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Amoebiasis

Straight to the point of care

Last updated: Sep 27, 2023


Table of Contents
Overview 3
Summary 3
Definition 3

Theory 4
Epidemiology 4
Aetiology 4
Pathophysiology 5
Classification 11
Case history 12

Diagnosis 16
Approach 16
History and exam 23
Risk factors 24
Investigations 26
Differentials 31

Management 32
Approach 32
Treatment algorithm overview 32
Treatment algorithm 33
Primary prevention 34
Secondary prevention 34
Patient discussions 35

Follow up 36
Monitoring 36
Complications 37
Prognosis 39

Guidelines 40
Diagnostic guidelines 40
Treatment guidelines 40

References 41

Images 45

Disclaimer 54
Amoebiasis Overview

Summary
Amoebiasis is a common cause of diarrhoea in infants in low-income countries and an emerging sexually
transmitted infection in some developed countries. Amoebiasis also causes colitis that can present with

OVERVIEW
diarrhoea and/or dysentery that can be acute or last more than 1 week. Abdominal tenderness and weight
loss are common with amoebic colitis.

Amoebic liver abscess presents with right upper quadrant pain. May not present with diarrhoea, but will
usually have a preceding history of diarrhoea.

Rare cause of brain abscess.

Most patients will have travelled to or resided in an endemic area in the 12 months preceding presentation.
Men who have sex with men and persons who engage in oral-anal sexual contact are at high risk for sexually
transmitted amoebiasis.

Diagnosis is confirmed by detection of Entamoeba histolytica antigen or DNA in stool or antibodies against
the parasite in serum.

Treatment is with nitroimidazoles (including metronidazole or tinidazole) followed by luminal agents such as
paromomycin or diloxanide furoate to prevent relapse. Reinfection is common in endemic regions; patients
should be counselled on how to reduce the risk of reinfection.

Definition
Amoebiasis is caused by the parasite Entamoeba histolytica. It causes diarrhoea and colitis. Spread of
infection from the intestine can result in liver abscess (via haematogenous dissemination). Extension from
liver abscess can lead to pleural and pericardial effusion. Rarely, brain abscess may occur. Fulminant
amoebiasis, presenting as peritonitis due to intestinal perforation, is a rare but life-threatening form of
amoebiasis.[1] [2] [3] [4] [5] [6]

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Amoebiasis Theory

Epidemiology
There is a higher incidence of amoebiasis in developing versus developed countries. It occurs most
commonly in areas of poor sanitation.[9] Most amoebic infections occur in Central and South America, Africa,
THEORY

and Asia.[2] Entamoeba histolytica infection in the US is seen most commonly in immigrants and travellers
from endemic areas, with approximately 3000 cases seen annually.[4] In most cases, disease presents within
the first year of return to or arrival in the country. Long-term travellers (duration >6 months) are much more
likely than short-term travellers (duration <1 month) to develop infection.[9]

Intestinal infection with E histolytica affects all ages and both sexes equally. However, 90% of amoebic
liver abscesses occur in men aged 20 to 40 years.[1] [2] [3] [4] [5] The increased risk of amoebiasis-related
mortality in men may reflect the increased prevalence of amoebiasis among men who have sex with men
(MSM), although it was previously reported that the non-pathogenic amoeba E dispar is more common in
this setting than E histolytica. [1] [2] [10][11] Other groups at greater risk for severe disease include people
who are pregnant, immunocompromised, or receiving corticosteroids, people with diabetes, and those who
consume alcohol.[9]

Outbreaks in institutions, particularly those for people who are intellectually disabled, have occurred.[1]
[2] MSM, oral-anal sexual contact, lower educational achievement, and older age were associated with
increased risk for amoebiasis among people seeking voluntary counselling and testing for HIV infection
in Taiwan.[12] Comorbid HIV infection and past history or positive serology of syphilis have also been
associated with increased prevalence of amoebiasis. The reasons for these associations are unclear, but
may reflect similar risk factors for these infections.[10] [13] [14] [15]

Globally, E histolytica accounts for 2% to 4% of cases of diarrhoea presenting to a hospital or a clinic.[1] [2]
[3] [4] [5] [6] [7]

Aetiology
Amoebiasis is contracted by ingestion of the cyst of Entamoeba histolytica, which is found in faecally
contaminated food and water. Transmission can also occur directly through sexual intercourse (especially
oral-anal sexual contact) or contact with faecally contaminated objects. Cysts are environmentally stable,
being resistant to chlorination and desiccation.

Cyst of Entamoeba histolytica : iodine stain of stool sample


Reproduced from Current Concepts (2003); used with permission

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Amoebiasis Theory

THEORY
Cyst of Entamoeba histolytica: unstained (A), and iodine
stained (B) after formalin-ether concentration of stool sample.
Original photos from National Center for Global Health and Medicine, Tokyo, Japan.

Pathophysiology
The life-cycle of E histolytica typically begins with ingestion of faecally contaminated food or water. Sexual
transmission due to anal-oral contact is also possible.[11] [16] [17] The infective cyst form of the parasite
survives passage through the stomach and small intestine. It excysts in the bowel lumen to form motile and
potentially invasive trophozoites.

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THEORY Amoebiasis Theory

Life-cycle of Entamoeba histolytica


Reproduced from New England Journal of Medicine (2003); used with permission

In most infections, the trophozoites aggregate in the intestinal mucin layer and form new cysts, resulting in
a self-limiting and asymptomatic infection. However, galactose/N-acetyl-galactosamine (Gal/GalNAc) lectin-
mediated adherence to and lysis of the colonic epithelium can initiate trophozoite invasion into the colon in
some cases.

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Amoebiasis Theory

THEORY
Trophozoites of Entamoeba histolytica : trichrome stain of stool sample
Reproduced from Clinical Infectious Diseases (1999); used with permission

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THEORY Amoebiasis Theory

Trophozoite of Entamoeba histolytica with pseudopod (red arrow): direct unstained stool sample.
Original photo from National Center for Global Health and Medicine, Tokyo, Japan.

