Infectious Diarrhea

Medical Experts

Contributor

Barker

Assistant Professor of Pathology (Clinical), University of Utah

Chief Operations Officer, ARUP Laboratories

Medical Director, Next Generation Sequencing (NGS) Infectious Disease, R&D Special Operations, Reagent Laboratory, Technology Transfer, Transportation

Contributor

Mathison

Blaine Mathison, BS, M(ASCP)

Adjunct Instructor, Department of Pathology, University of Utah

Technical Director of Parasitology, Technical Operations Infectious Diseases, ARUP Laboratories

Contributor

Shakir

Salika M. Shakir, PhD, D(ABMM)

Assistant Professor of Pathology (Clinical), University of Utah

Medical Director, AFB, Molecular Automated Detection Laboratory, ARUP Laboratories

Contributor

Jackson

Brian R. Jackson, MD, MS

Adjunct Professor of Pathology and Biomedical Informatics, University of Utah

Medical Director, Business Development, ARUP Laboratories

Diarrhea, characterized by three or more loose, watery stools in a 24-hour period, is extremely common worldwide. This condition is usually acute and self-limited but can be persistent or chronic. Although acute diarrhea may have either an infectious or noninfectious etiology, most cases are infectious. Infectious cases are most commonly viral but can also be bacterial or parasitic. Testing is recommended for individuals who are experiencing or at high risk for severe illness, those with persistent or chronic diarrhea, or when pathogen identification is important for public health or patient care.^,^, Laboratory tests such as nucleic acid amplification tests (NAATs), immunoassays, stool culture, and ova and parasite examination can help identify the causative agent of infectious diarrhea and inform proper medical management or public health response.

Quick Answers for Clinicians

What is an ova and parasite examination, and when is it recommended for diagnosing infectious diarrhea?

An ova and parasite examination involves staining and microscopically reviewing stool specimens to detect parasites. Historically, this process was time and resource consuming and had variable sensitivity, but advances in artificial intelligence (AI)-based image analysis have improved sensitivity and throughput. If parasites are suspected, molecular tests (such as polymerase chain reaction [PCR]) or antigen tests are generally recommended first. If these tests are negative, a comprehensive ova and parasite examination should be performed. Due to the shedding cycles of many parasites, examining three or more stool specimens collected on separate days is recommended for diagnostic accuracy. Ova and parasite examination is especially useful in cases of persistent or chronic diarrhea with a suspected parasitic cause, e.g., in patients with a history of travel to areas where intestinal parasites are common, exposure to travelers from such areas, or immunocompromised status.

How does diagnostic testing for diarrhea differ between immunocompetent and immunocompromised patients?

The diagnostic workup for immunocompromised patients, especially those with moderate to severe primary or secondary immunodeficiencies, should encompass a broader differential diagnosis that includes viral, bacterial, and parasitic testing. Patients with AIDS should undergo testing for Cryptosporidium, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium complex, and cytomegalovirus, along with testing for common causative pathogens.^,

When should testing for Clostridioides difficile be considered?

Laboratory testing for Clostridioides difficile (formerly Clostridium difficile) is described fully in the ARUP Consult Clostridioides (Clostridium) difficile topic. For adolescents and adults, guidelines recommend testing for C. difficile infection (CDI) when patients present with unexplained, new-onset diarrhea, characterized by three or more loose (unformed) stools within 24 hours, while not receiving laxatives. For children 2 years or older, CDI testing is advised in the presence of persistent and worsening diarrhea and CDI risk factors (inflammatory bowel disease [IBD] or immunocompromised status), but only after other infectious and noninfectious causes have been ruled out. CDI testing is not routinely recommended for infants 12 months or younger. Recent long-term hospitalization, recent antibiotic use, chronic gastrointestinal conditions such as IBD, weakened immune system, chemotherapy, are risk factors for C. difficile infection.^,

What should be considered in the diagnostic workup of patients experiencing fever or bloody diarrhea?

