Acute Gastroenteritis in Children

Burden of Childhood Diarrhea

Although global mortality due to diarrheal diseases has declined substantially (39%) during the past 2 decades, it remains unacceptably high. In 2015, diarrheal disease caused an estimated 499,000, or 8.6% of all childhood deaths, making it the 4th most common cause of child mortality worldwide. Over the same period, a smaller decline (10%) was observed in the incidence of diarrhea disease among children younger than 5 yr. Almost 1.0 billion episodes occurred in 2015 worldwide, resulting in an estimated 45 million childhood disability-adjusted life years. Approximately 86% of the episodes occurred in Africa and South Asia (63% and 23%, respectively). The decline in diarrheal mortality, despite the lack of significant changes in incidence, is the result of preventive rotavirus vaccination and improved case management of diarrhea, as well as improved nutrition of infants and children. These interventions have included widespread home- and hospital-based oral rehydration solution (ORS) therapy and improved nutritional management of children with diarrhea.

In addition to the risk of mortality, high rates of diarrhea can be associated with long-term adverse outcomes. Diarrheal illnesses, especially episodes among young children that are recurrent, prolonged, or persistent, can be associated with malnutrition, stunting, micronutrient deficiencies, and significant deficits in psychomotor and cognitive development.

Pathogens

Rotavirus is the most common cause of AGE among children throughout the world. Several other viruses occur less frequently. Norovirus and sapovirus are the 2 genera of Caliciviruses that cause AGE. Norovirus genogroup II, genotype 4 (GII.4) has predominated globally during the past decade. Among the more than 50 serotypes of adenovirus, 40 and 41 are most often associated with diarrhea. Astroviruses are identified less often (see Table 366.1 ).

The major bacterial pathogens that cause AGE are nontyphoidal Salmonella (NTS), Shigella, Campylobacter , and Yersinia (see Table 366.2 ). Five pathotypes of Escherichia coli infect humans: Shiga toxin–producing (STEC), also known as enterohemorrhagic (EHEC), enterotoxigenic (ETEC), enteropathogenic (EPEC), enteroaggregative (EAEC), and enteroinvasive (EIEC). Two serogroups of Vibrio cholerae (O1 and O139) produce epidemic cholera and cause nearly all sporadic cases. Clostridium difficile disease can be both nosocomial and community acquired in children. Bacterial pathogens that cause foodborne illness due to their ability to produce emetic and/or enterotoxins include Bacillus cereus , Clostridium perfringens , and Staphylococcus aureus. The significance of isolating Aeromonas and Plesiomonas in a diarrheal stool remains uncertain.

Giardia intestinalis, Cryptosporidium spp. , Cyclospora cayetanensis , and Entamoeba histolytica are the most common parasites that cause diarrhea in the United States (see Table 366.3 ). At least 13 species of Cryptosporidium are associated with human disease, but C. hominis and to a less extent C. parvum are most common . The genus Entamoeba comprises 6 species that colonize humans, but only E. histolytica is considered a human pathogen . G. intestinalis (formerly G. lamblia and G. duodenalis ) is a flagellate protozoan that infects the small intestine and biliary tract. Other protozoa that uncommonly cause AGE are Isospora belli (now designated Cystoisospora belli ) and Blastocystic hominis.