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Amoebiasis Theory

THEORY
Amoebic ulcerations of the colon: colonic ulcers averaging 1 mm to 2 mm in diameter on gross pathology
Reproduced from New England Journal of Medicine (2003); used with permission

Neutrophils responding to invasion contribute to cellular damage at the site of invasion. Once the intestinal
epithelium is invaded, extraintestinal spread into the peritoneum, liver, and other sites is possible.

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THEORY Amoebiasis Theory

Posterior-anterior and lateral CXR of a patient with amoebic liver abscess: CXR
findings include elevated right hemidiaphragm and evidence of atelectasis
Reproduced from New England Journal of Medicine (2003); used with permission

Factors controlling invasion versus encystation include parasite quorum sensing signalled by the Gal/GalNAc
lectin interactions of amoebae with the bacterial flora of the intestine, and host innate and acquired immune
responses.

Trophozoites are always present in the gut in patients with amoebic diarrhoea and dysentery (diarrhoea with
blood or mucus), and diagnosis should concentrate on identifying the parasite in stool by antigen detection
and the serum antibody response against the invasive parasite.[1] [2]

Invasion of the trophozoites through the intestinal epithelium leads to amoebic diarrhoea and colitis. Invasion
involves a unique nibbling process by the parasite on the intestinal lining, termed amoebic trogocytosis.[18]

Haematogenous dissemination via the portal venous system results in amoebic liver abscess and infection in
other sites such as the brain, although this is rare.[1] [2] [3] [4] [5]

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Amoebiasis Theory

THEORY
Entamoeba histolytica brain abscess
Reproduced from Transactions of the Royal Society of Tropical Medicine and Hygiene (2007); used with permission

Classification
Taxonomy classification[6]
Infectious:

• Entamoeba histolytica
Commensal:

• Entamoeba dispar
• Entamoeba moshkovskii
• Entamoeba bangladeshi

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Amoebiasis Theory
• Entamoeba coli
• Entamoeba hartmanni
• Entamoeba polecki
• Entamoeba gingivalis
THEORY

Clinical manifestations[2]
1. Asymptomatic colonisation

• Presence of E histolytica in stool in the absence of colitis or extraintestinal manifestations


2. Intestinal amoebiasis

3. Extraintestinal amoebiasis

• Amoebic liver abscess


• Splenic abscess
• Empyema
• Pericarditis
• Brain abscess

Case history
Case history #1
A 23-year-old woman complains of diarrhoea lasting several weeks. She has lost weight, but has not had
a fever, and has not noticed blood in the stool. The diarrhoea started while she was travelling in Mexico.

Case history #2
A 39-year-old man presents to the accident and emergency department with right shoulder pain that
he has been experiencing for 2 months. He reports that the pain has radiated to his back. He has been
having night sweats and chills and has lost around 5 kg in weight. He has also had abdominal pain for
3 days and a non-productive cough. He was born in Iran and recently emigrated to the US. Physical
examination identifies hepatomegaly and decreased breath sounds over the lower two-thirds of the right
lung. Neurological examination is normal.

Other presentations
Amoebiasis is asymptomatic in 80% of cases. Diarrhoea is the most common illness caused by
Entamoeba histolytica , although intestinal disease may present as dysentery (diarrhoea with blood or
mucus) rather than diarrhoea alone. An amoeboma, which is a mass of granulation tissue in the colon
that can be similar in appearance to colonic carcinoma, may also be detected.

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Amoebiasis Theory

THEORY
Cyst of Entamoeba histolytica: unstained (A), and iodine
stained (B) after formalin-ether concentration of stool sample.
Original photos from National Center for Global Health and Medicine, Tokyo, Japan.

Less common extraintestinal manifestations are peritonitis from perforation of the intestine, which
sometimes mimics acute appendicitis, and pleural or pericardial effusions from direct extension of a liver
abscess and brain abscess (almost all patients with brain abscess due to E histolytica also have a liver
abscess).[1] [2] [3][4] [5] [6][7] [8] Amoebic acute appendicitis is also a possible but rare manifestation of
amoebiasis; amoebic appendicitis is more likely to be complicated than non-amoebic appendicitis.[8]

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THEORY Amoebiasis Theory

Amoebic appendicitis with skin fistula two weeks after appendectomy (enhanced computed tomography).
Original photo from National Center for Global Health and Medicine, Tokyo, Japan.

Hematoxilin-Eosin stain (A-C) and Periodic acid-Schiff stain (D-F) of resected appendix
of amoebic appendicitis. Entamoebas are deeply dyed by Periodic acid-Schiff stain.
Original photo from National Center for Global Health and Medicine, Tokyo, Japan.

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Amoebiasis Theory

THEORY

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Amoebiasis Diagnosis

Approach
Confirmatory laboratory tests should be performed before starting therapy for those in whom amoebiasis is
suspected. Diagnostic tools include stool antigen detection, stool (or abscess aspirate in the case of extra-
intestinal disease) polymerase chain reaction (PCR) testing, stool microscopy, serology, and colonoscopy
with histologic examination.

