Description

• After malaria and schistosomiasis, the third-leading parasitic cause of death worldwide.
• Most common in developing countries, immigrants from or travelers to endemic regions, those who perform anal sex, and immunocompromised individuals
• Most infected patients are asymptomatic or have minimal GI symptoms (~90%):
  • Severe infection (i.e., amebic colitis) can occur in very young patients, pregnant women, patients on steroid therapy, alcoholics, malnourished individuals, and in malignancy (1,2).
• Infection is spread by the fecal–oral route and caused by the ingestion of E. histolytica cysts (infective form) in contaminated food (garden vegetables), fecally contaminated soil, or water. Then, excystation occurs in the terminal ileum or colon to form highly motile trophozoites (invasive form). The trophozoites then encyst and are excreted in the feces or invade the intestinal mucosal barrier and spread hematogenously via the portal circulation to the liver or other distant organs. Excreted cysts reach the environment to complete the cycle.
• Amebiasis is primarily an infection of the colon, but extraintestinal (liver, kidney, bladder, skin, lung, brain, male or female genitalia) disease can occur. Amebic liver abscess is the most common complication of invasive amebiasis. It can develop during the acute attack or 1–3 months later.
• The genus Entamoeba contains many species, including E. histolytica, E. dispar, E. moshkovskii, E. polecki, E. coli, and E. hartmanni. Only E. histolytica has been clearly associated with disease; the others are considered nonpathogenic (3). E. dispar and E. moshkovskii are nonpathogenic strains that are morphologically identical to E. hystolytica. Previously counted asymptomatic infections by so-called nonpathogenic strains of E. histolytica are now evidenced to be due to E. dispar and E. moshkovskii. Latest availability of sensitive and specific antigen detection and polymerase chain reaction (PCR) can differentiate E. histolytica from E. dispar and E. moshkovskii in stool.
• System(s) affected: Gastrointestinal (GI); Nervous; Renal/Urologic; Reproductive; Skin/Exocrine
• Synonym(s): Amebic colitis; Amebic dysentery

Geriatric Considerations
More severe in elderly

Pediatric Considerations
More severe in neonates

Pregnancy Considerations
More severe in pregnancy

Epidemiology

• Infection can affect patients of all ages.
• Amebic colitis affects both sexes equally (1).
• Amebic liver abscess incidence greater in men than women for unknown reasons.
• HIV-infected patients are not at increased risk for intestinal or extraintestinal amebiasis.

Pediatric Considerations
Very young children seem to be predisposed to fulminant colitis.

• US ~4%; 10% of the world’s population. Asymptomatic E. dispar infection is 10 times more common than E. histolytica infection.
• Entamoeba infection is as high as 50% in areas of Central and South America, Africa, and Asia. Prevalence rates of E. histolytica in asymptomatic persons in developing countries range from 1–21%.

Risk Factors

• Low socioeconomic status
• Institutional living
• Male homosexuality
• Immunocompromised
• Severe disease and increased mortality are common in pregnancy, patients on steroid treatment, malignancy, malnutrition, and alcoholism.
• Invasive disease is more common in certain geographic locations, including some parts of Mexico, South Africa, and India.

General Prevention

• Eradication of fecal contamination of food and water through improved sanitation, hygiene, and water treatment
• Individuals traveling to endemic areas should be advised on proper food and water handling.
• Amebic cysts are not killed by soap or low concentration of chlorine or iodine. Water should be boiled for >1 minute and uncooked vegetables washed with a detergent soap or soaked in acetic acid or vinegar for 10–15 minutes before consumption.
• Avoid sexual practices that involve fecal–oral contact with potential contamination of infective cysts.
• Treat patients and close contacts, since reinfection is common.
• Amebiasis does not confer lifelong immunity; reinfection is possible (4).

Pathophysiology

• Invasion to the colonic mucosa is mediated by a galactose/N-acetylgalactosamine (GAL/GalNAc)-specific lectin, able to activate lytic and apoptotic pathways, and direct inhibition of the complement system by the trophozoite (4).
• Extraintestinal disease can result from hepatobiliary and/or hematogenous spread.

Etiology

Infection results from ingestion of E. histolytica cysts in contaminated food, water, or by direct fecal–oral transmission.

