Entamoeba and Entamoeba
histolytica
Bobbi S Pritt, Mayo Clinic, Rochester, Minnesota, USA
C Graham Clark, London School of Hygiene and Tropical Medicine, London, UK
Based in part on the previous version of this Encyclopedia of Life Sciences
(ELS) article, Entamoeba and Entamoeba histolytica by Louis S
Diamond and C Graham Clark.
Entamoeba species are unicellular eukaryotes that para-
sitise all classes of vertebrates and some invertebrates.
Only three species of Entamoeba have been proven to cause
disease and sometimes death in their hosts: Entamoeba
histolytica, a parasite of humans, Entamoeba nuttalli, a
parasite of nonhuman primates and Entamoeba invadens, a
parasite of reptiles. Other species appear to live as com-
mensals in their hosts and do not cause evident disease.
Amoebiasis is defined as infection with E. histolytica
regardless of symptoms. Most cases of amoebiasis are
asymptomatic, but E. histolytica can rarely cause intestinal
or disseminated disease. Identification of E. histolytica is
complicated by the existence of two morphologically
identical amoebae that may also colonise the human
intestinal tract, Entamoeba dispar and Entamoeba mosh-
kovskii, neither of which are thought to cause disease.
Entamoeba spp. are commonly studied to gain further
insight into protozoal evolution, amoeboid locomotion
and cell-killing ability, among other topics.
Introduction
Entamoeba species are unicellular eukaryotes that para-
sitise all classes of vertebrates and some invertebrates.
Many species have been described, mostly from mammals
and reptiles, but the identication of most new species has
been based only on morphology and/or their host species.
Since most Entamoeba species look very much alike, many
of these are probably not really distinct species and, simi-
larly, some parasites thought to belong to the same species
will likely prove eventually to be distinct. Recent studies
eLS subject area: Microbiology
How to cite:
Pritt, Bobbi S; and Clark, C Graham (October 2011) Entamoeba and
Entamoeba histolytica. In: eLS. John Wiley & Sons, Ltd: Chichester.
DOI: 10.1002/9780470015902.a0001963.pub3
eLS & 2011, John Wiley & Sons, Ltd. www.els.net
Advanced article
. Introduction
Article Contents
. Morphology
. Classification
. The Human Pathogen: E. histolytica, and its Morphologic
Mimics
. Reasons for Interest in Entamoeba Species in Addition to
their Being Parasites
Online posting date: 17th October 2011
based on analysis of amoeba deoxyribonucleic acid (DNA)
have shown that both these errors do actually occur (Clark
et al., 2006; Stensvold et al., 2010, 2011).
Only three species of Entamoeba have been proven to
cause disease and sometimes death in their hosts: Entamoeba
histolytica, a parasite of humans, Entamoeba nuttalli, a
parasite of nonhuman primates and Entamoeba invadens, a
parasite of reptiles. All other species appear to live as com-
mensals in their hosts, causing no evident harm. In humans,
commensal Entamoeba spp. include Entamoeba coli, Enta-
moeba hartmanni, Entamoeba dispar, Entamoeba gingivalis,
Entamoeba moshkovskii and Entamoeba polecki. There are
occasional reports of these Entamoeba species causing
symptoms, for example, E. moshkovskii and E. dispar in the
human intestinal tract and E. gingivalis in the human oral
cavity, but the conclusions of these reports require
conrmation.
E. histolytica is endemic in many countries around the
world and is thought to be a leading parasitic cause of
human morbidity and mortality (see below). Similarly,
E. invadens can be responsible for signicant losses of
reptiles in zoological collections. In turtles it exists pri-
marily as a commensal organism, but infections of snakes
and lizards, as well as turtles in poor health, can result in a
disease that closely resembles invasive disease caused by
E. histolytica in humans. Research into E. invadens has
focused on its usefulness as a model organism for studying
the process of Entamoeba cyst formation. Encystation
of E. invadens can be induced in the laboratory under
controlled conditions, which has yet to be achieved for
E. histolytica. However, the validity of comparing E. his-
tolytica and E. invadens is in question as DNA analysis
shows that these organisms are not very closely related
within the genus Entamoeba (see below).