Clinical evaluation
Amoebiasis should be considered in any individual who presents with diarrhoea or liver abscess and who
has travelled or lived in an endemic area in the previous 12 months. Other populations at risk of infection
are institutionalised individuals, men who have sex with men, and commercial sex workers and their
sexual contacts.[13]

Presentation is subacute in many cases; most patients have a gradual illness onset days or weeks after
infection.[9] Key symptoms of infection are diarrhoea that has lasted for several days or longer and
abdominal pain. Entamoeba histolytica diarrhoea is usually lacking blood or mucus, and is therefore
indistinguishable from diarrhoea caused by a variety of other enteropathogens. Patients may report
blood in their stool, however. Weight loss is reported by about 50% of patients.[1] Right upper quadrant
(RUQ) abdominal pain in a man aged 20 to 40 years, with or without coincident diarrhoea, could indicate
an amoebic liver abscess.[1] [2] [3] [4] [5] Patients may report altered mental status if brain abscess
is present. Amoebic acute appendicitis is a possible but rare manifestation of amoebiasis; amoebic
appendicitis is more likely to be complicated than non-amoebic appendicitis.[8]

Physical examination
Fever is rare with intestinal infection but common with hepatic infection. With hepatic infection, jaundice,
RUQ tenderness, and hepatomegaly may be present. Liver abscesses may extend into the pleural or
pericardial cavities (rare), resulting in signs of a pleural or pericardial effusion. Splenic abscess is a rare
manifestation of amoebiasis. Neurological abnormalities, such as limb weakness, may be present in
patients with a brain abscess.
DIAGNOSIS

Laboratory evaluation
Of the available diagnostic tests, antigen testing and PCR can differentiate between E histolytica and
the non-pathogenic E dispar . PCR has the highest sensitivity and is the method of choice for diagnosis;
however, protocols (DNA extraction and primer-probe sets) are not fixed, and only limited institutes can
return reliable results. Also, cost is a barrier to its use as a routine test in many endemic areas. Laboratory
diagnosis of intestinal amoebiasis in many countries still relies on antigen-detection or ova and parasite
microscopy.[23]

Microscopy

Stool microscopy relies on observation of cysts and trophozoites in faeces, colonic scrapings, aspirates
and tissue samples.[24] It is not specific for the diagnosis of amoebiasis, as E histolytica cysts and
trophozoites are indistinguishable from those of E dispar , E moshkovskii , and E bangladeshi .
Historically, E dispar and E moshkovskii have been considered non-pathogenic, but evidence is
mounting that E moshkovskii can cause illness; E bangladeshi has only recently been identified, so
its pathogenic potential is not well understood.[9] Whilst it lacks specificity, stool microscopy for ova,
cysts, and parasites has the advantage of being readily available and may demonstrate other infectious

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Amoebiasis Diagnosis
causes. The presence of erythrophagocytic trophozoites is highly suggestive of E histolytica infection.
UK guidelines recommend that stool samples which are positive on microscopy for Entamoeba spp.
should be sent for confirmatory PCR testing.[24]

PCR

Where available, PCR is now the method of choice for diagnosis of E histolytica .[9] [24] PCR and
real-time quantitative PCR (qPCR) testing of stool is highly sensitive and specific for the detection of
E histolytica .[25] Real-time qPCR is more sensitive than traditional PCR.[25] Stool samples which are
positive on microscopy for E histolytica/dispar should be sent for confirmatory PCR testing.[24]

Liver abscesses should be aspirated to determine aetiology. The pus should be analysed by PCR
or qPCR to identify whether the causal infection is amoebic and cultured to determine whether it is
pyogenic.[1] [2]

Antigen testing

Antigen testing on stool samples is an alternative to PCR. Antigen tests have been well studied and
have several advantages, including their technical simplicity, relative low cost and rapid turnaround.[24]
Available testing kits include the TechLab E histolytica II (ELISA), the TechLab E. HISTOLYTICA QUIK
CHEK, or The Cellabs Entamoeba CELISA Path. These are highly specific for E histolytica ; other
detection kits detect the E histolytica-E dispar-E moshkovskii species complex.[26]

Serum antibody testing

In patients with suspected amoebic disease, especially possible liver abscess without concurrent
intestinal infection (where there are unlikely to be detectable parasites in the stool), serum antibody
testing for E histolytica can be a useful diagnostic adjunct.[2] [26] Tests for antibodies are approximately
90% sensitive for amoebic liver abscess and 70% sensitive for amoebic colitis.[2] A major problem
with serological tests however, is that the patient continues to test positive for years after an episode of
amoebiasis; as a result, a substantial number (10% to 35%) of residents of developing countries have
antibodies to amoebae. Therefore, negative serology is helpful for exclusion of disease, but positive

DIAGNOSIS
serology cannot distinguish between acute and previous infection.[2]

Cyst of Entamoeba histolytica : iodine stain of stool sample


Reproduced from Current Concepts (2003); used with permission

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Amoebiasis Diagnosis

Cyst of Entamoeba histolytica: unstained (A), and iodine


stained (B) after formalin-ether concentration of stool sample.
Original photos from National Center for Global Health and Medicine, Tokyo, Japan.
DIAGNOSIS

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Amoebiasis Diagnosis

DIAGNOSIS
Trophozoites of Entamoeba histolytica : trichrome stain of stool sample
Reproduced from Clinical Infectious Diseases (1999); used with permission

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DIAGNOSIS Amoebiasis Diagnosis

Trophozoite of Entamoeba histolytica with pseudopod (red arrow): direct unstained stool sample.
Original photo from National Center for Global Health and Medicine, Tokyo, Japan.

Colonoscopy
May be helpful if clinical suspicion is high and antigen detection tests are negative.[2] Biopsy specimens
should be taken from the edge of an ulcer. Histology may show trophozoites, but the sensitivity
of histopathological diagnosis using biopsy samples obtained by colonoscopy is low (45.5%).[27]
Endocytoscopy may allow for real-time visualisation of amoebae in the colonic mucosa of patients with
colitis.[28] Amoebiasis is occasionally diagnosed during detailed examination to investigate chronic
diarrhoea and positive results on faecal occult blood testing.[29] [30]

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Amoebiasis Diagnosis

Amoebic ulcerations of the colon: colonic ulcers averaging 1 mm to 2 mm in diameter on gross pathology
Reproduced from New England Journal of Medicine (2003); used with permission

Imaging
If liver involvement is suspected, a liver ultrasound should initially be performed. CXR and chest/
abdominal CT are indicated if an effusion due to abscess extension is suggested by clinical findings.

