Diarrhea 

Updated: Oct 31, 2018
Author: Stefano Guandalini, MD; Chief Editor: Carmen Cuffari, MD 

Overview

Practice Essentials

Diarrhea is the reversal of the normal net absorptive status of water and electrolyte absorption to secretion. The augmented water content in the stools (above the normal value of approximately 10 mL/kg/d in the infant and young child, or 200 g/d in the teenager and adult) is due to an imbalance in the physiology of the small and large intestinal processes involved in the absorption of ions, organic substrates, and thus water.

Signs and symptoms

Acute diarrhea is defined as the abrupt onset of 3 or more loose stools per day and lasts no longer than 14 days; chronic or persistent diarrhea is defined as an episode that lasts longer than 14 days. The distinction has implications not only for classification and epidemiologic studies but also from a practical standpoint, because protracted diarrhea often has different etiologies, poses different management problems, and has a different prognosis.

The clinical presentation and course of diarrhea therefore depend on its cause and on the host. Consider the following to determine the source/cause of the patient’s diarrhea:

  • Stool characteristics (eg, consistency, color, volume, frequency)

  • Presence of associated enteric symptoms (eg, nausea/vomiting, fever, abdominal pain)

  • Use of child daycare (common pathogens: rotavirus, astrovirus, calicivirus; Campylobacter, Shigella, Giardia, and Cryptosporidium species [spp])

  • Food ingestion history (eg, raw/contaminated foods, food poisoning)

  • Water exposure (eg, swimming pools, marine environment)

  • Camping history (possible exposure to contaminated water sources)

  • Travel history (common pathogens affect specific regions; also consider rotavirus and Shigella, Salmonella, and Campylobacter spp regardless of specific travel history, as these organisms are prevalent worldwide)

  • Animal exposure (eg, young dogs/cats: Campylobacter spp; turtles: Salmonella spp)

  • Predisposing conditions (eg, hospitalization, antibiotic use, immunocompromised state)

Signs and symptoms of diarrhea may include the following:

  • Dehydration: Lethargy, depressed consciousness, sunken anterior fontanel, dry mucous membranes, sunken eyes, lack of tears, poor skin turgor, delayed capillary refill

  • Failure to thrive and malnutrition: Reduced muscle/fat mass or peripheral edema

  • Abdominal pain/cramping

  • Borborygmi

  • Perianal erythema

See Clinical Presentation for more detail.

Diagnosis

Fecal laboratory studies include the following:

  • Examination for ova and parasites

  • Leukocyte count

  • pH level: A pH level of 5.5 or less or the presence of reducing substances indicates carbohydrate intolerance, which is usually secondary to viral illness

  • Examination of exudates for presence/absence of leukocytes

  • Cultures: Always culture for Salmonella, Shigella, and Campylobacter spp and Y enterocolitica in the presence of clinical signs of colitis or if fecal leukocytes are present; look for Clostridium difficile in those with diarrhea characterized by colitis and/or bloody stools; assess for Escherichia coli, particularly O157:H7, with bloody diarrhea and a history of eating ground beef; screen for Vibrio and Plesiomonas spp with a history of eating raw seafood or foreign travel

  • Enzyme immunoassay for rotavirus or adenovirus antigens

  • Latex agglutination assay for rotavirus

Other laboratory studies may include the following:

  • Serum albumin levels: Low in protein-losing enteropathies from enteroinvasive intestinal infections (eg, Salmonella spp, enteroinvasive E coli)

  • Fecal alpha1-antitrypsin levels: High in enteroinvasive intestinal infections

  • Anion gap to determine nature of the diarrhea (ie, osmolar vs secretory)

  • Intestinal biopsy: May be indicated in the presence of chronic or protracted diarrhea, as well as in cases in which a search for a cause is believed to be mandatory (eg, in patients with acquired immunodeficiency syndrome [AIDS] or patients who are otherwise severely immunocompromised)

See Workup for more detail.

Management

Acute-onset diarrhea is usually self-limited; however, an acute infection can have a protracted course. Management is generally supportive: In most cases, the best option for treatment of acute-onset diarrhea is the early use of oral rehydration therapy (ORT).[1]

Pharmacotherapy

Vaccines (eg, rotavirus) can help increase resistance to infection. Antimicrobial and antiparasitic agents may be used to treat diarrhea caused by specific organisms and/or clinical circumstances. Such medications include the following:

  • Cefixime

  • Ceftriaxone

  • Cefotaxime

  • Erythromycin

  • Furazolidone

  • Iodoquinol

  • Metronidazole

  • Paromomycin

  • Quinacrine

  • Sulfamethoxazole and trimethoprim

  • Vancomycin

  • Tetracycline

  • Nitazoxanide

  • Rifaximin

See Treatment and Medication for more detail.

Background

Acute diarrhea is defined as the abrupt onset of 3 or more loose stools per day. The augmented water content in the stools (above the normal value of approximately 10 mL/kg/d in the infant and young child, or 200 g/d in the teenager and adult) is due to an imbalance in the physiology of the small and large intestinal processes involved in the absorption of ions, organic substrates, and thus water. A common disorder in its acute form, diarrhea has many causes and may be mild to severe.

Childhood acute diarrhea is usually caused by infection of the small and/or large intestine; however, numerous disorders may result in diarrhea, including a malabsorption syndrome and various enteropathies. Acute-onset diarrhea is usually self-limited; however, an acute infection can have a protracted course. By far, the most common complication of acute diarrhea is dehydration.

Although the term "acute gastroenteritis" is commonly used synonymously with "acute diarrhea," the former term is a misnomer. The term gastroenteritis implies inflammation of both the stomach and the small intestine, whereas, in reality, gastric involvement is rarely if ever seen in acute diarrhea (including diarrhea with an infectious origin); in addition, enteritis is also not consistently present. Examples of infectious acute diarrhea syndromes that do not cause enteritis include Vibrio cholerae– induced diarrhea and Shigella -induced diarrhea. Thus, the term acute diarrhea is preferable to acute gastroenteritis.

Diarrheal episodes are classically distinguished into acute and chronic (or persistent) based on their duration. Acute diarrhea is thus defined as an episode that has an acute onset and lasts no longer than 14 days; chronic or persistent diarrhea is defined as an episode that lasts longer than 14 days. The distinction, supported by the World Health Organization (WHO), has implications not only for classification and epidemiological studies but also from a practical standpoint because protracted diarrhea often has a different set of causes, poses different problems of management, and has a different prognosis.

Pathophysiology

Diarrhea is the reversal of the normal net absorptive status of water and electrolyte absorption to secretion. Such a derangement can be the result of either an osmotic force that acts in the lumen to drive water into the gut or the result of an active secre­tory state induced in the enterocytes. In the former case, diarrhea is osmolar in nature, as is observed after the ingestion of nonabsorbable sugars such as lactulose or lactose in lactose malabsorbers. Instead, in the typical active secretory state, enhanced anion secretion (mostly by the crypt cell compartment) is best exemplified by enterotoxin-­induced diarrhea.

In osmotic diarrhea, stool output is proportional to the intake of the unabsorbable substrate and is usually not massive; diarrheal stools promptly regress with discontinuation of the offending nutrient, and the stool ion gap is high, exceeding 100 mOsm/kg. In fact, the fecal osmolality in this circumstance is accounted for not only by the electrolytes but also by the unabsorbed nutrient(s) and their degradation products. The ion gap is obtained by subtracting the concentration of the elec­trolytes from total osmolality (assumed to be 290 mOsm/kg), according to the formula: ion gap = 290 – [(Na + K) × 2].

