#98623: Foodborne Disease

Bacterial contamination of food can occur at any of a number of stages along the farm-to-table continuum: during growing, harvesting, processing, storing, shipping, or final preparation (in a restaurant or home). Most available information on the incidence of bacterial foodborne disease is derived from FoodNet surveillance of disease caused by the eight common foodborne bacterial pathogens [39]:

Preliminary data indicate that in 2019, these bacteria were the cause of 25,111 cases of foodborne infections reported in FoodNet's 10 states (Table 2) [2]. One of the food safety objectives in Healthy People 2030 is to reduce the incidences of four bacterial infections—Salmonella, Campylobacter, STEC O157, and Listeria [2,70]. In 2019, compared with the previous three years, the incidence of infections either increased for some pathogens (e.g., Campylobacter, Cyclospora, STEC, Vibrio, Yersinia) or remained unchanged (e.g., Listeria, Salmonella, Shigella) [2]. Infections caused by Salmonella serotypes Typhimurium and Heidelberg have decreased considerably over the past 10 years, in part due to the widespread practice of vaccinating chickens against Typhimurium. Despite these decreases, the overall incidence of Salmonella has not substantially declined in the past 15 years, as infections with other Salmonella serotypes (i.e., Javiana, Newport, Infantis) have increased [2].

As discussed, while bacterial contamination of food can occur at several points, viral contamination usually occurs during food handling. Viruses may also be transmitted to humans through mollusks from contaminated waters [44,68]. Produce can be a vehicle if exposed to contaminated water. The pathogenicity of viruses is enhanced by their capacity to withstand dehydration, low pH, and other adverse, environmental conditions [68]. They endure on human hands, in fresh and dried fecal matter, in water, and on nonbiologic surfaces (fomites) such as kitchen counters and carpets [71].

More than 100 types of enteric viruses cause food-related illness, but in the United States, three types of viruses are most common [71]:

Noroviruses and hepatitis A virus are the viruses most often transmitted through food [68]. Noroviruses are the most common cause of outbreaks of nonbacterial gastroenteritis; they accounted for 36% of outbreaks in 2016 [3].

Parasitic infection can be spread through food or water but is more commonly transmitted through contaminated water [72]. Parasitic protozoa do not multiply in foods, but they are able to survive in or on moist foods for months in a cool, damp environment [72]. Four parasites present the greatest risk of foodborne illness: Cryptosporidium,Cyclospora,Giardia, and Toxoplasma gondii [72]. Infections caused by Cryptosporidium and Cyclospora are monitored through FoodNet.

The number of confirmed bacterial foodborne outbreaks fluctuates from year to year, showing an increase in the early 2000s followed by a decrease according to the most recent full report for 2017 [3]. In 2005, 188 outbreaks (4,348 illnesses) were reported. The number increased to 257 (6,410 illnesses) in 2007, then decreased to 841 outbreaks (14,481 illnesses) in 2017 (Table 3) [44,3]. Bacteria were the confirmed cause of 20 deaths in 2017 [3].

FoodNet surveillance data show that the highest incidence of bacterial foodborne disease is found among children younger than 5 years of age, followed by children 5 to 9 years of age (Table 4) [76]. The most common causative pathogens in these two age groups are Salmonella,Campylobacter, and Shigella [76,77]. Only Vibrio and Listeria infections occur more frequently in older individuals than in children. Among individuals 60 years of age or older, Salmonella and Campylobacter are the leading causes of bacterial foodborne infection [76].

Few studies have been conducted to evaluate differences in food-related illness according to race or ethnicity, but the available reports suggest that the rates of some bacterial infections are higher among black, Hispanic, and Asian populations than among the white population [79,80,81]. The infections occurring at higher rates are associated with food consumption habits specific to certain populations. For example, outbreaks of Yersinia have been associated with chitterlings (chitlins), a common food item in the black community, particularly in the South, and outbreaks of Listeria and Salmonella have been linked to Mexican-style cheeses and carnitas, respectively, in the Hispanic population [46,80,82]. These disparities call attention to the need for education on foodborne illnesses that is targeted to distinctive needs of specific populations.

The incidence of foodborne disease caused by bacterial pathogens also varies substantially according to geographic location. For example, the incidence of Campylobacter is more than three times higher in California (29.37 per 100,000) than in Maryland (8.34 per 100,000), while the incidence of Shigella ranges from 0.77 (per 100,000) in New York to 6.71 (per 100,000) in Georgia [76]. A survey of testing practices among laboratories in the FoodNet areas indicated that the regional differences in these incidences are not attributable to variations in stool culture practices [83].

Viral pathogens, principally norovirus, are a leading cause of foodborne gastroenteritis outbreaks investigated since 2000. In 2016, a viral etiology was identified for 326 reported foodborne outbreaks affecting 6,406 persons [3]. In all but four of these outbreaks, the causative agent was a norovirus; hepatitis A accounted for 3 of the outbreaks [3]. More than two-thirds of outbreaks of norovirus are linked to restaurants [3].

Viral gastroenteritis is the leading cause of food-related illness in the United States [34]. The illness may be caused by a number of viruses, but noroviruses are the leading cause of illness from contaminated food or water [34]. More than 5 million cases of foodborne noroviruses are reported each year [34,84].

Approximately 1,566 cases of hepatitis A infection each year are attributed to a food source [71]. Most individuals 18 years of age or older have lifelong protection against reinfection through immunity [34]. The percentage of adults with hepatitis A immunity increases with age, from 10% for individuals who are 18 to 19 years of age to 65% for individuals older than 50 years of age [34]. In 2016, the incidence of hepatitis A virus was highest in Hawaii (285 cases) and California (229 cases) and lowest in Wyoming (0 cases) [85].

Rotavirus infection is the leading cause of severe acute diarrhea among infants and young children worldwide, but foodborne transmission represents only approximately 1% of cases [71,86]. Prior to the introduction of a rotavirus vaccine in 2006, almost all U.S. children were infected with the virus before 5 years of age [86]. Rotavirus occurs primarily in the winter and spring [86]. In 2017 in California, the CDC examined three rotavirus outbreaks that resulted in mostly mild-to-moderate illness among vaccinated and unvaccinated children and adults. One unvaccinated child died [87].

In the United States, parasites cause far fewer outbreaks or isolated incidences of foodborne infection than either bacteria or viruses. In 2017, a parasite was confirmed as the cause of 11 outbreaks (122 illnesses) [3]. Cryptosporidium is the leading cause of waterborne illness in the United States, and some years has been among the leading foodborne pathogens identified by the FoodNet program [2,186]. The incidence of Cryptosporidium is highest among children younger than 5 years of age and children 5 to 9 years of age and is lowest among individuals 10 to 19 years of age [78]. Although the overall incidence of Cyclospora has been low, preliminary FoodNet data from 2019 reports an increased incidence of 1,209%. This is in part attributed to the increased use of culture-independent diagnostic tests [2]. The highest incidence is among individuals 60 years of age or older [78].

As with bacterial pathogens, the incidence of foodborne infection caused by Cryptosporidium and Cyclospora varies according to geographic location. In 2009, the incidence of Cryptosporidium ranged from 7.36 per 100,000 in New Mexico to 1.26 per 100,000 in Tennessee [76]. The incidence of Cyclospora was highest in Connecticut (0.51 per 100,000), and no cases were reported in California, Colorado, or Oregon [76].

The incidence of infection with Giardia attributable to a food or water source is not clear, but giardiasis is most frequently associated with consumption of contaminated water [34]. In general, the infection is more prevalent among children than adults, which may be related to the potential for immunity after infection [34]. The parasite is believed to affect approximately 22.5% of the U.S. population [34]. From 2005 to 2007, there were approximately 65 cases of foodborne outbreaks associated with Giardia-infected food [34]. Toxoplasma gondii has been found in nearly one-third of the worldwide population [88]. In the United States, the seroprevalence of toxoplasmosis has decreased among U.S.-born individuals (12 to 49 years of age) from 14.1% in 1988–1994 to 9% in 1999–2004 [89,90]. The seroprevalence is higher in women of childbearing age (15 to 44 years of age), with a rate of 11% in 1999–2004 [89]. According to the CDC, Toxoplasma gondii is the second leading cause of foodborne illness-related deaths and hospitalizations in the United States, causing more than 300 deaths and 4,400 hospitalizations each year [34,91]. Toxoplasma gondii also can lead to acute ocular disease, with an estimated 4,800 cases occurring each year [34].

Most foodborne infections result in self-limited illness that resolves within a few days to a week. Severity of illness caused by bacterial foodborne disease varies by etiology, as evidenced by hospitalization rates reported by FoodNet for 2016 (Table 5) [92]. The case-fatality rate also varies by pathogen; mortality rates in 2015 were 12.9% for Listeria, 2.6% for Vibrio, 0.4% for Salmonella, and 0.2% for Campylobacter[93]. Hospitalization and mortality rates are somewhat higher among persons older than 65 years of age, and the hospitalization rate for children younger than 5 years of age ranges from 11.3% for Shigella to 100% for Listeria foodborne infections [93].

