Diarrhea

Indications for Testing

Persistent or chronic diarrhea
Bloody diarrhea
Diarrhea in association with systemic illness
Immunocompromised status
Returned traveler
Hospitalized patient
Outbreak identification

Laboratory Testing

Acute diarrhea (≤14 days)

ACUTE DIARRHEA (≤14 days)
For most cases, no testing is necessary at initial presentation – most etiologies of acute diarrhea are viral and do not require treatment Exceptions (Steffen, 2014) Immunocompromised or hospitalized patients Returned travelers with any of the following Fever >101.3 F degrees Bloody stools Dysentery
Virus	Testing Options
Norovirus	PCR – most sensitive/specific test; available as a standalone test or in a viral panel EIA (antigen detection) – not as sensitive as PCR Electron microscopy – insensitive and lab specific
Rotavirus	PCR – viral panel EIA – more sensitive than scanning electron microscopy (SEM) Immunochromatographic assay (ICA) – performs better than latex agglutination Latex agglutination – not recommended
Adenovirus 40/41	PCR – viral panel EIA – good sensitivity/specificity compared to electron microscopy
Sapovirus, astrovirus	PCR – viral panel
Bacterial Testing
Indications	Testing Options
May be appropriate for certain groups (eg, returned travelers)	Stool culture Sensitivity highly variable; excellent specificity Sensitivity depends on specimen collection and transport Generally identifies Campylobacter, Salmonella, Shigella Should include E. coli for Shiga-like toxin by EIA (antigen) Sensitivity lower than PCR Turnaround time 24-96+ hrs Gastrointestinal bacterial panel by PCR PCR detects the following Campylobacter jejuni/coli Campylobacter upsaliensis Salmonella spp Shiga-like toxin 1 from E. coli Shiga-like toxin 2 from E.coli Shigella spp/enteroinvasive E. coli (EIEC) Campylobacter antigen by immunochromatography – may be used in place of culture Only specific for C. jejuni/C. coli For Yersinia and Vibrio spp – stool culture does not readily recover these spp; laboratory must include a specific culture condition or selective media for identification Clostridium difficile testing – refer to ARUP Consult topic
Parasitic Testing
Indications	Testing Options
May be indicated initially in the following Returned travelers with appropriate travel history Immunocompromised patients Community outbreaks	Do not use ova and parasite exams for most patients in acute setting Variable sensitivity Not cost effective Requires 3+ specimens Does not readily detect Cystoisospora, Cryptosporidium, Cyclospora, or Microsporidia Cannot differentiate E. histolytica from E. dispar If parasitic testing deemed necessary – refer to testing options in persistent or chronic diarrhea table below

Persistent diarrhea (>14 days) or chronic diarrhea (>30 days)

PERSISTENT (>14 days) or CHRONIC DIARRHEA (>30 days)
If no previous testing has been performed, consider also testing for Salmonella sp, Shigella sp, and Campylobacter spp (Steffen, 2014) Parasitic testing leads to highest yields at this stage
Test	Indications
PCR panel	Available with or without Microsporidia PCR; detects the following Cryptosporidium hominis, C. parvum Cyclospora cayetanensis Dientamoeba fragilis Entamoeba histolytica Giardia lamblia/intestinalis/duodenalis Very sensitive and specific for listed organisms
Individual specific organism testing
Organism	Testing Options
Giardia duodenalis (synonyms Giardia lamblia, Giardia intestinalis)	Giardia antigen by EIA – preferred if not using PCR panel If first specimen is negative and suspicion still exists, consider repeating for Giardia
Cryptosporidium hominis, C. parvum	Cryptosporidium spp antigen (EIA or DFA) – preferred if not using PCR panel Microscopic detection in stool Requires special stains (eg, modified acid fast and multiple stool specimens) Less sensitive than stool EIA
Entamoeba histolytica	Intestinal disease Entamoeba antigen (EIA) preferred if not using PCR panel
Cystoisospora belli, Cyclospora cayetanensis	Microscopic examination of stool using special stain (eg, modified acid fast) if not using PCR
Dientamoeba fragilis	Ova and parasite exam – preferred if not using PCR panel Very difficult to identify in stains; insensitive
Microsporidia	Microscopic examination of stool using microsporidial stain (eg, modified acid fast) if not using PCR Stool examination May require testing of multiple specimens

