Diagnostic approach to diarrhea in children in resource-abundant settings

INTRODUCTION — This topic will discuss the approach to diarrhea in children living in resource-abundant settings. The approach to diarrhea in children living in resource-limited settings is discussed separately. (See "Approach to the child with acute diarrhea in resource-limited settings" and "Persistent diarrhea in children in resource-limited settings".)

DEFINITION — Diarrhea refers to the passage of loose or watery stools. The World Health Organization (WHO) defines a case as the passage of three or more loose or watery stools per day [1]. Nevertheless, absolute limits of normalcy are difficult to define; any deviation from the child's usual pattern should raise concern (particularly with ill appearance, the passage of blood or mucus, or dehydration) regardless of the actual number of stools or their water content.

CAUSES — Acute infectious gastroenteritis due to viruses accounts for most bouts of diarrhea in resource-abundant settings, resulting in more than 1.5 million outpatient visits and 200,000 hospitalizations in the United States annually [1]. However, watery and/or frequent stools may be the initial manifestation of a wide spectrum of other acute and chronic disorders (table 1) [2]. Norovirus has surpassed rotavirus as the most common pathogen in regions where vaccination against rotavirus has become routine [3].

Life-threatening conditions — A number of disorders causing diarrhea may be life-threatening in children and occasional patients with diarrhea from any cause may develop severe dehydration (table 1 and algorithm 1A) [4].

Sepsis — Diarrhea is commonly associated with sepsis caused by Salmonella spp and toxigenic strains of Staphylococcus aureus (staphylococcal toxic shock syndrome [TSS]):

●Salmonella bacteremia and sepsis occurs in 1 percent of all patients with nontyphoidal Salmonella gastroenteritis, respectively. Infants younger than one year of age and immunocompromised children (eg, patients with primary immunodeficiency, human immunodeficiency virus [HIV] infection, transplantation, or receiving tumor necrosis factor blocking agents such as etanercept or infliximab) are at higher risk. Affected patients typically have fever, diarrhea, and ill appearance. Septic shock may be present. Blood cultures provide the diagnosis and should be obtained in all children with fever and bloody diarrhea who are ill enough to require hospitalization. (See "Nontyphoidal Salmonella bacteremia and extraintestinal infection".)

●Profuse non-bloody and watery diarrhea frequently occurs as part of the initial presentation in patients with staphylococcal TSS. Hypotension is often severe and unresponsive to aggressive fluid resuscitation. The diagnosis of TSS is based upon clinical presentation (table 2). The isolation of S. aureus is not required for the diagnosis of staphylococcal TSS. S. aureus is recovered from wound or mucosal sites in 80 to 90 percent of patients with TSS and recovered from blood cultures in approximately 5 percent of cases. (See "Staphylococcal toxic shock syndrome", section on 'Clinical manifestations' and "Staphylococcal toxic shock syndrome", section on 'Diagnosis'.)

Intussusception — Intussusception is most common from 6 to 12 months of age, and the vast majority of cases occur in the first two years of life. Most children with intussusception develop sudden onset of intermittent, severe, crampy abdominal pain, accompanied by inconsolable crying and drawing up of the legs toward the abdomen. Bloody diarrhea is often a late finding, although rarely may be the sole presenting feature. The episodes of pain usually occur at 15- to 20-minute intervals. They become more frequent and may be followed initially by emesis of gastric contents. Bilious emesis may develop as the obstruction progresses. Between the painful episodes, the child may behave normally. As a result, initial symptoms can be confused with gastroenteritis. As symptoms progress, there may be intermittent episodes of lethargy that worsen over time, which can be mistaken for meningitis. A sausage-shaped abdominal mass may be felt, on occasion, in the right side of the abdomen. Abdominal radiographs may reveal a paucity of gas on the right, which may be better visualized with left lateral decubitus imaging. The diagnosis is established by abdominal ultrasound or air contrast enema. (See "Intussusception in children", section on 'Evaluation' and "Intussusception in children", section on 'Ultrasonography'.)

Hemolytic uremic syndrome — Healthy cattle are the main vectors of Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC), with the bacteria being present in the cattle intestine and feces. Infection in humans occurs following ingestion of contaminated undercooked meat, unpasteurized milk or milk products, water, fruits or vegetables, or coming into contact with animals in petting zoos. (See "Shiga toxin-producing Escherichia coli: Microbiology, pathogenesis, epidemiology, and prevention", section on 'Transmission'.)

Hemolytic uremic syndrome (HUS), although uncommon, merits consideration in any child with bloody diarrhea, particularly in the first five years of life, because it is a potentially fatal illness. It complicates 6 to 9 percent of enterohemorrhagic E. coli infections with the 0157:H7 strain and usually begins 5 to 10 days after the onset of diarrhea. HUS, which has a sudden onset, is characterized by the triad of (see "Clinical manifestations and diagnosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome in children", section on 'Typical course'):

●Microangiopathic hemolytic anemia

●Thrombocytopenia

●Acute renal failure

Children typically have a prodromal illness with abdominal pain, vomiting, and bloody diarrhea that precedes the development of HUS by several days to weeks, as a result of which a patient may have no signs of hemolysis or renal failure when seen earlier in the course. The diarrhea and associated gastrointestinal complaints may mimic those of ulcerative colitis, other enteric infections, and appendicitis. The diagnosis of HUS in children is generally made on clinical grounds based on the characteristic clinical and laboratory findings previously described: a prodrome of diarrhea due to a Shiga toxin-producing E. coli, followed by abrupt onset of the characteristic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. (See "Clinical manifestations and diagnosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome in children", section on 'Diagnosis'.)

Antibiotic treatment should be avoided in patients with HUS because it may cause relatively rapid worsening of clinical status or prolong the course of disease. (See 'Therapeutic interventions' below.)

The treatment of HUS is discussed separately. (See "Treatment and prognosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome in children".)