Life cycle
The majority of Entamoeba species have two stages in their
life cycle: (1) the trophozoite, the motile, feeding and
reproductive stage where cells divide by binary ssion, and
(2) the environmentally resistant cyst, the stage that is
1
 Entamoeba and Entamoeba histolytica
involved in transmission of the parasite between hosts.
Infection of a host usually occurs by ingestion of the cyst,
which is resistant to stomach acids due to the structure of its
thick cell wall. This is followed by excystation and division
of the trophozoite, which will then colonise the hosts
intestinal tract and feed on bacteria. Trophozoites will
encyst when triggered by various environmental conditions
and pass into the environment through the faeces to con-
tinue the infectious cycle. Note that invasion of tissue is not
part of the life cycle (see below). In a few species cysts are
not produced and transmission to a new host occurs
through the trophozoite. For example, E. gingivalis is a
parasite of the human oral cavity rather than the intestines
and infection is thought to occur by direct passage of tro-
phozoites from one persons mouth to another. See also:
Protozoan Asexuality
Morphology
Trophozoite
The shape of an individual trophozoite is extremely vari-
able. Fixed and stained specimens found in human faeces
range in size from 5.0 mm (E. hartmanni) to 50 mm (E. coli).
Fixed resting trophozoites of the human pathogen E. his-
tolytica range from 20 to 40 mm in diameter, whereas
unxed motile forms can elongate to reach 60 mm in length.
The cytoplasm in most species is dierentiated into two
zones, a clear refractile outer zone (ectoplasm) and a
granular inner zone (endoplasm) containing numerous
vacuoles. The two are not clearly dierentiated in E. his-
tolytica, which is highly vacuolated, rich in glycogen and
may contain white blood cells, bacteria, cellular debris and
red blood cells.
The nucleus, usually one per cell, is unique in appearance
and is a dening characteristic of the genus Entamoeba. It is
vesicular, usually spherical and contains a small, dense
structure known as the karyosome (endosome) and an
outer beaded membrane. Subtle dierences in the
morphology of the nuclei exist and have been used in sep-
arating species. In Figure 1, four trophozoites of E. histo-
lytica are shown, each exhibiting the characteristic
Entamoeba-type nucleus.
Cyst
Cysts are typically round and may vary in diameter from
extremes of 3.8 mm (E. hartmanni) to 33 mm (E. coli) in xed
and stained preparations. Cysts of E. histolytica typically
range from 10 to 16 mm. Cysts appear glassy when
unstained, and consist of cytoplasm surrounded by a
refractile wall in stained preparations. Glycogen is present
in concentrated areas in the immature cyst but becomes
diuse as the cyst matures.
A striking feature of the cyst is the presence of chroma-
toid bodies. These structures, which appear dark when
stained with haematoxylin or modied trichrome, are
2 eLS & 2011, John Wiley & Sons, Ltd. www.els.net
Figure 1 Trophozoites of Entamoeba histolytica in fluid drained from the
chest of a patient suffering from amoebic empyema. Note the nuclear
morphology, a distinguishing feature of the genus. Trichrome stain. The
scale bar (lower right) represents 10 mm. From the collection of Kerrison
Juniper Jr, MD (deceased).
aggregates of ribosomes that appear to be crystalline arrays
under transmission electron microscopy. Large chroma-
toid bodies may be present in immature cysts and their
shape is often characteristic for certain species. They are
absent as distinct bodies in the mature cyst due to dis-
aggregation of the ribosome arrays of which they are
composed.
Unlike other eukaryotes, Entamoeba appears to lack
many of the typical cytoplasmic organelles when viewed
by electron microscopy, including mitochondria, rough
endoplasmic reticulum, centrioles, microtubules or Golgi
apparatus. However, functional equivalents of some of
these organelles are now known to be present.
One to eight nuclei are present in Entamoeba cysts and
their appearance is similar to those found in the tropho-
zoite, although they are usually somewhat smaller in spe-
cies where multiple nuclei occur. A cyst of E. histolytica is
shown in Figure 2.