DIAGNOSIS

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Amoebiasis Diagnosis

Posterior-anterior and lateral CXR of a patient with amoebic liver abscess: CXR
findings include elevated right hemidiaphragm and evidence of atelectasis
Reproduced from New England Journal of Medicine (2003); used with permission

Patients with neurological symptoms should have a CT or MRI of the brain.[1] [5]
DIAGNOSIS

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Amoebiasis Diagnosis

DIAGNOSIS
Entamoeba histolytica brain abscess
Reproduced from Transactions of the Royal Society of
Tropical Medicine and Hygiene (2007); used with permission

History and exam


Key diagnostic factors
presence of risk factors (common)
• Key risk factors include exposure in endemic areas, institutionalisation, men who have sex with men,
and male sex.

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Amoebiasis Diagnosis
diarrhoea (common)
• Patients may have had diarrhoea for 1 week or more at the time of presentation.[1] [26] Entamoeba
histolytica diarrhoea is usually lacking blood or mucus, and is therefore indistinguishable from
diarrhoea caused by a variety of other enteropathogens.
• Less than 50% of patients with a liver abscess will have diarrhoea at time of presentation, although a
past history of diarrhoea or dysentery is common.

Other diagnostic factors


generalised abdominal pain (common)
• Present in some patients with amoebiasis.

right upper quadrant abdominal pain (common)


• May indicate an amoebic liver abscess.[1] [5]

weight loss (common)


• About half of patients may report weight loss due to the subacute nature of the disease.[1]

cough (common)
• Common in patients with liver abscess. Caused by phrenic nerve irritation and/or pleural effusion.[1]

fever (uncommon)
• Rare in intestinal infections but common in extraintestinal infections, such as liver and brain
abscesses.[1]

altered mental status or limb weakness (uncommon)


• Present with amoebic brain abscess.[1][5] [3]

dyspnoea (uncommon)
DIAGNOSIS

• Extension of liver abscess can cause pleural or pericardial effusion.

guarding and rebound tenderness of the abdomen (uncommon)


• Present with acute necrotising colitis, toxic megacolon, or peritonitis due to amoebiasis.[1]

jaundice (uncommon)
• More common with pyogenic than amoebic liver abscess.[1] [5]

right lung decreased air entry and percussion note (uncommon)


• If pleural effusion present.

Risk factors
Strong
exposure in endemic areas
• Most patients with amoebiasis will have visited or resided in an endemic area within the previous 12
months.[1] [2] [4] [19] [20]

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Amoebiasis Diagnosis
institutionalisation of intellectually disabled people
• Outbreaks in institutions for people with intellectual disability have been reported.[2] [3][4] [5]

men who have sex with men


• There is an increased prevalence of sexually transmitted amoebiasis among men who have sex with
men.[2] [11] [17] Commensal amoeba Entamoeba dispar is responsible for most infections, but
Entamoeba histolytica infections also occur in this population.[2] [3][4] [5][11] [21]

oral-anal sexual contact


• Oral-anal sexual contact is a risk factor for sexual transmission of amoebiasis.[3] [11] [17] Clustering of
Entamoeba histolytica strains has been found due to oral-anal sexual contact.[16]
• Those with multiple partners, including commercial sex workers, may be at increased risk.[13] [16]

male sex
• Ninety percent of amoebic liver abscesses are found in men aged 20 to 40 years.[1] [2] [3][4] [5]

Weak
HIV infection, past or current syphilis infection
• Comorbid HIV infection and past history or positive serology of syphilis have been associated with
increased prevalence of sexually transmitted amoebiasis. The reasons for these associations are
unclear, but may reflect similar risk factors for these infections.[10] [13] [14] [22] The strength of these
associations may depend on the local epidemiology.

DIAGNOSIS

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Amoebiasis Diagnosis

Investigations
1st test to order

Test Result
stool microscopy identification of
Entamoeba in stool
• Not as sensitive or specific as other tests but still used clinically to
confirm amoebic intestinal infection.[1] [2] [3] [4] [5]
• Stool microscopy relies on observation of cysts and trophozoites
in faeces, colonic scrapings, aspirates and tissue samples.[24] It
is not specific for the diagnosis of amoebiasis, as E histolytica
cysts and trophozoites are indistinguishable from those of E dispar
, E moshkovskii , and E bangladeshi . Whilst it lacks specificity,
stool microscopy has the advantage of being readily available
and may demonstrate other infectious causes. The presence of
erythrophagocytic trophozoites is highly suggestive of E histolytica
infection.
• UK guidelines recommend that stool samples which are positive on
microscopy for Entamoeba spp. should be sent for confirmatory
PCR testing.[24]
PCR or qPCR of stool or liver abscess pus for E histolytica DNA amplification of amoebic
DNA
• Where available, PCR is now the method of choice for diagnosis of
E histolytica .[9] [24] However, protocols (DNA extraction and primer-
probe sets) are not fixed, and only limited institutes can return reliable
results. Also, cost is a barrier to its use as a routine test in many
endemic areas, meaning that laboratory diagnosis in many countries
still relies on antigen-detection or microscopy for ova and parasites.
PCR and real-time quantitative PCR (qPCR) testing of stool is highly
sensitive and specific for the detection of E histolytica .[25] Real-
time qPCR is more sensitive than traditional PCR.[25] Stool samples
which are positive on microscopy for E histolytica/dispar should be
sent for confirmatory PCR testing.[24] Liver abscesses should be
aspirated to determine aetiology. The pus should be analysed by
DIAGNOSIS