Differential Diagnosis

Gastrointestinal disorders
- Post-diarrheal malabsorption
- Inflammatory bowel disease
- Irritable bowel syndrome
- Celiac disease
- Pancreatic insufficiency
- Diverticulitis
Immunodeficiency syndromes
Cystic fibrosis
Lactose intolerance
Malignancy
- Primary or metastatic cancer
  - Colorectal cancer
  - VIPoma syndrome
Laxative abuse

Diarrhea in Healthy Pediatric Patients Testing Algorithm

Read more about Diarrhea in Healthy Pediatric Patients Testing Algorithm

Diarrhea in Hospitalized Adult Patients Testing Algorithm

Read more about Diarrhea in Hospitalized Adult Patients Testing Algorithm

Diarrhea in Immunocompromised Hosts Testing Algorithm

Read more about Diarrhea in Immunocompromised Hosts Testing Algorithm

Diarrhea in Primary Care Adults Testing Algorithm

Read more about Diarrhea in Primary Care Adults Testing Algorithm

Diarrhea in Returned Traveller or Immigrant Testing Algorithm

Read more about Diarrhea in Returned Traveller or Immigrant Testing Algorithm

Diarrhea may be infectious or noninfectious and presents with acute (<14 days) or persistent (>14 days) symptoms. Community-acquired disease is most common. Viruses (norovirus predominates) are the most common cause of acute infectious diarrhea in community dwellers. Bacterial diarrhea represents only ~1-5% of diarrhea cases, and is often associated with clustering of cases or outbreaks. Clostridium difficile cases, while often nosocomially-acquired, are increasing in community dwellers. Parasites are an infrequent or rare cause of acute diarrhea and tend to be sporadic in nature except in at-risk populations (eg, returned travelers, immunocompromised individuals).

Epidemiology

Incidence – the CDC estimates >350 million acute diarrheal incidences annually (Mead, 1999)
- The CDC's Foodborne Diseases Active Surveillance Network (FoodNet) reports ~48 million cases of foodborne illness annually

Risk Factors

Immunocompromised status
- HIV, primary immunodeficiency
  - Most common organisms include viruses, C. difficile, Campylobacter jejuni, Salmonella spp, E. coli, Giardia, Cryptosporidium spp, and microsporidia
- Transplantation (solid organ and stem cell)
  - Most diarrhea is not infectious
  - When infectious, most common organisms include viruses (norovirus most common), C. difficile, and microsporidia
Advanced age (>65 years)
- Salmonella spp and Shigella spp may require treatment so identification is important
Comorbid illnesses (eg, chronic heart, liver, or kidney disease; diabetes mellitus)
- Increased risk of complications (eg, sepsis)
Institutional residency
- Norovirus
Daycare setting
- Norovirus
- Giardia
- Cryptosporidium spp
- Salmonella spp

Clinical Presentation

Community-acquired
- Acute diarrhea (acute gastroenteritis)
  - Duration – 1-14 days
  - Transmission – foodborne, waterborne, or outbreak-associated
  - Most commonly caused by viruses and occasionally bacteria
- Persistent diarrhea
  - Duration – >14 days, often longer
  - Often noninfectious
  - Testing for parasites may be considered
  - Persistent diarrhea may be malabsorptive following an infectious diarrhea
Hospital-acquired
- Presentation may be similar community-acquired disease
- Most commonly caused by viruses
- Prominent bacterial agent to rule out if correct history – C. difficile

Organisms associated with diarrhea (CDC, 2014)

Norovirus

Epidemiology
- Incidence
  - Leading cause of nonbacterial gastroenteritis worldwide
  - Norovirus causes millions of infections annually, with outbreaks commonly occurring in all age groups and in varied environments
    - Cruise ships
    - Restaurants (salad bar contamination most common)
    - Schools
    - Daycares
    - Healthcare facilities
  - Transmission
    - Fecal-oral route by ingestion of contaminated food (eg, shellfish) or water
    - Can be airborne (in vomitus)
    - Low infectious dose; can survive relatively high levels of disinfectants and varying temperatures
Clinical Presentation
- Usually mild or self-limiting disease with high transmission rates
- Most common symptoms
  - Acute onset diarrhea and vomiting with abdominal cramps, nausea, fever, headache
- Symptoms occur within 24-48 hrs of infection and may continue for 12-60 hrs
- Transplant patients often have chronic diarrhea
  - Symptoms in small bowel transplant patients resemble allograft rejection

