Causes of acute infectious diarrhea and other foodborne illnesses in resource-abundant settings

INTRODUCTION — Most cases of acute diarrhea in adults are of infectious etiology and are self-limited. In resource-abundant settings, many diarrheal pathogens are transmitted through contaminated food or water, sometimes resulting in outbreaks with several or multiple affected individuals. The infectious etiologies of acute diarrhea and other foodborne illnesses in resource-rich countries will be reviewed here.

The approach to evaluation and management of acute diarrhea in adults and children in resource-abundant settings is discussed elsewhere. (See "Approach to the adult with acute diarrhea in resource-abundant settings" and "Diagnostic approach to diarrhea in children in resource-abundant settings".)

The approach to acute diarrhea in resource-limited settings is also discussed elsewhere. (See "Approach to the adult with acute diarrhea in resource-limited settings" and "Approach to the child with acute diarrhea in resource-limited settings".)

CLINICAL CLUES TO THE MICROBIAL CAUSE — For most patients with acute diarrhea or other foodborne illness, the precise causative pathogen cannot be reliably distinguished based on clinical presentation alone. However, there are certain features that raise the probability of certain pathogens over others (table 1). These include:

●The specific clinical manifestations – Among patients presenting with acute diarrhea, the most likely causative pathogens differ between watery diarrhea, in which small bowel pathogens predominate, and inflammatory diarrhea (with fever and bloody or mucoid stool), in which large bowel pathogens predominate. (See 'Watery diarrhea' below and 'Inflammatory diarrhea' below.)

Most foodborne infections will typically manifest as a mixture of diarrhea, nausea, vomiting, and abdominal discomfort. With certain pathogens, vomiting rather than diarrhea may predominate (see 'Vomiting' below). Furthermore, some foodborne diseases are characterized by non-gastrointestinal symptoms that can be distinctive and suggestive of the cause. Examples include botulism, ciguatera fish poisoning or scombroid, and Listeria monocytogenes central nervous system infection. (See 'Non-gastrointestinal syndromes' below.)

●The type of exposure – For patients with diarrhea or other suspected foodborne illness, identifying the particular food exposure can potentially suggest certain pathogens, particularly if the illness is occurring in the setting of an outbreak connected to a known food source (table 2).

Not all cases of acute diarrhea are food- or waterborne. Other important exposures include animal contact, travel to resource-limited settings, occupation (eg, in daycare centers), and recent antibiotic use or health care exposures.

●The time to onset – For suspected foodborne illness, the timing of symptom onset following exposure to the suspect food can be informative. Ingested preformed toxins (eg, those produced by Staphylococcus aureus and Bacillus cereus) cause illness within hours of exposure, whereas ingested pathogens that subsequently produce toxin (eg, enterotoxigenic Escherichia coli) or directly damage or invade across the intestinal epithelial cell wall (eg, Salmonella, Campylobacter, Shigella) usually result in symptoms after approximately 24 hours or longer (table 1) [1]. Protozoal pathogens (eg, Cryptosporidium parvum) generally produce enteric illness after an incubation period of approximately seven days.

Details on the evaluation of patients with acute diarrhea and indications for testing to identify the microbiologic cause are discussed in detail separately. (See "Approach to the adult with acute diarrhea in resource-abundant settings".)

DIARRHEA

Burden of disease — Acute infectious diarrhea in resource-abundant countries is very common, although the overall burden has not been as well studied as in resource-limited settings. Population-based studies suggest an incidence range of 0.7-1.4 illnesses/person/year in the United States, depending on the symptom profile [2-4].

Insight into the burden of foodborne illnesses has also been provided by analysis of outbreaks reported to public health institutions During 2021, the Centers for Disease Control and Prevention (CDC) identified 22,019 infections, 5,359 hospitalizations, and 153 deaths due to foodborne disease in the United States [5].

Overview of causes — Infectious or noninfectious causes may be responsible for acute diarrhea and, in selected patients, both can occur simultaneously. Among infectious causes, a wide variety of pathogens cause acute diarrhea and other foodborne illnesses in resource-abundant settings.

Infectious diarrheal diseases may be categorized by the portion of the intestine that they are prone to infect, since the presenting symptoms vary by region of the intestine involved in disease; this, in turn, can suggest involvement of particular pathogens [6,7]:

●Small bowel – The small bowel functions as a fluid- and enzyme-secretory and nutrient-absorbing organ. Dysregulation of these two processes due to infections of the small bowel leads to a watery diarrhea that occurs in large volume and is associated with abdominal cramping, bloating, gas, and weight loss [8]. For the most part, when only small bowel is involved, fever is rarely a significant symptom, and the stool does not contain occult blood or inflammatory cells. Enteric viruses (and specifically norovirus) are the most common causes of watery diarrhea (table 1). (See 'Watery diarrhea' below.)