According to statistics published in 1999, bacteria accounted for 72% of the deaths associated with foodborne disease; parasites accounted for 21%, and viruses for 7% [36]. In 2016, bacteria accounted for 81% of deaths associated with foodborne disease; parasites accounted for three deaths, and viruses accounted for none [92]. Since 1999, Listeria has been the pathogen most likely to cause death from food-related illness, with 20% to 30% of infections in high-risk individuals being fatal [94,95].

Diarrhea and vomiting can lead to intravascular volume depletion, dehydration, and electrolyte imbalance. Oral rehydration should be started for patients who have mild or moderate fluid losses. An oral rehydration solution should be used rather than a sports drink, which does not replace fluid and sodium losses correctly. Intravenous therapy should be used for severe dehydration and for debilitated patients. Studies have indicated that for children with mild-to-moderate volume depletion caused by gastroenteritis, oral rehydration is as effective as intravenous therapy [115]. For young children (i.e., 5 to 33 months of age), rice-based oral fluid therapy plus recombinant human lactoferrin and lysozyme has been shown to reduce the duration of diarrhea better than reduced-osmolarity oral hydration therapy [116].

The use of antimicrobial therapy should be limited, as antibiotic resistance has increased for many enteric pathogens [21]. Empirical antimicrobial therapy is usually reserved for patients with severe illness. Antibiotics should not be administered to reduce secondary transmission risk.

The decision to treat and selection of antimicrobial therapy should be based on clinical considerations and epidemiologic clues or positive identification of the causative pathogen, such as [21]:

The antimicrobial selection for specific foodborne infections will be discussed in detail later in the course.

Healthcare practitioners should educate the patient or parents about what actions he or she should take to prevent secondary transmission, emphasizing the importance of appropriate hand hygiene, the use of disinfectant cleaner to wash surfaces, and the need to remain out of work, school, or daycare until symptoms have resolved. Many educational resources are available, and efforts should be made to provide resources that are language and culture appropriate.

Salmonella infection, or salmonellosis, is the leading cause of bacterial foodborne disease. According to preliminary FoodNet data for 2019, the incidence was 17.1 per 100,000 [2]. Compared with 2016–2018, the 2019 incidence was significantly lower for Salmonella serotype Typhimurium. While overall the rate of foodborne salmonellosis has not declined in recent years, a decline in the incidence of serotypes Typhimurium and Heidelberg have been observed [2]. Salmonella remains the second most common cause of outbreak-related foodborne illness, accounting for 113 outbreaks (29% of single-pathogen outbreaks) in 2017 [3].

The highest incidence of salmonellosis occurs among children, with a rate of approximately 110.0 cases per 100,000 in children younger than 1 year of age [76]. However, the population affected can vary according to the food source of infection; the 2008 Salmonella (Saintpaul) outbreak caused by contaminated Mexican peppers primarily affected adults 20 to 29 years of age [44]. The incidence of Salmonella infection is highest in the summer and fall [76,123].

Transmission of Salmonella is generally animal-to-human, caused by human ingestion of food that has been exposed to the gastrointestinal systems or fecal matter of animals (e.g., birds, reptiles, mammals) or contact with pet reptiles (especially turtles), baby chicks, and ducklings [69]. Contaminated foods are typically eggs and raw/processed meats [69]. Although modern disinfection practices render eggshell contamination rare, egg yolks may harbor Salmonella from the ovaries of infected hens [124]. In the northeastern United States, one in 10,000 eggs is contaminated [124]. Raw fruits and vegetables (e.g., cantaloupe, tomatoes, alfalfa sprouts) are usually externally contaminated, although Salmonella can infect the inside of a growing fruit or vegetable [69].

The onset of symptoms is usually 1 to 3 days after ingestion of contaminated food [21]. Salmonellosis is characterized by diarrhea, abdominal cramps, vomiting, and nausea that typically lasts 4 to 7 days [21,69]. Some individuals with infection may be asymptomatic, and others may present with colitis, bacteremia (sustained or intermittent), and/or focal infections (e.g., meningitis, osteomyelitis) [69].

Salmonella infection is diagnosed with a routine stool culture and is a nationally notifiable disease [21]. Antimicrobial treatment is avoided in the usual case of gastrointestinal salmonellosis, as this often leads to antimicrobial resistance and prolongs the carrier state. If the patient is at increased risk for the invasive form of the disease (i.e., not isolated to the gastrointestinal tract), antimicrobial agents such as fluoroquinolones or expanded-spectrum cephalosporins are suggested [17]. In addition, ampicillin, gentamicin, and trimethoprim-sulfamethoxazole (TMP-SMX) have been effective [21,69].

The use of fluoroquinolones is not recommended for children if safe and effective alternatives are available; physicians should weigh the benefits of therapy against potential adverse musculoskeletal events, such as tendinitis and tendon rupture [17,69]. In July 2008, the FDA requested the addition of a boxed warning to fluoroquinolone prescribing information emphasizing these risks [125].

CAMPYLOBACTER JEJUNI

Campylobacter jejuni is a spiraled, motile, thermophilic, gram-negative rod considered unique among other foodborne pathogens because of its microaerophilic growth needs (i.e., 5% O₂, 10% CO₂) [69,74]. Campylobacter jejuni are more sensitive to low pH, heat, and arid conditions than other common foodborne pathogens [126]. The infective dose is 400 cells [34].

Campylobacter infection, campylobacteriosis, is the leading cause of infectious foodborne illness in the United States, with an incidence of 19.5 cases per 100,000 each year [2]. Compared with 2016–2018, the incidence of reported Campylobacter foodborne infections increased 13% in 2018 [2]. Most cases of campylobacteriosis are sporadic and not associated with an outbreak. However, in 2017, 23 outbreaks were reported (17 confirmed and 6 suspected), affecting 147 individuals [3]. In 2012, a multistate outbreak of Campylobacter infections resulting in 147 illnesses was associated with ingestion of unpasteurized milk. The common source traced to a single dairy holding a permit to produce unpasteurized milk [127]. In 2016, 7 outbreaks of Campylobacter infection from dairy products resulted in 57 illnesses and 5 hospitalizations [3].

Campylobacter is associated with poultry, livestock, flies on farms, wild and caged animals, and pets [35,128]. Most cases of foodborne Campylobacter infection are caused by the consumption of undercooked poultry or from cross-contamination of other foods by these items. Outbreaks are most often associated with unpasteurized dairy products, poultry, and produce irrigated with contaminated water [35,127].

Symptoms usually occur 2 to 5 days after consumption of contaminated food [21]. The classic symptoms of campylobacteriosis are similar to those associated with acute appendicitis. Symptoms include so-called sticky diarrhea with blood/fecal leukocytes, abdominal pain, fever, nausea, and muscular pain; vomiting is rare [21,69]. Symptoms generally last for 2 to 10 days [21].

Acute Campylobacter infection may cause intestinal hemorrhage, toxic colitis, meningitis, bacteremia, and HUS [69]. HUS is characterized by renal impairment, microangiopathic hemolytic anemia, and thrombocytopenia and most frequently affects children with campylobacteriosis [34,69]. Other potential long-term complications of campylobacteriosis include reactive arthritis (1% to 7%), irritable bowel syndrome (25%), and Guillain-Barré syndrome (0.1%) [69,129,130]. The mortality rate associated with campylobacteriosis is 0.1% [34].

Most clinical laboratories can isolate Campylobacter spp. on request. Treatment is recommended only for severe cases of Campylobacter infection or for individuals who have a compromised immune system. When antimicrobial therapy is warranted, macrolides, such as erythromycin, or fluoroquinolones are the preferred drugs; however, resistance to these agents has increased with the use of antibiotics in chickens (as therapeutic agents or growth promoters) [17,131]. In general, Campylobacter is susceptible to chloramphenicol and clindamycin [131].

According to preliminary data from 2019, Shigella is the fourth leading cause of foodborne illness in the United States, with an incidence of 4.8 per 100,000 [2]. The most prevalent pathogenic species is Shigella sonnei, which has been isolated in 75% to 80% of Shigella infections [133,134,135]. Outbreaks may continue for months in closed populations [136]. The other Shigella spp. isolated in association with outbreaks are Shigella flexneri (18%), Shigella boydii (1%), and Shigella dysenteriae (<1%) [134]. In 2017, Shigella accounted for 4 reported outbreaks, 54 illnesses, and 10 hospitalizations [3].

