Indian J Gastroenterol (July–August 2012) 31(4):153–162
DOI 10.1007/s12664-012-0192-2
REVIEW ARTICLE
Amebic infection in humans
Gourdas Choudhuri & Murali Rangan
Received: 19 January 2012 / Accepted: 21 May 2012 / Published online: 19 August 2012
# Indian Society of Gastroenterology 2012
Abstract Clinical human infections with the protozoa
Entamoeba histolytica is still estimated to occur in 50 mil-
lion people worldwide, of which approximately 100,000 die
annually. Although most clinical symptoms are due to in-
volvement of the large intestine, 1 % present with involve-
ment of the liver in the form of a liver abscess, a potentially
fatal condition. Distinguishing an invasive form (E. histo-
lytica) from a morphologically identical non-invasive one
(E. dispar) requires molecular or enzymatic characteriza-
tion. Further, the pattern of infection, interpretation of pres-
ence of antibodies in the host, manifestations of disease,
approach to investigations and strategies for management
remain complex. This article also provides a comprehensive
review of the parasite and host factors that govern the
complex relationship of the prozoa and humans, and tries
to explain why some develop a particular form of the disease
in endemic zones. Application of modern imaging and im-
age guided therapy seems to be playing a major role in
diagnosis and management of the potentially most serious
form of the disease, amebic liver abscess. Despite lack of
controlled studies there is a tendency to lower the threshold
of their use in clinical practice, and indeed in-hospital mor-
tality rate seems to be falling for amebic liver abscess. In a
world getting increasingly swamped by non-infectious met-
abolic diseases, awareness of amebic infections, its bed-side
diagnosis, the use of appropriate laboratory tests, and deci-
sion making in management are shrinking. This review tries
to update the scientific developments in amebiasis.
G. Choudhuri (*) : M. Rangan
Department of Gastroenterology,
Sanjay Gandhi Postgraduate Institute of Medical Sciences,
Lucknow 226 014, India
e-mail: choudhuri.gour@gmail.com
Keywords Colitis . Entamoeba histolytica . Liver abscess .
Parasites . Zymodemes
Introduction
Even though amebic infection is globally distributed, most
of the morbidity and mortality resulting from it is seen in the
developing world especially the Indian subcontinent, Cen-
tral and South America and Africa. Approximately 50 mil-
lion people suffer from symptomatic infections and 40,000
to 100,000 die every year across the globe from them [1]. A
number of cases and outbreaks have been reported from
Mexico, Hue city in Vietnam, and Egypt [2–4]. The most
infamous single point source outbreak was reported from a
hotel in Chicago in 1933, where mixture of water between
sewage and tap-water pipes led to at least 800 cases of
amebiasis. A cross-sectional population survey conducted
in two adjacent villages in rural India documented E. histo-
lytica in 18.1 % of fecal smears and antiamebic antibodies in
28.7 % subjects [5]. In a 3 year study in pre-school children
in Dhaka, 2.2 % developed amebic dysentery [6].
Amebic liver abscess (ALA) develops in less than 1 % of
patients infected with E. histolytica, but still represents a
large number of patients with a dramatic, potentially fatal
illness. While the frequency of “Western” diseases such as
diabetes, hypertension and coronary artery disease have
skyrocketed in developing countries, “old” diseases such
as amebic infections have not declined significantly, sub-
jecting these populations to a dual burden of diseases. One
study from a single hospital in Vietnam identified more than
1,200 cases of ALA during an 8-year period [3]. In a study
published from Delhi, more than half of the cases of liver
abscess were of amebic etiology [7].
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Organism and life cycle
Entamoeba histolytica, the causative protozoan organism,
bears its name from its ability to destroy host tissues. There
are two morphologically identical strains, one pathogenic
(E. histolytica) and the other non-pathogenic, called E.
dispar. Further, a number of non-pathogenic amebae, such
as E. moshkovskii, E. hartmanni, E. gingivalis, E. coli,
Endolimax nana, and Iodamoeba butschlii, can colonize
the human gastrointestinal tract. Among these, E. mosh-
kovskii has been reported to produce mild gastrointestinal
discomfort [8].