Rotavirus

Epidemiology
- Incidence
  - Most important cause of severe dehydrating diarrhea worldwide in children <5 yrs
    - Declined 67% in U.S. since introduction of vaccine
    - Universal infection – nearly all children have circulating antibodies by 2-3 yrs
- Transmission
  - Fecal-oral route
Clinical Presentation
- Varies from asymptomatic to severe dehydration leading to death
- Mild fever and emesis for 2-3 days
- Watery diarrhea for 3-5 days following fever
  - Bloody diarrhea rare
- Severe and prolonged disease may occur in patients
  - Significant malnutrition
  - Immune deficiencies (eg, HIV)
  - Other chronic disease such as diabetes mellitus, congenital heart disease, or pulmonary disease
  - May involve extra-intestinal sites – central nervous system, liver, spleen, or kidney, especially in immunocompromised children

Campylobacter

Epidemiology
- Incidence
  - Leading cause of bacterial gastroenteritis worldwide with peak incidence in children <5 yrs
- Occurrence
  - Campylobacter-caused diarrheal cases are sporadic, but most occur in the spring and fall
- Transmission
  - Associated with incorrect food handling practices, consumption of poorly cooked poultry or raw milk, contact with pets, travel
  - Outbreaks most often associated with raw milk and contaminated water
Clinical Presentation
- Varies from asymptomatic infection to severe inflammatory diarrhea
- Onset of symptoms occurs 2-5 days after ingestion of contaminated food or water
- Symptoms – generally last 7-10 days
  - Abdominal pain
  - Watery stools containing blood and mucous
  - Fever
  - Nausea or vomiting
- Complications
  - Reactive arthritis (increased risk if individual is positive for HLA-B27 phenotype)
  - Guillain-Barré syndrome
  - Hemolytic syndrome
  - Complications in patients with HIV or hypogammaglobulinemia include relapse and osteomyelitis (especially with HLA-B27 phenotype)
  - Local complications – hemorrhage, megacolon
  - Bacteremic complications – cellulitis, meningitis

Salmonella

Epidemiology
- Incidence
  - Most U.S. cases are related to international travel or immigrant status
  - Remaining cases are from large, sporadic outbreaks
    - Incidence nearly equal to Campylobacter
- Transmission
  - Undercooked or uncooked foods, contact with infected animals
    - Associated foods include raw meat and vegetables, poultry, eggs, milk, salad dressing, shrimp, and peanut butter
  - Nonsymptomatic patients can transmit disease to others
Clinical Presentation
- Typhoid fever
  - Incubation period is 3-21 days
  - Prodrome of chills, headache, sore throat, fever, anorexia, cough
  - Progresses to rash (rose spots), epistaxis, diarrhea, relative bradycardia
  - Blood cultures are of higher yield than stool cultures for typhoid fever
    - 90% have positive blood cultures in week 1; drops to 50% by week 3
  - Complications
    - Late complications found in untreated adults – intestinal perforation, gastrointestinal hemorrhage
    - Rare complications – pancreatitis, hepatic and splenic abscesses, endocarditis, pericarditis, orchitis, meningitis, parotitis, osteomyelitis
    - Up to 5% of infected patients develop chronic carrier state
      - Usually occurs in patients with gall bladder disease or gastric carcinomas
- Enteritis
  - Onset of symptoms 6-48 hours after exposure; typically resolves after 1-2 days
    - Fever, headache
    - Intestinal symptoms – diarrhea (watery), abdominal pain

Shiga-toxigenic E. coli

Epidemiology
- Incidence
  - Under recognized illness
  - Not uncommon
- Transmission
  - Person-to-person contact is a source of outbreak in daycare facilities and nursing homes
  - Outbreaks from consumption of undercooked meats and produce (washing produce has been shown to be ineffective)
Clinical Presentation
- Watery diarrhea progressing to bloody diarrhea
- Abdominal pain
- Symptoms usually resolve within 8 days
- HUS – fever, renal dysfunction and hemolytic anemia, thrombocytopenia
  - Virulence is attributable to production of Shiga-like toxin 1 and/or 2
  - Most frequent in children <15 yrs and adults >65 yrs