Epidemiology in the United States and Other Middle- and High-Income Countries

Risk Factors Related to Economic Development. Insufficient access to adequate hygiene, sanitation, and clean drinking water are the main factors leading to the heavy burden of AGE in developing countries. Nonetheless, infectious AGE remains ubiquitous in middle- and high- income countries, although the severe consequences have become uncommon. In fact, economic development poses its own risks for transmission of enteric pathogens. The ability to mass-produce and widely distribute food has led to large multistate outbreaks of AGE due to NTS, STEC, and other agents. Globalization has cultivated a taste for tropical fruits and vegetables, creating a mechanism for importation of novel pathogens. The increasing frequency of antimicrobial resistance among bacteria that causes AGE has been linked to the use of antibiotics as growth-promotors for animals bred for food. Recreational swimming facilities and water treatment systems have provided a vehicle for massive outbreaks of Cryptosporidium , a chlorine-resistant organism. Venues serving catered food to large groups of people, such as hotels and cruise ships, are conducive to outbreaks, as are institutions where hygiene is compromised, such as daycare centers, prisons, and nursing homes. Hospitalization and modern medical therapy have created a niche for nosocomial C. difficile toxin infection ( Table 366.5 ).

Endemic Diarrhea. In the United States, rotavirus was the most common cause of medically attended AGE among children younger than 5 yr until the introduction of rotavirus vaccine for routine immunization of infants. Annual epidemics swept across the country beginning in the southwest in November and reaching the northeast by May, affecting nearly every child by the age of 2 yr. Since vaccine introduction, healthcare utilization for AGE has decreased markedly. Norovirus is the leading cause of AGE among children in the United States seeking healthcare, followed by sapovirus, adenovirus 40 and 41, and astrovirus (see Table 366.1 ).

Foodborne Transmission. The most comprehensive resource for describing the burden of bacterial and protozoal diarrhea in the United States is the Foodborne Diseases Active Surveillance Network (FoodNet) maintained by the Centers for Disease Control and Prevention (CDC) (see Table 366.4 ). FoodNet performs active laboratory-based surveillance of 9 bacterial and protozoal enteric infections commonly transmitted by food. Among children 0-19 yr of age in 2015, NTS was most common, followed by Campylobacter and Shigella , then STEC and Cryptosporidium . Vibrio, Yersinia, and Cyclospora were the least common (see Table 366.5 ). Children younger than 5 yr have the highest incidence of disease, and the elderly have the highest frequency of hospitalization and death. Only 5% of these infections are associated with recognized outbreaks.

Noninfectious agents may also cause foodborne gastrointestinal symptoms due to a direct toxic effect of the food (mushrooms) or contamination (heavy metals) ( Table 366.6 ).

Diarrhea Outbreaks. The U.S. Foodborne Disease Outbreak Surveillance System quantifies enteric infections associated with foodborne outbreaks. In 2015, among all age groups, norovirus was the most common agent (46%), followed by NTS (23%). Less common are C . perfringens (6%) , STEC (5%), Campylobacter (5%) , and S . aureus (2%), followed much less often (each 1%) by B . cereus , Clostridium botulinum, Shigella, Cryptosporidium, Yersinia, Listeria, Vibrio parahaemolyticus, and Shigella . Outbreaks of enteric pathogens propagated by direct person-to-person contact are most often caused by norovirus and Shigella species; other pathogens include NTS, rotavirus, Giardia , Cryptosporidium , C . difficile, and C. jejuni.

Nosocomial Diarrhea. C. difficile is the most common cause of healthcare-associated infection in the United States. Severe disease occurs most often in those with predisposing conditions (e.g., recent antibiotics, gastric acid suppression, immunosuppression, gastrointestinal comorbidities). In contrast to adults, rates of colostomy and in-hospital mortality have not increased in children despite increasing rates of community and hospital-acquired C. difficile infection, suggesting that C. difficile may be less pathogenic in children. Moreover, high rates of asymptomatic carriage (and presence of toxin) among children younger than 2 yr creates diagnostic uncertainty, so testing and treatment should be reserved for those with supporting clinical evidence (see Table 366.2 ).

