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Indian J Gastroenterol (July–August 2012) 31(4):153–162

DOI 10.1007/s12664-012-0192-2


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 Keywords Colitis . Entamoeba histolytica . Liver abscess .
Entamoeba histolytica is still estimated to occur in 50 mil- Parasites . Zymodemes
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 Introduction
fatal condition. Distinguishing an invasive form (E. histo-
lytica) from a morphologically identical non-invasive one Even though amebic infection is globally distributed, most
(E. dispar) requires molecular or enzymatic characteriza- of the morbidity and mortality resulting from it is seen in the
tion. Further, the pattern of infection, interpretation of pres- developing world especially the Indian subcontinent, Cen-
ence of antibodies in the host, manifestations of disease, tral and South America and Africa. Approximately 50 mil-
approach to investigations and strategies for management lion people suffer from symptomatic infections and 40,000
remain complex. This article also provides a comprehensive to 100,000 die every year across the globe from them [1]. A
review of the parasite and host factors that govern the number of cases and outbreaks have been reported from
complex relationship of the prozoa and humans, and tries Mexico, Hue city in Vietnam, and Egypt [2–4]. The most
to explain why some develop a particular form of the disease infamous single point source outbreak was reported from a
in endemic zones. Application of modern imaging and im- hotel in Chicago in 1933, where mixture of water between
age guided therapy seems to be playing a major role in sewage and tap-water pipes led to at least 800 cases of
diagnosis and management of the potentially most serious amebiasis. A cross-sectional population survey conducted
form of the disease, amebic liver abscess. Despite lack of in two adjacent villages in rural India documented E. histo-
controlled studies there is a tendency to lower the threshold lytica in 18.1 % of fecal smears and antiamebic antibodies in
of their use in clinical practice, and indeed in-hospital mor- 28.7 % subjects [5]. In a 3 year study in pre-school children
tality rate seems to be falling for amebic liver abscess. In a in Dhaka, 2.2 % developed amebic dysentery [6].
world getting increasingly swamped by non-infectious met- Amebic liver abscess (ALA) develops in less than 1 % of
abolic diseases, awareness of amebic infections, its bed-side patients infected with E. histolytica, but still represents a
diagnosis, the use of appropriate laboratory tests, and deci- large number of patients with a dramatic, potentially fatal
sion making in management are shrinking. This review tries illness. While the frequency of “Western” diseases such as
to update the scientific developments in amebiasis. 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
G. Choudhuri (*) : M. Rangan study from a single hospital in Vietnam identified more than
Department of Gastroenterology, 1,200 cases of ALA during an 8-year period [3]. In a study
Sanjay Gandhi Postgraduate Institute of Medical Sciences,
Lucknow 226 014, India published from Delhi, more than half of the cases of liver
e-mail: abscess were of amebic etiology [7].
154 Indian J Gastroenterol (July–August 2012) 31(4):153–162

Organism and life cycle histolytica secretes cysteine proteinases that digest extracel-
lular matrix proteins and cause invasion and inflammation
Entamoeba histolytica, the causative protozoan organism, of the gut and liver. So far, seven distinct genes encoding
bears its name from its ability to destroy host tissues. There pre-pro forms of papain-family proteinases have been iden-
are two morphologically identical strains, one pathogenic tified [13]. E. histolytica trophozoites can secrete 10–1,000
(E. histolytica) and the other non-pathogenic, called E. times more cysteine proteinase than E. dispar [13]. These
dispar. Further, a number of non-pathogenic amebae, such enzymes activate host inflammatory response by amplifying
as E. moshkovskii, E. hartmanni, E. gingivalis, E. coli, interleukin-1 [14] and, via the transcription factor NFkB
Endolimax nana, and Iodamoeba butschlii, can colonize pathway trigger interleukin-1B, interleukin-8, and cycloox-
the human gastrointestinal tract. Among these, E. mosh- ygenase (COX)-2. By lysing neutrophils, they can release
kovskii has been reported to produce mild gastrointestinal mediators that cause diarrhea and tissue damage.
discomfort [8]. Invasive disease can be caused only by E. histolytica,
Infection occurs primarily through ingestion of cysts in which can be distinguished from its non-virulent form E.
fecally contaminated food or water. Unusual modes of dispar by cultural characteristics [15], virulence in animal
spread, particularly important in homosexuals, include di- models or tissue culture, selective agglutination by lectins
rect transmission through oral and anal sex. E. histolytica [16], reaction with monoclonal antibodies [17], isoenzyme
has a simple, two-stage life cycle consisting of an infectious patterns [18], ribosomal RNA sequence analysis and restric-
cyst and a motile trophozoite [9]. The mature cyst measures tion fragment length polymorphism analysis [19]. Differ-
5 to 20 μm in diameter and contains four nuclei. The ences in virulence may be based on the genetic
trophozoite measures 10 to 60 μm and contains a single background of E. histolytica strains [20]. tRNA-linked short
nucleus with a central karyosome. Within the lumen of the tandem repeats (STR) loci were found to be useful as
intestine, the cyst undergoes nuclear division first followed genetic markers in identifying virulent and avirulent strains
by cytoplasmic division, giving rise to eight trophozoites of E. histolytica [21].
[9]. Disease occurs with the invasion of the colonic epithe-
lium and wall by trophozoites which may then spread hem- Zymodemes
atogenously to distant sites. Factors that protect the host or
promote invasion in humans are still poorly understood. Based on the isoenzyme patterns of four enzymes: glucose
phosphate isomerase (GPI), hexokinase (HK), malate en-
zyme (ME), and phosphoglucomutase (PGM), 20 strains
Current understanding of pathogenesis or sub-types of amebae called zymodemes can be identified
[22–24]. The enzyme markers associated with pathogenicity
The reason why only some develop invasive amebic infec- are the presence of a fast-moving band of hexokinase, and
tions among all those exposed to the parasite may have to do presence of a β band and absence of α band of PGM [25].
with interplay between virulence factors of the parasite and Zymodemes II, VI, VII, XI, XII, XIII, XIV, XIX, and XX
defense mechanisms of the host. are pathogenic of which II and XI are often isolated from
liver abscesses [26].
Virulence factors Usually only one strain colonizes the colon of a host and
tends to remain consistent with regard to its isoenzyme
The disease begins with E. histolytica trophozoites that pattern over time; hence persons harboring non-pathogenic
emerge after excystation adhering to colonic epithelial cells zymodemes may not require treatment.
through the lectin, galactose/N-acetyl-D-galactosamine
[10]. Human cells touched by amebic trophozoites become Host immunity
immobile within minutes, and lose their cytoplasmic gran-
ules and structures, and eventually their nucleus. Cytolysis The role of immunity in amebic infection is unclear. Nearly
is undertaken by the amebapores, a family of at least three everyone with invasive amebiasis develops a systemic and a
small peptides capable of forming pores in lipid bilayers of mucosal humoral immune response that can be measured by
cells [11]. E. histolytica trophozoites can also kill mamma- several immunologic tests. Several observational studies
lian cells by induction of programmed cell death or apopto- from Mexico [27] and India [5] suggest that the presence
sis via the caspase pathway [12]. of antibodies is associated with lower rates of infection. It
Invasion of the parasite through the mucosa into the has also been seen that more than 90 % of individuals
submucosa is the hallmark of amebic colitis with lateral colonized by E. histolytica spontaneously clear the infection
extension by digestion of host tissue proteins giving rise to within 1 year, suggesting the development of an effective
the classic flask-shaped ulcers seen in cross section. E. 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
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 Indian J Gastroenterol (July–August 2012) 31(4):153–162

