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Diarrhea is the passage of unusually loose or watery stools, typically at least three times in a 24-hour period, and should be considered in a child who is passing stools more frequently than usual with a consistency looser than what is considered normal for that individual. Diarrhea is classified broadly by the duration of symptoms. Acute diarrhea is usually a self-limited illness that lasts for 2 weeks or less. Chronic diarrhea persists for more than 2 weeks. The etiologies of acute and chronic diarrhea differ by age ( Table 14.1 ).
TABLE 14.1
Differential Diagnosis of Acute and Chronic Diarrhea by Age
| Infants | Children | Adolescents |
|---|---|---|
| Acute | ||
| Common | Infectious gastroenteritis Food poisoning Antibiotic-associated diarrhea Food poisoning Systemic infection |
Infectious gastroenteritis Food poisoning Antibiotic-associated diarrhea Hyperthyroidism |
| Infectious gastroenteritis Systemic infection Medication induced (e.g., antibiotics, laxatives) Food protein–induced enterocolitis syndrome (FPIES) Food poisoning Overfeeding |
||
| Rare | ||
| Hirschsprung-associated enterocolitis Neonatal opioid withdrawal |
||
| Chronic | ||
| Disorders of Absorption and Transport of Nutrients and Electrolytes Primary lactase deficiency Secondary (e.g., postinfectious) lactase deficiency Congenital sucrose-isomaltase deficiency Trehalase deficiency Congenital chloride diarrhea Congenital sodium diarrhea Acrodermatitis enteropathica Glucose-galactose malabsorption Fanconi-Bickel syndrome Lysinuric protein intolerance Chylomicron retention disease Abetalipoproteinemia Enterokinase deficiency Maltase-glucoamylase deficiency Primary bile acid diarrhea Familial diarrhea syndrome Diarrhea-associated DGAT1 variants Defects in Enterocyte Structure Congenital tufting enteropathy Microvillus inclusion disease Trichohepatoenteric syndrome (syndromic diarrhea) Neuro-Enteroendocrine Diarrhea Enteric anendocrinosis Mitchell-Riley syndrome Proprotein convertase 1/3 deficiency X-linked lissencephaly Secretory tumors (e.g., neuroblastoma) Defects in Intestinal Immune-Related Homeostasis Cow’s milk or soy milk protein colitis Eosinophilic gastroenteritis and colitis Early-onset enteropathy with colitis IPEX syndrome IPEX-like disorders XIAP deficiency Autoimmune enteropathy Other primary immune deficiency disorders (e.g., SCID) Pancreatic Insufficiency Cystic fibrosis Shwachman-Diamond syndrome Johansson-Blizzard syndrome Pearson syndrome |
Disorders of Absorption and Transport of Nutrients and Electrolytes Lactose intolerance Secondary (e.g., postinfectious) lactase deficiency Congenital sucrose-isomaltase deficiency Primary bile acid diarrhea Familial diarrhea syndrome Disorders of Intestinal Motility Toddler’s diarrhea Irritable bowel syndrome Infectious Etiologies Giardiasis Cryptosporidium Defects in Enterocyte Structure Trichohepatoenteric syndrome (syndromic diarrhea) Neuro-Enteroendocrine Diarrhea Proprotein convertase 1/3 deficiency X-linked lissencephaly Secretory tumors (e.g., neuroblastoma, VIPoma) Defects in Intestinal Immune-Related Homeostasis Celiac disease Inflammatory bowel disease Eosinophilic gastroenteritis and colitis Early-onset enteropathy with colitis XIAP deficiency Autoimmune enteropathy Pancreatic Insufficiency Cystic fibrosis Chronic pancreatitis |
Disorders of Absorption and Transport of Nutrients and Electrolytes Lactose intolerance Laxative abuse Disorders of Intestinal Motility Irritable bowel syndrome Pseudoobstruction and bacterial overgrowth Infectious Etiologies Giardiasis Cryptosporidium Neuro-Enteroendocrine Diarrhea Primary adrenal insufficiency Defects in Intestinal Immune-Related Homeostasis Inflammatory bowel disease Celiac disease Eosinophilic gastroenteritis and colitis Pancreatic Insufficiency Chronic pancreatitis |
DGAT1, diacylglycerol O-acyltransferase 1; IPEX, immune disregulation, polyendocrinopathy, enteropathy, X-linked; SCID, severe combined immunodeficiency; VIP, vasoactive intestinal peptide; XIAP, X-linked inhibitor of apoptosis.