Shigella spp

Epidemiology
- Incidence
  - Common in countries with poor sanitation
  - Accounts for small percentage of reported outbreaks of foodborne illness in U.S.
- Transmission
  - Fecal-oral route; no nonhuman hosts
  - Higher risk groups – daycare personnel and clients, nursing home residents, and men who have sex with men
Clinical Presentation
- Onset of symptoms 12-50 hrs after exposure
- Diarrhea
  - Frequently bloody
  - May contain mucous or pus
- Fever
- Abdominal pain, cramps
- Dysentery (10-30 stools/day)
- Associated with Reiter syndrome (arthritis, uveitis, urethritis)
- Complications
  - Reactive arthritis (increased risk of development if patient is positive for HLA-B27 allele)
  - HUS (usually S. dysenteriae type 1)

Yersinia spp

Epidemiology
- Incidence – most often in young children
- Transmission
  - Soil, water, animals, food
  - Y. pseudotuberculosis and Y. pestis are uncommon causes of gastrointestinal disease
  - Y. enterocolitica can be found in meats (eg, beef, pork), oysters, fish, and unpasteurized milk
Clinical Presentation
- Onset of symptoms 24-48 hrs after ingestion of contaminated food or drink
- Diarrhea (loose, watery, or bloody stools), abdominal pain, and fever
  - Infections with Y. enterocolitica and Y. pseudotuberculosis can be asymptomatic, mild, or severe, with infection resolving within a few weeks (with or without use of antibiotics)
  - Yersinia infections are known for mimicking appendicitis
- Complications include reactive arthritis which can manifest 1-4 wks post-infection (increased risk of development if patient is positive for HLA-B27 allele)
  - The most commonly affected joints are knees and ankles, but other joints such as toes, fingers and wrists can be involved
  - In most cases, 2-4 joints become involved sequentially and asymmetrically over a period of a few days to 2 wks
    - Joint fluid is sterile
  - Chronic joint disease or ankylosing spondylitis occurs rarely
  - Acute arthritis persists for 1-4 mos
  - Reiter syndrome (arthritis, uveitis, and urethritis) may occur
  - Less common nonsuppurative sequelae of Y. enterocolitica infections include reactive uveitis, iritis, conjunctivitis, glomerulonephritis, urethritis, HUS

Vibrio spp

Epidemiology
- Incidence
  - Several pandemics of Vibrio cholerae infection have occurred; no major outbreaks in U.S. since 1911
  - V. vulnificus outbreak reported in New Orleans after hurricane Katrina; usually several lethal cases annually in Florida, typically in summer months
- Transmission
  - Ingestion of contaminated seafood or through open wounds in sea water
  - V. parahaemolyticus is the leading cause of bacterial diarrhea associated with foods such as seafood, crab, shrimp, lobster
Clinical Presentation
- Healthy individuals typically have onset of symptoms within 16 hrs of ingestion of contaminated seafood
- Watery diarrhea, abdominal pain, cramps, vomiting
- Immunocompromised individuals and patients with cirrhosis may present with primary septicemia
  - Associated with >50% mortality
- No associated long-term complications

Giardia duodenalis (synonyms Giardia lamblia, Giardia intestinalis)

Epidemiology
- Incidence
  - Most common cause of parasite-associated diarrhea in the U.S.
  - Increased frequency in children, homosexual males, and institutional care facilities
- Transmission
  - Waterborne, foodborne, or fecal-oral
Clinical Presentation
- Most infections are asymptomatic
- Symptoms may last from weeks to months
  - Acute or chronic nonbloody diarrhea, nausea, vomiting, dehydration, abdominal discomfort, malabsorptive symptoms (eg, flatulence, greasy malodorous stools)
- Intermittent or recurrent symptoms are common

Cryptosporidium spp

Epidemiology
- Incidence
  - Increased risk in HIV infection, households of infected patients, daycare centers, and foreign travel
- Transmission
  - Waterborne, sporadic or outbreak-associated
    - Found in large outbreaks associated with contaminated water sources
    - Can occur year round when artificial water storage systems are involved
Clinical Presentation
- Immunocompetent patients
  - Usually asymptomatic or mild, self-limiting gastroenteritis
  - Nonbloody, watery diarrhea, dehydration, nausea, vomiting, abdominal pain, low-grade fever and malaise lasting from a few days to occasionally >30 days
- Immunocompromised patients (particularly T-cell deficiencies)
  - Chronic diarrhea (often more severe than expected for pathogen), dehydration, weight loss
  - HIV – chronic diarrhea; others include cholecystitis, hepatitis, pancreatitis

