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Amebiasis

(Entamebiasis)

by Richard D. Pearson, MD

Amebiasis is infection with Entamoeba histolytica. It is commonly asymptomatic, but symptoms ranging from mild diarrhea to severe dysentery may occur. Extraintestinal infections include liver abscesses. Diagnosis is by identifying E. histolytica in stool specimens or by serologic tests. Treatment for symptomatic disease is with metronidazole or tinidazole followed by paromomycin or other drugs active against cysts in the lumen.

Three species of Entamoeba are morphologically indistinguishable, but molecular techniques show that they are different species:

  • E. histolytica (pathogenic)

  • E. dispar (harmless colonizer, more common)

  • E. moshkovskii (uncertain pathogenicity)

Disease is caused by E. histolytica and tends to occur in regions with poor socioeconomic conditions and poor sanitation. Most infections occur in Central America, western South America, western and southern Africa, and the Indian subcontinent. In developed countries (eg, US), most cases occur among recent immigrants and travelers returning from endemic regions.

Worldwide each year, an estimated 40 to 50 million people develop amebic colitis or extraintestinal disease, and about 40,000 to 70,000 die.

Pathophysiology

Entamoeba sp exist in 2 forms:

  • Trophozoite

  • Cyst

The motile trophozoites feed on bacteria and tissue, reproduce, colonize the lumen and the mucosa of the large intestine, and sometimes invade tissues and organs. Trophozoites predominate in liquid stools but rapidly die outside the body. Some trophozoites in the colonic lumen become cysts that are excreted with stool.

Cysts predominate in formed stools and resist destruction in the external environment. They may spread directly from person to person or indirectly via food or water. Amebiasis can also be sexually transmitted by oral-anal contact.

E. histolytica trophozoites can adhere to and kill colonic epithelial cells and PMNs and can cause dysentery with blood and mucus but with few PMNs in stool. Trophozoites also secrete proteases that degrade the extracellular matrix and permit invasion into the intestinal wall and beyond. Trophozoites can spread via the portal circulation and cause necrotic liver abscesses. Infection may spread by direct extension from the liver to the right lung and pleural space or, rarely, through the bloodstream to the brain and other organs.

Symptoms and Signs

Most infected people are asymptomatic but chronically pass cysts in stools. Symptoms that occur with tissue invasion include intermittent diarrhea and constipation, flatulence, and cramping abdominal pain. Tenderness over the liver or ascending colon may occur, and stools may contain mucus and blood.

Amebic dysentery

This form, common in the tropics, manifests with episodes of frequent semiliquid stools that often contain blood, mucus, and live trophozoites. Abdominal findings range from mild tenderness to frank abdominal pain, with high fevers and toxic systemic symptoms. Abdominal tenderness frequently accompanies amebic colitis. Between relapses, symptoms diminish to recurrent cramps and loose or very soft stools, but emaciation and anemia may develop. Symptoms suggesting appendicitis may occur. Surgery in such cases may result in peritoneal spread of amebas.


Chronic amebic infection

This infection can mimic inflammatory bowel disease and manifests as intermittent nondysenteric diarrhea with abdominal pain, mucus, flatulence, and weight loss. Chronic infection may also manifest as tender, palpable masses or annular lesions (amebomas) in the cecum and ascending colon.


Extraintestinal amebic disease

Extraintestinal disease originates from infection in the colon and can involve any organ, but a liver abscess is the most common.

Liver abscess is usually single and in the right lobe. It can manifest in patients who have had no prior symptoms, is more common among men than among women (7:1 to 9:1), and may develop insidiously. Symptoms include pain or discomfort over the liver, which is occasionally referred to the right shoulder, as well as intermittent fever, sweats, chills, nausea, vomiting, weakness, and weight loss. Jaundice is unusual and low grade when present. The abscess may perforate into the subphrenic space, right pleural cavity, right lung, or other adjacent organs (eg, pericardium).

Skin lesions are occasionally observed, especially around the perineum and buttocks in chronic infection, and may also occur in traumatic or operative wounds.


Diagnosis

  • Intestinal infection: Microscopic examination and, when available, enzyme immunoassay of stool

  • Extraintestinal infection: Imaging and serologic testing or a therapeutic trial

Nondysenteric amebiasis may be misdiagnosed as irritable bowel syndrome, regional enteritis, or diverticulitis. A right-sided colonic mass may also be mistaken for cancer, TB, actinomycosis, or lymphoma.

Amebic dysentery may be confused with shigellosis, salmonellosis, schistosomiasis, or ulcerative colitis. In amebic dysentery, stools are usually less frequent and less watery than those in bacillary dysentery. They characteristically contain tenacious mucus and flecks of blood. Unlike stools in shigellosis, salmonellosis, and ulcerative colitis, amebic stools do not contain large numbers of WBCs because trophozoites lyse them.

Hepatic amebiasis and amebic abscess must be differentiated from other hepatic infections and tumors.

Diagnosis of amebiasis is supported by finding amebic trophozoites, cysts, or both in stool or tissues; however, pathogenic E. histolytica are morphologically indistinguishable from nonpathogenic E. dispar and E. moshkovskii. Specific DNA detection assays for E. histolytica have been developed. DNA testing is available at the Centers for Disease Control and Prevention (CDC) and is likely to become increasingly available at reference laboratories in the future.

