Diarrhea

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
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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

Differential Diagnosis

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

Risk Factors

  • Immunocompromised status
    • HIV,  primary immunodeficiency
      • Most common organisms include viruses, C. difficile, Campylobacter jejuniSalmonella 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 heartliver, 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)

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 Detection by RT-PCR 0051281
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

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

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

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

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

Limitations

Turnaround time 24->96 hours

Sensitivity highly variable

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

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

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

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

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

Giardia Antigen by EIA 0060048
Method: Qualitative Enzyme Immunoassay

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

Limitations

Will not detect parasites other than Cryptosporidium spp

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

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

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

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

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

Limitations

Ova may not be detectable in early disease

Does not specifically detect Cryptosporidium, CyclosporaCystoisospora, 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

Related Tests

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

Grimwood K, Forbes DA. Acute and persistent diarrhea. Pediatr Clin North Am. 2009; 56(6): 1343-61. PubMed

Hill DR, Ryan ET. Management of travellers' diarrhoea. BMJ. 2008; 337: a1746. PubMed

Hunt JM. Shiga toxin-producing Escherichia coli (STEC). Clin Lab Med. 2010; 30(1): 21-45. PubMed

Khan MA, Bass DM. Viral infections: new and emerging. Curr Opin Gastroenterol. 2010; 26(1): 26-30. PubMed

Mathis A, Weber R, Deplazes P. Zoonotic potential of the microsporidia. Clin Microbiol Rev. 2005; 18(3): 423-45. PubMed

Mead PS, Slutsker L, Dietz V, McCaig LF, Bresee JS, Shapiro C, Griffin PM, Tauxe RV. Food-related illness and death in the United States. Emerg Infect Dis. 1999; 5(5): 607-25. PubMed

Patel MM, Hall AJ, Vinjé J, Parashar UD. Noroviruses: a comprehensive review. J Clin Virol. 2009; 44(1): 1-8. PubMed

Pawlowski SW, Warren CAlcantara, Guerrant R. Diagnosis and treatment of acute or persistent diarrhea. Gastroenterology. 2009; 136(6): 1874-86. PubMed

Pierce KK, Kirkpatrick BD. Update on human infections caused by intestinal protozoa. Curr Opin Gastroenterol. 2009; 25(1): 12-7. PubMed

Recommendations for Diagnosis of Shiga Toxin–Producing Escherichia coli Infections by Clinical Laboratories. October 16, 2009, Vol. 58, No. RR-12. Centers for Disease Control and Prevention. Atlanta, GA [Accessed: Nov 2015]

Steffen R, Hill DR, DuPont HL. Traveler's diarrhea: a clinical review. JAMA. 2015; 313(1): 71-80. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology

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

Last Update: April 2016