Fulminant C. difficile colitis (pseudomembranous colitis) — This disorder results from an overgrowth of toxin-producing clostridial organisms in the bowel. The typical presentation is acute watery diarrhea with lower abdominal pain, low-grade fever, and leukocytosis, starting during or shortly after antibiotic administration. Occasionally the course can be fulminant, progressing from diarrhea to toxic megacolon and shock. Community-associated infection with a highly toxigenic strain of Clostridioides difficile has been reported in otherwise healthy children who had minimal or no exposure to antibiotics. (See "Clostridioides difficile infection in children: Clinical features and diagnosis" and "Clostridioides difficile infection in children: Microbiology, pathogenesis, and epidemiology", section on 'Toxins'.)

The approach to diagnosis for C. difficile in children depends upon the age of the patient and clinical findings and is discussed separately. (See "Clostridioides difficile infection in children: Clinical features and diagnosis", section on 'Approach to diagnosis'.)

Appendicitis — Appendicitis typically begins with diffuse abdominal pain followed by vomiting, often in association with constipation. The three classic clinical features are (see "Acute appendicitis in children: Clinical manifestations and diagnosis", section on 'Clinical manifestations'):

●Periumbilical pain that subsequently migrates to the right lower quadrant

●Tenderness in the right lower quadrant

●Abdominal guarding and rebound

Observational studies suggest that children younger than five years of age are more likely to have diarrhea at presentation than school-aged children. The presumed mechanism for the diarrhea is irritation of the colon by the inflamed appendix. The stools are usually of low volume and with mucus. (See "Acute appendicitis in children: Clinical manifestations and diagnosis", section on 'Clinical features by age'.)

The diagnosis of appendicitis as the cause of diarrhea may be delayed because the classic constellation of findings is absent. This is particularly true in very young children or among patients of any age who have both a perforated appendix and a long duration of illness. However, abdominal tenderness may be greater than would be expected with gastroenteritis. An approach to the diagnosis of appendicitis is provided in the algorithm (algorithm 2). (See "Acute appendicitis in children: Clinical manifestations and diagnosis", section on 'Clinical features by age'.)

Toxic megacolon — Toxic megacolon is a potentially lethal complication of preexisting bowel disease or infectious colitis that is characterized by total or segmental nonobstructive colonic dilatation plus systemic toxicity. Signs and symptoms of acute colitis that are frequently resistant to therapy are often present for at least one week prior to the onset of acute dilatation. Severe bloody diarrhea is the most common presenting symptom, while improvement of diarrhea may herald the onset of megacolon. Physical examination invariably reveals a toxic appearing patient with altered sensorium, tachycardia, fever, postural hypotension, lower abdominal distension and tenderness, with or without signs of localized or generalized peritonitis. However, large doses of steroids, analgesics, or a clouded sensorium may mask the signs or symptoms of toxic megacolon. (See "Toxic megacolon", section on 'Clinical manifestations'.)

The diagnosis of toxic megacolon should be considered in all patients presenting with abdominal distension and acute or chronic diarrhea. The diagnosis is clinical, based upon the finding of an enlarged dilated colon on abdominal imaging accompanied by severe systemic toxicity. (See "Toxic megacolon", section on 'Diagnosis'.)

Toxic megacolon can occur as a complication of Shigella infection, pseudomembranous colitis, Hirschsprung disease, or inflammatory bowel disease. These conditions are reviewed separately. (See "Congenital aganglionic megacolon (Hirschsprung disease)" and "Management of the hospitalized child or adolescent with acute severe ulcerative colitis" and "Shigella infection: Epidemiology, clinical manifestations, and diagnosis", section on 'Intestinal complications'.)

Congenital secretory diarrheas — Congenital secretory diarrheas are characterized by profuse watery diarrhea beginning at or shortly after birth and are rare. They are caused by a variety of inherited disorders that disrupt nutrient digestion, absorption, or transport, enterocyte development and function, or enteroendocrine function. Although they are not usually life-threatening, congenital secretory diarrheas may lead to profound dehydration in the young infant over a short course of time. (See "Approach to chronic diarrhea in neonates and young infants (<6 months)", section on 'Congenital diarrheas and enteropathies'.)

Common conditions — The most common causes of diarrhea are infections with viruses and bacteria, diarrhea due to a systemic infection other than gastrointestinal, diarrhea associated with antibiotic administration, and feeding-related diarrhea [4].

Viral gastroenteritis — Viral gastroenteritis is, by far, the single most common diarrheal disorder seen in the emergency department and in general practice. Based upon prospective series of infants and children using various highly accurate methods for identification of viral infection, a viral pathogen is identified in up to 60 percent of all children with isolated diarrhea and over 75 percent of children with vomiting and diarrhea [5-7]. Since 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as an important viral etiology of diarrhea in children. The incubation time from exposure, predominant season, severity and duration of illness depends upon the specific virus (table 3). Stool testing for specific viruses is typically not necessary but may be employed during outbreaks to determine the etiology. (See "Acute viral gastroenteritis in children in resource-abundant countries: Clinical features and diagnosis", section on 'Etiology' and "COVID-19: Clinical manifestations and diagnosis in children".)

Non-bloody diarrhea, vomiting, and fever are the most common findings in children with viral gastroenteritis. Gross blood or mucus in the stool are uncommon in viral gastroenteritis and should prompt consideration of bacterial enteritis or other etiology. (See "Acute viral gastroenteritis in children in resource-abundant countries: Clinical features and diagnosis", section on 'Clinical presentation'.)

Bacterial enteritis — Bacterial enteritis typically affects children older than two years of age and occurs through oral-fecal contamination and after exposure to poultry, other farm animals, or contaminated meat or produce. Bacterial enteritis is a less frequent cause of diarrhea in children in resource-abundant regions than viral infection but has been identified in 17 percent of children with isolated diarrhea and 8 percent of those with vomiting and diarrhea; Salmonella spp and Campylobacter spp were most frequently recovered with isolated diarrhea [7].