Classification
In the most recent traditional classication system for
protists, the genus Entamoeba is placed in the family
Endamoebidae, order Endamoebida, class Entamoebidea
and phylum Rhizopoda (Corliss, 1994). It is widely rec-
ognised, however, that this is a classication of convenience
and does not necessarily reect the real genetic relation-
ships among organisms. A more recent reorganisation of
the eukaryotic classication system based partly on genetic
analyses (Adl et al., 2005) places the Entamoebida on its
own as a division of the supergroup Amoebozoa. See also:
Amoeba
What we can say with some certainty is that all species in
the genus Entamoeba are related to each other and that we
know of no very close relatives of Entamoeba among the
 Entamoeba and Entamoeba histolytica

Figure 2 A cyst of Entamoeba histolytica seen in faeces from an infected asymptomatic carrier. Three of the four nuclei are clearly visible. Note the large,
dark-staining chromatoid bodies. These are composed of ribosomal aggregates. Iron haematoxylin stain. The cyst is 14 mm in diameter. Courtesy of John E
Williams, London School of Hygiene and Tropical Medicine.

other groups of protists, not even among the amoebae. Table 1 The seven species of Entamoeba infecting humans
Its closest identied relative appears to be the giant amoeba
No. of nuclei in
Pelomyxa, followed by the group containing an intesti-
Species Cyst mature cyst
nal commensal amoeba, Endolimax, and the free-living
amoeboagellates of the genera Mastigamoeba and Oral cavity
Mastigella (Kudryavtsev et al., 2005; Shadwick et al., Entamoeba gingivalis No
2009). (Gros, 1849) Brumpt, 1914
The species within the Entamoeba genus were classically Large bowel
distinguished from one another by morphologic features, Entamoeba polecki von Yes 1
such as the presence or absence of a cyst stage and the Prowazek, 1912a
number of nuclei appearing in the cyst (which can be one, Entamoeba dispar Brumpt, Yes 4
four or eight). These characteristics as they apply to the 1925
seven species known to parasitise humans are presented in Entamoeba hartmanni von Yes 4
Table 1. Although this classication was initially supported Prowazek, 1912
by analysis of Entamoeba DNA, which showed species Entamoeba histolytica Yes 4
forming distinct clusters that correlated with the number of Schaudinn, 1903
cyst nuclei, recent studies have shown that the picture is Entamoeba moshkovskii Yes 4
more complicated. For example, Entamoeba bovis is a Tshalaia, 1941
commensal of ungulates that produces cysts with a single Entamoeba coli (Grassi, Yes 8
nucleus. However, DNA analysis has shown that it is not 1879) Casagrandi and
specically related to other species of Entamoeba that Barbagallo, 1895
produce similar cysts (E. polecki and Entamoeba suis) but a
Previously the species Entamoeba chattoni was also listed as infecting
instead is more closely related to E. histolytica and its humans but it is now known to be a subtype of E. polecki (Stensvold
relatives, which produce cysts with four nuclei (Stensvold et al., 2011).

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 Entamoeba and Entamoeba histolytica
et al., 2010). The diversity of Entamoeba species is still
increasing as more hosts are examined, and a full picture of
their relationships remains to be established.
Among the species that produce cysts with four nuclei,
perhaps surprisingly E. invadens is not closely related to E.
histolytica despite being morphologically very similar and
causing a similar disease in its hosts. This calls into question
its appropriateness as a model for studying cyst formation
in E. histolytica (see above), but no alternative exists at
present. Likewise, E. hartmanni is also not closely related to
E. histolytica, despite the fact that for many years it was
considered to be simply a smaller size class or strain (race)
due to is morphological similarity in other respects. The
closest relatives of E. histolytica are (in increasing genetic
distance): E. nuttalli, E. dispar, Entamoeba ecuadoriensis
and E. moshkovskii. E. nuttalli was only recently rerecog-
nised as a distinct organism (Tachibana et al., 2007).
It causes invasive disease identical to that produced by
E. histolytica but is genetically distinct and is restricted to
nonhuman primate hosts. E. dispar has a much longer
history and is much better studied but was only accepted as
a distinct species in 1997 (see discussion below). E. ecua-
doriensis has only been isolated once, from sewage, and was
originally thought to be a strain of E. moshkovskii but is
now known to be a distinct species (Clark et al., 2006). It
has been little studied. E. moshkovskii is genetically diverse
and was also originally described from sewage but is now
known to infect humans and other vertebrates with varying
frequency (Clark and Diamond, 1997). It is primarily a
free-living organism, almost certainly derived from an
ancestor that was a parasite, and is capable of living at
temperatures ranging from 4 to 378C and in environments
ranging from tidal pools to freshwater lakes. This move
from parasite to free-living is not as radical as it sounds
since the primary food source of all Entamoeba species is
bacteria, which are found in almost every environment.
