Diarrheal diseases refer to a group of gastrointestinal syndromes characterized by increased stool frequency and changes in stool consistency, caused by multiple pathogens and factors. These diseases are among the most common illnesses in infants and young children. The incidence is highest in children aged 6 months to 2 years, with approximately half of the cases occurring within the first year of life. They are one of the leading causes of malnutrition and growth and developmental delays in children. Several factors contribute to the susceptibility of infants and young children to diarrhea:
Immaturity of the Digestive System
The production of gastric acid and digestive enzymes is lower in infants, and enzymatic activity tends to be underdeveloped, making it difficult to adapt to significant changes in food type and quantity. Infants have a high rate of water metabolism and limited tolerance to dehydration, which increases the risk of fluid imbalance when water is lost. Immature development of the nervous system, endocrine system, circulation, liver function, and kidney function during infancy can also lead to disruptions in gastrointestinal function.
Rapid Growth and High Nutritional Requirements
Infants have higher relative nutritional demands due to their rapid growth. Since their diet predominantly consists of liquid food and intake is often substantial, this places a heavy burden on the gastrointestinal tract.
Immature Immune System and Intestinal Mucosal Immunity
Gastric acid production in infants is lower, and gastric emptying occurs more rapidly, reducing the stomach's ability to kill bacteria.
Serum immunoglobulin levels, particularly IgM and IgA, as well as secretory IgA (SIgA) in the gastrointestinal tract, are relatively low. The intestinal mucosal immune defense response and the mechanism of oral tolerance are underdeveloped, making infants more susceptible to intestinal infections and food allergy-related diarrhea.
Disruption of Intestinal Flora
Normal intestinal flora serves as a defense against invasive pathogenic microorganisms. In neonates, normal intestinal flora has not yet been fully established after birth. Changes in diet or the inappropriate use of broad-spectrum antibiotics can disrupt the balance of intestinal flora, increasing the risk of intestinal infections. Intestinal flora also plays a role in synthesizing vitamin K, so an imbalance in intestinal flora in young infants may not only lead to diarrhea but also result in symptoms such as vomiting or blood-streaked stool.
Artificial Feeding
Breast milk contains various protective components, such as secretory IgA (SIgA), lactoferrin, macrophages, neutrophils, lysozymes, and lysosomal enzymes, which offer strong resistance to intestinal infections. Although animal milk contains some similar components, they are often destroyed during heating. Additionally, formula feeding is more susceptible to contamination of food or utensils, resulting in a significantly higher incidence of intestinal infections in formula-fed infants compared to breastfed infants.
Etiology
The causes of infant and young child diarrhea can be classified into infectious and non-infectious factors.
Infectious Factors
Infections within the gastrointestinal tract can be caused by viruses, bacteria, fungi, and parasites, with viruses and bacteria being the most common, particularly viruses.
Viral Infections
Approximately 80% of infant diarrhea cases during cold seasons are caused by viral infections. The primary pathogens of viral gastroenteritis include rotavirus (RV) from the Reoviridae family; norovirus and sapovirus from the Caliciviridae family; astrovirus; and enteric adenovirus. Other enteroviruses, such as Coxsackievirus, ECHO virus, and torovirus from the Coronaviridae family may also be involved.
Bacterial Infections (excluding nationally notifiable infectious diseases)
Diarrheagenic Escherichia coli (E. coli)
Based on their virulence mechanisms and pathogenicity, diarrheagenic E. coli strains are classified into 5 major groups:
- Enteropathogenic E. coli (EPEC): The first E. coli strain identified as causing diarrhea. After invading the intestine, EPEC adheres to the intestinal mucosal epithelial cells, leading to microvilli damage, folding atrophy, mucosal congestion, edema, and diarrhea, potentially affecting the entire gastrointestinal tract.
- Enterotoxigenic E. coli (ETEC): Adheres to the brush border of small intestine epithelial cells, proliferates extracellularly, and produces heat-labile toxin (LT) and heat-stable toxin (ST), leading to diarrhea.
- Enteroinvasive E. coli (EIEC): Invades the intestinal mucosa, causing an inflammatory response, and adheres to and invades the colonic mucosa, resulting in epithelial inflammation and necrosis, leading to dysentery-like diarrhea. EIEC shares similarities with Shigella, including cross-reactivity of their O-antigens.
- Enterohemorrhagic E. coli (EHEC): Adheres to the colon and produces a Shigella-like toxin (vero toxin), causing mucosal necrosis and fluid secretion, leading to hemorrhagic colitis.