Infection occurs primarily through ingestion of cysts in
fecally contaminated food or water. Unusual modes of
spread, particularly important in homosexuals, include di-
rect transmission through oral and anal sex. E. histolytica
has a simple, two-stage life cycle consisting of an infectious
cyst and a motile trophozoite [9]. The mature cyst measures
5 to 20 μm in diameter and contains four nuclei. The
trophozoite measures 10 to 60 μm and contains a single
nucleus with a central karyosome. Within the lumen of the
intestine, the cyst undergoes nuclear division first followed
by cytoplasmic division, giving rise to eight trophozoites
[9]. Disease occurs with the invasion of the colonic epithe-
lium and wall by trophozoites which may then spread hem-
atogenously to distant sites. Factors that protect the host or
promote invasion in humans are still poorly understood.
Current understanding of pathogenesis
The reason why only some develop invasive amebic infec-
tions among all those exposed to the parasite may have to do
with interplay between virulence factors of the parasite and
defense mechanisms of the host.
Virulence factors
The disease begins with E. histolytica trophozoites that
emerge after excystation adhering to colonic epithelial cells
through the lectin, galactose/N-acetyl-D-galactosamine
[10]. Human cells touched by amebic trophozoites become
immobile within minutes, and lose their cytoplasmic gran-
ules and structures, and eventually their nucleus. Cytolysis
is undertaken by the amebapores, a family of at least three
small peptides capable of forming pores in lipid bilayers of
cells [11]. E. histolytica trophozoites can also kill mamma-
lian cells by induction of programmed cell death or apopto-
sis via the caspase pathway [12].
Invasion of the parasite through the mucosa into the
submucosa is the hallmark of amebic colitis with lateral
extension by digestion of host tissue proteins giving rise to
the classic flask-shaped ulcers seen in cross section. E.
Indian J Gastroenterol (July–August 2012) 31(4):153–162
histolytica secretes cysteine proteinases that digest extracel-
lular matrix proteins and cause invasion and inflammation
of the gut and liver. So far, seven distinct genes encoding
pre-pro forms of papain-family proteinases have been iden-
tified [13]. E. histolytica trophozoites can secrete 10–1,000
times more cysteine proteinase than E. dispar [13]. These
enzymes activate host inflammatory response by amplifying
interleukin-1 [14] and, via the transcription factor NFkB
pathway trigger interleukin-1B, interleukin-8, and cycloox-
ygenase (COX)-2. By lysing neutrophils, they can release
mediators that cause diarrhea and tissue damage.
Invasive disease can be caused only by E. histolytica,
which can be distinguished from its non-virulent form E.
dispar by cultural characteristics [15], virulence in animal
models or tissue culture, selective agglutination by lectins
[16], reaction with monoclonal antibodies [17], isoenzyme
patterns [18], ribosomal RNA sequence analysis and restric-
tion fragment length polymorphism analysis [19]. Differ-
ences in virulence may be based on the genetic
background of E. histolytica strains [20]. tRNA-linked short
tandem repeats (STR) loci were found to be useful as
genetic markers in identifying virulent and avirulent strains
of E. histolytica [21].
Zymodemes
Based on the isoenzyme patterns of four enzymes: glucose
phosphate isomerase (GPI), hexokinase (HK), malate en-
zyme (ME), and phosphoglucomutase (PGM), 20 strains
or sub-types of amebae called zymodemes can be identified
[22–24]. The enzyme markers associated with pathogenicity
are the presence of a fast-moving band of hexokinase, and
presence of a β band and absence of α band of PGM [25].
Zymodemes II, VI, VII, XI, XII, XIII, XIV, XIX, and XX
are pathogenic of which II and XI are often isolated from
liver abscesses [26].
Usually only one strain colonizes the colon of a host and
tends to remain consistent with regard to its isoenzyme
pattern over time; hence persons harboring non-pathogenic
zymodemes may not require treatment.
