Diarrhea, Parasitic Evaluation

Diagnosis

Indications for Testing

  • Diarrheal disease for >3-7 days and/or appropriate risk factors (eg, immunocompromised, foreign travel, drinking unpurified water)

Laboratory Testing

  • Guide to confirming diagnosis in foodborne disease (CDC)
  • Initial diagnostic approach – antigen testing to exclude most common parasites (Giardia duodenalis, Cryptosporidium spp, E. histolytica); test for persistent diarrhea (≥7 days) or known risk factors
    • Giardia duodenalis (synonyms Giardia lamblia, Giardia intestinalis)
      • Giardia stool antigen by EIA (preferred, most sensitive)
      • Repeat testing is recommended if initial test is negative and clinical suspicion is high
    • Cryptosporidium
      • Cryptosporidium spp stool antigen (EIA or DFA) preferred
      • Microscopic detection in stool requires special stains (eg, modified acid fast and multiple stool specimens); less sensitive than stool EIA
    • Entamoeba histolytica
      • Intestinal disease – Entamoeba stool antigen (EIA) is sensitive and specific
      • Extraintestinal disease (eg, liver abscess) – serologic testing preferred (Entamoeba histolytica antibody, IgG)
        • Stool antigen or ova and parasite exam are generally negative
    • Isospora belli
      • Microscopic examination of stool including special stain (eg, modified acid fast)
        • Oocytes appear red
    • Microsporidia
      • DFA stain – more sensitive and specific 
      • Ova and parasite examination with request for microsporidial stain – may require testing of multiple specimens
    • Strongyloides stercoralis
      • Serology is most sensitive; mild to moderate eosinophilia on CBC may be the only clue to parasitic infection if stools are negative
      • Ova and parasite examination with request for special stains
        • Ova and parasite exam may miss organisms in light infections; multiple specimens may be required
  • If diarrhea persists >3 days, and if patient has defined risk factors or a negative antigen testing, consider serology testing and ova and parasite examination with special stains to detect less-common pathogens
    • Comprehensive stool ova and parasite examination of 3 specimens collected on separate days is recommended (including request for special stains) for the following
      • Patients with history of travel or residence in endemic area
      • Exposure history
      • Immunocompromised state
      • High pretest probability for parasitic infection
  • Consider referral to a gastroenterologist for complete evaluation if infectious workup is negative and diarrhea persists

Differential Diagnosis

Clinical Background

Etiology of diarrhea may be infectious or noninfectious presenting with acute (<7 days) or chronic (>7 days) symptoms. 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

Epidemiology

  • Occurrence of parasite-associated disease
    • 5-15% in young children attending daycare
    • 1-2% in adults

Organism

  • Giardia duodenalis (synonyms Giardia lamblia, Giardia intestinalis)

    Epidemiology

    • Incidence – 150-700/100,000 in adults
      • Increased frequency in children, homosexual males and institutional-care facilities
      • Most common cause of parasite-associated diarrhea in the U.S.
    • Transmission –  waterborne, foodborne, or person-to-person  

    Organism

    • Protozoal parasite that inhabits the small intestine

    Clinical Presentation

    • Most infections are asymptomatic
    • Symptoms may last from weeks to months
      • Acute or chronic nonbloody diarrhea, nausea, abdominal discomfort, malabsorptive symptoms (eg, flatulence, greasy malodorous stools)
    • Intermittent or recurrent symptoms are common

    Treatment

    • May resolve/clear spontaneously in some cases; however, treatment recommended for both symptomatic and asymptomatic disease to reduce transmission

    Prevention

    • Cooking food adequately
    • Boiling or filtering potentially contaminated water
  • Cryptosporidium spp

    Epidemiology

    • Incidence – 20-100/100,000
      • Increased frequency in HIV infection, households of infected patients, daycare centers, and foreign travel
    • Transmission – waterborne, sporadic or outbreak-associated

    Organism

    • Protozoan parasite frequently associated with waterborne outbreaks
    • >12 species (genotypes) – C. parvum and C. hominis most common

    Clinical Presentation

    • Immunocompetent individuals
      • Usually asymptomatic or mild, self-limiting gastroenteritis
      • Nonbloody diarrhea, nausea, vomiting, abdominal pain, low-grade fever and malaise lasting from a few days to occasionally >30 days
    • Immunocompromised individuals
      • Chronic diarrhea (often more severe than expected for pathogen), dehydration, weight loss

    Treatment

    • Immunocompetent – generally no treatment necessary
    • Immunocompromised and those with severe disease – supportive, no single effective therapy; nitazoxanide may be considered
  • Entamoeba histolytica

    Epidemiology

    • Prevalence
      • Estimated 4% of population in industrialized nations infected with E. histolytica
        • Increased frequency in homosexual men, immigrants, institutional-care settings, foreign travel, HIV  patients
    • Sex – M>F for liver abscess disease
    • Transmission – waterborne, foodborne, or person-to-person

    Organism

    • Enteric protozoa – only E. histolytica considered pathogenic out of Entamoeba spp