The ability to tolerate a wide temperature and osmolarity
range is what has allowed E. moshkovskii to colonise a wide
range of environments.
The Human Pathogen: E. histolytica,
and its Morphologic Mimics
Historical aspects
E. histolytica was rst described in a patient with dysentery
in 1875 by the Russian physician Fedor Losch (Losch,
1875). The amoeba was later dierentiated from the larger
human commensal E. coli, and ocially named in 1903 by
Fritz Schaudinn (Schaudinn, 1903). At this time, scientists
and physicians could not understand why many people
were infected with what appeared to be the same organism
but did not develop any disease symptoms. In 1925, Emile
Brumpt proposed that this paradox could be explained by
the existence of two species, one that caused disease and a
second that did not (Brumpt, 1925). He proposed the name
4 eLS & 2011, John Wiley & Sons, Ltd. www.els.net
E. dispar for the latter. However, previous studies in which
human volunteers were infected with material from
patients recovering from invasive amoebiasis showed that
many could harbour disease-causing E. histolytica with-
out developing symptoms (Walker and Sellards, 1913). As
a result, Brumpts ideas were dismissed.
It was not until the past 25 years that scientic advances
in amoebic culture, isoenzyme analysis and molecular
techniques allowed for the recognition of two morpho-
logically identical yet separate species of Entamoeba. E.
histolytica was recognised as the species responsible for all
cases of human invasive disease, whereas E. dispar was not
associated with disease (Diamond and Clark, 1993; Clark,
1998). Later, E. moshkovskii joined E. dispar as a mor-
phologically identical and presumed nonpathogenic
human parasite. These new understandings have drastic-
ally altered our view of the epidemiology of E. histolytica
infection (see below).
Life cycle
Like most Entamoeba species, E. histolytica has both a cyst
and trophozoite stage. Infection is transmitted through the
faecal-oral route, with humans ingesting the infectious and
environmentally resistant cyst form in food or water con-
taminated with human faeces. Experimental studies in
nonhuman New World primates (Hegner et al., 1932)
suggest that ingested cysts of E. histolytica pass unharmed
through the stomach and excyst in the distal portion of the
small intestine, although this has yet to be conrmed in the
human host.
Following excystation, trophozoites reside in the lumen
of the colon, typically as nonpathogenic commensal
parasites. Here, they feed on intestinal bacteria, reproduce
by binary ssion, and eventually encyst and pass out of the
host to infect new humans. The formation of cysts is
thought to be a requirement for environmental survival
since E. histolytica trophozoites have been shown to dis-
integrate within several hours outside of the human host
(Tan et al., 2010). Signals stimulating cyst formation are
not fully understood, but are thought to include changes in
composition of the intestinal bacterial ora and osmotic
conditions (Singh and Ehrenkaufer, 2009).
As many as 90% of infected individuals do not develop
signs or symptoms of disease and are referred to as
asymptomatic carriers (Ali et al., 2008). Although these
individuals do not develop disease, they may shed large
numbers of cysts into the environment and serve as
important reservoirs of infection.
In rare instances, infection with E. histolytica results in
invasion of the intestinal lining by trophozoites, following
digestion of the protective bowel mucin layer by parasite
specic proteases (Stanley, 2003). The signals that lead to a
change from asymptomatic colonisation to symptomatic
invasion of the intestinal mucosa by E. histolytica have
yet to be fully elucidated, although some virulence factors
have been identied, such as cysteine peptidases that
degrade intestinal mucin, a galactose/N-acetylgalactosamine

Figure 3 Trophozoites of Entamoeba histolytica in exudate from a rectal
ulcer biopsy of a patient with bloody diarrhoea suffering from acute
amoebic dysentery. The dark-staining bodies within the cytoplasm of some
of the parasites are ingested red blood cells. Trichrome stain. The scale bar
(lower right) represents 10 mm. From the collection of Kerrison Juniper Jr,
MD (deceased).
