Amebiasis

Overview

Epidemiology

• Annually, over 50 million cases of amebiasis occur worldwide.
• Annually, over 100,000 deaths occur worldwide due to amebiasis or an amebiasis-related complication.
• Endemic regions include India, Mexico, and areas of Central and South America, likely because of poor sanitation and low socioeconomic conditions.

Etiology

Causative organism: anaerobic protozoan parasites of the Entamoeba genus

• Most common species causing symptomatic disease: E. histolytica
• Most common species causing infection worldwide: E. dispar
  • E. dispar has a lifecycle similar to that of E. histolytica but is noninvasive.
  • E. dispar infection is almost always asymptomatic.
• Other species worldwide:
  • E. moshkovskii
  • E. bangladeshi

Transmission occurs through the ingestion of cysts:

• Fecal-oral route
• Contaminated food or water

Risk factors and high-risk populations:

• Geographic:
  • Inhabitants of an endemic region
  • Travelers who spend more than 1 month in an endemic region
  • Institutionalized patients
• Health status:
  • Men who have sex with men
  • Advanced age
  • Pregnancy
  • Corticosteroid use
  • Malignancy
  • Malnutrition
  • Alcoholism

Pathophysiology

Life cycle of Entamoeba species (spp.)

The life cycle of Entamoeba spp. is dependent on the infection of a host because transition through the life stages occurs within the host’s intestinal tract. 

Cyst stage:

1. Found in formed and diarrheal stools from an infected host
2. Ingested via the fecal-oral route or contaminated water and food: Ingestion of just 1 cyst is sufficient to cause infection.
3. Ingested cysts become trophozoites in the small intestine.

Trophozoite stage:

4. Trophozoites migrate to the large intestine.
5. In 10% of cases, trophozoites invade the intestinal mucosa causing bloody diarrhea, local tissue destruction, and other complications.
6. Trophozoites undergo binary fission and produce cysts; both forms are excreted in the diarrheal stool.
7. Trophozoites quickly die outside the GI tract, but the cysts can survive for weeks.

Pathogenesis of invasive infection

1. Trophozoites colonize the large intestine and secrete proteases to invade mucosal cells and cause necrosis and apoptosis.
2. Trophozoites then release lytic enzymes that allow penetration into the intestinal vasculature.
3. A chain reaction of tissue destruction ensues, including the breakdown of intercellular tight junctions that leads to “flask-shaped” ulcers and fistulas.
4. Trophozoites that have entered the portal circulation may migrate to infect other organs.

Clinical Presentation

The incubation period is usually 2–4 weeks once ingested, but symptoms may develop up to 1 year after infection.

90% of all Entamoeba infections are asymptomatic:

• E. histolytica has the highest likelihood of causing symptoms (approximately 10% of cases).
• E. dispar infections are almost always asymptomatic/noninvasive.

Clinical amebiasis

• Onset: 2–4 weeks
• Symptoms may include:
  • Loose stools, ranging from mild to severe diarrhea (94%–100% of cases)
  • Abdominal pain, often in the RUQ (12%–80%)
  • Bloody stools (94%–100%)
  • Weight loss (50%)
  • Fever (up to 38%)

Complications

• Superimposed bacterial intestinal infections as a result of mucosal breakdown
• Amebic dysentery:
  • Severe diarrhea with visible blood and mucus
  • Trophozoites present in the stool
• Fulminant colitis:
  • Bowel necrosis
  • Bowel perforation leading to peritonitis (0.5%)
  • Toxic megacolon
• Persistent diarrhea, weight loss, and abdominal pain, such that they become chronic conditions
• Abscesses:
  • Liver: “anchovy paste” exudate (> 4%)
  • Rarely, abscesses may occur in the lungs, spleen, or brain.
• Fistulas with neighboring organs due to invasive destruction of the intestinal walls

Diagnosis

The diagnosis of amebiasis is based on clinical suspicion as well as confirmatory testing. Several testing modalities may be used.

• Stool antigen testing:
  • Rapid, 90% sensitive, specific
  • Can differentiate between causative species
  • May involve:
    • ELISA
    • Radioimmunoassay
    • Immunofluorescence
• Stool PCR:
  • 100% sensitive and specific
  • Expensive
  • Detects DNA or RNA in stools
  • Can differentiate between causative species
• Stool microscopy:
  • Demonstration of cysts or trophozoites
  • RBCs within the cytoplasm are suggestive of an E. histolytica infection.
  • A minimum of 3 samples per day is needed for accuracy.
• Serology:
  • Presence of antiamebic antibodies is suggestive of an E. histolytica infection.
  • E. dispar does not generally invoke antibody production.
  • Antibodies are detected 5–7 days after infection.
    • Antibodies may persist for years after an acute infection.
    • Serology cannot distinguish between acute and prior infections.
• Colonoscopy with histologic examination:
  • Not performed routinely due to risk of perforation of amebic ulcerations
  • Biopsies are performed to obtain samples for microscopy or antigen testing.
  • Mucosal thickening and flask-shaped ulcers may be visible.

Management and Prevention

Management

All E. histolytica infections should be treated regardless of the absence or severity of symptoms; however, E. dispar infections do not need to be treated.