Diarrhea is further classified by pathophysiology, which typically involves one or more of the following mechanisms: (1) osmotic diarrhea , characterized by an increased intraluminal osmotic load leading to passive diffusion of fluid into the gastrointestinal lumen; (2) secretory diarrhea , characterized by increased active secretion of fluid into the gastrointestinal lumen beyond the capacity to be reabsorbed; and (3) altered gastrointestinal tract motility. Differentiating osmotic from secretory diarrhea allows for a more directed diagnostic evaluation ( Table 14.2 ). Osmotic diarrhea may be related to the malabsorption of carbohydrate, fat, or protein or to the presence of nonabsorbable substances in the gastrointestinal lumen. The characteristics of the stool may provide information that allows for the identification of the malabsorbed substance, particularly for isolated carbohydrate and fat malabsorption ( Table 14.3 ). Secretory diarrhea is characterized by an excess of crypt cell fluid and electrolyte secretion that exceeds the absorptive capabilities of the villi and is classified by the presence or absence of normal villi. Inflammatory diarrhea of both infectious and noninfectious etiologies usually involves both osmotic and secretory components. Finally, surgical bowel resection may decrease the surface area available for the resorption of both fluid and solutes, leading to both secretory and osmotic diarrhea. The causes of diarrhea based on pathophysiology are presented in Table 14.4 .
TABLE 14.2
Differentiating Osmotic from Secretory Diarrhea
| Osmotic | Secretory | |
|---|---|---|
| Stool volume | Small (<200 mL/24 hr) | Large (>200 mL/24 hr) |
| Response to fasting | Diarrhea improves | Diarrhea continues |
| Stool sodium | <70 | >70 |
| Stool osmotic gap ∗ | >50 | <50 |
| Stool pH | <5 | >6 |
TABLE 14.3
Distinguishing Isolated Carbohydrate from Isolated Fat Malabsorption
| Isolated Carbohydrate Malabsorption | Isolated Fat Malabsorption | |
|---|---|---|
| Stool character | Loose and watery, non–foul-smelling | Bulky large stool, foul-smelling, oil droplets visible |
| Perianal rash/skin erosion | Present | Present |
| Signs of fat-soluble vitamin deficiency | Variable | Present |
| Stool pH | Acidic (usually <6) | Alkaline |
| Stool reducing/nonreducing substances | Present | Absent |
TABLE 14.4
Differential Diagnosis of Diarrhea by Pathophysiology
Osmotic Diarrhea
|
Secretory Diarrhea
|
Inflammatory (Combination of Secretory and Osmotic)
|
Decreased Surface Area for Absorption
|
IPEX, immune disregulation, polyendocrinopathy, enteropathy, X-linked.