Host immunity
The role of immunity in amebic infection is unclear. Nearly
everyone with invasive amebiasis develops a systemic and a
mucosal humoral immune response that can be measured by
several immunologic tests. Several observational studies
from Mexico [27] and India [5] suggest that the presence
of antibodies is associated with lower rates of infection. It
has also been seen that more than 90 % of individuals
colonized by E. histolytica spontaneously clear the infection
within 1 year, suggesting the development of an effective
immune response. Cross-sectional field studies have shown
Indian J Gastroenterol (July–August 2012) 31(4):153–162 155

an inverse relationship between presence of serum antibod- Table 1 Clinical syndromes associated with E. histolytica infection
ies and cysts in the stools suggesting some protective role of Intestinal amebiasis Extraintestinal amebiasis
antibodies [5]. Also, serial follow up of asymptomatic cyst
passers who were initially seronegative, showed clearing of • Asymptomatic cyst passers • Amebic liver abscess
the luminal infection by the host with the development of • Acute amebic colitis • Perforation and peritonitis
antibodies [28]. In patients with ALA, antibodies develop Mucosal disease • Pleuropulmonary amebiasis
by the seventh day and may persist for as long as 10 years Transmural disease • Amebic pericarditis
[29]. They are directed at the GalNAc lectin but their de- Ulcerative post-dysenteric colitis • Cutaneous amebiasis
velopment does not halt the progression of disease [30]. In a • Appendicitis
study in Bangladesh, mucosal IgA antibodies in children • Ameboma
were associated with a short-lived acquired resistance to E. • Amebic stricture
histolytica infection [31]. The Th1 immune response may
also have a role to play, but its mechanism and effects are
unclear [32]. 33–35]. Chronic large bowel symptoms do not therefore
seem to have any association with either past or present
infection with E. histolytica, questioning the existence of
Pathology the clinical entity of non-dysenteric intestinal amebiasis.
Acute amebic colitis presenting with dysentery, some-
An influx of neutrophils occurs early in infection, but few times with the presence of frank blood, is commonly seen
inflammatory cells are seen in well established ulcers. in endemic regions. The nature and intensity of symptoms
Organisms may show ingested red blood cells (erythropha- are highly variable. The risk factors include alcoholism,
gocytosis). Amebic colitis may morphologically appear as malnutrition, extremes of age, pregnancy, therapy with cor-
mucosal thickening, multiple discrete ulcers separated by ticosteroids and homosexual behavior. In contrast to bacte-
regions of normal-appearing colonic mucosa, diffusely in- rial dysentery, which typically begins abruptly, amebic
flamed and edematous mucosa, necrosis and sometimes colitis has a gradual onset over 1 or more weeks (Table 2).
perforation of the intestinal wall. The cecum and ascending Although more than 90 % of patients with amebic colitis
colon are affected most commonly, although in severe dis- present with diarrhea and tenesmus, frank blood in stools
ease the entire colon may be involved. and fever are rare. The most feared complication of amebic
dysentery, acute necrotizing colitis with toxic megacolon,
occurs in 0.5 %, manifests as an acute dilatation of the
Clinical features colon, and carries a high mortality. Other unusual compli-
cations include the formation of enterocutaneous, rectova-
Intestinal amebiasis ginal, and enterovesicular fistulas and ameboma.
Ameboma, a proliferative granulomatous inflammation
Detection of amebic cysts in the stool of asymptomatic occuring at ulcer site resulting in an infectious pseudotumor,
people is common and usually indicates infection with rarely develops and become the leading point of an intus-
non-pathogenic strains that remain as commensals in the susception or cause intestinal obstruction. Severe amebic
host’s lumen [5]. As there is no tissue invasion, antibodies colitis may result in perforation and peritonitis, bleeding,
are usually not detected in the serum. Cyst passers rarely colonic stricture formation, colocutaneous fistula and intus-
develop features of invasive amebiasis on long term follow susception. The term post-amebic colitis is used for
up [28, 33], with more than 90 % eradicating the parasite
spontaneously within a year. The mere presence of amebic
Table 2 Comparison of clinical features in amebic colitis and invasive
cysts in stools of asymptomatic people, therefore, does not bacterial dysentry
merit treatment with cysticidal drugs (Table 1).