- Enteroaggregative E. coli (EAEC): Adheres in clusters to the lower small intestine and colonic mucosa without producing enterotoxins or causing tissue damage.
Campylobacter jejuni
Among Campylobacter species associated with enteritis are jejuni, coli, and fetus subspecies. 95%–99% of Campylobacter-related enteritis is caused by Campylobacter jejuni. This pathogen invades the jejunum, ileum, and colon, leading to invasive diarrhea. Certain strains can also produce enterotoxins.
Yersinia
Aside from invading the small intestine and colon mucosa, Yersinia can also produce enterotoxins, leading to both invasive and secretory diarrhea.
Other Bacteria
Salmonella (primarily non-typhoidal and paratyphoidal strains), Aeromonas hydrophila, Clostridium difficile, Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus species can also cause diarrhea.
Fungal Infections
Fungal pathogens causing diarrhea include Candida albicans, Aspergillus, and Mucor species. Candidal enteritis, particularly caused by Candida albicans, is more common in infants.
Parasitic Infections
Common parasites include Giardia lamblia, Entamoeba histolytica, and Cryptosporidium.
Extraintestinal Infections
Certain infections, such as otitis media, upper respiratory tract infections, pneumonia, urinary tract infections, skin infections, or acute infectious diseases, may present with diarrhea due to fever, toxins released by the pathogens, antibiotic treatment, or local rectal irritation (e.g., cystitis or appendiceal abscess). In some cases, pathogens (mainly viruses) can concurrently infect the gastrointestinal tract.
Antibiotic-Associated Diarrhea (AAD)
Prolonged or excessive use of broad-spectrum antibiotics for extraintestinal infections can disrupt the normal intestinal flora, reducing beneficial bacteria and promoting the overgrowth of resistant organisms such as Staphylococcus aureus, Proteus, Pseudomonas aeruginosa, Clostridium difficile, or Candida albicans. This imbalance can lead to antibiotic-associated diarrhea, which is challenging to manage with standard treatments. Exclusion of other triggers, such as concurrent viral or bacterial infections, is necessary for diagnosis.
Non-Infectious Factors
Dietary Factors
Improper feeding practices can lead to diarrhea. This is more common in formula-fed infants due to irregular feeding schedules, inappropriate feeding volumes, abrupt changes in food type, or early introduction of starchy or fatty foods. Premature introduction of complementary foods during breastfeeding, or consumption of fruit juices high in fructose or sorbitol, can cause osmotic diarrhea. Dietary irritants (e.g., spices or high-fiber foods) may also trigger diarrhea.
Allergic diarrhea occurs in conditions such as food-allergy-related enteropathy, enterocolitis, or proctocolitis.
Primary or secondary disaccharidase deficiencies, particularly lactase deficiency or decreasing enzyme activity, can impair sugar digestion and absorption, resulting in diarrhea.
Climatic Factors
Sudden changes in temperature or abdominal cooling may increase intestinal motility. Hot weather can reduce digestive juice secretion or lead to overconsumption of milk due to thirst, potentially disrupting digestive function and causing diarrhea.
Pathogenesis
The mechanisms that lead to diarrhea include:
- The presence of large amounts of unabsorbable, osmotically active substances in the intestinal lumen—"osmotic diarrhea."
- Excessive secretion of electrolytes into the intestinal lumen—"secretory diarrhea."
- Significant exudation of fluids due to inflammation—"exudative diarrhea."
- Abnormal intestinal motility—"functional diarrhea."
In clinical practice, many cases of diarrhea are not caused by a single mechanism but rather by the combined action of multiple mechanisms.
Infectious Diarrhea
Pathogenic microorganisms often enter the gastrointestinal tract through contaminated food or water and may also spread via contaminated household items, hands, toys, or carriers. Whether microorganisms cause intestinal infections depends on the host's defense capabilities, the quantity and virulence of the pathogens.
Viral Enteritis
Various viruses replicate within the columnar epithelial cells at the tips of the small intestinal villi after invading the intestine. This leads to vacuolar degeneration and necrosis of the cells, resulting in swelling, disorganization, and shortening of the microvilli. Affected mucosal epithelial cells are shed, impairing the ability of the small intestine to reabsorb water and electrolytes, which leads to fluid accumulation in the intestinal lumen and diarrhea. Additionally, the damaged intestinal mucosal cells exhibit insufficient secretion and reduced activity of disaccharidases, hindering the digestion of dietary sugars. Undigested sugars accumulate in the intestinal lumen and are metabolized by bacteria into small, short-chain organic acids, increasing the osmotic pressure of intestinal fluids. The destruction of microvilli reduces sodium transport mechanisms in epithelial cells, exacerbating water and electrolyte loss.