Acute Diarrhea
History
Acute diarrhea in children is most often infectious ( Table 14.5 ), although it may be secondary to noninfectious inflammatory processes, toxins, or medications. The etiology of acute diarrhea is suggested by both the history and characteristics of the stool ( Fig. 14.1 and Table 14.6 ). Fever or blood in the stool suggests an infectious cause. Watery diarrhea is typical of viral gastroenteritis, as well as some bacterial and parasitic infections. Dysentery , characterized by severe diarrhea and the presence of blood and mucus in the stool, suggests bacterial colitis. Vomiting and diarrhea developing within hours of food ingestion suggests exposure to preformed toxins in the food, rather than the acquisition of an enteric pathogen from the food, which is characterized by a predominantly diarrheal illness developing within days of exposure ( Fig. 14.2 ). A recent history of travel suggests traveler’s diarrhea , more than 80% of which is caused by bacterial species that are endemic to the area of travel, to which the patient has not been previously exposed. Recent travel may also suggest parasitic or helminthic infection. Exposure to health care settings suggests nosocomial diarrhea . Patients with a history of immunodeficiency or malnourishment may be more likely to have an infection with atypical or opportunistic organisms or to have a more protracted and severe course. Hematuria or oliguria may suggest hemolytic uremic syndrome (HUS) as a complication of infection with Escherichia coli 0157:H7 or Shigella. Other extraintestinal manifestations may also provide a clue to the diagnosis ( Table 14.7 ).
TABLE 14.5
Common Gastrointestinal Pathogens and Their Key Epidemiologic Features
Modified from Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett’s Principles and Practices of Infectious Diseases . 9th ed. Philadelphia: Elsevier; 2020:1332, Table 96.1.
| Organism | Key Epidemiologic Features |
|---|---|
| Viruses | |
| Adenovirus | Serotypes 40 and 41 among the leading causes of infantile gastroenteritis globally |
| Astrovirus | Outbreaks in closed populations |
| Norovirus | Most common cause of medically attended gastroenteritis in United States: winter vomiting illness; environmentally hardy |
| Rotavirus | Most common global cause of gastroenteritis in young children, particularly in settings without rotavirus vaccination |
| Sapovirus | Mainly affects infants and toddlers |
| Bacteria | |
| Aeromonas spp. | Widely distributed in aquatic environments; may cause diarrhea or extraintestinal infection |
| Bacillus cereus | Vomiting illness; rare fatal cases with hepatic necrosis; testing for toxin available |
| Campylobacter jejuni | Associated with poultry; common cause of traveler’s diarrhea in Asia; associated with postinfectious arthritis and Guillain-Barré syndrome |
| Clostridioides difficile | Leading cause of mortality from gastrointestinal infection in United States: community acquired and antibiotic associated |
| Clostridium botulinum | Vomiting illness due to preformed toxin ingestion; infant botulism due to germination of spores presents with progressive weakness |
| Enteroaggregative Escherichia coli | Persistent diarrhea in young children, associated with malnutrition |
| Enterohemorrhagic E. coli (STEC) | Associated with hemolytic uremic syndrome in children |
| Enteroinvasive E. coli | Associated with dysentery |
| Enteropathogenic E. coli | Acute watery diarrhea |
| Enterotoxigenic E. coli | Most common cause of traveler’s diarrhea |
| Listeria | Associated with raw dairy products; pregnancy complications with systemic illness |
| Nontyphoidal Salmonella spp. | Intestinal carriage can be prolonged |
| Plesiomonas shigelloides | May cause watery diarrhea, dysentery, or extraintestinal infection |
| Shigella spp. | Most common global cause of dysentery |
| Staphylococcus aureus | Vomiting due to preformed staphylococcal enterotoxin ingestion |
| Vibrio cholerae | Outbreaks of watery diarrhea associated with lack of sanitation and humanitarian crises |
| Vibrio parahaemolyticus | Associated with shellfish consumption |
| Yersinia enterocolitica | Zoonosis; able to grow in refrigerated food; associated with postinfectious polyarthritis |
| Yersinia pseudotuberculosis | Appendicitis-like syndrome |
| Protozoa | |
| Cryptosporidium hominis/parvum | Major cause of childhood diarrhea in children in low-income countries; daycare centers |
| Cyclospora cayetanensis | Opportunistic infection; associated with foodborne outbreaks |
| Cystoisospora belli | Tropical and subtropical areas; opportunistic infection |
| Entamoeba histolytica | May cause liver abscess |
| Giardia lamblia | Associated with drinking from contaminated streams; daycare centers |
| Microsporidium | Ubiquitous in the environment; opportunistic infection |
| Parasites | |
| Anisakis simplex | Vomiting illness after consuming raw fish |
STEC, Shiga toxin–producing enterohemorrhagic E. coli (original, alternative definition of enterohemorrhagic E. coli ).