nonspecific colonic symptoms that may persist following a leading to a more severe disease. E. coli and Klebsiella are
bout of severe acute amebic colitis. In such cases, the colon the commonly cultured organisms. Presentation with jaun-
is free of parasites and the clinical findings resemble those dice and encephalopathy may resemble acute liver failure
of irritable bowel syndrome. [41, 42].

Extraintestinal amebiasis Left lobe abscess

Less than 1 % of the infections are extraintestinal, of which Thirty-five percent of patients present with a left lobe ab-
amebic liver abscess is overwhelmingly the most common. scess, half having associated lesions in the right lobe [43].
Other extraintestinal sites of infection rarely occur and typ- These patients have longer duration of symptoms (3-
ically result either from direct extension of liver abscesses 4 weeks) and present with an epigastric lump. Risk of
(e.g. amebic pericarditis or lung abscess) or hematogenous serious, often life-threatening complications due to rupture
spread (e.g. brain abscess). are higher, and can lead to pericardial effusion or tampo-
nade, pleural effusion or peritonitis. Timely removal of pus
Liver abscess by catheter drainage or needle aspiration is more often
needed in these patients in addition to antiamebic drugs.
ALA develops in less than 1 % of those infected but still
represents a large number of patients with men aged 18 to 50 Compression lesions
being disproportionately affected (M:F 10:1) [36–38]. The
underlying reason for this huge gender difference is not A posteriorly located ALA in the right lobe may present as
clear, but alcohol consumption in men and protective effects inferior vena cava obstruction or hepatic outflow obstruction
of hormones and iron deficiency anemia among menstruat- [44]. This is suggested by bilateral pedal edema, ascites, and
ing women has been postulated. Alcohol impairs Kupffer visible veins on anterior and posterior abdominal wall,
cell function and can impair both cellular and humoral which disappear after resolution of the abscess.
immunologic responses [39].
Although liver abscess develops after intestinal infection, Extension of the abscess
and patients rarely remember a recent attack of dysentery,
ulcers are found in the large bowel on colonoscopy in more Leakage of the abscess may occur into the pleural cavity,
than half of patients with ALA [40]. Multiple, large, and with empyema thoracis, or into the pericardium causing
left-sided ulcers were more common in elderly patients and cardiac tamponade. Intraabdominal extension following per-
in those in whom diarrhea was the presenting symptom. foration into the peritoneal cavity is usually associated with
The common site for ALA is the posterior, external and shock and generalized peritonitis and may occur in up to
superior portions of right lobe of the liver and occurs as a 7 % of cases. Rupture into the colon and biliary tree has also
single lesion in 30 % to 70 %. Unusual presentations include been reported. A subhepatic collection may also be localized
multiple abscesses, left lobe abscesses, abscesses presenting and walled off. Such presentations, though infrequent, occur
as compressive lesion, and abscesses rupturing into viscera. in patients who are diagnosed late, and account for most of
The clinical presentation is usually abrupt, with high the mortality associated with the disease.
fever followed by pain in the upper abdomen. Fever is
present in most cases; occurs frequently in spikes, but is Jaundice in ALA
sometimes constant over several days, with rigors and pro-
fuse sweating. The pain is constant, and may be intense and Hyperbilirubinemia occurs in 6 % to 29 % of cases and is
radiate to the scapular region and right shoulder, sometimes attributed to various mechanisms, such as pressure on bili-
increasing with coughing or deep breathing. Anorexia, ary ducts, intrahepatic or canalicular cholestasis [45, 46].
weight loss, non-productive cough, nausea, vomiting, diar- Bromosulfophthalein excretion, which represents the biliru-
rhea or dysentery may be present. Physical examination bin transport maximum of hepatic parenchymal cells, is
reveals a febrile patient with tenderness over an enlarged significantly reduced. Damaged biliary ducts and hepatic
liver or over right lower intercostal spaces. veins in amebic liver abscess may sometimes form bilio-
vascular fistulae. When it involves a venous system (portal
Multiple liver abscesses or hepatic), the pressure gradient directs the bile and blood
mixture toward the right side of heart - termed bilhemi,
Fifteen percent of patients have multiple abscesses and leading to a rapid rise of bilirubin without much increase
present with fever, toxemia, deep jaundice, and encephalop- in liver enzymes [47]. Normalization occurs with effective
athy. Toxemia is suggestive of an added bacterial infection drainage of pus or bile [48].
Indian J Gastroenterol (July–August 2012) 31(4):153–162 157

