eMedicine Specialties > Pediatrics: General Medicine > Parasitology

Amebiasis

Author: Vinod K Dhawan, MD, FACP, FRCP(C), Professor, Department of Clinical Medicine, University of California at Los Angeles; Professor of Medicine, Charles R Drew University of Medicine and Science; Chief, Division of Infectious Diseases, MLK-Harbor Hospital
Coauthor(s): Thomas R Naparst, MD, Clinical Instructor in Emergency Medicine, New York University School of Medicine; Consulting Staff, Department of Emergency Medicine, New York Downtown Hospital
Contributor Information and Disclosures

Updated: Aug 11, 2008

Introduction

Background

Amebiasis is a parasitic infection caused by the protozoon Entamoeba histolytica. Amebiasis is the third leading parasitic cause of death worldwide, surpassed only by malaria and schistosomiasis. On a global basis, amebiasis affects approximately 50 million persons each year, resulting in nearly 100,000 deaths.

Fedor Aleksandrovich Lošch, in St. Petersburg, Russia, first described amebiasis in 1875. He originally named the organism Amoeba coli and documented its pathogenicity in a dog fed with dysenteric stools from a patient. In 1886 in Egypt, Kartulis proved amebae to be the cause of intestinal and hepatic lesions in patients with diarrhea. In 1891, Councilman and Lafleur, at Johns Hopkins University Hospital, distinguished between bacillary and amebic dysentery. In 1913 in the Philippines, Walker and Sellards described the pathogenic role of amebae in extensive studies.

The parasite has 2 forms: a motile form, called the trophozoite, and a cyst form, responsible for the person-to-person transmission of infection. The trophozoite of E histolytica inhabits the large intestine to produce lesions of amebic colitis. Invasion of the colonic mucosa leads to dissemination of the organism to extracolonic sites, predominantly the liver. Faced with an adverse colonic environment, the trophozoite changes to the cystic form, better adapted to survival.

The trophozoite of E histolytica averages 25 mm, ranging from 10-60 mm (see Media file 1). It has a clear ectoplasm and a somewhat granular endoplasm that contains several vacuoles. The trophozoite has a single 3-mm to 5-mm nucleus with fine peripheral chromatin and a central nucleolus. Ingested RBCs may be present within the trophozoite.

The cyst of E histolytica averages 12 mm, ranging from 5-20 mm (see Media file 2). It has 1-4 nuclei that are morphologically similar to the nuclei of the trophozoite. The cyst may have iodine-stainable glycogen clumps and chromatoid bodies with smooth rounded edges.

The life cycle of E histolytica is depicted in Media file 3. Humans are the only reservoir of E histolytica. Cysts passed in the feces can survive in moist environmental conditions for weeks to months. Upon ingestion of fecally contaminated food or water, the cysts travel to the small intestine, where the trophozoites are released. In 90% of patients, the trophozoites re-encyst and produce asymptomatic infection, which usually spontaneously resolves within 12 months. In the remaining 10% of patients who are infected, the parasite causes symptomatic amebiasis. Under unfavorable conditions, the trophozoite reverts to the cyst form, and the life cycle is repeated.

Entamoeba dispar is a nonpathogenic protozoon morphologically identical to E histolytica. The previously reported asymptomatic infections due to the so-called nonpathogenic strains of E histolytica are now recognized to be due to E dispar. These 2 species of Entameba can be distinguished by the monoclonal antibodies. Specific and sensitive means to detect E histolytica in stool are now available and include antigen detection and polymerase chain reaction (PCR). Other morphologically distinct organisms, such as Entamoeba coli and Entamoeba hartmanni, are also nonpathogenic. Infections due to E histolytica cause a spectrum of illnesses, as follows:

• Intestinal disease
  • Asymptomatic infection
  • Symptomatic noninvasive infection
  • Acute proctocolitis (dysentery)
  • Fulminant colitis with perforation
  • Toxic megacolon
  • Chronic nondysenteric colitis
  • Ameboma
  • Perianal ulceration
• Extraintestinal disease
  • Liver abscess
  • Pleuropulmonary disease
  • Peritonitis
  • Pericarditis
  • Brain abscess
  • Genitourinary disease