TABLE 14.6
Clinical Syndromes Associated with Community-Acquired Gastrointestinal Infection
From Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett’s Principles and Practices of Infectious Diseases . 9th ed. Philadelphia: Elsevier; 2020:1335, Table 96.3.
| Clinical Syndrome | Signs and Symptoms | Pathogenic Mechanism | Example Pathogens |
|---|---|---|---|
| Acute watery diarrhea ∗ | Loose stools, often with mucus but not blood Occasional vomiting and anorexia Low-grade fever Malaise |
Local infection in the gut | Norovirus genogroups I, II, and IV; enteric adenovirus types 40 and 41; rotavirus; enterotoxigenic Escherichia coli ; enteropathogenic E. coli ; Cryptosporidium ; Clostridium perfringens ; Bacillus cereus |
| Dysentery (acute bloody diarrhea) | Loose stools with gross blood and mucus Fever Abdominal cramps and, in some cases, tenesmus May be clinically toxic |
Local invasion of the gut | Shigella, enteroinvasive E. coli, Campylobacter jejuni, Entamoeba histolytica, nontyphoidal Salmonella, Yersinia enterocolitica, Aeromonas, Plesiomonas, Clostridioides difficile |
| Profuse purging | Copious watery stools resembling “rice water” Low-grade fever Overt signs of dehydration |
Toxin mediated | Vibrio cholerae O1 and O139, enterotoxigenic E. coli |
| Persistent diarrhea | Similar to acute diarrhea, but symptoms persist for at least 14 days | Local infection in the gut and/or immune compromise of host | Giardia lamblia, Cryptosporidium hominis/parvum, Cystoisospora belli, Cyclospora cayetanensis, enteropathogenic E. coli, enteroaggregative E. coli |
| Acute vomiting | Sudden onset of nausea and vomiting Little or no diarrhea |
Local infection in the gut or intoxication | Norovirus, food poisoning due to Staphylococcus aureus, Bacillus cereus |
| Enteric fever | Fever Lymphadenopathy |
Local invasion of the gut with systemic spread | Salmonella enterica serovar Typhi, S. enterica serovar Paratyphi A, B, or C |
∗ Etiologic agents that can cause dysentery can also cause acute watery diarrhea.
TABLE 14.7
Extraintestinal Manifestations of Enteric Pathogens
Modified from Long SS, Prober CG, Fischer M, eds. Principles and Practice of Pediatric Infectious Diseases . 5th ed. Philadelphia: Elsevier; 2018:54, Table 55.3 .
| Manifestation | Related Enteric Pathogens |
|---|---|
| Erythema nodosum ∗ | Yersinia spp., Campylobacter spp., Salmonella spp. |
| Glomerulonephritis ∗ | Shigella spp., Campylobacter spp., Yersinia spp. |
| Guillain-Barré syndrome ∗ | Campylobacter spp. |
| Hemolytic anemia ∗ | Campylobacter spp., Yersinia spp. |
| Hemolytic uremic syndrome ∗ | STEC |
| Immunoglobulin A nephropathy ∗ | Campylobacter spp. |
| Reactive arthritis ∗ | Salmonella spp., Shigella spp., Yersinia spp., Campylobacter spp., Cryptosporidium spp. |
| Postinfectious irritable bowel syndrome | Campylobacter spp., Salmonella spp., Shigella spp., STEC, Giardia intestinalis |
| Meningitis | Listeria monocytogenes, Salmonella spp. (infants ≤3 mo at high risk) |
| Intestinal perforation | Salmonella spp. (including Typhi), Shigella spp., Campylobacter spp., Yersinia spp. |
| Encephalopathy, seizure | Shigella spp. |
| Toxic megacolon | Shigella spp., Clostridioides difficile |
| Aortitis, osteomyelitis | Salmonella spp. |
STEC, Shiga toxin–producing Escherichia coli .