Zoonotic Transmission. Many diarrheal pathogens are acquired from animal reservoirs (see Tables 366.1 to 366.3, 366.5 ). The ability of NTS to undergo transovarian passage in hens allows infection of intact grade A pasteurized eggs, a source of multiple large outbreaks. Although Campylobacter is prevalent in poultry, its lower outbreak potential has been attributed to its lack of transovarian spread in hens and stringent growth requirements, which limit its ability to replicate in foods. On the other hand, Campylobacter has an extensive reservoir in domestic and wild animals and remains a major cause of sporadic bacterial foodborne disease in industrialized countries, usually from consumption of contaminated chicken, meat, beef, and milk. Its ubiquitous animal reservoir also has resulted in widespread contamination of surface waters, resulting in diarrhea among hikers and campers who drink from streams, ponds, and lakes in wilderness areas. The predilection for STEC to asymptomatically colonize the intestines of ruminant animals explains why unpasteurized dairy products, fruits harvested from fields where cattle graze, and undercooked hamburger are common vehicles. The major animal reservoir for Yersinia is pigs, so ingestion of raw or undercooked pork products is an important risk factor. Pets can be the source of NTS (asymptomatic young birds, amphibians, and reptiles), Campylobacter , and Yersinia (puppies and kittens that are usually ill with diarrhea).

Seasonality. Seasonality provides a clue to implicate specific pathogens, although patterns may differ in tropical and temperate climates. Rotavirus and norovirus peak in cool seasons, whereas enteric adenovirus infections occur throughout the year, with some increase in summer. Salmonella, Shigella, and Campylobacter favor warm weather, whereas the tendency for Yersinia to tolerate cold manifests as a winter seasonality, with higher prevalence in northern countries, and ability to survive in contaminated blood products during refrigeration.

Epidemiology in Low- and Middle-Income Countries

The Global Enteric Multicenter Study (GEMS) evaluated children younger than 5 yr living in 7 low-income countries in sub-Saharan Africa and South Asia and seeking healthcare for moderate-to-severe diarrhea ( Fig. 366.1 ). Although a broad array of pathogens were identified, most episodes of moderate-to-severe diarrhea were attributed to 4 pathogens: rotavirus, Cryptosporidium, Shigella , and ETEC producing heat-stable toxin (ST) either alone or in combination with heat-labile toxin (LT), herein termed ST-ETEC, and, to less extent, adenovirus 40 and 41. On the other hand, several etiologic agents that are common causes of AGE in high-resource settings are notable for their low frequency in resource-limited settings: NTS, STEC, norovirus, and C. difficile toxin. The 3 agents associated with most deaths among children under 5 yr are rotavirus (29%), Cryptosporidium (12%), and Shigella (11%). The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) was a study of less severe, community-based diarrhea. Viral causes predominated (36.4% of the overall incidence), but Shigella had the single highest attributable incidence (26.1 attributable episodes per 100 child-years).

Pathogenesis of Infectious Diarrhea

Intrinsic properties of the organism help to define the mode of transmission and incubation period ( Table 366.8 ). Enteropathogens that are infectious in small inocula ( Shigella, STEC , norovirus, rotavirus, G. intestinalis, Cryptosporidium spp. , C. difficile, E. histolytica ) are readily transmitted by person-to-person contact via the fecal-oral route. Pathogens with larger infectious doses, such as cholera, NTS, ETEC, and Campylobacter , generally require food or water vehicles (see Tables 366.1 to 366.3 ). Pathogens that produce preformed toxins ( S. aureus, B. cereus emetic toxin) have shorter incubation periods (1-6 hr) compared with 8-16 hr for those that must elaborate enterotoxins in situ (e.g., C. perfringens and B. cereus enterotoxin ). Incubation periods of 1-5 days are seen with pathogens that attach to the epithelium and elaborate enterotoxins (e.g., V. cholerae , ETEC) or cytotoxins (e.g., S . dysenteriae type 1 and STEC) or those that invade and disrupt the intestinal epithelium ( Shigella , NTS, Campylobacter , and Yersinia ). The requirement for protozoa to progress through a life cycle to trigger pathogenic processes results in a more extended incubation period. Other properties affecting transmissibility are bioavailability as conferred by a copious and/or prolonged fecal shedding, extended infectivity in the environment, and resistance to disinfection (all exhibited by norovirus and Cryptosporidium ), or a large environmental or animal reservoir (e.g., Campylobacter ). The ability to circumvent immune surveillance by frequent antigenic changes resulting from recombinational events (e.g., norovirus) or a large serotype diversity (e.g., Shigella ) maintains a susceptible host population.