In secretory diarrhea, the epithelial cells’ ion transport processes are turned into a state of active secretion. The most common cause of acute-onset secretory diarrhea is a bacterial infection of the gut. Several mechanisms may be at work. After colonization, enteric pathogens may adhere to or invade the epithelium; they may produce enterotoxins (exotoxins that elicit secretion by increasing an intracellular second messenger) or cytotoxins. They may also trigger release of cytokines attracting inflammatory cells, which, in turn, contribute to the acti­vated secretion by inducing the release of agents such as prostaglandins or platelet-activating factor. Features of secretory diarrhea include a high purg­ing rate, a lack of response to fasting, and a normal stool ion gap (ie, 100 mOsm/kg or less), indicating that nutrient absorption is intact.

Frequency

United States

In the United States, one estimate before the introduction of specific antirotavirus immunization in 2006 assumed a cumulative incidence of 1 hospitalization for diarrhea per 23-27 children by age 5 years, with more than 50,000 hospitalizations. By these estimates, rotavirus was associated with 4-5% of all childhood hospitalizations and a cost of nearly $ 1 billion.[2] Furthermore, acute diarrhea is responsible for 20% of physician referrals in children younger than 2 years and for 10% in children younger than 3 years.

The impact of vaccination on rotavirus morbidity has been remarkable, with significant reduction of diarrhea-associated hospitalizations and visits to emergency departments in children in the years 2007-2008 compared with the prevaccine period.[3]

A study by Olortegui et al that included 2,082 children reported that 35% of the children experienced astrovirus infections and astrovirus prevalence in diarrheal stools was 5.6%, and severity exceeded all enteropathogens except rotavirus.[36]

International

In developing countries, an average of 3 episodes per child per year in children younger than 5 years is reported; however, some areas report 6-8 episodes per year per child. In these settings, malnutrition is an important additional risk factor for diarrhea, and recurrent episodes of diarrhea lead to growth faltering and substantially increased mortality.[4] Childhood mortality associated with diarrhea has constantly but slowly declined during the past 2 decades, mostly because of the widespread use of oral rehydration solutions; however, it appears to have plateaued over the past several years.

Because the single most common cause of infectious diarrhea worldwide is rotavirus, and because a vaccine has been in use for over 3 years now, a reduction in the overall frequency of diarrheal episodes is hoped for in the near future.

A study by Lübbert et al found the incidence of Clostridium difficile infection in Germany in 2012 to be 83 cases per 100,000 population. The chance of recurrence increased with each relapse; an initial recurrence of the infection was found in 18.2% of patients with index events, with 28.4% of these patients having a second recurrence and 30.2% of second-recurrence patients having a third recurrence.[5]

Mortality/Morbidity

Mortality from acute diarrhea is overall globally declining but remains high. Most estimates have diarrhea as the second cause of childhood mortality, with 18% of the 10.6 million yearly deaths in children younger than age 5 years.

Despite a progressive reduction in global diarrheal disease mortality over the past 2 decades, diarrhea morbidity in published reports from 1990-2000 slightly increased worldwide compared with previous reports. In the United States, an average of 369 diarrhea-associated deaths/year occurred among children aged 1-59 months during 1992-1998 and 2005-2006.[6] The vast majority of diarrhea-associated infant deaths were reported in 2005-2007, with 86% of deaths occurring among low-birthweight (< 2500 g) infants.[7]

Furthermore, in countries in which the toll of diarrhea is highest, poverty also adds an enormous additional burden, and long-term consequences of the vicious cycle of enteric infections, diarrhea, and malnutrition are devastating.[4]

Sex

Most cases of infectious diarrhea are not sex specific. Females have a higher incidence of Campylobacter species infections and hemolytic uremic syndrome (HUS).

Age

Viral diarrhea is most common in young children. Rotavirus and adenovirus are particularly prevalent in children younger than 2 years. Astrovirus and norovirus usually infect children younger than 5 years. Yersinia enterocolitis typically infects children younger than 1 year, and the Aeromonas organism is a significant cause of diarrhea in young children.

Very young children are particularly susceptible to secondary dehydration and secondary nutrient malabsorption. Age and nutritional status appear to be the most important host factors in determining the severity and the duration of diarrhea. In fact, the younger the child, the higher is the risk for severe, life-threatening dehydration as a result of the high body-water turnover and limited renal compensatory capacity of very young children. Whether younger age also means a risk of run­ning a prolonged course is an unsettled issue. In developing countries, persis­tent postenteritis diarrhea has a strong inverse correlation with age.

 

Presentation

History

Acute diarrhea in developed countries is almost invariably a benign, self-limited condition, subsiding within a few days. The clinical presentation and course of illness depend on the etiology of the diarrhea and on the host. For example, rotavirus is more commonly associated with vomiting, dehydration, and a greater number of work days lost than nonrotavirus gastroenteritis.

  • A prospective study conducted in the United States in 604 children aged 3-36 months in community settings before the introduction of rotavirus vaccine found that the highest incidence of acute diarrhea was in January and August, with an overall incidence of 2.21 episodes per person-year.[8] Close to 90% of episodes were acute (ie, lasting < 14 d, with a median duration of 2 d and a median of 6 stools per day).

  • Diarrhea implies an increase in stool volume and diminished stool consistency.

    • In children younger than 2 years, diarrhea is defined as daily stools with a volume greater than 10 mL/kg.

    • In children older than 2 years, diarrhea is defined as daily stools with a weight greater than 200 g. In practice, this typically means loose-to-watery stools passed 3 or more times per day.

    • Individual stool patterns widely vary; for example, breastfed children may normally have 5-6 stools per day.

  • Flatulence associated with foul-smelling stools that float suggests fat malabsorption, which can be observed with infection with Giardia lamblia.

  • Knowledge of the characteristics of consistency, color, volume, and frequency can be helpful in determining whether the source is from the small or large bowel. Table 1 outlines these characteristics and demonstrates that an index of suspicion can be easily generated for a specific set of organisms.

Table 1. Stool Characteristics and Determining Their Source (Open Table in a new window)

Stool Characteristics

Small Bowel

Large Bowel

Appearance

Watery

Mucoid and/or bloody

Volume

Large

Small

Frequency

Increased

Highly increased

Blood

Possibly positive but never gross blood

Commonly grossly bloody

pH

Possibly < 5.5

>5.5

Reducing substances

Possibly positive

Negative

WBCs

< 5/high power field

Commonly >10/high power field

Serum WBCs

Normal

Possible leukocytosis, bandemia

Organisms

Viral

  • Rotavirus

  • Adenovirus

  • Calicivirus

  • Astrovirus

  • Norovirus

Invasive bacteria

  • Escherichia Coli (enteroinvasive, enterohemorrhagic)

  • Shigella species

  • Salmonella species

  • Campylobacter species

  • Yersinia species

  • Aeromonas species

  • Plesiomonas species

Enterotoxigenic bacteria

  • E coli

  • Klebsiella

  • Clostridium perfringens

  • Cholera species

  • Vibrio species

Toxic bacteria

  • Clostridium difficile

Parasites

  • Giardia species

  • Cryptosporidium species

Parasites

  • Entamoeba organisms

See the list below:

  • Associated systemic symptoms include the following:

    • Some enteric infections commonly have systemic symptoms, whereas others less commonly are associated with systemic features.

    • Table 2 outlines the frequency of some of these symptoms with particular organisms. It also outlines incubation periods and usual duration of symptoms of common organisms. Certain organisms (eg, C difficile, Giardia, Entamoeba species) may be associated with a protracted course.