Non-invasive amebic infection as well as chronic mild Features Amebic colitis Invasive bacterial
dysentery
colonic symptoms can both occur fairly commonly in the
community, their co-existence often suggesting a causal role Usual duration of symptoms >7 days 2–7 days
and a diagnostic label of “chronic amebiasis”. Several ele- Diarrhea 94 %–100 % 100 %
gant studies have disproved this assumption, and shown that Fecal occult blood 100 % 40 %
the frequency of colonic symptoms, serological evidence of Abdominal pain 12 %–80 % 50 %
E. histolytica infection, histological abnormalities, or re- Weight loss Common Unusual
sponse to therapeutic trial with metronidazole are no differ- Fever >38 °C Minority Majority
ent between cyst-positive and cyst-negative individuals [28,
156
nonspecific colonic symptoms that may persist following a
bout of severe acute amebic colitis. In such cases, the colon
is free of parasites and the clinical findings resemble those
of irritable bowel syndrome.
Extraintestinal amebiasis
Less than 1 % of the infections are extraintestinal, of which
amebic liver abscess is overwhelmingly the most common.
Other extraintestinal sites of infection rarely occur and typ-
ically result either from direct extension of liver abscesses
(e.g. amebic pericarditis or lung abscess) or hematogenous
spread (e.g. brain abscess).
Liver abscess
ALA develops in less than 1 % of those infected but still
represents a large number of patients with men aged 18 to 50
being disproportionately affected (M:F 10:1) [36–38]. The
underlying reason for this huge gender difference is not
clear, but alcohol consumption in men and protective effects
of hormones and iron deficiency anemia among menstruat-
ing women has been postulated. Alcohol impairs Kupffer
cell function and can impair both cellular and humoral
immunologic responses [39].
Although liver abscess develops after intestinal infection,
and patients rarely remember a recent attack of dysentery,
ulcers are found in the large bowel on colonoscopy in more
than half of patients with ALA [40]. Multiple, large, and
left-sided ulcers were more common in elderly patients and
in those in whom diarrhea was the presenting symptom.
The common site for ALA is the posterior, external and
superior portions of right lobe of the liver and occurs as a
single lesion in 30 % to 70 %. Unusual presentations include
multiple abscesses, left lobe abscesses, abscesses presenting
as compressive lesion, and abscesses rupturing into viscera.
The clinical presentation is usually abrupt, with high
fever followed by pain in the upper abdomen. Fever is
present in most cases; occurs frequently in spikes, but is
sometimes constant over several days, with rigors and pro-
fuse sweating. The pain is constant, and may be intense and
radiate to the scapular region and right shoulder, sometimes
increasing with coughing or deep breathing. Anorexia,
weight loss, non-productive cough, nausea, vomiting, diar-
rhea or dysentery may be present. Physical examination
reveals a febrile patient with tenderness over an enlarged
liver or over right lower intercostal spaces.
Multiple liver abscesses
Fifteen percent of patients have multiple abscesses and
present with fever, toxemia, deep jaundice, and encephalop-
athy. Toxemia is suggestive of an added bacterial infection
Indian J Gastroenterol (July–August 2012) 31(4):153–162
leading to a more severe disease. E. coli and Klebsiella are
the commonly cultured organisms. Presentation with jaun-
dice and encephalopathy may resemble acute liver failure
[41, 42].
Left lobe abscess
Thirty-five percent of patients present with a left lobe ab-
scess, half having associated lesions in the right lobe [43].
These patients have longer duration of symptoms (3-
4 weeks) and present with an epigastric lump. Risk of
serious, often life-threatening complications due to rupture
are higher, and can lead to pericardial effusion or tampo-
nade, pleural effusion or peritonitis. Timely removal of pus
by catheter drainage or needle aspiration is more often
needed in these patients in addition to antiamebic drugs.
Compression lesions
A posteriorly located ALA in the right lobe may present as
inferior vena cava obstruction or hepatic outflow obstruction
[44]. This is suggested by bilateral pedal edema, ascites, and
visible veins on anterior and posterior abdominal wall,
which disappear after resolution of the abscess.
