Entamoeba Histolytica

Presentation and Cause

Entamoeba histolytica is an anaerobic, protozoan parasite that infects humans and other primates.¹ Infection can occur when a person ingests water or food that has been contaminated with fecal material containing mature E histolytica cysts — the infective stage of the parasite — or ingests E histolytica cysts present on their fingers or on the surfaces of objects.¹ E histolytica can also be spread through oral-anal sexual activity.²  

These mature, quadrinucleated cysts release motile trophozoites in the small intestine; the trophozoites — the activated, growing stage of the parasite — migrate to the large intestine, where they secrete specific proteolytic enzymes. Severity of symptoms associated with E histolytica infection is dependent on parasite density.

Affected people are generally asymptomatic or experience mild symptoms. Symptoms of E histolytica infection are similar to those of inflammatory bowel disease and can include diarrhea, constipation, weight loss, and abdominal cramps.² 

Severe infection can result in amebiasis (amebic dysentery), amebic colitis, and amebic liver abscesses.^1,2 According to the Centers for Disease Control and Prevention (CDC), approximately 10% to 20% of people infected with E histolytica become ill.¹ In the United States, amebic colitis is more common than amebiasis and amebic liver abscesses, and amebiasis is observed primarily in immigrants and individuals who travel to and from endemic areas.² Symptoms of amebic colitis can include abdominal cramps, pain, and bloody diarrhea.² Peritonitis and intestinal perforation may occur when E histolytica trophozoites invade the intestinal mucosa, causing ulceration.² Penetration of trophozoites through the colon wall and their dissemination into the bloodstream may result in amebic liver abscesses, which have been reported in approximately 5% of patients with intestinal amebiasis.² Patients may experience right upper quadrant pain and fever.² In rare cases, amebic abscesses may spread to the skin, brain, lungs, or other areas of the body.²

Although amebiasis is relatively uncommon in the United States, approximately 40 to 50 million symptomatic infections with E histolytica occur worldwide annually.^2-3 Severe disease occurs more frequently in the elderly, children, and people who are malnourished, immunosuppressed, or pregnant.² In the United States, those at greatest risk for E histolytica infection include people living in institutions, recent immigrants from endemic areas (especially India, Africa, and  Central and South America), people traveling to and from areas of endemic disease, and men who have sex with men.^3,4

Diagnostic Workup 

A diagnosis of intestinal amebiasis can be confirmed by identifying the pathogen in stool samples.² Several species of Entamoeba may be present, including E dispar, E moshkovskii, E bangladeshi, E coli, E hartmanni, E polecki, and E gingivalis. Molecular testing is the only way to distinguish between Entamoeba species.² However, trophozoites found outside the intestine or trophozoites containing erythrocytes indicate invasive infection with E histolytica.² Evaluation of stool samples using enzyme immunoassay testing can distinguish between E histolytica and other morphologically indistinguishable Entamoeba species.²

Patients with amebic colitis have small, pinpoint ulcerations of the colonic mucosa that may progress into flask-shaped ulcers.² Although these ulcerations may be present anywhere in the colon, they are most commonly found in the ascending colon, the cecum, or rectosigmoid colon.²

A suspected diagnosis of amebic liver abscess is typically confirmed with ultrasound, computed tomography (CT), and testing for parasitic host antibodies.^2,4 Pleural effusion, elevation of the right hemidiaphragm, and right lung base atelectasis are common radiographic findings.⁴ E histolytica cysts and trophozoites are found in the stool in less than half of patients once liver abscesses are present, so obtaining a stool sample is not useful.² Patients with amebic liver abscesses may have leukocytosis with neutrophilia, increased liver transaminase levels, and normal alkaline phosphatase levels.⁴