Clinical features can include high fever, tenesmus, severe abdominal pain, and gross blood or mucus in the stool. Seizures may be associated with Shigella gastroenteritis. However, bacterial enteritis can be indistinguishable from viral gastroenteritis. Diagnosis is made by stool culture. (See "Acute viral gastroenteritis in children in resource-abundant countries: Clinical features and diagnosis", section on 'Bacterial or parasitic gastroenteritis'.)

Common bacterial causes of acute gastroenteritis in children include:

●Some E. coli spp (see "Shiga toxin-producing Escherichia coli: Microbiology, pathogenesis, epidemiology, and prevention" and "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment" and "Clinical manifestations and diagnosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome in children")

●Salmonella strains (see "Nontyphoidal Salmonella: Microbiology and epidemiology" and "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis" and "Nontyphoidal Salmonella: Gastrointestinal infection and asymptomatic carriage")

●Shigella spp (see "Shigella infection: Epidemiology, clinical manifestations, and diagnosis")

●C. difficile (see "Clostridioides difficile infection in children: Microbiology, pathogenesis, and epidemiology" and "Clostridioides difficile infection in children: Clinical features and diagnosis")

●Campylobacter jejuni (see "Campylobacter infection: Microbiology, pathogenesis, and epidemiology" and "Campylobacter infection: Clinical manifestations, diagnosis, and treatment")

●Yersinia enterocolitica (see "Yersiniosis: Infection due to Yersinia enterocolitica and Yersinia pseudotuberculosis")

Less common causes include Aeromonas hydrophila and Campylobacter upsaliensis. (See "Campylobacter: Infection with less common species and related bacteria", section on 'Campylobacter upsaliensis'.)

Extraintestinal infections — Extraintestinal infections (such as otitis media, urinary tract infections [UTIs], and pneumonia) can cause acute diarrhea without blood that is usually mild and self-limited and accompanied by fever or vomiting. (See "Acute otitis media in children: Clinical manifestations and diagnosis", section on 'Clinical presentation'.)

Diagnosis of these infections can usually be made by their extraintestinal manifestations and/or specific ancillary studies (eg, urinalysis, urine or blood culture, or chest radiograph):

●Bacterial sepsis – Patients with sepsis may have accompanying diarrhea but, with the exception of Salmonella sepsis and staphylococcal TSS, they do not present with diarrhea as a chief complaint or predominant symptom. (See "Sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis".)

●UTI – Clinical features of UTI include suprapubic and/or flank tenderness, dysuria, urgency, and frequency; however, diarrhea, with or without fever, may be the only symptom of an otherwise asymptomatic UTI in infants and young children. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Clinical presentation'.)

●Otitis media – Symptoms and signs of otitis media include ear pain, fussiness, bulging of the tympanic membrane, and hearing loss. Young children, usually under one to two years of age, with otitis media may present with diarrhea rather than ear pain. (See "Acute otitis media in children: Clinical manifestations and diagnosis", section on 'Clinical diagnosis' and "Acute otitis media in children: Clinical manifestations and diagnosis", section on 'Clinical presentation'.)

●Pneumonia – Clinical features of pneumonia include fever and symptoms or signs of respiratory distress (eg, tachypnea, nasal flaring, grunting, retractions, crackles, decreased breath sounds). (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Clinical presentation'.)

Antibiotic-associated diarrhea — Antibiotic-associated diarrhea (AAD) occurs commonly with many antibiotics prescribed for children, including amoxicillin, amoxicillin with clavulanic acid, cephalosporins, and clindamycin. In one prospective series, 18 percent of children less than two years of age developed diarrhea associated with antibiotic use [8]. The pathophysiology of AAD is poorly understood but is likely related to disruption in fecal flora with overgrowth of enteropathogens [9]. C. difficile is the specific pathogen that is most associated with AAD and has the greatest potential for severe outcomes. (See 'Fulminant C. difficile colitis (pseudomembranous colitis)' above.)

The diagnosis of AAD should be suspected in any child who develops diarrhea while on antibiotics. The approach to diagnosis for C. difficile in children depends upon the age of the patient and clinical findings and is discussed separately. (See "Clostridioides difficile infection in children: Clinical features and diagnosis", section on 'Approach to diagnosis'.)

Functional diarrhea — Increased intake of hyperosmolar fluids such as fruit juices in toddlers and young school children may cause diarrhea as the result of an increased osmotic load. When associated with excess carbohydrate intake, functional diarrhea also been called toddler's diarrhea or nonspecific diarrhea of childhood. Patients have painless passage of four or more large, unformed stools per day. Early morning stools are typically more formed than stools passed later in the day. Diarrhea typically improves when the volume of formula volume or intake of osmotically active carbohydrates (eg, fruit juice, sorbitol, or fructose) is reduced. (See "Overview of the causes of chronic diarrhea in children in resource-abundant settings", section on 'Functional diarrhea in young children'.)

Starvation stools — Diarrhea may also occur when intake of solid foods is limited (sometimes referred to as "starvation stools"). Although typically referring to a type of chronic diarrhea in malnourished children, diarrhea can also persist in well-nourished children with acute viral gastroenteritis who are only given clear liquids during the course of their illness. After fluid repletion is complete, resumption of a normal diet in patients with viral gastroenteritis helps to avoid this condition. (See "Acute viral gastroenteritis in children in resource-abundant countries: Management and prevention", section on 'Diet'.)

Treatment of children with severe malnutrition and starvation stools is discussed separately. (See "Management of complicated severe acute malnutrition in children in resource-limited settings", section on 'Overview of inpatient management'.)

Lactase deficiency — Lactase deficiency, when it occurs in younger children, is usually a transient problem caused by mucosal injury from an enteric infection. The lactose intolerance associated with acute viral gastroenteritis usually is mild and self-limiting, lasting several days to one to two weeks. Breastfeeding and infant formula can be resumed when severe dehydration is corrected and can continue without change for the child with mild dehydration. (See "Acute viral gastroenteritis in children in resource-abundant countries: Management and prevention", section on 'Diet'.)