Viral AGE causes a cytolytic infection of the small intestinal villus tips resulting in decreased absorption of water, disaccharide malabsorption, inflammation, and cytokine activation. The rotavirus protein NSP4 acts as a viral enterotoxin that produces secretory diarrhea. In addition, rotavirus activates the enteric nervous system causing decreased gastric emptying and increased intestinal mobility. There is a genetic susceptibility to both rotavirus and norovirus infection that is mediated by histo-blood group antigens on the epithelial cell surface and in mucus secretions ( Fig. 366.2 ).

Pathogens primarily manifesting as secretory diarrhea attach to the surface of the epithelium and stimulate secretion of water and electrolytes by activating adenylate cyclase and raising intracellular cAMP ( V. cholerae and heat- LT–producing ETEC) and/or cGMP (ETEC producing heat-ST) ( Figs. 366.3 and 366.4 ). The diarrheagenic phenotype of C. difficile is attributed to production of toxins A (an enterotoxin) and B (an enterotoxin and cytotoxin). The epidemic hypervirulent NAP1 C. difficile also makes binary toxin, which may enhance colonization and augment toxin production.

Shigella , NTS, Campylobacter , and Yersinia all possess an invasive phenotype and elicit diarrhea by a variety of mechanisms that generally involves elicitation of inflammatory cytokines with or without associated toxin production ( Fig. 366.5 ). The pathogenesis of Shigella , the most common cause of bacillary dysentery, has been characterized in greatest detail. Following invasion, Shigella induces extensive destruction and inflammation of the intestinal epithelium producing ulcers and microabscesses that manifest with diarrheal stools containing blood and pus. Production of enterotoxins contributes to secretory diarrhea, which can be seen early in shigellosis or as the sole manifestation. A single serotype of Shigella , S . dysenteriae type 1, elaborates the Shiga toxin which increases the severity of illness and is responsible for development of hemolytic uremic syndrome (HUS).

Cryptosporidia sporozoites released from ingested cysts penetrate intestinal epithelial cells and develop into trophozoites within the intracellular, but extracytoplasmic, environment. After undergoing asexual multiplication and sexual development, they are released in the colon as infectious oocysts capable of causing autoinfection. Host factors, in particular T-cell function, play a critical role in disease severity. Cyclospora cysts are not infectious in freshly passed stools but must sporulate in the environment for 1-2 wk to become infectious; they are usually transmitted in contaminated produce and water (see Table 366.4 ).

Clinical Manifestation of Diarrhea

General Findings. Diarrhea is usually defined as the passage of 3 or more abnormally loose or liquid stools per day. Frequent passage of formed stools is not diarrhea, nor is the passing of loose, pasty stools by breastfed babies. Clinical clues to the possible etiology of gastroenteritis are noted in Table 366.9 .

In the past, many guidelines divided patients into subgroups for mild (3–5%), moderate (6–9%), and severe (≥10%) dehydration. However, it is difficult to distinguish between mild and moderate dehydration based on clinical signs alone. Therefore most guidelines now combine mild and moderate dehydration and simply use none, some, and severe dehydration. The individual signs that best predict dehydration are prolonged capillary refill time >2 sec, abnormal skin turgor, hyperpnea (deep, rapid breathing suggesting acidosis), dry mucous membranes, absent tears, and general appearance (including activity level and thirst). As the number of signs increases, so does the likelihood of dehydration. Tachycardia, altered level of consciousness, and cold extremities with or without hypotension suggest severe dehydration.