Extension of the abscess
Leakage of the abscess may occur into the pleural cavity,
with empyema thoracis, or into the pericardium causing
cardiac tamponade. Intraabdominal extension following per-
foration into the peritoneal cavity is usually associated with
shock and generalized peritonitis and may occur in up to
7 % of cases. Rupture into the colon and biliary tree has also
been reported. A subhepatic collection may also be localized
and walled off. Such presentations, though infrequent, occur
in patients who are diagnosed late, and account for most of
the mortality associated with the disease.
Jaundice in ALA
Hyperbilirubinemia occurs in 6 % to 29 % of cases and is
attributed to various mechanisms, such as pressure on bili-
ary ducts, intrahepatic or canalicular cholestasis [45, 46].
Bromosulfophthalein excretion, which represents the biliru-
bin transport maximum of hepatic parenchymal cells, is
significantly reduced. Damaged biliary ducts and hepatic
veins in amebic liver abscess may sometimes form bilio-
vascular fistulae. When it involves a venous system (portal
or hepatic), the pressure gradient directs the bile and blood
mixture toward the right side of heart - termed bilhemi,
leading to a rapid rise of bilirubin without much increase
in liver enzymes [47]. Normalization occurs with effective
drainage of pus or bile [48].
Indian J Gastroenterol (July–August 2012) 31(4):153–162
Diagnosis
The gold standard for the diagnosis of amebic colitis
remains finding of hematophagous trophozoites of E.
histolytica in microscopic examination of fresh stool
specimen or colonoscopic detection of typical ulcers with
biopsy showing trophozoites. Since the cecum and as-
cending colon are most frequently affected in amebiasis,
colonoscopy is preferred to sigmoidoscopy. Classically,
multiple punctate ulcers measuring 2 to 10 mm are seen
with normal intervening tissue; the colonic epithelium,
however, may simply appear indurated with no visible
ulcerations, and, in severe cases where the ulcers have
coalesced, the epithelium may appear necrotic or resem-
ble that of ulcerative colitis. Histologic examination of a
biopsy specimen taken from the edge of an ulcer reveals
amebic trophozoites and a variable inflammatory infil-
trate. Identification of amebae can be aided by periodic
acid–Schiff staining of biopsy tissue, which stains troph-
ozoites magenta.
Microscopy
Microscopic techniques employed in a diagnostic clinical
laboratory include wet preparation, concentration, and perma-
nently stained smears for the identification of E. histolytica in
feces. Microscopic examination of a direct saline (wet) mount
is a very insensitive method (<10 %) as it has to be performed
within 1 h on fresh specimen. As Entamoeba trophozoites
generally degenerate rapidly in unfixed fecal specimens [49],
specimens should be preserved with a fixative, (e.g. Schau-
dinn’s fluid) and stained (e.g. Trichrome, iron-hematoxylin).
Atleast 3 stool examinations within 10 days improves the
detection rate to 85 % to 95 % [50]. The presence of RBCs
in the cytoplasm is still considered diagnostic for E. histolytica
in patients with dysentery and may be used to distinguish
between E. histolytica and E. dispar.
Culture methods
Culture techniques for the isolation of Entamoeba species
include xenic (diphasic and monophasic) and axenic sys-
tems. Xenic cultivation is the growth of the parasite in the
presence of an undefined flora [51] while axenic one
involves growing them in the absence of any other metab-
olizing cells [51]. Culture of E. histolytica can be performed
from fecal specimens, rectal biopsy specimens, or liver
abscess aspirates. The success rate for culture of E. histo-
lytica is between 50 % and 70 % in reference laboratories
and of E.dispar much less as the latter is quite fastidious
[51]. It is however expensive, time consuming, not easily
available, and hence not used as a routine diagnostic
procedure.
157
Isoenzyme analysis
A total of 24 different zymodemes have been described, of
which 21 are from human isolates (9 of E. histolytica and 12
of E. dispar). There are three main ones for E. histolytica (II,
XIV, and XIX) and one for E. dispar (I). A fast moving band
of Hexokinase is usually associated with invasive forms,
while non-invasive strains demonstrate a slow moving band.
Isoenzyme analysis, being cumbersome and complicated,
has been superseded by DNA-based methods for profiling
the parasite.