Entamoeba histolytica

Epidemiology
- Incidence
  - Increased risk in homosexual men, immigrants, institutional care settings, foreign travel, HIV patients
  - Typically limited to individual cases, with possible spread to sex partners or close contacts
- Transmission
  - Waterborne, foodborne, or fecal-oral
Clinical Presentation
- Most individuals are asymptomatically colonized (~90%)
  - Subacute onset
- Disease may be intestinal or extraintestinal
  - Intestinal disease
    - Fulminant or chronic, with abdominal pain, tenderness, tenesmus, and bloody diarrhea
  - Extraintestinal disease
    - May include liver, brain, and lung abscesses

Cystoisospora belli

Epidemiology
- Incidence
  - Increased risk in AIDS patients, recent immigrants, and travelers from endemic regions
- Transmission
  - Waterborne
Clinical Presentation
- Immunocompetent patients
  - Acute, self-limiting watery or malodorous diarrhea (similar to Giardia or Cryptosporidium infection)
- Immunocompromised patients
  - Chronic diarrhea (occasionally severe), dehydration, weight loss
  - HIV – cholecystitis, reactive arthritis in addition to diarrhea

Microsporidia

Epidemiology
- Incidence
  - Undetermined in non-HIV populations
  - Increased risk in HIV patients presenting with chronic diarrhea
    - Predominately affects immunocompromised hosts
    - Includes Enterocytozoon bieneusi, Encephalitozoon intestinalis, Pleistophora, Septata, Vittaforma spp
    - ~15% prior to combination antiretroviral therapy (cART)
    - Rates are lower for patients on cART
- Transmission
  - Waterborne
Clinical Presentation
- Immunocompetent patients
  - Rare cause of acute, self-limiting diarrhea
- Immunocompromised patients
  - Chronic diarrhea, dehydration, anorexia, weight loss, abdominal pain, nausea, vomiting
    - Most often in patients with HIV

Cyclospora cayetanensis

Epidemiology
- Incidence
  - Unknown in U.S.; usually tropical/subtropical regions
- Transmission
  - Food or waterborne
  - Clustered outbreaks associated with contaminated food products
  - Outbreaks have been occurring recently in higher frequency
    - Not associated with foreign travel, but rather, foreign food products sold domestically
Clinical Presentation
- Immunocompetent patients
  - Anorexia, nausea, emesis, flatulence, watery diarrhea, low grade fever, fatigue, cramping
  - Typically does not resolve without treatment
- Immunocompromised patients
  - May cause chronic diarrhea
- Endemic – frequently cases of mild or asymptomatic disease

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Norovirus Group 1 and 2 by PCR 0051281
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Recommended Use

Most sensitive and specific test for diagnosing norovirus-associated gastroenteritis

Limitations

Negative result does not rule out the presence of PCR inhibitors (heme) in the patient specimen or norovirus nucleic acid concentrations below the level of detection of the assay

Does not rule out presence of bacterial or other viral causes of gastroenteritis

Rotavirus Antigen by EIA 0065088
Method: Qualitative Enzyme Immunoassay

Recommended Use

Diagnose rotavirus-associated gastroenteritis

Limitations

Does not rule out presence of bacterial or other viral causes of gastroenteritis

Negative result does not exclude the possibility of rotavirus infection

Low virus quantity or improper/inadequate sampling can cause false-negative results

Rotavirus and Adenovirus 40-41 Antigens 0065067
Method: Qualitative Enzyme Immunoassay

Recommended Use

Diagnose rotavirus- and adenovirus-associated gastroenteritis

Limitations

Does not rule out presence of bacterial or other viral causes of gastroenteritis

Negative result does not exclude the possibility of rotavirus infection

Low virus quantity or improper/inadequate sampling can cause false-negative results

Positive adenovirus results should be interpreted with caution since adenovirus is capable of latency and recrudescence

Asymptomatic shedding may persist for months after infection

False-positive adenovirus results can occur with high levels of Staphylococcus aureus expressing Protein A; however, staphylococcal enterocolitis is uncommon in adults and extremely rare in infants and children