History

• Noninvasive infection (symptoms are often nonspecific):
  • Asymptomatic
  • Mild diarrhea
  • Abdominal discomfort
• Invasive infection (amebic colitis):
  • Gradual onset of bloody diarrhea
  • Abdominal pain
  • Fever (10–30%)
  • Weight loss and anorexia
  • Fulminant colitis with severe bloody diarrhea, worsening abdominal pain with peritonitis, and fever.
• Extraintestinal infection:
  • Amebic liver abscess:
    • Fever (up to 90%), right-upper-quadrant (RUQ) pain <10 days duration
    • Subacute presentation is associated with mild fever, weight loss, and anorexia.
    • Cough can occur. Jaundice is not common.
    • Up to 70% present without colitis.
    • Symptoms may start years after exposure.
  • Pleuropulmonary amebiasis: Pleuritic chest pain, cough, and respiratory distress after rupture of amebic liver abscess through the diaphragm
  • Cerebral amebiasis: Headache, nausea, vomiting, and rapid mental status change with rapid progression

Physical Exam

• Amebic colitis:
  • Diffuse abdominal tenderness (12–85%)
  • Fever (10–30%)
  • Weight loss (40%)
  • Heme-positive stools (70–100%)
• Amebic liver abscess:
  • Fever (85–90%)
  • RUQ tenderness (85–90%)
  • Hepatomegaly (30–50%)
  • Weight loss (30–50%)
  • Jaundice (6–10%)

Diagnostic Tests and Interpretation

• Microscopic stool examination for trophozoites from a single sample is only 33–50% sensitive. Serial stool sampling × 3 in no more than 10 days increases detection to 85–95% but with poor specificity, as it cannot differentiate E. histolytica from nonpathogenic E. dispar and E. moshkovskii.
• Antigen detection assays are the best available tool to diagnose intestinal amebiasis. ELISA detects E. histolytic-specific antigens, with an overall sensitivity of 71–100% and specificity of 93–100%. Antigen testing from serum and liver aspirate in amebic liver abscess yields a sensitivity of 96% and 100%, respectively.
• E. histolytica infection results in the development of antibodies, whereas E. dispar infection does not. Antibodies become usually positive in 5–7 days of acute infection and may persist for years. Cannot differentiate between new and past infection. Indirect hemagglutination (IHA) is 90% sensitive in patients with symptomatic intestinal infection. Serum antilectin antibodies (IgG) are helpful in E. histolytica infection with amebic liver abscess, with a sensitivity of 97.9% and specificity of 94.8%.
• PCR techniques are more sensitive for detection of E. histolytica in fecal or liver aspirate samples but are not routinely available.
• In bladder infections: Amoebae and/or cysts in urine
• Liver enzymes, alkaline phosphatase (80%), and ESR may be elevated, and anemia and leucocytosis without eosinophilia (80%) may be present in amebic liver abscess.

Follow-Up and Special Considerations
Follow-up stool examination after completion of therapy to ensure intestinal eradication

Imaging

Initial Imaging Approach
US and CT scanning are sensitive but nonspecific for amebic liver abscess; usually solitary lesions in the right hepatic lobe (70–80%)

• US- or CT-guided needle aspiration for suspected amebic abscess with studies of aspirate
• Colonoscopy with biopsy can be performed in highly suspicious cases with negative stool and antigen testing. Contraindicated in fulminant colitis due to increased perforation risk.

• Colon biopsy:
  • Amebic invasion through the mucosa and into submucosa is the hallmark of amebic colitis, which gives the classical flask-shaped ulcers.
  • Periodic acid–Schiff-stained trophozoites in magenta color
  • Neutrophils at the periphery
• Liver biopsy:
  • Necrosis surrounded by a rim of trophozoites
• Liver aspirate:
  • Red-brown material (anchovy paste)

Differential Diagnosis

• Other infectious causes of colitis:
  • Shigellosis
  • Campylobacter infection
  • Pseudomembranous colitis
  • Occasionally salmonellosis or Yersinia infection
  • Viral hepatitis
• Noninfectious causes of colitis:
  • Ulcerative colitis
  • Crohn colitis
  • Ischemic colitis in elderly
  • Hepatocellular adenoma
• Hepatic amebiasis must be distinguished from pyogenic liver abscess or superinfection of amebic abscess.

