Entamoeba Histolytica Entamoeba Histolytica

Library Entamoeba histolytica Lecture Yakut Akyön Yılmaz Hacettepe university, authorMedical Faculty, Medical Microbiology Department Onlineby ©

ESCMID AMOEBA Library Sub phylum: Sarcodina Super class: Rhizopoda FilFamily: EbidEntamoebidae Ordo: LectureAmobida Class: Lobosea Genus: Entamoebaauthor Species: Entamoeba histolytica Onlineby Entamoeba hartmanni © Entamoeba coli EtEntamoeb a polkilecki Entamoeba gingivalis ESCMID Entamoeba histolytica 1875 Losch (Russia) Library 1886 Kartulis (Egypt) 1913 Walker‐Sellards (Philipines) 1891 CouncilmanLecture‐Lafleur (USA) 1933 Chicagoauthor epidemy 1950 Onlineby Indiana epidemy 2002 © Georgia epidemy 1900’ Emile Brumpt 1970’ zymodem analyses 1990’ESCMID molecular Entamoeba histolytica Causative agent Library of the disease amoebiasis (old name : Amoebic Dysentery).

dogs,Lecture cats and primates may be infected ¾parasiteauthor is primarily a human parasite and is transmitted from human to human. Onlineby ©

ESCMID EPIDEMIOLOGY Library • 10% world population is infected with Entamoeba histoltica/dispar • Majority with non invasiveLecture E. dispar • 90% infections are asymptomatic • 10% Æ symptomatic author Onlineby © • Amoebiasis is the third most common cause of death from parasite disease ESCMID TRANSMISSION ÆTwo forms Library Cyst Trophozoite Infective form is the cystLecture Route Æ faeco‐oral routeauthor Rarely anal inocOnlineulation by Ingestion of food &© water contaminated with cyst (hands) ArthropodsESCMID Entamoeba histolytica Library Cyst (infectious) Trophozoite Thick walled Plasmalemma (Thin)

1‐4 circular nucleus 1 circular nucleus Lecture Spherical (14 – 20 µm) Irregular (12 – 17 µm) author Onlineby ©

ESCMID Entamoeba histolytica Cysts Library Infective form ¾Cyst wall is resistant to environmental conditions. ¾Cysts remain viable in moist Lectureenvironment for 1 month

¾Remain alive in humidtyauthor ¾Boiling andOnline didryingby w ill kill them ¾susceptible to© heat (above 40 °C), freezing (below –5 °C) Can be detected in hard stool, can not be detected in watery diarhea ESCMID Entamoeba histolytica Library Trophozoite Motile, living form Causes ameobiasis •Can spread to theLecture body •Rarely can be responsible of transmission •Motile in diarheal authorstool •For diagnosisOnline itby should be fixed immediately or kept in +4© 0C • Trophozoites colonize the large intestine and invade the mucosa.

• They live within the crypts and mucosa of the large intestinal lining.

• TrophozoitesESCMID may live and multiply indefinitely within the crypts of the large intestine mucosa feeding on starches and mucous secretions. Trophozoites and Cysts Library

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ESCMID Entamoeba histolytica Trophozoites

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ESCMID Entamoeba histolytica Cysts

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UninucleateESCMID cyst Binucleate cyst Entamoeba histolytica Cysts Library

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Quadrinucleate or mature cysts ESCMID Library

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ESCMID TYPES Library Two forms of amoebias is 1. intestinal amoebiasis 2. extraintestinal amoebiasisLecture Æhepatic Æpulmonary author ÆcerebralOnlineby © Ægenito urinary

ESCMID Entamoeba histolytica Library PiPatogenesis Trophozoites Æ adhere to epihitheli lilal cells resolve the mucosa epithelialLecture cells ulilceration and idinvade the mucosa causes dysentery (diarhea author+ blood) spreads vi a blooOnlined and byllhiymp hatic system causes abscess extra©‐intestinal in sites

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Adhesion is mediated by several cell‐surface proteins. One such adhesin is a multimericESCMID protein complex with specific binding affinity for galactose (Gal) or N‐ acetyl‐D‐galactosamine (GalNAc). Entamoeba histolytica Clinical classification(()WHOLibrary)

Asymptomatic infection (intestine) cyst spreaders

Symptomatic infection Lecture •Intestinal amebiasis(colon and rectum) Acute dysentericauthor (dysentery) CCochronic non‐dysente ric (self‐limited) •ExtraintestinalOnline Amoebiasisby Amoebic© Liver Abscess (ALA) Amoebic Pulmoner Abscess (APA) Other sites (brain, skin, genito‐urinary ESCMID system,?) Entamoeba histolytica Library Asymptomatic infection (intestine) “cyst spreaders”

•Most frequent Lecture •Asymptomatic for weeks‐months •Self‐limited author •Two species •E. histolyticaOnline(pathogen)by •E. dispar (non©‐pathogen)

ESCMID Entamoeba histolytica Intestinal Amoebiasis Library Two types Acute dysenteric (dysentery) Chronic non‐dysentericLecture (self‐limited, porter state) author Onlineby ©