Typically, only primates harbor Shigella [34,69]. The pathogen is transmitted via the fecal-oral route through person-to-person contact, ingestion of contaminated food/water, and fomite contamination [34,69]. Because incidence rates peak in the late summer, the most common routes of Shigella exposure may differ from Salmonella and Campylobacter [123].

Shigellosis manifests as diarrhea (usually mucoid, possibly bloody), which may be accompanied by abdominal cramps/pain, fever, and tenesmus; symptoms usually occur within 8 to 48 hours after ingestion of the contaminated food and last 4 to 7 days [21,34]. Symptoms vary by Shigella species. For example, Shigella flexneri, Shigella boydii, and Shigella dysenteriae typically present with bloody diarrhea and severe systemic symptoms, whereas Shigella sonnei typically causes watery stools [69].

As with STECs, Shigella dysenteriae type I produces Shiga toxins, which cause HUS [34,69]. However, the development of HUS is delayed with Shigella dysenteriae, with a median of 7 days from the onset of Shigella-induced diarrhea to the development of HUS, compared with the typical 4 days for HUS caused by STEC infections [34,137].

Reactive arthritis will develop in approximately 2% to 7% of individuals with shigellosis, and Reiter syndrome will develop in 3% [74,138]. The mortality rate associated with the infection is less than 1% in the United States [76,139].

Stool samples or rectal swabs should be obtained during the acute phase of the disease and cultured for Shigella [69]. Blood samples should be examined for signs of bacteremia in patients who are severely ill, are malnourished, or have a compromised immune system [69]. Shigella infection is a nationally notifiable disease.

Shigella dysenteriae type I Shiga toxins are often identified with use of enzyme-linked immunosorbent assays [69]. Shigella-induced neutrophilia is typically greater than that caused by STECs; the degree of neutrophilia at the onset of disease may be used to predict the development and potential severity of HUS [139].

Antimicrobial therapy is not advised for most cases of infection with Shigella spp. because of high rates of resistance [34,69]. These resistance rates have been reported to be approximately 78% for ampicillin, 56% for streptomycin, 47% for sulfisoxazole, and 46% for TMP-SMX [134]. In addition, resistance to both ampicillin and TMP-SMX has been found in 38% of cases [134].

For patients with severe disease, most resistant Shigella strains can be treated with azithromycin (oral) or ceftriaxone (intramuscular) [69]. Fluoroquinolones may be effective for adults with suspected shigellosis who have fever, tenesmus, and inflammation [17]. Early and appropriate antimicrobial treatment of Shigella dysenteriae type I infections may prevent HUS [69,74].

In contrast to STECs, enterotoxigenic E. coli adheres to and effaces the small intestine [74]. The infective dose is 108 cells [74].

Epidemiology

Enterotoxigenic E. coli is a major cause of bacteria-related diarrhea in individuals who travel outside the United States, especially to developing countries [133,144]. The infection has become more frequently identified as a cause of foodborne illness in the United States [145].

Contamination and Transmission

Enterotoxigenic E. coli is spread through fecally contaminated food or water. Infected food handlers may also be a source of contamination [74,144].

Clinical Presentation and Disease Course

Symptoms usually occur 1 to 3 days after ingestion of contaminated food or water [21,144]. Symptoms include watery diarrhea for 3 to 7 days, abdominal cramps, nausea, and malaise; low-grade fever is an infrequent symptom [21,69,144]. Manifestation of the infection ranges from minor discomfort to a severe cholera-like syndrome [74].

Diagnostic Testing

Distinguishing enterotoxigenic E. coli from nonpathogenic E. coli is difficult for most clinical laboratories, but enterotoxigenic E. coli can be identified in research laboratories accessed through the state health department [69,144]. Testing for the organism must be specifically requested [21,144].

Treatment

Treatment with antibiotics is not routinely needed for enterotoxigenic E. coli infection [21]. For severe illness, recommended antimicrobial agents are TMP-SMX, ciprofloxacin, and azithromycin [69]. Fluoroquinolones may also decrease the duration of illness caused by enterotoxigenic E. coli and other travel-related bacterial pathogens from 3 to 5 days to 1 to 2 days [17,144].

Since 2000, the incidence of listeriosis has decreased considerably, by 34% between 1989 and 1993, by 36% from 1996 to 2006, and by 26% from 2014 to 2016 [2,133]. In 2008, 33 individuals were affected by three confirmed outbreaks [66]. In 2017, 8 confirmed foodborne listeriosis outbreaks resulted in 32 illnesses, and 31 hospitalizations [3]. In 2011, health officials in Colorado notified the CDC of seven cases of listeriosis associated with consumption of cantaloupe from the same farm [146].

Pregnant women are at high risk for the disease, but symptoms are nonspecific and diagnosis is difficult [147]. Maternal infection leads to premature birth or spontaneous abortion in many cases [34,148,149]. The mortality rate associated with Listeria infection is approximately 20% to 30% [94,95].

Ubiquitous in the environment, Listeria is found in many species of mammals (particularly herd animals), birds, and marine life [34,69]. Contaminated soil or water can cause contamination of fruits and vegetables or farm animals. Raw (unpasteurized) milk is a primary source. As many as 10% of humans are carriers of the pathogen [34].

Foodborne listeriosis often begins with fever, muscle aches, nausea, and possibly diarrhea; gastrointestinal symptoms usually begin within 9 to 48 hours after ingestion [21]. In pregnant women, infection usually manifests as mild flu-like symptoms [21]. Potential complications include bacteremia and meningitis [21]. Listeriosis-related meningitis is associated with a mortality rate of approximately 70% [34]. Invasive disease typically manifests 2 to 6 weeks after ingestion [21].

Samples of blood, cerebrospinal fluid, gastric washings, meconium, placental tissue, and other infected tissue are appropriate for culture and gram stain [34,69]. Infection with Listeria is a nationally notifiable disease. Since 2004, the CDC has requested that patients with listeriosis be interviewed with use of a standardized Listeria Initiative questionnaire. Use of this tool provides timely exposure information for case-control analyses [149].

Intravenous ampicillin, penicillin, or TMP-SMX is recommended for invasive disease; cephalosporins are ineffective [21,69]. Patients with meningitis should be treated with antibiotics for 14 to 21 days [69].

Vibrio cholerae is classified into two serotypes: O1 and non-O1 [150]. O1 is further subdivided into two biotypes: classical and El Tor. El Tor is the major cholera-causing biotype [69,151,152]. Of the non-O1 serotypes, O139 and O141 cause clinical cholera [69,152,153]. The infective dose is 10⁷ cells [34].

Epidemiology

The AMA, the ANA, and the CDC have identified street-vended foods from Latin America or Asia as potential carriers of Vibrio cholerae.

(https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5304a1.htm Last Accessed: January 26, 2022)

Level of Evidence: Expert Opinion/Consensus Statement

Cholera is rare in the United States as well as in other industrialized nations [3,154]. However, it is still common in some parts of the world. In 2016, a total of 38 countries reported a cumulative total of 132,121 cases, including 2,420 deaths, to the World Health Organization. However, because cholera is under-reported, as many as 2.9 million cases and 95,000 deaths are suspected to actually occur each year. There has been an ongoing global pandemic in Asia, Africa, and Latin America for the last five decades [152].

Contamination and Transmission

The ingestion of fecally contaminated water or food is the most common mode of transmission [74,133,152]. Person-to-person transmission is rare.

Clinical Presentation and Disease Course

Symptom onset is 1 to 3 days after ingestion [21]. Most patients with cholera will experience minimal or no symptoms [133]. However, the disease can be associated with profuse, watery diarrhea that lasts 3 to 7 days; there is usually no abdominal pain or fever [69,152]. Stool is colorless with flecks of mucus—sometimes referred to as "rice water"—and the initial stool may exceed one liter [69,152]. In approximately 5% to 10% of cases, the individual becomes severely dehydrated and metabolic acidosis and hypokalemia may develop within hours [21,69,152]. Vibrio cholerae infection can progress to hypovolemic shock, seizures, coma, and death, particularly in children [69].

Diagnostic Testing

Vibrio cholerae can be detected in culture of stool or vomitus, but the test must be specifically requested [21,152]. Isolates should be forwarded to the state health department for serogrouping [69]. Cholera is a nationally notifiable disease.

Treatment

Rehydration should begin as soon as cholera is suspected and should be aggressive [21,69,152]. If possible, antimicrobial susceptibility testing is recommended because many Vibrio cholerae type O139 strains are resistant to TMP-SMX [69]. Oral doxycycline (single dose) or tetracycline (3-day regimen) is recommended, especially for adults [21]. Although tetracycline stains developing teeth in children younger than 8 years of age, the American Association of Pediatrics has noted that the benefit of tetracycline therapy outweighs the risks for children with severe cholera [69]. Tetracycline-resistant strains may be effectively treated with ciprofloxacin, ofloxacin, or TMP-SMX [21,69].