Physical Examination
Physical examination should focus on assessing the level of hydration and the need for fluid resuscitation ( Table 14.8 ). The general examination may reveal nonenteric infections that could present with diarrhea, such as otitis media, pneumonia, or sepsis. Abdominal tenderness or masses suggest appendicitis, intussusception, or, less commonly, toxic megacolon. Generalized toxicity or shock may occur with HUS or with sepsis, such as from invasive Salmonella or staphylococcal toxic shock syndrome.
TABLE 14.8
Assessment of Degree of Dehydration
| General Appearance | Mild | Moderate | Severe |
|---|---|---|---|
| Infants/young children | Thirsty; alert; restless | Thirsty; restless or listless | Drowsy or lethargic; limp, cold, sweaty, cyanotic |
| Older children | Thirsty; alert; restless | Thirsty; alert (usually) | Usually conscious (but at reduced level), apprehensive; cold, sweaty, cyanotic extremities; wrinkled skin on fingers/toes; muscle cramps |
| Signs and Symptoms | |||
| Tachycardia | Absent | Present | Present |
| Palpable pulses | Present | Present (weak) | Decreased |
| Blood pressure | Normal | Orthostatic hypotension | Hypotension |
| Cutaneous perfusion | Normal | Normal | Reduced/mottled |
| Skin turgor | Normal | Slight reduction | Reduced |
| Fontanel | Normal | Slightly depressed | Sunken |
| Mucous membranes | Moist | Dry | Very dry |
| Tears | Present | Present/absent | Absent |
| Respirations | Normal | Deep, may be rapid | Deep and rapid |
| Urine output | Normal | Oliguria | Anuria/severe oliguria |
Viral Diarrhea
Rotavirus Infection
Rotavirus is the most frequent cause of severe diarrhea in unvaccinated infants and young children. The introduction of an effective vaccine has decreased the incidence, with most infections occurring in unvaccinated children under 3 years of age. In countries with a higher baseline socioeconomic status, it is typically seen in winter months, with prevalence decreasing substantially in summer months. Transmission is by the fecal-oral route and the incubation period ranges from 1 to 3 days. Patients typically present with the acute onset of fever and vomiting followed 1–2 days later by watery diarrhea. Symptoms generally persist for 3–8 days. In moderate to severe cases, dehydration, electrolyte abnormalities, and acidosis may occur. In immunocompromised children, persistent infection and chronic diarrhea can develop, with persistently positive diagnostic assays. Chronic infection is to be differentiated from postinfectious malabsorption seen in some immunocompetent children, in whom the small intestinal mucosa may require 3–8 weeks to recover its absorptive ability. Diagnosis is confirmed by nucleic acid amplification assays, enzyme immunoassay (EIA), immunochromatography, or latex agglutination assay for group A rotavirus antigen detection in the stool.
Norovirus Infection
Norovirus is a single-stranded RNA virus of the Calciviridae family and is the leading cause of epidemic outbreaks of acute gastroenteritis, as well as the most common cause of foodborne illness and foodborne disease outbreaks in the United States. Young children have the highest incidence of infection. Transmission is via the fecal-oral route or through contaminated food or water. Norovirus gastroenteritis typically presents with the abrupt onset of vomiting accompanied by watery diarrhea, abdominal cramps, nausea, and vomiting. Systemic manifestations, including myalgia, fatigue, and headache, may accompany gastrointestinal symptoms. Diagnosis is confirmed by nucleic acid amplification assays that detect viral RNA from the stool. Norovirus can cause persistent infection in immunocompromised patients and is difficult to clear without reconstitution of the immune system.
