Diarrhea

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics
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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 by 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

    Gastrointestinal Viral Panel by PCR 2013577
    Method: Qualitative Polymerase Chain Reaction

    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

    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 CA, 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 MR. Association of Campylobacter upsaliensis with persistent bloody diarrhea. J Clin Microbiol. 2012; 50(11): 3792-4. PubMed

    Couturier BA, Jensen R, Arias N, Heffron M, Gubler E, Case K, Gowans J, Couturier MR. Clinical and Analytical Evaluation of a Single-Vial Stool Collection Device with Formalin-Free Fixative for Improved Processing and Comprehensive Detection of Gastrointestinal Parasites J Clin Microbiol. 2015; 53(8): 2539-48. 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: August 2016