PCR or qPCR to identify whether the causal infection is amoebic and


cultured to determine whether it is pyogenic.[1] [2]
stool antigen detection positive for parasite
antigen
• Antigen testing on stool samples is an alternative to PCR. Antigen
tests have been well studied and have several advantages, including
their technical simplicity, relative low cost and rapid turnaround.[24]
Only the Cellabs Entamoeba CELISA Path, the TechLab Entamoeba
histolytica II, or the TechLab Histological Quik Chek tests specifically
identify E histolytica ; other antigen detection tests detect the E
histolytica-E dispar-E moshkovskii species complex.[26]
serum antibody test positive for antiamoebic
antibodies
• In patients with suspected amoebic disease, especially possible
liver abscess without concurrent intestinal infection (where there are
unlikely to be detectable parasites in stool), serum antibody testing
for E histolytica can be a useful diagnostic adjunct.[2] [26] Tests
for antibodies are approximately 90% sensitive for amoebic liver
abscess and 70% sensitive for amoebic colitis.[2] A major problem
with serological tests however, is that the patient continues to test
positive for years after an episode of amoebiasis; as a result, a
substantial number (10% to 35%) of residents of developing countries

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Amoebiasis Diagnosis

Test Result
have antibodies to amoebae. Therefore, negative serology is helpful
for exclusion of disease, but positive serology cannot distinguish
between acute and previous infection.[2]

DIAGNOSIS

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Amoebiasis Diagnosis

Other tests to consider

Test Result
colonoscopy granular, friable, and
diffusely ulcerated
• May be helpful if clinical suspicion is high and antigen detection
mucosa
tests are negative.[2] Biopsy specimens should be taken from the
edge of an ulcer. Histology may show trophozoites, but the sensitivity
of histopathological diagnosis using biopsy samples obtained by
colonoscopy is low (45.5%).[27] Endocytoscopy may allow for real-
time visualisation of amoebae in the colonic mucosa of patients with
colitis.[28]

Amoebic ulcerations of the colon: colonic ulcers


averaging 1 mm to 2 mm in diameter on gross pathology
Reproduced from New England Journal
of Medicine (2003); used with permission
liver ultrasound homogeneous
DIAGNOSIS

hypoechoic round or oval


• Useful only in a patient with amoebic liver, not amoebic intestinal,
lesion
infection.[1]
• Unable to distinguish from a pyogenic abscess.[2]
CXR right hemidiaphragm
elevation or right-sided
• Performed if clinical findings suggestive of effusion and presence of
pleural effusion
liver abscess.

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Amoebiasis Diagnosis

Test Result

Posterior-anterior and lateral CXR of a patient with


amoebic liver abscess: CXR findings include elevated
right hemidiaphragm and evidence of atelectasis
Reproduced from New England Journal
of Medicine (2003); used with permission
CT liver/chest/head rounded, well-defined,
low-at tenuation lesion;
• Unable to distinguish from a pyogenic abscess.[2]
wall commonly enhances
with contrast; pleural
effusion

DIAGNOSIS

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Amoebiasis Diagnosis

Test Result
DIAGNOSIS

Entamoeba histolytica brain abscess


Reproduced from Transactions of the Royal Society of
Tropical Medicine and Hygiene (2007); used with permission
MRI brain space-occupying lesion(s)
• Required if neurological symptoms.

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Amoebiasis Diagnosis

Differentials

Condition Differentiating signs / Differentiating tests


symptoms
Infectious diarrhoea • Differential diagnosis is • Presence of specific
broad as various bacteria, infectious agent on stool or
parasites, and viruses cause serological testing.
diarrhoea.[31]

Ulcerative colitis • Absence of history of travel • Stool and antigen testing


to endemic areas. negative for infectious
• Bloody diarrhoea. agents.
• Typical colonoscopy and
biopsy appearance.

Pyogenic liver abscess • Occurs predominantly in • Infective organism identified


females. in blood or pus culture.
• Jaundice is more common
with pyogenic liver abscess
than with amoebic liver
abscess.
• Associated with hepatobiliary
disease.

Necrotic hepatoma • Absence of history of • Aspirate of hepatoma


travel to endemic areas or negative for infectious cause.
diarrhoea.

Fascioliasis (liver flukes) • There are no physical • Key diagnostic test is


differentiating characteristics. positive serum antibody for
fascioliasis.
• Eosinophilia.

Echinococcal liver cyst • There may be no clinical • Positive serum antibody test

DIAGNOSIS
features of an echinococcal for echinococcus.
liver cyst (which is • Aspiration of cyst should
sometimes an incidental be avoided because of the
finding in a patient not possibility of anaphylaxis.
presenting with abdominal
complaints). It may present
with anaphylaxis caused by
spillage of cyst contents into
the peritoneum.

Screening
Family members in the household of an index case should be screened.[2]

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Amoebiasis Management

Approach
All Entamoeba histolytica infections should be treated.[1] [5] Treatment should be given as soon as the
diagnosis is considered, after samples have been taken for testing, as amoebiasis is a potentially fatal
illness.

Symptomatic patients should initially be given a nitroimidazole (metronidazole or tinidazole). Nitroimidazoles


have excellent tissue penetration and are active for both luminal and invasive infection. There is no
recognised resistance to this class of antiamoebic medicine. This should be followed with a luminal agent
(such as paromomycin or diloxanide) to eradicate gut colonisation and prevent relapse.[1] [5] [9][32] [33] [34]
For most of these medicines, adverse effects are generally minor, whereas the infection itself is potentially
fatal.