Recent studies suggest that rotavirus non-structural protein 4 (NSP4) plays a critical role in the pathogenesis. NSP4 is a multifunctional fluid secretion inducer and acts by:
- Stimulating Cl⁻ secretion and water efflux through effects on cells in the lamina propria.
- Altering epithelial cell integrity, influencing membrane permeability.
- Potentially forming a channel or activating a calcium-activated channel, leading to increased secretion.
- Acting on non-infected cells via paracrine effects, amplifying the effects of infection.
- Directly targeting the enteric nervous system (ENS) to induce cholera toxin-like diarrhea.
Bacterial Enteritis
The pathogenesis of diarrhea varies with the type of pathogenic bacteria.
Enterotoxigenic Enteritis
Bacteria such as Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) can cause secretory diarrhea by producing enterotoxins. These pathogens typically proliferate within the intestinal lumen and adhere to the brush border of intestinal epithelial cells without invading the mucosa. Two types of enterotoxins are released: heat-labile toxin (LT) and heat-stable toxin (ST).
LT binds to receptors on the membranes of small intestinal epithelial cells, activating adenylate cyclase. This converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), which inhibits Na+, Cl-, and water absorption in villous epithelial cells while promoting Cl- secretion in intestinal glands.
ST activates guanylate cyclase, converting guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). Increased cGMP also reduces Na+ and water absorption and enhances Cl- secretion in epithelial cells.
Both toxins significantly increase intestinal fluid volume, overwhelming the absorptive capacity of the colon and resulting in diarrhea characterized by watery stool. This leads to dehydration and electrolyte imbalances in affected children.
Invasive Enteritis
Invasive bacteria such as Shigella, Salmonella, enteroinvasive E. coli, Campylobacter jejuni, Yersinia, and Staphylococcus aureus can invade the intestinal or colonic wall, causing exudative diarrhea. These pathogens provoke mucosal congestion, edema, and inflammatory cell infiltration, leading to exudation, ulceration, and other lesions. Stools may contain large numbers of white and red blood cells, resembling dysentery, and systemic toxic symptoms may develop. Due to inflammatory lesions, the colon may fail to adequately absorb fluids from the small intestine. Additionally, some pathogens produce enterotoxins, potentially causing watery diarrhea as well.
Non-Infectious Diarrhea
Non-infectious diarrhea is primarily associated with improper dietary intake. When food is over-consumed or improperly composed, it may remain undigested and unabsorbed in the upper small intestine, facilitating bacterial proliferation in the lower intestine. Food fermentation and decomposition produce short-chain organic acids, which increase osmotic pressure within the intestinal lumen. Toxic products from food decomposition irritate the intestinal wall, increasing intestinal motility and causing diarrhea. This may lead to further complications such as dehydration and electrolyte imbalances.
Clinical Manifestations
Diarrhea caused by different etiologies often exhibits varying clinical features and courses. Clinical diagnosis frequently considers the duration of the condition, severity, and potential pathogens. Diarrhea lasting less than two weeks is classified as acute diarrhea, two weeks to two months as persistent diarrhea, and more than two months as chronic diarrhea. Some researchers in other countries refer to diarrhea lasting more than two weeks as chronic diarrhea or refractory diarrhea.
Acute Diarrhea
Common Clinical Manifestations of Diarrhea
Mild Cases
Mild diarrhea is often caused by dietary factors or extraintestinal infections. The onset may be either abrupt or gradual, with symptoms primarily involving the gastrointestinal tract. These include poor appetite, occasional regurgitation or vomiting, and an increased frequency of defecation. Stools may be scant in volume, watery or loose, yellow or yellow-green in color, with a sour odor, and often containing white or yellowish milk curds and bubbles. Dehydration and systemic toxic symptoms are typically absent, and recovery generally occurs within a few days.
Severe Cases
Severe diarrhea is usually associated with intestinal infections. It often has an acute onset but may also progress from mild cases. In addition to pronounced gastrointestinal symptoms, systemic symptoms such as dehydration, electrolyte imbalances, and systemic intoxication become prominent. These systemic symptoms may include fever or hypothermia, irritability or lethargy, somnolence, pallor, altered consciousness, and in severe cases, coma or shock.
Gastrointestinal symptoms include poor appetite and frequent vomiting, with severe cases exhibiting coffee-ground-like vomitus. Defecation occurs frequently, with stools numbering 10 to more than 20 times per day. Stools are often watery or egg-drop soup-like, yellow in color with small amounts of mucus, and in rarer cases, may contain traces of blood.