Noncholera Vibrio is commonly found in all seawater [34,69]. The species of noncholera Vibrio that cause gastroenteritis include Vibrio parahaemolyticus and Vibrio vulnificus [21]. Vibrio parahaemolyticus naturally inhabits coastal waters in the United States and Canada and is present in higher concentrations during the summer [133]. Vibrio vulnificus normally inhabits warmer seawater [133,152]. The infective dose is 10⁷ cells [34].

Epidemiology

According to preliminary data from 2019, the incidence of Vibrio infection is 0.9 per 100,000, and the incidence is highest among individuals 60 years of age and older [2]. The risk for infection is greatest for individuals who consume raw/undercooked seafood (especially oysters, shrimp, and crabs) and individuals who have liver disease [69]. In 2017, 2 suspected outbreaks of Vibrio were reported, affecting 19 individuals [3].

Contamination and Transmission

Ingestion of raw or undercooked seafood (e.g., mollusks, crustaceans) is the primary mode of transmission [21,34,152].

Clinical Presentation and Disease Course

The time from ingestion to onset of symptoms can be as short as 2 to 48 hours (Vibrio parahaemolyticus) or 1 to 7 days (Vibrio vulnificus) [21]. Unlike cholera, noncholera Vibrio infection, or vibriosis, causes abdominal cramps along with watery diarrhea [34,69]. More than half of patients have a fever, chills, and headache, and at least 25% experience vomiting [69]. Bacteremia may develop in individuals with a compromised immune system [69].

Diagnostic Testing

Vibriosis can be diagnosed by culture of stool or vomitus samples, and the test must be specifically requested [21,34,69,152]. Vibrio infection became a nationally notifiable disease in January 2007 [133].

Treatment

Treatment is recommended only for severe disease. Recommended antimicrobial agents include tetracycline and doxycycline, as well as gentamicin and cefotaxime (Vibrio parahaemolyticus) and ceftazidime (Vibrio vulnificus) [21].

In 2019, the incidence of yersiniosis was 1.4 per 100,000, an increase of 153% compared with that reported for 2016–2018 [2]. The incidence is highest among children younger than 5 years of age. Yersinia enterocolitica O:3 is the most frequently identified serotype [34,69].

Pigs are the primary reservoirs for Yersinia [155]. However, humans may be carriers for several months after infection [69,155]. Commonly associated foods are raw/undercooked pork, oysters, fish, unpasteurized milk, and ice cream [34,69]. The organism can grow at 4°C, which means that refrigerated meats can be sources of infection [34,132]. Waterborne infections are rare [69].

Symptoms associated with Yersinia infection usually occur within 24 to 48 hours after ingestion of contaminated food [21]. The clinical presentation of yersiniosis is age-specific. In infants and young children, mucoid diarrhea with blood and leukocytes, as well as fever, is common, whereas in adolescents and adults, an appendicitis-like syndrome (i.e., diarrhea, vomiting, fever, abdominal pain) usually occurs [34,69]. Yersinia enterocolitica may lead to reactive arthritis in 2% to 3% of individuals with infection, even in the absence of obvious symptoms [34,69]. Bacteremia is a potential complication among children with excessive iron storage or who have compromised immune systems [69].

Yersinia can be detected in a stool, vomitus, or blood culture, if specifically requested [21,34]. Serology testing is available in some research and reference laboratories.

Antimicrobial therapy is recommended if septicemia or invasive disease develops [21]. Options for antimicrobial agents include gentamicin, cefotaxime, doxycycline, and ciprofloxacin [21].

The CDC has attributed nearly 1 million domestically acquired foodborne illnesses to Clostridium perfringens [156]. In 2017, Clostridium perfringens accounted for the second greatest number of illnesses (843) in 41 reported outbreaks (19 confirmed and 22 suspected) of foodborne disease [3].

Small numbers of Clostridium perfringens are present in some foods after cooking and multiply to the level of an infective dose if cooked foods are cooled or stored at inappropriate temperatures [34,156]. Common source outbreaks are associated with inadequately cooked or improperly stored and reheated meat products and gravy [43,156].

Symptoms of Clostridium perfringens poisoning include watery diarrhea, abdominal cramps, and nausea; fever is rare [21,34]. The onset of symptoms is usually 8 to 22 hours after ingestion of contaminated food. Illness is usually relatively mild and rarely leads to hospitalization. Symptoms usually resolve within 24 to 48 hours, although less severe symptoms may last for 1 to 2 weeks in some patients (i.e., older individuals, individuals with compromised immune systems) [21,34,156].

Perfringens poisoning is diagnosed primarily by the clinical presentation, but the toxin can be detected in stool samples. A stool culture can also be done to detect Clostridium perfringens, but because these bacteria are normally found in stool, a quantitative analysis should be done [21,156]. Food can also be cultured, and an exceptionally high number of the bacteria indicates contamination [34]. Antimicrobial therapy is not indicated for perfringens poisoning, as it is ineffective against the toxin [21,156].

Foodborne botulism is relatively rare, primarily due to the improvements in commercial canning processes, which have reduced the incidence of botulism. However, outbreaks do occur. A small outbreak (eight cases) in 2007 involved a commercial brand of canned chili sauce [49]. During 2008 and 2009, the CDC and state and local health departments in Ohio and Washington investigated three outbreaks of botulism caused by unsafe home canning of vegetables [157]. In 2011, consumption of commercially produced (and then improperly stored) potato soup was associated with toxin type A botulism in two individuals in separate states [158]. In 2017, there were 3 confirmed and 1 suspected foodborne outbreaks of Clostridium botulinum resulting in 17 illnesses, 16 hospitalizations, and 1 death [3].

The incidence of foodborne botulism in Alaska remains more than 800 times the overall U.S. rate [159]. Approximately 27% of all foodborne botulism cases in the United States have occurred in that state [160]. Between 1950 and 2016, 200 outbreaks (366 cases; 303 confirmed, 63 suspected) of foodborne botulism were recorded in Alaska and involved Alaska Natives [160,161]. In 2016, 205 confirmed cases of botulism were reported to the CDC, with foodborne botulism accounting for 29 of the cases (14%) [162]. Infant botulism was more common than foodborne botulism, with 150 cases (73%) reported in 2016 [162]. Most cases of infant botulism have occurred in breastfed babies when nonhuman-milk foods were introduced [69,119]. The rate of mortality associated with the disease is approximately 5% [133].

Botulism is caused by ingestion of Clostridium botulinum toxin produced in food [133]. The most common source is home-canned foods that have been prepared in an unsafe manner. Infant botulism occurs when Clostridium botulinum spores germinate and produce toxin in the gastrointestinal tract of infants. The risk of infant botulism is high among infants who eat honey before the age of 1 year, as honey is a source of the spores that produce Clostridium botulinum [69].

Symptoms of foodborne botulism typically occur within 12 to 72 hours after ingestion of contaminated food but may occur as late as 10 days following ingestion [21,163]. Characteristic symptoms include weakness with disproportionate involvement of cranial nerves (diplopia, dysarthria, dysphagia) and symmetric descending flaccid paralysis in the absence of sensory changes that usually accompany other disorders with similar symptoms, such as stroke or Guillain-Barré syndrome [34,69]. If symptoms of muscle paralysis are left untreated, they may progress to cause permanent paralysis of the arms, legs, trunk, and respiratory muscles.

Infant botulism is characterized by constipation, lethargy, lack of appetite, drooling, and weakness, which begin 1 to 30 days after ingestion of contaminated food [21]. Subsequent symptoms include descending symmetrical paralysis manifested as bulbar palsies (e.g., poor head and muscle control, flat affect, ptosis, impaired swallow reflexes, sluggish pupillary reaction) [21]. Intubation and ventilatory support are necessary in the vast majority of cases [69].

Serum, stool, gastric fluid, vomitus, or food samples can be used to detect botulism neurotoxins [133]. Because its clinical presentation is similar to neurologic conditions, diagnostic testing should be done to rule out these conditions [133,163]. For example, the incremental increase of evoked muscle potentials at high frequency 20–50 Hz nerve stimulation may distinguish botulism from Guillain-Barré syndrome or myasthenia gravis [69]. Clostridium botulinum is a category A bioterrorism agent, and infection is a nationally notifiable disease [133].

Treatment should begin when botulism is suspected on the basis of symptoms and should not be delayed while waiting for confirmation from laboratory results [69,163]. If diagnosed early, foodborne botulism can be treated with an equine antitoxin that will prevent worsening of the disease. Antitoxins can be obtained from the CDC Drug Service [163]. Induced vomiting, gastric lavage, rapid purgation, or high enema can remove contaminated food in the gut [21,69]. A respirator is often needed, and complete recovery can take many weeks to months.