●Large bowel – The main function of the large bowel is to absorb fluid and salt and to excrete potassium. Thus, large intestinal diarrheas present with frequent, regular, small-volume, often painful bowel movements. Fever and bloody or mucoid stools are common, and red blood cells and inflammatory cells can be seen routinely on the stool smear. Bacterial pathogens are more common causes of inflammatory, large intestinal diarrhea (table 1). (See 'Inflammatory diarrhea' below.)

Most common causes overall — The causes of infectious diarrhea vary from region to region, from rural to urban settings, and depending on co-morbidities, such as HIV or other immune-compromising conditions.

In the United States between 2009 and 2013, the microbiologic cause was unknown in 31 percent of outbreaks of acute gastroenteritis transmitted by person-to-person spread [9]. When active surveillance is performed, norovirus has been identified as the most common cause of medically attended acute GI illness in the United States [10,11].

The CDC's Foodborne Diseases Active Surveillance Network (FoodNet) monitors cases of enteric organisms; the three leading pathogens in 2016 to 2018 were Campylobacter, nontyphoidal Salmonella, and Shiga toxin-producing E. coli; Listeria was associated with the highest mortality [12].

Relative frequencies of bacterial and parasitic pathogens are generally comparable in resource-abundant settings, with some exceptions. In a prospective study of acute gastroenteritis in the United Kingdom, the most common bacterial isolate was Campylobacter, in 4.6 and 13 percent of community and general practice cases, respectively [13]. Salmonella, enterohemorrhagic E. coli, Shigella, Yersinia, Listeria, Giardia, Cryptosporidium, and Cyclospora were uncommon; each was identified in less than 1 percent of overall cases.

Severe or bloody diarrhea — Bacteria are more likely pathogens in cases of severe or bloody diarrhea compared with milder watery diarrhea [13-16].

This was illustrated in a study of 173 healthy adults with severe acute community-acquired diarrhea (defined as ≥4 fluid stools per day for more than three days); a bacterial pathogen was identified in 87 percent of cases [14], much more frequently than seen with acute diarrhea in general. (See 'Most common causes overall' above.)

With bloody diarrhea, the likelihood of particular bacteria, including E. coli O157:H7, is also higher. In a prospective study that evaluated approximately 550 episodes of reported bloody diarrhea for which stool cultures were obtained, a bacterial pathogen was identified in 31 percent of specimens [15]. Shigella was the most common isolate (49 percent), followed by Campylobacter (20 percent), Salmonella (19 percent), and E. coli O157:H7 (8 percent). In an earlier study that included approximately 900 visibly bloody stool specimens, E. coli O157:H7 accounted for 39 percent of cultured isolates from visibly bloody specimens but only 7 percent of cultured isolates from all stools (bloody and nonbloody). Bloody diarrhea was much less common in patients with culture-negative diarrhea.

Outbreaks — Outbreaks of diarrheal illnesses are most often related to food sources but can also be associated with animal contacts and recreational water exposure (eg, swimming or wading pools). In the United States between 2009 to 2013, more than 10,000 outbreaks of gastroenteritis occurred due to presumed person-to-person spread or environmental contamination [9].

The most frequently implicated foods in 120 multistate foodborne outbreaks in the United States between 2010 to 2014 included fruits, vegetable row crops, beef, sprouts, and seeded vegetables [17]. Ill food handlers are also important sources for foodborne outbreaks, particularly due to norovirus and other pathogens easily transmitted by person-to-person contact [18].

Waterborne outbreaks associated with recreational water exposure (eg, swimming or wading pools) are another source of acute diarrhea and commonly involve other pathogens. They have been associated most frequently with Cryptosporidium (50 percent) with treated water sources and with toxigenic E. coli (25 percent) and norovirus (25 percent) with freshwater sources [19].

Noninfectious causes — Noninfectious causes of acute diarrhea include drug adverse effects, food allergies, primary gastrointestinal diseases such as inflammatory bowel disease, and other disease states, such as thyrotoxicosis and the carcinoid syndrome. (See appropriate topic reviews for more details.)

Watery diarrhea — Many pathogens can cause watery diarrhea (usually of large volume and associated with abdominal bloating, without fever or bloody stools). In resource-abundant countries, the most common causes are enteric viruses, specifically norovirus (table 1). Clostridioides difficile (which is also associated with inflammatory diarrhea), Clostridium perfringens, enterotoxigenic E. coli (ETEC), Giardia lamblia, and Cryptosporidium parvum are also important pathogens.