Adenovirus 40-41 Antigens by EIA 0065066
Method: Qualitative Enzyme Immunoassay

Recommended Use

Diagnose adenovirus-associated gastroenteritis

Refer to rotavirus and adenovirus 40-41 antigens for combination testing

Stool Culture and E. coli Shiga-like Toxin by EIA 0060134
Method: Culture/Identification

Recommended Use

Preferred test for suspected bacterial diarrhea evaluation

Cultures include Salmonella, Shigella, Campylobacter, and E. coli 0157 as well as EIA for Shiga-like toxin from E. coli

Excellent specificity

Limitations

Turnaround time 24->96 hours

Sensitivity highly variable

Clostridium difficile toxin B gene (tcdB) by PCR 2002838
Method: Qualitative Polymerase Chain Reaction

Recommended Use

Recommended rapid, stand-alone diagnostic test for C. difficile-associated diarrhea

Gastrointestinal Bacterial Panel by PCR 2012678
Method: Qualitative Polymerase Chain Reaction

Recommended Use

Use as a sensitive alternative to traditional stool culture to detect the most common gastrointestinal bacterial pathogens: Salmonella, Shigella/Enteroinvasive E. coli, Campylobacter jejuni/coli, and shiga-toxigenic E. coli

This test can also detect Campylobacter upsaliensis, which cannot be readily cultured

Analytical sensitivity

Limit of detection
- Shigella – 36,200 copies/mL
- Salmonella – 1,520 copies/mL
- Campylobacter jejuni/coli – 3,780 copies/mL
- Campylobacter upsaliensis – 1,510 copies/mL
- Shiga-like toxin 1 – 5,180 copies/mL
- Shiga-like toxin 2 – 4,080 copies/mL

Analytical specificity -- no cross reactivity seen for 43 organisms (bacteria, viruses, and parasites) tested

Limitations

A negative result does not rule out the presence of PCR inhibitors in the patient specimen or test-specific nucleic acid in concentrations below the level of detection by this test

Molecular assays will not detect rare or unusual enteric bacterial pathogens that are not specifically targeted by the test (eg, Aeromonas, Pleisiomonas, Yersinia, Vibrio, and enterotoxigenic E. coli)

A bacterial isolate is not obtained if antimicrobial susceptibility testing is indicated

Gastrointestinal Parasite and Microsporidia by PCR 2011660
Method: Qualitative Polymerase Chain Reaction

Recommended Use

Aid in the diagnosis of GI infections caused by common protozoal pathogens

Most comprehensive and sensitive alternative to traditional, insensitive ova and parasite examinations of stool specimens for parasite evaluations

Do not order for patients with diarrhea developed during prolonged hospitalization

Detect Cryptosporidium hominis, C. parvum, Cyclospora cayetanensis, Dientamoeba fragilis, Entamoeba histolytica, Giardia lamblia/intestinalis/duodenalis, and microsporidia by PCR

Limitations

Due to the periodic shedding of some parasites, a result of “not detected” cannot completely rule out infection with these parasites

If clinical signs and symptoms persist, an additional specimen for testing may be indicated

Viral and bacterial gastroenteritis are more common than parasitic gastroenteritis and should be considered as alternative diagnoses

Asymptomatic infections are known to occur, and therefore correlation of test results with clinical signs and symptoms is imperative

Does not detect helminths (flatworms, roundworms, and flukes), nonpathogenic protozoa, or Cystoisospora

Gastrointestinal Parasite Panel by PCR 2011150
Method: Qualitative Polymerase Chain Reaction

Recommended Use

Aid in the diagnosis of GI infections caused by common protozoal pathogens

Use as a sensitive alternative to traditional, insensitive ova and parasite examinations of stool specimens

Do not order for patients with diarrhea developed during prolonged hospitalization

Detects Cryptosporidium hominis, C. parvum, Cyclospora cayetanensis, Dientamoeba fragilis, Entamoeba histolytica, and Giardia lamblia/intestinalis/duodenalis

Limitations

Due to the periodic shedding of some parasites, a result of “not detected” cannot completely rule out infection with these parasites

If clinical signs and symptoms persist, an additional specimen for testing may be indicated

Viral and bacterial gastroenteritis are more common than parasitic gastroenteritis and should be considered as alternative diagnoses

Asymptomatic infections are known to occur, and therefore correlation of test results with clinical signs and symptoms is imperative

Does not detect helminths (flatworms, roundworms, and flukes), nonpathogenic protozoa, Cystoisospora, or microsporidia