Infant botulism can be treated with botulism immune globulin, which can be obtained from the Infant Botulism Prevention Program, California Department of Public Health [163,164].

Infection with Bacillus cereus is infrequent, but sporadic outbreaks occur from year to year. In 2008, 15 outbreaks of the illness were reported (three confirmed and 12 suspected), affecting a total of 73 individuals [66]. In 2017, there were 11 reported foodborne outbreaks (3 confirmed and 8 suspected) and 341 illnesses [3].

Bacillus cereus food poisoning is transmitted through ingestion of contaminated food, and there is a broad range of potential food sources, including meats, milk, vegetables, and fish (diarrheal-type illness) and rice products and other starchy foods, such as potato, pasta, and cheese products (emetic-type illness) [34]. Bacillus cereus occurring in grains and beans was the pathogen-food category pair responsible for the most illnesses in outbreaks [3]. Outbreaks also have often involved food mixtures, such as sauces, puddings, soups, casseroles, and pastries. Bacillus cereus is heat resistant and can survive cooking (even at recommended temperatures). In addition to contaminated food, transmission of infection can also occur with improper food handling or storage; person-to-person transmission is rare [34].

The symptoms caused by the diarrheal type of Bacillus cereus food poisoning are similar to those of Clostridium perfringens infection. Symptoms include watery diarrhea and abdominal cramps that may be accompanied by nausea but usually not vomiting. The onset of symptoms is typically 6 to 16 hours after ingestion of contaminated food [21,34]. Symptoms usually resolve within 24 to 48 hours [21].

The enteric type of Bacillus cereus food poisoning causes symptoms similar to those associated with foodborne Staphylococcus aureus infection. The onset of nausea and vomiting occurs within one to six hours after ingestion of contaminated food and may be accompanied by diarrhea and/or abdominal cramps [21,34]. Symptoms usually resolve within 24 hours.

The diagnosis of either type of Bacillus cereus food poisoning is based primarily on the clinical presentation. Laboratories do not routinely identify the enteric type of Bacillus cereus; testing for the toxin in food and stool samples should be considered if an outbreak is suspected [21]. Antimicrobial therapy is not indicated for Bacillus cereus food poisoning [21].

Brucellosis is rare in the United States, with an incidence of less than 0.5 per 100,000 [44]. Most cases are caused by Brucella melitensis, the majority of which are reported from California, Florida, Texas, and Arizona [166]. There were no foodborne outbreaks of Brucella reported in 2017 [3].

In the United States, milk or dairy products from contaminated animals are the most common sources of infection with Brucella [133,166]. Transmission through person-to-person contact is extremely rare.

Symptoms typically occur 7 to 21 days after ingestion of contaminated food [21]. The clinical presentation of brucellosis is nonspecific and includes fever with chills, sweating, malaise, headache, and myalgia as well as diarrhea, which may be bloody during the acute stage of disease [21]. Symptoms may last for weeks. Meninges, bone, and/or the heart may be involved, which can lead to such complications as meningitis, osteomyelitis, and endocarditis [69,166]. Disease is usually more severe in adults than in children [69].

Samples of blood, bone marrow, or other tissues are tested for the bacteria and must be incubated for 4 weeks before testing [69,166]. The CDC has designated Brucella as a category B bioterrorism agent, and infections are nationally notifiable [133].

Recommended therapy for brucellosis is doxycycline and rifampin for at least 6 weeks [166]. Individuals who have complications should be treated with the combination of rifampin, tetracycline, and an aminoglycoside [21].

In 2017, Staphylococcus aureus enterotoxin was implicated in 12 reported outbreaks involving 128 illnesses, and no hospitalizations [3].

Staphylococcus aureus is transmitted through person-to-person contact, usually as a result of a food handler who is infected with the bacteria [133]. The bacteria will multiply on improperly stored foods, especially pastries, custards, salad dressings, cheeses, meat products, and expressed human milk [69,133]. Staphylococcal toxins are resistant to heat and cannot be destroyed by cooking [133].

Staphylococcal food poisoning is characterized by the rapid onset of nausea and vomiting, which may occur within 30 minutes of ingestion (range: 1 to 6 hours) [21,133,167]. Other symptoms include abdominal pain, diarrhea, and fever [21,167]. The disease is usually mild, with recovery within 1 to 3 days [21,133].

Staphylococcus aureus toxins can be identified from stool, vomitus, and food, but microbiologic testing is not usually done [21,167]. Staphylococcal enterotoxin B is classified as a category B bioterrorism agent and is nationally notifiable [133].

Antimicrobial agents should not be used to treat foodborne Staphylococcus aureus infection, as they are not effective against the toxins [167].

Norovirus is the leading cause of gastroenteritis and foodborne disease outbreaks in the United States. According to estimates derived from surveillance data, norovirus causes 2 million illnesses, 56,000 to 71,000 hospitalizations, and 570 to 800 deaths annually [172]. In 2017, norovirus was the most common cause of confirmed single-etiology foodborne outbreaks, accounting for 140 (35%) outbreaks and 4,092 (46%) illnesses; moreover, it was the suspect etiologic agent for an additional 177 outbreaks and 2,140 food-related illnesses [3]. The incidence of norovirus infection increases during the winter months, and periodic outbreaks tend to occur in association with the emergence of new GII strains that evade population immunity [171].

In 2009, the CDC launched CaliciNet, an outbreak surveillance network for noroviruses in the United States [173,174]. The CDC uses the information to link norovirus outbreaks, monitor trends, and identify emerging strains. As of 2018, 34 laboratories in 29 states and the District of Columbia have been certified by the CDC to participate in CaliciNet [175].

Between 2009 and 2012, norovirus was the etiologic pathogen identified in 1,008 foodborne outbreaks, accounting for 48% of all reported outbreaks with a single known cause [176]. Eating in restaurants was the most common setting (65%), and food handlers were implicated as the source in 70% of outbreaks in which factors contributing to contamination could be identified. Other factors included contamination of food during preparation (92%) and consumption of raw food (75%) [176]. Specific food categories were implicated in only 67 outbreaks, the most frequent being leafy vegetables (30%), fruits (21%), and mollusks (19%) [176].

Foodborne infection with either norovirus or sapovirus is transmitted via the fecal-oral route through infected food handlers, exposure to contaminated surfaces, consumption of contaminated food, or rarely, ingestion of contaminated water [171,176,177]. Aerosolized norovirus particles in vomitus can also contribute to spread of the disease, and these particles can travel a distance of up to 3 feet [177,178,179]. The most common sources are prepared foods (e.g., sandwiches, salads) and raw produce [84].

The symptoms associated with infection with either norovirus or sapovirus are nausea, vomiting, abdominal cramps, diarrhea (usually watery), fever, myalgia, and headache [21,177]. Diarrhea is more common among adults, and vomiting is more common among children [21,177]. The onset of disease is 24 to 48 hours but may be as few as 12 hours [21,177]. Symptoms usually resolve within 24 to 72 hours [177]. Viral shedding lasts 2 weeks in otherwise healthy individuals and longer in individuals with compromised immune systems [171].

The diagnosis of norovirus or sapovirus is usually made on the basis of the clinical presentation and the lack of positive results on stool cultures for bacteria [21]. The absence of white blood cells in the stool is also an indicator of the virus [21]. Reference/research laboratories can identify norovirus or sapovirus in stool with reverse transcriptase polymerase chain reaction (RT-PCR), immunoassays, or electron microscopy [171,177].

The hepatitis A vaccine, which became available in 1995, led to a 95% decrease in the incidence of the disease [180]. However, the incidence of hepatitis A increased 1,325% between 2015 and 2019, primarily because of person-to-person outbreaks reported in 31 states among people who use injection drugs and people experiencing homelessness [85]. In 2019, there were 18,846 reported cases of acute hepatitis, an incidence of 5.7 per 100,000 [85]. Five confirmed outbreaks of foodborne hepatitis A (35 individuals) were reported in 2017 [3]. Outbreaks of hepatitis A have been caused by fruits (strawberries) and vegetables (green onions) that were contaminated during packing or shipping from farms outside the United States; one of these outbreaks involved 601 individuals who had consumed green onions at a single restaurant in Pennsylvania [50].

Foodborne hepatitis A is transmitted via person-to-person contact (fecal-oral); waterborne transmission is rare in the United States and other developed countries [180]. The virus is destroyed if heated to 185°F for 1 minute; however, the virus may be spread from cooked food if it is contaminated after cooking [69]. Because children with hepatitis A are often asymptomatic, they play a key role in transmission.

According to the AMA, the ANA, and the CDC, treatment for foodborne rotavirus infection is generally limited to supportive care. Severe diarrhea may require fluid and electrolyte replacement.