Pathogens that are more classically associated with inflammatory diarrhea can also cause watery diarrhea, particularly early in the course of infection. (See 'Inflammatory diarrhea' below.)

Norovirus and other enteric viruses

●Norovirus – Norovirus (also known as Norwalk-like virus) is the leading cause of medically attended acute gastroenteritis in the United Status [11,20]. Norovirus has a low infectious dose (around 10 particles) and can be readily transmitted from the vomitus and the stool of an infected person (including through contaminated prepared food). Norovirus may also be transmitted in aerosol form or via person-to-person contact [21]. Noroviruses are responsible for the epidemic form of family- and community-wide outbreaks of acute explosive vomiting and diarrhea.

Symptoms generally begin 24 to 48 hours after exposure and last for 48 to 72 hours. Recovery is rapid and full but does not result in long-lasting immunity. If needed for public health reasons or in the case of severe infection, diagnosis can be made by antigen detection through enzyme immunoassay or reverse transcriptase polymerase chain reaction (RT-PCR)-based assays. (See "Norovirus".)

●Other viruses – Rotavirus, enteric adenoviruses (eg, adenovirus serotypes 40 and 41), astrovirus, and sapovirus predominantly cause infection in children. In adults, diarrhea associated with these viruses has been described mainly in immunocompromised or institutionalized patients. (See "Acute viral gastroenteritis in children in resource-abundant countries: Clinical features and diagnosis", section on 'Etiology'.)

Clostridioides difficile — C. difficile-associated diarrhea is one of the most common hospital-associated infections. It is typically associated with recent antibiotic use. However, severe cases have also been described in patients classically considered at low risk, including healthy individuals in the community without those traditional risk factors and peripartum women [22,23]. Clinicians should thus consider the diagnosis of C. difficile infection in all patients with severe diarrhea. C. difficile can sometimes be associated with inflammatory diarrhea (with fever and bloody or mucoid diarrhea) as well.

The epidemiology, clinical features, diagnosis, and treatment of C. difficile are discussed in detail elsewhere. (See "Clostridioides difficile infection in adults: Epidemiology, microbiology, and pathophysiology" and "Clostridioides difficile infection in adults: Clinical manifestations and diagnosis" and "Clostridioides difficile infection in adults: Treatment and prevention".)

Clostridium perfringens — C. perfringens is an important cause of foodborne, toxin-mediated watery diarrhea in resource-abundant settings. In the United States, it is thought to be the second most common cause of foodborne bacterial infection (behind nontyphoidal Salmonella spp), with an estimated one million illnesses each year [24]. However, C. perfringens is less frequently reported as a cause of outbreaks since symptoms are relatively mild, and testing is not routinely performed.

Type A strains cause typical foodborne outbreaks. C. perfringens spores can survive normal cooking temperatures and can germinate and proliferate in foods that are improperly stored. Outbreaks are most commonly associated with inadequately heated or reheated meats, poultry, or gravy [25]. Following ingestion of a large quantity of organisms with the food, C. perfringens releases an enterotoxin in the gastrointestinal tract resulting in watery diarrhea and abdominal cramping. Vomiting and fever can occur but are uncommon. The incubation period ranges from 6 to 24 hours (usually 10 to 12 hours) and symptoms generally resolve within 24 to 48 hours. Restaurants and catering facilities are the most frequent food sources; outbreaks occur year-round, with a median size of approximately 20 individuals [25]. Outbreaks have also been described in inpatient psychiatric facilities; it has been postulated that antipsychotic (and other) medications impair intestinal mobility and increase susceptibility to infection [26].

C. perfringens-associated diarrhea should be suspected in single-source outbreaks that involve improperly cooked or stored meat. Both stool and food should be tested for the bacteria and the toxin. These tests are generally performed at reference laboratories. Infection is confirmed with a positive stool culture (ie, growth of at least 10⁶ colony-forming units [CFU] C. perfringens per gram). C. perfringens can be confirmed as the source of an outbreak when stool cultures are positive from at least two affected individuals, when enterotoxin is detected in stool from at least two affected individuals, or when culture of the suspect food source grows at least 10⁵ CFU C. perfringens per gram [27].

Supportive care, including oral or intravenous hydration, is warranted to prevent or treat volume depletion, but antibiotic treatment is unnecessary, as the infection is characteristically self-limited.

Type C strains produces a beta toxin, which can cause hemorrhagic necrosis of the jejunum, called enteritis necroticans or pigbel. Pigbel usually occurs in resource-limited countries (particularly Papua New Guinea) following pork consumption, but has been rarely described in the United States (in association with consumption of pig intestines [chitterlings]) and other resource-abundant settings [28,29]. The simultaneous ingestion of sweet potatoes, which contain trypsin inhibitors preventing the intestinal degradation of the toxin, may be a potentiating factor. Pigbel is characterized by abdominal distention and pain, with dilated thickened loops of bowel with segmental necrosis.