Patients with fever or bloody diarrhea should undergo stool testing for Salmonella, Shigella, Campylobacter, Yersinia, Clostridioides difficile, and Shiga toxin-producing Escherichia coli (STEC).^, Bacterial identification of Salmonella, Shigella, or Campylobacter can guide treatment and prevent unnecessary antibiotics or procedures. Early detection of a STEC infection can inform management, as individuals infected with Shiga toxin are at increased risk for hemolytic uremic syndrome. Negative stool tests can point to noninfectious causes. Enteric (typhoid) fever should be considered when an individual presents with fever (with or without diarrhea) and has had direct contact with an infected person, consumed food prepared by an infected person, recently traveled to an endemic area, or worked in a laboratory with an increased risk of exposure to Salmonella enterica or Salmonella typhi.^,

Indications for Testing

A detailed clinical and exposure history is needed to determine if testing for infectious etiology is indicated.^, Factors that may indicate testing include:

Bloody or mucoid stool, fever greater than 101°F, severe abdominal cramping or tenderness, or signs of sepsis^,^,
Persistent or chronic diarrhea
Immunocompromised status^,^,
Recent hospitalization^,^,
A setting of suspected outbreak (for epidemiologic purposes)^,^,
Recent international travel or contact with recent travelers (if fever of unknown etiology is also present, treatment is required, or diarrhea lasts 14 days or longer)^,

Laboratory Testing

Testing for diarrheal causes involves several possible methods: culture-independent diagnostic tests (CIDTs) such as NAATs or enzyme immunoassays (EIAs), stool culture, and ova and parasite examination.

A broad range of viral, bacterial, and parasitic agents should be considered. The selection of specific pathogens should be guided by patient evaluation and epidemiologic risk factors, and in the context of a potential outbreak, in collaboration with public health authorities. When using a test to detect multiple pathogens (e.g., gastrointestinal pathogen polymerase chain reaction [PCR] panel, comprehensive ova and parasite examination, stool culture), ensure that any specific pathogens of interest are included or can be detected. If a CIDT is used for initial evaluation, a reflex culture may be necessary for cases requiring public health surveillance or for antimicrobial susceptibility testing.

The following table outlines recommended testing based on clinical indications and suspected infectious agents. Testing recommendations are also displayed visually in the Infectious Diarrhea Testing Algorithm. Refer to the 2017 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea for a table containing exposures and conditions associated with diarrhea-causing pathogens.