Diagnosis Isoenzyme analysis

The gold standard for the diagnosis of amebic colitis A total of 24 different zymodemes have been described, of
remains finding of hematophagous trophozoites of E. which 21 are from human isolates (9 of E. histolytica and 12
histolytica in microscopic examination of fresh stool of E. dispar). There are three main ones for E. histolytica (II,
specimen or colonoscopic detection of typical ulcers with XIV, and XIX) and one for E. dispar (I). A fast moving band
biopsy showing trophozoites. Since the cecum and as- of Hexokinase is usually associated with invasive forms,
cending colon are most frequently affected in amebiasis, while non-invasive strains demonstrate a slow moving band.
colonoscopy is preferred to sigmoidoscopy. Classically, Isoenzyme analysis, being cumbersome and complicated,
multiple punctate ulcers measuring 2 to 10 mm are seen has been superseded by DNA-based methods for profiling
with normal intervening tissue; the colonic epithelium, the parasite.
however, may simply appear indurated with no visible
ulcerations, and, in severe cases where the ulcers have Antibody detection tests
coalesced, the epithelium may appear necrotic or resem-
ble that of ulcerative colitis. Histologic examination of a Serological tests that detect antibodies to E. histolytica indicate
biopsy specimen taken from the edge of an ulcer reveals present or prior infection and are of particular value in areas of
amebic trophozoites and a variable inflammatory infil- low endemicity. Many different assays have been developed for
trate. Identification of amebae can be aided by periodic the detection of antibodies, including indirect hemagglutina-
acid–Schiff staining of biopsy tissue, which stains troph- tion, latex agglutination, immunoelectrophoresis, gel diffusion
ozoites magenta. test, counter-immunoelectrophoresis, immunodiffusion,
complement fixation, indirect immunofluorescence assay
Microscopy and enzyme-linked immunosorbent assay (ELISA) [52].
ELISA is the most popular assay in diagnostic laboratories
Microscopic techniques employed in a diagnostic clinical throughout the world and has been used to study the
laboratory include wet preparation, concentration, and perma- epidemiology of asymptomatic disease and the diagnosis
nently stained smears for the identification of E. histolytica in of symptomatic amebiasis after fecal examination. The
feces. Microscopic examination of a direct saline (wet) mount tests are strongly positive in patients with invasive disease
is a very insensitive method (<10 %) as it has to be performed such as ALA, and have sensitivity often reaching 100 %
within 1 h on fresh specimen. As Entamoeba trophozoites [53] within 7 days of infection. In endemic zones, the mere
generally degenerate rapidly in unfixed fecal specimens [49], presence of antibodies in a doubtful clinical setting does
specimens should be preserved with a fixative, (e.g. Schau- not help make a diagnosis.
dinn’s fluid) and stained (e.g. Trichrome, iron-hematoxylin).
Atleast 3 stool examinations within 10 days improves the Antigen detection tests
detection rate to 85 % to 95 % [50]. The presence of RBCs
in the cytoplasm is still considered diagnostic for E. histolytica Immunological tests can detect amebic antigen in samples
in patients with dysentery and may be used to distinguish such as liver pus, or stools. Their sensitivity approaches that
between E. histolytica and E. dispar. of stool culture and are rapid to perform. Antigen-based
ELISA kits that are specific for E. histolytica use monoclo-
Culture methods nal antibodies against the Gal/GalNAc-specific lectin or the
serine-rich antigen of the parasite.
Culture techniques for the isolation of Entamoeba species
include xenic (diphasic and monophasic) and axenic sys- Polymerase chain reaction (PCR) based tests
tems. Xenic cultivation is the growth of the parasite in the
presence of an undefined flora [51] while axenic one PCR can be done in variety of clinical specimens, in-
involves growing them in the absence of any other metab- cluding feces, tissues, and liver abscess aspirate [52].
olizing cells [51]. Culture of E. histolytica can be performed PCR of the small-subunit rRNA gene (18S rDNA) is
from fecal specimens, rectal biopsy specimens, or liver reported to be approximately 100 times more sensitive
abscess aspirates. The success rate for culture of E. histo- than the available ELISA kits [54]. In an attempt to
lytica is between 50 % and 70 % in reference laboratories increase the sensitivity of the PCR assay, a nested mul-
and of E.dispar much less as the latter is quite fastidious tiplex PCR was developed for the simultaneous detection
[51]. It is however expensive, time consuming, not easily and differentiation of E. histolytica and E. dispar from
available, and hence not used as a routine diagnostic DNA extracted from microscopy-positive fecal samples
procedure. [55]. Utilizing this multiplex technique, the sensitivity
158 Indian J Gastroenterol (July–August 2012) 31(4):153–162