(https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5304a1.htm Last Accessed: January 26, 2022)

Level of Evidence: Expert Opinion/Consensus Statement

The incubation period of hepatitis A is 2 to 5 weeks (average: 4 weeks) [181]. Jaundice occurs in most infected older children and adults [21]. In children younger than 6 years of age, jaundice is uncommon; only 30% of children are symptomatic at this age [21]. Other common symptoms among children and adults are dark urine, fever, malaise, and loss of appetite [21,69].

Symptoms persist for several days to months [21,69]. Communicability extends from 1 to 2 weeks before the onset of disease to about 1 week after the development of jaundice [180]. The risk for severe illness is higher for individuals with chronic liver disease or clotting-factor disorders [69,180]. Hepatitis A-induced acute liver failure is uncommon (0.4%) and is most likely to manifest in people with chronic liver disease [69].

The presence of anti-hepatitis A immunoglobulin (Ig) M in serum represents current or recent infection; anti-hepatitis IgG in the absence of IgM indicates past infection [69]. Increases in serum levels of bilirubin and alanine aminotransferase are also indicators of infection [21].

In the United States, annual epidemics of rotavirus spread from the Southwest to the Northeast between fall and spring [69]. Prior to introduction of the rotavirus vaccine in 2006, almost all children in the United States had been infected by 5 years of age [182]. By extension, the virus affects approximately 20% of adults having close contact with an infant [69].

Rotavirus is transmitted via the fecal-oral route through person-to-person contact or fomites. Rotavirus is stable in the environment [182].

The primary symptoms of rotavirus infection are vomiting, watery diarrhea, and low-grade fever, all of which occur 1 to 3 days after infection [21]. Temporary lactose intolerance may occur [34]. Symptoms typically last 4 to 8 days and are milder in adults than in children [21]. Infection can become persistent in individuals who have compromised immune systems [69].

Diagnosis of rotavirus infection is made primarily on the basis of the clinical presentation and the nondetection of bacteria in stool cultures. The virus can be detected in a stool sample with use of a radioimmunoassay [182].

Astroviruses and adenoviruses infect children more often than adults, and the incidence is highest among children younger than 4 years of age [69,183]. According to the most recent data, no outbreaks of astrovirus have occurred in the United States [44].

Astroviruses and adenoviruses are transmitted via the fecal-oral route through an infected food handler or exposure to a contaminated surface [69]. Enteric adenovirus may also be transmitted via respiratory secretions [34].

The incubation period for these viruses ranges from 10 to 70 hours [21]. Associated symptoms include diarrhea, nausea, vomiting, abdominal pain, fever, malaise, and headache [21,69]. Symptoms typically resolve within 2 to 9 days, and the virus is shed for a median of 5 days after the onset of symptoms [21,69]. In individuals with a compromised immune system, viral shedding is often persistent [69].

Commercial assays are available to detect astroviruses and adenoviruses in stool samples, although testing is uncommon [21].

Prevalence studies show 2% of the population of North America harbors Cryptosporidium in the gastrointestinal tract; serologic surveys indicate that 80% of the population has had a past infection [34]. Two confirmed outbreaks of foodborne infection with Cryptosporidium were reported in 2017, affecting 12 individuals [3]. The incidence of Cryptosporidium was 3.7 per 100,000 in 2017, ranking it fourth among the infectious foodborne pathogens monitored in the FoodNet program [2]. Rates of cryptosporidiosis peak strongly in the late summer [123].

Foodborne acquisition of cryptosporidiosis usually occurs by way of an infected food handler [21]. Animals raised for food may also serve as vehicles for transmission, and the parasite most commonly infects herd animals (e.g., cows, goats, sheep) [34]. Fresh produce may also become contaminated [34].

Infection with Cryptosporidium causes noninflammatory, profuse watery diarrhea lasting up to two to three weeks, often accompanied by stomach cramps, nausea and vomiting, slight fever, anorexia, and weight loss [21,185]. Some individuals may be asymptomatic [69,185]. The onset of symptoms is usually within 2 to 10 days [21,185]. Although infection is self-limiting in otherwise healthy individuals (10 to 14 days), it can become chronic in individuals with compromised immune systems [185].

A confirmed case requires evidence of Cryptosporidium organisms or DNA in stool, intestinal fluid, or tissue samples. Light microscopy of stained specimens is a common means of testing; other methods include direct florescent antibody (DFA) test, enzyme immunoassay (EIA), and polymerase chain reaction (PCR) [69,186]. These tests must be ordered specifically [21]. Because shedding may be intermittent, three stool samples collected on different days should be tested before suspected cryptosporidiosis can be ruled out [69]. Cryptosporidium infection is a nationally notifiable disease.

Treatment is usually reserved for severe disease, and paromomycin (7-day course) is the recommended drug [21]. Treatment with nitazoxanide (3-day course) is suggested for children 1 to 11 years of age [21].

Cyclosporiasis occurs most commonly in tropical and subtropical areas [97,184]. The disease is not known to be endemic in the United States; however, since 1990, multiple foodborne outbreaks of cyclosporiasis, affecting thousands of individuals, have been documented in the United States and Canada [184,187,188]. During the period of 1997–2008, the CDC was notified of 1,110 laboratory-confirmed cases of sporadic cyclosporiasis, occurring in 37 states, including seven in which cyclosporiasis is not an explicitly reportable disease. More than one-third of the case-patients had a documented history of international travel [97]. In 2009, 141 cases of Cyclospora were reported to the CDC [187]. In 2019, FoodNet surveillance identified 755 cases of Cyclospora foodborne disease, an incidence rate of 1.5 per 100,000 persons [2]. In 2018, multiple outbreaks of cyclosporiasis (2,299 confirmed cases) linked to produce items were reported to the CDC from 33 states [188,189]. Approximately one-third of the illnesses were associated with one of two large multistate outbreaks in the Midwest: one outbreak involved prepackaged vegetable trays (broccoli, cauliflower, carrots) sold at a convenience store chain; and one involved salads (carrots, romaine, spinach, kale, red leaf lettuce) sold at a fast food chain. Additional clusters were associated with basil and cilantro. Two basil-associated clusters of 8 confirmed cases were identified in two states in the West and Midwest. Multiple cilantro-associated clusters were identified, including three associated with unrelated Mexican-style restaurants in the Midwest. The CDC received reports of 53 confirmed cases associated with these three clusters. FDA traceback investigations are ongoing [189].

Individuals become infected with Cyclospora by ingesting oocysts that have become environmentally contaminated [187]. Direct person-to-person transmission of Cyclospora is unlikely because shed oocysts are noninfectious [184]. Washing of contaminated produce decreases, but does not eliminate, the risk of transmission [69]. A large outbreak of Cyclospora on imported raspberries demonstrates the potential risk for transmission from contaminated water or infected food handlers [51].

The onset of symptoms of cyclosporiasis is typically at least 1 week after ingestion of contaminated food (range: 2 to 14 days) [21,187]. Symptoms include profuse, usually watery diarrhea, loss of appetite with resultant weight loss, stomach cramps, nausea and vomiting, and fatigue [21,187]. Illness may become persistent (10 to 12 weeks) and relapsing if left untreated [21,187].

Oocysts can be detected in stool samples, but testing must be specifically requested [21,187]. Cyclosporiasis is a nationally notifiable infection. The recommended treatment is oral TMP-SMX for 7 to 10 days [21,184,187].

Giardiasis affects approximately 2% of the U.S. adult population [34,190]. In 2015, three outbreaks of laboratory-confirmed giardiasis affected 12 individuals [190]. Similar to cryptosporidiosis, the incidence of giardiasis peaks in late summer [34,123].

Transmission of giardiasis is most commonly waterborne. However, infection can be transmitted through ingestion of cysts in food or by the fecal-oral route [34,190].

The onset of symptoms is usually 1 week after ingestion of contaminated food [21,190]. Symptoms of giardiasis include watery diarrhea, abdominal pain, bloating, nausea, and vomiting, which usually last for 1 to 3 weeks or longer [184]. However, many individuals with giardiasis are asymptomatic [69,190]. Disaccharide intolerance develops in approximately 40% of individuals [34]. Lasting immunity after infection is common [34]. Chronic, debilitating giardiasis may occur and affects more adults than children [34,69].

Diagnosis can be determined through the identification of cysts in stained fecal smears, of trophozoites in a smear of stool or duodenal fluid, or of antigens in stool samples [34,69]. The sensitivity of diagnostic testing is higher when samples of diarrhea are tested and when testing is done on specimens obtained on alternating days [69]. At least three stool specimens may be needed for accurate results [21]. Giardiasis is a nationally notifiable disease.

Metronidazole is the recommended agent for treatment, although it is not FDA-approved for this indication [21,184]. Other options include tinidazole, nitazoxanide, paromomycin, furazolidone, or quinacrine [184].

