Amebic Colitis: New Insights into
Pathogenesis and Treatment
Tracy E. Bercu, MD, William A. Petri, Jr, MD, PhD,
and Brian W. Behm, MD
Corresponding author
William A. Petri, Jr, MD, PhD
Division of Infectious Diseases and International Health,
University of Virginia Health System, P.O. Box 801340,
Charlottesville, VA 22908, USA.
E-mail: Wap3g@virginia.edu
Current Gastroenterology Reports 2007, 9:429–433
Current Medicine Group LLC ISSN 1522-8037
Copyright © 2007 by Current Medicine Group LLC
Amebiasis, caused by the protozoan parasite Entamoeba
histolytica, affects more than 50 million people world-
wide, with over 100,000 deaths annually. The majority
of cases are asymptomatic; however, significant mor-
bidity and mortality are associated with illness in the
remaining 10% of cases. Recent advances in the under-
standing of the mechanism of infection by E. histolytica,
the role of the innate immune system, and the role of
genetic disposition to infection will allow the develop-
ment of novel detection and treatment methods. The
disease mechanisms, clinical findings, therapeutic strat-
egies, and important developments regarding amebiasis
are discussed here.
Introduction
Infection with Entamoeba histolytica organisms com-
monly produces amebic colitis, and less often, amebic
liver or brain abscesses. In developing countries, colo-
nization with E. histolytica has been observed in 5%
or more of poor children. In a 4-year study in Dhaka,
Bangladesh, 40% of preschool children were found to be
infected with E. histolytica annually [1]. In Hue City,
Vietnam, the annual incidence of amebic liver abscesses
has been reported to be 21 cases/100,000 inhabitants [2].
Long-term effects of E. histolytica disease have been
associated with malnutrition and decreased cognitive
abilities in preschool children [3]. In addition, approxi-
mately 3% of returning travelers with an acute diarrheal
illness requiring medical care have been found to have
amebiasis [4]. Globally, more than 50 million people are
infected annually, and amebic dysentery remains a com-
mon cause of illness worldwide.
Pathogenesis
Amebic infection is initiated through ingestion of fecally
contaminated water or food containing E. histolytica
cysts. After ingestion, the cysts pass through the stomach
and into the small intestine, where excystation occurs
in the terminal ileum, resulting in production of motile
and potentially invasive trophozoites. The trophozoites
then aggregate in the intestinal mucin layer within the
colon and cecum, where they form new cysts, which are
excreted in feces and can survive for weeks in a hospitable
environment. Infection can lead to intestinal colonization,
colitis, or extraintestinal disease from the hematogenous
spread of trophozoites to the liver, brain, and lungs. The
acquisition of E. histolytica infection is usually associ-
ated with exposure through residence in an endemic area
for longer than 1 month and is often only detected when
symptomatic disease results.
Amebic colitis occurs when the Entamoeba tro-
phozoite penetrates the intestinal mucus layer, killing
epithelial cells, neutrophils, and lymphocytes, all the
while evading the host immune system. This ability of
E. histolytica to lyse tissue is the characteristic for which
the organism is named. The clinical syndrome of intes-
tinal amebiasis occurs only after direct invasion of the
intestinal epithelium. The trophozoite galactose-binding
(Gal/GalNAc) surface lectin mediates parasite adherence,
cytolysis, and phagocytosis of human cells, allowing
invasion. Cytolysis occurs through rapid increases in
host cell cytosolic Ca2+, calpain activation, and caspase
3–induced apoptosis [5]. Cell death leads to exposure of
phosphatidylserine (PS) on the outer host cell membrane
and subsequent recognition of PS by E. histolytica ulti-
mately leads to phagocytosis, a characteristic required
for virulence [6]. A recent study provides evidence that
the microenvironment of the host intestine, particularly
intestinal mucins and bacteria, appear to enhance expres-
sion of specific genes, which affects the E. histolytica
phenotype, enhancing phagocytosis [7•]. Decreased
parasite adherence and virulence have also been shown
to occur through downregulation of transcription and
expression of the light subunit of the amebic lectin when
E. histolytica is cultivated with Escherichia coli serotype
O55, known to bind strongly to the Gal/GalNAc amebic
430 Large Intestine
lectin [8]. In order for E. histolytica to cause invasive
intestinal and extraintestinal infection, it must disrupt
the protective mucus layer. Cysteine proteases secreted
from the ameba appear to cleave specific cysteine-rich
domains of the MUC2 mucin, the major structural com-
ponent of the colonic mucus gel, thereby disrupting the
mucus barrier [9••].