Management of E histolytica Infection

Patients infected with E histolytica often improve without treatment.³ Ideally, all patients with known amebiasis should receive antiparasitic therapy.² Asymptomatic patients should be treated with paromomycin, diloxanide furoate, or iodoquinol to rid the intestine of infection and prevent shedding of cysts.² However, iodoquinol and diloxanide furoate are not commonly available in the United States.³ Disseminated or invasive disease should be treated initially with tinidazole or metronidazole, followed by iodoquinol or paromomycin.² 

Asymptomatic (noninvasive) amebiasis in children should be treated with paromomycin at 25 to 35 mg/kg/d in 3 divided doses for 7 days.^3,4 Invasive disease, including amebic colitis and liver abscess, should be treated first with metronidazole at 35 to 50 mg/kg/d in 3 divided doses for 7 to 10 days, or with tinidazole at 50 mg/kg/d up to 2 g total per day for 3 to 5 days.^3,4 Tinidazole may administered to children 3 years of age and older.^3,4 After treatment with metronidazole or tinidazole, a luminal agent such as paromomycin, diloxanide, or iodoquinol must be administered to ensure eradication of the parasite from the intestine.^3,4

Adult patients should be treated first with metronidazole or tinidazole, followed by a course of paromomycin to rid the body of cysts.⁴ Dosing for adults with E histolytica infection is summarized below.⁴

Table. Recommended Treatment for Entamoeba histolytica Infection in Adults

Infection Type	Agent	Dosage
Asymptomatic	Paromomycin	25 to 30 mg/kg/d in 3 divided doses for 7 days
Invasive disease	Metronidazole	750 mg 3 times daily for 10 days or 2.4 g once daily for 2-3 days
Invasive disease	Tinidazole	2 g once daily for 3 days
Amebic liver abscesses	Metronidazole	750 mg 3 times daily for 10 days
Amebic liver abscesses	Tinidazole	2 g once daily for 3-5 days
Amebic liver abscesses	Chloroquine*	600 mg once daily for 2 days, then 300 mg once daily for 14 to 21 days

In addition to pharmacotherapy, patients with amebic liver abscesses may require percutaneous ultrasound-guided needle aspiration to relieve symptoms or if the infection does not respond to conservative therapy. Surgery may be considered if rupture of the abscess into the pericardium or peritoneum is imminent.⁴ 

Prevention of amebiasis is difficult in areas of the world lacking access to clean drinking water and with poor sanitation.³ People traveling to areas where amebiasis is endemic should avoid drinking tap water and eating unpeeled and uncooked fruits and vegetables.⁴

Monitoring

After completing a course of treatment for E histolytica infection, patients should undergo stool testing to confirm that the infection has cleared.⁴ Patients with amebic liver abscesses may require up to 20 months to fully recover, with ultrasound testing recommended for re-evaluation.⁴

Patients undergoing treatment with metronidazole should be educated about the Antabuse-like effect (disulfiram-ethanol reaction of severe nausea and vomiting) that can occur with alcohol consumption.⁴ Possible side effects of metronidazole and tinidazole include bloating, nausea, vomiting, and metallic taste.⁴ Paromomycin may cause nausea, vomiting, and diarrhea.⁴

References

1. Centers for Disease Control and Prevention. Parasites – amebiasis – Entamoeba histolytica infection general information. Updated December 29, 2021. Accessed March 6, 2023.

2. Mathison BA, Pritt BS. Medical parasitology. In: McPherson RA, Pincus MR, eds. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 24th ed. Elsevier, Inc; 2022:1290-1351.e3. 

3. Tien V, Singh U. Entamoeba histolytica (amebiasis). In: Long S, Prober C, Fischer M, Kimberlin D, eds. Principles and Practice of Pediatric Infectious Diseases. 6th ed. Elsevier, Inc; 2023:1341-1346.e3.

4. Virk A. Amebiasis, giardiasis, and other intestinal protozoan infections. In: Sanford CA, Pottinger PS, Jong EC, eds. The Travel and Tropical Medicine Manual. 5th ed. Elsevier, Inc; 2017:429-443.

Author Bio

Jen Seabright, PharmD, is a freelance medical writer in Pittsburgh, PA.