and specificity were increased to 94 % and 100 %, Scintigraphy

respectively. The introduction of real-time PCR, a quan-
titative method increases the sensitivity further. Although Nuclear scanning with Technetium Tc99m displays a photo-
PCR-based methods are very useful, their application in penic area. Gallium scanning may be useful in distinguish-
routine diagnosis is still limited due to difficulties in ing amebic abscess from a pyogenic one in patients with a
DNA extraction from fecal samples and cost and time negative serology or an atypical clinical presentation as the
involved in the entire process. former does not contain leukocytes within the cavity while
the latter appears as a hot spot [56, 63].
Imaging techniques

Chest roentgenography Differential diagnosis

Abnormalities, seen on average in 59 % of patients, include The diagnosis of amebic liver abscess should be considered
an elevated right hemidiaphragm, atelectasis, and right pleu- in patients presenting with typical clinical features especial-
ral effusion [56–58]. ly in endemic areas and among those who have recently
traveled to these zones. A history of recent diarrhea, if
Ultrasonography present, may help. The principal clinical entities that have
to be distinguished from ALA include other space-
Ultrasonography is the preferred imaging technique for occupying lesions of the liver such as pyogenic liver ab-
the detection of amebic abscess because of its lower cost, scess, echinococcal cyst, and hepatic tumors [64]. A strong-
noninvasiveness, and quick easy availability. It can also ly positive amebic serology is often helpful.
guide needle aspiration for diagnostic and therapeutic Patients with pyogenic liver abscess are more likely to be
purposes. The classic ultrasonographic appearance is of older, have significant comorbidities such as diabetes, and have
a round or oval homogenous hypoechoic lesion with a history of recent biliary disease and/or surgery. Females, with
borders that appear ill-defined initially, and become a higher frequency of biliary stone disease, are often affected.
well-defined subsequently, typically located near the The lesions are usually multiple, amebic serology is usually
postero-superior surface of the liver. Early lesions may negative and blood cultures are often positive.
be hyper or iso-echoic when solid necrotic material is Echinococcal lesions are typically asymptomatic but can
present, becoming progressively hypoechoic at the center present as an abscess with secondary infection. Eosinophil-
as the necrosis liquefies [56, 59]. Differentiating amebic ia, calcification or presence of “daughter” cysts may help
from pyogenic abscess sonographically can be difficult identify them. Malignant hepatic tumors such as hepatoma
although the latter tends to be scattered and irregular may rarely present as cystic lesions and may pose confusion
walled. in cirrhotic patients.

Computed tomography
Computed tomography (CT) may be more sensitive for
smaller lesions, particularly if helical CT is used. They Pharmacological treatment
appear as a hypodense avascular liver mass with well-
defined margins and alternating hypodense and hyperdense Agents for treatment of amebiasis are categorized as luminal
halos after contrast administration. Extrahepatic extension or tissue amebicides on the basis of the location of their anti-
of the lesion, when present, may be another indicator that amebic activity. The luminal amebicides include iodoquinol,
the lesion is amebic in origin [56, 60]. diloxanide furoate, and paromomycin. Tissue amebicides
include nitro-imidazoles (metronidazole, tinidazole, ornida-
Magnetic resonance imaging zole, secnidazole, satronidazole), nitazoxanide, erythromy-
cin, and chloroquine. Of these, metronidazole and tinidazole
Amebic abscess appears as high-signal intensity on T2- are most popular, with cure rates of over 90 %. The new
weighted images. The area around the abscess, adjacent to antiparasitic nitazoxanide appears to be efficacious, but data
the parenchyma, may appear hyperintense or hypointense, is limited. Erythromycin has no activity against amebic liver
corresponding to areas of edema and hypervascularity inter- disease, and chloroquine has no activity against intestinal
spersed with areas of thrombosis. Magnetic resonance im- disease.
aging may have a role in patients with renal insufficiency If asymptomatic patients with non-invasive disease re-
[61, 62]. 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 Rates of resolution of abdominal pain, abscess cavities, hepato-
nitroimidazole followed by a cysticidal agent to prevent megaly, and duration of hospitalization were heterogeneous.
recurrent disease, if cysts remain in the stool. Most patients Patients with uncomplicated liver abscess may be treated initial-
with colitis respond promptly with resolution of diarrhea in ly with antiamebic agents alone, with addition of drainage by
2 to 5 days. Despite conflicting reports on the safety of catheter offered to those who either fail to respond or show
metronidazole for the developing fetus during pregnancy, features of impending rupture.
women with severe disease merit treatment (Table 3).
Aspiration or drainage of abscess
In most cases, clinical improvement with antiamebic drug
Routine aspiration of liver abscess is not indicated for diag- therapy alone is seen within a few days to a week. Radio-
nostic or therapeutic purposes [65]. A combination of ultra- logic disappearance of the cavity may however take 3 to 9
sonographic finding with a positive serology in the (range 3 to 131) months. Three patterns of radiologic reso-
appropriate clinical setting is adequate to start drug therapy. lution of ALA have been described: (1) rapid resolution
Aspiration is indicated if there is lack of clinical improve- within 3 months in one third of the patients, (2) gradual
ment in 48–72 h, left lobe abscess, thin rim of liver tissue reduction of abscess with complete disappearance within
around the abscess (<10 mm) with impending rupture, and 12 months in two-thirds, or (3) rapid reduction in size up
in seronegative abscesses. The aspirate is reddish brown or to about 25 % of initial volume in 3 months, and then
chocolate in colour and resembles anchovy sauce due to persistence of the cavity for a prolonged period of time up
admixture of blood and liquified liver tissue. Antiamebic to 19 months in a small percentage (5.9 %) of patients [73].
therapy alone is as effective as routine needle aspiration Follow up imaging studies are not necessary in patients who
combined with antiamebic therapy in the treatment of have clinical resolution after treatment for uncomplicated
patients with uncomplicated amebic liver abscess [66, 67]. ALA.
Evacuation of “pus” from the abscess is sometimes re-
quired and can be done either by needle aspiration or by Surgery
placement of a percutaneous catheter, the latter scoring over
the former in resolution of symptoms and abscess cavity Open surgical drainage is rarely indicated and may be re-
[68]. In our experience too, catheter drainage led to prompt quired in the setting of a large abscess with a poor yield on
resolution of symptoms and early collapse of the abscess needle aspiration or clinical deterioration despite attempted
cavity, with the additional advantage of allowing liquefac- needle aspiration, and in complicated ALA [74]. Surgical
tion and gradual continuous drainage of pus that was initial- mortality is, however, very high. Hence, it should only be
ly thick and not easy to aspirate through a needle [69–71]. used when the cavity has ruptured into adjacent viscera or
Percutaneous procedure plus metronidazole
vs. metronidazole alone for uncomplicated amebic liver abscess Role of endoscopy

