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Introduction

Background

Amebiasis is caused by Entamoeba histolytica, a protozoan found worldwide. The highest

prevalence of amebiasis is in developing countries where barriers between human feces and food

and water supplies are inadequate.

Although most cases of amebiasis are asymptomatic, dysentery and invasive extraintestinaldisease can occur. Amebic liver abscess is the most common manifestation of invasive

amebiasis, but other organs can also be involved, including pleuropulmonary, cardiac, cerebral,

renal, genitourinary, and cutaneous sites. In developed countries, amebiasis primarily affects

migrants from and travelers to endemic regions, men who have sex with men, andimmunosuppressed or institutionalized individuals.

E histolytica is transmitted via ingestion of the cystic form (infective stage of the protozoa.!iable in the environment for wee"s to months, cysts can be found in fecally contaminated soil,fertilizer, or water or on the contaminated hands of food handlers. #ecal$oral transmission can

also occur in the setting of anal sexual practices or direct rectal inoculation through colonic

irrigation devices. %xcystation then occurs in the terminal ileum or colon, resulting in

trophozoites (invasive form. The trophozoites can penetrate and invade the colonic mucosal barrier, leading to tissue destruction, secretory bloody diarrhea, and colitis resembling

inflammatory bowel disease. In addition, the trophozoites can spread hematogenously via the

portal circulation to the liver or even to more distant organs.

Amebic infection was first described by #edor &osch in ')* in +t. etersburg, -ussia. In '/,

+ir 0illiam 1sler reported the first 2orth American case of amebiasis, when he observed amebaein stool and abscess fluid from a physician who previously resided in anama. The species name

E histolytica was first coined by #ritz +chaudin in '/3. In ''3, in the hilippines, 0al"er and+ellards documented the cyst as the infective form of E histolytica. The life cycle was then

established by 4obell in '5*.

Pathophysiology

E histolytica is a pseudopod$forming, nonflagellated protozoal parasite that causes proteolysis

and tissue lysis (hence its name and can induce host$cell apoptosis. 6umans and perhaps

nonhuman primates are the only natural hosts. Ingestion of E histolytica cysts from theenvironment is followed by excystation in the terminal ileum or colon to form highly motile

trophozoites. 7pon colonization of the colonic mucosa, the trophozoite may encyst and is then

excreted in the feces or may invade the intestinal mucosal barrier and gain access to the bloodstream and disseminate to the liver, lung, and other sites. %xcreted cysts reach the environment to

complete the cycle.

4isease may be caused by only a small number of cysts, but the processes of encystation and

excystation are poorly understood. The adherence of trophozoites to colonic epithelial cells

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seems to be mediated by a galactose8 N $acetylgalactosamine (9A&89al2Ac:specific lectin.',5 A

mucosal immunoglobulin A (IgA response against this lectin can result in fewer recurrent

infections.3 ;oth lytic and apoptotic pathways have been described.


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corticosteroids, and malnourished individuals.' In '3, a total of 5)/ cases of amebiasis were

reported to the /$*/million cases annually worldwide, resulting in >/,///$'//,/// deaths.'',','3

• Asymptomatic intestinal amebiasis occurs in /B of infected individuals. 6owever, only

>B$'/B of individuals with asymptomatic amebiasis who were monitored for one year

eventually developed colitis or extraintestinal disease.''

• /B.'>

• The mortality rate due to amebic liver abscess has fallen to '$3B in the last century

following the introduction of effective medical treatment. 2evertheless, amebic liver

abscess is complicated by sudden intraperitoneal rupture in 5$)B of patients, leading to ahigher mortality rate.'

Race

• In Eapan and Taiwan, 6I! seropositivity is a ris" factor for invasive extraintestinal

amebiasis.'* This has not been observed elsewhere.

Sex

• Amebic colitis affects both sexes equally.'

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• Amebic liver abscess is )$'5 times more common in men than in women, with a

predominance among men aged '$*/ years. The reason for this sexual disparity is

un"nown, although hormonal effects may be implicated, as the prevalence of amebicliver abscess is also increased among postmenopausal women. Alcohol may also been an

important ris" factor. The sexual distribution is equal in children.'

Age

!ery young children seem to be predisposed to fulminant colitis.

linical

!istory

• Amebic colitis

o The most common presentation of amebic colitis is gradual onset of bloody

diarrhea, abdominal pain, and tenderness spanning several wee"sF duration.

o -ectal bleeding without diarrhea can occur, especially in children.

o 1nly approximately '/$3/B of patients with amebic colitis develop fever.

o 0eight loss and anorexia may occur.

o #ulminant or necrotizing colitis usually manifests as severe bloody diarrhea and

widespread abdominal pain with evidence of peritonitis and fever.

o redisposing factors for fulminant colitis include poor nutrition, pregnancy,

corticosteroid use, and very young age.