(Gal/GalNAc)-specic lectin required for adherence to
colonic epithelial cells and various pore-forming proteins
(amoebapores) implicated in cytotoxicity and apoptosis
of host cells (Stanley, 2003). Members of these protein
classes have also been found to immobilise host cells and
selectively inactivate axons of the enteric nervous system
(Lourenssen et al., 2010). Some evidence for genetic vari-
ation between strains playing a role in the outcome of
infection has also been found (Ali et al., 2007).
Invasive amoebiasis typically begins in the large bowel,
where trophozoite invasion causes abdominal pain and
bloody diarrhoea (dysentery, Figure 3). Trophozoites
invade the bowel lining (mucosa) and extend into the
submucosa, spreading laterally through the submucosa to
form the so-called ask-shaped ulcer, named because its
base is wider than its apex (Figure 4).
Once within the bowel wall, amoebae may enter the cir-
culatory system and travel to other organs to produce
abscesses. Since most blood from the intestines rst travels
to the liver, it is not surprising that this organ is the most
common extraintestinal site of infection. Other organs, such
as the lungs and pleura, pericardium and skin, may also be
involved. Passage of amoebae between two physically close
organs via a rupture of a lesion, such as a liver abscess
located close to the thoracic cavity, may allow for non-
haematogenous spread of infection. Cerebral amoebiasis is
a much rarer and usually fatal complication of amoebiasis.
E. histolytica in the brain must be dierentiated from free-
living amoebae such as Acanthamoeba spp., Balamuthia
mandrillaris and Naegleria fowleri which may also (rarely)
parasitise the human central nervous system.
Variation in parasite virulence, host susceptibility and
environmental factors may all play important roles in the
outcome of E. histolytica infection. From a reproductive
standpoint, there does not appear to be any advantage
gained by tissue invasion as the organism does not form
cysts there and thus cannot give rise to new infections.
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Entamoeba and Entamoeba histolytica
Bowel lumen
epithelium
Ulcer
Sub-
mucosa
Figure 4 Classic flask-shaped ulcer of amoebiasis, in which the base is
wider than the apex. This is created as trophozoites invade through the
intestinal epithelium and invade laterally in the submucosa. Haematoxylin
and eosin stain, 200 times original magnification. Reproduced by
permission of Mayo Clinic Proceedings.
It should be noted that the entire life cycle of E. histo-
lytica as described above only occurs in humans, some
arboreal New and Old World monkeys and the chimpan-
zee. Experimental animals, such as dogs, cats and rodents,
cannot be infected via the oral route, and instead are
infected via rectal or intracaecal inoculation. This clearly
limits our ability to use these animals to study the patho-
genesis and pathology of invasive disease.
Clinical presentation
Amoebiasis refers to infection with E. histolytica with or
without symptoms of disease. As mentioned previously,
most infections with E. histolytica are asymptomatic.
However, approximately 10% of infected individuals
experience symptomatic disease, ranging from mild intes-
tinal inammation (colitis) to severe and even dissemin-
ated infection (Stanley, 2003). Importantly, symptomatic
amoebiasis can occur days to years after initial infection
and must remain in the dierential diagnosis for patients
with exposure to endemic areas. See also: Amoebiasis
Patients with colitis commonly present with abdominal
pain and bloody diarrhoea without fever (Pritt and Clark,
2008). Fulminating amoebic colitis is a rare but potentially
life-threatening form of infection in which patients present
with profuse bloody diarrhoea, severe abdominal pain
and fever. Colonic perforation and peritonitis may ensue,
with up to 40% mortality rate (Aristizbal et al., 1991; Lucas
and Upcroft, 2001). Tumour-like inammatory masses
(amoebomas) may also form and lead to intestinal
obstruction and possibly a misdiagnosis of colon cancer
(Lucas and Upcroft, 2001; Stockinger, 2004).
Patients with liver abscess most commonly present with
right upper quadrant abdominal pain, weight loss and
fever, without concurrent jaundice. Of note, liver abscess
can occur in patients who have no history of intestinal
disease or concurrent intestinal infection. Therefore,
5
 Entamoeba and Entamoeba histolytica
amoebic liver abscess should be considered in all patients
from endemic areas with suggestive clinical ndings,
regardless of intestinal symptoms.