In older children and adolescents, a primary lactase deficiency can causes chronic lactose intolerance. Ingestion of lactose may result in symptoms of abdominal pain, bloating, flatulence, and diarrhea. In addition, adolescents may have symptoms of vomiting. The abdominal pain may be cramping in nature and is often localized to the periumbilical area or lower quadrants. In children, the stools may be bulky, frothy, and watery. A presumptive diagnosis of lactose intolerance can be made in patients with mild symptoms that occur within a few hours after significant lactose ingestion (eg, >2 servings of dairy/day or >1 serving in a single dose that is not associated with a meal) and resolve after five to seven days of avoidance of lactose-containing foods. The diagnostic approach to lactose intolerance is discussed in greater detail separately. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management", section on 'Diagnostic evaluation'.)

Other conditions

●Parasitic infections – Parasitic infections are uncommon among immunocompetent children in resource-abundant settings but may occur in those patients with recent immigration, travel to an underdeveloped country, backcountry camping, exposure to poultry or other farm animals, or consumption of processed meat. Parasitic infections are also more frequently seen in immunocompromised patients and can cause severe illness. In immunocompetent hosts, parasitic infections typically cause watery diarrhea, abdominal cramping, vomiting, and low-grade fever.

Typical parasitic causes of acute gastroenteritis in immunocompetent children include:

•Giardia (see "Giardiasis: Epidemiology, clinical manifestations, and diagnosis")

•Cryptosporidium (see "Cryptosporidiosis: Epidemiology, clinical manifestations, and diagnosis")

•Cystoisospora belli (formerly known as Isospora belli) (see "Epidemiology, clinical manifestations, and diagnosis of Cystoisospora (Isospora) infections")

•Microsporidia and Cyclospora (see "Microsporidiosis" and "Cyclospora infection")

•Amebiasis (children or immigrants from endemic areas such as India, Africa, Mexico, Central and South America and, less commonly, among travelers to these regions; diarrhea may contain blood or mucus) (see "Intestinal Entamoeba histolytica amebiasis", section on 'Clinical manifestations')

•Intestinal tapeworms (see "Tapeworm infections")

In immunocompetent patients, the diagnosis of parasitic infection should be pursued when history uncovers risk factors for exposure and when diarrhea is persistent without an etiology. The evaluation typically begins with stool microscopy for ova and parasites. However, more sensitive and specific testing is also available for giardia and cryptosporidium. Such testing is indicated when stool microscopy is negative and an alternative diagnosis is not found as discussed separately.(See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Cryptosporidiosis: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

●Toxic exposures – Toxic exposures to contaminated food, toxic plants, toxic mushrooms, organophosphates, and carbamates can also cause diarrhea. History of exposure is key to making the diagnosis:

•Foodborne disease – Foodborne disease that presents with profuse watery diarrhea is characteristic of Clostridium perfringens (meat, poultry, and gravy) or enterotoxigenic E. coli (ETEC; potato salad and cruise ship diarrhea). (See "Causes of acute infectious diarrhea and other foodborne illnesses in resource-abundant settings", section on 'Watery diarrhea'.)

•Plant poisoning – Self-limited vomiting and diarrhea can be expected after ingestions of flower bulbs of the Amaryllidaceae family (narcissus, daffodil, and amaryllis), plant berries (eg, Ilex spp [holly], Phoradendron spp [mistletoe], Pyracantha spp, and poinsettia plants). More severe gastrointestinal toxicity can occur after ingestion of pokeweed (Phytolacca americana), castor bean (Ricinus communis), jequirity bean (Abrus precatorius), solanaceous plants ("nightshades"; eg, Solanum dulcamara or S. niger), and autumn crocus (Colchicum autumnale). (See "Potentially toxic plant ingestions in children: Clinical manifestations and evaluation", section on 'Gastrointestinal toxicity'.)

•Mushroom poisoning – A variety of mushroom species cause acute gastroenteritis soon after ingestion without any further toxicity. Often these exposures occur when children take a bite of a "little brown mushroom" while playing outside in the backyard. With ingestion of these mushrooms, symptoms occur within one to three hours and include nausea, vomiting, and abdominal cramping as well as diarrhea. Close attention to the history of ingestion and the timing associated with the onset of symptoms is important to differentiate acute gastroenteritis from the more concerning delayed gastroenteritis that may indicate consumption of a more lethal variety of mushroom toxins (eg, amatoxins, gyromitrin, orellanine). (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Acute gastroenteritis' and "Clinical manifestations and evaluation of mushroom poisoning", section on 'Delayed symptom onset (>6 hours after ingestion)'.)

•Organophosphate or carbamate compound poisoning – Diarrhea is a component of the cholinergic excess seen after ingestion, inhalation, or skin contamination of organophosphates and carbamates. Toxicity typically occurs within minutes to hours of exposure. Other findings include salivation, tearing, vomiting, bronchorrhea, bronchospasm, and bradycardia. Weakness, fasciculations, and paralysis may also develop. In addition, the patient may have a petroleum distillate or garlic odor. Diagnosis is made on clinical grounds. Direct measurement of red blood cell acetylcholinesterase activity provides a measure of the degree of toxicity. (See "Organophosphate and carbamate poisoning", section on 'Clinical features' and "Organophosphate and carbamate poisoning", section on 'Diagnosis'.)

●Laxative-induced diarrhea – Caregivers may give children laxatives in an attempt to treat constipation or, rarely, as a form of medical child abuse. Adolescents with eating disorders may misuse laxatives in an attempt to lose weight. The physician should inquire about laxative use when diarrhea is persistent or when other signs of an eating disorder are present. When intentional laxative use is suspected but is not disclosed on history, suggestive laboratory findings include hypokalemia, metabolic alkalosis, a positive laxative screen for diphenolic laxatives (eg, bisacodyl) and polyethylene glycol-containing laxatives, elevated stool magnesium or phosphate, or an elevated stool osmotic gap. (See "Eating disorders: Overview of epidemiology, clinical features, and diagnosis" and "Factitious diarrhea: Clinical manifestations, diagnosis, and management", section on 'Diagnosis'.)

