndrome. Entero-toxins synthesized in vivo are responsible for the syndrome caused by V. cholerae O1, V. cholerae non-O1,30 and ETEC.31 Enterotoxins or cytotoxins, or both, may also play a role in the pathogenesis of this syndrome, when it is caused by Salmonella,32 Shigella,33,34 or V. parahaemolyticus.35

Severe cholera manifests as a profuse, watery diarrhea accompanied by muscular cramps. With the exception of cholera, which may last for 5 days, and disease caused by V. cholerae non-O1, which may last for 2 to 12 days, these illnesses usually resolve within 3 to 4 days. In one documented ETEC outbreak, the median duration of illness was 7 days.36

VomitingandNonbloodyDiarrheawithin24to48Hours. Noro-viruses (formerly Norwalk-like viruses), the most common of known foodborne pathogens, are discussed in further detail in Chapter 175. They were last estimated to cause 9.2 million foodborne illnesses per year.2 Even more cases of acute gastroenteritis are caused by nonfood-borne transmission of noroviruses, directly from one person to another or by fomite contamination.37 Vomiting and diarrhea are often the presenting symptoms, with onset 1 to 2 days after exposure. The syn-drome progresses to include watery, nonbloody diarrhea, abdominal pain, and nausea. Vomiting is more common among children, whereas diarrhea is more likely to predominate among adults; however, both symptoms occur in most patients regardless of age.37 Fever occurs in one third to one half of patients, is usually low grade, and lasts for less than 24 hours. Symptoms usually resolve in 1 to 3 days, but 10% of patients may require medical care and hospitalization for rehydra-tion.38 A group of related viruses in the Caliciviridae family, most notably the sapoviruses, may also cause similar foodborne illness, but such reports are few.39

It is impossible to distinguish between norovirus and some bacterial causes of gastroenteritis, such as ETEC, for a single patient based on clinical course, but a few simple criteria have been used epidemiologi-cally to assess whether norovirus was the likely cause of outbreaks. Criteria that suggest norovirus infection include (1) failure to detect a bacterial or parasitic pathogen in stool specimens, (2) the occurrence of vomiting in at least 50% of patients, (3) a mean duration of illness of only 12 to 60 hours, and (4) a mean incubation period of only 24 to 48 hours.40 With the recent advent of molecular diagnostic tests such as reverse transcription polymerase chain reaction (RT-PCR), these epidemiologic criteria have been validated as highly specific (99%) and moderately sensitive (68%).41

Fever and Abdominal Cramps within 16 to 48 Hours, withoutDiarrhea. Yersina enterocolitica has been incriminated as a cause of foodborne outbreaks in the United States and is a more common cause of foodborne disease in northern Europe and Canada.42-45 In young children, febrile diarrhea is the most common presentation.42 In older children and adults, the clinical illness may be prolonged, and one syndrome may closely resemble acute appendicitis; nausea and vomit-ing are relatively uncommon, occurring in less than 25% to 40% of the cases.45-47 The duration of illness usually ranges from 24 hours to 4 weeks.43,47

Bloody Diarrhea without Fever within 72 to 120 Hours. The dis-tinctive syndrome of hemorrhagic colitis has been linked to Shiga toxin–producing E. coli (STEC), most often serotype O157:H7.48,49 These strains produce cytotoxins, called Shiga toxins or verotoxins, that affect Vero kidney cell cultures and are neutralized by antisera to Shiga toxins.50,51 The toxins damage vascular endothelial cells in target organs such as the gut and kidney.52 The illness is characterized by severe abdominal cramping and diarrhea, which is initially watery but may later be grossly bloody.48 Patients with uncomplicated infection usually remain afebrile. The mean incubation period in outbreaks is 3 to 8 days. The duration of uncomplicated illness ranges from 1 to 12 days. The development of fever and leukocytosis may herald hemolytic

disease, which are caused by preformed enterotoxins, C. perfringens and long-incubation B. cereus food poisoning are caused by toxins produced in vivo, accounting for the longer incubation period. In C. perfringens food poisoning, the most common symptoms are diarrhea and abdominal cramps. Although five types of C. perfringens toxins have been described, type A almost always causes this syndrome.20 C. perfringens enterotoxin A is a heat-labile protein produced during sporulation.21 Animal studies in rabbits and rats indicate that the enterotoxin has greatest activity in the ileum, and that it damages the brush borders of epithelial cells at villus tips.22

B. cereus strains that cause a similar long-incubation syndrome including diarrhea (96%) and abdominal cramps (75%), sometimes vomiting (33%), and rarely fever,19 elaborate two three-component enterotoxins and one single-component enterotoxin.18 Pathogenesis is likely a multifactorial process involving gene regulation of the different virulence factors.18

Although nausea occurs in many patients with C. perfringens and long-incubation B. cereus food poisoning, vomiting occurs infre-quently. In fact, occurrence of vomiting in more than one third of affected persons suggests that these organisms are not involved. Although these illnesses last longer than staphylococcal and short-incubation B. cereus food poisoning last, symptoms usually resolve within 24 hours.19,23 However, in some long-incubation B. cereus out-breaks, the mean duration of illness can be several days.18,24

Fever, Abdominal Cramps, and Diarrhea within 6 to 48 Hours.The major etiologic considerations for this syndrome are Campylo-bacter jejuni, E. coli, Salmonella, Shigella, and Vibrio parahaemolyticus. Bloody diarrhea and vomiting occur in a varying proportion of patients infected with these pathogens. These illnesses usually resolve within 2 to 7 days.

Nontyphoidal Salmonella is the most common bacterial cause of reported foodborne outbreaks in the United States.1,2 The median incubation period is 6 to 48 hours.

Although C. jejuni and E. coli O157:H7 infection typically have longer median incubation periods of 3 to 4 days, illness may occur within 48 hours. C. jejuni is not as commonly associated with food-borne outbreaks as Salmonella, but it is still the most common food-borne bacterial pathogen in the United States.2

Infrequently, outbreaks of a febrile gastroenteritis caused by L. monocytogenes in previously healthy persons have been reported.25,26 This syndrome is characterized by watery and frequent diarrhea, fever, abdominal cramps, headache, and myalgias, with a median incubation period of 20 to 31 hours.

Although an infrequent infection in the United States, Vibrio chol-erae non-O1 infection can cause this syndrome with bloody diarrhea in a quarter of patients in the United States, and sometimes fever.27-29

Abdominal Cramps and Watery Diarrhea within 16 to 72Hours. The major etiologic considerations for this syndrome are enterotoxigenic strains of E. coli (ETEC), V. parahaemolyticus, V. chol-

Preformed Toxin Toxin Production in Vivo Tissue Invasion

Staphylococcus aureus Clostridium perfringens Campylobacter jejuni

Bacillus cereus (short incubation)

B. cereus (long incubation) Salmonella

Clostridium botulinum

C. botulinum (infant botulism)

Shigella

Enterotoxigenic Escherichia coli

Invasive E. coli

Vibrio cholerae O1 or O139 Listeria monocytogenes

V. cholerae non-O1

Shiga toxin–producing E. coli

TABLE 99-3

Major Pathogenic Mechanisms in Some Foodborne Bacteria

1416 PART II Major Clinical Syndromes

Vibrio vulnificus can cause primary bacteremia after ingestion of raw oysters. This severe syndrome is seen almost exclusively in patients with underlying liver disease, especially if associated with iron overload.71

Several species of Trichinella roundworms cause trichinellosis in humans, who are only accidental hosts, when raw or undercooked pork or wild game meat contaminated with larvae of this parasite is consumed. The signs and symptoms depend partly on number of larvae ingested and characteristics of the host’s immunity. Gastroin-testinal symptoms, such as nausea, diarrhea, vomiting, and abdominal cramps may develop as early as 24 to 48 hours after ingestion, corre-sponding to the enteral phase of infection. This may be followed by fever, myalgia, and periorbital edema up to 8 weeks post- consumption, corresponding to the parenteral phase of infection.72

Other infectious agents and diseases with primary symptoms outside the gastrointestinal and neurologic systems that can be transmitted by foods include (with a known food vehicle) group A β-hemolytic strep-tococci, typhoid fever, brucellosis (e.g., from goat’s milk cheese), anthrax (meat), tuberculosis (raw milk), Q fever (raw milk), hepatitis A (shellfish, fresh produce), toxoplasmosis (meat), anisakiasis (fish), and tapeworms (beef, pork, and fish).

PostinfectionSyndromes. Reactive arthritis may develop after infec-tion with Salmonella, Yersinia, Campylobacter, or Shigella,73 and rarely, with Giardia.74 Reactive arthritis consists of the classic triad of aseptic inflammatory polyarthritis, urethritis, and conjunctivitis, although not all components occur in all patients. Persons who are HLA-B27 posi-tive are fifty times more likely to develop reactive arthritis, suggesting an important component of genetic predisposition.73 Among 217 patients in an outbreak caused by Salmonella serotype Enteritidis enterocolitis in Washington state, 29% had symptoms of reactive arthritis.75 Increased severity and longer duration of diarrheal illness were associated with the development of reactive arthritis.