Gastrointestinal Viral Panel by PCR 2013577
Method: Qualitative Polymerase Chain Reaction

Recommended Use

Aid in the diagnosis of GI infections caused by viral pathogens

Use as a sensitive alternative to traditional antigen testing

Detects adenovirus (serotypes 40 and 41), astrovirus, norovirus (genogroups 1 and 2), rotavirus, and sapovirus

Giardia Antigen by EIA 0060048
Method: Qualitative Enzyme Immunoassay

Recommended Use

Test for persistent diarrhea (>14 days) or known risk factors

Diagnose Giardia duodenalis (synonyms Giardia lamblia, Giardia intestinalis) as etiology of diarrheal disease

Rapid (24-hour) turnaround

Sensitive method for detection of Giardia

Limitations

Will not detect parasites other than G. duodenalis

Testing of second specimen may be indicated if first specimen is negative and clinical suspicion is high

Cryptosporidium Antigen by EIA 0060045
Method: Qualitative Enzyme Immunoassay

Recommended Use

Test for persistent diarrhea (>14 days) or known risk factors if Cryptosporidium spp is the suspected infectious agent

Rapid (24-hour) turnaround

Most sensitive test for detection of Cryptosporidium spp

Limitations

Will not detect parasites other than Cryptosporidium spp

Parasitology Stain by Modified Acid-Fast 0060046
Method: Qualitative Concentration/Stain

Recommended Use

Test for persistent diarrhea (>14 days) or known risk factors

Detect Cryptosporidium, Cyclospora and Cystoisospora

Limitations

Not intended for detection of other stool parasites

Less sensitive than EIA for Cryptosporidium spp

Microsporidia by PCR 2011626
Method: Qualitative Polymerase Chain Reaction

Recommended Use

Preferred test to diagnose Microsporidia in immunocompromised patients with persistent diarrhea if Encephalitozoon spp (E. instestinalis/E. hellem/E. cuniculi) or Enterocytozoon bieneusi is the suspected infectious agent

More sensitive than direct staining

Limitations

Presence of nucleic acid does not indicate presence of viable organisms; results should be used in conjunction with appropriate clinical symptoms for diagnostic purposes

Negative result does not rule out presence of PCR inhibitors in specimen or assay-specific nucleic acid in concentrations below the level of detection

Does not detect all possible pathogenic microsporidia spp

Limitations of PCR test should be considered during final diagnosis

If test yields a negative result and suspicion of microsporidia infection is high, a modified trichrome stain should be considered

Microsporidia Stain by Modified Trichrome 0060050
Method: Qualitative Stain

Recommended Use

Can be used for follow-up of negative PCR result when suspicion of less common microsporidia are suspected

Limitations

Presence of nucleic acid does not indicate presence of viable organisms; results should be used in conjunction with appropriate clinical symptoms for diagnostic purposes

Does not detect all possible pathogenic microsporidia spp

Entamoeba histolytica Antigen, EIA 0058001
Method: Qualitative Enzyme Immunoassay

Recommended Use

Test for persistent diarrhea (>14 days) or known risk factors if E. histolytica is the suspected infectious agent

Specific and sensitive test for detection of intestinal E. histolytica

Limitations

Rarely positive in extraintestinal disease

Will not detect parasites other than E. histolytica

Ova and Parasite Exam, Fecal (Immunocompromised or Travel History) 2002272
Method: Qualitative Concentration/Trichrome Stain/Microscopy

Recommended Use

Not recommended for most patients

If parasite infection is suspected as cause of persistent diarrhea (>14 days) and/or known risk factor for parasitic diarrhea, specific pathogen testing is recommended (refer to gastrointestinal parasite panel by PCR; Giardia antigen by EIA; Entamoeba histolytica antigen, EIA; or Cryptosporidium antigen by EIA)

Do not order for patients who develop diarrhea during a prolonged hospitalization

Requires at least 3 separate stool specimens collected on separate days

Detects G. duodenalis, E. histolytica, Dientamoeba fragilis, helminth eggs, protozoa, larval worms, and segments of tapeworms

Limitations

Ova may not be detectable in early disease

Does not specifically detect Cryptosporidium, Cyclospora, Cystoisospora, or microsporidia