• Amebic liver abscess

o The most typical presentation of amebic liver abscess is fever, right upper

quadrant pain, and tenderness of less than '/ daysF duration.

o 7nli"e amebic colitis, amebic liver abscess is associated with fever in *$/B of

cases.

o A more subacute presentation can be seen, with concomitant weight loss and

anorexia.

o


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o Acute abdominal symptoms and signs should prompt rapid investigation for

intraperitoneal rupture.

o +ixty to )/B of patients with amebic liver abscess do not have concomitant

colitis, although a history of dysentery within the previous year may be obtained.

o Amebic liver abscess may manifest years after travel to or residency in an

endemic area.

o A history of alcohol abuse is common, but a clear causal relationship is unclear.

• leuropulmonary amebiasisG


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o 6epatomegaly (3/$*/B

o Eaundice (?$'/B

auses

• Amebiasis is an infection caused by the protozoal organism E histolytica, which can

cause colitis and other extraintestinal manifestations, including liver abscess (mostcommon and pleuropulmonary, cardiac, and cerebral dissemination.

• E histolytica is transmitted primarily through the fecal$oral route. Infective cysts can be

found in fecally contaminated food and water supplies and contaminated hands of food

handlers. +exual transmission is possible, especially in the setting of oral$anal practices.

"i##erential "iagnoses

Abdominal Abscess Inflammatory ;owel 4iseaseArteriovenous alformations erforated abdominal viscus


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o The presence of intracytoplasmic red blood cells in trophozoites is diagnostic of E

histolytica infection, although recent studies demonstrated the same phenomenon

with E dispar .

o The 0orld 6ealth 1rganization (061 recommends that intestinal amebiasis be

diagnosed with an E histolytica $specific test, thus rendering the classic stool ovaand parasite examination obsolete.

•


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o ultiple serologic assays are available for the diagnosis of amebiasis.

o %&I+A is the most used assay throughout the world and is used to measure the

presence of serum antilectin antibodies (Ig9. The sensitivity for detection of

antibodies to E histolytica in patients with amebic liver abscess is ).B, whereas

the specificity is >.B. #alse$negative results can occur within the first )$'/ daysfollowing infection.

o Immunofluorescent assay (I#A is also rapid, reliable, and reproducible. In the

setting of amebic liver abscess, the sensitivity and specificity of I#A was shown to be 3.?B and ?.)B, respectively.

o Indirect hemagglutination (I6A is very specific (.'B but is less sensitive than

%&I+A.

o Immunoelectrophoresis, counter$immunoelectrophoresis (


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o Application of


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•


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• #ulminant colitis requiring surgical evaluation

• eritonitis and suspected amebic liver abscess rupture

Surgical are

• rompt surgical evaluation is needed in suspected cases of fulminant colitis, peritonitis,

or perforated viscus.

• +urgical intervention is usually indicated in different clinical scenariosG uncertain

diagnosis (possibility of pyogenic liver abscess@ concern of bacterial suprainfection in

amebic liver abscess@ failure to respond to metronidazole after >$day treatment duration@empyema after amebic liver abscess rupture@ large left$sided amebic liver abscess

representing ris" of rupture in the pericardium@ and severely ill patient with imminent

amebic liver abscess rupture.'

• +urgical drainage of uncomplicated amebic liver abscess is generally unnecessary and

should be avoided.

• ercutaneous catheter drainage improves the outcome in the treatment of amebic

empyema and is life$saving in amebic pericarditis.

• ercutaneous catheter drainage should be used Dudiciously in the setting of localized

intraabdominal fluid collections. Although controversial, it might be used to aspirate large

amebic liver abscesses (L3// cm3.'

onsultations

• Infectious disease specialist

• 9eneral surgeon

• 9astrointestinal specialist

Medication

•Asymptomatic amebiasis should be treated with a luminal agent (iodoquinol, paromomycin, diloxanide furoate to eradicate infection. This recommendation is based

on two argumentsG #irst, invasive disease may develop@ second, shedding of E histolytica

cysts in the environment is a public health concern. '

• Asymptomatic E dispar infections should not be treated, but education should be pursued

since it is a mar"er of fecal$oral contamination.'


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• Amebic colitis is first treated with a nitroimidazole derivative (metronidazole being the

only one available in the 7nited +tates, followed by a luminal agent to eradicate

colonization.'