FOODBORNE DISEASE SYNDROMES CAUSED BY NONBACTERIAL TOXINS

Nausea, Vomiting, and Abdominal Cramps within 1 Hour. The major etiologic considerations for this syndrome are heavy metals; copper, zinc, tin, and cadmium have caused foodborne outbreaks.76-80 Latency periods for symptom onset most often range from 5 to 15 minutes. Nausea, vomiting, and abdominal cramps result from direct irritation of the gastric and intestinal mucosa and usually resolve within 2 to 3 hours if minor amounts are ingested. Progression to serious illness and even death is possible if larger amounts are consumed.

Paresthesiaswithin1Hour. When patients have this symptom, fish poisoning, shellfish poisoning (Table 99-4), the so-called Chinese res-taurant syndrome, and niacin poisoning are some of the major pos-sibilities. Histamine fish poisoning (scombroid) is characterized by symptoms resembling those of a histamine reaction. Burning of the mouth and throat, flushing, headache, and dizziness are common; abdominal cramps, nausea, vomiting, and diarrhea also occur in most cases.81 In severe cases, urticaria and bronchospasm may also occur. Symptoms are thought to result from histamine. Histamine build-up in fish is caused by a high concentration of histidine in fish flesh being combined with a high concentration of marine bacteria, usually caused by inadequate refrigeration, which catalyze the decarboxyl-ation of histidine to histamine.82,83 In an outbreak traced to tuna sashimi, a strain of Klebsiella pneumoniae capable of producing large quantities of histamine was implicated.84 Symptoms usually resolve in a few hours.

Three types of shellfish poisoning should be considered in a food-borne outbreak presenting with paresthesias: paralytic (PSP), neuro-toxic (NSP), and amnesic (ASP).85-87 PSP is characterized by paresthesias of the mouth, lips, face, and extremities.87-89 In severe cases, dyspnea, dysphagia, muscle weakness or frank paralysis, ataxia, and respiratory

uremic syndrome (HUS), which is typically diagnosed about 1 week after the beginning of the diarrheal illness, when the diarrhea is resolv-ing. HUS occurs in about 8% of infected individuals and occurs in people of all ages, but the highest rates are among children less than 5 years old and the elderly. The fatality rate for HUS in children is 3% to 5%; mortality rates as high as 16% to 35% have been observed in nursing homes.53 Other E. coli serogroups that produce Shiga toxins can also cause hemorrhagic colitis and HUS. Outbreaks of non-O157 STEC reported in the United States have involved serotypes O111, O26, O121, O103, and O104.54

Nausea, Vomiting, Diarrhea, and Paralysis within 18 to 36Hours. The occurrence of acute gastrointestinal symptoms simultane-ously with or just before the onset of descending weakness or paralysis strongly suggests the diagnosis of foodborne botulism. Constipation is common once the neurologic syndrome is well established, but nausea and vomiting occur at onset in approximately 50% of the patients, and diarrhea occurs in nearly 20%.55 The pathogenesis of the acute gastro-intestinal symptoms is not understood; the botulinal toxins, which inhibit acetylcholine release from nerve endings,56,57do not appear to be responsible.58 Botulism in humans is usually caused by one of three immunologically distinct, heat-labile protein neurotoxins, designated A, B, and E,59 which are produced after germination of Clostridium botulinum spores in inadequately processed foods. The disease in older children and adults results from ingestion of preformed toxin. The syndromes of infant botulism and adult intestinal colonization result from ingestion of spores, with subsequent toxin production in vivo.58,60,61 Both illnesses last from several weeks to several months. Clinical suspicion is critical for botulism to be correctly diagnosed.62

Guillain-Barré syndrome has been associated with serologic evi-dence of recent infection with C. jejuni.11 In a multicenter study of 118 patients in the United States with Guillain-Barré syndrome, 36% had serologic evidence of a preceding C. jejuni infection.11 When preceding diarrheal illness is reported, it typically occurs 1 to 3 weeks before the onset of neurologic symptoms.11 In contrast to botulism, this syn-drome is usually manifested by an ascending paralysis accompanied by sensory findings and abnormal nerve conduction velocity.

Persistent Diarrhea within 1 to 3 Weeks. Multiple distinctive per-sistent diarrheal syndromes can be foodborne, including cyclosporia-sis, cryptosporidiosis, giardiasis, and Brainerd diarrhea.

Since the mid 1990s, outbreaks of cyclosporiasis linked to various types of imported fresh produce have been recognized in the United States.63 The incubation period averages about 1 week (range, about 2 days to about 2 or more weeks), and the most common symptom is watery diarrhea.63 Other common symptoms include anorexia, weight loss, abdominal cramps, nausea, and body aches; vomiting and low-grade fever may be noted. Untreated illness can last for several weeks or months, with a remitting-relapsing course and prolonged fatigue.

A distinctive chronic watery diarrhea, known as Brainerd diarrhea, was first described in persons who had consumed raw milk.64 After a mean incubation period of 15 days, affected persons developed acute, watery diarrhea with marked urgency and abdominal cramping. Diar-rhea persisted for over a year in 75% of patients. No etiologic agent was identified. A restaurant-associated outbreak and a cruise ship–associated outbreak of a similar illness have suggested that water may also transmit the agent.65,66

SystemicIllness. Some foodborne diseases manifest mainly as inva-sive infections in immunocompromised patients. Listeriosis typically affects pregnant women, fetuses, and persons with compromised cel-lular immunity. In pregnant women, infection commonly causes mis-carriage while in neonates, the elderly, and immunocompromised persons, it causes fever, myalgias, and primary bacteremia or menin-gitis.67 Identified sources are most often foods, including deli meat, especially turkey, and raw soft cheeses, such as queso fresco.68-70 The incubation period ranges from 2 to 6 weeks, and the fatality rate is approximately 20%.

99 Foodborne Disease 1417

Table 99-4). Ciguatera is characterized by abdominal cramps, nausea, vomiting, and diarrhea, preceded or followed by numbness and par-esthesias of the lips, tongue, and throat.102,103 Malaise, headache, pru-ritus, dry mouth, metallic taste, myalgias, arthralgias, blurred vision, photophobia, and transient blindness also have been reported.104,105 Sharp shooting pains in the legs and a sensation of looseness and pain in the teeth are characteristic.103 In severe cases, reversal of hot and cold temperature sensations, sinus bradycardia, hypotension, cranial nerve palsies, and respiratory paralysis may occur.103,106

The illness is caused by two dinoflagellate toxins: ciguatoxin and maitotoxin.87 Ciguatoxin is a lipid-soluble, relatively heat-stable com-pound107 that is acquired by fish through the food chain. Ciguatoxin inhibits red blood cell cholinesterase activity,108 increases membrane sodium permeability,109 and changes the electrical potential of cells through its action on sodium channels.110 Maitotoxin, the most toxic nonproteinaceous molecule known, is water soluble. By opening calcium channels of plasma membranes, it causes neurotransmitter release.111 Duration of the acute illness ranges from a few days to a few months; pain in the extremities has been reported to occur intermit-tently for years after an episode of ciguatera. Other natural marine toxins have been associated with similar syndromes, including palytoxin.111

Miscellaneous Mushroom Poisoning Syndromes with Onsetwithin2Hours. At least five clinical syndromes may occur within 2 hours of ingestion of toxic mushrooms (Table 99-5).112-114 Species con-taining ibotenic acid and muscimol cause an illness that mimics acute alcoholic intoxication and is characterized by confusion, restlessness, and visual disturbances followed by lethargy; symptoms resolve within 24 hours. Species containing muscarine cause an illness characterized by evidence of parasympathetic hyperactivity (e.g., salivation, lacrima-tion, diaphoresis, blurred vision, abdominal cramps, diarrhea). Some patients experience miosis, bradycardia, and bronchospasm. Symp-toms usually resolve within 24 hours. Species containing the toxic

insufficiency may occur. Respiratory failure may occur during the first 12 hours of the illness.87-89 Some patients also have nausea, vomiting, and diarrhea.85,87,89 The disease is caused by saxitoxin and closely related neurotoxic substances in the dinoflagellates Gonyaulax catenella and Gonyaulax tamarensis. Bivalve mollusks feed on these dinoflagel-lates; the toxins are concentrated in their flesh but do not affect the mollusks.88 Typically, cases of saxitoxin poisoning in Florida have followed consumption of local pufferfish.90 The structure of saxitoxin has been determined91; it is heat stable and blocks the propagation of nerve and muscle action potentials, interfering with the increase in sodium permeability by acting at a metal cation-binding site in sodium channels or nerve membranes.87,92 The mechanisms of action of the other neurotoxins are unknown. Duration of the illness ranges from a few hours to a few days.93