Viral Diarrhea. Symptoms of rotavirus AGE usually begin with vomiting followed by frequent passage of watery nonbloody stools, associated with fever in about half the cases (see Table 366.1 ). The diarrhea lacks fecal leukocytes, but stools from 20% of cases contain mucus. Recovery with complete resolution of symptoms generally occurs within 7 days. Although disaccharide malabsorption is found in 10–20% of episodes, it is rarely clinically significant.

Other viral agents elicit similar symptoms and cannot be distinguished from rotavirus based on clinical findings. In an outbreak setting, the pattern of a brief incubation period (12-48 hr), short duration of illness, and clustering of cases is shared by caliciviruses and preformed bacterial toxin. However, unlike preformed toxins, caliciviruses cause secondary infections, which confirm the contagious nature of the outbreak. Diarrheal illnesses caused by enteric adenovirus infections tend to be more prolonged than rotavirus (7 to 10 days), whereas astroviruses cause a shorter course (~5 days) usually without significant vomiting.

Bacterial Diarrhea. Although there is considerable overlap, fever >40°C, overt fecal blood, abdominal pain, no vomiting before diarrhea onset, and high stool frequency (>10 per day) are more common with bacterial pathogens (see Tables 366.2 and 366.9 ). Although high fever and overt fecal blood are often absent in bacterial enteritis, when present, there is a high probability of a bacterial etiology. The classical bacterial agents, NTS, Shigella, Campylobacter, and Yersinia, present with 1 of 5 syndromes.

• 1

  Acute diarrhea, the most common presentation, may be accompanied by fever and vomiting. Clinically silent bacteremia associated with uncomplicated NTS AGE can be seen among otherwise healthy children younger than 2 yr living in industrialized countries.

• 2

  Bloody diarrhea or frank dysentery is classically caused by Shigella . Watery diarrhea typically precedes dysentery and is often the sole clinical manifestation of mild infection. Progression to dysentery indicates colitis and may occur within hours to days. Patients with severe infection may pass more than 20 dysenteric stools in 1 day. Dysenteric illnesses due to Campylobacter have been confused with inflammatory bowel disease.

• 3

  Invasive, nonfocal disease ( enteric fever ) is a febrile illness associated with bacteremia without localized infection. Diarrhea may be minimal or absent. Although classically the result of S. Typhi or Paratyphi A and B, enteric fever can result from systemic spread of the classical bacterial enteropathogens. Although enteric fever caused by S. Typhi or Paratyphi A and B primarily affect preschool and school-age children in endemic countries, other bacterial enteropathogens most often cause disease in infants (particularly <3 mo), the immunocompromised, and children with malnutrition. Additional risk factors include hemolytic anemia and intravascular lesions for NTS, and iron overload, cirrhosis, and chelation therapy for Yersinia sepsis. The distinct clones of NTS that have arisen in sub-Saharan Africa described earlier are causing enteric fever–type illnesses often in the absence of AGE. Shigella sepsis is rare and is seen most often in malnourished and immunocompromised hosts.

• 4

  Extraintestinal invasive infections can result from either local invasion or bacteremic spread ( Table 366.10 ). Examples of local invasion include mesenteric adenitis, appendicitis, and rarely cholecystitis, mesenteric venous thrombosis, pancreatitis, hepatic, or splenic abscess. Bacteremic spread may result in pneumonia, osteomyelitis, meningitis (3 conditions seen most commonly with NTS), abscesses, cellulitis, septic arthritis, and endocarditis. Shigella can cause noninvasive contiguous infections such as vaginitis and urinary tract infections.

  Table 366.10

  Intestinal and Extraintestinal Complications of Enteric Infections

  From Centers for Disease Control and Prevention: Managing acute gastroenteritis among children, MMWR Recomm Rep 53:1–33, 2004.