Table 2. Organisms and Frequency of Symptoms (Open Table in a new window)

Organism

Incubation

Duration

Vomiting

Fever

Abdominal Pain

Rotavirus

1-7 d

4-8 d

Yes

Low

No

Adenovirus

8-10 d

5-12 d

Delayed

Low

No

Norovirus

1-2 d

2 d

Yes

No

No

Astrovirus

1-2 d

4-8 d

+/-

+/-

No

Calicivirus

1-4 d

4-8 d

Yes

+/-

No

Aeromonas species

None

0-2 wk

+/-

+/-

No

Campylobacter species

2-4 d

5-7 d

No

Yes

Yes

C difficile

Variable

Variable

No

Few

Few

C perfringens

Minimal

1 d

Mild

No

Yes

Enterohemorrhagic E coli

1-8 d

3-6 d

No

+/-

Yes

Enterotoxigenic E coli

1-3 d

3-5 d

Yes

Low

Yes

Plesiomonas species

None

0-2 wk

+/-

+/-

+/-

Salmonella species

0-3 d

2-7 d

Yes

Yes

Yes

Shigella species

0-2 d

2-5 d

No

High

Yes

Vibrio species

0-1 d

5-7 d

Yes

No

Yes

Y enterocolitica

None

1-46 d

Yes

Yes

Yes

Giardia species

2 wk

1+ wk

No

No

Yes

Cryptosporidium species

5-21 d

Months

No

Low

Yes

Entamoeba species

5-7 d

1-2+ wk

No

Yes

No

See the list below:

  • Daycare considerations are as follows:

    • Certain organisms are spread quickly in daycare. These organisms include rotavirus; astrovirus; calicivirus; and Campylobacter, Shigella, Giardia, and Cryptosporidium species.

    • Increase in daycare usage has raised the incidence of rotavirus and Cryptosporidium species.

  • Food history can be helpful.

    • Ingestion of raw or contaminated food is a common cause of infectious diarrhea.

    • Organisms that cause food poisoning include the following:

      • Dairy food -Campylobacter and Salmonella species

      • Eggs -Salmonella species

      • Meats -C perfringens and Aeromonas, Campylobacter, and Salmonella species

      • Ground beef - Enterohemorrhagic E coli

      • Poultry -Campylobacter species

      • Pork -C perfringens, Y enterocolitica

      • Seafood - Astrovirus and Aeromonas, Plesiomonas, and Vibrio species

      • Oysters - Calicivirus and Plesiomonas and Vibrio species

      • Vegetables -Aeromonas species and C perfringens

    • Guidelines on fruit juice intake for children by the American Academy of Pediatrics recommend that in the evaluation of children with chronic diarrhea, excessive flatulence, abdominal pain, and bloating, the pediatrician should determine the amount of juice being consumed. [9]
  • Water exposure can contribute to diarrhea.

    • Water is a major reservoir for many organisms that cause diarrhea.

    • Swimming pools have been associated with outbreaks of infection with Shigella species; Aeromonas organisms are associated with exposure to the marine environment.

    • Giardia, Cryptosporidium, and Entamoeba organisms are resistant to water chlorination; therefore, exposure to contaminated water should raise index of suspicion for these parasites.

  • A history of camping suggests exposure to water sources contaminated with Giardia organisms.

  • Travel history may indicate a cause for diarrhea.

    • Enterotoxigenic E coli is the leading cause of traveler's diarrhea.

    • Rotavirus and Shigella, Salmonella, and Campylobacter organisms are prevalent worldwide and need to be considered regardless of specific travel history.

    • Risk of contracting diarrhea while traveling is, by far, highest for persons traveling to Africa.

    • Travel to Central and South America and Eastern European countries is also associated with a relatively high risk of contracting diarrhea.

    • Other organisms that are prevalent in particular parts of the world include the following:

      • Nonspecific foreign travel history - Enterotoxigenic E coli and Aeromonas, Giardia, Plesiomonas, Salmonella, and Shigella species

      • Underdeveloped tropical visit -C perfringens

      • Travel to Africa -Entamoeba species, Vibrio cholerae

      • Travel to South America and Central America -Entamoeba species, V cholerae, enterotoxigenic E coli

      • Travel to Asia -V cholerae

      • Travel to Australia -Yersinia species

      • Travel to Canada -Yersinia species

      • Travel to Europe -Yersinia species

      • Travel to India -Entamoeba species, V cholerae

      • Travel to Japan -Vibrio parahaemolyticus

      • Travel to Mexico -Aeromonas, Entamoeba, Plesiomonas, and Yersinia species

      • New Guinea -Clostridium species

  • Animal exposure can contribute to diarrhea.

    • Exposure to young dogs or cats is associated with Campylobacter organisms.

    • Exposure to turtles is associated with Salmonella organisms.

  • Certain medical conditions predispose patients to infection, including the following:

    • C difficile - Hospitalization, antibiotic administration

    • Plesiomonas species - Liver diseases or malignancy

    • Salmonella species - Intestinal dysmotility, malnutrition, achlorhydria, hemolytic anemia (especially sickle cell disease), immunosuppression, malaria

    • Rotavirus - Hospitalization

    • Giardia species -Agammaglobulinemia, chronic pancreatitis, achlorhydria, cystic fibrosis

    • Cryptosporidia species - Immunocompromised or immunosuppressed state

Physical

The following may be observed:

  • Dehydration

    • Dehydration is the principal cause of morbidity and mortality.

    • Assess every patient with diarrhea for signs, symptoms, and severity.

    • Lethargy, depressed consciousness, sunken anterior fontanel, dry mucous membranes, sunken eyes, lack of tears, poor skin turgor, and delayed capillary refill are obvious and important signs of dehydration. Table 3 below details dehydration severity and symptoms.

Table 3. Dehydration Severity, Signs, and Symptoms (Open Table in a new window)

Hydration

0-5% Dehydration

(Mild)

5-10% Dehydration

(Moderate)

10% or More

(Severe)

General

Well

Restless

Lethargic

Eyes

Normal

Sunken

Very sunken

Tears

Present

Absent

Absent

Mouth

Moist

Dry

Very dry

Thirst

Drinks normally

Thirsty

Drinks poorly

Skin

Pinch retracts immediately

Pinch retracts slowly

Pinch stays folded

 

See the list below:

  • Failure to thrive and malnutrition

    • Reduced muscle and fat mass or peripheral edema may be clues to the presence of carbohydrate, fat, and/or protein malabsorption.

    • Giardia organisms can cause intermittent diarrhea and fat malabsorption.

  • Abdominal pain

    • Nonspecific nonfocal abdominal pain and cramping are common with some organisms.

    • Pain usually does not increase with palpation.

    • With focal abdominal pain worsened by palpation, rebound tenderness, or guarding, be alert for possible complications or for another noninfectious diagnosis.

  • Borborygmi: Significant increases in peristaltic activity can cause an audible and/or palpable increase in bowel activity.

  • Perianal erythema

    • Frequent stools can cause perianal skin breakdown, particularly in young children.

    • Secondary carbohydrate malabsorption often results in acidic stools.

    • Secondary bile acid malabsorption can result in a severe diaper dermatitis that is often characterized as a "burn."

Causes

Although infectious agents are by far the most common cause for sporadic or endemic episodes of acute diarrhea, one should not dismiss other causes that can lead to the same presentation.