Medication (Drugs)

• Noninvasive infection: Treat with luminal agents only:
  • Paromomycin: Adult: 500–750 mg PO t.i.d. or 25–35 mg/kg/d PO divided t.i.d. for 5–10 days. Pediatric: Administer as in adults
• Invasive infection: Treat with nitroimidazole (metronidazole/tinidazole) followed by luminal agent:
  • Metronidazole: Adult: 500–750 mg t.i.d. PO for 10 days. Pediatric: 35–50 mg/kg PO divided t.i.d. for 10 days. IV therapy does not offer significant difference, as metronidazole is well absorbed orally. It is then followed by a paromomycin (for 5–10 days) or diiodohydroxyquin (650 mg PO t.i.d. for 20 days) to eliminate intestinal carriage.
  • Tinidazole: 2 g/d for 3 days with food for intestinal infection and 2 g/d for 3–5 days for liver abscess; better tolerated than metronidazole (2)[A]
• Contraindications:
  • Known allergy to given medication
  • Diiodohydroxyquin should be used with caution in patients with thyroid disease. It is contraindicated in renal and hepatic patients, and may cause optic nerve and peripheral neuropathy.
• Significant possible interactions:
  • Metronidazole and tinidazole: Disulfiram reaction with concomitant use of ethanol

• Most agents are avoided in pregnancy (especially 1st trimester) because of concerns of teratogenicity, but invasive disease must still be treated:
  • Paromomycin is sometimes recommended for noninvasive disease because it is not absorbed.
• Infectious disease consultation should be obtained.

• Luminal agent for noninvasive infection:
  • Diiodohydroxyquin (also called iodoquinol): Adult: 650 mg t.i.d. PO for 20 days (if available). Pediatric: 30–40 mg/kg PO t.i.d. for 20 days
• Invasive infection:
  • Dehydroemetine (as effective as metronidazole, but cardiotoxic): 1–1.5 mg/kg/d IM for 5 days
  • Chloroquine (less effective): 600 mg base/d PO for 2 days, then 200 mg/d PO for 2–3 weeks (pediatric dose: 10 mg/kg/d up to maximum of 300 mg/d)
  • Treatment for invasive infection should be followed by a luminal agent.

Surgery/Other Procedures

• Surgery may be necessary in severe amebic colitis, peritonitis, and perforated viscus.
• Surgical drainage of uncomplicated amebic liver abscess should be avoided.

Follow-Up Recommendations

Patient Monitoring
Stool studies should be repeated after the completion of therapy to ensure eradication, since no regimen is completely effective.

Diet

As tolerated

Patient Education

Maintain good hygiene and avoid situations of re-exposure.

Prognosis

• Untreated invasive amebiasis is frequently fatal.
• With treatment, improvement usually occurs within a few days.
• Irritable bowel symptoms may persist for weeks after successful treatment, and relapses are possible.

Complications

• Amebic colitis:
  • Fulminant or necrotizing colitis
  • Toxic megacolon
  • Ameboma
  • Rectovaginal fistula
• Amebic liver abscess:
  • Rupture to intraperitoneal, intrathoracic, or intrapericardial spaces with secondary bacterial infection
  • Direct extension to pleura or pericardium
  • Hematogenous dissemination and formation of brain abscess

See Also

Diarrhea, Acute; Diarrhea, Chronic

ICD-9

• 006.0 Acute amebic dysentery without mention of abscess
• 006.3 Amebic liver abscess
• 006.9 Amebiasis, unspecified
• 006.8 Amebic infection of other sites
• 006.4 Amebic lung abscess
• 006.5 Amebic brain abscess
• 006.6 Amebic skin ulceration

ICD-10

• A06.9 Amebiasis, unspecified
• A06.0 Acute amebic dysentery
• A06.4 Amebic liver abscess
• A06.3 Ameboma of intestine
• A06.1 Chronic intestinal amebiasis
• A06.2 Amebic nondysenteric colitis
• A06.5 Amebic lung abscess
• A06.6 Amebic brain abscess
• A06.7 Cutaneous amebiasis
• A06.89 Other amebic infections

SNOMED

• 111910009 Amebic infection (disorder)
• 388759003 Infection due to Entamoeba histolytica (disorder)
• 387754006 amebic dysentery (disorder)
• 75119003 Amebic liver abscess (disorder)
• 240664007 Amebic abscess of skin
• 27908001 Amebic brain abscess
• 65095005 Amebic lung abscess