A Cochrane review analyzed 7 randomised trials comparing an Various endoscopic treatment modalities have been used for
image-guided percutaneous procedure plus metronidazole vs. patients with bilhemia, including biliary drainage by sphinc-
metronidazole alone in patients with uncomplicated amebic liver terotomy, stenting, nasobiliary drain, balloon occlusion of
abscess [72]. Pooled analysis of three homogenous trials showed fistula, and covered stent placement [75–79]. The principle
that needle aspiration did not significantly improve fever reso- of therapy of bilio-vascular fistula is to decrease the pressure
lution (RR 0.60, 95 % confidence interval (CI) 0.22 to 1.61). 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 Indian J Gastroenterol (July–August 2012) 31(4):153–162

of bile flow and closure of the bilio-venous fistula. Endo- 2. Caballero-Salcedo A, Viveros-Rogel M, Salvatierra B, et al. Seroe-
scopic sphincterotomy carries a risk of complications, and a pidemiology of amebiasis in Mexico. Am J Trop Med Hyg.
repeat endoscopy is required to remove stent. Hence, naso- 3. Van Pham L, Duong Manh H, Pham Nhu H. Amebic abscess of the
biliary drain can be used instead of stenting [48]. liver: ultrasound guided puncture. Ann Chir. 1996;50:340–3.
4. Abd-Alla MD, Ravdin JI. Diagnosis of amebic colitis by antigen
capture ELISA in patients presenting with acute diarrhea in Cairo,
Egypt. Trop Med Int Health. 2002;7:365–70.
Prognostic markers 5. Choudhuri G, Prakash V, Kumar A, Shahi SK, Sharma M. Protec-
tive immunity to entamoeba histolytica infection in subjects with
antiamebic antibodies residing in a hyperendemic zone. Scand J
There are two major categories of patients with ALA: those Infect Dis. 1991;23:771–6.
with a good prognosis and those with a poor prognosis. These 6. Haque R, Duggal P, Ali IM, et al. Innate and acquired resistance to
groups can be easily identified by evaluation of clinical, bio- amebiasis in Bangladeshi children. J Infect Dis. 2002;186:547–52.
chemical, and sonographic criteria. Bilirubin level >3.5 mg/dL, 7. Mohan S, Talwar N, Chaudhary A, Andley M, Ravi B, Kumar A.
Liver abscess: a clinicopathological analysis of 82 cases. Int Surg.
encephalopathy, volume of abscess cavity, and hypoalbumine- 2006;91:228–33.
mia (serum albumin level <2.0 g/dL) are independent risk 8. Khairnar K, Parija SC. A novel nested multiplex polymerase chain
factors for mortality [80]. The duration of symptoms and the reaction (PCR) assay for differential detection of Entamoeba his-
type of treatment do not influence mortality. tolytica, E. moshkovskii and E. dispar DNA in stool samples.
BMC Microbiol. 2007;7:47.
9. Stanley SL Jr. Amebiasis. Lancet. 2003;361:1025–34.
10. Mann BJ. Structure and function of the Entamoeba histolytica Gal/
GalNAc lectin. Int Rev Cytol. 2002;216:59–80.
Prevention 11. Leippe M. Amoebapores. Parasitol Today. 1997;13:178–83.
12. Berninghausen O, Leippe M. Necrosis versus apoptosis as the
Prevention and control of E. histolytica infection depends on mechanism of target cell death induced by Entamoeba histolytica.
interruption of feco-oral transmission. Water can be made safe Infect Immun. 1997;65:3615–21.
13. Que X, Reed SL. Cysteine proteinases and the pathogenesis of
for drinking and food preparation by boiling (for 1 min), amebiasis. Clin Microbiol Rev. 2000;13:196–206.
halogenation (with chlorine or iodine), or filtration. In the 14. Zhang Z, Wang L, Seydel KB, et al. Entamoeba histolytica cyste-
United States and Europe, modern water treatment facilities ine proteinases with interleukin-1 beta converting enzyme (ICE)
activity cause intestinal inflammation and tissue damage in ame-
effectively remove E. histolytica. The importance of safe
biasis. Mol Microbiol. 2000;37:542–8.
drinking water is highlighted by an outbreak of amebiasis in 15. Pysova I, Tumova P, Tolarova V, Nohynkova E. Nonpathogenic
Tbilisi, Republic of Georgia, where there is an ongoing water- Entamoeba dispar quickly outgrows pathogenic Entamoeba histo-
borne epidemic due to decay of water treatment facilities lytica in mixed xenic cultures. Lett Appl Microbiol. 2009;48:500–
following the demise of the Soviet Union [81]. 3.
16. Pacheco-Yepez J, Campos-Rodriguez R, Rojas-Hernandez S, et al.
Development of a vaccine does not seem easy as natural Differential expression of surface glycoconjugates on Entamoeba
infections with E. histolytica do not seem to result in long term histolytica and Entamoeba dispar. Parasitol Int. 2009;58:171–7.
immunity to re-infection; a large study in a Vietnamese pop- 17. Petri WA Jr, Snodgrass TL, Jackson TF, et al. Monoclonal anti-
ulation showed that individuals with a previous amebic liver- bodies directed against the galactose-binding lectin of Entamoeba
histolytica enhance adherence. J Immunol. 1990;144:4803–9.
abscess were as susceptible to a new episode of amebic liver- 18. Ortner S, Clark CG, Binder M, Scheiner O, Wiedermann G,
abscess as the E. histolytica-naive population [82]. Several Duchene M. Molecular biology of the hexokinase isoenzyme
potential antigen-based vaccines have however been tested on pattern that distinguishes pathogenic Entamoeba histolytica from
animals, including the serine-rich E. histolytica protein nonpathogenic Entamoeba dispar. Mol Biochem Parasitol.
(SREHP), the E. histolytica Gal/GalNAcspecific lectin, the 19. Zaki M, Meelu P, Sun W, Clark CG. Simultaneous differentiation
29-kDa cysteine-rich E. histolytica antigen, the amebapore and typing of Entamoeba histolytica and Entamoeba dispar. J Clin
protein, and the cysteine proteinase [83, 84]. Of these, the Microbiol. 2002;40:1271–6.
Gal/GalNAc-specific lectin currently seems to hold the most 20. Ali IK, Mondal U, Roy S, Haque R, Petri WA Jr, Clark CG.
Evidence for a link between parasite genotype and outcome of
promise, based on the fact that intestinal anti-lectin IgA anti- infection with Entamoeba histolytica. J Clin Microbiol.
bodies confer protection, and the ongoing modification of 2007;45:285–9.
such vaccines including a DNA vaccine [85, 86]. 21. Escueta-de Cadiz A, Kobayashi S, Takeuchi T, Tachibana H,
Nozaki T. Identification of an avirulent Entamoeba histolytica
strain with unique tRNA-linked short tandem repeat markers.
Parasitol Int. 2010;59:75−81.
References 22. Sargeaunt PG, Williams JE. Electrophoretic isoenzyme patterns of
Entamoeba histolytica and Entamoeba coli. Trans R Soc Trop Med
Hyg. 1978;72:164–6.
1. Walsh J. Prevalence of Entamoeba histolytica infection. In: Ravdin 23. Sargeaunt PG, Williams JE, Grene JD. The differentiation of
J, ed. Amebiasis: Human Infection by Entamoeba histolytica. New invasive and non-invasive Entamoeba histolytica by isoenzyme
York: John Wiley and Sons; 1988. electrophoresis. Trans R Soc Trop Med Hyg. 1978;72:519–21.
Indian J Gastroenterol (July–August 2012) 31(4):153–162 161