  • Causes of diarrhea with acute onset include the following:

    • Infections

      • Enteric infections (including food poisoning

      • Extraintestinal infections

    • Drug-induced

      • Antibiotic-associated

      • Laxatives

      • Antacids that contain magnesium

      • Opiate withdrawal

      • Other drugs

    • Food allergies or intolerances

      • Cow's milk protein allergy

      • Soy protein allergy

      • Multiple food allergies

      • Olestra

      • Methylxanthines (caffeine, theobromine, theophylline)

    • Disorders of digestive/absorptive processes

      • Glucose-galactose malabsorption

      • Sucrase-isomaltase deficiency

      • Late-onset (adult-type) hypolactasia, resulting in lactose intolerance

    • Chemotherapy or radiation-induced enteritis

    • Surgical conditions

      • Acute appendicitis

      • Intussusception

    • Vitamin deficiencies

      • Niacin deficiency

      • Folate deficiency

    • Vitamin toxicity

      • Vitamin C

      • Niacin, vitamin B3

    • Ingestion of heavy metals or toxins (eg, copper, tin, zinc)

    • Ingestion of plants (eg, hyacinths, daffodils, azalea, mistletoe, Amanita species mushrooms

  • Infectious causes of acute diarrhea in developed countries

    • Viruses

      • Rotavirus - 25-40% of cases

      • Norovirus - 10-20% of cases

      • Calicivirus - 1-20% of cases

      • Astrovirus - 4-9% of cases

      • Enteric-type adenovirus - 2-4% of cases

    • Bacteria

      • Campylobacter jejuni - 6-8% of cases

      • Salmonella - 3-7% of cases

      • E Coli - 3-5% of cases

      • Shigella - 0-3% of cases

      • Y enterocolitica - 1-2% of cases

      • C difficile - 0-2% of cases

      • Vibrio parahaemolyticus - 0-1% of cases

      • V cholerae - Unknown

      • Aeromonas hydrophila - 0-2% of cases

    • Parasites

      • Cryptosporidium - 1-3% of cases

      • G lamblia - 1-3% of cases

A study by Yi et al of 207 stool samples from hospitalized children in metropolitan Atlanta, Ga, with health-care–associated vomiting and/or diarrhea found that 20 children (10%) were positive for rotavirus and 7 children (3%) were positive for norovirus. The results indicated that these pathogens have an important role in pediatric nosocomial illness.[10]

 

DDx

 

Workup

Laboratory Studies

The following may be noted in patients with diarrhea:

  • In patients with diarrhea, a stool pH level of 5.5 or less or presence of reducing substances indicates carbohydrate intolerance, which is usually secondary to viral illness and transient in nature.

  • Enteroinvasive infections of the large bowel cause leukocytes, predominantly neutrophils, to be shed into stool. Absence of fecal leukocytes does not eliminate the possibility of enteroinvasive organisms. However, presence of fecal leukocytes eliminates consideration of enterotoxigenic E coli, Vibrio species, and viruses.

  • Examine any exudates found in stool for leukocytes. Such exudates highly suggest colitis (80% positive predictive value). Colitis can be infectious, allergic, or part of inflammatory bowel disease (Crohn disease, ulcerative colitis).

  • Many different culture mediums are used to isolate bacteria. Table 3 lists common bacteria and optimum culture mediums for their growth. A high index of suspicion is needed to choose the appropriate medium.

  • With stool not cultured within 2 hours of collection, refrigerate at 4°C or place in a transport medium. Although stool cultures are useful when positive, yield is low.

  • Always culture stool for Salmonella, Shigella, and Campylobacter organisms and Y enterocolitica in the presence of clinical signs of colitis or if fecal leucocytes are found.

  • Look for C difficile in persons with episodes of diarrhea characterized by colitis and/or blood in the stools. Remember that acute-onset diarrheal episodes associated with C difficile may also occur without a history of antibiotic use.

  • Bloody diarrhea with a history of ground beef ingestion must raise suspicion for enterohemorrhagic E coli. If E coli is found in the stool, determine if the type of E coli is O157:H7. This type of E coli is the most common, but not only, cause of HUS.

  • History of raw seafood ingestion or foreign travel should prompt additional screening for Vibrio and Plesiomonas species.

Table 4. Common Bacteria and Optimum Culture Mediums (Open Table in a new window)

Organism

Detection Method

Microbiologic Characteristics

Aeromonas species

Blood agar

Oxidase-positive flagellated gram-negative bacillus (GNB)

Campylobacter species

Skirrow agar

Rapidly motile curved gram-negative rod (GNR); Campylobacter jejuni 90% and Campylobacter coli 5% of infections

C difficile

Cycloserine-cefoxitin-fructose-egg (CCFE) agar; enzyme immunoassay (EIA) for toxin; latex agglutination (LA) for protein

Anaerobic spore-forming gram-positive rod (GPR); toxin-mediated diarrhea; produces pseudomembranous colitis

C perfringens

None available

Anaerobic spore-forming GPR; toxin-mediated diarrhea

E coli

MacConkey eosin-methylene blue (EMB) or Sorbitol-MacConkey (SM) agar

Lactose-producing GNR

Plesiomonas species

Blood agar

Oxidase-positive GNR

Salmonella species

Blood, MacConkey EMB, xylose-lysine-deoxycholate (XLD), or Hektoen enteric (HE) agar

Nonlactose non–H2S-producing GNR

See the list below:

  • Culture mediums used to isolate bacteria include the following:

    • Blood agar - All aerobic bacteria and yeast; detects cytochrome oxidase production

    • MacConkey EMB agar - Inhibits gram-positive organisms; permits lactose fermentation

    • XLD agar; HE agar - Inhibits gram-positive organisms and nonpathogenic GNB; permits lactose fermentation H2S production

    • Skirrow agar - Selective for Campylobacter species

    • SM agar - Selective for enterohemorrhagic E coli

    • CIN agar - Selective for Y enterocolitica

    • TCBS agar - Selective for Vibrio species

    • CCFE agar - Selective for C difficile

  • Rotavirus antigen can be identified by enzyme immunoassay and latex agglutination assay of the stool. The false-negative rate is approximately 50%, and false-positive results occur, particularly in the presence of blood in the stools.

  • Adenovirus antigens can be detected by enzyme immunoassay. Only serotypes 40 and 41 are able to induce diarrhea.

  • Examination of stools for ova and parasites is best for finding parasites. Perform stool examination every 3 days or every other day.

  • The leukocyte count is usually not elevated in viral-mediated and toxin-mediated diarrhea. Leukocytosis is often but not constantly observed with enteroinvasive bacteria. Shigella organisms cause a marked bandemia with a variable total white blood cell count.

  • At times, a protein-losing enteropathy can be found in patients with extensive inflammation in the course of enteroinvasive intestinal infections (eg, Salmonella species, enteroinvasive E coli). In these circumstances, low serum albumin levels and high fecal alpha1-antitrypsin levels can be found.

Other Tests

Because the pathogenesis of diarrhea can be either osmolar (due to the presence of an excess of unabsorbed substrates in the gut lumen) or secretory (due to active anion secretion from the enterocytes), the anion gap in the stools is occasionally used to ascertain the nature of the diarrhea. The stool anion gap is calculated according to the formula: 290 - [(Na+K) X 2]. If the value is more than 100, osmolar diarrhea can be assumed to be present. If the value is less than 100, the diarrhea has a secretory origin.

Procedures

Intestinal biopsy is not required in evaluating an otherwise healthy child with acute-onset diarrhea, but it may be indicated in the presence of chronic or protracted diarrhea, as well as in cases in which a search for a cause is believed to be mandatory (eg, in patients with acquired immunodeficiency syndrome [AIDS] or patients who are otherwise severely immunocompromised).

 

Treatment

Medical Care

In 2003 the Center for Disease Control (CDC) put forth recommendations for the management of acute pediatric diarrhea in both the outpatient and inpatient settings including indication for referral.[1]

Indications for medical evaluation of children with acute diarrhea include the following:

  • Younger than 3 months

  • Weight of less than 8 kg

  • History of premature birth, chronic medical conditions, or concurrent illness

  • Fever of 38ºC or higher in infants younger than 3 months or 39ºC or higher in children aged 3-36 months

  • Visible blood in the stool

  • High-output diarrhea

  • Persistent emesis

  • Signs of dehydration as reported by caregiver, including sunken eyes, decreased tears, dry mucous membranes, and decreased urine output

  • Mental status changes

  • Inadequate responses to oral rehydration therapy (ORT) or caregiver unable to administer ORT

The report also includes information on assessment of dehydration and what steps should be taken to adequately treat acute diarrhea.