Bacterial Diarrhea
Most bacterial diarrheal illnesses are foodborne and affect infants and young children more frequently than adults. Bacterial infections of the intestine cause diarrhea via direct invasion of the intestinal mucosa, followed by intraepithelial cell multiplication or invasion of the lamina propria. Cellular invasion may be followed by the production of cytotoxin, which disrupts cell function, and/or the production of enterotoxin, which alters cellular electrolyte and water balance. Bacterial adherence to the mucosal surface may result in flattening of the microvilli and disruption of normal cell functioning. Symptomatic differentiation from viral causes of diarrhea may be difficult, and sequelae or extraintestinal manifestations of infections are varied (see Table 14.7 ).
SalmonellaInfection
Nontyphoidal Salmonella organisms are estimated to cause 1 million annual gastrointestinal infections in the United States. The attack rate is highest in infancy; the incidence of symptomatic infections is lower in patients older than 6 years. Salmonella infection may cause an asymptomatic intestinal carrier state that is rare in children, enterocolitis with diarrhea, or bacteremia without gastrointestinal manifestations but with subsequent local infections, such as meningitis or osteomyelitis. Salmonella infection is usually spread through contaminated water supplies or food (e.g., meat, chicken, eggs, raw milk, and fresh produce). Most infections in the United States are sporadic rather than epidemic. Although an infected food handler may contaminate food sources, farm animals or pets are more often the vector. Cats, turtles, lizards, snakes, and iguanas may also harbor Salmonella organisms. Outbreaks may occur among children in institutional settings; outbreaks in daycare centers are rare.
After a 12- to 72-hour incubation period, gastroenteritis develops and is characterized by the sudden onset of diarrhea, abdominal cramps and tenderness, and fever. The diarrhea is watery, with stools containing polymorphonuclear leukocytes and, on occasion, blood. The peripheral blood white blood cell count is usually normal. Symptoms slowly resolve within 3–5 days, although excretion of the organism may persist for several weeks. The organism is readily isolated from culture of the stool or a rectal swab or may be identified via multiplex PCR assays that detect multiple bacterial, viral, and parasitic enteric pathogens.
Shigella Infection
Most Shigella infections in the United States occur in young children aged 1–4 years, with a peak seasonal incidence in late summer and early autumn. It may also be the most common bacterial cause of diarrhea outbreaks in daycare settings. The organism is transmitted via the fecal-oral route, most often by the hands. During a 12- to 72-hour incubation period, patients may develop a nonspecific prodrome characterized by fever, chills, nausea, and vomiting. A predominantly rectosigmoid colitis develops and results in abdominal cramps and watery diarrhea. In more severe infections ( bacillary dysentery ), blood and mucus are passed in small, very frequent stools (see Table 14.6 ). High fever in young infants may induce febrile seizures, and some patients may develop HUS. Bacterial culture of the stool or a rectal swab, or the use of multiplex PCR assays, allows for differentiating this organism from other pathogens. If positive, antibiotic treatment is usually indicated.
CampylobacterInfection
Many animal species, including poultry, farm animals, and household pets, serve as reservoirs for Campylobacter jejuni . Transmission occurs through ingestion of contaminated food, especially undercooked food, and through person-to-person spread via the fecal-oral route. The disease is common in infants and adolescents, and both daycare and college outbreaks have been reported. Asymptomatic carriage is uncommon. Campylobacter infection symptoms may range from mild diarrhea to frank dysentery. The organism causes diffuse, invasive enteritis that involves the ileum and colon. Fever, cramping, abdominal pain, and bloody diarrhea are characteristic and may mimic symptoms of acute appendicitis or inflammatory bowel disease (IBD). Fever and diarrhea usually resolve after 5–7 days; prolonged illness or relapse occasionally occurs. Campylobacter infection is also known to cause meningitis, abscesses, pancreatitis, and pneumonia. Guillain-Barré syndrome has been reported after Campylobacter infection. Identification is via stool or rectal swab bacterial culture or via multiplex PCR assay. If positive, antibiotic treatment is indicated.
