Entamoeba histolytica

Entamoeba histolytica 

• cosmopolitan distribution 

• no animal reservoirs 

• facultative pathogen 

• most clear the infection spontaneous in 

6-12 months with mild or no symptoms 

• can cause a serious invasive disease 

• worldwide incidence = 0.2-50% 

• estimated that 10% of world’s 

population may be infected 

• 50 million cases invasive amebiasis/yr 

• 100,000 deaths/yr

1875 Lösch correlated dysentery with amebic 

trophozoites 

1925 Brumpt proposed two species: E. 

dysenteriae and E. dispar 

1970's 

Facultative Pathogenicity 

of Entamoeba histolytica 

biochemical differences noted between 

invasive and non-invasive isolates 

80's/90's several antigenic and DNA differences 

demonstrated 

• rRNA 2.2% sequence difference 

1993 Diamond and Clark proposed a new species 

(E. dispar) to describe non-invasive strains 

1997 WHO accepted two species

Entamoeba histolytica 

Life Cycle

Excystation 

• cyst wall disruption 

• ameba emerges 

• nuclear division (4→8) 

• cytoplasmic division 

(8 amebala) 

• trophozoites colonize 

large intestine 

• feed on bacteria and 

debris 

• replicate by binary 

fission

Excystation 

• cyst wall disruption 

• ameba emerges 

• nuclear division (4→8) 

• cytoplasmic division 

(8 amebala) 

• trophozoites colonize 

large intestine 

• feed on bacteria and 

debris 

• replicate by binary 

fission

Encystation 

• trophozoite rounds up 

• secretion of cyst wall 

• aggregation of ribosomes 

(= chromatoid bodies) 

• 2 rounds of nuclear division 

(1→4 nuclei) 

• survive weeks to months

trophozoite 

immature 

cyst 

mature 

cyst

Pathogenesis of Amebiasis 

• NON-INVASIVE 

• ameba colony on intestinal mucosa 

• asymptomatic cyst passer 

• non-dysenteric diarrhea, abdominal 

cramps, other GI symptoms 

• INVASIVE 

• necrosis of mucosa → ulcers, dysentery 

• ulcer enlargement → dysentery, peritonitis 

• metastasis → extraintestinal amebiasis

• ulcers with raised borders 

• little inflammation between lesions

• ‘flasked-shaped ulcer’ 

• trophozoites at boundary of necrotic 

and healthy tissue 

• trophozoites ingesting host cells 

• dysentery (blood and mucus in feces)

‘hematophagous’ trophozoites

Lateral and Downward Expansion 

of Ameba into Lamina Propria 

• localized sloughing 

• ulcers coalesce 

• perforation of intestinal wall

Disease Manifestations 

• ulcer enlargement → 

severe dysentery 

• perforation of intestinal 

wall → peritonitis 

• local abscesses 

• 2 o bacterial infections 

• occasional ameboma 

(=amebic granuloma) 

• cessation of cyst 

production 

ameboma = inflammatory thickening 

of intestinal wall around the abscess 

(can be confused with tumor)

Extraintestinal Amebiasis 

• metastasis via blood stream 

• primarily liver (portal vein) 

• other sites less frequent 

• ameba-free stools common 

• high antibody titers 

Amebic Liver Abscess 

• chocolate-colored ‘pus’ 

• necrotic material 

• usually bacteria free 

• lesions expand and 

coalesce 

• further metastasis, direct 

extension or fistula

Pulmonary Amebiasis 

• rarely primary 

• rupture of liver abscess 

through diaphragm 

• 2 o bacterial infections 

common 

• fever, cough, dyspnea, 

pain, vomica

Cutaneous Amebiasis 

• intestinal or hepatic fistula 

• mucosa bathed in fluids 

containing trophozoites 

• perianal ulcers 

• urogenital (eg, labia, 

vagina, penis)







vagina, penis)







vagina, penis)

Facultative Pathogenicity 

• 85-90% of infected individuals 

are asymptomatic 

• ~10% of the symptomatic will 

develop severe invasive disease

Molecular Epidemiology 

• molecular probes used to survey for 

E. dispar and E. histolytica 

• E. dispar ~10-fold > E. histolytica 

• discrete endemic pockets of E. histolytica 

• many asymptomatic E.h. infections 

• ~10% of the E.h. infections are 

associated with invasive amebiasis 

• ~25% seropositive for E. histolytica in 

endemic areas

pathogenecity 

virulence 

ability to cause disease 

(genetic component) 

relative capacity to cause 

disease (degree of pathology) 

• a pathogen has an inherent ability to 

break host cell barriers 

• virulence usually correlates with ability 

to replicate within host 

• various degrees of virulence may be 

exhibited depending on conditions

• contact-dependent killing of epithelial cells 

• breakdown of tissues (extracellular matrix) 

• secreted proteases? 

• contact-dependent killing of neutrophils, 

leukocytes, etc.