Treatment of dehydration due to diarrhea includes the following:

  • Minimal or no dehydration

    • Rehydration therapy - Not applicable

    • Replacement of losses

      • Less than 10 kg body weight - 60-120 mL oral rehydration solution for each diarrhea stool or vomiting episode

      • More than 10 kg body weight - 120-140 mL oral rehydration solution for each diarrhea stool or vomiting episode

  • Mild-to-moderate dehydration

    • Rehydration therapy - Oral rehydration solution (50-100 mL/kg over 3-4 h)

    • Replacement of losses

      • Less than 10 kg body weight - 60-120 mL oral rehydration solution for each diarrhea stool or vomiting episode

      • More than 10 kg body weight - 120-140 mL oral rehydration solution for each diarrhea stool or vomiting episode

  • Severe dehydration

    • Rehydration therapy - Intravenous lactated Ringer solution or normal saline (20 mL/kg until perfusion and mental status improve), followed by 100 mL/kg oral rehydration solution over 4 hours or 5% dextrose (half normal saline) intravenously at twice maintenance fluid rates

    • Replacement of losses

      • Less than 10 kg body weight - 60-120 mL oral rehydration solution for each diarrhea stool or vomiting episode

      • More than 10 kg body weight - 120-140 mL oral rehydration solution for each diarrhea stool or vomiting episode

      • If unable to drink, administer through nasogastric tube or intravenously administer 5% dextrose (one fourth normal saline) with 20 mEq/L potassium chloride

ORT is the cornerstone of treatment, especially for small-bowel infections that produce a large volume of watery stool output. ORT with a glucose-based oral rehydration syndrome must be viewed as by far the safest, most physiologic, and most effec­tive way to provide rehydration and maintain hydration in children with acute diarrhea worldwide, as recommended by the WHO; by the ad hoc committee of European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN); and by the American Academy of Pediatrics.[11] However, the global use of ORT is still insufficient. Developed countries, in particular the United States, seem to be lagging behind despite studies that demonstrate beyond doubt the efficacy of ORT in emergency care settings, in which intravenous rehydration unduly continues to be widely privileged.

Not all commercial ORT formulas promote optimal absorption of electrolytes, water, and nutrients. The ideal solution has a low osmolarity (210-250) and a sodium content of 50-60 mmol/L. Administer maintenance fluids plus replacement of losses. Educate caregivers in methods necessary to replace this amount of fluid. Administer small amounts of fluid at frequent intervals to minimize discomfort and vomiting. A 5-mL or 10-mL syringe without a needle is a very useful tool. The syringe can be quickly used to place small amounts of fluid in the mouth of a child who is uncooperative. Once the child becomes better hydrated, cooperation improves enough to take small sips from a cup. This method is time intensive and requires a dedicated caregiver. Encouragement from the physician is necessary to promote compliance. Oral rehydration is now universally recommended to be completed within 4 hours.

The addition of zinc to oral rehydration solution has been proven effective in children with acute diarrhea in developing countries and is recommended by the WHO.[12] However, no evidence suggests efficacy in children living in developed countries, in which the prevalence of zinc deficiency is assumed to be extremely low.

The composition of almost all other beverages (carbonated or not) that are commercially available and frequently used in children with diarrhea is completely inadequate for rehydration or for maintaining hydration, considering the sodium content, which is invariably extremely low, and osmolarity that is often dangerously elevated. For instance, Coca-Cola, Pepsi-Cola, and apple juice have an osmolarity of 493, 576, and 694-773, respectively.

However, research conducted in a community clinic in Nicaragua indicated that green tea and pomegranate extract combined with a standard oral rehydration solution help children with diarrhea improve faster.[13] Results showed the average time to achieve a Bristol Stool Scale (BSS) score of 4 or less was significantly shorter in the extract group than in the control group (3.1 vs 9.2 hours, respectively). In addition, a BSS score of 4 or less in the first bowel movement after treatment was achieved by more patients in the extract group than the control group (60% vs 29%, respectively). BSS scores in the extract group were maintained on day 2.[13]

At completion of hydration, resumption of feeding is strongly recommended. In fact, many studies convincingly demonstrate that early refeeding hastens recovery. Also, robust evidence suggests that, in the vast majority of episodes of acute diarrhea, refeeding can be accomplished without the use of any special (eg, lactose-free or soy-based) formulas.

Antimotility agents are not indicated for infectious diarrhea, except for refractory cases of Cryptosporidium infection. Antimicrobial therapy is indicated for some nonviral diarrhea because most is self-limiting and does not require therapy.

Therapies recommended for some nonviral diarrheas include the following:

  • Aeromonas species: Use cefixime and most third-generation and fourth-generation cephalosporins.

  • Campylobacter species: Erythromycin shortens illness duration and shedding.

  • C difficile: Discontinue potential causative antibiotics. If antibiotics cannot be stopped or this does not result in resolution, use oral metronidazole or vancomycin. Vancomycin is reserved for the child who is seriously ill.

  • C perfringens: Do not treat with antibiotics.

  • Cryptosporidium parvum: Administer paromomycin; however, effectiveness is not proven. Nitazoxanide, a newer anthelmintic, is effective against C parvum.

  • Entamoeba histolytica: Metronidazole followed by iodoquinol or paromomycin is administered in symptomatic patients. Asymptomatic carriers in nonendemic areas should receive iodoquinol or paromomycin.

  • E coli: Trimethoprim-sulfamethoxazole (TMP-SMX) should be administered if moderate or severe diarrhea is noted; antibiotic treatment may increase likelihood of hemolytic-uremic syndrome (HUS). Parenteral second-generation or third-generation cephalosporin is indicated for systemic complications.

  • G lamblia: Metronidazole or nitazoxanide can be used.

  • Plesiomonas species: Use TMP-SMX or any cephalosporin.

  • Salmonella species: Treatment prolongs carrier state, is associated with relapse, and is not indicated for nontyphoid-uncomplicated diarrhea. Treat infants younger than 3 months and high-risk patients (eg, immunocompromised, sickle cell disease). TMP-SMX is first-line medication; however, resistance occurs. Use ceftriaxone and cefotaxime for invasive disease.

  • Shigella species: Treatment shortens illness duration and shedding but does not prevent complications. TMP-SMX is first-line medication; however, resistance occurs. Cefixime, ceftriaxone, and cefotaxime are recommended for invasive disease.

  • V cholerae: Treat infected individuals and contacts. Doxycycline is the first-line antibiotic, and erythromycin is second-line antibiotic.

  • Yersinia species: TMP-SMX, cefixime, ceftriaxone, and cefotaxime are used. Treatment does not shorten disease duration; reserve for complicated cases.

Consultations

See the list below:

  • Surgeon

    • Certain organisms cause abdominal pain and bloody stools.

    • Symptoms resembling appendicitis, hemorrhagic colitis, intussusception, or toxic megacolon may be appreciated.

    • If the infectious etiology in individuals with such symptoms is not certain, seek consultation with a surgeon.

  • Infectious-disease specialist: Consider consultation with an infectious-disease specialist for any patient who is immunocompromised because of HIV infection, chemotherapy, or immunosuppressive drugs because atypical organisms are more likely, and complications can be more serious and fulminate.

Diet

Breastfed infants with acute diarrhea should be continued on breast milk without any need for interruption. In fact, breastfeeding not only has a well-known protective effect against the development of enteritis, it also promotes faster recovery and provides improved nutrition. This is even more important in developing countries, where with­drawal of breastfeeding during diarrhea has been shown to have a deleterious effect on the development of dehydra­tion in infants with acute watery diarrhea.