• Amebic liver abscess can be cured without drainage and even by one dose of

metronidazole. days of treatment.etronidazole failure may be an indication for surgical intervention. Treatment with a

luminal agent should also follow.'

• 4isseminated amebiasis should be treated with metronidazole, which can cross the brain$

blood barrier.

• %mpirical antibacterial agents should be used concomitantly if perforated viscus is a

concern.

A&ebicides

arasite biochemical pathways are sufficiently different from the human host to allow selective

interference by chemotherapeutic agents in relatively small doses.

Iodoquinol (Yodoxin)

Amebicidal against E histolytica.


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2one reported

• Dosing

• Interactions

• Contraindications

• Precautions

4ocumented hypersensitivity@ hepatic dysfunction

• Dosing

• Interactions

•

Contraindications

• Precautions

Pregnancy

< $ #etal ris" revealed in studies in animals but not established or not studied in humans@ may

use if benefits outweigh ris" to fetus

Precautions


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Adult

5*$3* mg8"g8d 1 divided tid for ) d

Pediatric

Administer as in adults

• Dosing

• Interactions


• Precautions

2ephrotoxic potential may increase with concurrent administration of other aminoglycosides,

penicillins, cephalosporins, amphotericin ;, and loop diuretics@ may decrease serum

concentrations of digoxin

• Dosing

• Interactions


• Precautions

4ocumented hypersensitivity@ intestinal obstruction

• Dosing

• Interactions


• Precautions

Pregnancy



Precautions

;ecause of narrow therapeutic index and toxic hazards associated with extended administration,

not for long$term therapy@ caution in renal failure, hypocalcemia, myasthenia gravis, and

conditions that depress neuromuscular transmission@ adDust dose in renal impairment@ may cause


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abdominal cramping, nausea, emesis, and diarrhea@ malabsorption, ototoxicity, and

nephrotoxicity can occur if administered in high doses or in ulcerative colitis

Diloxanide (Entamide, Furamide)

4ichloroacetamide derivative. Amebicidal against trophozoite and cyst forms of E histolytica.

2ot available in 7nited +tates.

• Dosing

• Interactions


•

Precautions

Adult

*// mg 1 tid for '/ d

Pediatric

M5 yearsG 2ot recommended

L5 yearsG 5/ mg8"g 1 divided tid for '/ d

• Dosing

• Interactions


• Precautions

2one reported

• Dosing

• Interactions


• Precautions

4ocumented hypersensitivity

• Dosing


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• Interactions


• Precautions

Pregnancy



Precautions

9I adverse effects (eg, flatulence, abdominal cramps, nausea, emesis, diarrhea may occur

Metronidaole (Flagyl)

Active against various anaerobic bacteria and protozoa. Appears to be absorbed into cells.

Intermediate metabolized compounds are formed and bind 42A and inhibit protein synthesis,

causing cell death. Antimicrobial effect may be due to production of free radicals.

Indicated for invasive amebiasis.

• Dosing

• Interactions


• Precautions

Adult

*//$)*/ mg 1 tid for '/ d

Pediatric

3*$*/ mg8"g 1 divided tid for '/ d

• Dosing

• Interactions


• Precautions


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Adult

Intestinal amebiasisG ?// mg 1 bid for * d@ alternatively, 5 g 1 qd for 3 d with food

6epatic amebic abscessG 5 g 1 qd for 3$* d with food

Pediatric

M3 yearsG 2ot establishedL3 yearsG

Intestinal amebiasisG */ mg8"g8d 1 for 3 d with food@ not to exceed 5 g8dose

Amebic liver abscessG */ mg8"g8d 1 for 3$* d with food@ not to exceed 5 g8dose, limited data

exist for pediatric patients treated L 3 d (monitor closely

Follo()up

Further Inpatient are

• atients with suspected fulminant colitis, liver abscess intractable to medical treatment,

or suspected amebic liver abscess rupture should be admitted to the hospital for further

evaluation.

Further *utpatient are

• #ollow$up stool examination after therapy completion is recommended to ensure

intestinal eradication.

"eterrence/Pre+ention

• Amebiasis is prevented by eradicating fecal contamination of food and water through

improved sanitation, hygiene, and water treatment.

• Amebic cysts are not "illed by soap or low concentrations of chlorine or iodine@

therefore, water in endemic areas should be boiled for more than ' minute and vegetablesshould be washed with a detergent soap and soa"ed in acetic acid or vinegar for '/$'*

minutes before consumption.