Patients that may be at increased risk for severe disease
include both the very young, the very old, pregnant women
and those with underlying conditions (e.g. malignancy,
diabetes, alcoholism and malnutrition) or immunosup-
pression (Petri and Singh, 1999).
Laboratory diagnosis
Entamoeba species have traditionally been identied by
light microscopic examination of direct, concentrated or
permanently stained faecal specimens. Unfortunately this
method does not allow for dierentiation of E. histolytica
from the morphologically identical E. dispar and E.
moshkovskii. The only morphologic means for identifying
E. histolytica in faecal specimens is when ingested red blood
cells are present within the trophozoite cytoplasm; this is
strongly associated with the pathogenic species (Figure 3)
(WHO/PAHO/UNESCO, 1997). However, this obser-
vation is rare and there is evidence that E. dispar may also
internalise red blood cells (Haque et al., 1995; Trissl et al.,
1978). Therefore it is essential that morphologic ndings be
interpreted in the context of the patients clinical presen-
tation and species conrmation be performed whenever
possible (WHO/PAHO/UNESCO, 1997).
In contrast to microscopic examination, immunological
techniques (e.g. enzyme-linked immunosorbent assays)
and molecular techniques (i.e. polymerase chain reaction)
can provide denitive speciation of E. histolytica cysts and
trophozoites from faeces. Several immunologic methods
are commercially available (Haque et al., 2000).
Serologic assays for detection of anti-E. histolytica IgM
and IgG-class antibodies are also commercially available.
Antibody detection is of particular use for detection of
invasive or disseminated amoebiasis and is the test of
choice for diagnosing amoebic liver abscess.
Less commonly, histologic examination is used to iden-
tify E. histolytica infection in intestinal biopsies or abscess
material. Although examination of intestinal biopsies may
reveal ulcers with undermined edges (the ask-shaped
ulcer), extraintestinal abscesses are largely composed of
necrotic tissue and viable trophozoites are rarely visible.
Though culturing of E. histolytica is possible, it is time
consuming and not routinely available in the clinical
diagnostic setting (Clark and Diamond, 2002). Similarly,
isoenzyme analysis, traditionally used to for dierentiation
of E. histolytica from E. dispar, is not used in clinical
laboratories due to the requirement for in vitro cultures and
technical challenges (Fotedar et al., 2007).
Treatment
In 1997, the WHO and Pan American Health Organization
produced guidelines regarding E. histolytica management.
These guidelines suggest that Entamoeba cysts or tropho-
zoites identied in human faeces should be speciated
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whenever possible and that patients identied as having
E. histolytica in their faeces should be treated, regardless
of whether or not symptoms are present (WHO/PAHO/
UNESCO, 1997). These guidelines also specify that treat-
ment should not be administered when only E. dispar is
identied, except in certain circumstances.
Intestinal amoebic colitis and asymptomatic colonisa-
tion are commonly treated with luminal amoebicides such
as oral paromomycin (Abramowicz, 2010). These agents
do not penetrate bowel tissues or spread systemically
(Ravdin and Stauer, 2005) and thus additional therapies
are recommended for extraintestinal or invasive infections.
Most commonly used for this latter purpose are derivatives
of nitroimidazoles such as tinidazole, ornidazole and
metronidazole. When invasive disease is present this is
treated rst, but should be followed by a course of luminal
amoebicide to eradicate those parasites still in the bowel
lumen.
Patients with invasive or extraintestinal amoebiasis
are typically managed by medical therapy alone. Invasive
procedures such as surgical or percutaneous abscess
drainage are not generally recommended due to the
increased risk of complications such as bacterial sepsis and
wound dehiscence (Salles et al., 2003). However, surgical
intervention may be appropriate in cases of intestinal per-
foration or obstruction and when imminent abscess rup-
ture is suspected.
Epidemiology
Humans are the primary host for the parasite. Transmis-
sion mostly commonly occurs through contamination of
food or water with faeces containing infectious cysts. It is
not surprising, therefore, that the infection is most com-
mon in regions with poor sanitation, overcrowding and
decreased access to clean water.