Although many patients with PSP experience the onset of symptoms within 1 hour of ingestion, the incubation period is often inversely related to the amount of toxin ingested. A European outbreak involved 120 patients who ingested contaminated mussels; the median incuba-tion period was 3.5 hours, with a range of 1 to 10 hours.93

The clinical features of NSP are similar to those of PSP except that reverse temperature perception may occur and paralysis does not.85,87 Several poorly characterized neurotoxins known as brevetoxins are responsible for this illness and are primarily found in the dinoflagellate Kerenia brevis (formerly Gymnodinium breve).94 In contrast to the neu-rotoxins of PSP, brevetoxins cause an uncontrollable influx of sodium into the cell.94 Symptoms of the illness typically resolve within 48 hours.87

The clinical features of ASP are initially nonspecific and include vomiting, abdominal cramping, and diarrhea. Confusion, amnesia, coma, and cardiovascular instability follow within hours in severe cases; these signs tend to occur in older persons and in persons with underlying renal disease. The hallmark of the disease is antegrade amnesia, which was reported in 25% of affected persons in a large Canadian outbreak.86 The disease is caused by domoic acid, a toxin produced by the dinoflagellate Nitzschia pungens and concentrated in the flesh of mollusks. Amnesia is the result of bilateral destruction of the hippocampi by the toxin and can be permanent.95

The monosodium l-glutamate (MSG) symptom complex, also known as Chinese restaurant syndrome, is characterized by a burning sensation in the neck, chest, abdomen, or arms and by a sensation of tightness over the face and chest.96 Headache, flushing, diaphoresis, lacrimation, weakness, nausea, abdominal cramps, and thirst fre-quently occur.96,97 Symptoms appear to be caused by excessive amounts of MSG in foods, although other undefined substances may also play a role.96,98 The illness usually resolves within several hours.

Niacin poisoning produces pruritus and a burning facial erythema within 20 minutes of ingestion, which rapidly resolves.99 Other, more severe adverse effects such as amblyopia, hyperglycemia, hyperurice-mia, myopathy, and hepatotoxicity may occur.100,101

Paresthesias within 1 to 6 Hours. The major diagnostic consider-ations for this syndrome are PSP and ciguatera fish poisoning (see

SyndromeIncubation

Period Duration Season

Histamine fish poisoning (scombroid)

5 min-1 hr Few hours Year-round

Ciguatera 1-6 hr Few days to few months Feb.-Sept.

Paralytic shellfish poisoning

5 min-4 hr Few hours to few days May-Nov.

Neurotoxic shellfish poisoning

5 min-4 hr Few hours to few days Spring, fall

Amnesic shellfish poisoning

15 min-6 hr Few days to permanent Uncertain

TABLE 99-4 Fish and Shellfish Poisoning Syndromes

Syndrome Mushroom Species Toxins

Short IncubationDelirium Amanita muscaria,

Amanita pantherinaIbotenic acid, muscimol

Parasympathetic hyperactivity

Inocybe spp.Clitocybe spp.

MuscarineMuscarine

Hallucinations, somnolence, dysphoria

Psilocybe spp.Panaeolus spp.

Psilocybin, psilocinPsilocybin

Disulfiram reaction Coprinus atramentarius Coprine, 1-aminocyclopropanol, cyclopropanone hydrate

Gastroenteritis Many Various uncharacterized toxins

Long IncubationGastroenteritis,

hepatorenal failureAmanita phalloides Amatoxins, phallotoxins

Amanita virosa Amatoxins

Amanita verna Amatoxins

Galerina autumnalis Amatoxins

Galerina marginata Amatoxins

Galerina venenata Amatoxins

Gastroenteritis, muscle cramping, hepatic failure, hemolysis, seizures, coma

Gyromitra spp. Gyromitrin

Gastroenteritis, acute renal failure*

Amanita smithiana Allenic norleucine

*Gastroenteritis symptoms may present with short or long incubation periods (30 minutes to 12 hours).

TABLE 99-5 Mushroom Poisoning Syndromes

1418 PART II Major Clinical Syndromes

frequently recognized pathogen in the United States and has been responsible for several large outbreaks traced to municipal water sup-plies.122,123 This illness is characterized by diarrhea, nausea, abdominal pain, bloating, flatulence, and occasionally malabsorption. The incuba-tion period is typically 1 to 2 weeks, and the duration of illness may be several weeks, occasionally longer. Large waterborne outbreaks caused by Cryptosporidium spp.,124 E. coli O157:H7,125,126 shigellae,127 hepatitis A,128 Salmonella serotype Typhi,129 nontyphoid salmonellae,130 ETEC,131 C. jejuni,132,133 Brainerd diarrhea,134 noroviruses,135-137 Entamoeba histo-lytica,138 and Toxoplasma139 have been reported.

EpidemiologyIn addition to the clinical syndrome and incubation period, other clues to the cause of an outbreak of foodborne disease may be provided by the type of food responsible and the setting in which it is eaten (Table 99-7).

FOODS

Outbreaks of staphylococcal food poisoning are associated with foods of high protein content, such as ham, poultry, potato and egg salads, and cream-filled pastries, which are thought to be contaminated during preparation by a food handler. In the classic staphylococcal foodborne outbreak, a food handler’s hand has a purulent skin lesion, but this is true in only a minority of outbreaks. In contrast, outbreaks of B. cereus food poisoning of the short-incubation type are most often associated with fried rice that has been cooked and held warm for extended periods. The growth of B. cereus under similar experimental conditions in rice has been well documented.140

C. perfringens outbreaks usually occur after the ingestion of meat (especially beef and poultry) and gravies; organisms have been isolated from raw meat, poultry, and fish specimens. Outbreaks are more likely to occur when these items are stored between 15° C (59° F) and 50° C (122° F), allowing spores to germinate and then produce toxin.141 Long-incubation B. cereus food poisoning is frequently associated with meat or vegetable dishes. In addition to being a frequent contaminant of raw meats, vegetables, and milk products, B. cereus was isolated from 25% of dried foods such as seasoning mixes, spices, and dried potatoes in one study142 and from more than 50% of dried beans and cereals in another.143 A long-incubation B. cereus outbreak was traced to a meal delivery service operation in which food was held at and above room temperature for an extended period.144

E. coli O157:H7 outbreaks were initially recognized mostly after consumption of undercooked ground beef. However, more recent outbreaks have been traced to a broad range of foods, including leafy greens, apple cider, alfalfa sprouts, venison, and salami.145 Healthy cattle commonly carry E. coli O157:H7 in their intestines and excrete it in manure. Produce may become contaminated with E. coli O157:H7 through environmental contamination by cattle feces or by use of water in processing that has been contaminated with fecal matter. Outbreaks have also been caused by consumption of contaminated drinking and swimming water and by person-to-person transmission in daycare centers.126,146

Salmonella, which is carried in the intestines of food animals in the United States, is transmitted by a wide variety of food vehicles, includ-ing poultry, beef, egg, dairy products, or produce. Shell eggs can be internally contaminated with Salmonella serotype Enteritidis because of an ovarian infection in the hen.147 Foods made with raw or under-cooked shell eggs are a dominant source of outbreaks and sporadic cases of S. serotype Enteritidis infection in the United States.148 Salmo-nella outbreaks also have been traced to fresh produce, including melons, tomatoes, unpasteurized orange juice, jalapeño peppers, and alfalfa sprouts.149-153 Large outbreaks have been caused by conta-minated chocolate candy, peanut snacks, cereals, and peanut butter.154-157

Illnesses due to E. coli O157:H7, Salmonella, Campylobacter, Listeria, and other pathogens have been associated with consumption of raw

substances psilocybin and psilocin cause an acute psychotic reaction manifested by hallucinations and inappropriate behavior, which usually resolves within 12 hours. The mushroom Coprinus atramen-tarius contains a disulfiram-like substance that can result in headache, flushing, paresthesias, nausea, vomiting, and tachycardia if alcohol is consumed during the 48-hour period after ingestion. Species contain-ing allenic norleucine such as Amanita smithiana cause gastrointestinal symptoms (e.g., anorexia, nausea, vomiting, diarrhea) within 30 minutes to 12 hours after ingestion. Progression to liver injury and acute renal failure typically occurs 4-6 days after ingestion. Another clinical syndrome is characterized by nausea, vomiting, abdominal cramps, and diarrhea after the ingestion of mushrooms containing gastrointestinal irritants that are not well characterized.