  • Bananas, rice, applesauce, and toast diet

    • A banana, rice, applesauce, and toast (BRAT) diet was introduced in the United States in 1926 and has enjoyed vast popularity. However, no evidence shows that this diet is useful, and its poor protein content may be a contraindication; therefore, it is not recommended.

    • A strong body of evidence now suggests that resuming the prediarrhea diet is perfectly safe and must be encouraged, obviously respecting any (usually temporary) lack of appetite.

  • Lactose ingestion

    • Although rotavirus can cause secondary transient lactose intolerance, this finding is believed to be generally not clinically relevant; use lactose-containing formulas in all individuals with diarrhea.

    • In an incident of worsening of diarrhea proven to be secondary to a clinically important lactose malabsorption in infants positive for rotavirus, a very transient use of lactose-free formulas (5-6 d) can be considered.

 

Guidelines

Guidelines Summary

British Society of Gastroenterology guidelines for the investigation of chronic diarrhoea in adults[35]

Clinical assessment

  • Recommend a careful detailed history to plan investigations.
  • Recommend screening blood tests for the exclusion of anemia, celiac disease, etc, as well as stool tests for inflammation.
  • Recommend making a positive diagnosis of irritable bowel syndrome (IBS) following basic blood and stool screening tests.

Cancer or inflammation

  • Recommend excluding colorectal cancer in those with altered bowel habit ± rectal bleeding by colonoscopy.
  • Suggest use of testing for fecal blood loss by fecal immunochemical testing in primary or secondary care, either as an exclusion test or to guide priority of investigations in those with lower gastrointestinal symptoms (chronic diarrhea) but without rectal bleeding.
  • Fecal calprotectin is recommended to exclude colonic inflammation in those suspected with IBS and under the age of 40.

Secondary clinical assessment

  • If symptoms persist despite normal first-line investigations and treatment, then referral for further investigations is recommended.
  • We recommend blood and stool tests to exclude malabsorption and common infections (especially in the immunocompromised or elderly).

Common disorders

  • In those with functional bowel or IBS-diarrhea, a positive diagnosis of bile acid diarrhea should be made either by selenium-75-homocholic acid taurine ( 75SeHCAT) testing or serum bile acid precursor 7α-hydroxy-4-cholesten-3-one (7αHCO, or 7αC4) (depending on local availability).
  • Recommend colonoscopy with biopsies of the right and left colon (not rectal) to exclude microscopic colitis.

Malabsorption

  • If lactose maldigestion is suspected, suggest hydrogen breath testing (if available) or withdrawal of dietary lactose/carbohydrates from the diet.
  • Magnetic resonance (MR) enterography (MRE) is recommended for evaluation of small bowel abnormalities depending on availability.
  • Video capsule endoscopy (VCE) is recommended for assessing small bowel abnormalities depending on local availability.
  • We do not recommend small bowel barium follow through or barium enteroclysis for the evaluation of small bowel abnormalities because of its poor sensitivity and specificity.
  • Recommend enteroscopy only for targeted lesions identified by MRE or VCE and not for diagnosis of chronic diarrhea.
  • Recommend fecal elastase testing when fat malabsorption is suspected. We do not recommend  para-aminobenzoic acid (PABA) testing.
  • MR imaging (MRI) (rather than computed tomography (CT)) is recommended for assessing structural anomalies of the pancreas in suspected chronic pancreatitis.
  • If small bowel bacterial overgrowth is suspected, we recommend an empirical trial of antibiotics, as there is insufficient evidence to recommend routine hydrogen or methane breath testing.

Surgical and structural disorders

  • We recommend use of anorectal manometry and endoanal ultrasound only when other local pathology has been excluded and conservative measures exhausted.
  • Recommend radiologic modalities for the investigation of fistulae—MRI or CT with contrast follow through.

Rare causes

  • Diarrhea due to hormone secreting tumors is rare; hence, we recommend testing only when other causes of diarrhea have been excluded.

 

 

Medication

Medication Summary

Diarrheal diseases have been the object of numerous forms of treatment, both dietetic and pharmacologic, for centuries. However, the evidence is now clear that, in most cases, the best option for treatment of acute-onset diarrhea is the early use of oral rehydration therapy (ORT).[1] Pharmacological treatment is rarely of any use, and antidiarrheal drugs are often harmful.

In terms of recommended antimicrobial treatment in the immunocompetent host, enteric bacterial and protozoan pathogens can be grouped as follows:

Agents for whom antimicrobial therapy is always indicated: The consensus includes only V cholerae, Shigella species, and G lamblia.

Agents for whom antimi­crobial therapy is indicated only in selected circumstances, include the following:

  • Infections by enteropathogenic E coli, when running a prolonged course

  • Enteroinvasive E coli, based on the sero­logic, genetic, and pathogenic similarities with Shigella

  • Yersinia infections in subjects with sickle cell disease

  • Salmonella infections in very young infants, if febrile or with positive blood culture findings

Probiotics

Recently, some strains of probiotics (defined as live microorganisms that when ingested in adequate doses, provide a benefit to the host) have been found to be effective as an adjunct when treating children with acute diarrhea. Data from well-conducted randomized controlled trials on efficacy of probiotics in children with diarrhea are definitely positive. They consistently show a statistically significant benefit and moderate clinical benefit of a few, now well-identified probiotic strains (mostly Lactobacillus GG and Saccharomyces boulardii but also Lactobacillus reuteri) in the treatment of acute watery diarrhea (primarily rotaviral) in infants and young children in developed countries.

Such a beneficial effect seems to result in a reduction of the duration of diarrhea of about one day and seems to be exerted mostly on rotaviral diarrhea, with much less evidence of efficacy in invasive bacterial diarrhea. The effect is not only strain-dependent but also dose-dependent, with doses of at least 5 billion/d being required for effect.[14] Shortening the duration of diarrhea by one day may not appear to be hugely beneficial. However, in consideration of the high morbidity of the infection, even a reduction of this order is indeed desirable because it affords considerable savings in terms of loss of working days and direct health costs.

Furthermore, probiotics may reduce the risk of spreading rotavirus infection by shortening diarrhea duration and volume of watery stool output and by reducing the fecal shedding of rotavirus, and they have been found useful in preventing the dissemination of hospital-acquired diarrheas.

A recent position paper jointly published by the ESPGHAN and the European Society for Pediatric Infectious Disease (ESPID) stated, ‘‘Probiotics may be an effective adjunct to the management of diarrhea. However, because there is no evidence of efficacy for many preparations, we suggest the use of probiotic strains with proven efficacy and in appropriate doses for the management of children with acute gastroenteritis as an adjunct to rehydration therapy (II, B). The following probiotics showed benefit in meta-analyses of randomized controlled trials: Lactobacillus GG (I, A) and S boulardii (II, B).’’

Table 5 illustrates current assessment of the efficacy of probiotics in conditions characterized by diarrhea.

Table 5. Probiotic Efficacy in Diarrhea (Open Table in a new window)

Condition

Patients and Controls

Most-Studied Probiotics

Evidence of Efficacy

(- to +++)

Prevention of Daycare Diarrhea

2000

Lactobacillus GG

Bifidobacterium lactis

Lactobacillus reuteri

Lactobacillus casei

Bifidobacterium bifidum + Streptococcus thermophilus

+

Prevention of Nosocomial Diarrhea

1000

Lactobacillus GG

++

Prevention of Antibiotic-Associated Diarrhea

2000

Lactobacillus GG

Saccharomyces boulardii

+++

Infectious Diarrhea

3500

Lactobacillus GG

Saccharomyces boulardii

+++

Persistent Diarrhea

460

Lactobacillus GG

+

 

Antibiotic and antiparasitics agents

Class Summary

Antimicrobial agents, in addition to the immune system, help destroy offending organisms. Their use is confined to specific etiologies and/or clinical circumstances.

