Diarrhea, characterized by loose, watery stools, is extremely common worldwide. This condition is usually acute (lasting ≤14 days) and self-limiting, particularly in resource-rich settings. However, symptoms of diarrhea can be serious, particularly in resource-poor settings, immunocompromised populations, or pediatric populations. In addition to acute illness, diarrhea may present persistently (lasting >14 days) or chronically (lasting >30 days).
Diarrhea may have an infectious or noninfectious etiology. This topic will focus on viral, bacterial, and parasitic causes of infectious diarrhea. The most common cause of infectious diarrhea is viral infection. Bacterial diarrhea represents only 1-5% of diarrhea cases and is often associated with clustering of cases or outbreaks. Parasites are an infrequent or rare cause of acute diarrhea and tend to be sporadic in nature; parasite-caused acute diarrhea generally occurs either in isolated cases or large temporal outbreaks (eg, Cyclospora, Cryptosporidium). Exceptions include at-risk populations such as returned travelers and immunocompromised individuals. Laboratory testing using methods such as nucleic acid amplification (NAA), direct antigen detection, and culture is used to identify the causative agent of infectious diarrhea and inform proper medical management.
In healthcare settings and in specific populations (ie, newborns/infants and elderly or immunocompromised patients), these infections can lead to significant morbidity. Rapid diagnosis is important for appropriate treatment and infection control measures.
Quick Answers for Clinicians
The gold standard for diagnosis of parasitic diarrhea involves manual staining and microscopic review of stool samples. Ova and parasite examination is a common laboratory test in patients with diarrhea, although parasitic diarrhea is relatively rare and manual ova and parasite examination is a time- and resource-consuming process with variable sensitivity. Due to the various shedding cycles of many parasites, collection of several stool samples during a 5- to 7-day period is recommended to maximize diagnostic accuracy. Ova and parasite examination has low diagnostic yield in acute diarrhea.
An artificial intelligence (AI)-based method for ova and parasite examination with increased sensitivity and throughput was recently developed. This methodology increases the efficiency and sensitivity of the process, but the overall method has an approximate sensitivity of only 70% on a single stool specimen.
A broader differential diagnosis is recommended for immunocompromised patients compared with immunocompetent patients. This is particularly important for patients with moderate and severe primary or secondary immunodeficiencies. Patients with AIDS who present with persistent diarrhea should undergo additional testing, including testing for Cryptosporidium, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium complex, and cytomegalovirus.
Laboratory testing for Clostridioides difficile (formerly known as Clostridium difficile) is described fully in the ARUP Consult Clostridioides difficile topic. Briefly, the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) recommend C. difficile infection (CDI) testing for patients with CDI risk factors and unexplained and new-onset diarrhea, with three or more loose (unformed) stools within 24 hours. In children older than 2 years, persistent and worsening diarrhea along with CDI risk factors is an indication for CDI testing. However, the IDSA and SHEA recommend testing in toddler-age children only after other infectious/noninfectious causes have been ruled out, and CDI testing is not routinely recommended in neonates or infants.
People with fever or bloody diarrhea should be evaluated for enteropathogens for which antimicrobial agents may have clinical benefit, including Salmonella enterica subspecies, Shigella, Yersinia, and Campylobacter.
Enteric fever should be considered when a febrile person (with or without diarrhea) has a history of travel to areas in which causative agents are endemic, has consumed foods prepared by people with recent endemic exposure, or has had laboratory exposure to the Salmonella enterica subspecies enterica serovar Typhi or S. enterica subspecies enterica serovar Paratyphi.
Noninfectious diarrhea has many potential causes and is often chronic, persistent, or alternating with constipation. Gastrointestinal disorders that may cause diarrhea include inflammatory bowel disease, irritable bowel syndrome, Crohn's disease, celiac disease, malabsorption disorders, pancreatic insufficiency, and diverticulitis. Immunodeficiency syndromes (eg, HIV), cystic fibrosis, lactose intolerance, colorectal cancer, chemotherapy, antibiotic treatment, and laxative abuse are other potential causes of noninfectious diarrhea. If noninfectious diarrhea is suspected, clinical judgment should be exercised to determine an appropriate laboratory testing strategy to identify the underlying etiology.
Indications for Testing
Appropriate laboratory testing for diarrhea is determined by careful clinical evaluation of patient history and symptoms. Important information includes the severity and duration of symptoms, presence or absence of blood in stool, possible exposure to an infectious agent, recent travel, presence of systemic illness, and level of immunocompetence.
Laboratory testing for infectious diarrhea is informed by clinical evaluation. The tables below detail testing options for acute, persistent, and chronic diarrhea based on the suspected infectious agent. For more information on determining possible etiologic agents of infectious diarrhea, please refer to the 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. For all laboratory testing, positive results must be correlated with clinical symptoms for diagnosis. Detailed testing recommendations can be found in the Infectious Diarrhea Testing Algorithm.
In most cases of acute diarrhea (persisting ≤14 days), no testing is necessary at initial presentation because most etiologies are viral and do not require treatment. In settings where a viral outbreak is suspected, laboratory testing in patients with acute diarrhea may be considered for epidemiologic purposes.