Many of the most recent studies concerning the patho-
genesis of intestinal amebiasis focus on host immunity in
relation to disease susceptibility. Preliminary data from
a study conducted in Dhaka, Bangladesh has shown that
mucosal IgA against the carbohydrate recognition domain
of the Gal/GalNAc lectin is associated with short-lived (1.5
years) protection from E. histolytica infection and disease.
In addition, increased systemic interferon gamma production
in response to amebic antigen was found to predict future
asymptomatic infection in children [10]. Preliminary results
from a study investigating genetic predisposition of humans
to disease has shown that HLA regions DQB1/DRB1 appear
to be associated with protection from invasive and multiple
infections with E. histolytica. Another yet unpublished study
found that two genotypes (05 and 44) were associated with
asymptomatic and symptomatic infections, respectively.
Clinical Manifestations
Approximately 90% of cases of intestinal infection
with E. histolytica result in intestinal colonization.
Patients with noninvasive infection may present with
a number of nonspecific gastrointestinal complaints
along with nonbloody diarrhea and normal mucosa on
colonoscopy. In contrast to bacterial dysentery, which
typically presents with a rapid onset of symptoms,
patients with amebic colitis tend to present with more
insidious symptoms. Commonly, patients present with
a 1-week to several-week history of cramping abdomi-
nal pain, watery or bloody diarrhea, and weight loss.
Only one third of patients are febrile, and most do not
exhibit grossly bloody stools. However, virtually all
patients with amebic colitis will have heme-positive
stools on further testing. Unusual manifestations of
amebic colitis include acute necrotizing colitis, toxic
megacolon, perianal ulceration with fistula forma-
tion, and ameboma (resulting from intraluminal tissue
granulation). The colonic lesions in amebic colitis may
appear as classic flask-shaped ulcerations, thickening
of the mucosal wall, or necrosis of the intestinal wall,
depending on the degree of invasion (Fig. 1). Because of
the varying clinical manifestations, amebic colitis may
masquerade as shigellosis, inflammatory bowel disease,
ischemic colitis, or even carcinoma of the colon [11].
Diagnosis
Diagnosis of intestinal amebic infection in developed coun-
tries is typically through a combination of serology and
antigen detection using either enzyme-linked immunosor-
bent assay (ELISA) or polymerase chain reaction (PCR)
methods. Serum ELISA detection of antibody to E. histo-
lytica has a sensitivity of greater than 65% and specificity
of greater than 90%, which can be misleading because more
than 90% of patients recovering from amebiasis have detect-
able serum antibodies [12]. Thus, additional testing must be
completed. ELISA testing for stool antigen has greater than
95% sensitivity and specificity. The E. histolytica II stool
antigen detection test (TechLab, Blacksburg, VA) is the only
test that meets the World Health Organization recommen-
dation for E histolytica–specific diagnosis. Other methods
do not distinguish E. histolytica from the nonpathogenic
species E. dispar. Traditional PCR for E. histolytica has a
sensitivity of 72% and specificity of 99% [13].
Colonoscopy is also useful for the diagnosis of amebic
colitis but is not required if stool antigen detection or PCR
is positive. Amebic colitis can appear as punctuate hemor-
rhagic areas or small ulcers (up to centimeters in diameter)
with exudative centers and hyperemic borders. The cecum
and ascending colon are affected most commonly, although
in severe disease the entire colon may be involved. In addi-
tion, early in the infection process, endoscopy results may
be entirely normal. As disease progression occurs, mucosa
may become hyperemic due to inflammatory changes, and
pseudomembranes can occur, resembling inflammatory
bowel disease. Biopsy or aspirate from colonic ulcers can
be examined microscopically for motile trophozoites. The
use of cathartics or enemas in preparation for colonoscopy
should be avoided because these preparations can interfere
with morphologic identification of the parasite [11]. Stool
antigen detection can also be difficult in the early stages of
disease, and thus a high degree of suspicion is required for
accurate diagnosis.
In developing countries, where amebiasis is endemic,
diagnostic methods are limited due to lack of advanced
technology. Microscopic identification remains the most
common means of diagnosis. New methods of bedside
testing for Entamoeba infections are being developed.
Recent research using prototype rapid antigen and rapid
antibody bedside testing for E. histolytica has shown
that these tests are reliable for diagnosis of amebiasis
in endemic areas [14]. Further research is underway to
improve these methods of bedside detection.
Diagnosis of extraintestinal disease can be difficult
without invasive testing. Amebic liver abscesses appear
identical to bacterial abscesses by ultrasound or CT,
and it is rare to identify E. histolytica in stool samples
from patients with liver abscesses. Recently, it has been
shown that the Techlab Entamoeba histolytica II anti-
gen detection test can be used to diagnose patients with
amebic liver abscesses with an accuracy of 96% [15].