Toxoplasmosis is one of the most common human infections worldwide. An estimated 22.5% of the population 12 years of age and older has been infected with the parasite. More than 60 million people in the United States carry the Toxoplasma parasite. In some locations, up to 95% of the local human population either is or has been infected with Toxoplasma gondii[34,191]. It is more common in warm climates and at lower altitudes [184].

Cats are the main reservoirs of Toxoplasma gondii, and they become infected through carnivorism [184,191]. Although cats shed oocysts for only 1 to 2 weeks, large numbers may be shed, and they can survive in the environment for several months (even years under certain conditions), with considerable resistance to disinfectants, freezing, and drying [34,184]. Humans become infected by ingesting raw or undercooked, cyst-contaminated meat, not only meats like pork and beef, but also seafoods, like clams and oysters, or by ingesting oocysts from fecally contaminated hands or food [34,69,184,191,192]. Congenital toxoplasmosis develops as a result of maternal infection during pregnancy and can lead to a range of serious morbidity and mortality [34,184,191].

The incubation period for Toxoplasma gondii is 5 to 23 days [21]. Infected individuals are usually asymptomatic or have nonspecific symptoms [34,191]. Lymphadenopathy, with or without flu-like symptoms, will develop in approximately 10% to 20% of affected individuals [184]. Symptoms usually resolve within a few months to a year. Fetuses (infected through maternal transmission) and individuals with AIDS are the most susceptible to complications [69,191]. Although not evident at birth, mental retardation, visual impairment, and learning disabilities are likely to develop in children born with congenital toxoplasmosis [69,191].

The CDC indicates that congenital Toxoplasma gondii infection may be diagnosed by isolation of the organism from placenta, umbilical cord, or infant blood. Polymerase chain reaction of white blood cells, cerebrospinal fluid, or amniotic fluid, or IgM and IgA serology, performed by a reference laboratory are the definitive tests.

(https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5304a1.htm Last Accessed: January 26, 2022)

Level of Evidence: Expert Opinion/Consensus Statement

Serologic testing for Toxoplasma gondii antibodies is the most commonly used diagnostic test [34,69,191]. It is important to note that chronic Toxoplasma gondii is difficult to diagnose in patients with HIV, as serologic tests are considered unreliable in this population [69].

Treatment is not necessary for individuals with healthy immune systems who are not pregnant. Pyrimethamine plus sulfadiazine has been used to treat central nervous system toxoplasmosis in individuals with HIV infection [184].

Epidemiology

Ciguatera fish poisoning is endemic in tropical and subtropical regions of the Pacific basin, Indian Ocean, and Caribbean [52,202]. The illness occurs much less frequently in the United States, with 141 single exposures reported in 2016 [191,203]. However, the CDC estimates that 2% to 10% of poisonings may not be reported [201]. Worldwide, an estimated 50,000 cases of ciguatera poisoning occur each year [52,204].

Clinical Presentation and Disease Course

Gastrointestinal symptoms (e.g., diarrhea, vomiting, abdominal pain) occur in more than 50% of individuals within 2 to 6 hours after ingestion of the toxin and may last 1 to 2 days; neurologic symptoms, which include reversal of temperature sensations, distal and perioral numbness and/or tingling, and dizziness, usually occur within a few hours to 3 days and can be persistent, lasting weeks to several months [21,201,202]. Within 2 to 5 days, cardiovascular symptoms (less common but potentially severe), such as bradycardia, hypotension, and T wave abnormalities, may appear [21,202].

Muscular weakness, paresthesias, and fatigue may last for weeks to months [201,202]. Women of childbearing age may have increased pain during menses, and intercourse may be painful for both men and women [52,205]. Among individuals with chronic symptoms, relapse may occur after stressful conditions or ingestion of fish (any type), alcohol, caffeine, or nuts, 3 to 6 months after the initial poisoning [201,206].

Serious illness may involve severe hypotension with bradycardia, respiratory difficulties, and paralysis [202,206]. Death as a result of respiratory and cardiovascular failure occurs in approximately 2% of infected individuals [207]. Children are most vulnerable to severe illness [208].

Treatment

Intravenous mannitol should be given within 24 to 48 hours to relieve neurologic symptoms [21,201,208]. Gut emptying and charcoal decontamination is recommended acutely; however, gastrointestinal symptoms may prohibit this measure [201]. Atropine may be necessary for bradycardia, and dopamine or calcium gluconate may be administered for shock [202]. Amitriptyline (and similar medications) may be effective in relieving chronic symptoms of fatigue and paresthesias [201]. Opiates and barbiturates should be avoided, as they may interact with the toxin and cause hypotension [201].

Epidemiology

Six outbreaks of foodborne disease attributed to shellfish poisoning (three amnesic, three paralytic) were reported in 2009–2015 [44]. In 2014, health officials in Alaska received reports of 177 cases of paralytic shellfish poisoning comprising 70 incidents from consumption of noncommercially harvested Alaskan shellfish [209]. Children are particularly sensitive to paralytic shellfish toxins, and the mortality rate is particularly high in children [210]. Individuals older than 65 years of age are predisposed to the severe neurologic effects of amnesic shellfish poisoning [21]. The incidence of shellfish poisoning has been declining as a result of careful monitoring, beach closures, and improved public awareness [193].

Clinical Presentation and Disease Course

The shellfish toxins differ according to the timing from ingestion of the toxin to the onset of symptoms, the symptoms caused, and the severity of illness [21,201].

Paralytic shellfish poisoning is the most severe type of illness. It has a mortality rate of 6% worldwide (higher in developing countries) [193]. This toxin (e.g., saxitoxin) causes tingling, burning, numbness, drowsiness, incoherent speech, and respiratory paralysis within 15 minutes to 3 hours after ingestion [193,201]. Other symptoms may include headache, dizziness, nausea, vomiting, rapid-onset pain, and anuria [201]. With severe illness, respiratory paralysis is common, occurring within 2 to 12 hours in severe poisoning, and persisting for as long as 72 hours to one week. Death may occur if respiratory support is not provided [193,201]. Patients surviving 9 hours usually recover, and recovery begins 12 hours after the onset of symptoms and may take a few days to resolve completely [201].

With diarrheic shellfish poisoning, symptoms occur 30 minutes to 12 hours after ingestion of the toxin [193,201]. Diarrhea occurs in almost all affected individuals (92%), and nausea and vomiting are also common (80% and 79%, respectively) [201]. Other symptoms may include abdominal pain, chills, headache, and fever [21]. Illness usually resolves within 2 to 3 days, and recovery is complete, with no aftereffects [21,201]. No cases of death from diarrheic shellfish poisoning have been reported [193].

Symptoms of neurotoxic shellfish poisoning occur within a few minutes to 3 hours. The toxin (e.g., brevetoxin) causes both gastrointestinal and neurologic symptoms, generally mild and self-limited [193,211]. Gastrointestinal symptoms may include diarrhea and vomiting. Neurologic symptoms may include tingling and/or numbness of the lips, tongue, and throat; muscle aches; dizziness; and reversal of temperature sensations [21,193,212]. Neurotoxic shellfish poisoning is the least common of the shellfish poisonings and is less severe than ciguatera poisoning. Recovery is complete within hours to 2 to 3 days [21,201]. No fatalities have been reported [211].

Amnesic shellfish poisoning (e.g., domoic acid poisoning) causes symptoms of gastroenteritis (nausea, vomiting, abdominal cramps, diarrhea) within 24 hours after ingestion [201]. Although a potentially serious poisoning, only one human outbreak has been reported [213]. The primary symptom was vomiting, occurring in approximately 76% of infected individuals; abdominal cramps occurred in about half of those affected [201,213]. In cases of severe poisoning, neurologic symptoms (i.e., dizziness, headache, seizures, disorientation, short-term memory loss, respiratory difficulty, coma) occur within 48 hours [201]. Cognitive dysfunction is most likely to be permanent in individuals who have neurologic symptoms within 48 hours after ingestion of the toxin, in men older than 60 years of age, and in individuals who have pre-existing conditions such as renal disease, diabetes, and hypertension with a history of transient ischemic attacks [201]. All reported fatalities associated with this toxin have involved individuals older than 65 years of age [201].

Treatment

Gut decontamination and administration of activated charcoal or dilute bicarbonate solution is recommended when shellfish poisoning is diagnosed during the early stage of illness [201]. Treatment should include oral rehydration therapy, as it may enhance renal excretion of the toxin [201]. Respiratory support is recommended for individuals with moderately severe cases [21]. Anticholinesterase agents are not advised and may be harmful [201,214]. If seizures occur, intravenous diazepam or phenobarbital is recommended; the seizures may be resistant to phenytoin [201,215].