AbdominalCrampsandDiarrheawithin6to24Hours,FollowedbyHepatorenalFailure. Species of poisonous mushrooms contain-ing amatoxins and phallotoxins are responsible for this syndrome (see Table 99-5).112,113,115 The most common implicated species are Amanita phalloides, Amanita virosa, and Amanita verna.112,116 The illness is typi-cally biphasic; the abdominal cramps and diarrhea, which may be severe, usually resolve within 24 hours. The patient then remains well for 1 to 2 days before evidence of hepatic and renal failure supervenes. A mortality rate of 20% to 50% has been reported.117,118

A similar clinical syndrome occurs after ingestion of mushrooms of the Gyromitra genus, which contain the toxic substance gyromitrin. Hemolysis, seizures, and coma can occur, but this toxin does not cause acute renal failure.112

WATERBORNE DISEASE

The evaluation of a suspected foodborne outbreak may reveal that water was the vehicle. Some pathogens incriminated in waterborne outbreaks are different from those most often responsible for foodborne disease; the responsible etiologic agents for waterborne outbreaks associated with acute gastrointestinal illness reported to the CDC from 2001 through 2006 are shown in Table 99-6.119-121 Giardia intestinalis is a

Etiologic Agent

Outbreaks*Outbreak-

Associated Illnesses

Number % Number %

Campylobacter spp. 6 4.3 215 2.0

Cryptosporidium spp. 55 39.0 6,451 58.7

Entamoeba histolytica 1 0.7 59 0.5

Escherichia coli O157:H7 10 7.1 116 1.1

E. coli O26:NM 1 0.7 4 0.0

Giardia intestinalis 11 7.8 250 2.3

Noroviruses 22 15.6 1,525 13.9

Plesiomonas shigelloides 2 1.4 5 0.0

Salmonella, nontyphoidal 1 0.7 70 0.6

Shigella spp. 10 7.1 218 2.0

Multiple etiologic agents† 11 7.8 2,012 18.3

Miscellaneous chemicals 11 7.8 60 0.5

Total 141 100.0 10,985 100.0

TABLE 99-6

Waterborne Disease Outbreaks of Gastroenteritis and Outbreak-Associated Illnesses of Known Cause Associated with Recreational Water, Drinking Water, Water Not Intended for Drinking (Excluding Recreational Water), and Water of Unknown Intent— Reported to CDC, 2001-2006

CDC, Centers for Disease Control and Prevention.

*Excludes 29 outbreaks of unknown cause that resulted in 1259 outbreak-associated illnesses and three outbreaks of known cause that resulted in 44 illnesses; gastrointestinal illness was present in two outbreaks associated with microcystin toxin and one outbreak associated with Pseudomonas aeruginosa but was not defined as the predominant illness.

†Multiple etiologic agents; includes outbreaks with the following unlisted etiologies: E. coli O145, Helicobacter canadensis, Yersinia enterocolitica and one unidentified agent. Outbreaks involving multiple chemicals are included in Miscellaneous chemicals.

99 Foodborne Disease 1419

Etiology Foods Season Geographic Predilection

BacterialSalmonella Beef, poultry, eggs, dairy products, produce Summer, fall None

Staphylococcus aureus Ham, poultry, and egg salads, pastries Summer None

Campylobacter jejuni Poultry, raw milk Spring, summer None

Clostridium botulinum Home-canned vegetables, preserved fish, honey (infants) Summer, fall None

Clostridium perfringens Beef, poultry, gravy Fall, winter, spring None

Shigella Egg salad, lettuce Summer None

Vibrio parahaemolyticus Shellfish Spring, summer, fall Coastal states

Bacillus cereus Fried rice, meats, vegetables Year-round None

Yersinia enterocolitica Milk, pork, chitterlings Winter Unknown

Vibrio cholerae O1 Shellfish Variable Tropical, Gulf Coast, Latin America

Vibrio cholerae non-O1 Shellfish Unknown Tropical, Gulf Coast

Shiga toxin–producing Escherichia coli Ground beef, raw milk, fresh produce Summer, fall Northern states

ViralNoroviruses Salads, shellfish Year-round None

Chemical

Ciguatera Barracuda, snapper, amberjack, grouper Spring, summer (in Florida) Tropical reefs

Histamine fish poisoning (scombroid) Tuna, mackerel, bonito, skipjack, mahi-mahi Year-round Coastal

Mushroom poisoning Mushrooms Spring, fall Temperate

Heavy metals Acidic beverages Year round None

Monosodium-l-glutamate Chinese food Year round None

Paralytic shellfish poisoning Shellfish Summer, fall Temperate coastal zones

Neurotoxic shellfish poisoning Shellfish Spring, fall Subtropical

TABLE 99-7 Etiology of Foodborne Disease Outbreaks by Food, Season, and Geographic Predilection

milk. Despite these risks, raw milk is still legally sold in many states and is sometimes given to groups of schoolchildren who visit dairy farms. From 1998 to 2005, a total of 45 foodborne outbreaks due to unpasteurized milk (or cheese suspected to be made from unpas-teurized milk) were reported to CDC, accounting for 1007 illnesses, 104 hospitalizations, and 2 deaths.158

Shigella outbreaks are most often associated with cool, moist foods, such as potato and egg salads, that require much handling after cooking. Outbreaks have been caused by fresh produce, including raw vegetables at a salad bar, parsley, and lettuce.159-161 C. jejuni infection most often follows the ingestion of undercooked poultry, although outbreaks have also occurred from raw or contaminated milk and contaminated water sources.162,163 V. parahaemolyticus outbreaks in the United States are associated with the ingestion of bivalve mollusks and crustaceans.164

V. cholerae O1 and non-O1 outbreaks have been traced to contami-nated shellfish eaten raw or inadequately cooked.165 Crabs, shrimp, and raw oysters were implicated as the vehicles of transmission of a unique strain of V. cholerae O1 in Louisiana.166 Crabs brought in travelers’ luggage from Latin America have caused cholera in the United States.167 Sporadic cases of diarrhea associated with V. cholerae non-O1 strains in the United States also have been linked to shellfish ingestion.27

Foodborne infections with Y. enterocolitica have been caused by consumption of raw pork and contaminated milk and by cross- contamination from the preparation of pork chitterlings in the house-hold.42-47 Traveler’s diarrhea caused by ETEC was associated with consumption of salads in Mexico,168 and a foodborne outbreak of ETEC occurred after ingestion of imported cheese.169 Traveler’s diar-rhea due to ETEC among cruise ship passengers has been linked to water bunkered in foreign ports.170 In recent years, outbreaks of “traveler’s diarrhea at home” related to consumption of fresh produce have become more common.171

Botulism outbreaks are most often associated with the ingestion of low-acid (pH ≥ 4.4) home-canned vegetables, fruits, and fish. Out-breaks of botulism also have occurred after ingestion of unusual vehi-cles, including baked potatoes, sautéed onions, and chopped garlic in oil.62,172 Recent outbreaks of botulism due to bottled carrot juice and canned chili sauce were the first related to commercially distributed

products in almost 20 years.173,174 Honey was the source of C. botuli-num in some cases of infant botulism,175 and for that reason, parents are advised to avoid giving honey to infants.

In norovirus outbreaks, contamination of food occurs either directly with fecal matter at the source, such as shellfish caught in sewage-contaminated waters or raspberries irrigated with water contaminated by sewage, or perhaps more often by an ill food handler.37,176 Foods that require much handling without subsequent cooking are typically implicated, including sandwiches and salads.177 In one large multistate outbreak, steamed shellfish from the Gulf Coast were implicated. These were probably contaminated by ill oystermen, who, lacking toilet facilities on their oyster boats, defecated and vomited directly into the shallow oyster beds.178

Cyclospora infection results from ingestion of mature (infective) oocysts in contaminated food or water. Cyclosporiasis is endemic in various tropical and subtropical regions of the world. Outbreaks of cyclosporiasis in the United States have been linked to multiple types of imported fresh produce, including raspberries, basil, mesclun lettuce, and snow peas.63,179-181

Largely due to improvements in swine husbandry in the past several decades, and likely because of efforts to educate consumers on cooking pork to kill any Trichinella larvae present, the most frequent source of trichinellosis outbreaks in the United States has shifted from com-mercial pork to wild game animals, including bear, cougar, and wild boar.182,183

Outbreaks of heavy metal poisoning are most often associated with acidic beverages such as lemonade, fruit punch, and carbonated drinks that have been stored in corroded metallic containers such as punch bowls77 or that have been in contact with metallic tubing (e.g., in vending machines)184 for periods sufficient to leach the metallic ions from the container.

Histamine fish poisoning outbreaks are associated with scombroid fish, the most common of which are tuna, mackerel, bonito, and skip-jack. In addition, the nonscombroid fish mahi-mahi has caused out-breaks of scombroid-like fish poisoning. Ciguatera fish poisoning has been associated with more than 400 species of fish. Barracuda, red snapper, amberjack, and grouper are most commonly implicated. The disease is more often associated with large fish; in one study, 69% of

1420 PART II Major Clinical Syndromes

is most common west of the Mississippi River, whereas type B is most common in the East and type E is most common in Alaska.172

Ciguatera is endemic in tropical and subtropical regions between latitudes 35° north and 35° south. Most outbreaks in the United States have been reported from the Caribbean, Florida, or Hawaii.196 Travel-ers who return from these areas with the characteristic syndrome should be questioned regarding fish consumption. PSP and NSP out-breaks occur more frequently in coastal areas.

