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Entamoeba histolytica cosmopolitan distribution no animal reservoirs facultative pathogen most clear the infection spontaneous in 6-12 months with mild.

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Presentation on theme: "Entamoeba histolytica cosmopolitan distribution no animal reservoirs facultative pathogen most clear the infection spontaneous in 6-12 months with mild."— Presentation transcript:

1 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 = % estimated that 10% of worlds population may be infected 50 million cases invasive amebiasis/yr 100,000 deaths/yr

2 1875 Lösch correlated dysentery with amebic trophozoites 1925 Brumpt proposed two species: E. dysenteriae and E. dispar 1970's 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 Facultative Pathogenicity of Entamoeba histolytica

3 Entamoeba histolytica Life Cycle

4 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

5 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

6 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

7 trophozoite immature cyst mature cyst

8 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

9 ulcers with raised borders little inflammation between lesions

10 flasked-shaped ulcer trophozoites at boundary of necrotic and healthy tissue trophozoites ingesting host cells dysentery (blood and mucus in feces)

11 hematophagous trophozoites

12 Lateral and Downward Expansion of Ameba into Lamina Propria localized sloughing perforation of intestinal wall ulcers coalesce

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15 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)

16 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

17 Pulmonary Amebiasis rarely primary rupture of liver abscess through diaphragm 2 o bacterial infections common fever, cough, dyspnea, pain, vomica

18 Cutaneous Amebiasis intestinal or hepatic fistula mucosa bathed in fluids containing trophozoites perianal ulcers urogenital (eg, labia, vagina, penis)

19 Cutaneous Amebiasis intestinal or hepatic fistula mucosa bathed in fluids containing trophozoites perianal ulcers urogenital (eg, labia, vagina, penis)

20 Cutaneous Amebiasis intestinal or hepatic fistula mucosa bathed in fluids containing trophozoites perianal ulcers urogenital (eg, labia, vagina, penis)

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22 85-90% of infected individuals are asymptomatic ~10% of the symptomatic will develop severe invasive disease Facultative Pathogenicity

23 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 Molecular Epidemiology

24 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 pathogenecity ability to cause disease (genetic component) virulence relative capacity to cause disease (degree of pathology)

25 contact-dependent killing of epithelial cells breakdown of tissues (extracellular matrix) secreted proteases? contact-dependent killing of neutrophils, leukocytes, etc.

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27 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 -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

28 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 -helix Ed had 80% less activity than Eh

29 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

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32 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

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34 Antigen Detection Assay

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36 Treatment 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 70s lower since AIDS/safe sex asymptomatic iodoquinol or paromomycin endemic areas? symptomatic metronidazole or tinidazole followed by lumenal agents drain liver abscess only with high probability of rupture!


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