Pathophysiology

Amebiasis is acquired by the fecal-oral route through consumption of fecally contaminated food or water. Direct oral-anal contact (anilingus) can also lead to fecal exposure to E histolytica. The ingestion of E histolytica cysts is followed by excystation in the small bowel and invasion of the colon by the trophozoites. The incubation period varies from 2 days to 4 months. Invasive disease begins with the adherence of E histolytica to colonic mucins, epithelial cells, and leukocytes. Adherence of the trophozoite is mediated by a galactose-inhibitable adherence lectin. This lectin is a 260-kd surface protein that contains a 170-kd subunit and a 35-kd subunit. The heavier subunit has galactose-binding activity and at least 6 distinct epitopes. These epitopes are different in E dispar.

After adherence, trophozoites invade the colonic epithelium to produce the ulcerative lesions typical of intestinal amebiasis (see Media file 4). The trophozoites of E histolytica lyse the target cells by using lectin to bind to the target cells' membranes and using the parasite's ionophorelike protein to induce a leak of ions (ie, Na⁺, K⁺, Ca⁺) from the target cell cytoplasm. Numerous hemolysins, encoded by plasmid (ribosomal DNA [rDNA]) and cytotoxic to the intestinal mucosal cells, have been described in E histolytica. An extracellular cysteine kinase causes proteolytic destruction of the tissue, producing flask-shaped ulcers (see Media file 5). Phorbol esters and protein kinase C activators augment the cytolytic activity of the parasite.

Spread of amebiasis to the liver occurs via the portal blood. The pathogenic strains evade the complement-mediated lysis in the bloodstream. Trophozoites ascend the portal veins to produce liver abscesses filled with acellular proteinaceous debris. This material has the appearance of anchovy paste. The trophozoites of E histolytica lyse the hepatocytes and the neutrophils. This explains the paucity of inflammatory cells within the liver abscesses. The neutrophil toxins may contribute to hepatocyte necrosis. Triangular areas of hepatic necrosis may also occur due to ischemia caused by portal venous obstruction. The trophozoites of E histolytica may be present along the periphery of these hepatic lesions (see Media file 6).

Serum antibodies in patients with amebic liver abscess develop in 7 days and persist for as long as 10 years. E dispar infections do not elicit antibody response, unlike asymptomatic E histolytica infections. Mucosal immunoglobulin A (IgA) response to E histolytica occurs during invasive amebiasis. However, no evidence suggests that invasive amebiasis is increased in incidence or severity in patients with IgA deficiency.

Cell-mediated immunity is important in limiting the disease and preventing recurrences. Antigen-specific blastogenic responses occur, leading to production of lymphokines, including interferon-d (IFN-d), which activates the killing of E histolytica trophozoites by the macrophages. This killing depends on contact, oxidative pathways, nonoxidative pathways, and nitric oxide (NO). Lymphokines, such as tumor necrosis factor-alpha (TNF-a), are capable of activating the amebicidal activity of neutrophils. Incubation of CD8⁺ lymphocytes with E histolytica antigens in vitro elicits cytotoxic T-cell activity against the trophozoites. During acute invasive amebiasis, T-lymphocyte response to E histolytica antigens is depressed by a parasite-induced serum factor.

Frequency

United States

In the United States, amebiasis is most commonly seen in immigrants from developing countries and travelers to those areas. In one study, the rate of acute amebic diarrhea ranged from 1.5% in travelers returning from Southeast Asia to 3.6% in those returning from Central America, with an overall rate of 2.7%.¹ Additionally, increased prevalence of amebiasis in the United States is noted in institutionalized persons (especially with mental retardation), male homosexuals, and those who live in communal settings.

The prevalence rate of amebiasis in the United States is approximately 4%. E dispar infection, which is always asymptomatic, is 10 times more common than E histolytica infection. Moreover, only 10% of E histolytica infections cause invasive disease. Therefore, only 1% of persons with stool microscopy findings that reveal Entamoeba develop symptomatic amebiasis.

International

Worldwide, approximately 50 million cases of invasive E histolytica disease occur each year, with as many as 100,000 deaths. This represents the tip of the iceberg because only 10%-20% of infected individuals become symptomatic.