As globalization and centralization of the food supply continue to increase, multistate and multinational outbreaks are increasingly iden-tified.197 Interpretation of geographic settings of isolated illnesses has evolved as a result. Seemingly isolated illnesses within a geographic area may actually be part of a larger multistate or multinational out-break. In 2008, melamine contamination of dairy products in China led to contaminated products being found in several countries around the world.198

EPIDEMIOLOGIC ASSESSMENT

If an outbreak of foodborne disease is suspected, public health authori-ties should be contacted so that it can be investigated. Investigating the outbreak is important to identify and rapidly control the source and to prevent similar outbreaks from happening again. Some outbreaks are the result of contaminated food served at a single meal. As a common meal is identified through interviews with ill people, food-specific attack rates should be determined for all foods and beverages served at the meal (Table 99-8). Both ill and well persons who were present at the same meal must be interviewed. Food-specific attack rates are determined by calculating the proportion of persons who consumed a food that became ill. Food-specific attack rates may iden-tify the responsible vehicle of transmission. To be incriminated, a food must have a significantly higher attack rate among those who ate it than for those who did not, and usually most of those who became ill ate the food. On occasion, more than one food item may be statistically associated with illness. On these occasions, a stratified analysis may indicate whether both items were contaminated by the etiologic agent or whether one item was contaminated while the other was often consumed with it (e.g., meat loaf and gravy) (see Table 99-8). For example, if meat loaf and gravy were both statistically associated with illness, stratified analysis may indicate that attack rates were high for those who ate meat loaf regardless of whether they ate gravy, and were low for those who did not eat meat loaf regardless of whether they ate gravy, indicating that the meat loaf alone was responsible for the outbreak.

red snapper weighing 2.8 kg or more were toxic, compared with only 18% of smaller fish.185 PSP, NSP, and ASP occur after ingestion of bivalve mollusks, most often oysters, clams, and mussels.

The possibility that foodborne illness could be the result of an inten-tional contamination should also be considered. An outbreak of sal-monellosis in Oregon in 1984 involved 751 persons who ate or worked at 10 area restaurants. Epidemiologic investigation determined that illness was associated with eating from salad bars, but no single item was implicated. A subsequent criminal investigation revealed that members of a religious commune had deliberately contaminated the salad bars.186 In 1996, an outbreak of Shigella dysenteriae type 2 infec-tions affecting 12 laboratory workers was caused by consumption of deliberately contaminated muffins.187 The use of botulinum toxin by terrorists has also become a concern.188

CHANGES IN THE POPULATION

The increasing average age in many countries means that more of the population has a heightened susceptibility to severe foodborne infec-tions. In the United States, a growing segment of the population has immune impairment as a consequence of infection with the human immunodeficiency virus (HIV) or underlying chronic disease. People with compromised immunity due to infection with HIV have higher reported rates of salmonellosis, campylobacteriosis, and listeriosis than do persons not infected with HIV.189,190 Salmonella and possibly Cam-pylobacter infections are more likely to be severe, recurrent, or per-sistent in such patients. Furthermore, extraintestinal disease caused by Salmonella and L. monocytogenes infection are more likely to be reported among HIV-infected persons than in the general population.189,190

Special attention should be paid to immigrant and refugee popula-tions in the United States, as certain customs and rituals may involve consumption of raw or undercooked food, and language barriers may prevent effective communication of guidelines for proper handling, storage, and cooking of such foods. Therefore, these groups may be more susceptible to certain foodborne illnesses.

SEASONALITY

The time of year may also provide a clue to the cause of a foodborne outbreak. Illnesses caused by the bacterial pathogens S. aureus, Salmo-nella, Shigella, and C. jejuni are most common during the summer months. Illnesses caused by C. perfringens occur throughout the year but least often during the summer months. Shellfish-associated Vibrio infections are largely limited to late summer and early fall and are closely related to the temperature of the water in the oyster beds.191 Y. enterocolitica is typically a winter infection, often occurring after winter holidays at which pork chitterlings are served.42 Although possible year-round, winter is generally the season of peak norovirus activity in closed settings, which can provide additional opportunity for foodborne contamination.192

In general, chemical food poisoning occurs throughout the year. Exceptions are PSP, which often occurs in association with a red tide87 and is most common in the summer and fall; ciguatera, which is most common in the spring and summer in Florida193; and mushroom poisoning, which is most common in the spring, late summer, and fall.

GEOGRAPHIC LOCATION

The geographic setting may also provide a clue to the cause of food-borne disease. E. coli O157:H7 infections are more common in the northern tier of states bordering Canada, for unexplained reasons.49 Salmonella serotype Enteritidis infections were most common in the Northeast during the 1980s but then increased in frequency in the rest of the country.148 V. parahaemolyticus outbreaks are most frequently reported from coastal states.194,195

Cases of V. cholerae O1 and non-O1 infection have been most often reported from the Gulf Coast of the United States.165 Type A botulism

Food-Specific Attack Rates

No. of People Eating Food

No. of People Not Eating Food

Food Total Ill Percent Ill Total Ill Percent Ill

Meat loaf 100 88 88* 10 2 20*

Gravy 80 80 100† 30 10 33†

Potatoes 95 78 82 15 12 80

Salad 90 74 82 20 16 80

Water 70 58 82 40 32 80

Stratified Analysis

No. of People Eating Meat Loaf

No. of People Not Eating Meat Loaf

Total Ill Percent Ill Total Ill Percent Ill

No. of people eating gravy 75 67 89† 5 1 20*

No. of people* not eating gravy

25 21 84† 5 1 20

*P < .05 (Fisher’s exact test).†P < .05 (chi-square analysis).

TABLE 99-8

Example of Use of Food-Specific Attack Rates and Stratified Analysis to Identify Food Vehicle in a Foodborne Outbreak

99 Foodborne Disease 1421

be collected from patients not already treated with antimicrobials and should be transported under refrigeration to the laboratory in trans-port medium Cary-Blair or another suitable medium. They should be frozen if they cannot be plated within 48 hours. For optimal viral diagnosis, liquid stools should be collected early in the illness and transported under refrigeration without freezing. Parasitic diagnosis depends on collection of a stool sample and its transport in specialized parasitic transport media. Information on the collection of specimens for diagnosis and investigation of foodborne outbreaks is available on the Internet at http://www.cdc.gov/foodborneoutbreaks/guide_sc.htm.

To confirm the etiologic agent in outbreaks, specimens should be collected and tested from multiple ill individuals involved in the out-break. Foods may also be collected and tested to confirm the etiology and food vehicle. Many of the tests used for outbreak identification and confirmation are available only in specialized public health or food microbiology laboratories.

Although noroviruses are a common cause of foodborne disease, most clinical laboratories are unable to test specimens for these viruses. However, all state public health laboratories can make the diagnosis in the outbreak setting. The current test for noroviruses uses reverse transcription polymerase chain reaction (RT-PCR).39 RT-PCR has led to increased numbers of infections identified and enhanced outbreak detection. Many public health laboratories can also perform genetic sequencing of PCR products to identify the specific norovirus strain involved in the outbreak and potentially link multiple cases and envi-ronmental sources. CaliciNet, a surveillance system currently under development, will link norovirus RNA sequence data from public health laboratories to facilitate identification of multistate outbreaks and emergence of new epidemic strains.

The identification, investigation, and confirmation of foodborne outbreaks of bacterial etiology have been aided greatly by the establish-

Other outbreaks are the result of a food that was contaminated before it was distributed to multiple restaurants, grocery stores, and kitchens, so that cases may be dispersed across a broad geographic area. Such a cluster of presumably related cases can be identified by subtype-based surveillance, such as Salmonella serotype surveillance and PulseNet.199 Once such a cluster is identified, hypothesis-generating interviews may suggest that some foods are more often consumed by case-patients than is expected. Once a specific food exposure is sus-pected, systematic interviews of a group of ill persons and a group of comparable healthy people may provide strong statistical evidence associating illness with a food vehicle.

Once a food vehicle for the infections is identified, the investigation turns to the question of how contamination is likely to have occurred. Steps of food preparation, holding temperatures, and hygienic circum-stances in the kitchen are assessed. Detailed epidemiologic investiga-tion into the sources of food ingredients may lead to assessments of the originating farm or processing plant. These assessments may result in changes in industry practices to prevent future illnesses.

Laboratory DiagnosisAppropriate specimens for laboratory confirmation vary with the etio-logic agents but include feces, vomitus, serum, plasma, and blood (Table 99-9). In addition, specimens from leftover food, the food preparation environment, and food handlers may be examined. The laboratory should be alerted to suspected causes so that special tech-niques can be used for identification of C. perfringens, vibrios, C. jejuni, E. coli O157:H7, Cyclospora, and Y. enterocolitica and so that organisms that may appear similar to the normal flora (e.g., other E. coli, B. cereus) are not overlooked.

