Infectious Diarrhea

Medical Experts

Contributor

Couturier

Marc R. Couturier, PhD

Former Head of Clinical Operations for Clinical Microbiology and Immunology; Medical Director, Emerging Public Health Crises, Parasitology/Fecal Testing, and Infectious Disease Antigen Testing, 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 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 can help 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

What is the role of ova and parasite examination in the diagnosis of infectious diarrhea?

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.

Which is the optimal sample type for the laboratory investigation of infectious diarrhea?

The preferred specimen for the laboratory diagnosis of infectious diarrhea is diarrheal stool (not formed stool).^,

How does a diarrhea diagnosis differ between immunocompetent and immunocompromised patients?

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.

When should testing for Clostridioides difficile be considered?

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.

In people with fever or bloody diarrhea, which clinical, demographic, or epidemiologic features have diagnostic or management implications?

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. Because antibiotics and antidiarrheals can worsen illness and increase the risk of hemolytic uremic syndrome in patients with Shiga toxin-producing Escherichia coli (STEC),^, all stools tested for Salmonella, Shigella, or Campylobacter should also be tested for STEC.

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.

When should laboratory testing for vibriosis be considered, and how is this testing performed?

Vibriosis, an infection caused by certain Vibrio species, including Vibrio vulnificus, can be severe, life threatening, and may require intensive care or limb amputation. Vibrio bacteria are found in salty and brackish water; exposure to coastal waters and floodwaters or open wound exposure to contaminated waters following natural disasters (eg, hurricanes) may lead to gastroenteritis, septicemia, and wound infections attributable to V. vulnificus.^, Laboratory testing for Vibrio species may be performed on stool, wound exudates, or blood specimens, and Vibrio may be detected by culture-independent diagnostic testing (CIDT), followed by confirmation with culture.^, However, if Vibrio wound infection is suspected, treatment should proceed without waiting for laboratory confirmation, as this infection may progress to necrotizing fasciitis (sometimes referred to as flesh-eating disease).^,^,

What are some noninfectious causes of diarrhea?

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

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.

Acute Diarrhea

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.^,

Acute Diarrhea (Lasting ≤14 Days)
Bacterial Testing
Indications	Testing Options
Recent travel, fever, bloody or mucoid stools, or signs of sepsis	Gastrointestinal pathogens PCR panel Stool culture Escherichia coli Shiga-like toxin testing (EIA or PCR), performed on culture If indicated, specific culture for Yersinia and Vibrio
Clinical suspicion for Clostridioides difficile	Refer to ARUP Consult Clostridioides difficile topic
Parasitic Testing
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
EIA, enzyme immunoassay; PCR, polymerase chain reaction Miller, 2018; Shane, 2017; Gould, 2009

Persistent or Chronic Diarrhea

Infectious causes of persistent (lasting >14 days) and chronic (lasting >30 days) diarrhea often include parasites or bacteria.

Persistent (Lasting >14 Days) or Chronic Diarrhea (Lasting >30 Days)
Comprehensive Testing
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
Organism	Testing Options
Cryptosporidium hominis Cryptosporidium parvum Cyclospora Cayetanensis Dientamoeba fragilis Entamoeba histolytica Giardia duodenalis	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 histolytica	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	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 Miller, 2018; Shane, 2017