Amoebiasis is a serious health concern in many parts of
the world. One of the best estimates suggested the existence
of 500 million cases in the world (Walsh, 1988). However,
this estimate was published before the recognition that
humans could harbour the morphologically identical
E. dispar. By using immunologic or molecular methods
that can discriminate between the morphologically iden-
tical species, it is now estimated that individuals colonised
with E. dispar out-number those infected with E. histolytica
by roughly 9 to 1 (Ali et al., 2007, 2008). Taking this into
consideration we are still left with the gure of at least 50
million E. histolytica infections worldwide, an enormous
number.
The reported prevalence of amoebiasis can vary greatly.
A study of outpatients in Brazil found that 6.8% of 1578
stool specimens were positive for E. histolytica (Benetton
et al., 2005), whereas other studies show prevalence rates of
0.8% in rural Brazil, 1% in Iran and 11.2% in Vietnam
(Ximenez et al., 2009). It is incorrect to consider amoebiasis
a tropical disease. In fact, the rst case of amoebiasis was
diagnosed in St. Petersburg from an individual who
was from Northern Russia (Losch, 1875). E. histolytica was

also widespread in parts of the United States, with the
largest recorded outbreak of amoebiasis worldwide
occurring at the Chicago Worlds Fair during which more
than 1400 individuals became ill due to a contaminated
water supply (Bundesen, 1934). In general, infection may
occur anywhere that faecal contamination of food and
water and/or a general lapse of personal hygiene (i.e. hand
washing with soap) occurs.
In resource-rich countries, amoebiasis is largely a disease
of immigrants and travellers from endemic countries. In the
United States, between 1% and 3% of immigrants are
thought to be infected, with approximately 50% of cases
reported from individuals of Asian, Mexican or Pacic
Island descent (Stanley, 2003). With the increasing rate of
immigration worldwide, more developed countries are
likely to see an increased incidence of E. histolytica infec-
tion in the future.
Although most infections with E. histolytica do not
result in clinical disease, complications of invasive and
extraintestinal disease are estimated to cause 40 000
100 000 deaths per year. This makes E. histolytica the third
most common cause of mortality due to a parasite, fol-
lowing malaria and schistosomiasis (Diamond and Clark,
1993; WHO/PAHO/UNESCO, 1997).
Prevention and control
The obvious answer to controlling the spread of E. histo-
lytica as well as other enteric infections is through changing
public health practices, teaching better personal hygiene,
providing means for eective disposal of excreta, and
making potable water available to all. One of the United
Nations Millennium Development Goals is to reduce by
half the number of individuals without access to potable
water and proper sanitation by 2015 (United Nations,
2010). Although many developing nations have made great
strides in these areas, a quarter of the population in these
countries continues to consume contaminated water and
approximately 1.1 billion people do not have access to
latrine facilities (United Nations, 2010). Unfortunately,
achieving these goals require enormous expenditures of
money not readily available in the countries where
amoebiasis is so prevalent.
Vaccination
Several laboratories are engaged in development of a pro-
tective vaccine. However, the problem is so complex and so
little is known about natural immunity to invasive
amoebiasis that, even if an eective acquired immunity
does occur, it is unlikely that a vaccine is near at hand. A
prospective study of children in Bangladesh demonstrated
that mucosal IgA antibodies to the E. histolytica Gal/
GalNAc specic lectin were naturally acquired following
infection (Stanley, 2001). Unfortunately, 20% of the chil-
dren in this study experienced repeated infection, sug-
gesting that immunity is short-lived and/or not eective in
preventing reinfection.
eLS & 2011, John Wiley & Sons, Ltd. www.els.net
Entamoeba and Entamoeba histolytica
However, some laboratories are exploring the develop-
ment of vaccines designed to stimulate the production of
intestinal IgA antibodies (Lotter et al., 2004; Stanley, 2001;
Lotter and Tannich, 2006). Although early eorts are
encouraging, there is no hope for an eective vaccine
against E. histolytica in the near future. Even if such a
vaccine were available, it is unlikely that the people most
likely to benet from vaccination will be able to aord it.
Reasons for Interest in Entamoeba
Species in Addition to their Being
Parasites
Although the role of E. histolytica as a pathogen with a
signicant impact on human health is the primary reason
for interest in it, a number of its other attributes have
attracted the attention of scientists. Only a few of these will
be mentioned here. Some of this interest grew out of studies
related to the disease and certainly all of them are due in
part to E. histolytica being a parasite were it not for this
fact it is likely that it would not have been studied nearly as
extensively as it is not the easiest of organisms with which to
work. Interest in E. histolytica is growing now that its
genome has been sequenced (Loftus et al., 2005).