• Avoiding sexual practices that involve fecal$oral contact may reduce the ris" of sexual

transmission of infective cysts.

• +creen family members or close contacts of an index case, since reinfection is possible.

• %ffective recombinant antigen$based vaccines in animals prevent amebic liver abscess

and generate mucosal antiamebic antibodies. In humans, natural E histolytica infectiondoes not seem to result in long$term immunity, as individuals with a previous amebic

liver abscess are as susceptible to a new infection as other members of the population.'


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o&plications

• Amebic colitis

o #ulminant or necrotizing colitis

o Toxic megacolon

o Ameboma

o -ectovaginal fistula

• Amebic liver abscess

o Intraperitoneal, intrathoracic, or intrapericardial rupture, with or without

secondary bacterial infection

o 4irect extension to pleura or pericardium

o 4issemination and formation of brain abscess

Prognosis

• #ollowing treatment, invasive amebiasis carries a good prognosis.

• #ulminant colitis and amebic liver abscess rupture are associated with higher mortality

rates.

• rior infection and treatment do not protect against future colonization or recurrent

invasive amebiasis.

Patient ,ducation

• Individuals traveling to endemic areas should be advised on the proper food and water

handling.

o 7ncoo"ed vegetables should be washed and soa"ed in acetic acid or vinegar for

'/$'* minutes.

o &ocal water should be boiled for more than ' minute.

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AMEBIASIS (amebic dysentery, amebic hepatitis)

EtiologyE. histolytica is the major cause of amebic dysentery.

Epidemiology

0.5 to 50% of the population world wide harbors E. histolytica parasites with the higher rates of infectionbeing in underdeveloped countries. 1 to 3% of the population of the US are infected. !nfection isassociated with poor hygiene. "umans are the principal host# although dogs# cats and rodents may beinfected.

Morphology

Trophozoite$ his form has an ameboid appearance and is usually 15&30 micrometers in diameter#although more invasive strains tend to be larger. he organism has a single nucleus with a distinctive smallcentral 'aryosome ()igure 1#*+. he fine granular endoplasm may contain ingested erythrocytes ()igure1,+. he nuclear chromatin is evenly distributed along the periphery of the nucleus.

Cyst: Entameba histolytica cysts are spherical# with a refractile wall- the cytoplasm contains dar' stainingchromatoidal bodies and 1 to nuclei with a central 'aryosome and evenly distributed peripheralchromatin ()igure /+.

i!e cycle!nfection occurs by ingestion of cysts on fecally contaminated food or hands. he cyst is resistant to thegastric environment and passes into small intestine where it decysts. he metacyst divides into four and


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then eight amoebae which move to the large intestine. he majority of the organisms are passed out of thebody with the feces but# with larger bolus of infection# some amebae attach to and invade the mucosaltissue forming flas'&shaped lesions (bomb craters+. he organisms encyst for mitosis and are passedthrough with feces ()igure 3+. here are no intermediate or reservoir hosts.

)igure 1

*# *$ rophooites of 2ntamoeba histolytica. richrome stain. he trophooites are elongated (up to 0 4m in length+# as theytend to be in diarrheal stool. (!n non diarrheal stool# they are more rounded# and measure 15&/0 4m.+ he nuclei show a centrallyplaced 'aryosome with a uniformly distributed peripheral chromatin. ,, 67 6arasite !mage 8ibrary

, rophooites of 2ntamoeba histolytica. richrome stain. wo diagnostic characteristics are seen here$ twoof the trophooites have ingested erythrocytes# and the nuclei have typically a small# centrally located 'aryosome# as well as thin#uniform peripheralchromatin. ,, 67 6arasite !mage 8ibrary

2ntamoeba histolytica cyst and trophooite# haemato7ylin stained 9 r 6eter arben# :ueenslandUniversity of echnology clinical parasitology collection. Used with permission

2ntamoeba histolytica trophooites in section of intestine (";2+ 9 r 6eter arben# :ueenslandUniversity of echnology clinical parasitology collection. Used with permission

arasitic amoeba (%ntamoeba histolytica causes amebic dysentery N ulcers (vegetative trophozoite

stage. Amebic dysentery is spread by fecal contamination of food and water and is most common where sanitationis poor.9 4ennis un"el icroscopy, Inc. Used with permission

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)igure /

A ; ,ysts of 2ntamoeba histolytica# stained with trichrome (+ and iodine (*+. 2achcyst has nuclei# of which 3 (in + and / (in *+ are visible in this focal plane (the fourth nucleus is coming into focus in +. henuclei have characteristically centrally located 'aryosomes. he cyst in contains a large chromatoid body. 2ntamoebahistolytica cysts measure 1/&15 4m ,, 67 6arasite !mage 8ibrary