E. histolytica vs E. dispar 

CRITERIA E. dispar E. histolytica 

In Vitro Culture xenic axenic 

ConA Agglutination - + 

Complement Resistance - + 

Zymodemes (isoenzymes) I & III II 

Numerous Antigenic Differences 

(eg., GIAP Epitopes) 1-2 1-6 

Numerous DNA Sequence Differences 

(eg., rRNA) 

2.2% sequence diversity 

RFLP/DNA Probes 

B133 

cEH-NP1 

P145 

cEH-P1

Galactose Inhibitable Adherence Protein 

• trophozoites adhere to mucins, epithelial 

cells, leukocytes, etc 

• mediated by galactose-inhibitable lectin activity 

• lectin activity due to surface protein (GIAP) 

• 170 kDa heavy chain mediates binding (multigene 

family) 

• 35 kDa light chain anchor to membrane 

• α-GIAP Abs abrogate complement resistance 

• ~85% identity between Eh and Ed 

• Are there differences in adherence? 

• after contact the target cell is lysed and 

phagocytosed by the trophozoite

Host Cell Lysis and Phagocytosis 

• Amebapore 

• pore-forming peptide 

• potent anti-bacterial 

activity 

• located in vacuoles, not 

secreted 

• Eh and Ed sequences 

are 95% identical 

• Glu→Pro change 

breaks α-helix 

• Ed had 80% less 

activity than Eh

Entamoeba Proteases 

• Eh expresses and secretes higher 

levels of cysteine proteases 

• 6 cys-protease genes (ehcp1-6) 

• ehcp1 and 5 are missing in Ed 

• 90% inhibition of ehcp5 did not affect 

trophozoite mediated destruction of 

host cell monolayers

Prevalence 

Epidemiologic Risk Factors 

• lower socioeconomic status 

• crowding 

• lack of indoor plumbing 

• endemic area 

• institutionalization 

• communal living 

• promiscuity among male 

homosexuals 

Severity 

Modified from Ravdin (1995) Clin. Inf. Dis. 20:1453 

• children, esp. neonates 

• pregnancy and 

postpartum states 

• corticosteroid use 

• malignancy 

• malnutrition

Clinical Syndromes 

Associated with Amebiasis 

Intestinal Disease 

• asymptomatic cyst passer 

• symptomatic nondysenteric 

infection 

• amebic dysentery 

• fulminant colitis 

! + perforation (peritonitis) 

• ameboma (amebic granuloma) 

• perianal ulceration 

Extraintestinal Disease 

• liver abscess 

• pleuropulmonary amebiasis 

• brain and other organs 

• cutaneous and genital diseases 

Intestinal Symptoms 

• range 

• mild to intense 

• transient to long lasting 

• nondysenteric 

• diarrhea 

• cramps 

• flatulence 

• nausea 

• dysenteric 

• blood/mucus in stools 

• cramps/pain 

• tenesmus 

• ameboma 

• palpable mass 

• obstruction

Diagnosis 

Intestinal 

• stool examination 

! cysts and/or trophozoites 

• sigmoidoscopy 

! lesions, aspirate, biopsy 

• antigen detection 

! histolytica/dispar 

Extraintestinal (hepatic) 

• symptoms 

! history of dysentery 

! RUQ pain 

! enlarged liver 

• serology (current or past?) 

• imaging (CT, MRI, ultrasound) 

• abscess aspiration 

! only select cases 

! reddish brown liquid 

! trophozoites at abscess wall

Antigen Detection Assay 

α-GIAP Monoclonal 

Antibodies 

mAb E.h. E.d. 

3F4 + + 

8A3 + + 

7F4 + - 

8C12 + - 

1G7 + - 

H85 + - 

Reactivities of mAbs against 

E. histolytica and E. dispar 

Possible Outcomes 

and Interpretations 

capture/detection mAbs 

3F4/8A3 

8C12/1G7 interpretation 

+ + E. histolytica 

+ - E. dispar 

- + inconclusive 

- - negative

Diagnosis 

Intestinal 

• stool examination 

! cysts and/or trophozoites 

• sigmoidoscopy 

! lesions, aspirate, biopsy 

• antigen detection 

! histolytica/dispar 

Extraintestinal (hepatic) 

• symptoms 

! history of dysentery 

! RUQ pain 

! enlarged liver 

• serology (current or past?) 

• imaging (CT, MRI, ultrasound) 

• abscess aspiration 

! only select cases 

! reddish brown liquid 

! trophozoites at abscess wall

Treatment 

asymptomatic 

• iodoquinol or 

paromomycin 

• endemic areas? 

symptomatic 

• metronidazole or 

tinidazole 

• followed by lumenal 

agents 

drain liver abscess 

• only with high 

probability of rupture! 

Control and 

Epidemiology 

• avoid fecal-oral transmission 

• not normally associated with 

travelers diarrhea 

• > 1 month stay 

• institutions 

• mass drug treatment little 

affect 

• ↑ staff and improved housing 

conditions lowers prevalence 

• male homosexuals 

• 40-50% in NYC and SF during 

late 70’s 

• lower since AIDS/safe sex

Entamoeba histolytica

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