  COMPLICATION	ASSOCIATED ENTERIC PATHOGEN(S)
  Intestinal Complications
  Persistent diarrhea Recurrent diarrhea (usually immunocompromised persons) Toxic megacolon Intestinal perforation Rectal prolapse Enteritis necroticans–jejunal hemorrhagic necrosis	All causes Salmonella, Shigella , Yersinia , Campylobacter, Clostridium difficile , Entamoeba histolytica , Cryptosporidium, Giardia Shigella , C. difficile , E. histolytica Shigella , Yersinia, C. difficile , E. histolytica Shigella , STEC, C. difficile Clostridium perfringens type C beta toxin
  Extraintestinal Complications
  Dehydration, metabolic abnormalities, malnutrition, micronutrient deficiency Bacteremia with systemic spread of bacterial pathogens, including endocarditis, osteomyelitis, meningitis, pneumonia, hepatitis, peritonitis, chorioamnionitis, soft tissue infection, and septic thrombophlebitis	All causes Nontyphoidal Salmonella, Shigella, Yersinia, Campylobacter
  Local spread (e.g., vulvovaginitis and urinary tract infection) Pseudoappendicitis Exudative pharyngitis, cervical adenopathy Rhabdomyolysis and hepatic necrosis	Shigella Yersinia, Campylobacter (occasionally) Yersinia Bacillus cereus emetic toxin
  Postinfectious Complications
  Reactive arthritis	Salmonella, Shigella, Yersinia, Campylobacter, Cryptosporidium, C. difficile
  Guillain-Barré syndrome	Campylobacter
  Hemolytic uremic syndrome	STEC , Shigella dysenteriae 1
  Glomerulonephritis, myocarditis, pericarditis	Shigella, Campylobacter, Yersinia
  Immunoglobulin A (IgA) nephropathy	Campylobacter
  Erythema nodosum	Yersinia, Campylobacter, Salmonella
  Hemolytic anemia	Campylobacter, Yersinia
  Intestinal perforation	Salmonella, Shigella, Campylobacter, Yersinia, Entamoeba histolytica
  Osteomyelitis, meningitis, aortitis	Salmonella, Yersinia, Listeria

  STEC, Shiga toxin–producing Escherichia coli.

• 5

  Vertical transmission of Shigella , NTS, and Campylobacter can produce perinatal infection resulting in a spectrum of illness from isolated diarrhea or hematochezia to fulminant neonatal sepsis. One species of Campylobacter, C. fetus, is particularly virulent in pregnant women and can result in chorioamnionitis, abortion, and neonatal sepsis and meningitis.

Crampy abdominal pain and nonbloody diarrhea are the first symptoms of STEC infection, sometimes with vomiting. Within several days, diarrhea becomes bloody and abdominal pain worsens. Bloody diarrhea lasts between 1 and 22 days (median 4 days). In contrast to dysentery, the stools associated with STEC hemorrhagic colitis are large volume and rarely accompanied by high fever. ETEC produce a secretory watery diarrhea that affects infants and young children in developing countries and is the major causative agents of travelers’ diarrhea, accounting for about half of all episodes in some studies. EPEC remains a leading cause of persistent diarrhea associated with malnutrition among infants from developing countries. EIEC, which are genetically, biochemically, and clinically nearly identical to Shigella , causes rare foodborne outbreaks in industrialized countries. EAEC has been associated with persistent diarrhea in immunocompromised persons and sporadic diarrhea in infants in countries with varying levels of economic development; however, some other studies have not found an association with disease.

C. difficile toxin is associated with several clinical syndromes. The most common is mild to moderate watery diarrhea, low-grade fever, and mild abdominal pain. Occasionally, the illness will progress to full-blown pseudomembranous colitis characterized by diarrhea, abdominal cramps, and fever. The colonic mucosa contains 2-5 mm raised, yellowish plaques. Fatal cases are associated with toxic megacolon, systemic toxicity, and multisystem organ failure, possibly related to systemic absorption of toxin. A vomiting illness is associated with S. aureus and B. cereus emetic toxin, while diarrhea is the major manifestation of C. perfringens and B. cereus enterotoxins.