Fluid, electrolyte, and acid-base imbalances occur due to fluid loss from vomiting and diarrhea coupled with insufficient fluid intake. These lead to varying degrees (mild, moderate, or severe) of dehydration. Depending on the proportion of water and electrolyte loss, dehydration may be isotonic, hypotonic, or hypertonic, with isotonic and hypotonic types being more common. Clinical signs include sunken eye sockets and fontanelles, reduced urine output, diminished or absent tear production, dry oral mucosa, decreased skin elasticity, and changes in peripheral circulation due to hypovolemia.
Severe diarrhea is often associated with metabolic acidosis and hypokalemia. Metabolic acidosis results from several factors:
- Significant loss of bicarbonate through diarrhea.
- Reduced food intake, impaired intestinal absorption, and insufficient caloric supply, leading to increased fat breakdown and excessive ketone production.
- Dehydration causing reduced blood volume and hemoconcentration, which slows blood flow and leads to tissue hypoxia, increasing anaerobic glycolysis and subsequent lactate accumulation.
- Dehydration reducing renal blood flow, impairing the kidneys’ ability to excrete acids and retain sodium, resulting in the retention of acidic metabolic byproducts.
Clinical manifestations of metabolic acidosis may include dull affect, reddish lips, deep and labored breathing, cool acetone-scented breath. However, symptoms in very young infants may be less typical. Despite total body potassium being depleted during dehydration and metabolic acidosis, hemoconcentration and the shift of potassium from intracellular to extracellular compartments can result in normal serum potassium levels early in the course. Once dehydration and acidosis are corrected, potassium excretion increases with urination, leading to a rapid drop in blood potassium. Additional factors such as continued potassium loss through diarrhea and the shift of potassium into cells during glycogen synthesis also contribute to hypokalemia. Clinical manifestations of hypokalemia may include lethargy, muscle weakness, abdominal distension, arrhythmias, and signs of alkalosis.
Hypocalcemia and hypomagnesemia may also occur during diarrhea. Poor dietary intake, malabsorption, and increased loss of calcium and magnesium in the stool contribute to decreased total body calcium and magnesium. This is more common in children with active rickets or malnutrition. During dehydration and metabolic acidosis, hemoconcentration and increased ionized blood calcium typically prevent overt hypocalcemia symptoms. However, after correcting dehydration and acidosis, symptoms of hypocalcemia such as carpopedal spasms and seizures may develop. In rare cases, prolonged diarrhea and malnutrition may result in tremors or convulsions following intravenous rehydration. If calcium replacement therapy is ineffective, concomitant hypomagnesemia should be considered.
Clinical Features of Several Common Types of Enteritis
Rotavirus Enteritis
This is the most common cause of diarrhea in infants. It occurs sporadically or in small outbreaks and is primarily transmitted through the fecal-oral route, though aerosol transmission through the respiratory tract can also lead to infection. The incubation period is 1–3 days, most commonly affecting infants aged 6–24 months. The onset is abrupt and often accompanied by fever and symptoms of upper respiratory tract infection, but systemic toxic symptoms are usually mild or absent. Vomiting typically occurs during the first 1–2 days, followed by diarrhea. Stools are frequent, watery, and yellow, sometimes resembling egg-drop soup, with small amounts of mucus but no foul odor. Dehydration, metabolic acidosis, and electrolyte imbalances are common complications.
Rotavirus infection can also involve multiple organs, leading to multisystemic complications such as neurological, respiratory, cardiac, hepatic, and hematologic abnormalities. These may manifest as afebrile convulsions, myocardial damage, pulmonary inflammation, hepatobiliary dysfunction, and other conditions. The disease is self-limiting, with vomiting resolving in a few days and diarrhea subsiding within 3–8 days, though some cases may last longer. Stool examination may occasionally reveal a small number of white blood cells. Large quantities of virus are shed in the stool 1–3 days after infection, sometimes persisting up to 6 days. Serum antibodies typically rise three weeks post-infection. Virus isolation is difficult, but detection using electron microscopy, PCR, or nucleic acid probe techniques is possible. Clinically, virus antigen is often detected in stool using ELISA or colloidal gold methods.