Careful specimen collection and transport are critical to successful diagnosis.200 Rectal or stool swabs for bacteriologic diagnosis should

Patient Food Handler Environment

Stools Vomitus Urine Blood Stools Nose Hands FoodFood-Preparation

Environment

BacterialSalmonella C — C C C — — C,P C,P

Staphylococcus aureus C C,P,T — — — C C C,P,T —

Campylobacter jejuni C — — — C — — C,P C,P

Clostridium botulinum C,T C,T T — — — — C,T —

Clostridium perfringens C,T — — — — — — C,P,T —

Shigella C,P — — — C,P — — C,P C,P

Vibrio parahaemolyticus C — — — — — — C C

Bacillus cereus C C,P — — — — — C,P,T —

Yersinia enterocolitica C — — S C — — C C

Vibrio cholerae O1 and non-O1 C — — S C — — C C

Shiga toxin–producing Escherichia coli C,T,P — C,T,P S C,T,P — — C,T,P C,T,P

ViralNorovirus I,P — — S I,P — — P —

ParasiticCryptosporidium O — — — O — — O —

Cyclospora O — — — O — — O —

Giardia O — — — O — — — —

Trichinella — — — S — — — O,P —

ChemicalCiguatera — — — — — — — T —

Histamine fish poisoning (scombroid) — — — — — — — T —

Mushroom T T T T — — — T —

Heavy metals — — — — — — — T —

Monosodium-l-glutamate — — — — — — — T —

Paralytic shellfish poisoning — — — — — — — T —

Neurotoxic shellfish poisoning — — — — — — — T —

C, culture; I, immune electron microscopy; O, other; P, polymerase chain reaction probe; S, serology; T, toxin testing.

TABLE 99-9 Appropriate Laboratory Specimens for Documenting the Cause of a Foodborne Outbreak

1422 PART II Major Clinical Syndromes

and detection of Shiga toxin. Infection with other STEC can be diag-nosed by demonstration of Shiga toxin by enzyme immunoassay (EIA) or Shiga toxin–genes in broth or plate cultures of a stool specimen with subsequent isolation of the organism by culture.209 Isolates of E. coli O157 or Shiga toxin positive broth cultures should be forwarded to the jurisdiction public health laboratory for full characterization and PFGE subtyping.

In the outbreak setting, ETEC can be identified by detecting heat-labile (LT) and heat-stable (ST) toxins in stool using a commercial latex agglutination assay for LT and ELISA for ST.210 STEC, ETEC, enteroinvasive, and enteropathogenic E. coli may be identified in the stool of ill people or foods by gene detection assays (gene probe or PCR assays).210 For outbreaks caused by diarrheagenic E. coli or for well-characterized outbreaks with no identifiable etiologic agent, arrangements can be made through state health departments to send E. coli isolates to the CDC for virulence testing and serotyping.

Botulism outbreaks may be confirmed by the demonstration of botulinum toxin in the serum or stool of ill people or in incriminated food by the mouse neutralization test, or by the isolation of C. botuli-num from the feces of ill people or from the incriminated food.211 Laboratory confirmation by testing of clinical specimens can be obtained in about 70% to 75% of the cases of botulism.212

Laboratory detection of parasitic pathogens typically depends on visualization of characteristic forms in the feces or immunoassays. Alternatively, testing for Trichinella infection involves collection of serum specimens for testing via ELISA, or less frequently, obtaining a muscle biopsy specimen for diagnosis via direct microscopic examina-tion. The enteric parasites (Cyclospora, Cryptosporidium, Giardia, and E. histolytica) are identified after specialized concentration and stain-ing methods.213,214 Toxoplasmosis is typically diagnosed by serologic testing. Trichinellosis is identified by serologic testing and muscle biopsy. Additional information concerning detection and identifica-tion of Cyclospora and other parasites can be found at http://www.dpd.cdc.gov/dpdx.

Outbreaks caused by heavy metals or chemicals, such as pesticides, may be documented by demonstration of the metallic ion or chemical in the incriminated food. Chemicals and their metabolic breakdown products may be detected in urine specimens from ill persons collected within 48 hours of exposure, as well as in the first vomitus after expo-sure. Histamine fish poisoning may be confirmed by demonstration of histamine in the fish; concentrations of 100 mg in 100 g of fish flesh correlates with toxicity. The diagnosis of ciguatera is usually based on the clinical picture. However, ciguatera outbreaks may be documented by demonstration of ciguatoxin in the incriminated fish using ELISA techniques.215 Shellfish poisoning may be confirmed either by demon-stration of the toxin in mollusks by the mouse bioassay technique or by finding elevated numbers of the responsible dinoflagellate in the water from which the mollusks were harvested. Outbreaks of Chinese restaurant syndrome may be confirmed by demonstration of elevated monosodium l-glutamate levels in the food. Mushroom poisoning may be confirmed either by the identification of the responsible toxin in gastric contents, blood, urine, or fecal specimens by thin-layer chro-matography or radioimmunoassay (RIA) or by the identification of the mushroom by a mycologist.

About half of the reported foodborne disease outbreaks in the United States are of unknown cause. In some cases, appropriate diag-nostic procedures are not conducted. In others, diagnostic specimens are not collected in a timely manner or not transported properly. Many of these outbreaks may be due to typical agents.216 In still others, no agent is identified despite testing, raising the possibility that etiologic agents not routinely tested for are responsible; possibilities include ETEC, enteroaggregative E. coli, Plesiomonas shigelloides, rotaviruses, and norovirus. Although enterococci and gram-negative rods (Aeromo-nas hydrophila, Klebsiella, Enterobacter, Proteus, Citrobacter, and Pseu-domonas) have been reported as causes of foodborne outbreaks on rare occasions, their role has not been well documented, and they may be present in foods without causing illness. Because these organisms may be part of the normal fecal flora, documentation of their presence in

ment of standardized pulsed-field gel electrophoresis (PFGE) methods used by public health laboratories in the United States and Canada in a molecular subtyping network called PulseNet.199 Pathogens subtyped by PFGE include Shiga toxin–producing E. coli (e.g., E. coli O157:H7), Salmonella, Shigella, L. monocytogenes, V. cholerae and V. parahaemo-lyticus, and Campylobacter. Standard PFGE methods are being devel-oped for other pathogens.199 PulseNet is growing internationally, which will enable better identification of outbreaks of international scale. Additional information concerning PulseNet is available at http://www.cdc.gov/pulsenet and http://www.pulsenetinternational.org.

Outbreaks of staphylococcal food poisoning may be confirmed by the isolation of S. aureus of the same PFGE pattern from vomitus or feces of two or more ill people. The detection of enterotoxin or entero-toxin genes by PCR, or the isolation of greater than 105 organisms per gram in epidemiologically implicated food is also confirmatory. The demonstration of S. aureus enterotoxin may be accomplished by reverse passive latex agglutination (RPLA) or enzyme-linked immu-nosorbent assay (ELISA), which are available in commercial kits.200

B. cereus outbreaks may be documented by isolating organisms from the feces of two or more ill people who shared the same meal or by isolating 105 or more B. cereus organisms per gram of incriminated food. Multilocus sequence typing, if available, may be of value in confirming that isolates were derived from a common source, as 14% of healthy adults have been reported to have transient gastrointestinal colonization with B. cereus.201 Plasmid analysis may also be useful.202 Although insensitive, commercial immunoassays are available for two of the three diarrheagenic enterotoxins of B. cereus, while a qualitative cell cytotoxicity assay has been effective in screening for the presence of cereulide, the emetic toxin in B. cereus.18,203 Some laboratories use PCR for the four toxin genes to establish genetic toxin types of organisms.

The laboratory confirmation of C. perfringens outbreaks is more difficult. Because both heat-sensitive and heat-resistant strains of C. perfringens type A have been implicated as causes of food poisoning, selective isolation procedures involving heat treatment of food and fecal specimens should not be used. Because C. perfringens organisms are part of the normal flora in many people, the number of organisms should be greater than 106 per gram of stool in two or more ill people to confirm C. perfringens as the etiologic agent in an outbreak. Con-firmation may also be attained by the demonstration of the entero-toxin in the stool of two or more ill people or isolation of greater than 105 organisms per gram of epidemiologically implicated food.204 Dem-onstration of C. perfringens enterotoxin in stools of ill people and not in those of control subjects is possible with ELISA or latex agglutina-tion.205-207 PFGE may also be used to subtype organisms and confirm an outbreak.

E. coli O157:H7, Salmonella, Shigella, C. jejuni, V. cholerae, V. para-haemolyticus, and Y. enterocolitica outbreaks may be detected by isola-tion of the organisms from the feces of ill people. Beyond serotyping, PFGE is increasingly used as a means of outbreak detection especially for E. coli O157:H7, Salmonella, Shigella, and Listeria. PFGE is usually done by public health laboratories and not clinical laboratories. Strains of V. parahaemolyticus isolated from patients’ stool samples may produce hemolysins such as thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH) that are detected by PCR. Isola-tion, serotyping, and PFGE of Salmonella, Shigella, C. jejuni, Vibrio spp., and Y. enterocolitica from the incriminated food may also be confirmatory. Molecular characterization of V. cholerae O1 with PFGE may help to define the geographic origins of the infecting organism.208 Serologic testing of acute and convalescent sera may be helpful in confirming the diagnosis of patients in outbreaks of cholera, typhoid fever, and Shiga toxin–producing E. coli (STEC), but it currently plays no important role in the investigation of nontyphoid Salmonella, Shigella, C. jejuni/coli, and V. parahaemolyticus outbreaks.