Enterotoxigenic E. coli — Enterotoxigenic E. coli (ETEC) is a common cause of diarrhea in resource-limited settings, and thus is associated with travelers' diarrhea in resource-abundant countries. It is not thought to be a common cause of domestically acquired diarrhea in resource-abundant settings, but it has been linked to sporadic outbreaks of diarrhea in the United States [30] and has also become a common pathogen in cruise ship diarrhea outbreaks [31]. Furthermore, it may be underdiagnosed as a cause of diarrhea because ETEC looks like any other E. coli on standard laboratory media used for stool culture and specific diagnostic tests for ETEC have not been routinely used [32].

ETEC is transmitted via fecal contamination of food or water from an infected person. Thus, prepared foods are a likely source for this pathogen. If ETEC is clinically suspected, the laboratory should be alerted to test for it specifically. The diagnosis can be made using DNA probes to identify toxin genes. (See "Pathogenic Escherichia coli associated with diarrhea", section on 'Enterotoxigenic E. coli' and "Travelers' diarrhea: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Giardia lamblia — Giardia lamblia (also known as Giardia duodenalis or Giardia intestinalis) causes both epidemic and sporadic cases of diarrhea. In the United States, it is one of the most common parasitic causes of diarrhea [24]. G. lamblia has been associated with waterborne and foodborne diarrhea and is a common pathogen in daycare center outbreaks.

Symptomatic acute infection develops approximately 7 to 14 days after exposure. In addition to diarrhea, abdominal cramps, bloating, and foul-smelling stools are common. Symptoms can persist for several weeks, and some patients can have more chronic infection. Giardiasis can be diagnosed with antigen detection assays, nucleic acid detection assays, and microscopic examination of stool. The clinical features, diagnosis, and treatment of giardiasis are discussed in detail elsewhere. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis" and "Giardiasis: Treatment and prevention".)

Cryptosporidium parvum — Cryptosporidium parvum is an important cause of diarrhea in both children and adults globally. In the United States, it is one of the most common parasitic causes of acute foodborne diarrhea, and approximately 10 percent of C. parvum infections are considered foodborne [24]. Cryptosporidium is endemic in cattle and transmission can occur through spread from an infected animal or person, or from a fecally contaminated environment, such as a food preparation site or water source. Numerous waterborne community outbreaks have occurred in various resource-abundant countries from contaminated drinking or swimming water [19,33,34]. Person-to-person transmission is also common, particularly among household members, sexual partners, children in daycare centers and their caretakers, and health care workers.

Infection with Cryptosporidium presents as a severe dehydrating but self-limited diarrheal illness in immunocompetent hosts. In immunocompromised hosts, it may have a more prolonged and severe course [35]. The diagnosis of cryptosporidiosis is generally made by microscopy, PCR, or enzyme immunoassays. The clinical features, diagnosis, and treatment of Cryptosporidium infections are discussed in detail elsewhere. (See "Cryptosporidiosis: Epidemiology, clinical manifestations, and diagnosis" and "Cryptosporidiosis: Treatment and prevention".)

Other pathogens

●Other toxin-producing bacteria – Staphylococcus aureus and Bacillus cereus produce enterotoxins that can be associated with acute diarrhea, but more often cause vomiting. (See 'Vomiting' below.)

Vibrio cholerae does not frequently cause infections outside resource-limited settings, where it is an important cause of severe watery diarrhea, but domestically acquired cases are rarely reported in resource-abundant settings. In the United States, such cases have been associated with eating seafood from the Gulf Coast [36]. (See "Cholera: Epidemiology, clinical features, and diagnosis" and "Infections due to non-O1/O139 Vibrio cholerae".)

●Listeria monocytogenes – L. monocytogenes is an uncommon cause of foodborne outbreaks of diarrhea. It is clinically significant mainly because it can cause invasive infections, particularly in older adults, immunocompromised patients, and pregnant women. (See 'Systemic illness' below and "Clinical manifestations and diagnosis of Listeria monocytogenes infection".)

●Bacteroides fragilis – B. fragilis has been associated with both community- and hospital-associated diarrhea [37,38]. In a study of 152 hospitalized patients with non-C. difficile diarrhea and 85 controls without diarrhea, PCR analysis of stool samples identified B. fragilis enterotoxin gene sequences significantly more frequently in patients with diarrhea (9 compared with 2 percent) [38].