A number of conditions in resource-abundant settings can present with diarrhea that is usually chronic (table 1). They include (see "Overview of the causes of chronic diarrhea in children in resource-abundant settings"):

●Primary immunodeficiencies (see "Approach to the child with recurrent infections", section on 'The child with an immunodeficiency')

●Diarrhea related to HIV infection (see "Evaluation of the patient with HIV and diarrhea")

●Food allergies including milk protein allergy (see "Clinical manifestations of food allergy: An overview", section on 'Gastrointestinal symptoms' and "Milk allergy: Clinical features and diagnosis", section on 'Clinical features')

●Celiac disease (see "Diagnosis of celiac disease in children", section on 'Patients with symptoms suggesting celiac disease')

●Inflammatory bowel disease (see "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Clinical manifestations')

●Cystic fibrosis (see "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Pancreatic disease')

●Acrodermatitis enteropathica (see "Zinc deficiency and supplementation in children", section on 'Acrodermatitis enteropathica')

●Neuroendocrine secretory tumors (eg, gastrinoma, VIPoma, and mastocytosis) (see "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis", section on 'Clinical manifestations' and "VIPoma: Clinical manifestations, diagnosis, and management", section on 'Clinical features' and "Mastocytosis (cutaneous and systemic) in children: Epidemiology, clinical manifestations, evaluation, and diagnosis", section on 'Gastrointestinal complaints' and "Mastocytosis (cutaneous and systemic) in children: Epidemiology, clinical manifestations, evaluation, and diagnosis", section on 'Signs and symptoms')

●Endocrine disorders (particularly hyperthyroidism but also hypoparathyroidism and congenital adrenal hyperplasia) (see "Clinical manifestations of hypocalcemia", section on 'Hypoparathyroidism')

●Neonatal drug withdrawal (see "Prenatal substance exposure and neonatal abstinence syndrome (NAS): Management and outcomes" and "Prenatal substance exposure and neonatal abstinence syndrome (NAS): Clinical features and diagnosis", section on 'Clinical manifestations of NAS')

●Short gut syndrome (see "Chronic complications of short bowel syndrome in children", section on 'Chronic diarrhea')

●Small intestinal bacterial overgrowth (see "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis", section on 'Clinical features')

●Factitious diarrhea (in adolescents engaging in laxative abuse) (see "Factitious diarrhea: Clinical manifestations, diagnosis, and management", section on 'Clinical manifestations')

●Irritable bowel syndrome (see "Chronic abdominal pain in children and adolescents: Approach to the evaluation", section on 'Diagnosis of functional abdominal pain')

ACUTE DIARRHEA (TYPICAL DURATION <5 DAYS)

History — There are a number of historical factors to identify:

●Immune status of the child – Immunocompromise increases the risk of infection by unusual organisms, the prevalence of which varies with the degree of immunosuppression and the nature of the underlying condition.

●Fever and bloody or mucousy diarrhea – These two features of the diarrheal illness, either alone or in combination, are particularly helpful in sorting through the differential diagnosis in otherwise healthy children. (See 'Algorithmic approach to the patient' below.)

●Potential for dehydration – The number of episodes of diarrhea per day, the amount of oral fluid intake, and urine output (eg, number of wet diapers or frequency of urination in the past 24 hours) and a recent weight (if available) help identify patients who are likely to be dehydrated.

●Duration of diarrhea – An acute diarrheal illness is typically defined as a duration of five days or less but return to normal stool consistency after viral gastroenteritis, the most common etiology in resource-abundant regions may take longer. Diarrhea that has persisted beyond five days may warrant consideration of other diagnoses, especially in children who are ill-appearing, have bloody diarrhea in association with weight loss, or other findings suggesting a more serious underlying condition such as those discussed below. (See 'Chronic diarrhea (duration >1 month)' below.)

●Institutionalized children and those recently returning from resource-limited settings are more likely to have bacterial or parasitic pathogens. (See "Travelers' diarrhea: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Recent antibiotic use – Recent exposure to antibiotics suggests the possibility of antibiotic-associated diarrhea and, in patients with a fulminant course, pseudomembranous colitis. (See "Clostridioides difficile infection in children: Clinical features and diagnosis", section on 'Symptomatic disease'.)

●Dietary history – Diarrhea in patients taking large amounts of formula, fruit juices, or sorbitol suggests overfeeding or functional diarrhea. Pain, bloating, flatulence, and diarrhea after eating lactose-containing food supports the diagnosis of primary lactase deficiency in older children and adolescents.

Physical examination — The patient who requires volume resuscitation must be quickly identified.

Mild dehydration (less than 5 percent body weight) is often not discernable by physical examination but may be suggested by a history of decreased oral intake, increased losses (eg, vomiting or diarrhea), and decreased urine output. Clinical evidence of moderate (5 to 10 percent) or severe (>10 percent) dehydration membranes is usually apparent (table 4). The most useful signs for predicting a volume deficit of 5 percent or more include a tired or fatigued general appearance, delayed capillary refill time greater than two seconds, dry mucous membranes, and decreased tears. However, no single physical examination finding is particularly predictive, and a combination of findings should be present for children with moderate to severe dehydration. When available, comparison of current weight with a recently obtained prior weight can also help define the percent of dehydration. (See "Clinical assessment of hypovolemia (dehydration) in children", section on 'Estimating degree of hypovolemia'.)

In addition to identifying volume depletion, a thorough examination must be performed:

●Systemic, non-enteric infections, particularly otitis media, may cause diarrhea.

●A palpable mass or peritonitis suggests appendicitis, intussusception or, less commonly, toxic megacolon.

●Generalized toxicity and/or shock may occur with hemolytic uremic syndrome (HUS) or with sepsis, such as from Salmonella or staphylococcal toxic shock syndrome (TSS) [10]. (See "Clinical manifestations and diagnosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome in children", section on 'Typical course'.)

Laboratory testing and imaging — Otherwise well children with acute, non-bloody diarrhea and no exposure to increase the risk of bacterial enteritis are usually managed without any ancillary studies. (See 'Common conditions' above.)