Infection with E. coli O157:H7 can be diagnosed by isolating sorbi-tol-negative E. coli from stools of ill persons on sorbitol-MacConkey medium and confirming the serotype or by confirming the serotype

99 Foodborne Disease 1423

approval of these agents for use in poultry; such infections may be unaffected with fluoroquinolone treatment. Erythromycin eradicates carriage of susceptible C. jejuni and may shorten the duration of illness if given early in the disease. The treatment of choice for Cyclospora infection is trimethoprim-sulfamethoxazole.217 An individual with Trichinella infection may be treated with albendazole and supportive care, although once larvae encapsulate in the muscle during the late stages of infection, the drug will no longer be very effective.72,218 The role of antimicrobial agents in the management of food poisoning caused by V. parahaemolyticus; by enterotoxigenic, Shiga toxin–producing, or invasive E. coli; or by Y. enterocolitica is unsettled but probably minimal.217 Patients with E. coli O157-H7 infection should be hydrated well and evaluated expectantly for the development of hemolytic uremic syndrome, which often requires transfusion, renal dialysis, and prolonged intensive care.219 Antimicrobial agents are of no value in the management of staphylococcal, C. perfringens, or B. cereus food poisoning.

Multidrug-resistant (MDR) Salmonella has been increasing in the United States and has been associated with increased severity of disease.220 Highly resistant strains can complicate treatment for any infection, because an inapparent infection can be changed to severe salmonellosis by exposure to an antimicrobial agent to which it is resistant.221 An MDR strain of Salmonella serotype Typhimurium definitive type 104 (DT 104) has emerged globally and particularly in Europe and the United States.222 In one study, more than 90% of all DT 104 isolates were resistant to ampicillin, chloramphenicol, strep-tomycin, sulfonamides, and tetracycline (MDR-ACSSuT), and 30% of strains also showed resistance to trimethoprim and ciprofloxacin.223 From 2003 to 2005, 24% of all Salmonella Typhimurium tested in the National Antimicrobial Resistance Monitoring System (NARMS) for Enteric Bacteria were found to be MDR-ACSSuT.224

More recently, a multidrug-resistant strain of Salmonella serotype Newport that is associated with eating raw or undercooked ground beef emerged in the United States in the early 2000s.225 This strain is resistant to amoxicillin/clavulanate, ampicillin, cefoxitin, cephalothin, chloramphenicol, streptomycin, sulfonamides, and tetracycline and exhibits decreased susceptibility to ceftriaxone (MDR-AmpC). From 2003 to 2005, 16% of all Salmonella Newport tested in NARMS were found to be MDR-AmpC and as much as 38% were MDR-AmpC in the Northeast.224 The emergence of multidrug resistant Salmonella was probably related to agricultural uses of antimicrobials. This highlights the interconnected pool of pathogens between animal reservoirs and people and underlines the need for prudent use of antimicrobials in both sectors.

Patients with botulism present several additional therapeutic prob-lems, which are discussed in Chapter 245. Medical care providers who suspect botulism should immediately call their state health depart-ment’s emergency 24-hour telephone number. The state health depart-ment will contact the CDC to arrange for a clinical consultation by telephone and, if indicated, release of botulinum antitoxin. The CDC’s 24-hour telephone number for state health department officials to report suspected botulism cases, obtain clinical consultation on botu-lism cases, and request botulinum antitoxin release is 770-488-7100.

Patients with PSP and some patients with ciguatera may require ventilatory support, usually for only a few days. Although reports suggest that intravenous mannitol may ameliorate the acute neuro-logic symptoms of severe ciguatera, a double-blind randomized trial showed no benefit.226 Case reports indicate that tocainide may improve persistent dysesthesias.227 Therapy is otherwise supportive; no anti-toxins are available. If not contraindicated by the presence of ileus, enemas or cathartics may be administered in an effort to remove unabsorbed toxin from the intestinal tract. Because of the severe dys-esthesias associated with ciguatera, analgesics may also be required. Symptoms of histamine fish poisoning may be relieved by antihista-mines. In severe cases with bronchospasm, epinephrine or aminophyl-line may be required.

Therapy for short-incubation types of mushroom poisoning is pri-marily supportive. Patients who have ingested species containing phar-

ill people and their absence from well people is required to confirm their role in foodborne outbreaks.

TherapySupportive measures are the mainstay of therapy in most cases of food poisoning. Most diarrheal diseases can be managed with oral rehydra-tion.217 Antiemetics and antiperistaltic agents offer symptomatic relief, although the latter are contraindicated in patients with high fever, bloody diarrhea, or fecal leukocytes indicative of an invasive infection. Fatalities can still occur (Table 99-10). The most lethal foodborne diseases are botulism, listeriosis (affecting neonates and immunocom-promised persons), V. vulnificus infection (in those with impaired hepatic function), paralytic shellfish poisoning, and long-incubation mushroom poisoning. With other pathogens, fatalities may occur in infants or the elderly, or in persons with compromised host defenses; because the dose is overwhelming; or because the pathogen is resistant to treatment.

In any diarrheal illness, gastrointestinal fluid losses should be replaced either orally or parenterally. Antimicrobial agents may be used in the treatment of shigellosis and cholera and are lifesaving in invasive salmonellosis and typhoid fever, but they should be avoided in uncomplicated gastrointestinal infection caused by nontyphoid sal-monellae.217 Tetracycline shortens both the duration of clinical cholera and the excretion of V. cholerae O1. Early treatment of Campylobacter infection with fluoroquinolones can shorten the duration of illness. Fluoroquinolone-resistant Campylobacter infections emerged after the

Disease or Agent Percent Hospitalized Percent Died

BacterialBacillus cereus 0.6 0.00

Botulism, foodborne 80.0 7.69

Brucella spp. 55.0 5.00

Campylobacter spp. 10.2 0.10

Clostridium perfringens 0.3 0.05

Escherichia coli O157-H7 29.5 0.83

E. coli, non-O157 STEC 29.5 0.83

E. coli, enterotoxigenic 0.5 0.01

E. coli, other diarrheogenic 0.5 0.01

Listeria monocytogenes 92.2 20.00

Salmonella serotype Typhi 75.0 0.40

Salmonella, nontyphoidal 22.1 0.78

Shigella spp. 13.9 0.16

Staphylococcus food poisoning 18.0 0.02

Streptococcus, foodborne 13.3 0.00

Vibrio cholerae, toxigenic 34.0 0.60

Vibrio vulnificus 91.0 39.00

Other vibrios 12.6 2.50

Yersinia enterocolitica 24.2 0.05

ParasiticCryptosporidium parvum 15.0 0.50

Cyclospora cayetanensis 2.0 0.05

Giardia lamblia n/a n/a

Toxoplasma gondii n/a n/a

Trichinella spiralis 8.1 0.30

ViralNorwalk-like viruses n/a n/a

Rotavirus n/a n/a

Astrovirus n/a n/a

Hepatitis A virus 13.0 0.30

TABLE 99-10

Estimated Frequency of Hospitalizations and Deaths for Known Foodborne Pathogens, United States, 1997

Modified from Mead PS, Slutsker L, Dietz V, et al. Food-related illness and death in the United States. Emerg Infect Dis. 1999;5:607-624.

STEC, Shiga toxin–producing E. coli.

1424 PART II Major Clinical Syndromes

developed to ensure the safety of foods used in the space program. This approach requires a food producer to identify points where the risk of contamination can be controlled, and to use production systems that eliminate the hazards. HACCP programs focus on preventing food contamination rather than relying on a final inspection step to detect it after it has occurred. Milk pasteurization and commercial canning practices are long-established technologies that make foods safe. Strate-gies being applied now include provision of microbiologically safe food and water to animals, environmental microbiologic monitoring on the farm or in the processing plant to identify and control pathogens in the environment prior to food contamination, acid rinses and steam scalding of carcasses, and gamma, electron-beam, and X-irradiation of meats and some types of produce.230

New efforts also are being focused on identification of sites and sources of contamination of fresh produce harvested in the United States, Mexico, and Latin America. There are many points where produce can become contaminated during growth and harvesting, processing and washing, transport, and final processing. The surface of plants and fruits may be contaminated by soil, manure, or feces of animals or agricultural workers. Guidelines for produce growers and processors are available to minimize the microbial hazards associated with sources of contamination through the U.S. Food and Drug Administration (FDA) website at http://www.cfsan.fda.gov/~dms/prodguid.html. It is unknown whether contamination is more likely to occur when produce is grown outside the United States; however, water quality in the developing world is a particular concern. Unclean water supplies can lead to contamination because water is used to irrigate and wash produce and to make the ice that keeps produce cool during trucking. The extra handling required to prepare salads and salad bars, and the time delay between preparation and consumption associated with salad bars, may increase the potential for produce to cause illness. Pasteurizing juice and implementing HACCP programs are helpful to decrease the risk associated with consumption of produce.231

Much foodborne disease can be prevented if food is selected, pre-pared, and stored properly. In large kitchens and in homes, careful cooking and storage are necessary to kill pathogens and to prevent their growth when food is recontaminated after cooking. Because they serve high-risk populations, the kitchens of hospitals and nursing homes must pay particular attention to food safety. For example, routine use of pasteurized eggs instead of shell eggs prevents many nosocomial outbreaks of foodborne salmonellosis. A common error is storage of food at inappropriate temperatures. Bacterial pathogens grow in food at temperatures ranging from 40° F to 140° F; growth may be prevented if cold food is adequately refrigerated and hot food is held at temperatures higher than 140° F before serving.