Norovirus Enteritis
This occurs throughout the year, with outbreaks peaking during colder months (November to February). In countries with widespread rotavirus vaccination, norovirus has surpassed rotavirus as the leading cause of acute gastroenteritis in children. Norovirus outbreaks are most common in settings such as restaurants, childcare centers, hospitals, schools, military barracks, cruise ships, and nursing homes, frequently resulting in public health emergencies. The incubation period is typically 12–36 hours, with acute onset. Initial symptoms include paroxysmal abdominal pain, nausea, vomiting, and diarrhea. Systemic symptoms such as chills, fever, headache, fatigue, and muscle pain may occur, alongside respiratory symptoms. Severe vomiting and diarrhea can result in dehydration, metabolic acidosis, and hypokalemia. The disease is self-limiting, with symptoms lasting 12–72 hours. Laboratory stool and blood tests generally reveal no specific abnormalities.
Enteritis Caused by Enterotoxigenic Bacteria
This is more common in summer. The incubation period is 1–2 days, with an abrupt onset. Mild cases show slightly increased stool frequency and minimally altered stool characteristics. Severe cases involve frequent, voluminous diarrhea with watery or egg-drop soup stools containing mucus but no white blood cells upon microscopic examination. Vomiting is common, accompanied by dehydration, electrolyte imbalances, and acid-base disturbances. The disease is self-limiting, with a natural course of 3–7 days, though it can occasionally last longer.
Enteritis Caused by Invasive Bacteria
This category includes infections caused by invasive Escherichia coli, Campylobacter jejuni, Yersinia, and Salmonella Typhi. Cases occur throughout the year but are more frequent in summer. The incubation period varies. These pathogens commonly induce Shigella-like dysenteric lesions. Clinical manifestations differ depending on the segment of the intestine affected.
Common features include acute onset, high fever (sometimes with febrile convulsions), and frequent diarrhea. Stools are mucus-laden and contain pus, blood, and emit a foul odor. Symptoms often include nausea, vomiting, abdominal pain, and tenesmus. Severe toxic symptoms, such as high fever, altered consciousness, and even septic shock, may occur. Stool analysis reveals numerous white blood cells and variable amounts of red blood cells, with stool cultures identifying the causative bacteria.
Campylobacter jejuni primarily affects the jejunum and ileum, causing bloody stools and severe abdominal pain, often misdiagnosed as appendicitis. Complications include severe jejunocolitis, sepsis, pneumonia, meningitis, endocarditis, and pericarditis. Research has linked Campylobacter jejuni to Guillain-Barré syndrome.
Yersinia Enterocolitis frequently occurs in winter and early spring, causing lymphadenopathy and mesenteric lymphadenitis, which can mimic appendicitis. Pharyngitis and cervical lymphadenitis may also be associated.
Salmonella Typhimurium Enterocolitis presents as gastrointestinal or septicemic forms, with neonates and infants under age one being particularly susceptible. Neonates often develop the septicemic form, which commonly results in outbreaks, producing dark green mucoid or jelly-like stools.
Hemorrhagic Escherichia coli Enteritis
Stools are frequent, initially watery and yellow but later becoming bloody with a distinctive foul odor. Stool analysis reveals numerous red blood cells but often no white blood cells. Clinical features include abdominal pain, and in some cases, complications such as hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP).
Antibiotic-Associated Diarrhea
Staphylococcal Enteritis is often secondary to heavy antibiotic use or chronic diseases. Symptoms and disease progression correlate with the degree of gut microbiota dysbiosis. Presenting features include fever, vomiting, diarrhea, varying degrees of toxicity, dehydration, and electrolyte imbalances, with shock occurring in severe cases. Stools are typically dark green and voluminous with mucus, occasionally containing blood. Stains show numerous pus cells and clusters of Gram-positive cocci, and stool cultures isolate coagulase-positive staphylococci.
Pseudomembranous Colitis is caused by Clostridioides difficile, triggered by nearly all antibiotics except vancomycin and aminoglycosides used topically in the gastrointestinal tract. It may occur within one week of antibiotic use or as late as 4–6 weeks post-therapy. Common in postoperative patients or those with intestinal obstruction, intussusception, or Hirschsprung's disease. The pathogen produces toxin A (enterotoxin) and toxin B (cytotoxin), leading to symptoms ranging from mild diarrhea to frequent, yellow-green watery stools sometimes containing pseudomembranes due to necrotic mucosa. Severe cases involve stool with blood, dehydration, electrolyte imbalances, acid-base disturbances, abdominal pain, bloating, systemic toxicity, and shock. Stool anaerobic cultures, immunofluorescence, and cytotoxin neutralization tests aid in confirmation.
Fungal Enteritis is often caused by Candida albicans, primarily affecting children under two years. Frequently occurs alongside other infections or gut microbiota imbalance. Symptoms include chronic diarrhea, frothy yellow stools with mucus, and sometimes curd-like particles. Microscopic stool examination shows fungal spores and hyphae. Fungal culture is required for diagnosis if only a few spores are found.
