Diarrhea Causes and Considerations

Infectious Causes

• Norovirus is the most common cause of diarrheal disease outbreaks and represents a major source of acute gastroenteritis across all age groups 1, 2
• Rotavirus is the most common cause of acute diarrhea among children, accounting for one-fourth of all pediatric cases 3
• The Centers for Disease Control and Prevention recommends rotavirus vaccines, which have reduced rotavirus disease and hospitalizations markedly since licensure 4
• Important bacterial causes of diarrhea include Salmonella, Shigella, Yersinia, Campylobacter, and pathogenic strains of Escherichia coli 3, 4
• The majority of traveler's diarrhea is caused by bacterial pathogens and, to a lesser extent, viral pathogens, typically lasting <7 days 5
• Clostridium difficile is of increasing concern, especially in travelers with recent antimicrobial therapy 5
• Vibrio vulnificus infections occur in patients with chronic liver disease, iron overload states, or other immunocompromising conditions 1, 2
• Common parasitic causes of diarrhea include Giardia, Cryptosporidium, and Entamoeba histolytica 3
• Approximately 10% of traveler's diarrhea is caused by parasitic infections, which can persist for weeks to months, with giardiasis being the most common 5
• Cyclospora and Cystoisospora are additional parasitic causes of diarrhea 1, 4

Non-Infectious Causes

• Adverse effects of antiretroviral therapy or chemotherapy may account for persistent diarrhea in immunocompromised hosts 1, 2, 4
• The American Gastroenterological Association notes that chronic pancreatitis is a primary cause of steatorrhea presenting as pale, bulky, malodorous stools due to inadequate fat digestion 6
• Celiac disease is the most common small bowel enteropathy in Western populations, frequently presenting with steatorrhea 6
• Bile acid malabsorption produces diarrhea that characteristically occurs after meals and typically responds to fasting, particularly common after terminal ileum resection or cholecystectomy 6
• Hyperthyroidism causes diarrhea through endocrine effects on gut motility 6
• Diabetes mellitus causes diarrhea via multiple mechanisms: autonomic neuropathy, bacterial overgrowth, bile acid malabsorption, and medication effects 6

Special Populations

• Diarrhea in immunocompromised patients may involve bacterial, viral, parasitic, and fungal pathogens depending on underlying immune status 1, 2, 7
• HIV-infected patients are at risk for enteroaggregative E. coli, Cryptosporidium, microsporidia, Cystoisospora belli, CMV, and Mycobacterium avium complex (MAC) 1, 2, 7
• Diarrhea caused by Cryptosporidium, Cyclospora, Cystoisospora, or microsporidia is more likely to be severe, chronic, or relapsing in immunocompromised people, particularly those with impaired cell-mediated immunity 1, 4, 7
• Chronic and severe norovirus infection has been reported in patients receiving immunosuppression following organ transplantation 4, 5
• Risk factors for invasive nontyphoidal Salmonella infection include young and advanced age, HIV infection, cytotoxic chemotherapy, malnutrition, hemoglobinopathies, recent malaria, and cirrhosis 2
• Yersinia enterocolitica higher risk groups include young African American and Asian children, diabetics, and those with chronic liver disease, malnutrition, or iron-overload states 1, 2, 7

Clinical Pitfalls

• Microscopic examination of stool for ova and parasites is unlikely to include testing for Cryptosporidium and Cyclospora; clinicians should specifically request these tests 1, 2, 4, 7
• In patients with diarrhea lasting ≥30 days, testing for HIV may be appropriate 4, 5
• Normal vital signs and physical examination despite reported severe symptoms are consistent with factitious diarrhea 8
• Multipathogen nucleic acid amplification tests can detect multiple pathogens simultaneously, but the clinical significance of detecting multiple pathogens or nucleic acid alone (versus viable organisms) remains unclear 4, 5

Epidemiology and Etiology of Diarrheal Diseases

Parasitic Causes

• Entamoeba histolytica is a parasitic pathogen that produces amoebic dysentery characterized by bloody diarrhea and a relatively indolent onset (Journal of Infection, 2009) 9.