●Cyclospora cayetanensis – A small bowel pathogen, C. cayetanensis, has been identified in both sporadic cases and outbreaks of diarrhea associated with imported raspberries and fresh basil [39,40]. Approximately 90 percent of C. cayetanensis infections are foodborne [41]. Its clinical presentation is notable both for the duration of diarrhea (which may average more than three weeks) and for the intense fatigue and malaise that accompany the diarrhea. It can be diagnosed by direct acid-fast microscopy of stool [42], but most microbiology laboratories will not routinely look for C. cayetanensis unless specifically requested. (See "Cyclospora infection".)

●Aeromonas spp and Plesiomonas shigelloides – These gram-negative bacilli are widely distributed in water environments. Aeromonas spp have been associated with travelers' diarrhea and diarrhea following contact with fresh or brackish water. P. shigelloides has emerged as a cause of diarrhea associated with ingestion of raw seafood. Both are more frequent in warmer temperatures. They typically cause watery diarrhea but can also less commonly cause inflammatory diarrhea. Infections tend to be mild and self-limited, although severe and extraintestinal infections can occur. (See "Aeromonas infections" and "Plesiomonas shigelloides infections".)

●Other parasites – Cystoisospora and the agents of microsporidiosis can cause self-limited watery diarrhea in immunocompetent patients. They are more notable for causing chronic infection in immunocompromised patients, in particular patients with advanced HIV infection. (See "Cyclospora infection" and "Microsporidiosis".)

Intestinal tapeworms can cause diarrhea in addition to a variety of other symptoms, as well as asymptomatic infection. Examples include Taenia saginata, Taenia solium, and Dibothriocephalus latus. These are acquired by consumption of undercooked beef, pork, and fish, respectively. (See "Tapeworm infections".)

Inflammatory diarrhea — Inflammatory diarrhea is characterized by fever, severe abdominal pain, and bloody or mucoid diarrhea. The presence of inflammatory cells or a marker of inflammation in the stool is a defining feature [43]. Bacteria are more common pathogens in inflammatory than watery diarrhea (table 1). In the United States, Salmonella and Campylobacter are the most common causes.

Salmonella — Nontyphoidal salmonellosis is a leading cause of acute diarrhea in resource-abundant settings. Infection with nontyphoidal Salmonella spp is most commonly associated with ingestion of poultry, eggs, and milk products. However, it has also been associated with ingestion of other foods (fresh produce, meats, nut products, spices) and animal contact. Symptoms generally occur within 8 to 72 hours following exposure. Diarrhea, nausea, vomiting, and fever are typical in symptomatic infection; the diarrhea is not usually grossly bloody. The diagnosis is made by routine stool cultures. (See "Nontyphoidal Salmonella: Microbiology and epidemiology" and "Nontyphoidal Salmonella: Gastrointestinal infection and asymptomatic carriage".)

Campylobacter — Campylobacter infection is generally acquired from undercooked contaminated poultry in resource-abundant settings. Studies from various locations, including the United States, indicate that 70 to 80 percent of retail poultry is contaminated with Campylobacter [44], thus making cross-contamination during food preparation an important hazard. Campylobacter jejuni accounts for the vast majority of foodborne campylobacteriosis, with Campylobacter coli responsible for most of the remainder. (See "Campylobacter infection: Microbiology, pathogenesis, and epidemiology".)

Diarrhea caused by this organism can be watery or hemorrhagic (ie, either as a small bowel or large bowel pathogen) and usually starts two to five days following exposure. Campylobacter has also been linked causally with subsequent reactive arthritis and Guillain-Barré syndrome. Although Campylobacter are fastidious and slow growing, they are typically diagnosed by routine stool culture using selective plates. (See "Campylobacter infection: Clinical manifestations, diagnosis, and treatment".)

Shigella — Shigella is the classic cause of colonic or dysenteric diarrhea. Shigella will only colonize humans and some nonhuman primates, so transmission occurs through direct person-to-person spread and from fecally contaminated food or water. As few as 10 organisms can initiate disease. Mucoid or bloody diarrhea with abdominal cramps and fever typically occurs one to seven days (average three days) following exposure. Shigella can cause outbreaks of acute gastroenteritis in school and child-care based settings [45] and among men who have sex with men [46,47]. The organism can be isolated through routine stool culture, and antibiotic susceptibility testing is important because antibiotic resistance is increasing in Shigella [48]. (See "Shigella infection: Epidemiology, clinical manifestations, and diagnosis" and "Shigella infection: Treatment and prevention in adults".)