The usual source of contamination for Salmonella, Campylobacter, C. perfringens, vibrios, Y. enterocolitica, and other zoonoses is raw food of animal origin, not infected food handlers. However, poor personal hygiene by food handlers frequently contributes to norovirus, Staphy-lococcus, Shigella, and hepatitis A outbreaks. Although thorough cooking of food just before consumption eliminates the risk of many illnesses, protection against staphylococcal food poisoning is not pro-vided because the staphylococcal enterotoxins are heat stable, and moreover, many foods, such as fresh produce, are not cooked at all. Inadequate heat processing of home-canned foods can lead to botu-lism, and the use of contaminated equipment such as knives and meat slicers can transmit pathogens.232,233 Particular care in handling and cooking of raw poultry, beef, pork, shellfish, and eggs is important to prevent many foodborne diseases. Avoiding consumption of raw milk is important to prevent Salmonella, C. jejuni, E. coli O157, and other infections.162,234

Food-handling errors resulting in chemical intoxication are differ-ent from those leading to bacterial outbreaks. Heavy metal poisoning occurs when acidic beverages are stored in defective metallic contain-ers or when valves in vending machines malfunction. Ciguatera and shellfish poisoning occur when fish or shellfish are obtained from unsafe sources. Items contaminated with these toxins appear and taste

macologically active amounts of muscarine and who manifest evidence of parasympathetic hyperactivity may be treated with atropine.114 Therapy for the long-incubation illness includes cathartics and enemas to remove unabsorbed toxin, and a number of specific and supportive measures.115 Because hypoglycemia often occurs, intravenous glucose may be required. Liver failure may ultimately require transplantation. α-Lipoic acid (thioctic acid) is an experimental drug that was report-edly effective in case reports115; the drug may be obtained from Burton M. Berkson, M.D., Ph.D., in Las Cruces, New Mexico (575-524-3720 or 575-521-1609). Pyridoxine is indicated in the management of patients poisoned with Gyromitra species.

Therapy for acute heavy metal poisoning is supportive. Emesis should be induced if it does not occur spontaneously. Antiemetics are contraindicated, because retention of the toxic ions in the gut and subsequent systemic absorption may result. In severe cases with sys-temic manifestations of heavy metal toxicity, use of specific antidotes may be considered, but that is rarely necessary in these outbreaks.

SurveillancePublic health authorities monitor trends in specific diseases through reports of diagnosed cases provided by clinicians and microbiologists. State public health laws determine reportable conditions for each state and who is responsible for reporting. In turn, state public health offi-cials voluntarily submit reports of nationally notifiable diseases to the CDC for the compilation of nationwide surveillance data. Disease conditions reportable by law may vary from one state to another; the information about reportable conditions is available through state and local health departments. Disease and case definitions for nationally notifiable infectious diseases are available at http://www.cdc.gov/epo/dphsi/phs/infdis.htm.

Reports from physicians, nurses, laboratories, and other potential reporting groups are the starting point for public health activities that can prevent further cases from occurring—activities such as education, identification of potentially hazardous events, and epidemiologic investigation. Increasingly, public health notification occurs most rapidly through the clinical laboratory. For Salmonella, Shigella, Shiga toxin–producing E. coli, and Listeria, the bacterial isolate itself should be referred to a public health laboratory for serotyping and molecular subtyping. All state public health laboratories participate in the National Network for Molecular Subtyping, called PulseNet.228 Although knowing the specific serotype is rarely of importance in the management of a single case, it is fundamental to the recognition of outbreaks and in monitoring the success of control efforts. This means that ordering the diagnostic tests needed to determine the nature of the illness is of benefit not only to the patient, but to society as a whole. A single case of illness reported from a daycare center or family gather-ing not infrequently leads to discovery of an entire outbreak. Out-breaks can be apparent even though the specific diagnosis is not in hand, and investigation can succeed in identifying and controlling a source even without knowing the cause. This means that the astute clinician or microbiologist who calls the public health department epidemiologist to discuss a possible outbreak plays an important role in the control of foodborne and other diseases.

PreventionPrevention of foodborne disease depends on careful handling of raw products and finished foods all the way from the farm to the table, and on technologies that reduce or eliminate contamination in food.229 Raw animal products, including meat, milk, eggs, and shellfish, are common sources of contamination leading to foodborne diseases. Contamina-tion of raw animal products can be reduced by better animal produc-tion and slaughter practices. Monitoring of the safety of industrial food processing is increasingly important as the nation’s food supply becomes more centralized and preprocessed for the convenience of the consumer. A systematic approach to risk reduction, called the Hazard Analysis Critical Control Point (HACCP) program, was originally

99 Foodborne Disease 1425

General Recommendations• Thoroughly cook raw food from animal sources, such as beef, pork, or

poultry.• Wash raw vegetables thoroughly before eating.• Keep uncooked meats separate from vegetables, cooked foods, and

ready-to-eat foods.• Avoid unpasteurized (raw) milk or foods made from unpasteurized milk.• Wash hands, knives, and cutting boards after handling uncooked foods.

Recommendations for Persons at High Risk, Such as Pregnant Women and People with Weakened Immune Systems, in Addition to the Recommendations Listed Above• Do not eat hot dogs, luncheon meats, or deli meats, unless they are reheated

until steaming hot.• Avoid getting fluid from hot-dog packages on other foods, utensils, and food

preparation surfaces, and wash hands after handling hot dogs, luncheon meats, and deli meats.

• Do not eat soft cheeses such as feta, Brie, and Camembert, blue-veined cheeses, and Mexican-style cheeses such as queso blanco, queso fesco, and Panela, unless they have labels that clearly state they are made from pasteurized milk.

• Do not eat refrigerated pâtés or meat spreads. Canned or shelf-stable pâtés and meat spreads may be eaten.

• Do not eat refrigerated smoked seafood, unless it is contained in a cooked dish, such as a casserole. Refrigerated smoked seafood, such as salmon, trout, whitefish, cod, tuna, and mackerel, is most often labeled as “nova-style,” “lox,” “kippered,” “smoked,” or “jerky.” The fish is found in the refrigerator section or sold at deli counters of grocery stores and delicatessens. Canned or shelf-stable smoked seafood may be eaten.

TABLE 99-11

Recommendations from the Centers for Disease Control and Prevention for the Prevention of Listeriosis

normal; in addition, cooking of these items does not provide protec-tion, because the toxins are heat stable.

The role of the clinician goes beyond that of diagnosis and treatment to prevention. This means warning high-risk patients (e.g., those infected with HIV, infants and older adults, and those with chronic medical conditions) of the hazards of raw oysters, raw eggs, and unpas-teurized milk.189 Although listeriosis is a rare disease, the infection is often deadly. Pregnant women, persons at the extremes of age, and immunocompromised individuals should be informed about their risk for listeriosis and may choose to avoid relatively high-risk foods (Table 99-11).

Clinicians and microbiologists have an important role in the detec-tion of outbreaks, in particular in obtaining appropriate diagnostic tests for foodborne pathogens and reporting them to public health authorities. Public health surveillance of foodborne infections and outbreaks is important for appreciating the magnitude and complexity of the problem and guiding targeted prevention efforts. Reporting is essential if investigations are to be conducted to identify the source of the outbreak so that it can be corrected. Prompt reporting may also lead to the prevention of additional cases; there are well-documented outbreaks of botulism,235 salmonellosis,236 and E. coli O157:H7237 in which recognition and reporting of the initial illness could have pre-vented many subsequent cases. Diagnosing and reporting of illnesses with the potential for intrafamilial spread, or for spread within institu-tions such as daycare centers (e.g., shigellosis, E. coli O157:H7 infec-tion), can prevent secondary transmission. Reporting has been critical to stimulate concerted action to control major hazards, such as Salmo-nella serotype Enteritidis in eggs, or E. coli O157:H7 in beef. As we embark on the 21st century, clinicians, laboratory workers, public health authorities, food safety officials, and members of industry can all play critical roles in decreasing the burden of foodborne illnesses.

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