Traveler‑Related Diarrhea

• The majority of traveler’s diarrhea is bacterial; Enterotoxigenic E. coli (ETEC) is the most frequent cause, followed by Campylobacter, Salmonella, and Shigella species (Journal of Infection, 2009) 9.

Diagnostic Yield in Acute Diarrhea

• In approximately half of acute‑diarrhea cases, comprehensive laboratory testing fails to identify a causative pathogen; therefore, symptomatic management remains the primary therapeutic approach, with targeted testing reserved for fever, visible blood, severe illness, immunocompromised status, or diarrhea persisting > 7 days (Journal of Infection, 2009) 9.

Clostridioides difficile Epidemiology

• The incidence of severe C. difficile infection in the United States has doubled since 2001 (Clinical Infectious Diseases, 2017) 10.
• Community‑acquired C. difficile infections are rising even among individuals with minimal or no recent antibiotic exposure (Clinical Infectious Diseases, 2017) 10.

Management of Chronic Infectious Diarrhea with Steatorrhea in Travelers

Diagnostic Considerations

• Giardia lamblia infection is the most likely cause of a one‑month history of watery diarrhea with steatorrhea in a recent immigrant from a tropical region, as Giardia is a classic malabsorptive parasite. 11
• A single stool ova‑and‑parasite examination has low sensitivity; repeated stool examinations are required to reliably detect intestinal parasites. 12 13 14

Recommended Diagnostic Work‑up

Stool Testing

• Order repeat stool examinations that include Giardia antigen testing or PCR, which provide >95 % sensitivity and specificity for detection. 11 14
• Request specific microscopy or immunoassays for Cryptosporidium and Cyclospora, because routine ova‑and‑parasite panels often omit these organisms. 12 13
• Perform repeat bacterial stool cultures to identify enteric bacterial pathogens. 12 13

Laboratory Evaluation

• Obtain a complete blood count; eosinophilia in returning travelers is a useful marker suggesting parasitic infection. 12 13 14
• Conduct serologic testing for Strongyloides stercoralis in individuals who have visited highly endemic areas, even if eosinophilia is absent, because the infection can persist indefinitely and cause severe disease in immunocompromised hosts. 12 13 14
• Screen for celiac disease with IgA tissue transglutaminase antibody and a confirmatory test for patients with IgA deficiency. 11

Additional Investigations

• If microbiologic studies remain negative after initial testing, pursue upper endoscopy with duodenal biopsies to evaluate for tropical sprue or celiac disease. 15

Therapeutic Recommendations

• Initiate empiric antibiotic therapy for severe travelers’ diarrhea when symptoms persist for ≥1 month and the patient requires hospitalization. Azithromycin (500 mg daily for 3 days) is the preferred regimen, covering most bacterial pathogens and providing some activity against parasites. 15
• Fluoroquinolones may be considered as alternative agents, but their use should be cautious in Southeast Asia due to rising antimicrobial resistance. 15
• If Giardia infection is confirmed (or highly suspected), treat with metronidazole 250 mg three times daily for 5–7 days or tinidazole 2 g as a single dose. 13

Follow‑up and Escalation

• Re‑evaluate patients whose diarrhea persists ≥14 days despite empiric therapy; consider repeat microbiologic testing and endoscopic assessment. 15

Key Pitfalls to Avoid

• Do not rely on a single negative ova‑and‑parasite exam; low sensitivity necessitates repeat testing and targeted assays for Giardia, Cryptosporidium, and Cyclospora. 12 13
• Do not overlook Strongyloides infection; serologic screening is essential because hyperinfection can be life‑threatening, especially if immunosuppression is later required. 12 13 14
• Do not delay empiric azithromycin in patients with severe, prolonged diarrhea requiring admission, as early therapy improves outcomes. 15