Diarrhea, Viral Evaluation

Diagnosis

Indications for Testing

  • Diarrhea ≥3 days; prolonged diarrhea with history of travel
    • Most cases of norovirus and rotavirus are diagnosed clinically

Laboratory Testing

  • Guide to confirming diagnosis in foodborne disease (CDC)
  • CBC – may help eliminate bacteria as etiology if leukocytosis is not present
  • Stool culture – preferred test to rule out suspected diarrhea (most useful if diarrhea lasts ≥3 days or is bloody)
  • Norovirus 
    • Reverse transcription polymerase chain reaction (RT-PCR) detection for genogroups I and II – most sensitive/specific test for norovirus
    • EIA (antigen detection) – not as sensitive as PCR
    • Electron microscopy – insensitive and lab specific
  • Rotavirus
    • EIA
    • Latex agglutination
  • Ova and parasite exam
    • Does not aid in diagnosis of viral diarrhea
    • Consider ova and parasite exam and Giardia EIA and/or Clostridium difficile testing if patient has defined risk factors

Differential Diagnosis

Clinical Background

Etiology of diarrhea may be infectious or noninfectious presenting with acute (<7 days) or chronic (>7 days) symptoms. Viral agents are the most common cause of diarrheal illness. Norovirus (Norwalk-like virus) and rotavirus are the two predominant viral agents. Parasites are an infrequent or rare cause of acute diarrhea but a more common cause of chronic diarrhea.

  • Acute diarrhea (acute gastroenteritis) – duration 1-7 days
    • Frequently infectious
    • May be foodborne, waterborne, or outbreak associated
    • Most commonly caused by viruses and occasionally bacteria
    • Testing for gastrointestinal parasites generally not recommended for acute diarrheal episodes
  • Chronic diarrhea – duration >7 days, often longer
    • More commonly noninfectious
    • Testing for parasites should be considered
  • Predominant viral agents
    • Norovirus

      Epidemiology

      • Leading cause of nonbacterial gastroenteritis worldwide
      • In the U.S., norovirus causes millions of infections annually, with outbreaks commonly occurring in all age groups and in varied environments such as the following
      • Transmission occurs mainly through the fecal-oral route by ingestion of contaminated food (eg, shellfish) or water, but can be airborne (in vomitus)
        • Norovirus has a characteristically low infectious dose and can survive relatively high levels of disinfectants and varying temperatures, all of which facilitate its transmission

      Organism

      • Norovirus, formerly known as Norwalk-like virus, is a member of the Caliciviridae family
      • Single-stranded RNA virus
      • Genogroups I and II account for ~99% of norovirus infections in humans

      Clinical Presentation

      • Usually mild or self-limiting disease with high transmission rates – often ≥30% among contacts of infected patients
      • Most common symptoms – acute onset diarrhea and vomiting with abdominal cramps, nausea, fever, headache
      • Symptoms occur within 24-48 hours of infection, may continue for 12-60 hours
      • Transplant patients often have chronic diarrhea
        • Symptoms in small bowel transplant patients resemble allograft rejection

      Treatment

      • Supportive care – infection is self-limited

      Prevention

      • Hygiene/handwashing, disinfection of contaminated surfaces
      • Infection control measures are important in limiting the spread in hospital settings
      Rotavirus

      Epidemiology

      • Most important cause of severe dehydrating diarrhea in children <5 years
        • Rotavirus type A is responsible for 25-60% of severe infantile diarrhea worldwide
      • Transmission via fecal-oral route
      • Universal infection – nearly all children have circulating antibodies by 2-3 years

      Organism

      • Double-stranded RNA virus
        • Seven antigenic groups
        • Group A most common

      Clinical Presentation

      • Varies from asymptomatic to severe dehydration and death
      • Mild fever and emesis for 2-3 days
      • Watery diarrhea for 3-5 days following fever
        • Bloody diarrhea is rare
      • Severe and prolonged disease may occur in patients with the following

      Treatment

      • Supportive care

      Prevention

      • Handwashing and vaccination

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Nonspecific

May help in differentiation of bacterial from nonbacterial infection

Presence of anemia (low hemoglobin/hematocrit) suggestive of inflammatory or malignant process and not bacterial diarrhea

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

Preferred test for suspected bacterial diarrhea evaluation (most useful if diarrhea lasts ≥3 days or is bloody)

Cultures include Salmonella, Shigella, Campylobacter, and E. coli 0157 as well as EIA for Shiga-like toxin from E. coli

   
Norovirus Group 1 and 2 Detection by RT-PCR 0051281
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Most sensitive and specific test for diagnosing norovirus-associated gastroenteritis

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

Diagnose rotavirus-associated gastroenteritis

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

Diagnose rotavirus- and adenovirus-associated gastroenteritis  

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

 
Ova & Parasite Exam, Fecal (Immunocompromised or Travel History) 2002272
Method: Qualitative Concentration/Trichrome Stain/Microscopy

If parasite infection is suspected as cause of persistent diarrhea (>5 to 7 days), specific pathogen testing is recommended (eg, Giardia antigen by EIA)

Do not order for patients who develop diarrhea during a prolonged hospitalization

Ova may not be detectable in early disease

Less sensitive than stool antigen tests for Giardia duodenalis, Cryptosporidium spp, or Entamoeba histolytica with persistent diarrhea

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

Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Rotavirus and Adenovirus 40-41 Antigens 0065067
Method: Qualitative Enzyme Immunoassay

Diagnose rotavirus- and adenovirus-associated gastroenteritis