Protozoal Diarrhea. Illnesses due to intestinal protozoa tend to be more prolonged, sometimes for 2 wk or more, but usually self-limited in the otherwise healthy host (see Table 366.3 ). In general, the duration and severity of Cryptosporidium diarrhea is strongly influenced by the immune and nutritional status of the host. A protozoal etiology should be suspected when there is a prolonged diarrheal illness characterized by episodes of sometimes-explosive diarrhea with nausea, abdominal cramps, and abdominal bloating. The stools are usually watery but can be greasy and foul smelling due to concomitant malabsorption of fats, which is more likely to occur if the parasite load is high. Occasionally diarrhea may alternate with constipation.

In addition to diarrhea, E. histolytica causes a range of other syndromes. Amebic dysentery is characterized by bloody or mucoid diarrhea, which may be profuse and lead to dehydration or electrolyte imbalances. Hepatic amebiasis is limited to abscess formation in the liver, which may occur with or without intestinal disease.

Intestinal and Extraintestinal Complications

The major complications from diarrhea from any cause are dehydration, electrolyte, or acid-base derangements, which can be life-threatening (see Table 366.10 ). Avoiding delays in diagnosis and treatment, and appropriate supportive care using either oral, enteral, or intravenous hydration can prevent or treat most of these conditions. Children who experience frequent episodes of acute diarrhea or prolonged or persistent episodes (seen especially in low resource settings) are at risk for poor growth and nutrition and complications such as secondary infections and micronutrient deficiencies (iron, zinc, vitamin A). Ensuring continued nutritional support during diarrheal episodes is important because prolonged limitation of the diet may extend diarrheal symptoms. Reestablishing a normal diet generally restores villous anatomy and function with resolution of loose stools.

Viral AGE illnesses are usually self-limited and resolve after several days. Rarely, intussusception is triggered by lymphoid hyperplasia associated with viral AGE. Complications of bacterial AGE may be the result of local or systemic spread of the organism; in malnourished children and HIV-infected populations, associated bacteremia is well-recognized. Toxic megacolon, intestinal perforation, and rectal prolapse can occur, particularly in association with Shigella in developing countries and C. difficile . The most dreaded complication of pediatric diarrhea in the United States is HUS , the leading cause of acquired renal failure in children, developing in 5–10% of patients infected with STEC. It is usually diagnosed 2-14 days after the onset of diarrhea. HUS is unlikely to occur once diarrhea has remained resolved for 2 or 3 days with no evidence of hemolysis. Risk factors include age 6 mo to 4 yr, bloody diarrhea, fever, elevated leukocyte count, and treatment with antibiotics and antimotility agents. Two-thirds of patients no longer excrete the organism at the time they develop HUS ( Chapter 538.5 ).

Pseudoappendicitis secondary to mesenteric adenitis is a notable complication of Yersinia , and sometimes Campylobacter . Older children and adolescents are most often affected. It typically presents with fever and abdominal pain with tenderness localized to the right lower quadrant, with or without diarrhea, and can be confused with appendicitis. CT scan or sonogram may be helpful to distinguish true appendicitis.

Immune-mediated complications that are thought to result from immunologic cross reactivity between bacterial antigens and host tissues are more often seen in adults than children. These include reactive arthritis following infection with the classical bacterial enteropathogens and Guillain-Barré syndrome following Campylobacter infection.

Protozoan illnesses, when persistent, can lead to poor weight gain in the young and immunocompromised individuals, weight loss, malnutrition, or vitamin deficiencies. Infection with Entamoeba can cause severe ulcerating colitis, colonic dilation, and perforation. The parasite may spread systemically, most commonly causing liver abscesses. In high-risk settings, it is critical to exclude Entamoeba infection and tuberculosis before initiating corticosteroids for presumed ulcerative colitis.