on 17-Jul-2023 (Mon)

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).

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.

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)

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 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).

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.

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].

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).

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).

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].

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.

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).

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].

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].

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.

Watery diarrhea — Many pathogens can cause watery diarrhea (usually of large volume and associated with abdominal bloating, without fever or bloody stools). In resource-rich 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 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.

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.

C. perfringens is an important cause of foodborne, toxin-mediated watery diarrhea in resource-rich 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].

. 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

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-rich 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-rich countries.

ETEC is transmitted via fecal contamination of food or water from an infected person.

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.

Cryptosporidium parvum — Cryptosporidium parvum is an important cause of diarrhea in both children and adults globally.

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-rich 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.

Other toxin-producing bacteria – Staphylococcus aureus and Bacillus cereus produce enterotoxins that can be associated with acute diarrhea, but more often cause vomiting.

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-rich settings. In the United States, such cases have been associated with eating seafood from the Gulf Coast [36].

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.

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.

Salmonella — Nontyphoidal salmonellosis is a leading cause of acute diarrhea in resource-rich settings. Infection with nontyphoidal Salmonella spp is most commonly associated with ingestion of poultry, eggs, and milk products.

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

Campylobacter — Campylobacter infection is generally acquired from undercooked contaminated poultry in resource-rich 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. (

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.

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.

The organism can be isolated through routine stool culture, and antibiotic susceptibility testing is important because antibiotic resistance is increasing in Shigella [48].

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.

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.

Determining whether a patient is positive for EHEC has important therapeutic implications; antibiotic therapy is specifically avoided in EHEC infections [51,52].

Yersinia — Yersinia gastrointestinal infection is not especially common but occurs more frequently in resource-rich 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.

Amebiasis is a worldwide disease, but in resource-rich countries such as the United States, amebiasis is mainly seen in migrants from and travelers to endemic countries.

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

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.

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.

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.

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.

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].

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.

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.

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.

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.

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.

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)".)

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.

Listeriosis has been associated with various foods, particularly delicatessen or processed meat, raw hot dogs, unpasteurized soft cheese, pâtés, and fruit.

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.

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-rich settings, typhoid fever is usually seen in individuals who have traveled from endemic areas, but domestic acquisition still occurs.

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.

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.

Hepatitis — The main foodborne cause of hepatitis in resource-rich 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.

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