Antibody detection tests
Serological tests that detect antibodies to E. histolytica indicate
present or prior infection and are of particular value in areas of
low endemicity. Many different assays have been developed for
the detection of antibodies, including indirect hemagglutina-
tion, latex agglutination, immunoelectrophoresis, gel diffusion
test, counter-immunoelectrophoresis, immunodiffusion,
complement fixation, indirect immunofluorescence assay
and enzyme-linked immunosorbent assay (ELISA) [52].
ELISA is the most popular assay in diagnostic laboratories
throughout the world and has been used to study the
epidemiology of asymptomatic disease and the diagnosis
of symptomatic amebiasis after fecal examination. The
tests are strongly positive in patients with invasive disease
such as ALA, and have sensitivity often reaching 100 %
[53] within 7 days of infection. In endemic zones, the mere
presence of antibodies in a doubtful clinical setting does
not help make a diagnosis.
Antigen detection tests
Immunological tests can detect amebic antigen in samples
such as liver pus, or stools. Their sensitivity approaches that
of stool culture and are rapid to perform. Antigen-based
ELISA kits that are specific for E. histolytica use monoclo-
nal antibodies against the Gal/GalNAc-specific lectin or the
serine-rich antigen of the parasite.
Polymerase chain reaction (PCR) based tests
PCR can be done in variety of clinical specimens, in-
cluding feces, tissues, and liver abscess aspirate [52].
PCR of the small-subunit rRNA gene (18S rDNA) is
reported to be approximately 100 times more sensitive
than the available ELISA kits [54]. In an attempt to
increase the sensitivity of the PCR assay, a nested mul-
tiplex PCR was developed for the simultaneous detection
and differentiation of E. histolytica and E. dispar from
DNA extracted from microscopy-positive fecal samples
[55]. Utilizing this multiplex technique, the sensitivity
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and specificity were increased to 94 % and 100 %,
respectively. The introduction of real-time PCR, a quan-
titative method increases the sensitivity further. Although
PCR-based methods are very useful, their application in
routine diagnosis is still limited due to difficulties in
DNA extraction from fecal samples and cost and time
involved in the entire process.
Imaging techniques
Chest roentgenography
Abnormalities, seen on average in 59 % of patients, include
an elevated right hemidiaphragm, atelectasis, and right pleu-
ral effusion [56–58].
Ultrasonography
Ultrasonography is the preferred imaging technique for
the detection of amebic abscess because of its lower cost,
noninvasiveness, and quick easy availability. It can also
guide needle aspiration for diagnostic and therapeutic
purposes. The classic ultrasonographic appearance is of
a round or oval homogenous hypoechoic lesion with
borders that appear ill-defined initially, and become
well-defined subsequently, typically located near the
postero-superior surface of the liver. Early lesions may
be hyper or iso-echoic when solid necrotic material is
present, becoming progressively hypoechoic at the center
as the necrosis liquefies [56, 59]. Differentiating amebic
from pyogenic abscess sonographically can be difficult
although the latter tends to be scattered and irregular
walled.
Computed tomography
Computed tomography (CT) may be more sensitive for
smaller lesions, particularly if helical CT is used. They
appear as a hypodense avascular liver mass with well-
defined margins and alternating hypodense and hyperdense
halos after contrast administration. Extrahepatic extension
of the lesion, when present, may be another indicator that
the lesion is amebic in origin [56, 60].
Magnetic resonance imaging
Amebic abscess appears as high-signal intensity on T2-
weighted images. The area around the abscess, adjacent to
the parenchyma, may appear hyperintense or hypointense,
corresponding to areas of edema and hypervascularity inter-
spersed with areas of thrombosis. Magnetic resonance im-
aging may have a role in patients with renal insufficiency
[61, 62].
Indian J Gastroenterol (July–August 2012) 31(4):153–162
Scintigraphy
Nuclear scanning with Technetium Tc99m displays a photo-
penic area. Gallium scanning may be useful in distinguish-
ing amebic abscess from a pyogenic one in patients with a
negative serology or an atypical clinical presentation as the
former does not contain leukocytes within the cavity while
the latter appears as a hot spot [56, 63].