Asymptomatic patients also require treatment because of the risk for developing future invasive disease.[1]
[5] They should be treated with a luminal agent alone.[34] [35]

Amoebic liver abscess


Percutaneous aspiration is not commonly required. It may be required for patients who do not respond to
nitroimidazole treatment in 5 to 7 days, or with large (>5 cm diameter) or left lobe lesions. In patients with
large abscesses, draining the abscess in addition to treating with metronidazole or tinidazole could aid in
the early resolution of pain and tenderness.[1] [2] [5] [9][36] [37]

Treatment algorithm overview


Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

Acute ( summary )
symptomatic amoebiasis

1st nitroimida zole

plus luminal agent

liver abscess that adjunct aspiration


does not respond to
nitroimida zole after
5-7 days, large (>5 cm
diameter) or left lobe
lesions

asymptomatic amoebiasis

1st luminal agents


MANAGEMENT

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Amoebiasis Management

Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

Acute
symptomatic amoebiasis

1st nitroimida zole


Primary options

» metronidazole: children: 35-50 mg/kg/day


orally given in 3 divided doses for 7-10 days;
adults: 500-750 mg orally three times daily for
7-10 days

OR

» tinidazole: children: 50 mg/kg orally once


daily for 3 days (or 5 days if liver abscess),
maximum 2000 mg/day; adults: 2000 mg
orally once daily for 3 days (or 5 days if liver
abscess)

» Treatment should be given as soon as the


diagnosis is considered, after samples have
been taken for testing, as amoebiasis is a
potentially fatal illness.[1] [5]

» Nitroimidazoles have excellent tissue


penetration and are active for both luminal and
invasive infection.

» Treatment with nitroimidazole is followed


with a luminal agent to eliminate intestinal
colonisation.[32] [33]

» For most of these medicines, adverse effects


are generally minor, whereas the infection itself
is potentially fatal.
plus luminal agent
Treatment recommended for ALL patients in
selected patient group
Primary options

» paromomycin: children and adults: 25-35


mg/kg/day orally given in 3 divided doses for
5-10 days

OR
MANAGEMENT

» diloxanide furoate: children: 20 mg/kg/day


orally given in 3 divided doses for 10 days;
adults: 500 mg orally three times daily for 10
days

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Amoebiasis Management

Acute
» Luminal agents are used after completion of
acute therapy with the nitroimidazole to eradicate
gut infection and thereby reduce the risk of a
relapse of infection.[33]
liver abscess that adjunct aspiration
does not respond to
Treatment recommended for SOME patients in
nitroimida zole after
selected patient group
5-7 days, large (>5 cm
diameter) or left lobe » Percutaneous aspiration of an amoebic
lesions abscess is not commonly required, but may
be indicated for patients who do not respond
to nitroimidazole treatment in 5 to 7 days, or
those with large (>5 cm diameter) or left lobe
lesions. In patients with large abscesses,
draining the abscess in addition to treating with
metronidazole or tinidazole could aid in the early
resolution of pain and tenderness.[1] [2] [5] [9]
[36] [37]
asymptomatic amoebiasis

1st luminal agents


Primary options

» paromomycin: children and adults: 25-35


mg/kg/day orally given in 3 divided doses for
5-10 days

OR

» diloxanide furoate: children: 20 mg/kg/day


orally given in 3 divided doses for 10 days;
adults: 500 mg orally three times daily for 10
days

» Asymptomatic patients require treatment


because of the risk of developing future invasive
disease.[1] [5] They should be treated with a
luminal agent alone.[35]

Primary prevention
Primary prevention is accomplished by taking precautionary measures against ingestion of faecally
contaminated food and water, particularly in endemic areas, such as not drinking tap water and not
consuming food that may have been washed in contaminated water.[1] Patients with a high risk for sexual
transmission of amoebiasis should be counselled on safer sex.[11]

Secondary prevention
MANAGEMENT

There is evidence of household transmission of amoebiasis (common in developing countries, but extremely
rare in developed countries), so it is prudent for all household contacts of the patient to be screened for
amoebiasis using stool microscopy followed by confirmatory PCR, or directly by stool PCR.[1] [5] [24]

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Amoebiasis Management
To reduce risk of spreading infection, patients should be advised to wash hands regularly and not to share
household towels. Patients with diarrhoea should not return to work/other settings until 48 hours after
resolution of any episodes of diarrhoea. No additional formal exclusion periods or microbiological clearance
for public health reasons for confirmed cases of E histolytica infection are required.[24]

Reinfection occurs easily in endemic regions. Patients with a high risk for sexual transmission of amoebiasis
should be counselled on safer sex to avoid recurrence.[11]

Patient discussions
Patients treated for amoebiasis should be warned of the side effects of the medications that they are
receiving, of the need to adhere to the follow-up course of a luminal agent to eradicate colonisation (and
thereby prevent relapse), and of the symptoms and signs of complications of amoebiasis.

MANAGEMENT

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Amoebiasis Follow up

Monitoring
Monitoring
FOLLOW UP

It is reasonable, but not a uniform recommendation, to carry out a follow-up stool antigen detection test
on completion of nitroimidazole and luminal therapy to confirm eradication of colonisation. UK guidelines
specifically recommend that patients should undergo screening (via PCR testing of one stool sample)
one week after treatment completion. Any case that remains PCR positive following treatment completion
should be referred to an Infectious Diseases physician for further assessment.[24]

There is no need for follow-up imaging of an amoebic liver abscess after completion of therapy.

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Amoebiasis Follow up

Complications

Complications Timeframe Likelihood

FOLLOW UP
toxic megacolon short term low

Occurs in less than 1% of patients.

Occurrence may increase with corticosteroid use.

Requires surgery as unlikely to respond to antiamoebic medication.[1] [5]

acute necrotising colitis short term low

Occurs in less than 1% of patients.

Occurrence may increase with corticosteroid use.

Requires surgery as unlikely to respond to antiamoebic medication.[1] [5]

colonic perforation with peritonitis short term low

Fulminant amoebiasis, presenting as peritonitis due to intestinal perforation, is rare but life-threatening.

Occurrence may increase with corticosteroid use.

