Case No. 26Case No. 26LIM, YOONTAEKLIM, YOONTAEK

ClarkClark

CaseCase EF, a fresh college graduate, is applying for EF, a fresh college graduate, is applying for

a job at a pharmaceutical company.a job at a pharmaceutical company. Routine laboratory examinations were requRoutine laboratory examinations were requ

ested.ested. Fecalysis revealed: Fecalysis revealed: (+) (+) E. histoliticaE. histolitica AsymptomaticAsymptomatic

Entamoeba histolyticaEntamoeba histolytica Protozoan parasite, cause of diarrhea, dysentery, liver abProtozoan parasite, cause of diarrhea, dysentery, liver ab

scess and other syndromesscess and other syndromes Occurs primarily in developing countries, but immigrants, Occurs primarily in developing countries, but immigrants,

travelers, diagnosed with infection in U.S.travelers, diagnosed with infection in U.S. Must be distinguished clinically from Must be distinguished clinically from Entamoeba disparEntamoeba dispar, ,

a morphologically identical parasite that is non-invasive aa morphologically identical parasite that is non-invasive and does not cause diseasend does not cause disease

Onset of colitis usually gradual with symptoms > 1 wk, diOnset of colitis usually gradual with symptoms > 1 wk, distinguishing it from bacterial dysenterystinguishing it from bacterial dysentery

Infective stage : mature tetranucleated cystInfective stage : mature tetranucleated cyst

TransmissionTransmission Polluted water supplyPolluted water supply Unclean handling by injected individualsUnclean handling by injected individuals Droppings of flies and other insectsDroppings of flies and other insects Use of human excrement an vegetable Use of human excrement an vegetable

gardensgardens Gross carelessness in personal hygieneGross carelessness in personal hygiene In homosexual acquired through sexual, In homosexual acquired through sexual,

anal intercourseanal intercourse

SITES OF INFECTION SITES OF INFECTION ColonColon: dysentery, ameboma (tumor-like lesion of colonic l: dysentery, ameboma (tumor-like lesion of colonic l

umen; can be confused radiographically with cecal canceumen; can be confused radiographically with cecal cancer), toxic megacolonr), toxic megacolon

LiverLiver: abscess, can rupture causing peritonitis: abscess, can rupture causing peritonitis LungLung: empyema (right sided- direct extension from liver): empyema (right sided- direct extension from liver) HeartHeart: pericarditis (direct extension from liver): pericarditis (direct extension from liver) BrainBrain: abscess (hematogenous spread, rare): abscess (hematogenous spread, rare) SkinSkin: usually perineal, genital: usually perineal, genital GUGU: recto-vaginal fistula: recto-vaginal fistula

Diagnosis of amebic Diagnosis of amebic colitiscolitis

1.1. Observation of red cell-containing motile trophozoites on fresh stool smObservation of red cell-containing motile trophozoites on fresh stool smear (insensitive); always heme + stoolear (insensitive); always heme + stool

2.2. Colonoscopy: biopsy or scraping at margin of colonic mucosal ulcer: parColonoscopy: biopsy or scraping at margin of colonic mucosal ulcer: parasite may be seen; H&E shows necrosis, classic flask-shaped ulcerasite may be seen; H&E shows necrosis, classic flask-shaped ulcer

3.3. Stool antigen test that distinguishes Eh from E. dispar is available, more Stool antigen test that distinguishes Eh from E. dispar is available, more sensitive than microscopy of stoolsensitive than microscopy of stool

4.4. Serology 99% sens. for amebic liver abscess; 88% sens. for colitis, but Serology 99% sens. for amebic liver abscess; 88% sens. for colitis, but Abs may be present yrs. later so that serology may not be useful in immiAbs may be present yrs. later so that serology may not be useful in immigrants from Eh-endemic regionsgrants from Eh-endemic regions

5.5. Ultrasound of liver: cannot distinguish amebic from pyogenic abscess, bUltrasound of liver: cannot distinguish amebic from pyogenic abscess, but can guide aspiration if necessaryut can guide aspiration if necessary

6.6. Liver abscess aspiration--yields anchovy paste-like material, lack of WBLiver abscess aspiration--yields anchovy paste-like material, lack of WBCs (due to lysis by parasite) clue to diagnosis, parasites usually not seeCs (due to lysis by parasite) clue to diagnosis, parasites usually not seen n

Laboratory DiagnosisLaboratory Diagnosis MicroscopyMicroscopy

Microscopic identification of cysts and trophozoites in Microscopic identification of cysts and trophozoites in the stool is the common methodthe stool is the common method

Fresh stool: wet mounts and permanently stained preparationFresh stool: wet mounts and permanently stained preparations (e.g., trichrome). s (e.g., trichrome).

Concentrates from fresh stool: wet mounts, with or without ioConcentrates from fresh stool: wet mounts, with or without iodine stain, and permanently stained preparations (e.g., trichrodine stain, and permanently stained preparations (e.g., trichrome).me).