Differential diagnosis
The diagnosis of amebic liver abscess should be considered
in patients presenting with typical clinical features especial-
ly in endemic areas and among those who have recently
traveled to these zones. A history of recent diarrhea, if
present, may help. The principal clinical entities that have
to be distinguished from ALA include other space-
occupying lesions of the liver such as pyogenic liver ab-
scess, echinococcal cyst, and hepatic tumors [64]. A strong-
ly positive amebic serology is often helpful.
Patients with pyogenic liver abscess are more likely to be
older, have significant comorbidities such as diabetes, and have
a history of recent biliary disease and/or surgery. Females, with
a higher frequency of biliary stone disease, are often affected.
The lesions are usually multiple, amebic serology is usually
negative and blood cultures are often positive.
Echinococcal lesions are typically asymptomatic but can
present as an abscess with secondary infection. Eosinophil-
ia, calcification or presence of “daughter” cysts may help
identify them. Malignant hepatic tumors such as hepatoma
may rarely present as cystic lesions and may pose confusion
in cirrhotic patients.
Treatment
Pharmacological treatment
Agents for treatment of amebiasis are categorized as luminal
or tissue amebicides on the basis of the location of their anti-
amebic activity. The luminal amebicides include iodoquinol,
diloxanide furoate, and paromomycin. Tissue amebicides
include nitro-imidazoles (metronidazole, tinidazole, ornida-
zole, secnidazole, satronidazole), nitazoxanide, erythromy-
cin, and chloroquine. Of these, metronidazole and tinidazole
are most popular, with cure rates of over 90 %. The new
antiparasitic nitazoxanide appears to be efficacious, but data
is limited. Erythromycin has no activity against amebic liver
disease, and chloroquine has no activity against intestinal
disease.
If asymptomatic patients with non-invasive disease re-
quire to be treated, a luminal agent alone is adequate.
Indian J Gastroenterol (July–August 2012) 31(4):153–162 159

Patients with amebic colitis should be treated with an oral
nitroimidazole followed by a cysticidal agent to prevent
recurrent disease, if cysts remain in the stool. Most patients
with colitis respond promptly with resolution of diarrhea in
2 to 5 days. Despite conflicting reports on the safety of
metronidazole for the developing fetus during pregnancy,
women with severe disease merit treatment (Table 3).
Aspiration or drainage of abscess
Routine aspiration of liver abscess is not indicated for diag-
nostic or therapeutic purposes [65]. A combination of ultra-
sonographic finding with a positive serology in the
appropriate clinical setting is adequate to start drug therapy.
Aspiration is indicated if there is lack of clinical improve-
ment in 48–72 h, left lobe abscess, thin rim of liver tissue
around the abscess (<10 mm) with impending rupture, and
in seronegative abscesses. The aspirate is reddish brown or
chocolate in colour and resembles anchovy sauce due to
admixture of blood and liquified liver tissue. Antiamebic
therapy alone is as effective as routine needle aspiration
combined with antiamebic therapy in the treatment of
patients with uncomplicated amebic liver abscess [66, 67].
Evacuation of “pus” from the abscess is sometimes re-
quired and can be done either by needle aspiration or by
placement of a percutaneous catheter, the latter scoring over
the former in resolution of symptoms and abscess cavity
[68]. In our experience too, catheter drainage led to prompt
resolution of symptoms and early collapse of the abscess
cavity, with the additional advantage of allowing liquefac-
tion and gradual continuous drainage of pus that was initial-
ly thick and not easy to aspirate through a needle [69–71].
Percutaneous procedure plus metronidazole
vs. metronidazole alone for uncomplicated amebic liver abscess
Rates of resolution of abdominal pain, abscess cavities, hepato-
megaly, and duration of hospitalization were heterogeneous.
Patients with uncomplicated liver abscess may be treated initial-
ly with antiamebic agents alone, with addition of drainage by
catheter offered to those who either fail to respond or show
features of impending rupture.