Requires surgery as unlikely to respond to antiamoebic medication.[1] [5]

brain abscess short term low

Rare complication; little is known about prognosis.[3] Patients may report altered mental status or limb
weakness.

amoebic acute appendicitis short term low

Amoebic acute appendicitis is a rare manifestation of amoebiasis and is associated with a higher rate
of complications and mortality than non-amoebic appendicitis. Histopathological examination and extra
precautions are warranted when amoebic appendicitis is suspected.[8]

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Amoebiasis Follow up

Complications Timeframe Likelihood


FOLLOW UP

Amoebic appendicitis with skin fistula two weeks after appendectomy (enhanced computed tomography).
Original photo from National Center for Global Health and Medicine, Tokyo, Japan.

Hematoxilin-Eosin stain (A-C) and Periodic acid-Schiff stain (D-F) of resected appendix
of amoebic appendicitis. Entamoebas are deeply dyed by Periodic acid-Schiff stain.
Original photo from National Center for Global Health and Medicine, Tokyo, Japan.

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Amoebiasis Follow up

Complications Timeframe Likelihood


amoeboma variable low

FOLLOW UP
Annular granulation tissue in the caecum or ascending colon, extending from the wall into the lumen. Can
be mistaken for colonic carcinoma.

Responds to medical therapy.[1]

Prognosis

Amoebic colitis
Mortality rate is less than 2%.

Complications include toxic megacolon, colonic perforation with resultant peritonitis, and amoeboma
(granulation tissue in the intestinal lumen).[1] [2] [5]

Liver abscess
Mortality rate is less than 2%.

Complications include extension of the abscess into peritoneum, pleural cavity, or pericardium, and
haematogenous dissemination to the brain, lung, and skin.[1] [2] [5][3]

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Amoebiasis Guidelines

Diagnostic guidelines

United Kingdom

Interim public health operational guidelines for amoebiasis (Entamoeba


histolytica) (ht tps://www.gov.uk/government/publications/amoebiasis-public-
health-operational-guidelines)
Published by: Public Health England Last published: 2017

North America

CDC Yellow Book 2024: health information for international travel -amebiasis
(ht tps://wwwnc.cdc.gov/travel/page/yellowbook-home)
Published by: Centers for Disease Control and Prevention Last published: 2023
GUIDELINES

Treatment guidelines

United Kingdom

Interim public health operational guidelines for amoebiasis (Entamoeba


histolytica) (ht tps://www.gov.uk/government/publications/amoebiasis-public-
health-operational-guidelines)
Published by: Public Health England Last published: 2017

North America

CDC Yellow Book 2024: health information for international travel - amebiasis
(ht tps://wwwnc.cdc.gov/travel/page/yellowbook-home)
Published by: Centers for Disease Control and Prevention Last published: 2023

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Amoebiasis References

Key articles
• Centers for Disease Control and Prevention. CDC Yellow Book 2024: health information for

REFERENCES
international travel. Section 5: travel-associated infections & diseases - parasitic. Amebiasis. May 2023
[internet publication]. Full text (https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/
amebiasis)

• Public Health England. Interim public health operational guidelines for amoebiasis (Entamoeba
histolytica). Oct 2017 [internet publication]. Full text (https://www.gov.uk/government/publications/
amoebiasis-public-health-operational-guidelines)

• Gonzales MLM, Dans LF, Sio-Aguilar J. Antiamoebic drugs for treating amoebic
colitis. Cochrane Database Syst Rev. 2019 Jan 9;1:CD006085. Full text (https://
www.doi.org/10.1002/14651858.CD006085.pub3) Abstract (http://www.ncbi.nlm.nih.gov/
pubmed/30624763?tool=bestpractice.bmj.com)

References
1. Haque R, Huston CD, Hughes M, et al. Amebiasis. New Engl J Med. 2003;348:1565-73. Abstract
(http://www.ncbi.nlm.nih.gov/pubmed/12700377?tool=bestpractice.bmj.com)

2. Petri WA Jr, Singh U. Diagnosis and management of amebiasis. Clin Infect Dis. 1999;29:1117-25.
Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10524950?tool=bestpractice.bmj.com)

3. Solaymani-Mohammadi S, Lam M, Zunt JR. Entamoeba histolytica encephalitis diagnosed by


polymerase chain reaction of cerebrospinal fluid. Trans R Soc Trop Med Hyg. 2007;101:311-13.
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4. Watanabe K. Amebiasis. In: Rakel RE, ed. Conn's current therapy 2019. New York, NY: W.B.
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5. Stanley SL Jr. Amoebiasis. Lancet. 2003;361:1025-34. Abstract (http://www.ncbi.nlm.nih.gov/


pubmed/12660071?tool=bestpractice.bmj.com)

6. Diamond LS, Clark CG. A redescription of Entamoeba histolytica Schaudinn, 1903 (amended Walker,
1911) separating it from Entamoeba dispar Brumpt, 1925. J Eukaryot Microbiol. 1993;40:340-44.
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7. Ali IKM, Hossain MB, Roy S, et al. Entamoeba moshkovskii infections in children in Bangladesh.
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8. Otan E, Akbulut S, Kayaalp C. Amebic acute appendicitis: systematic review of 174 cases. World J
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(http://www.ncbi.nlm.nih.gov/pubmed/23665815?tool=bestpractice.bmj.com)

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BMJ Best Practice topics are regularly updated and the most recent version of the topics
41
can be found on bestpractice.bmj.com . Use of this content is subject to our disclaimer (.
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Amoebiasis References
9. Centers for Disease Control and Prevention. CDC Yellow Book 2024: health information for
international travel. Section 5: travel-associated infections & diseases - parasitic. Amebiasis. May 2023
[internet publication]. Full text (https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/
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11. Watanabe K, Gatanaga H, Escueta-de Cadiz A, et al. Amebiasis in HIV-1-infected Japanese


men: clinical features and response to therapy. PLoS Negl Trop Dis. 2011 Sep;5(9):e1318. Full
text (https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001318) Abstract (http://
www.ncbi.nlm.nih.gov/pubmed/21931875?tool=bestpractice.bmj.com)