Earlier estimates of E histolytica infection based on examination of stool for ova and parasites, are inaccurate because this test can not differentiate E histolytica from E dispar and Entamoeba moshkovskii, which are morphologically identical but nonpathogenic organisms. Prevalence rates of E histolytica, as determined by enzyme-linked immunosorbent assay (ELISA) or PCR tests on stool from asymptomatic persons in developing countries range from 1-21%.

Incidence of amebiasis is higher in developing countries. Areas of high prevalence include the Indian subcontinent, southern and western Africa, the Far East, South America, and Central America. In endemic areas, as many as 25% of patients may be carrying antibodies to E histolytica due to prior infections, which may be largely asymptomatic. A study in Bangladesh indicated that preschool children experienced 0.09 episodes of E histolytica -associated diarrhea and 0.03 episodes of amebic dysentery each year. The annual incidence of amebic liver abscess was reported to be 21 cases per 100,000 inhabitants in Hue City, Vietnam.² An epidemiologic study in Mexico City reported that 9% of the population was infected with E histolytica in the 5-year to 10-year period preceding the study. Various factors, such as poor education, poverty, overcrowding, contaminated water supply, and unsanitary conditions, contribute to the fecal-oral transmission.

Travel to endemic areas can predispose individuals to amebiasis. However, amebiasis is an uncommon cause of traveler's diarrhea. The disease usually occurs after a longer stay in endemic areas (eg, >1 mo).

Mortality/Morbidity

Amebic infections lead to significant morbidity while causing variable mortality as described below.

• Mortality rate in patients with uncomplicated amebic liver abscess is less than 1%.
• Fulminant amebic colitis has a mortality rate of more than 50%.
• Pleuropulmonary amebiasis has a mortality rate of 15-20%.
• Amebic pericarditis has a case fatality rate of 40%.
• Cerebral amebiasis is highly fatal, with a 90% death rate.
• Increased severity of amebiasis is noted in children (especially neonates), women who are pregnant or postpartum, individuals who use corticosteroids, individuals with malignancy, and malnourished individuals.

Sex

Invasive amebiasis, including amebic liver abscess, is much more common in adult males than in females. However, amebic liver abscess is equally common in both sexes among prepubertal children. Acuna-Soto and colleagues have noted that asymptomatic E histolytica infection is distributed equally between sexes.⁴ Therefore, the higher proportion of men with invasive amebiasis may be due to a male susceptibility to invasive disease.

Age

Symptomatic intestinal amebiasis occurs in all age groups. Liver abscesses due to amebiasis are 10 times more frequent in adults than in children.