The laboratory evaluation of children with chronic diarrhea in resource-abundant settings is discussed separately. (See "Approach to chronic diarrhea in children >6 months in resource-abundant settings".)

Additional studies are warranted for the following children:

●Ill-appearing – Ancillary studies that help distinguish among life-threatening conditions in ill-appearing patients with diarrhea include (see 'Life-threatening conditions' above):

•Complete blood count with differential

•Peripheral blood smear

•Reticulocyte count

•Rapid blood glucose

•Serum electrolytes, blood urea nitrogen (BUN), and creatinine

•Blood culture

•Stool culture

•Stool for C. difficile toxin

•Plain abdominal radiographs (upright or left lateral decubitus and AP views) in patients with signs of toxic megacolon, peritonitis, or perforation

•Abdominal ultrasound in patients with findings suggesting intussusception or appendicitis

●Significant dehydration – Children with significant dehydration requiring intravenous rehydration should have serum electrolytes, including a rapid blood glucose, since hypoglycemia occurs not infrequently in this setting, BUN, and creatinine measured. (See "Clinical assessment of hypovolemia (dehydration) in children".)

●Fever and blood or mucus in the stool but without toxic appearance:

•Stool culture for Salmonella, Shigella, Campylobacter spp, Yersinia, and Shiga toxin-producing Escherichia coli (STEC); if a stool specimen is not immediately available, a rectal swab coated with stool may be sent. In settings where multiplex stool tests are used, a high degree of clinical correlation and a confirmatory stool culture are required before any treatment is provided. (See "Approach to the adult with acute diarrhea in resource-abundant settings", section on 'Multipathogen molecular panels'.)

•C. difficile toxin (only for patients older than one year of age with compatible clinical features antibiotic exposure or other risk factors or predisposing conditions). (See "Clostridioides difficile infection in children: Clinical features and diagnosis", section on 'Indications for testing'.)

A bacterial pathogen will be identified in 15 to 20 percent of cases [11-13]. Stool for ova and parasites is indicated for children who have traveled to or reside in an endemic area.

●Recent immigration, travel to an underdeveloped country, backcountry camping, exposure to poultry or other farm animals, or consumption of processed meat – Stool for ova and parasites

●Fever and no source (children younger than two years of age) – Urine dipstick or urinalysis and urine culture. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Decision to obtain urine sample'.)

Algorithmic approach to the patient — An algorithmic approach provides clinical guidance to the diagnostic approach of diarrhea in children (algorithm 1A and algorithm 1B and algorithm 3) [4].

First, the physician should determine whether the child appears seriously ill (algorithm 1A) or has signs of a surgical abdominal process.

●A palpable mass or peritonitis suggests appendicitis, intussusception, or, less commonly, toxic megacolon. (See 'Intussusception' above and 'Appendicitis' above and 'Toxic megacolon' above.)

●Generalized toxicity and/or shock may occur with HUS and with sepsis, such as from Salmonella or staphylococcal TSS. (See 'Sepsis' above and 'Hemolytic uremic syndrome' above.)

●Seizures may be seen with shigellosis, occasionally before the onset of diarrhea. (See "Shigella infection: Epidemiology, clinical manifestations, and diagnosis", section on 'Neurologic disease'.)

●Altered mental status with tenting of the skin and parched mucous membranes suggest severe dehydration.

●Immunocompromised patients (algorithm 1B) are at risk for unusual infections and require a rigorous approach in accordance with protocols specific to the underlying disorder. (See "Evaluation of the patient with HIV and diarrhea".)

●Profuse diarrhea in association with excessive salivation, lacrimation, and urination suggests organophosphate ingestion. (See 'Other conditions' above.)

Next, the physician focuses on those with acute diarrhea (algorithm 1B), as these patients are more likely to require a diagnostic or therapeutic intervention. Immunocompromised patients are at risk for unusual infections and require a rigorous approach in accordance with protocols specific to the underlying disorder. (See "Evaluation of the patient with HIV and diarrhea".)

Fever and bloody or mucousy diarrhea, either alone or in combination, are particularly helpful in sorting through the differential diagnosis (algorithm 1B):

●Blood is seen in the stool of up to 10 percent of children with diarrhea. In most cases, the blood appears in small quantities as drops on the surface of the stool and should not be construed as ominous.

●A small percentage of children with diarrhea, however, have more profuse rectal bleeding. Particularly in these patients, one must exclude life-threatening disorders such as intussusception, HUS, and pseudomembranous colitis. (See 'Intussusception' above and 'Hemolytic uremic syndrome' above and 'Fulminant C. difficile colitis (pseudomembranous colitis)' above.)

●Mucousy diarrhea, with or without blood, suggests bacterial enteritis [12,13].

Febrile with non-bloody diarrhea — The presence of fever in an immunocompetent child with diarrhea is the hallmark of infection. Most febrile children with non-bloody diarrhea have viral enteritis. Although children with SARS-CoV-2 most often present with respiratory complaints, fever and diarrhea can be the sole presenting symptoms in infants and young children. (See "Acute viral gastroenteritis in children in resource-abundant countries: Clinical features and diagnosis".)

Afebrile with non-bloody diarrhea — Many afebrile children with non-bloody diarrhea will also have viral enteritis. For those taking antibiotics, such as amoxicillin, the diarrhea may be related to the medication [8,9].

Overfeeding may cause diarrhea during the first 6 to 12 months of life. The history of excessive formula intake in an overweight child indicates this diagnosis [14]. Excessive intake of fruit juices or sorbitol may cause functional diarrhea in older children.

Febrile with bloody diarrhea — Febrile children with bloody and/or mucousy diarrhea typically have infectious bacterial enteritis, although some may have viral infections. (See 'Bacterial enteritis' above and "Causes of acute infectious diarrhea and other foodborne illnesses in resource-abundant settings", section on 'Severe or bloody diarrhea'.)