Cefixime (Suprax)

Potent long-acting oral cephalosporin with increased gram-negative coverage. Inhibits bacterial cell wall synthesis by binding to 1 or more PBPs. Bacteria eventually lyse because of ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.

Ceftriaxone (Rocephin)

A third-generation cephalosporin antibiotic with activity against gram-positive and some gram-negative bacteria. Binds to PBPs, inhibiting bacterial cell wall growth.

Cefotaxime (Claforan)

Third-generation cephalosporin antibiotic with activity against gram-positive and some gram-negative bacteria. Binds to PBPs, inhibiting bacterial cell wall growth.

Erythromycin (E.E.S., E-Mycin, Eryc, Ery-Tab, Erythrocin)

Bacteriostatic macrolide with activity against most gram-positive organisms and atypical respiratory organisms. Useful for Campylobacter species and vibrio enteritis.

Furazolidone (Furoxone)

Antiparasitic agent with wide coverage. Nitrofuran with antiprotozoal activity. Alternative drug for children because availability in liquid suspension. Most common adverse effects are GI upset and brown discoloration of urine.

Iodoquinol (Vytone, Yodoxin)

Antiparasitic agents with wide coverage.

Metronidazole (Flagyl)

Very active against Giardia species, gram-negative anaerobes, and Entamoeba species. Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Often used in combination with other antimicrobial agents except for C difficile enterocolitis).

Paromomycin (Humatin)

Amebicidal and antibacterial aminoglycoside obtained from a strain of Streptomyces rimosus, active in intestinal amebiasis. Recommended for treatment of Diphyllobothrium latum, Taenia saginata, T solium, Dipylidium caninum, and Hymenolepis nana.

Quinacrine (Atabrine)

Very effective antiparasitic against Giardia species.

Sulfamethoxazole and trimethoprim (Bactrim, Septra, Cotrim)

Folate-synthesis blocker with wide antibiotic coverage. Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Effective in E coli infections. Dosage form contains 5:1 ratio of sulfamethoxazole to trimethoprim.

Vancomycin (Vancocin)

Effective treatment (when PO) for antibiotic-associated colitis due to C difficile. However, reserve for individuals whose symptoms are not responding to less expensive and almost equally effective metronidazole.

Tetracycline (Sumycin)

Treats gram-positive and gram-negative organisms as well as mycoplasmal, chlamydial, and rickettsial infections. Good agent in older children who present with severe Yersinia species infection.

Nitazoxanide (Alinia)

Inhibits growth of C parvum sporozoites and oocysts and G lamblia trophozoites. Elicits antiprotozoal activity by interfering with pyruvate-ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction, which is essential to anaerobic energy metabolism. Available as a 20-mg/mL oral susp.

Rifaximin (Xifaxan, RedActiv, Flonorm)

Nonabsorbed (< 0.4%), broad-spectrum antibiotic specific for enteric pathogens of the gastrointestinal tract (ie, Gram-positive, Gram-negative, aerobic and anaerobic). Rifampin structural analog. Binds to beta-subunit of bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis. Indicated for E coli (enterotoxigenic and enteroaggregative strains) associated with travelers' diarrhea.

Vaccines

Class Summary

These agents elicit active immunization to increase resistance to infection. Vaccines consist of microorganisms or cellular components, which act as antigens. Administration of the vaccine stimulates the production of antibodies with specific protective properties.

Rotavirus vaccine (RotaTeq, Rotarix)

Currently, 2 PO administered live-virus vaccines are marketed in the United States. Both are indicated to prevent rotavirus gastroenteritis, a major cause of severe diarrhea in infants.

RotaTeq is a pentavalent vaccine that contains 5 live reassortant rotaviruses and is administered as a 3-dose regimen against G1, G2, G3, and G4 serotypes, the 4 most common rotavirus group A serotypes. It also contains attachment protein P1A (genotype P[8]).

Rotarix protects against rotavirus gastroenteritis caused by G1, G3, G4, and G9 strains and is administered as a 2-dose series in infants aged 6-24 wk.

Clinical trials found that the vaccines prevented 74-78% of all rotavirus gastroenteritis cases, nearly all severe rotavirus gastroenteritis cases, and nearly all hospitalizations.

 

Follow-up

Further Outpatient Care

Follow-up care depends on the severity of diarrhea and the child's age. Uncomplicated diarrhea in a school-aged child may not require follow-up care if the caregiver is reliable and has quick access to a physician. Closely monitor young children to ensure that complications do not occur. Closely monitor children who require labor-intensive ORT. Neonates require strict follow-up care within a few days of illness to ensure that malabsorption and dehydration do not occur.

Further Inpatient Care

Admit neonates or young infants with moderate dehydration, suspected infection with enterohemorrhagic E coli, or bloody diarrhea.

Oral rehydration therapy (ORT) is the universally recommended form of treatment, proven to be successful even in children who vomit or have mild-to-moderate dehydration. Admit a child with severe dehydration. Also, ORT requires vigilance. If the caregiver cannot comply with protocol, consider admission.

Deterrence/Prevention

Vaccines are indicated for persons with high risk of exposure to some pathogens.

  • In February 2006, the United States Food and Drug Administration (FDA) approved an oral vaccine for rotavirus (RotaTeq). Soon thereafter, the AAP and the Advisory Committee on Immunization Practices (ACIP) recommended RotaTeq to be part of regularly scheduled childhood immunizations. RotaTeq is administered in a 3-dose series starting between age 6-12 weeks and completing before 32 weeks. An older rotavirus vaccine (RotaShield) was associated with an increased incidence of intussusception and is no longer on the market, but RotaTeq did not show an increased risk compared with placebo in clinical trials.

  • In April 2008, the FDA approved Rotarix, another oral vaccine, for prevention of rotavirus gastroenteritis. The current recommendation is to administer 2 separate doses of Rotarix to patients aged 6-24 weeks. Rotarix was efficacious in a large study, which reported that Rotarix protected patients with severe rotavirus gastroenteritis and decreased the rate of severe diarrhea or gastroenteritis of any cause.[15]

  • A study that involved over 63,000 patients who received Rotarix or placebo at age 2 months and at age 4 months reported a decreased risk of intussusception in patients who received Rotarix.[15] The intussusception data was determined over a 31-day observation period (inpatient or outpatient) after each dose of the Rotarix vaccine; this also included a 100-day surveillance period for all serious adverse events. Although more patients who received Rotarix were observed to have seizures or pneumonia-related deaths, this link has not been directly established to Rotarix. However, on March 22, 2010, the FDA recommended the temporary discontinuation of its use, pending further studies on the reported presence of an apparently benign pig virus in the Rotarix vaccine.

  • A Cochrane Database review evaluated the results of 43 trials with 190,551 participants comparing rotavirus vaccines, both the monovalent and pentavalent types (RV1 and RV5), with placebo. Both vaccines were found to be effective in preventing rotavirus diarrhea.[16]

  • The Salmonella typhi vaccine is recommended for travelers to countries with a high risk of this infection, persons with intimate exposure to a documented typhoid fever carrier, and workers with frequent exposure to this bacteria. Live-attenuated, killed whole-cell, and capsular polysaccharide vaccines are available.

  • The Vibrio species vaccine is available but only protects 50% of immunized persons for 3-6 months. It is not indicated for use.