Enterohemorrhagic E. coli — Enterohemorrhagic E. coli (EHEC), also known as Shiga toxin-producing E. coli (STEC), is an important cause of infectious colitis, which can be complicated by hemolytic uremic syndrome (HUS) [49]. While E. coli O157:H7 is the most common disease-causing serotype in the United States, there are many other EHEC serotypes, over 50 of which have been associated with diarrheal disease as well as HUS. EHEC is most commonly associated with ingestion of undercooked ground beef, but transmission has also occurred with other foods, including produce and other uncooked or unpasteurized products. (See "Shiga toxin-producing Escherichia coli: Microbiology, pathogenesis, epidemiology, and prevention".)

Symptom onset is typically three to four days (with a range of one to nine days) following exposure, with bloody diarrhea and abdominal pain. Sometimes, the diarrhea may initially be watery but often ultimately becomes bloody. Fever is often absent or low grade. EHEC can be diagnosed using Shiga toxin-based assays, which have advantages over the more conventional culture on sorbitol MacConkey agar. Use of sorbitol MacConkey plates (which can detect E. coli O157:H7 because it ferments sorbitol slowly compared with other E. coli) will fail to detect non-O157:H7 strains and appears to have diminished sensitivity compared with Shiga toxin-based tests [50]. Determining whether a patient is positive for EHEC has important therapeutic implications; antibiotic therapy is specifically avoided in EHEC infections [51,52]. (See "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment".)

Yersinia — Yersinia gastrointestinal infection is not especially common but occurs more frequently in resource-abundant than resource-limited countries. Yersinia enterocolitica occurs in the United States, while Yersinia pseudotuberculosis infection is more common in Europe. These infections are associated with consumption of undercooked pork, unpasteurized milk, or fecally contaminated water. Symptoms generally occur 1 to 14 days following exposure. In addition to diarrhea, some patients also have pharyngitis, which can be a distinguishing feature. Yersinia can be isolated through routine stool culture. (See "Yersiniosis: Infection due to Yersinia enterocolitica and Yersinia pseudotuberculosis".)

Other pathogens

●Entamoeba histolytica – Intestinal amebiasis is caused by Entamoeba histolytica. Amebiasis is a worldwide disease, but in resource-abundant countries such as the United States, amebiasis is mainly seen in migrants from and travelers to endemic countries. Institutionalized patients and men who have sex with men are also at increased risk of infection. Clinical amebiasis generally has a subacute onset, usually over one to three weeks. Symptoms range from mild diarrhea to severe dysentery producing abdominal pain, diarrhea, and bloody stools. Diagnosis is typically made by the combination of serology or antigen testing with identification of the parasite on microscopy of the stool. (See "Intestinal Entamoeba histolytica amebiasis".)

●Noncholera vibrios – Noncholera vibrios, particularly Vibrio parahaemolyticus, cause diarrhea associated with consumption of shellfish, particularly from warmer areas during the summer months. Grossly bloody diarrhea can also occur. If Vibrio spp are suspected, usually because of exposure history (travel or seafood consumption), the laboratory should be alerted to test for it specifically. Isolation of Vibrio spp from stool generally requires a selective medium, which most laboratories do not use for routine stool cultures. (See "Vibrio parahaemolyticus infections" and "Minor Vibrio and Vibrio-like species associated with human disease".)

●Invasive viruses – Cytomegalovirus (CMV) and herpes simplex virus (HSV) can uncommonly cause colitis, especially in immunocompromised individuals or those with inflammatory bowel disease. The diarrhea associated with these organisms is often bloody and inflammatory. Diagnosis is made by colonoscopy and biopsy, not by examination of stool. (See "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults", section on 'Gastrointestinal manifestations' and "AIDS-related cytomegalovirus gastrointestinal disease".)

VOMITING — The sudden onset of nausea and vomiting is likely due to the ingestion of a preformed toxin, such as S. aureus enterotoxin or B. cereus emetic toxin, or a chemical irritant. Gastroenteritis caused by other pathogens, mainly viruses, may also present with vomiting as the predominant symptom.

●S. aureus – S. aureus enterotoxin is heat-stable and is often associated with the consumption of foods prepared by a food handler, such as dairy, produce, meats, eggs, and salads [53,54]. The food handler usually contaminates the product; after the food is left at room temperature, the organisms multiply and can produce a substantial quantity of toxin. Following ingestion of S. aureus enterotoxin, nausea, vomiting, and abdominal cramps usually begin within one to six hours. Fever and/or diarrhea occur in a minority of patients. Because symptoms are caused by a preformed toxin, there is no risk of person-to-person spread. Vomitus and/or food can be tested for the enterotoxin, but the diagnosis of food poisoning due to S. aureus is usually clinical.