Persistent and Chronic Diarrhea
Persistent and chronic diarrhea have complex etiologies, including infections, food allergies, enzyme deficiencies, immune deficiencies, medication-related factors, and congenital abnormalities. The most common scenario is acute diarrhea that has not been fully or properly treated, leading to prolonged and unresolved symptoms. Malnourished infants and young children are particularly susceptible, for the following reasons:
- In severe malnutrition, gastric mucosal atrophy and reduced gastric acid secretion impair the stomach's bactericidal barrier, facilitating overgrowth of bacteria and yeast in gastric and duodenal secretions.
- In malnourished individuals, the mucosae of the duodenum and jejunum become thinner, and intestinal villi exhibit atrophy and degeneration with increased epithelial cell shedding. Activities of disaccharidases, particularly lactase, and brush-border peptidases decrease, resulting in reduced effective absorption area in the small intestine and leading to malabsorption of various nutrients.
- Severe malnutrition is associated with significant bacterial overgrowth in the upper small intestine, along with excessive proliferation of anaerobic bacteria and yeast in the duodenum. The degradation of conjugated bile acids by these bacteria leads to elevated concentrations of unconjugated bile acids that damage intestinal cells and interfere with the formation of fat micelles.
- Malnourished children often exhibit altered intestinal motility.
- Long-term misuse of antibiotics disrupts the balance of intestinal microbiota.
- Severe malnutrition results in immunodeficiency. Levels of IgM antibodies effective against Gram-negative bacteria, SIgA antibodies that provide mucosal protection, phagocyte function, and complement proteins all decrease, increasing susceptibility to pathogens and reducing oral immune tolerance to food protein antigens.
As a result, diarrhea in malnourished children is often prolonged and difficult to resolve. Persistent diarrhea exacerbates malnutrition, forming a vicious cycle in which both conditions contribute to each other, ultimately leading to multisystem organ dysfunction.
Etiological diagnosis of persistent and chronic diarrhea requires a detailed medical history, thorough physical examination, and appropriate use of diagnostic tools.
- Routine stool examination, intestinal microbiota analysis, stool acidity tests, reducing sugar tests, and stool culture.
- Small intestinal mucosal biopsy to assess pathophysiological changes associated with chronic diarrhea.
- Tests for food allergies, such as food elimination and challenge tests.
Additional assessments, if necessary, include imaging studies such as gastrointestinal radiology or CT scans, as well as colonoscopy for comprehensive evaluation and diagnosis.
Diagnosis and Differential Diagnosis
A clinical diagnosis can be established based on clinical manifestations and stool characteristics. It is necessary to assess for the presence, degree, and type of dehydration, electrolyte disturbances, and acid-base imbalances. From the perspective of clinical diagnosis and treatment, diarrhea can initially be divided into two groups based on the presence or absence of white blood cells in stool microscopy.
Absent or Minimal White Blood Cells in Stool
This indicates causes of diarrhea other than invasive bacterial infections (e.g., viral infections, non-invasive bacterial infections, improper feeding practices). Such cases often present with watery diarrhea, sometimes accompanied by dehydration. In addition to infectious causes, attention should also be given to the following conditions:
Physiological Diarrhea
This is commonly observed in infants younger than six months, who may appear plump and frequently have eczema. Diarrhea typically starts shortly after birth and manifests as increased stool frequency without other symptoms. Appetite is good, and there is no impact on growth or development. Some experts suggest this type of diarrhea may represent a specific form of lactose intolerance or be related to food allergies. Stool patterns usually normalize after the introduction of complementary foods.
Disorders Leading to Small Intestinal Malabsorption
These include conditions such as disaccharidase deficiencies, food allergy-related diarrhea, chloridorrhea, and primary bile acid malabsorption. Differentiation can be achieved based on the clinical features of each condition with tests such as stool acidity analysis, reducing sugar tests, food allergen identification, and food elimination-challenge tests.
Presence of Significant White Blood Cells in Stool
This suggests inflammatory lesions in the colon and terminal ileum due to invasive bacterial infections. Since it is difficult to distinguish these based on clinical symptoms alone, stool bacterial culture, bacterial serotyping, and toxicity testing may be necessary. Additionally, differentiation from the following conditions should be considered:
Bacterial Dysentery
This is often associated with epidemiological exposure. Onset is acute, with severe systemic symptoms. Stool frequency is high, with small volumes of purulent and bloody stool accompanied by tenesmus. Microscopic stool examination shows abundant pus cells, red blood cells, and phagocytes. Diagnosis is confirmed by stool culture growing Shigella species.