YersiniaInfection
Infection with either Yersinia enterocolitica or Yersinia pseudotuberculosis may cause various clinical syndromes, including gastroenteritis, mesenteric adenitis, pseudoappendicitis, and postinfectious reactive arthritis. The organism is present in animals and may be spread to humans by consumption of undercooked meat (especially pork), unpasteurized milk, and other contaminated foods. Person-to-person spread also occurs. Young children are particularly susceptible to disease, and the frequency of infections increases during the summer months.
The organisms may be identified via multiplex PCR assay or may be cultured from rectal swab or stool specimens, but selective media are required, and the organism may not be identified via culture for several weeks. The microbiology laboratory should be notified if Yersinia infection is suspected. Neonates, immunocompromised patients, and patients with bacteremia or extraintestinal infection should receive antibacterial therapy; treatment decreases the duration of fecal excretion and can additionally be considered in immunocompetent patients with moderate to severe symptoms.
Escherichia coli Infection
Although E. coli make up the predominant normal flora in the colon, some strains are pathogenic. Diarrhea caused by E. coli can be watery, inflammatory, or bloody, depending on the strain involved. These diarrheagenic E. coli strains are classified into five major groups on the basis of serogrouping or pathogenic mechanisms: (1) enteropathogenic E. coli (EPEC), an important cause of diarrhea in infants; (2) enterotoxigenic E. coli (ETEC), a cause of diarrhea in infants and a cause of traveler’s diarrhea; (3) enteroinvasive E. coli , a cause of watery ETEC-like illness or, less commonly, a dysentery-like illness; (4) enterohemorrhagic E. coli , a cause of hemorrhagic colitis and HUS; and (5) enteroaggregative E. coli , a cause of persistent diarrhea.
Enteric infections with E. coli are acquired via the fecal-oral route. Enterohemorrhagic strains are the only diarrhea-producing E. coli strains common in the United States and have been associated with foodborne epidemic outbreaks transmitted in some cases by undercooked meat.
EPEC is a well-established cause of infantile diarrhea, especially in countries with a lower baseline socioeconomic status. Asymptomatic carriage is common. At least two separate mechanisms are responsible for diarrhea: adherence to intestinal epithelial cells leading to villous injury and mucosal inflammation, and production of a toxin similar to that of Shigella organisms. Chronic infection resulting in failure to thrive may also occur.
ETEC is the major cause of traveler’s diarrhea; occasional nosocomial outbreaks have also occurred in hospitalized infants. At least three different types of E. coli enterotoxins (heat-labile, heat-stable toxin A, and heat-stable toxin B) have been identified. Definitive diagnosis requires enterotoxin identification, and this method is not widely available.
Enterohemorrhagic E. coli produces a Shiga-like cytotoxin and causes diarrhea, hemorrhagic colitis, and, in about 20% of infected persons, hemolytic uremic syndrome (HUS) . Both epidemic and sporadic cases have been recognized. Infection is more common in the summer and fall. A particular serotype, E. coli 0157:H7, has been linked to the development of HUS in young children. The most common manifestations of enterohemorrhagic E. coli infection begin with severe abdominal cramps and watery diarrhea, followed by grossly bloody stools and emesis. Fever is uncommon. Fecal leukocytes are absent or few. Other manifestations include asymptomatic infection and watery diarrhea without progression to hemorrhagic colitis. E. coli 0157:H7 is cleared from the stool in 5–12 days. If HUS develops, symptoms become noticeable in the week after the onset of diarrhea and consist of oliguric renal failure, microangiopathic hemolytic anemia, thrombocytopenia, and diarrhea. There is no role for antimicrobial therapy in enterohemorrhagic E. coli disease. Antibiotics neither shorten the duration of disease nor prevent progression to HUS; they may predispose to HUS.
