(See also Overview of Intestinal Protozoan and Microsporidia Infections Overview of Intestinal Protozoan and Microsporidia Infections The most important intestinal protozoan pathogens are Cryptosporidium species (see Cryptosporidiosis) Cyclospora cayetanensis (see Cyclosporiasis) Cystoisospora (Isospora) belli (see Cystoisosporiasis)... read more .)
Four 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 (less common, uncertain pathogenicity)
E. bangladeshi (less common, uncertain pathogenicity)
Amebiasis is caused by E. histolytica and tends to occur in regions with poor socioeconomic conditions and poor sanitation. The parasite is present worldwide, but 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 50 million people develop amebic colitis or extraintestinal disease, and as many as 100,000 die.
Pathophysiology of Amebiasis
Entamoeba species exist in 2 forms:
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 and, if ingested, would be killed by gastric acids. Some trophozoites in the colonic lumen become cysts that are excreted with stool.
E. histolytica trophozoites can adhere to and kill colonic epithelial cells and polymorphonuclear leukocytes (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 pleural space, lung, or skin, or rarely through the bloodstream to the brain and other organs.
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.
Symptoms and Signs of Amebiasis
Most people with amebiasis are asymptomatic but chronically pass cysts in stools.
Symptoms that occur with tissue invasion in the colon usually develop 1 to 3 weeks after ingestion of cysts and include
Intermittent diarrhea and constipation
Cramping abdominal pain
Tenderness over the liver or ascending colon and fever may occur, and stools may contain mucus and blood.
Amebic dysentery, 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. Sometimes, fulminant colitis complicated by toxic megacolon or peritonitis may develop.
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 of the colon
Chronic amebic infection of the colon can mimic inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more 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.
Hepatic or other extraintestinal amebic disease
Extraintestinal amebic 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 of Amebiasis
Intestinal infection: Microscopic examination, enzyme immunoassay of stool, molecular tests for parasite DNA in stool, and/or serologic testing
Extraintestinal infection: Imaging and serologic testing or a therapeutic trial with an amebicide
Nondysenteric amebiasis may be misdiagnosed as irritable bowel syndrome Irritable Bowel Syndrome (IBS) Irritable bowel syndrome is characterized by recurrent abdominal discomfort or pain with at least two of the following characteristics: relation to defecation, association with a change in frequency... read more , regional enteritis Crohn Disease Crohn disease is a chronic transmural inflammatory bowel disease that usually affects the distal ileum and colon but may occur in any part of the gastrointestinal tract. Symptoms include diarrhea... read more , or diverticulitis Colonic Diverticulitis Diverticulitis is inflammation with or without infection of a diverticulum, which can result in phlegmon of the bowel wall, peritonitis, perforation, fistula, or abscess. The primary symptom... read more . A right-sided colonic mass may also be mistaken for cancer, tuberculosis, actinomycosis, or lymphoma.
Amebic dysentery may be confused with shigellosis Shigellosis Shigellosis is an acute infection of the intestine caused by the gram-negative Shigella species. Symptoms include fever, nausea, vomiting, tenesmus, and diarrhea that is usually bloody. Diagnosis... read more , salmonellosis Overview of Salmonella Infections The genus Salmonella is divided into 2 species, S. enterica and S. bongori, which include > 2400 known serotypes. Some of these serotypes are named. In such cases, common usage sometimes shortens... read more , schistosomiasis Schistosomiasis Schistosomiasis is infection with blood flukes of the genus Schistosoma, which are acquired transcutaneously by swimming or wading in contaminated freshwater. The organisms infect the vasculature... read more , or ulcerative colitis Ulcerative Colitis Ulcerative colitis is a chronic inflammatory and ulcerative disease arising in the colonic mucosa, characterized most often by bloody diarrhea. Extraintestinal symptoms, particularly arthritis... read more . 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 white blood cells 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, as well as E. moshkovskii and E. bangladeshi, which are of uncertain pathogenicity. Immunoassays that detect E. histolytica antigens in stool are sensitive and specific and are done to confirm the diagnosis. Specific DNA detection assays for E. histolytica using polymerase chain reaction are available at diagnostic reference laboratories and have very high sensitivity and specificity.