Evolution
In part because it lacks many of the normal morpho-
logical features of eukaryotic cells, such as mitochondria, it
was long thought that Entamoeba species were primitive
organisms that had diverged from other eukaryotes before
these characteristics were acquired. Loss of structures and/
or functions is quite widespread in parasitic organisms and
genetic analyses have revealed traces of the former presence
of mitochondria and other organelles, indicating that
Entamoeba species are descended from ancestors that had
these structures but subsequently lost or modied them.
Several genes that code for proteins located in mito-
chondria in other eukaryotes have been found. In the case
of Entamoeba species mitochondria there is still a remnant
of the organelle present (Leon-Avila and Tovar, 2004).
Although its present function remains to be fully estab-
lished, signicant progress in understanding its role has
been made. Two studies have come to somewhat dierent,
although not necessarily mutually exclusive, conclusions
(Mi-ichi et al., 2009; Maralikova et al., 2010) and investi-
gations are ongoing. Organelles derived from mito-
chondria are being studied in a number of dierent
organisms and it is clear that each has distinctive features.
See also: Mitochondria: Origin
One of the surprising ndings to come out of the genome
sequence is the number of genes in E. histolytica that appear
to have been acquired by lateral transfer from bacteria.
Many genes have been identied in Entamoeba that are of
bacterial origin and not present in other eukaryotes (Loftus
et al., 2005; Clark et al., 2007) although as more genomes
7
 Entamoeba and Entamoeba histolytica
are sequenced this number is changing. Sometimes the
same genes appear to have been acquired independently in
separate eukaryotic groups.
Locomotion
Amoeboid movement is used by many species of protists
but it is also found in a variety of cell types in multicellular
organisms, for example, the various white blood cells of
animals. This similarity has led to the locomotion of
Entamoeba being studied in order to compare it with the
same process in other cell types. Related in mechanism to
locomotion, the process of ingesting bacteria (phago-
cytosis) has been studied in Entamoeba for comparative
purposes as it also occurs in certain blood cells. It was
shown long ago that E. histolytica has the ability to get rid
of antibodies that attach to its surface by capping or
sloughing o part of its surface membrane. We are now
able to study the rearrangements of structures involved in
locomotion, phagocytosis and capping using specic
molecular tags and it is clear that all three processes use
many of the same molecules. The genome sequence has also
revealed unusual aspects of Entamoeba locomotion (Clark
et al., 2007). For example, there are no genes coding for
components of intermediate laments. There are also a
very limited number of myosin types, two, compared to
most eukaryotes. In contrast it has very large numbers of
genes coding for proteins involved in sensing the environ-
ment and signalling within the cell. It will take a long time
to unravel all these processes. See also; Phagocytosis;
Protozoan Organelles of Locomotion
Cell killing
The characteristic of E. histolytica that gave it its name
(histo, tissue; lytica, destroyer) has attracted much atten-
tion, and not only because of its role in producing disease in
the host. Most pathogens have to evade cells of the immune
system or they will be killed. Some pathogens hide inside
cells but E. histolytica has the ability to kill the killer
immune cells instead. It turns out that some of the methods
used by E. histolytica to kill cells are the same as those used
by cells of the immune system to kill pathogens; for
instance, both produce pore-forming proteins that punch
holes in the membrane of the cell being attacked. Com-
parison of the structure of these molecules in Entamoeba
and in mammals has yielded insights into how they func-
tion. These proteins are also used to kill the amoebas prey
by punching holes in the membrane of bacteria, and this is
their normal function, however they will also kill host cells
when the amoeba comes into contact with them. The gen-
ome sequence has revealed that E. histolytica codes for a
remarkable number of enzymes involved in protein deg-
radation over 40 of the cysteine peptidase group alone
(Clark et al., 2007). How these dierent proteins are
coordinated and what their specic targets are remains to
be elucidated. See also: Pore-forming Toxins
8 eLS & 2011, John Wiley & Sons, Ltd. www.els.net
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