Indications and Recommended Testing for Infectious Diarrhea Etiology
Viral Testing^a
Indications	Recommended Testing
Immunocompromised status Infection control and outbreak investigations	Multiplexed NAAT (e.g., gastrointestinal pathogen PCR panel) containing common viruses such as norovirus, rotavirus, enteric adenovirus
Bacterial Testing^b
Indications	Recommended Testing
Fever Bloody or mucoid stools Severe abdominal cramping or tenderness Signs of sepsis	Multiplexed NAAT (e.g., gastrointestinal pathogen PCR panel) containing Salmonella, Shigella, Campylobacter, Yersinia, STEC,^cand/or stool culture Clostridioides difficile testing^d
Persistent abdominal pain (mimicking appendicitis) Fever Direct or indirect exposure to raw or undercooked pork	Multiplexed NAAT (e.g., gastrointestinal pathogen PCR panel) containing Yersinia enterocolitica and/or stool culture Yersinia spp require special culture conditions; notify the testing laboratory if culture is needed
Large-volume rice-water stools and/or travel to cholera-endemic regions within the 3 days preceding onset of diarrhea Exposure to coastal water Consumption of raw or undercooked shellfish (specifically oysters)	Multiplexed NAAT (e.g., gastrointestinal pathogen PCR panel) containing Vibrio spp CIDTs, like NAAT, may not differentiate noncholera Vibrio spp; therefore, a reflex culture may be necessary Vibrio spp require special culture conditions; notify the testing laboratory if culture is needed
Fever after travel to enteric fever-endemic areas or exposure to travelers or food prepared by travelers from an endemic area	Blood culture to detect presence of Salmonella spp such as Salmonella typhi or Salmonella paratyphi Multiple cultures may be needed; blood, bone marrow, and bile culture have highest clinical yield
Clinical suspicion for C. difficile: ≥2 yrs of age and a history of diarrhea following antimicrobial use Recent long-term stay in hospital or medical facility Persistent diarrhea without an etiology and without recognized risk factors Returning traveler with antimicrobial treatment within the preceding 8-12 wks Immunocompromised status, IBD, or recent gastrointestinal surgery	Stool toxin testing, GDH testing, and/or NAAT^d
Parasitic Testing
Indications	Recommended Testing
Possible exposure to infectious parasites from childcare settings, lakes, swimming pools, drinking water from shallow wells, or sexual practices involving anal contact Recent travel to areas where intestinal parasites are endemic or contact with travelers from those areas Diarrhea >14 days	Stool testing for intestinal parasites^e(NAAT, EIA, and/or ova and parasite examination) If specific parasites (e.g., Giardia and/or Cryptosporidium) are suspected, targeted testing is recommended over ova and parasite examination due to greater sensitivity
Immunocompromised status (e.g., diagnosis of AIDS or other primary or secondary immunodeficiencies)	Testing (e.g., stool culture, viral studies, ova and parasite examination) for a broad range of gastrointestinal pathogens including Cryptosporidium, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium complex, and CMV
^aViral diarrhea is typically acute and self-limited; therefore, testing is not usually clinically indicated. ^bCIDTs, when available, are recommended over culture for detection of bacterial pathogens due to higher sensitivity and faster turnaround time. ^cSTEC testing involves culture for Escherichia coli O157:H7 and Shiga toxin immunoassay or NAAT for Shiga toxin genes. ^dRefer to the ARUP Consult Clostridioides (Clostridium) difficile topic for more information. ^eThe most common parasites causing infectious diarrhea include Giardia duodenalis, Cryptosporidium spp, Cyclospora spp, Cystoisospora belli, Entamoeba histolytica, and possibly certain strains of Dientamoeba fragilis and Blastocystis spp. CMV, cytomegalovirus; DFA, direct fluorescent antibody; GDH, glutamate dehydrogenase; IBD, inflammatory bowel disease; STEC, Shiga toxin-producing Escherichia coli Sources: Shane, 2017; Rande,l 2018; Miller, 2024; CDC Clinical Overview of Vibriosis, 2024; AAP Red Book, 2024

Persistent or Chronic Diarrhea

Infectious causes of persistent and chronic diarrhea are often bacterial or parasitic. Pathogens associated with persistent or chronic diarrhea include Giardia duodenalis, Cryptosporidium, Cyclospora, Cystoisospora belli, and Entamoeba histolytica. In patients with chronic diarrhea, testing for Giardia infection via immunoassay or PCR is recommended. Testing for Clostridioides difficile can be considered in patients with persistent diarrhea in the absence of CDI risk factors or known cause.

Ova and parasite examination is unlikely to be clinically impactful in cases of persistent or chronic diarrhea unless informed by recent travel to regions with recognized diarrhea-related pathogens, in immunocompromised patients, or if there has been possible exposure to parasites.^, Consider other indications, patient history, and noninfectious causes to determine appropriate testing strategy.

Travelers’ Diarrhea

Diagnostic testing is generally not recommended for travelers’ diarrhea unless treatment is necessary.^, The leading cause of travelers’ diarrhea is enterotoxigenic E. coli (ETEC), which typically results in an acute, self-limiting illness. Approximately 10% of cases are due to parasitic infections, and giardiasis are the most common. If diarrhea persists for more than 14 days, testing for intestinal parasites is recommended. For travelers who have undergone antimicrobial therapy within the preceding 8-12 weeks, testing for C. difficile is also recommended.