)igure 3

8ife cycle of Entamoeba histolytica!nfection by 2ntamoeba histolytica occurs by ingestion of mature cysts (1+ in fecally contaminated food# water# or hands.27cystation (/+ occurs in the small intestine and trophooites (3+ are released# which migrate to the large intestine. hetrophooites multiply by binary fission and produce cysts (+ # which are passed in the feces. *ecause of the protection conferredby their walls# the cysts can survive days to wee's in the e7ternal environment and are responsible for transmission.(rophooites can also be passed in diarrheal stools# but are rapidly destroyed once outside the body# and if ingested would notsurvive e7posure to the gastric environment.+ !n many cases# the trophooites remain confined to the intestinal lumen ($ non&invasive infection+ of individuals who are thus asymptomatic carriers and cysts passers. !n some patients the trophooites invadethe intestinal mucosa (*$ intestinal disease+# or# through the bloodstream# e7traintestinal sites such as the liver# brain# and lungs(,$ e7tra&intestinal disease+# with resultant pathologic manifestations. !t has been established that the invasive and noninvasiveforms represent separate species# respectively 2. histolytica and 2. dispar# which are morphologically indistinguishable.ransmission can also occur through fecal e7posure during se7ual contact (in which case not only cysts# but also trophooitescould prove infective+. ,, 67 6arasite !mage 8ibrary

Symptoms

Ac"te$ )reflas's & figure + are due to enymatic degradation of tissue. he infection mayresult in appendicitis# perforation# stricture granuloma# pseudo&polyps# liver abscess (figure +- sometimes

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brain# lung and spleen abscesses can also occur. Strictures and pseudo&polyps result from the hostinflammatory response.

Imm"nologyhere is an antibody response after invasive infection (liver abscess or colitis+ but it is of r. ?ae ?elvin

)igure 5

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2ntamoeba coli$ rophooite# stained in trichrome# showing a characteristically large# eccentric 'aryosome#

and a coarse# vacuolated cytoplasm. he trophooites of 2. coli measure usually /0&/5 4m# but they can be elongated (as is thecase here+ and reach 50 4m. 67 6arasite !mage 8ibrary


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2ntamoeba hartmanni$ ,yst# with one nucleus visible at this focal plane- again rather similar to cysts of 2.histolytica# but differentiated by their smaller sie (5&10 4m compared to 10&/0 4m+ ,, 67 6arasite !mage 8ibrary

* 2ntamoeba hartmanni$ # *$ rophooites stained in trichrome $ the trophooites of 2.hartmanni are rather similar to those of 2. histolytica# with a small# often centrally located 'aryosome# fine peripheral chromatin#and finely granular cytoplasm- the main difference is in their small sie$ 5&1/ 4m compared to 10&0 4m for 2. histolytica. @otethat in (+ the trophooite has ingested a yeast# not an erythrocyte. (!ngestion of erythrocytes is pathognomonic of 2. histolytica.+,, 67 6arasite !mage 8ibrary

* , 2ndolima7 nana$ rophooite stained in trichrome (+ and cysts stainedin iodine (*+ and in trichrome (,+. @ote in the trophooite the characteristically large blot&li'e 'aryosome# and the lac' ofperipheral chromatin. he cysts are mature# they contain four nuclei that are much smaller than the nuclei of the trophooites anddo not have peripheral chromatin. he trophooites are usually C&10 4m in sie# while the cysts are usually &C 4m. ,, 676arasite !mage 8ibrary

* , !odamoeba bDtschlii$ rophooites stained in trichrome (+ and in hemato7ylin&eosin (*+# and cyst stained in trichrome (,+. @ote the large 'aryosomes in the trophooites# and in (*+ the 'aryosome surroundedby refractile achromatic granules. !n the cyst (,+# a large mass of glycogen pushes the nucleus aside. he trophooites areusually 1/&15 4m in sie# and the cysts are usually 10&1/ 4m. ,, 67 6arasite !mage 8ibrary

ientamoeba fragilis trophooites# trichrome stain. ientamoeba fragilis is not an ameba# but aflagellateE !t must be however morphologically differentiated from the amebas. he nucleus is a cluster of granules# with no

peripheral chromatin. Sie range 5&15 4m. his species has no cyst stage. !mages contributed by Aeorgia epartment of 6ublic"ealth>,, 67 6arasite !mage 8ibrary

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