●B. cereus – B. cereus is also capable of producing a heat-stable emetic enterotoxin, typically in starchy foods such as rice [55]. The preformed B. cereus emetic enterotoxin causes a rapid (within one to six hours) onset of nausea and profuse vomiting. The disease is usually self-limited, although is very rarely associated with acute hepatic necrosis [56]. The diagnosis is usually clinical; reference laboratories have the capability of testing food or vomitus for the toxin. (See "Bacillus cereus and other non-anthracis Bacillus species".)

●Enteric viruses – In addition to causing diarrhea, enteric viruses, and in particular norovirus, can also present with vomiting as the predominant feature. (See 'Norovirus and other enteric viruses' above and "Norovirus".)

●Parasitic infections – Gastrointestinal symptoms can occur after ingestion of raw fish containing nematodes, such as those from the Anisakis or Eustrongylides family. When acute, this can lead to nausea, vomiting, and epigastric pain 1 to 12 hours after ingestion of raw fish. The symptoms typically resolve after regurgitation of the worm. (See "Miscellaneous nematodes", section on 'Anisakiasis'.)

The parasite Kudoa septempunctata has been associated with foodborne outbreaks in Japan characterized by intense vomiting and diarrhea 3 to 16 hours after ingestion of raw olive flounder [57]. Symptoms generally resolve within 24 hours.

NON-GASTROINTESTINAL SYNDROMES — Some foodborne pathogens cause serious illness but are not predominantly associated with gastrointestinal disease. Some of the major pathogens are discussed briefly below.

Neurologic symptoms — Several toxin-mediated foodborne illnesses present with predominantly neurologic features, in addition to more typical gastrointestinal symptoms.

●Botulism – Foodborne botulism is characterized by visual disturbances and potentially life-threatening descending paralysis following consumption of foods in which Clostridium botulinum spores have germinated into toxin-producing vegetative cells. Gastrointestinal symptoms may also be present. Typical foods associated with botulism are those canned at home, fermented fish, herb-infused oils, and foods held warm for extended periods of time. Stool and serum can be tested for toxin by reference laboratories. (See "Botulism".)

●Ciguatera toxin – Ciguatera toxin disease is associated with consumption of large reef fish, such as grouper, red snapper, amberjack, and barracuda, that have consumed dinoflagellates that produce heat-stable ciguatoxin. Ciguatoxin causes nausea, vomiting, diarrhea, and abdominal pain in the first two to six hours. These symptoms can be followed by paresthesia, weakness, and/or reversal of hot or cold. Cardiovascular abnormalities can also develop. The diagnosis is clinical. (See "Ciguatera fish poisoning".)

●Other toxins – Shellfish may also contain toxins that fall into three groups (diarrheic, neurotoxic, and amnesic) causing the various symptoms that their names imply. Symptoms usually occur within 30 minutes to several hours following exposure. (See "Overview of shellfish, pufferfish, and other marine toxin poisoning".)

There are also a variety of mushroom toxins that result in a mixture of gastrointestinal and neurologic disturbances, including hallucinations and confusion. (See "Clinical manifestations and evaluation of mushroom poisoning" and "Management of mushroom poisoning (except amatoxin-containing mushrooms)".)

Systemic illness — Some foodborne pathogens are clinically significant because of their systemic manifestations (either febrile illnesses or disseminated disease) rather than gastrointestinal manifestations.

●L. monocytogenes – In addition to febrile gastroenteritis, L. monocytogenes can cause invasive disease, including bacteremia and central nervous system infections in older adults, immunocompromised individuals, and pregnant women. Listeriosis has been associated with various foods, particularly delicatessen or processed meat, raw hot dogs, unpasteurized soft cheese, pâtés, and fruit. (See "Epidemiology and pathogenesis of Listeria monocytogenes infection", section on 'Food epidemiology and outbreaks' and "Clinical manifestations and diagnosis of Listeria monocytogenes infection" and "Treatment and prevention of Listeria monocytogenes infection".)

●Vibrio vulnificus – V. vulnificus is associated with raw shellfish consumption and can cause gastrointestinal or skin infection that rapidly develops into bacteremia and systemic disease, particularly in immunocompromised patients and those with chronic liver disease. (See "Vibrio vulnificus infection".)

●Scombroid – Scombroid poisoning reflects ingestion of toxic levels of biogenic amines (including histamine) associated with bacterial overgrowth on improperly stored fish (typically bluefish, tuna, mackerel, marlin, or mahi) or occasionally cheese. Within minutes to hours of consumption, patients complain of flushing, burning sensation, urticaria, dizziness, and paresthesia. (See "Scombroid (histamine) poisoning".)