24. Sargeaunt PG, Williams JE, Neal RA. A comparative study of 46. Datta DV, Chhuttani PN. Cholestasis in patients with amebic liver
Entamoeba histolytica (NIH :200, HK9, etc.), “E. histolytica- abscess. Am J Dig Dis. 1971;16:977–84.
like” and other morphologically identical amoebae using isoen- 47. Glaser K, Wetscher WG, Pointner R, et al. Traumatic bilhemia.
zyme electrophoresis. Trans R Soc Trop Med Hyg. 1980;74:469– Surgery. 1994;116:24–7.
74. 48. Singh V, Bhalla A, Sharma N, Mahi SK, Lal A, Singh P. Patho-
25. Ortner S, Binder M, Scheiner O, Wiedermann G, Duchene M. physiology of jaundice in amebic liver abscess. Am J Trop Med
Molecular and biochemical characterization of phosphoglucomu- Hyg. 2008;78:556–9.
tases from Entamoeba histolytica and Entamoeba dispar. Mol 49. Proctor EM. Laboratory diagnosis of amebiasis. Clin Lab Med.
Biochem Parasitol. 1997;90:121–9. 1991;11:829–59.
26. Sargeaunt PG, Jackson TF, Wiffen SR, Bhojnani R. Biological 50. Li E, Stanley SL Jr. Protozoa. Amebiasis. Gastroenterol Clin North
evidence of genetic exchange in Entamoeba histolytica. Trans R Am. 1996;25:471–92.
Soc Trop Med Hyg. 1988;82:862–7. 51. Clark CG, Diamond LS. Methods for cultivation of luminal parasitic
27. De Leon A. Delayed prognosis in amebic hepatic abscess. Arch protists of clinical importance. Clin Microbiol Rev. 2002;15:329–41.
Invest Med (Mex). 1970;1 Suppl:205−6. 52. Fotedar R, Stark D, Beebe N, Marriott D, Ellis J, Harkness J.
28. Anand BS, Tuteja AK, Kaur M, et al. Entamoeba histolytica cyst Laboratory diagnostic techniques for Entamoeba species. Clin
passers. Clinical profile and spontaneous eradication of infection. Microbiol Rev. 2007;20:511–32.
Dig Dis Sci. 1993;38:1825–30. 53. Zengzhu G, Bracha R, Nuchamowitz Y, Cheng IW, Mirelman D.
29. Ravdin JI, Jackson TF, Petri WA Jr, et al. Association of serum Analysis by enzyme-linked immunosorbent assay and PCR of
antibodies to adherence lectin with invasive amebiasis and asymp- human liver abscess aspirates from patients in China for Entamoe-
tomatic infection with pathogenic Entamoeba histolytica. J Infect ba histolytica. J Clin Microbiol. 1999;37:3034–6.
Dis. 1990;162:768–72. 54. Mirelman D, Nuchamowitz Y, Stolarsky T. Comparison of use of
30. Petri WA Jr, Joyce MP, Broman J, Smith RD, Murphy CF, Ravdin enzyme-linked immunosorbent assay-based kits and PCR amplifi-
JI. Recognition of the galactose- or N-acetylgalactosamine-binding cation of rRNA genes for simultaneous detection of Entamoeba
lectin of Entamoeba histolytica by human immune sera. Infect histolytica and E. dispar. J Clin Microbiol. 1997;35:2405–7.
Immun. 1987;55:2327–31. 55. Haque R, Ali IK, Akther S, Petri WA Jr. Comparison of PCR,
31. Haque R, Ali IM, Sack RB, Farr BM, Ramakrishnan G, Petri WA isoenzyme analysis, and antigen detection for diagnosis of Ent-
Jr. Amebiasis and mucosal IgA antibody against the Entamoeba amoeba histolytica infection. J Clin Microbiol. 1998;36:449–52.
histolytica adherence lectin in Bangladeshi children. J Infect Dis. 56. Kimura K, Stoopen M, Reeder MM, Moncada R. Amebiasis:
2001;183:1787–93. modern diagnostic imaging with pathological and clinical correla-
32. Sanchez-Guillen Mdel C, Perez-Fuentes R, Salgado-Rosas H, et al. tion. Semin Roentgenol. 1997;32:250–75.
Differentiation of entamoeba histolytica/entamoeba dispar by PCR 57. Shamsuzzaman SM, Hashiguchi Y. Thoracic amebiasis. Clin Chest
and their correlation with humoral and cellular immunity in indi- Med. 2002;23:479–92.
viduals with clinical variants of amebiasis. Am J Trop Med Hyg. 58. Sharma OP, Maheshwari A. Lung diseases in the tropics. Part 2:
2002;66:731−7. Common tropical lung diseases: diagnosis and management. Tuber
33. Sinha P, Ghoshal UC, Choudhuri G, Naik S, Ayyagari A, Naik SR. Lung Dis. 1993;74:359–70.
Does Entamoeba histolytica cause irritable bowel syndrome? Indi- 59. Juimo AG, Gervez F, Angwafo FF. Extraintestinal amebiasis.
an J Gastroenterol. 1997;16:130–3. Radiology. 1992;182:181–3.
34. Anand AC. Is it curtains for chronic amebiasis? Indian J Gastro- 60. Radin DR, Ralls PW, Colletti PM, Halls JM. CT of amebic liver
enterol. 1997;16:127–9. abscess. AJR Am J Roentgenol. 1988;150:1297–301.
35. Anand AC, Reddy PS, Saiprasad GS, Kher SK. Does non- 61. Ralls PW, Henley DS, Colletti PM, et al. Amebic liver abscess:
dysenteric intestinal amebiasis exist? Lancet. 1997;349:89–92. MR imaging. Radiology. 1987;165:801–4.
36. Acuna-Soto R, Maguire JH, Wirth DF. Gender distribution in 62. Mendez RJ, Schiebler ML, Outwater EK, Kressel HY. Hepatic
asymptomatic and invasive amebiasis. Am J Gastroenterol. abscesses: MR imaging findings. Radiology. 1994;190:431–6.
2000;95:1277–83. 63. Rustgi AK, Richter JM. Pyogenic and amebic liver abscess. Med
37. Shandera WX, Bollam P, Hashmey RH, Athey PA, Greenberg SB, Clin North Am. 1989;73:847–58.
White AC Jr. Hepatic amebiasis among patients in a public teach- 64. Krige JE, Beckingham IJ. ABC of diseases of liver, pancreas, and
ing hospital. South Med J. 1998;91:829–37. biliary system. BMJ. 2001;322:537–40.
38. Barnes PF, De Cock KM, Reynolds TN, Ralls PW. A comparison 65. Sharma MP, Rai RR, Acharya SK, Ray JC, Tandon BN. Needle
of amebic and pyogenic abscess of the liver. Medicine (Baltimore). aspiration of amebic liver abscess. BMJ. 1989;299:1308–9.
1987;66:472–83. 66. Sharma MP, Dasarathy S. Amebic liver abscess. Trop Gastroen-
39. Seeto RK, Rockey DC. Amebic liver abscess: epidemiology, clin- terol. 1993;14:3–9.
ical features, and outcome. West J Med. 1999;170:104–9. 67. Sharma MP, Ahuja V. Management of amebic liver abscess. Arch
40. Misra SP, Misra V, Dwivedi M, Singh PA, Barthwal R. Factors Med Res. 2000;31:S4–5.
influencing colonic involvement in patients with amebic liver 68. Singh O, Gupta S, Moses S, Jain DK. Comparative study of
abscess. Gastrointest Endosc. 2004;59:512–6. catheter drainage and needle aspiration in management of large
41. Sharma MP, Acharya SK, Verma N, Dasarathy S. Clinical profile liver abscesses. Indian J Gastroenterol. 2009;28:88–92.
of multiple amebic liver abscesses. J Assoc Physicians India. 69. Rajak CL, Gupta S, Jain S, Chawla Y, Gulati M, Suri S. Percuta-
1990;38:837–9. neous treatment of liver abscesses: needle aspiration versus cathe-
42. Kapoor OP, Joshi VR. Multiple amebic liver abscesses. A study of ter drainage. AJR Am J Roentgenol. 1998;170:1035–9.
56 cases. J Trop Med Hyg. 1972;75:4–6. 70. Saraswat VA, Agarwal DK, Baijal SS, et al. Percutaneous catheter
43. Sharma MP, Sarin SK, Acharya SK. Left lobe amebic abscess of liver– drainage of amebic liver abscess. Clin Radiol. 1992;45:187–9.
a distinct clinical entity. J Assoc Physicians India. 1984;32:477–80. 71. Baijal SS, Agarwal DK, Roy S, Choudhuri G. Complex ruptured
44. Sharma MP, Sarin SK. Inferior vena caval obstruction due to amebic liver abscesses: the role of percutaneous catheter drainage.
amebic liver abscess. J Assoc Physicians India. 1982;30:243–4. Eur J Radiol. 1995;20:65–7.
45. Nigam P, Gupta AK, Kapoor KK, Sharan GR, Goyal BM, Joshi 72. Chavez-Tapia NC, Hernandez-Calleros J, Tellez-Avila FI,
LD. Cholestasis in amebic liver abscess. Gut. 1985;26:140–5. Torre A, Uribe M. Image-guided percutaneous procedure plus
162 Indian J Gastroenterol (July–August 2012) 31(4):153–162