Epidemiology

Although foodborne illness caused by ingestion of pufferfish (tetrodotoxin [TTX]) is rare in the United States, three outbreaks were reported in 2009–2015 [44; 193]. Most reports of pufferfish poisoning occur due to unskilled preparation by unlicensed cooks. The FDA allows importation into the United States through a single certified Japanese importer, but illegal importation continues and has resulted in multiple poisonings [216; 217]. The minimum lethal dose of TTX is estimated to be 2 mg but can vary depending on age and existing comorbidities. Reports of toxicity with consumption of 0.25–1.5 ounces of incorrectly prepared pufferfish have been reported by the CDC [193].

Clinical Presentation and Disease Course

Symptoms typically occur 5 to 45 minutes after ingestion of the toxin but may be observed as late as several hours later [21,34,193]. Higher toxin ingestion is associated with a more rapid onset of symptoms [193]. Pufferfish poisoning is characterized by slight numbness of the lips and tongue, followed by increasing paraesthesia in the face and extremities and sensations of lightness or floating [34,212]. Gastrointestinal symptoms (vomiting, diarrhea, abdominal pain) and difficulty walking may occur. As paralysis increases, patients are unable to move and have respiratory distress. Decreased levels of consciousness, seizures, and death have occurred in as few as 17 minutes [193]. Without treatment, death occurs in 4 to 8 hours [21,34]. Patients are conscious and often lucid until shortly before death [212]. The mortality rate has been reported to be nearly 60% [218]. If treatment is begun before poisoning becomes severe, life-threatening effects are highly unlikely after 24 hours [197].

Treatment

There is no known antidote for pufferfish poisoning [212]. Intravenous therapy, gastric lavage, and activated charcoal are recommended to reduce absorption of the toxin [196,201]. Individuals who have moderate-to-severe reactions to tetrodotoxin should be admitted to an intensive care unit, and respiratory support may be needed for 24 to 72 hours [193,197,212]. Atropine can be used to treat bradycardia in severe cases [219].

Epidemiology

Scombroid toxin was the causative agent in 101 foodborne outbreaks reported in the United States in 2009–2015 (95 confirmed and 6 suspected), affecting a total of 299 individuals [44]. In 2019, an outbreak of scombroid toxin fish poisoning involving 51 cases (two hospitalizations) from 11 states was linked to imported tuna from two Vietnamese manufacturers [242].

Clinical Presentation and Disease Course

Symptoms are immediate, usually occurring within 1 minute to 3 hours [220]. Symptoms include flushing, rash on the upper body, dizziness, and burning sensation of the skin, mouth, and throat [220]. Other symptoms may include throbbing headache and an unusual taste in the mouth, frequently described as peppery or pungent, but in some cases bitter or metallic [220]. Symptoms usually last about 3 to 6 hours but may persist for several days [220]. Patients with comorbidities such as coronary artery disease may experience acute coronary syndrome caused by scombroid-associated tachycardia and hypotension [34]. Death is rare.

Treatment

Gut decontamination and administration of activated charcoal or dilute bicarbonate solution is recommended when poisoning is diagnosed within the first few hours [220]. Treatment with antihistamine medication is recommended, and rehydration therapy (oral or intravenous) may also be needed [220].

From 1999 to 2016, 133,700 cases (average: 7,428 per year) of toxic mushroom exposure, mostly by ingestion, were reported to the National Poison Data System [203]. Cases were most frequently unintentional (83%) and caused no or only minor harm. Approximately 704 (about 39 per year) exposures resulted in major harm, including 52 (about 3 per year) fatalities. Cyclopeptide-producing mushrooms ingested by older adults accounted for the majority of fatalities. Mushroom poisonings usually result from misidentifying a wild mushroom, a non-native of the United States picking (and consuming) a mushroom that appears similar to one in his or her native country, or intentionally seeking to consume a mushroom with psychoactive compounds [34,203]. Children, the elderly, and persons with disabilities are at highest risk for the development of serious complications from mushroom poisoning [221].

A careful patient history is the most important component of the diagnostic process. The history should include: the quantity of mushrooms ingested; how they were prepared (or if they were eaten raw); the source of the mushroom; time of ingestion; and identification of other individuals who may have ingested the same mushrooms [221]. While failure to obtain history may be inconsequential for most mushroom ingestions, it is critical for patients who have ingested mushrooms containing amatoxin, orellanine, or gyromitrin, because their early removal from the GI tract may alter the outcome [221]. The clinical presentation and disease course vary according to the toxin. Diagnosis historically has relied on the timing between ingestion and onset of symptoms and the amount of mushrooms ingested (Table 13) [34,221]. However, a growing consensus suggests that mushrooms are best classified by the physiologic and clinical effects of their poisons rather than by the timing of symptom onset [221].

If definitive identification of the mushroom cannot be made, all ingestions should be considered serious and potentially lethal [221]. The treatment of most mushroom poisonings consists primarily of supportive care. For severe cases (as with ingestion of amanitin), life-support measures may be necessary [221].

Healthcare practitioners should take every available opportunity to provide their patients with information about the prevention of foodborne illnesses in the home and while traveling, focusing on the specific needs of certain populations. For example, pregnant women should be cautioned about the potential risks of infection with Listeria and Toxoplasma gondii. Parents should be advised of the need to avoid secondary transmission of viruses by keeping children with gastroenteritis out of daycare or school until symptoms have resolved. Individuals preparing for international travel (particularly to developing countries) should receive appropriate immunizations and will benefit from a description of ways to prevent traveler's diarrhea.

Educational resources for patients are available online, and some websites offer downloadable fact sheets and posters. The USDA Food Safety and Inspection Service website offers fact sheets on food safety for the general population as well as for a wide range of target populations, including ethnic minorities, older individuals, pregnant women, and individuals with cancer, diabetes, or HIV. Fact sheets are also available for preparing food for large groups, such as church suppers and other community meals. Consumer brochures and posters are commonly available in English and Spanish, and some are tailored to consumers' cultural food practices.

Individuals in high-risk groups are often confused about proper safe handling processes and are resistant to many food safety recommendations [229]. The findings of studies suggest that the primary barrier to accepting recommendations is the lack of understanding about the importance of the precautions [229,230]. Cultural and economic factors as well as simple food hygiene habits have also been shown to be barriers [231,232]. When discussing foodborne illnesses with high-risk individuals, healthcare professionals should emphasize why certain foods should be avoided or be prepared in a designated manner [229,233]. Providing consistent information in a patient-friendly form is key to patient compliance [234].

It has been suggested that education on food safety is most effective when it is targeted to changing behaviors that most likely result in foodborne illness [28]. The following behaviors have been recommended as the primary focus of education on food safety [28,235]:

Also recommended (of secondary importance) are keeping foods at safe temperatures and avoidance of foods likely to be contaminated [28]. These behaviors were also emphasized by food experts who were asked to identify and rank food-handling and consumption behaviors as being of primary or secondary importance in preventing infection with 13 foodborne pathogens [27]. According to these experts, the following are of primary importance [27]:

In addition, the experts indicated that keeping foods at safe temperatures were of secondary importance in preventing foodborne infection with Staphylococcus aureus, and avoidance of cross-contamination was of secondary importance in preventing infection with most pathogens [27].

The key messages identified as being of primary importance for education form the core of public health education campaigns on food safety. The most prominent campaigns have included "BAC Down!," "Be Safe," and "Ounce of Prevention."

"BAC Down!" is a collaborative initiative of the FDA and the Partnership for Food Safety Education. Its primary objective is to urge consumers to keep their refrigerators at 40°F or below to prevent foodborne illness such as listeriosis. "BAC Down!" uses the media, the Partnership's website, and eye-catching strategies for information dissemination at grocery stores. The Partnership also manages "Be Safe," which emphasizes four basic safe food-handling behaviors: Clean, Separate, Cook, and Chill. In addition, education on six steps to safer fresh fruits and vegetables and other topics are available in Spanish on the website.

The popular and successful "Ounce of Prevention" campaign is led by the National Center for Infectious Diseases, the CDC's coordinating center for infectious diseases, in partnership with Reckitt Benckiser, Inc. This campaign provides health educators and consumers with information and tips to prevent infectious diseases, including how to handle, store, and cook foods safely.

Practitioners are urged to seek supplemental information regarding foodborne agents, particularly agents that are prevalent in their geographic location. There is a variety of print and Internet information available on infectious foodborne agents (Resources). Many cases of foodborne illness affect individuals in the community, but outbreaks, especially of viral etiology, often occur in hospitals and long-term care facilities. Nevertheless, no foodborne illness risk management guidelines exist specifically for U.S. hospitals [236]. Because of this, healthcare professionals should also be familiar with the evidence-based isolation and control guidelines for infectious diseases developed by the Healthcare Infection Control Practices Advisory Committee [75].