• Medical approach (both are needed):
  1. Absorbable amebicides, such as metronidazole, can be used to treat infections within the tissue.
  2. Luminal amebicides, such as paromomycin, can eliminate cysts and trophozoites within the intestinal lumen.
• Surgical approach:
  • Drainage of abscesses that resist antibiotic treatment
  • Repair of bowel perforation
  • Colectomy for toxic megacolon

Prevention

• Primary prevention is based on the avoidance of uncooked food and untreated water in endemic areas.
• Water may be treated with iodine before consumption. Amebic cysts are not susceptible to chlorine treatment.
• A previous infection may confer partial immunity through IgA antibodies, but recurrent infections and persistent intestinal colonization have been documented.

Differential Diagnosis

All conditions that cause nonspecific or bloody diarrhea are differential diagnoses for amebiasis.

• Nonspecific diarrhea: diarrhea is a common GI problem in all age groups and is defined by the occurrence of > 3 episodes of loose stools in a day. Infectious causes include bacterial, viral (most common), or parasitic etiologies. Nonspecific diarrhea may also be physiologic (e.g., in response to stress) or caused by dietary factors. Most episodes of diarrhea without concerning features such as fever or bloody stools can be treated with supportive care. 
• Bacterial infections:
  • Shigellosis: an infection caused by Shigella that spreads through interpersonal contact or contaminated food and water. Shigellosis leads to inflammation and invasion of the intestinal mucosa, causing fever, abdominal pain, and bloody diarrhea. Diagnosis is made using Gram staining, culture, or PCR. Treatment of shigellosis includes rehydration, electrolyte replacement, and antibiotic therapy with ciprofloxacin, ceftriaxone, or cefixime.
  • Typhoid fever or enteric fever: an infection caused by Salmonella that spreads via fecal-oral transmission and consumption of contaminated food and water. Typhoid fever leads to invasion of the intestinal mucosa and possibly the bloodstream, causing abdominal pain, diarrhea, and sepsis. Diagnosis is generally made with stool cultures. Treatment includes rehydration, electrolyte replacement, and antibiotic therapy with fluoroquinolones.
  • Gastroenteritis/enterocolitis: conditions that include abdominal pain, nausea, vomiting, and watery to bloody diarrhea, which do not typically lead to sepsis in otherwise healthy patients. Some notable bacterial etiologies include Campylobacter spp., Yersinia spp., and Escherichia spp. These gram-negative bacilli spread via the consumption of undercooked food and contaminated food and water. The diarrhea is generally self-limiting, but treatment may include rehydration, electrolyte replacement, and ciprofloxacin if indicated.
  • Pseudomembranous colitis: an infection caused by C. difficile. Although the causative organism is commonly found in the normal gut microbiome, pathogenesis occurs when there is an overabundance. Common symptoms include foul-smelling and non-bloody diarrhea, abdominal pain, and nausea with vomiting. Diagnosis is made using stool PCR or enzyme assays. Treatment generally consists of discontinuing the offending antibiotic and commencing oral vancomycin.
• Parasitic infections:
  • Giardiasis: an infection caused by Giardia, which are flagellated protozoans causing infections after the consumption of cysts via the fecal-oral route or contaminated water. The hallmark symptom is foul-smelling steatorrhea resulting from malabsorption. Diagnosis is made based on stool microscopy or antigen testing. Treatment is with supportive care and antibiotics such as metronidazole. 
  • Strongyloidiasis: an infection caused by Strongyloides stercoralis, which is transmitted via the fecal-oral route, penetration through the skin, or penetration through the alveoli of the lungs. Strongyloidiasis leads to a constellation of nonspecific symptoms depending on the organ system that is most affected. Diagnosis can be made with a skin biopsy, stool studies, or serologic studies. Treatment includes the antihelmintic drugs, ivermectin and albendazole.
• Colonic ischemia: hypoperfusion to areas of the colon without redundant sources of arterial blood, known as “watershed” areas, due to thrombosis, embolism, or hypotension. The acute phase is characterized by a classic triad of severe abdominal pain, vomiting, and diarrhea that may be bloody, and a history of cardiovascular disease. Diagnosis is generally made with laboratory studies and CT with angiography. Treatment includes fluid replacement, antibiotics, systemic anticoagulation, and often surgery.
• Inflammatory bowel disease:
  • Crohn’s disease: a chronic, inflammatory, autoimmune disease that causes transmural inflammation and may involve any segment of the GI tract. The terminal ileum and proximal colon are typically involved. Presents present with crampy abdominal pain, non-bloody diarrhea, and extraintestinal symptoms. Definitive diagnosis is made using colonoscopy with biopsies, and treatment may involve antibiotics, corticosteroids, and/or immunomodulators.
  • Ulcerative colitis: a chronic, inflammatory, autoimmune disease that causes mucosal ulceration that always involves the rectum. Unlike those observed in Crohn’s disease, the ulcerations in ulcerative colitis are continuous. Patients present with colicky abdominal pain, bloody diarrhea, and tenesmus. Definitive diagnosis is made using colonoscopy with biopsies, and treatment may involve corticosteroids, immunomodulators, and resection surgery.
• Appendicitis: an acute inflammation of the appendix often due to obstruction by fecal matter. Appendicitis presents with periumbilical pain that migrates to the RLQ, and with fever, anorexia, nausea, and vomiting. Diagnosis is typically made clinically and is aided by either an ultrasound or CT scan. Treatment involves surgical appendectomy, but antibiotic therapy alone may be used in some cases.
• Diverticulitis: an inflammation of the diverticula (small outpouching regions of the colon) often due to obstruction with fecal matter. Diverticulitis presents with abdominal pain often in the LLQ, nausea, and diarrhea that may be bloody. The definitive diagnosis is usually based on the findings in a CT scan. Treatment involves bowel rest, IV fluids, and antibiotic therapy.