●Typhoid fever – The typhoidal Salmonella, such as S. Typhi or S. Paratyphi, primarily colonize humans, are transmitted via the consumption of fecally contaminated food or water, and cause a systemic febrile illness usually with little or no diarrhea. In resource-abundant settings, typhoid fever is usually seen in individuals who have traveled from endemic areas, but domestic acquisition still occurs. (See "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis".)

●Brucella spp – Brucellosis is acquired from consuming unpasteurized dairy products or from undercooked meat from animals that are infected with Brucella. Four species, Brucella melitensis, Brucella abortus, Brucella suis, and Brucella canis, are known to cause disease in humans and typically lead to fever and a variety of other symptoms, such as weight loss, malaise, night sweats, and arthralgias. (See "Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Toxoplasma gondii – T. gondii can be transmitted through undercooked meats, such as lamb or hamburger (steak tartar), or through soil, food, or water contaminated by infected cat feces. Infection is frequently asymptomatic in normal hosts but can produce fatal pneumonitis, myocarditis, and neurologic symptoms in the immunocompromised. Vertical transmission from mother to child can occur during pregnancy, leading to congenital toxoplasmosis. (See "Toxoplasmosis: Acute systemic disease" and "Toxoplasmosis in patients with HIV" and "Toxoplasmosis and pregnancy".)

Hepatitis — The main foodborne cause of hepatitis in resource-abundant setting is hepatitis A virus. It can be transmitted from raw shellfish and other foods, such as fresh produce, but transmission is most common through prepared food contaminated by an infected food handler. Typical manifestations include abrupt onset of nausea, vomiting, fever, and abdominal pain, followed by jaundice; fulminant hepatic failure rarely occurs. The long incubation period (15 to 50 days) can complicate determination of the infectious source. The diagnosis is confirmed by serology. (See "Hepatitis A virus infection in adults: Epidemiology, clinical manifestations, and diagnosis".)

Hepatitis E virus is also foodborne. It is not common in resource-abundant settings, although some locations have reported an increase in incidence. Most hepatitis E infections are asymptomatic or mildly symptomatic. (See "Hepatitis E virus infection".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute diarrhea in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Food poisoning (The Basics)" and "Patient education: Viral gastroenteritis in adults (The Basics)" and "Patient education: Rotavirus infection (The Basics)" and "Patient education: Cryptosporidiosis (The Basics)")

●Beyond the Basics topic (see "Patient education: Foodborne illness (food poisoning) (Beyond the Basics)")

SUMMARY

●Clinical clues – Most cases of acute diarrhea and foodborne illness in adults are of infectious etiology and are self-limited. For most patients, the precise causative pathogen cannot be reliably distinguished based on clinical presentation alone. However, certain clinical features raise the likelihood of certain pathogens over others. These features include the precise clinical manifestations (watery versus inflammatory diarrhea or extra-intestinal manifestations) (table 1) and the exposure history (table 2). (See 'Clinical clues to the microbial cause' above.)

●Causes – The causes of infectious diarrhea vary from region to region, from rural to urban settings, and depending on co-morbidities, such as HIV or other immune-compromising conditions. In general, however, most cases of acute infectious diarrhea are caused by viruses, in particular norovirus. Bacteria are more likely pathogens in cases of severe or bloody diarrhea. Salmonella and Campylobacter are the generally the most common bacterial causes. (See 'Overview of causes' above.)

●Watery diarrhea – Other than norovirus, important causes of watery diarrhea include Clostridium perfringens, enterotoxigenic Escherichia coli (ETEC), and Cryptosporidium parvum. The clinical presentation of Clostridioides difficile ranges from watery to more inflammatory diarrhea. (See 'Watery diarrhea' above.)

●Inflammatory diarrhea – Other than Salmonella and Campylobacter, important causes of inflammatory diarrhea (characterized by fever, severe abdominal pain, and bloody or mucoid diarrhea) include Shigella, enterohemorrhagic E. coli, and Yersinia. (See 'Inflammatory diarrhea' above.)

●Vomiting – The sudden onset of nausea and vomiting is likely due to the ingestion of a preformed toxin, such as Staphylococcus aureus enterotoxin or Bacillus cereus emetic toxin, or a chemical irritant. Viral gastroenteritis also often presents with vomiting as the predominant symptom. (See 'Vomiting' above.)

●Non-gastrointestinal syndromes – Some foodborne pathogens cause serious illness but are not predominantly associated with gastrointestinal disease. Important examples include botulism, ciguatera or other toxin poisoning, Listeria monocytogenes bacteremia or central nervous system infection, scombroid, and hepatitis A virus infection. (See 'Non-gastrointestinal syndromes' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Christine Wanke, MD, and David Acheson, MD, FRCP, who contributed to an earlier version of this topic review.