Follow-up

In patients with negative O & P and persistent diarrhea, follow up negative stool antigen EIA result for Giardia duodenalis (synonym Giardia intestinalis, Giardia lamblia), Cryptosporidium spp, or Entamoeba histolytica

For Cryptosporidium, refer to the Cryptosporidium antigen by EIA test; for Cyclospora and Cystoisospora, refer to parasitology stain by modified acid-fast; for microsporidia, refer to microsporidia stain

Guidelines

Foodborne Diseases Active Surveillance Network (FoodNet). Centers for Disease Control and Prevention. Atlanta, GA [Last updated Aug 2015; Accessed: Nov 2015]

Guerrant RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, Tauxe RV, Hennessy T, Griffin PM, DuPont H, Sack RB, Tarr P, Neill M, Nachamkin I, Reller LB, Osterholm MT, Bennish ML, Pickering LK, Infectious Diseases Society of America. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001; 32(3): 331-51. PubMed

Manatsathit S, DuPont HL, Farthing M, Kositchaiwat C, Leelakusolvong S, Ramakrishna BS, Sabra A, Speelman P, Surangsrirat S, Working Party of the Program Committ of the Bangkok World Congress of Gastroenterology 2002. Guideline for the management of acute diarrhea in adults. J Gastroenterol Hepatol. 2002; 17 Suppl: S54-71. PubMed

General References

Barr W, Smith A. Acute diarrhea. Am Fam Physician. 2014; 89(3): 180-9. PubMed

Bernstein DI. Rotavirus overview. Pediatr Infect Dis J. 2009; 28(3 Suppl): S50-3. PubMed

Calderaro A, Gorrini C, Montecchini S, Peruzzi S, Piccolo G, Rossi S, Gargiulo F, Manca N, Dettori G, Chezzi C. Evaluation of a real-time polymerase chain reaction assay for the laboratory diagnosis of giardiasis. Diagn Microbiol Infect Dis. 2010; 66(3): 261-7. PubMed

DuPont HL. Clinical practice. Bacterial diarrhea. N Engl J Med. 2009; 361(16): 1560-9. PubMed

Glass RI, Parashar UD, Estes MK. Norovirus gastroenteritis. N Engl J Med. 2009; 361(18): 1776-85. PubMed

Graves NS. Acute gastroenteritis. Prim Care. 2013; 40(3): 727-41. PubMed

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References from the ARUP Institute for Clinical and Experimental Pathology

Couturier BA, Hale DC, Couturier MR. Association of Campylobacter upsaliensis with persistent bloody diarrhea. J Clin Microbiol. 2012; 50(11): 3792-4. PubMed

Couturier BA, Jensen R, Arias N, Heffron M, Gubler E, Case K, Gowans J, Couturier MR. Clinical and Analytical Evaluation of a Single-Vial Stool Collection Device with Formalin-Free Fixative for Improved Processing and Comprehensive Detection of Gastrointestinal Parasites J Clin Microbiol. 2015; 53(8): 2539-48. PubMed

Hymas W, Atkinson A, Stevenson J, Hillyard D. Use of modified oligonucleotides to compensate for sequence polymorphisms in the real-time detection of norovirus. J Virol Methods. 2007; 142(1-2): 10-4. PubMed

Khot PD, Fisher MA. Novel approach for differentiating Shigella species and Escherichia coli by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol. 2013; 51(11): 3711-6. PubMed

Rawlins ML, Gerstner C, Hill HR, Litwin CM. Evaluation of a western blot method for the detection of Yersinia antibodies: evidence of serological cross-reactivity between Yersinia outer membrane proteins and Borrelia burgdorferi. Clin Diagn Lab Immunol. 2005; 12(11): 1269-74. PubMed

Shakespeare WA, Davie D, Tonnerre C, Rubin MA, Strong M, Petti CA. Nalidixic acid-resistant Salmonella enterica serotype Typhi presenting as a primary psoas abscess: case report and review of the literature. J Clin Microbiol. 2005; 43(2): 996-8. PubMed

Medical Reviewers

Couturier, Marc Roger, PhD, D(ABMM), Medical Director, Microbial Immunology, Parasitology and Fecal Testing, and Infectious Disease Rapid Testing at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Fisher, Mark A., PhD, D(ABMM), Medical Director, Bacteriology and Antimicrobials at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Hillyard, David R., MD, Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Professor of Clinical Pathology, Adjunct Professor of Biology, University of Utah

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