Necrotizing Enterocolitis (NEC)
Severe toxic symptoms are typically present, including abdominal pain, abdominal distension, frequent vomiting, and high fever. The stool appears dark red and pasty, gradually transitioning to the characteristic "red currant jelly" stool. This condition is often associated with shock. Abdominal X-rays may show localized intestinal distension, widened interbowel spaces, and intramural gas accumulation.
Food Protein Allergy-Related Proctocolitis
This condition commonly affects infants around two months of age who are breastfed or mixed-fed. Symptoms include mild diarrhea with blood-streaked stool but no involvement of other organ systems. Affected infants generally appear well. Stool examination may reveal an increased number of red blood cells, positive occult blood tests, and the presence of white blood cells.
Treatment
Treatment Principles
The goals include adjusting dietary intake, preventing and correcting dehydration, rational use of medications, enhancing nursing care, and preventing complications. Management priorities differ based on the stage of the diarrheal illness. In acute diarrhea, the focus is maintaining water and electrolyte balance, while in persistent and chronic diarrhea, attention should be given to intestinal dysbiosis and dietary therapy.
Treatment of Acute Diarrhea
Dietary Therapy
Diarrhea reduces food intake and absorption while increasing the body's nutritional needs due to mucosal damage, heightened metabolism during fever, and protein loss in invasive enteritis. Overly restrictive dietary measures or prolonged fasting can lead to malnutrition and acidosis, prolong the illness, and impair growth and development. Continued nutrition is therefore emphasized to meet physiological needs, replenish losses caused by the illness, and shorten recovery time. Dietary adjustments should consider the specific pathophysiological conditions of the disease, individual digestive and absorptive capacities, and usual dietary habits. For infants, breastfeeding and previously familiar diets should be resumed as soon as possible, with gradual increases in food volume and consistency. Easily digestible foods suited to the child's age should be provided. In cases of viral enteritis with secondary disaccharidase deficiency (mainly lactase deficiency), starch-based foods or lactose-free formulas may reduce diarrhea and shorten its duration. After diarrhea resolves, a nutrient-rich diet should be gradually reintroduced, with one additional meal daily for two weeks.
Correction of Water, Electrolyte, and Acid-Base Imbalances
Intravenous rehydration is required in cases of severe dehydration.
Calcium and Magnesium Supplementation
Calcium Supplementation
If convulsions or tetany occur during rehydration, 10% calcium gluconate at a dose of 1–2 mL/kg (maximum ≤10 mL) may be administered. It should be diluted in an equal volume of 5–10% glucose solution and slowly injected intravenously.
Magnesium Supplementation
If tetany worsens or does not improve despite calcium supplementation, hypomagnesemia should be considered, and blood magnesium levels measured. Treatment involves intramuscular injections of 25% magnesium sulfate at a dose of 0.1–0.2 mL/kg, administered 2–3 times per day until symptoms resolve.
Pharmacological Therapy
Infection Control
In patients with watery stool diarrhea (approximately 70% of cases), which is often caused by viruses or non-invasive bacteria, antibiotics are generally unnecessary. Antibiotics may be considered for patients with systemic toxicity that cannot be explained by dehydration, particularly in severe cases, neonates, young infants, or immunocompromised children.
Patients with mucus or bloody stool (approximately 30% of cases) often have invasive bacterial infections. Empirical antimicrobial therapy based on clinical presentation should be administered, with subsequent adjustments guided by stool culture and antimicrobial sensitivity testing. For infections involving Escherichia coli, Campylobacter jejuni, Yersinia enterocolitica, or Salmonella typhimurium, antibiotics targeting Gram-negative bacteria and macrolides are commonly used. For Staphylococcus aureus enteritis, pseudomembranous colitis, or fungal enteritis, initial antibiotics should be discontinued. Treatment options include oxacillin, vancomycin, rifaximin, metronidazole, or antifungal agents, depending on the symptoms.
Intestinal Microbiota Therapy
This approach promotes the restoration of the normal intestinal microbiome, inhibits pathogenic colonization, and controls diarrhea. Common agents include Bifidobacterium, Lactobacillus acidophilus, Clostridium butyricum, Saccharomyces boulardii, Streptococcus faecium, Bacillus licheniformis, Bacillus subtilis, Bacillus cereus, and Lactobacillus rhamnosus.