Clinical

History

• The incubation period is commonly 2-4 weeks but ranges from a few days to years. Amebiasis is more severe in very young patients, in elderly patients, and in patients receiving corticosteroids. The clinical spectrum of amebiasis ranges from asymptomatic infection to fulminant colitis and peritonitis to extraintestinal amebiasis, most commonly amebic liver abscess. The clinical expression of amebiasis may be related to geography. For instance, amebic colitis is the predominant presentation in Egypt, whereas amebic liver abscesses predominate in South Africa.
• Asymptomatic infections are common following ingestion of the parasite. E dispar does not cause invasive disease or antibody production. As many as 90% of E histolytica infections are also asymptomatic. The infection is self-limited but may be recurrent. Only antigen detection tests can distinguish between E histolytica and E dispar.
• Amebic colitis is gradual in onset, with symptoms presenting over 1-2 weeks, distinguishing it from bacterial dysentery. Diarrhea is the most common symptom. Patients with amebic colitis typically present with cramping abdominal pain, watery or bloody diarrhea, and weight loss. Fever is noted in 10% of patients. 
• Fulminant amebic colitis is a rare complication of amebic dysentery (<0.5%). It presents with a rapid onset of severe bloody diarrhea, severe abdominal pain, and high fever. Children younger than 2 years are at increased risk. Intestinal perforation is common. Patients may develop toxic megacolon, which is typically associated with the use of corticosteroids. Mortality rates with fulminant amebic colitis may exceed 40%. 
• Chronic amebic colitis is clinically similar to inflammatory bowel disease. Recurrent episodes of bloody diarrhea and vague abdominal discomfort develop in 90% of patients with chronic amebic colitis who have antibodies to E histolytica. Amebic colitis should be ruled out prior to treatment of suspected inflammatory bowel disease because corticosteroid therapy worsens amebiasis.
• A less common form of intestinal disease, ameboma, results from formation of annular colonic granulation in response to the infecting amebae, resulting in a large local lesion of the bowel. It presents as a right lower quadrant abdominal mass, which may be mistaken for carcinoma, tuberculosis, Crohn disease, actinomycosis, or lymphoma. Biopsy findings assist in establishing the correct diagnosis.
• Amebic liver abscess is the most common form of extraintestinal amebiasis.
• It results from spread of the organisms from the intestinal submucosa to the liver via the portal system. However, approximately 40% of patients who have amebic liver abscess do not have a history of prior bowel symptoms. 
• Amebic liver abscess occurs in as many as 5% of patients with symptomatic intestinal amebiasis and is 10 times as frequent in men as in women. 
• Approximately 80% of patients with amebic liver abscess present within 2-4 weeks of infection. An estimated 95% of amebic liver abscesses related to travel develop within 5 months.
• Amebic liver abscess presents with fever and a constant, dull, upper right abdominal or epigastrium pain. Involvement of the diaphragmatic surface of the liver may lead to right-sided pleuritic pain or referred shoulder pain. Associated GI symptoms occur in 10-35% of patients and include nausea, vomiting, abdominal distention, diarrhea, and constipation. 
• A small subset of patients with amebic liver abscess has a subacute presentation with vague abdominal discomfort, weight loss, and anemia. Jaundice is unusual. 
• Pleuropulmonary amebiasis is most commonly the result of contiguous spread from a liver abscess rupturing through the right hemidiaphragm. However, a case of amebic lung abscess acquired through hematogenous spread has been reported. The typical age group is 20-40 years. The male-to-female ratio is 10:1. Approximately 10% of patients with amebic liver abscess develop pleuropulmonary amebiasis, which presents with cough, pleuritic pain, and dyspnea. A hepatobronchial fistula is an unusual problem characterized by the expectoration of sputum resembling anchovy paste. The trophozoites of E histolytica may be found in the sputum sample.
• Amebic peritonitis is generally secondary to a ruptured liver abscess. Left lobe liver abscesses are more likely to rupture. Patients present with fever and rigid distended abdomen. Roughly 2-7% of liver abscesses rupture into the peritoneum.
• Amebic pericarditis is rare but is the most serious complication. It is usually caused by a rupture of the left liver lobe abscess and occurs in 3% of patients with hepatic amebiasis. It presents with chest pain and the features of congestive heart failure.
• Amebic abscesses resulting from hematogenous spread have occasionally been described in the brain Cerebral amebiasis has an abrupt onset and rapid progression to death in 12-72 hours. The patient presents with altered consciousness and focal neurologic signs. CT scanning reveals irregular lesions without a surrounding capsule or enhancement. A tissue biopsy sample reveals the trophozoites.
• Genitourinary involvement may cause painful genital ulcers or fallopian tube amebiasis.

Physical

• Patients with acute amebic colitis may have lower quadrant abdominal tenderness. Fever is noted in only a minority of patients. Dehydration is uncommon. Occult blood is nearly always present in stools.
• Amebic liver abscess may present with fever and tender hepatomegaly. Right lower intercostal tenderness may be elicited, particularly posteriorly. Breath sounds may be diminished at the right lung base, and rales may be heard. A small subset of patients has a subacute presentation with hepatomegaly, weight loss, and anemia. Jaundice is unusual.
• Pleuropulmonary amebiasis may produce findings of right-sided pleural effusions, empyema, basilar atelectasis, pneumonia, and lung abscess.
• Patients with amebic peritonitis present with fever and a tender, rigid, and distended abdomen. Amebic pericarditis presents with features of congestive heart failure. A pericardial friction rub may be audible.
• Cerebral amebiasis presents with altered consciousness and focal neurologic signs. CT scanning reveals irregular lesions without a surrounding capsule or enhancement.
• Genital ulcers due to amebiasis have a punched-out appearance and profuse discharge.

Causes

Amebiasis is a parasitic infection caused by the protozoon E histolytica.

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