12. Hung CC, Wu PY, Chang SY, et al. Amebiasis among persons who sought voluntary counseling
and testing for human immunodeficiency virus infection: a case-control study. Am J Trop Med Hyg.
2011;84:65-69. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/21212204?tool=bestpractice.bmj.com)

13. Nagata N, Shimbo T, Akiyama J, et al. Risk factors for intestinal invasive amebiasis in Japan,
2003-2009. Emerg Infect Dis. 2012 May;18(5):717-24. Full text (https://wwwnc.cdc.gov/eid/
article/18/5/11-1275_article) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/22515839?
tool=bestpractice.bmj.com)

14. Wu H, Wu PY, Li SY, et al. Maximising the potential of voluntary counselling and testing
for HIV: sexually transmitted infections and HIV epidemiology in a population testing for
HIV and its implications for practice. Sex Transm Infect. 2012 Dec;88(8):612-6. Full text
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pubmed/22717470?tool=bestpractice.bmj.com)

15. Yanagawa Y, Nagashima M, Gatanaga H, et al. Seroprevalence of Entamoeba histolytica at a


voluntary counselling and testing centre in Tokyo: a cross-sectional study. BMJ Open. 2020 Feb
25;10(2):e031605. Full text (https://www.doi.org/10.1136/bmjopen-2019-031605) Abstract (http://
www.ncbi.nlm.nih.gov/pubmed/32102805?tool=bestpractice.bmj.com)

16. Salit IE, Khairnar K, Gough K, et al. A possible cluster of sexually transmitted Entamoeba histolytica:
genetic analysis of a highly virulent strain. Clin Infect Dis. 2009 Aug 1;49(3):346-53. Full text
(https://www.doi.org/10.1086/600298) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/19580413?
tool=bestpractice.bmj.com)

17. Hung CC, Chang SY, Ji DD. Entamoeba histolytica infection in men who have sex with men. Lancet
Infect Dis. 2012 Sep;12(9):729-36. Full text (https://www.doi.org/10.1016/S1473-3099(12)70147-0)
Abstract (http://www.ncbi.nlm.nih.gov/pubmed/22917103?tool=bestpractice.bmj.com)

18. Ralston KS, Solga MD, Mackey-Lawrence NM, et al. Trogocytosis by Entamoeba histolytica
contributes to cell killing and tissue invasion. Nature. 2014;508:526-30. Full text (http://
www.ncbi.nlm.nih.gov/pmc/articles/PMC4006097) Abstract (http://www.ncbi.nlm.nih.gov/
pubmed/24717428?tool=bestpractice.bmj.com)

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can be found on bestpractice.bmj.com . Use of this content is subject to our disclaimer (.
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44 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Sep 27, 2023.
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Amoebiasis Images

Images

IMAGES
Figure 1: Cyst of Entamoeba histolytica: unstained (A), and iodine stained (B) after formalin-ether
concentration of stool sample.
Original photos from National Center for Global Health and Medicine, Tokyo, Japan.

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can be found on bestpractice.bmj.com . Use of this content is subject to our disclaimer (.
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IMAGES Amoebiasis Images

Figure 2: Amoebic appendicitis with skin fistula two weeks after appendectomy (enhanced computed
tomography).
Original photo from National Center for Global Health and Medicine, Tokyo, Japan.

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IMAGES
Figure 3: Hematoxilin-Eosin stain (A-C) and Periodic acid-Schiff stain (D-F) of resected appendix of amoebic
appendicitis. Entamoebas are deeply dyed by Periodic acid-Schiff stain.
Original photo from National Center for Global Health and Medicine, Tokyo, Japan.

Figure 4: Cyst of Entamoeba histolytica : iodine stain of stool sample


Reproduced from Current Concepts (2003); used with permission

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IMAGES Amoebiasis Images

Figure 5: Life-cycle of Entamoeba histolytica


Reproduced from New England Journal of Medicine (2003); used with permission

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Amoebiasis Images

IMAGES
Figure 6: Trophozoites of Entamoeba histolytica : trichrome stain of stool sample
Reproduced from Clinical Infectious Diseases (1999); used with permission

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IMAGES Amoebiasis Images

Figure 7: Trophozoite of Entamoeba histolytica with pseudopod (red arrow): direct unstained stool sample.
Original photo from National Center for Global Health and Medicine, Tokyo, Japan.

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Amoebiasis Images

IMAGES
Figure 8: Amoebic ulcerations of the colon: colonic ulcers averaging 1 mm to 2 mm in diameter on gross
pathology
Reproduced from New England Journal of Medicine (2003); used with permission

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IMAGES Amoebiasis Images

Figure 9: Posterior-anterior and lateral CXR of a patient with amoebic liver abscess: CXR findings include
elevated right hemidiaphragm and evidence of atelectasis
Reproduced from New England Journal of Medicine (2003); used with permission

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IMAGES
Figure 10: Entamoeba histolytica brain abscess
Reproduced from Transactions of the Royal Society of Tropical Medicine and Hygiene (2007); used with
permission

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Contributors:

// Authors:

Koji Watanabe, MD, PhD


Attending physician
AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
DISCLOSURES: KW is an author of a number of references cited in this topic.

// Acknowledgements:
Dr Koji Watanabe would like to gratefully acknowledge Dr William A. Petri, a previous contributor to this
topic. WAP is a consultant for TechLab, Inc. which manufactures diagnostic tests for amoebiasis and is also
the author of a number of references cited in this topic.

// Peer Reviewers:

Ran Nir-Pa z, MD
Senior Lecturer in Microbiology and Medicine
Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center,
Jerusalem, Israel
DISCLOSURES: RNP declares that he has no competing interests.

Christopher Huston, MD
Assistant Professor of Medicine
Division of Infectious Diseases, University of Vermont College of Medicine, Burlington, VT
DISCLOSURES: CH declares that he has no competing interests.

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