  • A study documented a diverse range of pathogens associated with community diarrhea in children in low-income and middle-income countries to make an estimate of pathogen-specific diarrhea burdens in the community. The study concluded that there was substantial heterogeneity in pathogen-specific burdens of diarrhea, with important determinants including age, geography, season, rotavirus vaccine usage, and symptoms. The authors also added that these findings suggest that although single-pathogen strategies have an important role in the reduction of the burden of severe diarrheal disease, the effect of such interventions on total diarrheal incidence at the community level might be limited.[17]

Complications

Common complications include the following:

  • Aeromonas caviae - Intussusception, gram-negative sepsis, hemolytic-uremic syndrome (HUS)

  • Campylobacter species -Bacteremia, meningitis, cholecystitis, urinary tract infection, pancreatitis, Reiter syndrome (RS)

  • C difficile - Chronic diarrhea

  • C perfringens serotype C - Enteritis necroticans

  • Enterohemorrhagic E coli - Hemorrhagic colitis

  • Enterohemorrhagic E coli O157:H7 - HUS

  • Plesiomonas species - Septicemia

  • Salmonella species - Seizures, HUS, perforation, RS

  • Vibrio species - Rapid dehydration

  • Y enterocolitica - Appendicitis, perforation, intussusception, peritonitis, toxic megacolon, cholangitis, bacteremia, RS

  • Rotavirus - Isotonic dehydration, carbohydrate intolerance

  • Giardia species - Chronic fat malabsorption

  • Cryptosporidium species - Chronic diarrhea

  • Entamoeba species - Colonic perforation, liver abscess

Enteric fever is caused by S typhi. This syndrome has an insidious onset of malaise, fever, abdominal pain, and bradycardia. Diarrhea and rash (rose spots) appear after 1 week of symptoms. Bacteria may have disseminated at that time, and treatment is required to prevent systemic complications such as hepatitis, myocarditis, cholecystitis, or GI bleeding.

HUS is caused by damage to vascular endothelial cells by verotoxin (released by enterohemorrhagic E coli and by Shigella organisms). Thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure characterize HUS. Symptoms usually develop one week after onset of diarrhea, when the organism may be absent.

RS can complicate acute infections and is characterized by arthritis, urethritis, conjunctivitis, and mucocutaneous lesions. Individuals with RS usually do not demonstrate all features.

Carrier states are observed after some bacterial infections.

  • After diarrhea caused by Salmonella organisms, 1-4% of individuals with nontyphoid and enteric fever infections become carriers. The carrier stage for Salmonella organisms is more likely for females, infants, and individuals with biliary tract disease.

  • Asymptomatic C difficile carriage may be observed in as many as 20% of hospitalized patients receiving antibiotics and in 50% of infants.

  • Rotavirus is excreted asymptomatically in feces of children who were previously infected, typically for as long as 1-2 weeks.

Prognosis

In developed countries, with proper management, prognosis is very good. However, data show an increase in diarrhea-associated deaths among US children from the mid-1980s through 2006. During 2005-2007, 1087 diarrhea-associated infant deaths were reported with 86% of deaths occurring among low birthweight (< 2500g) infants. Risk factors for these infants included male sex, black race, and low 5-minute Apgar score (< 7).[7]

Death is caused predominantly by dehydration and secondary malnutrition from a protracted course. Severe dehydration must be managed with parenteral fluids. Once malnutrition from secondary malabsorption begins, prognosis turns grim unless the patient is hospitalized and supplemental parenteral nutrition is started. Neonates and young infants are at particular risk of dehydration, malnutrition, and malabsorption syndromes.

Even though the mortality rate is low in developed countries, children can die from complications; however, prognosis for children in countries without modern medical care and children with comorbid conditions is more guarded.

Patient Education

Education is most important for prevention and treatment. Proper ORT prevents dehydration, and early refeeding speeds recovery of intestinal mucosa. With caregiver, emphasize proper hygiene and food preparation practices to prevent future infections and spread.

For patient education resources, see the Esophagus, Stomach, and Intestine Center, as well as Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Diarrhea.

 

Questions & Answers

Overview

What is diarrhea?

How are acute and chronic diarrhea defined?

What should be considered to determine the cause of diarrhea?

What are the signs and symptoms of diarrhea?

Which fecal lab studies are performed in the workup of diarrhea?

What lab studies are performed in the workup of diarrhea?

How is diarrhea treated?

Which drugs are used to treat diarrhea?

How is acute diarrhea defined?

What causes acute diarrhea in children and what is the most common complication of acute diarrhea?

Is acute gastroenteritis synonymous with acute diarrhea?

How are diarrheal episodes characterized?

What is the pathogenesis of diarrhea?

What is the pathophysiology of osmotic diarrhea?

What is the pathophysiology of secretory diarrhea?

What is the incidence of diarrhea in the US?

What is the global incidence of diarrhea?

What is the mortality and morbidity from diarrhea?

Does the incidence of diarrhea vary among males and females?

Does the incidence of diarrhea vary among age groups?

Presentation

What is the clinical presentation and disease course of acute diarrhea?

What is the incidence of acute diarrhea?

How is diarrhea defined in children?

What does flatulence associated with foul-smelling stools suggest?

What can be helpful in determining whether the source of diarrhea is from the small or large bowel?

What are the systemic symptoms of diarrhea?

Which organisms may increase the risk of diarrhea in daycare settings?

How can food history be helpful in the diagnosis of diarrhea and which organisms cause food poisoning?

How does water exposure increase the risk of diarrhea?

Why is travel history important in suspected diarrhea?

How does animal exposure increase the risk for diarrhea?

Which factors predispose patients to infectious causes of diarrhea?

Which physical findings suggest dehydration in patients with diarrhea?

What is the presentation of failure to thrive and malnutrition in children with diarrhea?

How is abdominal pain characterized in patients with diarrhea?

What is the presentation of borborygmi in patients with diarrhea?

What is the presentation of perianal erythema in patients with diarrhea?

What is the most common cause for sporadic or endemic episodes of acute diarrhea?

What are possible causes of acute onset diarrhea?

What are infectious causes of acute diarrhea in developed countries?

Which pathogens cause pediatric nosocomial diarrhea?

DDX

What are the differential diagnoses for Diarrhea?

Workup

Which findings suggest carbohydrate intolerance in patients with diarrhea?

Which findings suggest an enteroinvasive infectious cause of diarrhea?

What should be examined in the workup of diarrhea and what finding suggests colitis?

What is the role of culture in the workup of diarrhea?

What should prompt additional screening for Clostridium difficile (C diff) infection in the workup of diarrhea?

What should prompt additional screening for E coli in the workup of diarrhea?

What should prompt additional screening for Vibrio and Plesiomonas infections in the workup of diarrhea?

Which culture mediums are used to isolate bacteria in the workup of diarrhea?

Which test is performed to identify rotavirus infection in the workup of diarrhea?

Which test is performed to identify adenovirus in the workup of diarrhea?

How are parasitic causes of diarrhea identified?

When is leukocytosis present in diarrhea?

What does a finding of protein-losing enteropathy suggest in the workup of diarrhea?

What is the role of an anion gap test in the workup of diarrhea?

When are procedures performed in the workup of diarrhea?

Treatment

What are the CDC recommendations for the evaluation of acute pediatric diarrhea?

What are the CDC recommendations in the treatment of dehydration due to diarrhea?

What is oral rehydration therapy (ORT) for diarrhea and how is it administered?

What has been added to oral rehydration therapy (ORT) to improve effectiveness in treating diarrhea in developing countries?

Which beverages may be effective in the treatment of diarrhea?

When can feeding be resumed in children with diarrhea?

What is the role of antimotility and antimicrobial therapy for diarrhea?

What are the treatment options for nonviral diarrhea?

When should consultations be considered for patients with diarrhea?

How should infants with acute diarrhea be fed?

What diet is suggested in the treatment of diarrhea?

Medications

What is the best option for treatment of acute-onset diarrhea?

Which antimicrobial agents are used in the treatment of diarrhea?

What is the efficacy of probiotics in the treatment of diarrhea?

Which medications in the drug class Vaccines are used in the treatment of Diarrhea?

Which medications in the drug class Antibiotic and antiparasitics agents are used in the treatment of Diarrhea?