Serologic tests are positive in
About 95% of patients with an amebic liver abscess
> 70% of those with active intestinal infection
10% of asymptomatic carriers
Enzyme immunoassay (EIA) is the most widely used serologic test. 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).
Amebic intestinal infection
Microscopic 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 Collecting and Handling Specimens for Microscopic Diagnosis of Parasitic Infections Human parasites are organisms that live on or in a person and derive nutrients from that person (its host). There are 3 types of parasites: Single-cell organisms (protozoa, microsporidia) Multicellular... read more ). 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 is indistinguishable morphologically from E. dispar, E. moshkovskii, and E. bangladeshi but can be distinguished from a number of nonpathogenic amebas microscopically, including E. coli, E. hartmanni, E. polecki, Endolimax nana, and Iodamoeba bütschlii. Molecular analysis using polymerase chain reaction-based assays and enzyme immunoassay for fecal antigens are more sensitive and differentiate E. histolytica from other amebas.
In symptomatic patients, sigmoidoscopy or colonoscopy may show nonspecific inflammatory changes or characteristic flask-shaped mucosal lesions, which should be aspirated, and the aspirate should be examined for trophozoites and tested for specific E. histolytica antigen or DNA. Biopsy specimens from rectosigmoid lesions may also show trophozoites.
Amebic liver infection
Amebic extraintestinal 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 the following:
Those likely to be due to fungi or pyogenic bacteria
Those in which rupture seems imminent
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
Treatment of Amebiasis
Metronidazole or tinidazole initially
Iodoquinol, paromomycin, or diloxanide furoate subsequently for cyst eradication
For gastrointestinal symptoms and extraintestinal amebiasis, one of the following is used:
Oral metronidazole 500 to 750 mg 3 times a day in adults (12 to 17 mg/kg 3 times a day in children) for 7 to 10 days
Tinidazole 2 g orally once/day in adults (50 mg/kg [maximum 2 g] orally once/day in children > 3 years) for 3 days for mild to moderate gastrointestinal symptoms, 5 days for severe gastrointestinal symptoms, and 3 to 5 days for amebic liver abscess
Metronidazole and tinidazole should not be given to pregnant women. Alcohol must be avoided because these drugs have a disulfiram-like effect. In terms of gastrointestinal adverse effects, tinidazole is generally better tolerated than metronidazole.
Therapy for patients with significant gastrointestinal symptoms should include rehydration with fluid and electrolytes and other supportive measures.
Although metronidazole and tinidazole have some activity against E. histolytica cysts, they are not sufficient to eradicate cysts. Consequently, a 2nd oral drug is used to eradicate residual cysts in the intestine.
Options for cyst eradication are
Iodoquinol 650 mg orally 3 times a day after meals in adults (10 to 13 mg/kg [maximum of 2 g/day] orally 3 times a day in children) for 20 days
Paromomycin 8 to 11 mg/kg orally 3 times a day with meals for 7 days
Diloxanide furoate 500 mg orally 3 times a day in adults (7 mg/kg orally 3 times a day in children) for 10 days
Diloxanide furoate is not available commercially in the US.
The pathogenicity of E. moshkovskii and E. bangladeshi is uncertain. They have been identified in stools primarily in children with and without diarrhea in impoverished areas where fecal contamination of food and water is present. Molecular diagnostic tests to identify them are available only in research settings. The optimal treatment is unknown, but they are likely to respond to drugs used for E. histolytica.
Asymptomatic people who pass E. histolytica cysts should be treated with paromomycin, iodoquinol, or diloxanide furoate (see above for doses) to prevent development of invasive disease and spreading elsewhere in the body and to others.
Treatment is not necessary for E. dispar or asymptomatic E. moshkovskii and E. bangladeshi infections until more is known about their pathogenicity.
Prevention of Amebiasis
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.
E. histolytica is often asymptomatic, but can cause intestinal symptoms, dysentery, or liver abscesses.
Diagnose amebic intestinal infection using stool antigen tests, molecular tests for DNA, or microscopy.
Diagnose amebic liver abscess using ultrasonography, CT, or MRI, or 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 amebic trophozoites, followed by iodoquinol or paromomycin to kill cysts in the intestine.