Intestinal Mucosal Protectants
These agents, such as montmorillonite powder, adsorb pathogens and toxins, maintain intestinal absorptive and secretory functions, and enhance the barrier function of intestinal mucins, preventing pathogenic attacks.
Anti-Secretory Treatments
Enkephalinase inhibitors, such as racecadotril, can reduce intestinal secretion of water and electrolytes by enhancing endogenous enkephalins and may be used to treat secretory diarrhea.
Avoidance of Anti-Diarrheal Agents
Medications like loperamide suppress gastrointestinal motility, which could increase bacterial proliferation and toxin absorption, posing serious risks in infectious diarrhea.
Zinc Supplementation
Elemental zinc should be provided to children with acute diarrhea at a daily dose of 20 mg for those older than six months and 10 mg for infants younger than six months, for a duration of 10–14 days.
Treatment of Persistent and Chronic Diarrhea
Since persistent and chronic diarrhea are often accompanied by malnutrition and other complications, a comprehensive approach is required. Efforts are directed at identifying and treating the underlying causes, preventing dehydration, and correcting imbalances in electrolytes and acid-base levels. Improper use of antibiotics should be avoided to prevent refractory intestinal dysbiosis. Nutritional support therapy is crucial for promoting the repair of intestinal mucosal injuries, restoration of pancreatic function, and regeneration of disaccharidase enzymes in epithelial microvilli.
Dietary Adjustments
Breastfeeding should be continued, while formula-fed babies may require dietary adjustments to ensure adequate caloric intake.
Management of Disaccharide Intolerance
Children with disaccharide intolerance (especially lactose intolerance) may experience worsening diarrhea when consuming diets containing lactose, sucrose, or maltose. Reduction of disaccharide intake, including the use of lactose-free or lactose-reduced formula, can mitigate symptoms.
Treatment of Allergic Diarrhea
For cases unresponsive to disaccharide-free diets, food allergies (e.g., to cow's milk) should be suspected. Avoidance of allergenic foods, or use of amino acid-based or extensively hydrolyzed protein formulas, is recommended.
Elemental Diets
Elemental diets, composed of amino acids, glucose, medium-chain triglycerides, vitamins, and trace elements, are considered ideal for patients with intestinal mucosal damage. Dosage and concentration are adjusted based on the patient’s clinical condition.
Parenteral Nutrition
Intravenous nutrition may be necessary for some patients intolerant of oral feeding. Recommended regimens include daily lipid emulsions (2–3 g/kg), amino acid solutions (2–2.5 g/kg), glucose (12–15 g/kg), appropriate electrolytes and trace elements, fluid volumes (120–150 mL/kg), and caloric intake (50–90 kcal/kg). Transition to oral nutrition is made after clinical improvement.
Pharmacological Therapy
Antibiotics are used only in cases where specific pathogens have been identified and should be selected based on antimicrobial sensitivity testing. Microelement and vitamin supplementation (e.g., zinc, iron, niacin, vitamin A, vitamin B12, vitamin B1, vitamin C, and folic acid) is beneficial for intestinal mucosal repair. Probiotics and intestinal mucosal protectants are also recommended.
Prevention
Appropriate Feeding Practices
Breastfeeding is encouraged. When introducing complementary foods, it is important to limit to one new food at a time, gradually increase the quantity, and wean at the appropriate age. For formula-fed infants, suitable substitutes for breast milk should be chosen based on individual circumstances.
Identification of Physiological Diarrhea
In cases of physiological diarrhea in infants, inappropriate medical interventions should be avoided. Misinterpreting frequent stools as a sign of poor digestion should also be avoided, as it may lead to delays in the timely introduction of complementary foods.
Habits of Good Hygiene
Proper preservation of dairy products and regular disinfection of feeding implements, utensils, potties, toys, and other equipment is essential to maintain hygiene.
Infection Prevention
Infectious diarrhea, particularly that caused by highly transmissible pathogens such as Escherichia coli, Salmonella typhimurium, and norovirus, requires targeted prevention measures. During outbreaks in communal settings, treatment should be actively pursued, disinfection and isolation protocols implemented, and cross-infections prevented.
Standardized Use of Antibiotics
The prolonged misuse of broad-spectrum antibiotics should be avoided. Even in the treatment of non-gastrointestinal infections like sepsis or pneumonia that require antibiotics, especially broad-spectrum ones, probiotics should be used concurrently to prevent intestinal dysbiosis and the subsequent development of refractory diarrhea.
Vaccination
Rotavirus enteritis is widespread, and vaccination provides an effective prevention strategy. Oral vaccines are already in use, though research on their long-term efficacy is ongoing.