E. histolyticaE. histolytica trophozoites can also be identified in asp trophozoites can also be identified in aspirates or biopsy samples obtained during colonoscopy irates or biopsy samples obtained during colonoscopy or surgeryor surgery

Trophozoites of Trophozoites of Entamoeba histolyticaEntamoeba histolytica

Trichrome stain

Trophozoites of Entamoeba histolytica with ingested erythrocytes (trichrome stain)

Line drawing

Invasive formInvasive form Active, progressive, indirectionalActive, progressive, indirectional Found in liquid stoolFound in liquid stool Eccenteric karyosome, “bulls eyes”Eccenteric karyosome, “bulls eyes” 1 nucleus1 nucleus Presence of ingested RBCPresence of ingested RBC Killed by exposure to air or stomack acid Killed by exposure to air or stomack acid

-> cannot cause infection-> cannot cause infection

Cysts of Cysts of Entamoeba histolyticaEntamoeba histolytica

Line drawing

Wet mounts stained with iodine

Stained with trichrome

Infective stageInfective stage Found in formed stoolFound in formed stool 4 nuclei4 nuclei Cigar-shape chromatoidal bodyCigar-shape chromatoidal body With glycogen massWith glycogen mass

DiagnosisDiagnosis ImmunodiagnosisImmunodiagnosis

Antibody Detection; Antibody Detection; Enzyme immunoassay (EIA) kits foEnzyme immunoassay (EIA) kits for r Entomoeba histolyticaEntomoeba histolytica

95% of patients with extraintestinal amebiasis95% of patients with extraintestinal amebiasis 70% of patients with active intestinal infection70% of patients with active intestinal infection 10% of asymptomatic persons who are passing cysts10% of asymptomatic persons who are passing cysts Detectable Detectable E. histolyticaE. histolytica-specific antibodies may persist for ye-specific antibodies may persist for ye

ars after successful treatment, so the presence of antibodies ars after successful treatment, so the presence of antibodies does not necessarily indicate acute or current infectiondoes not necessarily indicate acute or current infection

Antigen DetectionAntigen Detection Useful as an adjunct to microscopic diagnosis in detecting paUseful as an adjunct to microscopic diagnosis in detecting pa

rasites and to distinguish between pathogenic and nonpathograsites and to distinguish between pathogenic and nonpathogenic infections enic infections

DiagnosisDiagnosis Molecular methodsMolecular methods

PCR is the method of choice for discriminating PCR is the method of choice for discriminating between the pathogenic species (between the pathogenic species (E. histolyticE. histolyticaa) from the nonpathogenic species () from the nonpathogenic species (E. disparE. dispar))

Treatment of amoebiasis Treatment of amoebiasis by Rangby Rang

Acute invasive intestinal amoebiasis resulting in acute seAcute invasive intestinal amoebiasis resulting in acute severe amoebic dysentery : metronidazole (or tindazole) follvere amoebic dysentery : metronidazole (or tindazole) followed by diloxanideowed by diloxanide

Chronic intestinal amoebiasis : diloxanideChronic intestinal amoebiasis : diloxanide Hepatic amoebiasis : metronidazole followed by diloxanidHepatic amoebiasis : metronidazole followed by diloxanid

ee Carrier state : diloxanideCarrier state : diloxanide

Treatment of amoebiasisTreatment of amoebiasisby katzungby katzung

Clinical settingClinical setting DOC (adult dosage)DOC (adult dosage) Alternative drugs Alternative drugs (adult)(adult)

Asymptomatic Asymptomatic intestinal infectionintestinal infection

Luminal agent :Luminal agent :Diloxanide furoate, 500mg tid 10daysDiloxanide furoate, 500mg tid 10daysIodoquinol, 650mg tid for 21daysIodoquinol, 650mg tid for 21daysParomomycin, 10mg/kg tid for 7daysParomomycin, 10mg/kg tid for 7days

Mild to moderate Mild to moderate intestinal infectionintestinal infection

Metronidazole, 750mg tid or 500mg IV every Metronidazole, 750mg tid or 500mg IV every 6hours 10days6hours 10days++Luminal agentLuminal agent

Luminal agentLuminal agent++Tetracyclin, 250mg tid 10days orTetracyclin, 250mg tid 10days orErythromycin, 500mg qid 10daysErythromycin, 500mg qid 10days

Severe intestinal Severe intestinal infectioninfection

Same as mild to moderate infectionSame as mild to moderate infection Luminal agentLuminal agent++Tetracyclin, 250mg tid 10days orTetracyclin, 250mg tid 10days orDehydroemetine or emetine, 1mg/kg SC or IDehydroemetine or emetine, 1mg/kg SC or IM 3~5daysM 3~5days

Hepatic abscess, ameboma Hepatic abscess, ameboma and other detraintestinal disand other detraintestinal diseaseease

Same as mild to moderate infectionSame as mild to moderate infection Dehydroemetine or emetine, 1mg/kg SC or IDehydroemetine or emetine, 1mg/kg SC or IM 8~10days followed by (in abscess only) cM 8~10days followed by (in abscess only) chloroquine, 500mg bid 2days then 500mg qhloroquine, 500mg bid 2days then 500mg qd 21daysd 21days++Luminal agentLuminal agent