ESCMID Colitis is the most common form of disease associated with amoebae Library

• Gradual onset of abdom ina l pain, watery Lecturestools containing mucus and blood •authorSome patients have only intermittent diarrhea Onlineby alilternating wihith © constipation • Fever is uncommon • Formation of ulcers ESCMID Colitis is the most common form of disease associated with amoebae Library

Lecture author Onlineby © • Amoeba invade mucosa and erode through laminia propria causing characterisitic flask shaped ulcers. ESCMID CLINICAL FEATURES Library IbiIncubation peridiod Æ 2‐6 week s

9 Grumbling abdominal pain 9 Two or more unformed stools/dayLecture 9 Periods of diarrhoea alternatingauthor with constipation 9 Mucous aadnd or blood mixed ssoo/tool/ ooeseffensive odour Onlineby 9 Tenderness in lower© abdominal region 9 Tenesmus 9 Fever, uncommon (% 33) ESCMID Entamoeba histolytica Library Chroni c amoebiasi s (i)(carrier) 37% symptomatic (5 years) Intermittent diarrhea, mucus, abdominal pain and/or weight loss Lecture Trophozoites in stool (rarely cyst) Serologically positive author Onlineby ©

ESCMID Ulceration can lead to secondary infection and extraintestinal lesions Library

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ESCMID COMPLICATIONS Library ¾Toxic megacolon, after wrong treatment with steroids ¾Amoeboma (rare) can beLecture mis‐diagnosed as cancer ¾Acute flfulminant colitis author ¾Peri aaanal uuceatolceration Onlineby ¾Stricture & intussusceptions© & peritonitis

ESCMID Entamoeba histolytica Library Diagnosis: Ova/parasite examination; trophozoite, cyst Concentration methods;Lecture cyst Trichrome staining (permenant staining) Sigmoidoscopy author Serologic testsOnline (chronicby cases) ©

ESCMID FEATURES AMOEBIC DYSENTRY BACTERIAL DYSENTRY INCUBATION PERIOD Long Libraryshort

ONSET Insidious Acute

Low abd pain, fever Generalised abd pain, SYMPTOMS absent, volumeLecture of stool fever, volume of stool copious, mod tenesmus less, severe tenesmus author LAB DIAG Few pppus cellsnumerous pppus cells Onlineby S TOOL STOOL Trophozoites© with No trophozoites MICROSCOPY ingggested RBCs CULTURE Bacilli not Dysentery bacilli demonstrated ESCMID Extraintestinal amoebiasis Entamoeba histolytica Library EtExtrai itntesti nal amoebiasi s

Amoebic Liver abscess (ALA) Amoebic pulmoner abscessLecture(()APA ) Other sites (brain, skin, authorgenito‐urinary system,?) Onlineby ©

ESCMID Extraintestinalamoebiasis ESCMID

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Library Entamoeba histolytica Amoebic Liver abscess Library (ALA)

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ESCMID PATHOGENESIS Library • IiInvasion of trophihozoites into porta l system & reaches liver • IfilInfiltrat ion of neutrophils into liver • Lysis of neutrophils on contactLecture with amoeba • Release of neutrophil toxin & damage liver parenchyma author • Necrosis of parenchymaOnlineby & abscess formation filled with chocolate brown© pus • Usually abscess forms in postero‐superior quadrant of the right lobe of liver ESCMID CLINICAL FEATURES Library 9Lead symptoms are right upper qua drant pain and fever 9Discomfort & tendernessLecture in right hypochondrium 9Pain in right shoulder author 9SiSwing ing temperatureOnlineby & sweati ng 9Cougg,h, malaise, &© loss of appetite 9Jaundice uncommon ESCMID COMPLICATIONS Library ¾Pleural effusion ¾Hepato bronchial fistula Lecture ¾Left lobe abscess may rupture into peritonial cavity, pleuralauthor space or pericardial cavityOnlineby ©

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Patient with amoebiasis liver absess, with perforation of abscess through abdominalauthor skin. Onlineby ©

ESCMIDGross Pathology of amoebic liver abscess Entamoeba histolytica Diagnosis: Library Stool examination CBC (leucocytosis?) Radiology (CT; MRI)Lecture Serology Culture author Examination of aspiration fluid Onlineby ©

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ESCMID Pus from aspiration fluid Pulmonary Amoebiasis Library • Direct pulmonary infection (blood circulation) • Secondary infection; after liver amoebiasis at the right pulmonary Lecture – Cases siilngle or several ab scess author Onlineby ©

ESCMID Cerebral Amoebiasis Library • Occur from complications of liver and ppyulmonary amoebiasis – Cases single or several Lectureabscess author Onlineby ©

ESCMID Spleen and Cutaneous

AmoebiasisLibrary • Spleen ab scess is al ways seen with l iver amoebiasis • Cutaneous amoebiasisLecture is seen in perianal site author Onlineby ©

ESCMID Amoebic Amebiasis of the Skin Library

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ESCMID Amoebiasis cutis: Clinical suspicion is the key to early diagnosisajd_594 52..55 Ghanshyam K Verma,1 Nand Lal Sharma,2 Vinay Shanker,1 Vikram K Mahajan,1 Rajani Kaushik,3 Santwana Verma4 and Nidhi Jindal1 (INDIA)

Figure 1 (a) Amoebiasis cutis lesion showingLibrary hyperpigmented borders, discoloration, pus discharging from sinuses and characteristic ulcers over the plaque. (b) Close -up view of (a). Also note condylomata lata-like nodular lesions around Lectureanal orifice.