Pseudomembranous colitis is an important consideration in febrile children with bloody diarrhea who have also received antibiotic therapy, especially if systemic toxicity, abdominal distension, and gross blood in the stools are present. (See "Clostridioides difficile infection in children: Clinical features and diagnosis", section on 'Symptomatic disease'.)

Possible exceptions include the following:

●Amebiasis merits consideration in children or immigrants from endemic areas (eg, India, Africa, Mexico, Central and South America) and, less commonly, among travelers to these regions. (See "Intestinal Entamoeba histolytica amebiasis", section on 'Epidemiology'.)

●Children with inflammatory bowel disease may present with an initial episode of acute, bloody diarrhea. In most of these cases, the physician can elicit a preceding history of weight loss and/or recurrent abdominal pain. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Findings suggesting colitis'.)

Afebrile with bloody diarrhea — Afebrile children with bloody diarrhea represent the most worrisome category because most patients with intussusception or HUS have this symptom constellation:

●Intussusception is a major concern in any child less than two years of age with grossly bloody diarrhea that does not appear to have an infectious cause. A history of severe, colicky abdominal pain in a lethargic child warrants an abdominal ultrasound or contrast enema. (See "Intussusception in children", section on 'Clinical manifestations'.)

●Bloody diarrhea with pallor, purpura, and hematuria with elevated serum BUN or creatinine and thrombocytopenia point to HUS. (See "Clinical manifestations and diagnosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome in children", section on 'Typical course'.)

The most common diagnosis, infectious bacterial enteritis, should be made only after exclusion of the more serious disorders by history, physical examination, and occasionally, laboratory or imaging studies.

Therapeutic interventions — Children with life-threatening causes for diarrhea warrant specific therapy dictated by the underlying condition. (See 'Life-threatening conditions' above.)

●Fluid resuscitation – Parenteral fluid resuscitation with an isotonic solution (eg, normal saline) should be initiated promptly in children with severe dehydration or circulatory compromise and may be particularly important in preventing oliguric renal failure in those patients with HUS. Patients with toxic megacolon and intussusception may also have significant ongoing third space losses that must be replaced. (See "Treatment and prognosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome in children", section on 'Fluid management' and "Hypovolemic shock in children in resource-abundant settings: Initial evaluation and management", section on 'Management'.)

Most children with diarrhea will not require intravenous fluid repletion. Treatment with oral rehydration solutions should be encouraged as the first line therapy for both rehydration and maintenance therapy in patients who have mild to moderate dehydration and can drink. (See "Oral rehydration therapy".)

●Antibiotics – Antibiotics should not be used routinely for well-appearing children with acute bloody diarrhea unless a specific pathogen has been isolated. Antibiotic therapy may be a risk factor for the development of HUS in patients with bloody diarrhea due to E. coli O157:H7, which may be indistinguishable from bloody diarrhea seen with other non-E. coli bacterial etiologies [15]. (See "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment", section on 'Antibiotics'.)

However, antibiotics are essential to the proper treatment of sepsis, peritonitis, and staphylococcal TSS. (See "Septic shock in children in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)", section on 'Empiric antibiotic therapy'.)

Indications for antibiotic therapy in patients with specific gastrointestinal pathogens are discussed separately:

•(See "Shigella infection: Treatment and prevention in children", section on 'Antibiotic therapy'.)

•(See "Nontyphoidal Salmonella: Gastrointestinal infection and asymptomatic carriage", section on 'Indications'.)

•(See "Campylobacter infection: Clinical manifestations, diagnosis, and treatment", section on 'Indications'.)

•(See "Yersiniosis: Infection due to Yersinia enterocolitica and Yersinia pseudotuberculosis".)

●Probiotics – Probiotics refer to products derived from food sources, especially cultured milk products. The list of such microorganisms continues to grow and includes a variety of different strains of bacteria. Probiotics appear to have only a modest effect on recovery from infectious diarrhea. Systematic reviews also suggest that probiotics (including various bacterial species and the yeast S. boulardii) are effective in reducing the incidence of diarrhea in patients who are taking antibiotics. However, discordant data have been published and there is little detailed information regarding the optimal dose or timing of supplementation or the effects on subgroups of patients. The use of probiotics for these indications is discussed in more detail separately. (See "Probiotics for gastrointestinal diseases", section on 'Infectious diarrhea'.)

Disposition — The majority of children with infectious diarrhea have mild to moderate dehydration and can be managed as outpatients after receiving appropriate assessment and have proven oral rehydration therapy will be successful. (See "Treatment of hypovolemia (dehydration) in children in resource-abundant settings".)

Hospital admission is warranted in children with any one of the following findings:

●Diagnosis of or strong clinical suspicion for a life-threatening cause of diarrhea, such as HUS or other systemic illnesses (see 'Life-threatening conditions' above)

●Severe dehydration or significant electrolyte abnormalities upon presentation (see "Clinical assessment of hypovolemia (dehydration) in children", section on 'Estimating degree of hypovolemia')

●Lack of improvement with rehydration

●Continued copious diarrhea that is likely to lead to recurrent dehydration if intravenous replacement of ongoing losses does not occur

●Inability to drink

●Caregiver inability to manage the child’s condition or recognize deterioration

Persistent diarrhea — The child who returns with the persistence of an acute diarrheal illness, initially presumed to be viral in origin and with no evidence of malnutrition or dehydration, often can be managed without an extensive evaluation.

Common causes, in addition to persistent viral infection, are:

●Starvation stools due to excessive use of a clear liquid diet for several days

●Secondary lactase deficiency following viral enteritis

●Bacterial infections

A stool culture should be obtained and testing for C. difficile toxin is indicated in children older than one year of age who have had recent antibiotic therapy or bloody diarrhea.

Gradual refeeding is recommended if starvation stools are suspected (ie, the child has remained on a clear liquid diet).