**Diloxanide furoate : not available in U.S.Diloxanide furoate : not available in U.S.

Treatment for Treatment for asymptomatic patientasymptomatic patient

Luminal agents alone should be used (not Luminal agents alone should be used (not absorbed)absorbed)

Iodoquinol: 650 mg tid x 20 daysIodoquinol: 650 mg tid x 20 days Paromomycin: 25-35 mg/kg/d in 3 divided Paromomycin: 25-35 mg/kg/d in 3 divided

doses x 7 daysdoses x 7 days

Metronidazole (nitroimidazole)Metronidazole (nitroimidazole) DOC for treatment of extraluminal amoebiasisDOC for treatment of extraluminal amoebiasis Kills trophozoites but has no effect on the cystsKills trophozoites but has no effect on the cysts Most effective drug available for invasive amoebiasis involving the intestMost effective drug available for invasive amoebiasis involving the intest

ine or the liver, but less against in the lumen of the gutine or the liver, but less against in the lumen of the gut MOA : damage to the DNA of the trophozoite by toxic oxygen products geMOA : damage to the DNA of the trophozoite by toxic oxygen products ge

nerated from the drugnerated from the drug PharmacokineticsPharmacokinetics

Given orallyGiven orally Rapidly and completely absorbed.Rapidly and completely absorbed. Peak conc : 1~3 hoursPeak conc : 1~3 hours T1/2 : 7 hoursT1/2 : 7 hours Excreted in urineExcreted in urine

Also used in Giardiasis (DOC), Trichomoniasis (DOC)Also used in Giardiasis (DOC), Trichomoniasis (DOC)

Metronidazole (nitroimidazole)Metronidazole (nitroimidazole) S/ES/E

Frequent: GI intolerance, metallic taste, headache, dark urine (haFrequent: GI intolerance, metallic taste, headache, dark urine (harmless)rmless)

Occasional: peripheral neuropathy (with prolonged use, usually reOccasional: peripheral neuropathy (with prolonged use, usually reversible), phlebitis at injection sites, disulfiram-like reaction with versible), phlebitis at injection sites, disulfiram-like reaction with alcohol, insomnia, stomatitis.alcohol, insomnia, stomatitis.

Drug interactionDrug interaction Disulfiram and ethanol : avoid co-administrationDisulfiram and ethanol : avoid co-administration Barbiturates may decrease metronidazole levels Barbiturates may decrease metronidazole levels

IodoquinolIodoquinol Lumninal agentLumninal agent 90% not absorbed90% not absorbed Unknown mechanismUnknown mechanism Effective for trophozoite in lumen but not in boweEffective for trophozoite in lumen but not in bowe

l wall or tissuel wall or tissue S/ES/E

GITGIT Increase protein bound iodineIncrease protein bound iodine Dermatitis, urticariaDermatitis, urticaria NeurotoxinNeurotoxin NephrotoxinNephrotoxin

Diloxanide furoateDiloxanide furoate Luminal agentLuminal agent Inactive against tissue trophozoiteInactive against tissue trophozoite Unknown mechanismUnknown mechanism Direct amoebicidal action, affecting the amoebae before Direct amoebicidal action, affecting the amoebae before

encystmentencystment DOC for asymptomatic infectionDOC for asymptomatic infection No serious side effectsNo serious side effects Contraindicated in pregnancyContraindicated in pregnancy S/ES/E

Itchy rash (urticaria) Itchy rash (urticaria) Itching (pruritus) Itching (pruritus) Excess gas in the stomach and intestines (flatulence) Excess gas in the stomach and intestines (flatulence) Vomiting Vomiting

Paromomycin sulfateParomomycin sulfate

An aminoglycosideAn aminoglycoside Luminal onlyLuminal only S/ES/E

GITGIT Renal toxicityRenal toxicity Caution with GIT ulceration since drug can be Caution with GIT ulceration since drug can be

absorbed with more toxicityabsorbed with more toxicity

Emetine & DehydroemetineEmetine & Dehydroemetine For tissue trophozoiteFor tissue trophozoite Oral unreliableOral unreliable IM or SC is preferred; never IV – toxicIM or SC is preferred; never IV – toxic Only for 3~5 days not more than 10daysOnly for 3~5 days not more than 10days Dehydroemetine is preferred (less tosic)Dehydroemetine is preferred (less tosic) For severe amoebiasis where metronidazole cannot be usedFor severe amoebiasis where metronidazole cannot be used Combine with luminal agentCombine with luminal agent S/ES/E

Pain at injection site : sterile abscessPain at injection site : sterile abscess Arrythmia, CHF, hypotensionArrythmia, CHF, hypotension

ContraindicationContraindication Cardiac diseaseCardiac disease Renal disease ( cannot be excreted & may accumulated )Renal disease ( cannot be excreted & may accumulated ) Young children & pregnancyYoung children & pregnancy

Thank you!Thank you!