The diagnosis of patients with amebic brain abscesses
can also be difficult. A recent case report described the
successful use of PCR of cerebrospinal fluid for diag-
nosis of an amebic brain abscess [16]. This method

Figure 1. Endoscopic appearance of amebiasis on colonoscopy. (Fig. 1A appears with permission from Haque et al. [21]; other panels are
from the slide collection of the late Dr. Harrison Juniper.)
appears to be effective and fast as a means to diagnose
amebic central nervous system infection.
Treatment and Prevention
Asymptomatic intestinal colonization with E. dispar
does not require treatment; however, all infections with
E. histolytica should be treated to reduce the risk of inva-
sive disease and transmission to others. Treatment plans
depend upon the site of infection and severity of disease.
Currently there is no known resistance in vivo to exist-
ing antimicrobial agents. Tinidazole has recently been
Amebic Colitis Bercu et al. 431
approved for use within the United States for treatment
of amebiasis. This medication requires a shorter course
of treatment than metronidazole and has been shown to
be as effective. Generally, asymptomatic luminal infec-
tion may be treated with paromomycin, 500 mg three
times a day (30 mg/kg/d divided into three doses) for 7
days. The main side effect of paromomycin is diarrhea.
Symptomatic intestinal amebiasis should be treated with
either tinidazole, 2 g/d for 3 days, or metronidazole, 750
mg three times a day for 10 days, followed by paromomy-
cin, 500 mg three times a day for 7 days. Extraintestinal
amebiasis should be treated with either tinidazole, 2 g/d
432 Large Intestine
for 3 to 5 days, or metronidazole, 750 mg three times
a day for 10 days, followed by paromomycin, 500 mg
three times a day for 7 days.
Vaccines against Entamoeba infection are also under
investigation. Most vaccines use the galactose and N-ace-
tyl-d-galactosamine–specific (Gal/GalNAc) lectin on the
surface of the ameba to stimulate an immune response.
One gerbil model used the E. histolytica galactose-inhib-
itable lectin fused to the Yersinia outer protein E (YopE)
to convey immunity against amebic liver abscesses [17•].
Another promising study used intranasal and intraperi-
toneal vaccination of mice with the native E. histolytica
lectin, which was found to prevent intestinal infection,
with efficacies of 84% and 100%, respectively [18]. Most
recently, the LecA gene was expressed for the first time
in transgenic plants through integration into chloroplast
genomes. Subcutaneous immunization of mice with
crude extract of the transgenic leaves resulted in high IgG
titers [19]; however, it is still unclear whether increased
IgG titers would provide protection against subsequent
infection. Use of transgenic plants for synthesis of this
lectin, should it prove antigenic, would enable economic
mass production of vaccines in the future. Currently,
no human vaccine trials have been undertaken.
Prevention of disease is aimed at purifying water in
endemic areas. Because amebic cysts are not killed by low
doses of chlorine or iodine, boiling of water is required
to ensure eradication of amebas. Vegetables must be
treated by washing in a detergent soap and then soaking
them in vinegar for 10 to 15 minutes to eliminate cysts.
One recent study in the United States showed a reduc-
tion in diarrheal illnesses caused by Giardia lamblia,
Cryptosporidium, Shigella flexneri, and E. histolytica
infection with the use of an extensive handwashing regi-
men in AIDS patients [20].
Conclusions
Intestinal amebiasis continues to cause considerable
morbidity and mortality worldwide. Through improved
technology and understanding of the parasitic and the
human genome as well as the host response to infection,
we will continue to develop insight into the complex
interactions that mitigate severe disease associated with
E. histolytica infection. In addition, the long-term cognitive
effects of diarrheal illness associated with E. histolytica are
just beginning to be understood. As technology develops,
novel diagnostic methods and treatments will continue
to be improved. Because purification of all water sources
in areas endemic with E. histolytica would be difficult to
achieve, progress in vaccine development would provide the
best method of limiting disease. Until that time, continued
advancement in the tools required to further understand
the genetic basis of disease may provide the most insight
into the pathophysiology of amebic colitis.
References and Recommended Reading
Papers of particular interest, published recently,
have been highlighted as:
• Of importance
•• Of major importance
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abscess in central Vietnam. Am J Trop Med Hyg 2002,
66:578–583.
3. Tarleton, JL, Haque R, Mondal D, et al.: Cognitive effects
of diarrhea, malnutrition, and Entamoeba histolytica infec-
tion on school age children in Dhaka, Bangladesh.
Am J Trop Med Hyg 2006, 74:475–481.
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Amebic Colitis Bercu et al. 433
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