    Clinical Presentation

    • Most individuals are asymptomatically colonized (~90%)
    • Disease may be intestinal or extraintestinal
      • Intestinal disease
        • May be asymptomatic or symptomatic, fulminant or chronic, with abdominal pain, tenderness, tenesmus, and bloody diarrhea
      • Extraintestinal disease
        • May include liver, brain, and lung abscesses

    Treatment

    • Generally recommended for both symptomatic and asymptomatic individuals to prevent transmission

    Prevention

    • Treating infected individuals
    • Boiling or filtering potentially contaminated water
  • Isospora belli

    Epidemiology

    • Incidence – unknown
      • Increased frequency in HIV  patients, institutional-care settings, daycare centers
    • Transmission – waterborne

    Organism

    • Coccidian parasite related to Cryptosporidium spp
    • Humans are the only known host and reservoir

    Clinical Presentation

    • Immunocompetent individuals
      • Acute, self-limiting watery or malodorous diarrhea (similar to Giardia or Cryptosporidium infection)
    • Immunocompromised individuals
      • Chronic diarrhea (occasionally severe), dehydration, weight loss

    Treatment

    • May be indicated in immunocompromised hosts
  • Microsporidia

    Epidemiology

    • Incidence – unknown
      • Increased frequency in HIV patients presenting with chronic diarrhea
    • Transmission – waterborne

    Organism

    • Obligate intracellular parasites – predominately affects immunocompromised hosts 
      • Includes Enterocytozoon bieneusi, Encephalitozoon intestinalis, Pleistophora, Septata, Vittaforma spp 

    Clinical Presentation

    • Immunocompetent individuals – rare cause of acute, self-limiting diarrhea
    • Immunocompromised individuals – chronic diarrhea, dehydration, anorexia, weight loss

    Treatment

    • May be indicated in immunocompromised patients
  • Strongyloides stercoralis

    Epidemiology

    • Incidence – unknown in U.S.
      • Increased frequency in endemic areas, institutional-care settings, daycare centers, homosexual males  
    • Transmission – infectious filariform larvae in soil or environment enters body by penetrating the skin

    Clinical Presentation

    • Cutaneous
      • Serpiginous urticarial rash due to larval migrations, also known as larva currens
      • Cutaneous larva migrans may also be observed with infections by other nematodes such as Ancylostoma spp, Uncinaria stenocephala, and Bunostomum phlebotomum 
    • Pulmonary
      • Symptoms are associated with primary larval migration
        • Increased in hyperinfection with larvae in pulmonary secretions
    • Intestinal
      • Generally asymptomatic, chronic infection
        • Occasionally intermittent diarrhea, abdominal pain
        • Rare – obstruction, ulcers, enterocolitis, malabsorption , hemorrhage, right upper-quadrant pain, sepsis
    • Hyperinfection
      • Frequent in immunocompromised patients
      • Host immunity no longer prevents larval reentry via intestinal wall
      • Disseminated infection with large numbers of larvae found in every tissue of the body
      • Life threatening

    Treatment

    • Indicated in all cases

Risk Factors

  • Testing for parasites should be considered in the following
    • Immunocompromised individuals
    • History of travel or residence in endemic area
    • History suggesting other etiologies such as coccidia (eg, Cyclospora spp, Isospora belli), microsporidia, or other less-common parasites

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
Giardia Antigen by EIA 0060048
Method: Qualitative Enzyme Immunoassay

Test for persistent diarrhea (≥7 days) or known risk factors

Rapid (24-hour) turnaround

Most sensitive method for detection of Giardia

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

Test for persistent diarrhea (≥7 days) or known risk factors

Rapid (24-hour) turnaround

Most sensitive test for detection of Cryptosporidium spp

Will not detect parasites other than Cryptosporidium spp  
Entamoeba histolytica Antigen, EIA 0058001
Method: Qualitative Enzyme Immunoassay

Test for persistent diarrhea (≥7 days) and known risk factors

Specific and sensitive test for detection of intestinal E. histolytica

Rarely positive in extraintestinal disease

Will not detect parasites other than E. histolytica

 
Entamoeba histolytica (amebiasis), Antibody, IgG 0050070
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Confirm past infection

Diagnose invasive extraintestinal disease

Preferred test for extraintestinal disease (eg, liver abscess)

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

Test for persistent diarrhea (≥7 days) or known risk factors

Detect Cryptosporidium, Cyclospora and Cystoisospora

Not intended for detection of other stool parasites

Less sensitive than EIA for Cryptosporidium spp

 
Microsporidia Stain by Modified Trichrome 0060050
Method: Qualitative Stain

Test for persistent diarrhea (≥7 days) or known risk factors

Detect microsporidia

Not intended for detection of other stool parasites

 
Strongyloides Antibody, IgG by ELISA, Serum 0099564
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Confirm clinical suspicion of Strongyloides infection

Most sensitive test in chronic infections

Antibody cross-reactions in patients with filariasis may occur

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Use to detect eosinophilia

   
Giardia lamblia Antibodies Panel by ELISA 2009410
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

May be used to detect Giardia

Insensitive relative to stool EIA

Includes IgG, IgA, and IgM

   
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