Clostridioides difficile Infection
Clostridioides difficile (previously termed Clostridium difficile ) causes acute and chronic diarrhea in children when the normal colonic flora is disrupted. Pseudomembranous colitis is the most severe form of this infection, occurring as a result of a severe inflammatory response to the C. difficile toxins. Transmission occurs through person-to-person contact and through environmental contamination via the spores formed by C. difficile , which retain viability for up to 1 week on dry surfaces.
The prevalence of carrier status for C. difficile in healthy, asymptomatic outpatients is as high as 50% in healthy infants but is usually less than 5% in patients over 5 years of age. C. difficile and its toxin have been identified in the feces of healthy infants in concentrations similar to those found in adults with pseudomembranous colitis. The apparent resistance of infants to C. difficile and its toxin is related to the developmental absence of the toxin-binding site in the immature intestine. Asymptomatic carriage rates in hospitalized patients may be as high as 20%. Infection is highly associated with recent antibiotic exposure, particularly to broad-spectrum antibiotics, which disrupt the endogenous colonic flora that inhibits the growth of C. difficile . Other risk factors for C. difficile diarrhea include IBD, cystic fibrosis, use of proton pump inhibitors, indwelling enteral feeding tubes, and immunocompromised status.
C. difficile infection should be considered in patients in whom diarrhea develops during or within several weeks of antibiotic therapy. Illness associated with this organism varies from a mild, self-limited, nonbloody diarrhea to severe hemorrhagic colitis, protein-losing enteropathy, toxic megacolon, colonic or cecal perforation, peritonitis, sepsis, shock, and death. In rare cases, manifestations of C. difficile infection include fever or abdominal pain without diarrhea.
The colitis is caused by potent toxins produced by the organism: toxin A , a lethal enterotoxin that causes hemorrhage and fluid secretion in the intestines, and toxin B , a cytotoxin detectable by its cytopathic effects in tissue culture. Both toxins play a role in disease pathogenesis, although toxin B may be more important.
Recommendations for diagnosis of C. difficile infection are to consider a two-step method to exclude false-positive testing, particularly in the setting of asymptomatic carriage in infants and younger children: nucleic acid amplification testing to identify microbial toxin genes and an enzyme immunoassay for toxins in stool. Testing is typically performed only on patients with diarrhea who are not concurrently taking laxatives or promotility agents that could otherwise explain the diarrhea; testing may be considered for patients without loose stools if C. difficile –induced ileus or toxic megacolon is suspected. Sigmoidoscopy or colonoscopy reveals pseudomembranes in up to 50% of cases, typically in association with more severe disease. Treatment is dependent on the severity of the disease and whether the infection is primary or recurrent. Antibacterials include metronidazole, oral vancomycin, and, in adults, fidaxomicin.
Aeromonas Infection
Aeromonas species are gram-negative bacilli that are found in a variety of freshwater sources and that are capable of causing a wide array of disease, including a mild, self-limited diarrheal illness in children. Occasionally, Aeromonas may cause dysentery or a protracted diarrheal illness. The most common manifestation is a watery, nonbloody, nonmucoid diarrhea seen during the late spring, summer, and early fall. More severe infections may resemble ulcerative colitis, with chronic bloody diarrhea and abdominal pain.
Plesiomonas Infection
Plesiomonas shigelloides is a Vibrio -like organism found in soil and warmer (>8°C) fresh or brackish water that is sometimes implicated in childhood diarrhea. It has been linked to consumption of raw shellfish or contaminated water, exposure to reptiles and tropical fish, and travel to endemic areas. The organism is most frequently found in subtropical or tropical climates though has a wide geographic distribution. After an incubation period of 1–2 days, patients typically develop watery diarrhea and vomiting, although some may develop dysentery. Diagnosis is via stool culture. Symptoms may last up to 2 weeks, although the disease is typically self-limited in immunocompetent individuals.
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