Outcome
In most cases, clinical improvement with antiamebic drug
therapy alone is seen within a few days to a week. Radio-
logic disappearance of the cavity may however take 3 to 9
(range 3 to 131) months. Three patterns of radiologic reso-
lution of ALA have been described: (1) rapid resolution
within 3 months in one third of the patients, (2) gradual
reduction of abscess with complete disappearance within
12 months in two-thirds, or (3) rapid reduction in size up
to about 25 % of initial volume in 3 months, and then
persistence of the cavity for a prolonged period of time up
to 19 months in a small percentage (5.9 %) of patients [73].
Follow up imaging studies are not necessary in patients who
have clinical resolution after treatment for uncomplicated
ALA.
Surgery
Open surgical drainage is rarely indicated and may be re-
quired in the setting of a large abscess with a poor yield on
needle aspiration or clinical deterioration despite attempted
needle aspiration, and in complicated ALA [74]. Surgical
mortality is, however, very high. Hence, it should only be
used when the cavity has ruptured into adjacent viscera or
peritoneum.
Role of endoscopy

A Cochrane review analyzed 7 randomised trials comparing an
image-guided percutaneous procedure plus metronidazole vs.
metronidazole alone in patients with uncomplicated amebic liver
abscess [72]. Pooled analysis of three homogenous trials showed
that needle aspiration did not significantly improve fever reso-
lution (RR 0.60, 95 % confidence interval (CI) 0.22 to 1.61).
Various endoscopic treatment modalities have been used for
patients with bilhemia, including biliary drainage by sphinc-
terotomy, stenting, nasobiliary drain, balloon occlusion of
fistula, and covered stent placement [75–79]. The principle
of therapy of bilio-vascular fistula is to decrease the pressure
gradient across the Oddi sphincter, thereby causing reversal

Table 3 Medical treatment of

amebic infection Drugs Dose Duration

Intraluminal infection Diloxanide furoate 500 mg TID 20 days

Paromomycin 30 mg/kg/day 10 days (in 3 divided doses)
Iodoquinol 650 mg TID 20 days
Invasive colitis Metronidazole 800 mg TID 5 days
Tinidazole 1 gm BD 3 days
Amebic liver abscess Metronidazole 800 mg TID 10 days
Chloroquine 150 mg BD 20 days
160
of bile flow and closure of the bilio-venous fistula. Endo-
scopic sphincterotomy carries a risk of complications, and a
repeat endoscopy is required to remove stent. Hence, naso-
biliary drain can be used instead of stenting [48].
Prognostic markers
There are two major categories of patients with ALA: those
with a good prognosis and those with a poor prognosis. These
groups can be easily identified by evaluation of clinical, bio-
chemical, and sonographic criteria. Bilirubin level >3.5 mg/dL,
encephalopathy, volume of abscess cavity, and hypoalbumine-
mia (serum albumin level <2.0 g/dL) are independent risk
factors for mortality [80]. The duration of symptoms and the
type of treatment do not influence mortality.
Prevention
Prevention and control of E. histolytica infection depends on
interruption of feco-oral transmission. Water can be made safe
for drinking and food preparation by boiling (for 1 min),
halogenation (with chlorine or iodine), or filtration. In the
United States and Europe, modern water treatment facilities
effectively remove E. histolytica. The importance of safe
drinking water is highlighted by an outbreak of amebiasis in
Tbilisi, Republic of Georgia, where there is an ongoing water-
borne epidemic due to decay of water treatment facilities
following the demise of the Soviet Union [81].
Development of a vaccine does not seem easy as natural
infections with E. histolytica do not seem to result in long term
immunity to re-infection; a large study in a Vietnamese pop-
ulation showed that individuals with a previous amebic liver-
abscess were as susceptible to a new episode of amebic liver-
abscess as the E. histolytica-naive population [82]. Several
potential antigen-based vaccines have however been tested on
animals, including the serine-rich E. histolytica protein
(SREHP), the E. histolytica Gal/GalNAcspecific lectin, the
29-kDa cysteine-rich E. histolytica antigen, the amebapore
protein, and the cysteine proteinase [83, 84]. Of these, the
Gal/GalNAc-specific lectin currently seems to hold the most
promise, based on the fact that intestinal anti-lectin IgA anti-
bodies confer protection, and the ongoing modification of
such vaccines including a DNA vaccine [85, 86].
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