Infectious Diarrhea

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

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 in adults is diarrheal stool (not formed stool). For pediatric patients, patients with ileus,  or patients for whom timely diarrheal stool samples cannot be obtained, a rectal swab may also be effective.  

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, 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.

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, 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.

Which testing algorithms are related to this topic?

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. In cases of suspected outbreak, a broader testing strategy may be required. 

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.

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

Bacterial PCR panel

Stool culture (specific culture condition/media is required for Yersinia and Vibrio spp)

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

(Do not use ova and parasite exams for most patients in acute setting)

EIA, enzyme immunoassay; PCR, polymerase chain reaction

Miller, 2018 ; Shane, 2017 

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
Chronic diarrhea or persistent diarrhea, recent travel, immigration, solid or hematopoietic transplant

Parasite 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
Giardia duodenalis (also referred to as Giardia lamblia, Giardia intestinalis)

Giardia antigen by EIA is preferred if not using PCR panel

If first specimen is negative and suspicion still exists, consider repeating EIA

Cryptosporidium hominis, C. parvum

Cryptosporidium spp antigen (EIA or DFA) is preferred if not using PCR panel

Microscopic detection in stool

  • Requires special stains (eg, modified acid-fast method and multiple stool specimens)
  • Is less sensitive than stool EIA
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 spp 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 

ARUP Laboratory Tests

Polymerase Chain Reaction

Viral Tests

Aids in the diagnosis of gastrointestinal infections caused by viral pathogens

Use as a sensitive alternative to traditional antigen testing

Use to detect astrovirus, sapovirus, rotavirus, or adenovirus type 40/41, and to differentiate norovirus group 1 and group 2

Use to detect and differentiate norovirus groups 1 and 2

Bacterial Tests

Use as a sensitive alternative to traditional stool culture to detect the most common gastrointestinal bacterial pathogens

Use to detect Salmonella, Shigella/enteroinvasive Escherichia coli, Campylobacter jejuni/coli, shiga-toxigenic E. coli, and Campylobacter upsaliensis (cannot be easily cultured)

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

Parasitic Tests

Most comprehensive and 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, G. duodenalis, and microsporidia

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

Culture and Enzyme Immunoassay

Viral Test

Use to diagnose rotavirus-associated gastroenteritis

Bacterial Tests

Use to detect presence of bacteria in blood

May help to differentiate bacterial from nonbacterial infection

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

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

Parasitic Tests

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

Staining

Parasitic Tests

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

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Pathology (Clinical), University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories

References

Additional Resources