In those children with diarrhea of intermediate duration (one to four weeks), the potential etiologies include:

●Appendiceal abscess (particularly in patients with fever associated with abdominal tenderness or a history of abdominal pain) (see "Acute appendicitis in children: Clinical manifestations and diagnosis")

●Bacterial enteritis or parasitic infestations (see "Acute viral gastroenteritis in children in resource-abundant countries: Clinical features and diagnosis", section on 'Bacterial or parasitic gastroenteritis')

CHRONIC DIARRHEA (DURATION >1 MONTH) — A brief initial evaluation of the child with chronic diarrhea in the acute setting (eg, emergency department) is described below. An expanded differential diagnosis and more comprehensive diagnostic approach to chronic diarrheal diseases in resource-abundant settings is discussed in detail separately. (See "Overview of the causes of chronic diarrhea in children in resource-abundant settings" and "Approach to chronic diarrhea in children >6 months in resource-abundant settings" and "Approach to chronic diarrhea in neonates and young infants (<6 months)".)

A child with chronic diarrhea who presents in an acute care setting is often not seriously ill. The evaluation usually requires a period of observation and ancillary studies based upon the most likely underlying etiology rather than urgent diagnostic and therapeutic intervention. Urgent conditions are suggested by a history of bloody diarrhea or the physical finding of abdominal tenderness (algorithm 3).

In resource-limited settings, chronic diarrhea typically is associated with serial enteric infections and malnutrition. This common pathophysiology calls for a distinct approach to diagnosis and treatment, which is discussed separately. (See "Persistent diarrhea in children in resource-limited settings".)

The following findings may indicate serious underlying disease in the child with chronic diarrhea:

●A history of delayed passage of meconium, constipation since birth, and abdominal distension are compatible with Hirschsprung disease. (See "Congenital aganglionic megacolon (Hirschsprung disease)", section on 'Clinical features'.)

●Malabsorptive stools (steatorrhea) and respiratory infections suggest cystic fibrosis. (See "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Pancreatic disease'.)

●Failure to thrive, thrush, and pneumonia occur in association with human immunodeficiency virus (HIV) infection or primary immunodeficiency. (See "Pediatric HIV infection: Classification, clinical manifestations, and outcome", section on 'Clinical manifestations' and "Severe combined immunodeficiency (SCID): An overview", section on 'Clinical manifestations'.)

●Bloody diarrhea with weight loss points to inflammatory bowel disease, particularly if the diarrhea is bloody, or to irritable bowel syndrome. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Clinical manifestations'.)

●Congenital secretory diarrheas begin at or shortly after birth with profuse, watery diarrhea.

The extent of ancillary testing depends upon the degree of illness and the suspected underlying diagnosis. (See "Approach to chronic diarrhea in children >6 months in resource-abundant settings".)

At minimum, a stool culture and a stool for ova and parasites would aid in the diagnosis of infections of the gastrointestinal tract and provide a head start on the evaluation for the physician who subsequently sees the child.

The child with chronic diarrhea who is well-appearing and tolerates oral fluids can be managed as an outpatient. The key factor in successfully diagnosing the etiology of the diarrhea is reliable follow-up with a primary care provider or, when serious underlying disease is suspected, referral to a pediatric specialist.

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 children".)

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 topic (see "Patient education: Diarrhea in children (The Basics)")

●Beyond the Basics topic (see "Patient education: Acute diarrhea in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Diagnostic approach – The approach to the evaluation of acute diarrhea in resource-abundant settings is summarized in the algorithms (algorithm 1A-B). The table summarizes the causes of diarrhea, highlighting the most common and the most life-threatening pediatric conditions (table 1). (See 'Acute diarrhea (typical duration <5 days)' above and 'Causes' above.)

The presence of fever and diarrhea with blood or mucus are two features of acute diarrheal illness, either alone or in combination, that are particularly helpful in sorting through the differential diagnosis, particularly in otherwise healthy, well-appearing children. (See 'History' above and 'Algorithmic approach to the patient' above.)

●Acute diarrhea – The patient with acute diarrhea who requires volume resuscitation must be quickly identified. Clinical evidence of dehydration is already apparent at a deficit of 5 percent of body weight, except in rare cases of hypernatremia (table 4). A combination of historical and physical examination findings rather than one single feature provides the most useful model for predicting a volume deficit of 5 percent or more. (See 'Physical examination' above.)

A palpable mass or peritonitis suggests appendicitis, intussusception or, less commonly, toxic megacolon. Generalized toxicity and/or shock may occur with hemolytic uremic syndrome (HUS), severe dehydration, or with sepsis, such as from Salmonella or staphylococcal toxic shock syndrome (TSS). (See 'Physical examination' above and 'Life-threatening conditions' above.)

In addition to identifying volume depletion and life-threatening conditions, a thorough examination must be performed because systemic, non-enteric infections, particularly otitis media, may cause acute diarrhea. (See 'Extraintestinal infections' above.)

Ancillary studies in children with acute diarrhea are based upon a careful history and physical examination. Most previously healthy children with self-limited diarrhea (eg, viral gastroenteritis, extraintestinal infections, functional diarrhea, starvation stools, or transient lactase deficiency) and no exposures to bacterial pathogens require no specific testing. (See 'Laboratory testing and imaging' above.)

An acute diarrheal illness is typically defined as a duration of five days or less but return to normal stool consistency after viral gastroenteritis, the most common etiology in resource-abundant regions may take longer. Diarrhea that has persisted beyond five days may warrant consideration of and evaluation for other diagnoses, especially in children who are ill-appearing, have bloody diarrhea in association with weight loss, or other findings suggesting a more serious underlying condition.

●Chronic diarrhea – A brief initial evaluation of the child with chronic diarrhea in the acute setting (eg, emergency department) is described above (algorithm 3). (See 'Chronic diarrhea (duration >1 month)' above.)

A more comprehensive diagnostic approach to chronic diarrheal diseases in resource-abundant and resource-limited settings is discussed in greater detail separately. (See "Overview of the causes of chronic diarrhea in children in resource-abundant settings" and "Approach to chronic diarrhea in children >6 months in resource-abundant settings" and "Approach to chronic diarrhea in neonates and young infants (<6 months)" and "Persistent diarrhea in children in resource-limited settings".)