Laboratory testing may be indicated for patients presenting with a fever greater than 101.3°F, bloody stools, or dysentery, and who are immunocompromised, hospitalized, or returned travelers.
|Recent travel, fever, bloody or mucoid stools, or signs of sepsis||
Gastrointestinal pathogens PCR panel
Order specific culture for Yersinia and Vibrio if indicated
|Clinical suspicion for Clostridioides difficile||Refer to ARUP Consult Clostridioides difficile topic|
|Recent travel/applicable travel history, immunocompromise, or possible exposure to community outbreak||
Parasite PCR panel
Parasite-specific testing (eg, antigen detection EIA) as indicated by symptoms or patient history
Persistent or Chronic Diarrhea
Infectious causes of persistent (lasting >14 days) and chronic (lasting >30 days) diarrhea often include parasites or bacteria.
|Indications for Testing||Testing Options|
|Comprehensive testing is appropriate for patients with chronic diarrhea or persistent diarrhea, recent travel, immigration, solid or hematopoietic transplant, and unknown etiology||
Gastrointestinal pathogens PCR panel
If patient history suggests a specific organism, specific testing may be appropriate instead of panel testing
|Individual/Specific Organism Testing|
|Parasite PCR panel|
|Giardia duodenalis (also referred to as Giardia lamblia, Giardia intestinalis)||
Giardia antigen by EIA
If first specimen is negative and suspicion still exists, consider repeating EIA
|Cryptosporidium hominis, C. parvum||
Cryptosporidium spp antigen (EIA or DFA)
Entamoeba antigen (EIA) is preferred if not using PCR panel
|Cystoisospora belli, Cyclospora cayetanensis||Microscopic examination of stool using special techniques (eg, modified acid-fast method and UV autofluorescence), if not using PCR|
|Dientamoeba fragilis||Ova and parasite exam is preferred if not using PCR panel|
Microsporidia-specific PCR (May not detect all possible pathogenic microsporidia species but detects common gastrointestinal pathogenic genera/species)
Microscopic examination of stool using microsporidial stain (eg, modified trichrome), if not using PCR (May require testing of multiple specimens)
DFA, direct fluorescent antibody; UV, ultraviolet
ARUP Laboratory Tests
Use to identify nucleic acids from multiple bacteria, viruses, and parasites directly from stool samples in Cary-Blair transport media obtained from individuals with signs and/or symptoms of gastrointestinal infection
This panel is not appropriate if C. difficile is suspected; instead, consider targeted C. difficile testing
Qualitative Polymerase Chain Reaction
Use to detect and differentiate norovirus groups 1 and 2
Qualitative Reverse Transcription Polymerase Chain Reaction
Recommended rapid, standalone diagnostic test for C. difficile-associated diarrhea
Qualitative Polymerase Chain Reaction
Use as a sensitive alternative to traditional, insensitive ova and parasite examinations of stool specimens
Do not order for patients who develop diarrhea during prolonged hospitalization
Use to detect C. hominis and parvum, C. cayetanensis, D. fragilis, E. histolytica, and G. duodenalis
Preferred test to diagnose microsporidia in immunocompromised patients with persistent diarrhea if Encephalitozoon spp or Enterocytozoon bieneusi is the suspected infectious agent
Use to diagnose rotavirus-associated gastroenteritis
Preferred test for suspected bacterial diarrhea evaluation
Testing includes cultures for Salmonella, Shigella, Campylobacter, E. coli O157, and EIA for Shiga-like toxin from E. coli
Use to detect the Shiga toxins, sensitive markers of toxigenic E. coli
Qualitative Enzyme-Linked Immunosorbent Assay (ELISA)
Use to identify presence of Campylobacter species in stool as potential cause of diarrhea in patients with appropriate exposure history or risk factors
Use to diagnose Yersinia-associated diarrhea in patients with appropriate exposure history or risk factors
Use to diagnose Vibrio-associated diarrhea in patients with appropriate exposure history or risk factors
Test for persistent diarrhea (lasting >14 days) or known risk factors if G. duodenalis is the suspected infectious agent
Test for persistent diarrhea (lasting >14 days) or known risk factors if Cryptosporidium spp is the suspected infectious agent
Test for persistent diarrhea (lasting >14 days) or known risk factors if E. histolytica is the suspected infectious agent
Can be used for follow-up of negative PCR result when suspicion of microsporidia infection remains high
Test for persistent diarrhea (lasting >14 days) or known risk factors if Cryptosporidium, Cyclospora, or Cystoisospora is the suspected infectious agent
If parasite infection is suspected as cause of persistent diarrhea (lasting >14 days), specific pathogen testing is recommended
Do not order for patients who develop diarrhea during a prolonged hospitalization
Qualitative Concentration/Trichrome Stain/Microscopy
Riddle MS, DuPont HL, Connor BA. ACG clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016;111(5):602-622.
Mathison BA, Kohan JL, Walker JF, et al. Detection of intestinal protozoa in trichrome-stained stool specimens by use of a deep convolutional neural network. J Clin Microbiol. 2020;58(6):e02053-19.
Miller JM, Binnicker MJ, Campbell S, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis. 2018;67(6):e1-e94.
Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017;65(12):e45-e80.
McDonald C, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48.
Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report. J Travel Med. 2017;24(suppl_1):S57-S74.
Barr W, Smith A. Acute diarrhea. Am Fam Physician. 2014;89(3):180-189.
Steffen R, Hill DR, DuPont HL. Traveler's diarrhea: a clinical review. JAMA. 2015;313(1):71-80.
CDC - Manual for the Surveillance of Vaccine-Preventable Diseases - Chapters
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Manual for the surveillance of vaccine-preventable diseases. [Updated: Jun 2020; Accessed: Mar 2021]