Diarrhea, Parasitic Evaluation

Diagnostic Algorithm

  Diarrhea, Acute Testing Algorithm

Clinical Background

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

• Acute diarrheal episodes (acute gastroenteritis)
  • Frequently infectious
  • May be food-borne, water-borne or outbreak associated
  • Most commonly caused by viruses; occasionally bacteria
  • Testing for gastrointestinal parasites generally not recommended for acute diarrheal episodes
    • Parasites are an infrequent or rare cause of acute diarrhea
      • 5-15% in preschool age children attending day care
      • 1-2% in adults
    • Giardia lamblia is the most common, followed by Cryptosporidium spp or Entamoeba histolytica
    • If diarrhea persists (eg, >7 days) consider targeted testing
      • First, G. lamblia stool antigen by enzyme immunoassay (EIA)
      • Cryptosporidium spp stool antigen (EIA)
      • E. histolytica stool antigen (EIA)
    • Exceptions to above statements
      • Immunocompromised patients or recently returned travelers
        • History that suggests other etiologies such as coccidia (eg, Cyclospora spp, Isospora belli), microsporidia or other less common parasites
          • Strongyloides stercoralis – may require special test procedures
          • Modified acid fast stain used for coccidia, serology and routine ova and parasite examination used for Strongyloides larvae
    • For patients with history of travel or residence in endemic area, immunocompromised patients or those with persistent symptoms and clinical concern for parasitic infection despite negative EIA, comprehensive stool ova and parasite examination with submission of ≥3 specimens over 10 days is recommended
• Chronic diarrhea (>7 days, often longer)
  • More commonly non-infectious
  • May be parasitic
    • Giardia lamblia is the most common, occasionally Cryptosporidium spp or Entamoeba histolytica
    • Targeted testing is preferred and most sensitive
      • First, G. lamblia stool antigen (EIA)
      • Cryptosporidium spp stool antigen (EIA)
      • E. histolytica stool antigen (EIA)
      • If diarrhea persists and above testing is negative, may consider repeating stool antigen (EIA) as above
        • Refer to gastroenterologist for complete evaluation of infectious and non-infectious causes
        • If immunosuppressed, recently returned traveler, or individual from endemic area
          • Ova and parasite examination with request for special stains
          • Strongyloides stercoralis serology

Giardia lamblia

Epidemiology

• Incidence
  • Annual incidence in adults estimated at 150-700 cases/100,000 population
  • Increased frequency in children, homosexual males and institutional care facilities
  • Most common cause of parasite-associated diarrhea in the U.S.
• Transmission –  water-borne, food-borne or person to person  

Organism

• Protozoal parasite that inhabits the small intestine

Clinical Presentation

• Most infections are asymptomatic
• Symptoms may include acute or chronic non-bloody diarrhea, nausea, abdominal discomfort, malabsorptive symptoms (eg, flatulence, greasy malodorous stools) lasting from weeks to months
• Intermittent or recurrent symptoms are common

Treatment

• May resolve/clear spontaneously in some cases
• Recommended in symptomatic and asymptomatic disease to reduce transmission

Prevention

• Cooking food adequately
• Boiling or filtering potentially contaminated water

Cryptosporidium

Epidemiology

• Incidence
  • Estimated 20-100 cases/100,000 population per year
  • Increased frequency in HIV infection, households of infected patients, child day-care centers, and travelers  
• Transmission – water-borne, sporadic or outbreak associated

Organism

• Protozoan parasite frequently associated with water-borne outbreaks

Clinical Presentation

• Immunocompetent individuals – usually asymptomatic or mild self-limited gastroenteritis; symptoms may include non-bloody diarrhea, nausea, vomiting, abdominal pain, low-grade fever and malaise lasting from days to occasionally more than a month
• Immunocompromised individuals – chronic more often severe diarrhea, dehydration, weight-loss

Treatment

• Generally not necessary in immunocompetent individuals
• Severe disease, immunocompromised host – supportive therapy, no single effective therapy; nitazoxanide may be considered

Entamoeba species

Epidemiology

• Prevalence
  • Estimated 4% prevalence of E. histolytica in industrialized nations
  • Increased frequency in homosexual men, immigrants, institutional care settings, travelers, HIV patients
• Transmission – water-borne, food-borne, or person-to-person

Organism

• Enteric protozoa among which only Entamoeba histolytica is considered pathogenic

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 symptomatic and asymptomatic individuals to prevent transmission

Prevention

• Boiling or filtering contaminated water

Isospora belli

Epidemiology

• Incidence
  • Unknown
  • Increased frequency in HIV, institutional care settings, day-care centers
• Transmission – water-borne

Organism

• Coccidian parasite related to Cryptosporidium spp

Clinical Presentation

• Immunocompetent individuals – acute self-limited 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 AIDS patients with chronic diarrhea
• Transmission – water-borne
• Occurrence –  immunocompromised persons (especially those with HIV infection)

Organism

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

Clinical Presentation

• Immunocompetent individuals – rare cause of acute self-limited 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, day-care centers, homosexual males  
• Transmission – infectious filariform larvae in soil or environment enters the 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; rarely, obstruction, ulcers, enterocolitis, malabsorption, hemorrhage, right upper-quadrant pain, sepsis
• Hyperinfection
  • Frequent in immunocompromised patients
  • Occurs when 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

Diagnosis

• Indications for testing
  • Diarrheal disease for more than 3 days or appropriate risk factors (eg, foreign travel, drinking unpurified water)
• Laboratory testing
  • Initial diagnostic approach – EIA to exclude most common parasites (Giardia lamblia, Cryptosporidium sp, and E. histolytica)
  • For patients with defined risk factors (eg, immunosuppression, travel history, or persistent symptoms in the absence of an alternative diagnosis), microscopic ova and parasite examination and serology (+ or – modified acid fast stain or microsporidia stain or stool) should be performed to detect less commonly encountered pathogens, for persistent symptoms or for negative tests
  • Specific organisms
    • Giardia lamblia
      • 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); less sensitive than stool EIA
    • Entamoeba species
      • For intestinal disease – Entamoeba histolytica stool antigen (EIA) is sensitive and specific
      • For 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)
    • Microsporidia
      • Microscopic examination of the stool
        • Requires special stain (microsporidia 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 exam may miss organisms in light infections, thus requiring examination of multiple specimens

Differential Diagnosis

• Viral or bacterial diarrhea
• Primary or metastatic cancer
• Tuberculous disease

Pharmacogenetics and Therapeutic Drug Monitoring

Screening

Monitoring

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

Comprehensive stool ova & parasite examination with submission of 3 specimens over 10 days is recommended (including request for special stains) for patients with history of travel or residence in endemic area, immunocompromised patients or persistent symptoms and clinical concern for parasitic infection despite negative EIA.

Guidelines

General References