3 years earlier as a painful nodule in the perianal region which ulcerated discharging purulent material. The ulcerauthor increased gradually to involve the buttocks, perineum and part of the left upper thigh. Historically,Online there wereby infrequent episodes of constipation or blood mixed loose stools. He had been previously investigated for cutaneous© tuberculosis andCd Cro hn ’s disease. CltCulture and pol ymerase c hihain reaction studies on the pus were negative for Mycobacterium tuberculosis while proctoscopy and barium enema were normal. Escherichia coli cultured from the pus was sensitive to ciprofloxacinESCMID DIAGNOSIS Library • SHOULD BE DIFFERENTIATED FROM NON‐ PATHOGENIC AMOEBA • STOOL EXAMINATION Lecture • TRICHROME STAIN (PERMENANT) author • STOOL ANTIGEN TESTÆELISA (MONOCLONAL Onlineby ABÆE. histolytica ©adhesine) • MOLECULAR (PCR, REAL TIME PCR)

ESCMID Amoeba in human Library

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E. coli Lecture E. histolytica author Onlineby ©

E. histolytica ESCMID E. coli Library

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Lecture author Entamoeba histolytica Epithelial cell Onlineby ©

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Entamoeba histolytica ESCMID macrophage Library

EntamoebaESCMID histolytic a Ephitelial cell Library

EntamoebaESCMID histolytic a Library

E. histolytica (HES staining)

ESCMID Amoebic liver abscess visualized on a computed tomogramtomogram Library (Peters and Pasvol, 2002)

Lecture author Onlineby CT scan guided aspiration of © amoebic liver abscess with chocolate coloured pus (anchovy sauce) ESCMID (Peters and Pasvol, 2002) Library

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ESCMID The treatment of Entamoeba histolytica Library • For asymptomatic iifnfect ions, iodoquinol, paromomycin, or diloxanide furoate (limits the spread of cysts) • For symptomatic intestinalLecture disease, or extraintestinal, infections (e.g., hepatic abscess),author metronidazole or tinidazole, immediately followedOnline byby treatment with iodoquinol, paromomycin, or diloxanide© furoate.

ESCMID PREVENTION/CONTROL Diagnose and treat patients Library Wash hands with soap & water at least 10 seconds after using toilet or changing baby diaper Clean bathroom & toiletsLecture often Avoid sharing towels author Avoid eating raw ve getables, wash them well (endemic areas)Onlineby © Boil water or treat with iodine tablets or filter (0.22 filtration) PreventESCMID food contamination with stool E. histolytica Diagnosis by Real‐time PCR Library • 230 stool samples Æ22 positive for E. histolytica (% 9.6 ) Lecture author Onlineby ©

Yakut Akyön Yılmaz, Fadile Zeyrek, Ahmet Pınar, Alpaslan Alp, Sibel Ergüven ESCMID Entamoeba histolytica – AMOEBIASIS, AMEBIC DYSENTRY; AMOEBIC LIVER ABSCESS Library • SdSecondary lilesions occur as a result o f METASTASIS of trophozoites to extraintestinal organs – liver is most frequently affected – Hepatic amoebiasis; pulmonary amebiasis; cerebral ameobiasis;Lecture cutaneous amebiasis; spleenic abscess. • Symptoms: Diarrhea; dysenteryauthor – stool containing blood, mucous and shreds of necrotic mucosa, acute abdominal pain, tendernessOnlineby and fever. Chronic ameobiasis – recurrent© attacks of dysentery. Abdom ina l ttdenderness, HEPATOMEGALY; weihtight loss and emaciation.

ESCMIDSUMMARY Library

ESCMID Entamoeba histolytica – AMOEBIASIS, AMEBIC DYSENTRY; AMOEBIC LIVER ABSCESS Library • Life cycle: ihbitinhabit the large iitntes tine; the cyst is the infective stage. On ingestion –excystinto amoebulae – trophozoites which is the vegetative stage –invade the mucosa to absorb nourishment from tissuesLecture dissolved by its cytolytic enzymes and alsoauthor ingest RBCs. • Pathology and Symptomatology: primary lesion is ULCER ‐ invasionOnline of theby wall of large intestine – ulcer is flask shaped.© Complications –amoebic granuloma (amoeboma); appendicitis, stricture, intestinal perforation ESCMID Clinical Spectrum of Amoebiasis Library

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