Serologic tests are positive in about 95% of patients with an amebic liver abscess, in >70% of those with active intestinal infection, and in 10% of asymptomatic carriers. Enzyme immunoassay (EIA) is the most widely used. Antibody titers can confirm E. histolytica infection but may persist for months or years, making it impossible to differentiate acute from past infection in residents from areas with a high prevalence of infection. Thus, serologic tests are helpful when previous infection is considered less likely (eg, in travelers to endemic areas).

Intestinal infection

Identification of intestinal amebas may require examination of 3 to 6 stool specimens and concentration methods (see Table: Collecting and Handling Specimens for Microscopic Diagnosis of Parasitic Infections). Antibiotics, antacids, antidiarrheals, enemas, and intestinal radiocontrast agents can interfere with recovery of the parasite and should not be given until the stool has been examined. E. histolytica has to be distinguished from E. dispar and E. moshkovskii as well as from other nonpathogenic amebas including E. coli, E. hartmanni, Endolimax nana, and Iodamoeba bütschlii. PCR-based assays and enzyme immunoassay for fecal antigens are more sensitive and differentiate E. histolytica from nonpathogens.

In symptomatic patients, proctoscopy often shows characteristic flask-shaped mucosal lesions, which should be aspirated, and the aspirate should be examined for trophozoites. Biopsy specimens from rectosigmoid lesions may also show trophozoites.


Extraintestinal infection

This infection is more difficult to diagnose. Stool examination is usually negative, and recovery of trophozoites from aspirated pus is uncommon. If a liver abscess is suspected, ultrasonography, CT, or MRI should be done. They have similar sensitivity; however, no technique can differentiate amebic from pyogenic abscess with certainty.

Needle aspiration is reserved for lesions of uncertain etiology, those in which rupture seems imminent, and those that respond poorly to drug therapy. Abscesses contain thick, semifluid material ranging from yellow to chocolate-brown. A needle biopsy may show necrotic tissue, but motile amebas are difficult to find in abscess material, and amebic cysts are not present.

A therapeutic trial of an amebicide is often the most helpful diagnostic tool for an amebic liver abscess.

Pearls & Pitfalls

  • Microscopic examination of stool is usually negative in patients with extraintestinal amebiasis.


Treatment

  • Metronidazole or tinidazole initially

  • Iodoquinol, paromomycin, or diloxanide furoate subsequently for cyst eradication

For mild to moderate GI symptoms , oral metronidazole 500 to 750 mg tid in adults (12 to 17 mg/kg tid in children) for 7 to 10 days is recommended. Metronidazole should not be given to pregnant women. Alcohol must be avoided because of the drug’s disulfiram-like effect. Alternatively, tinidazole 2 g po once/day in adults (50 mg/kg [maximum 2 g] po once/day in children >3 yr) for 3 days can be used. When taken with alcohol, tinidazole also has a disulfiram-like effect, and it should not be used during pregnancy; however, in terms of GI adverse effects, it is generally better tolerated than metronidazole.

For severe intestinal and extraintestinal amebiasis , oral metronidazole 750 mg tid in adults (12 to 17 mg/kg tid in children) for 7 to 10 days is used. Alternatively, tinidazole 2 g po once/day in adults (50 mg/kg [maximum 2 g] po once/day in children > 3 yr) for 5 days can be used.

In both cases, a course of metronidazole or tinidazole should be followed by a 2nd oral drug to eradicate residual cysts in the lumen. Options are

  • Iodoquinol 650 mg po tid after meals in adults (10 to 13 mg/kg [maximum of 2 g/day] po tid in children) for 20 days

  • Paromomycin 8 to 11 mg/kg po tid with meals for 7 days

  • Diloxanide furoate 500 mg po tid in adults (7 mg/kg po tid in children) for 10 days

Diloxanide furoate is not available commercially in the US.

Therapy should include rehydration with fluid and electrolytes and other supportive measures.

Asymptomatic people who pass E. histolytica cysts should be treated with paromomycin, iodoquinol, or diloxanide furoate (see above for doses). Although metronidazole and tinidazole have some activity against E. histolytica cysts, it is not sufficient for them to be used for cyst eradication.

Treatment is not necessary for E. dispar or E. moshkovskii infections. However, if fecal antigen or PCR-based assays to differentiate them from E. histolytica is not available, the decision to treat is made clinically (eg, by the likelihood of exposure to E. histolytica).

Prevention

Contamination of food and water with human feces must be prevented—a problem complicated by the high incidence of asymptomatic carriers. Uncooked foods, including salads and vegetables, and potentially contaminated water and ice should be avoided in developing areas. Boiling water kills E. histolytica cysts. The effectiveness of chemical disinfection with iodine- or chlorine-containing compounds depends on the temperature of the water and amount of organic debris in it. Portable filters provide various degrees of protection.

Work continues on the development of a vaccine, but none is available yet.

Key Points

  • E. histolytica usually causes dysentery but sometimes causes liver abscesses.

  • Diagnose intestinal infection using stool antigen tests or microscopy.

  • Diagnose extraintestinal infection using serologic tests, which are most helpful when previous infection is considered unlikely (eg, in travelers to endemic areas), or a therapeutic trial of an amebicide.

  • Treat with metronidazole or tinidazole to eliminate amebas, followed by iodoquinol or paromomycin to kill cysts in the intestine.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • FLAGYL
  • No US brand name
  • TINDAMAX
  • ANTABUSE
  • YODOXIN

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