metronidazole versus metronidazole alone for uncomplicated communicate with intrahepatic bile ducts. Endoscopy.
amebic liver abscess. Cochrane Database Syst Rev. 2009: 2006;38:249–53.
CD004886. 80. Sharma MP, Dasarathy S, Verma N, Saksena S, Shukla DK.
73. Sharma MP, Dasarathy S, Sushma S, Verma N. Long term follow- Prognostic markers in amebic liver abscess: a prospective study.
up of amebic liver abscess: clinical and ultrasound patterns of Am J Gastroenterol. 1996;91:2584–8.
resolution. Trop Gastroenterol. 1995;16:24–8. 81. Barwick RS, Uzicanin A, Lareau S, et al. Outbreak of amebiasis in
74. Akgun Y, Tacyildiz IH, Celik Y. Amebic liver abscess: changing Tbilisi, Republic of Georgia, 1998. Am J Trop Med Hyg.
trends over 20 years. World J Surg. 1999;23:102–6. 2002;67:623–31.
75. Struyven J, Cremer M, Pirson P, Jeanty P, Jeanmart J. Posttrau- 82. Blessmann J, Van Linh P, Nu PA, et al. Epidemiology of amebiasis
matic Bilhemia: diagnosis and catheter therapy. AJR Am J Roent- in a region of high incidence of amebic liver abscess in central
genol. 1982;138:746–7. Vietnam. Am J Trop Med Hyg. 2002;66:578–83.
76. Gable DR, Allen JW, Harrell DJ, Carrillo EH. Endoscopic treat- 83. Stanley SL Jr. Progress towards development of a vaccine for
ment of posttraumatic “bilhemia”: case report. J Trauma. amebiasis. Clin Microbiol Rev. 1997;10:637–49.
1997;43:534–6. 84. Huston CD, Petri WA Jr. Host-pathogen interaction in amebiasis
77. Bose SM, Mazumdar A, Singh V. Non-operative management of and progress in vaccine development. Eur J Clin Microbiol Infect
gunshot injury of liver causing bilhaemia. Aust N Z J Surg. Dis. 1998;17:601–14.
2000;70:382–4. 85. Miller-Sims VC, Petri WA Jr. Opportunities and obstacles in
78. Singh V, Narasimhan KL, Verma GR, Singh G. Endoscopic man- developing a vaccine for Entamoeba histolytica. Curr Opin Immu-
agement of traumatic hepatobiliary injuries. J Gastroenterol Hep- nol. 2002;14:549–52.
atol. 2007;22:1205–9. 86. Gaucher D, Chadee K. Construction and immunogenicity of a
79. Sharma BC, Agarwal N, Garg S, Kumar R, Sarin SK. En- codon-optimized Entamoeba histolytica Gal-lectin-based DNA
doscopic management of liver abscesses and cysts that vaccine. Vaccine. 2002;20:3244–53.