Case No. 26

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Case No. 26

• LIM, YOONTAEK
• Clark

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Case

• EF, a fresh college graduate, is applying for a
  job at a pharmaceutical company.
• Routine laboratory examinations were requested.
• Fecalysis revealed () E. histolitica
• Asymptomatic

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Entamoeba histolytica

• Protozoan parasite, cause of diarrhea, dysentery,
  liver abscess and other syndromes
• Occurs primarily in developing countries, but
  immigrants, travelers, diagnosed with infection
  in U.S.
• Must be distinguished clinically from Entamoeba
  dispar, a morphologically identical parasite that
  is non-invasive and does not cause disease
• Onset of colitis usually gradual with symptoms gt
  1 wk, distinguishing it from bacterial dysentery
• Infective stage mature tetranucleated cyst

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Transmission

• Polluted water supply
• Unclean handling by injected individuals
• Droppings of flies and other insects
• Use of human excrement an vegetable gardens
• Gross carelessness in personal hygiene
• In homosexual acquired through sexual, anal
  intercourse

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SITES OF INFECTION

• Colon dysentery, ameboma (tumor-like lesion of
  colonic lumen can be confused radiographically
  with cecal cancer), toxic megacolon
• Liver abscess, can rupture causing peritonitis
• Lung empyema (right sided- direct extension from
  liver)
• Heart pericarditis (direct extension from liver)
• Brain abscess (hematogenous spread, rare)
• Skin usually perineal, genital
• GU recto-vaginal fistula

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Diagnosis of amebic colitis

1. Observation of red cell-containing motile
   trophozoites on fresh stool smear (insensitive)
   always heme stool
2. Colonoscopy biopsy or scraping at margin of
   colonic mucosal ulcer parasite may be seen HE
   shows necrosis, classic flask-shaped ulcer
3. Stool antigen test that distinguishes Eh from E.
   dispar is available, more sensitive than
   microscopy of stool
4. 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
   immigrants from Eh-endemic regions
5. Ultrasound of liver cannot distinguish amebic
   from pyogenic abscess, but can guide aspiration
   if necessary
6. Liver abscess aspiration--yields anchovy
   paste-like material, lack of WBCs (due to lysis
   by parasite) clue to diagnosis, parasites usually
   not seen

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Laboratory Diagnosis

• Microscopy
• Microscopic identification of cysts and
  trophozoites in the stool is the common method
• Fresh stool wet mounts and permanently stained
  preparations (e.g., trichrome).
• Concentrates from fresh stool wet mounts, with
  or without iodine stain, and permanently stained
  preparations (e.g., trichrome).
• E. histolytica trophozoites can also be
  identified in aspirates or biopsy samples
  obtained during colonoscopy or surgery

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Trophozoites of Entamoeba histolytica
Trichrome stain
Line drawing
Trophozoites of Entamoeba histolytica with
ingested erythrocytes (trichrome stain)
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• Invasive form
• Active, progressive, indirectional
• Found in liquid stool
• Eccenteric karyosome, bulls eyes
• 1 nucleus
• Presence of ingested RBC
• Killed by exposure to air or stomack acid -gt
  cannot cause infection

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Cysts of Entamoeba histolytica
Line drawing
Stained with trichrome
Wet mounts stained with iodine
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• Infective stage
• Found in formed stool
• 4 nuclei
• Cigar-shape chromatoidal body
• With glycogen mass

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Diagnosis

• Immunodiagnosis
• Antibody Detection Enzyme immunoassay (EIA) kits
  for Entomoeba histolytica
• 95 of patients with extraintestinal amebiasis
• 70 of patients with active intestinal infection
• 10 of asymptomatic persons who are passing cysts
• Detectable E. histolytica-specific antibodies may
  persist for years after successful treatment, so
  the presence of antibodies does not necessarily
  indicate acute or current infection
• Antigen Detection
• Useful as an adjunct to microscopic diagnosis in
  detecting parasites and to distinguish between
  pathogenic and nonpathogenic infections

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Diagnosis

• Molecular methods
• PCR is the method of choice for discriminating
  between the pathogenic species (E. histolytica)
  from the nonpathogenic species (E. dispar)

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Treatment of amoebiasis by Rang

• Acute invasive intestinal amoebiasis resulting in
  acute severe amoebic dysentery metronidazole
  (or tindazole) followed by diloxanide
• Chronic intestinal amoebiasis diloxanide
• Hepatic amoebiasis metronidazole followed by
  diloxanide
• Carrier state diloxanide

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Treatment of amoebiasisby katzung
Clinical setting DOC (adult dosage) Alternative drugs (adult)
Asymptomatic intestinal infection Luminal agent Diloxanide furoate, 500mg tid 10days Iodoquinol, 650mg tid for 21days Paromomycin, 10mg/kg tid for 7days
Mild to moderate intestinal infection Metronidazole, 750mg tid or 500mg IV every 6hours 10days Luminal agent Luminal agent Tetracyclin, 250mg tid 10days or Erythromycin, 500mg qid 10days
Severe intestinal infection Same as mild to moderate infection Luminal agent Tetracyclin, 250mg tid 10days or Dehydroemetine or emetine, 1mg/kg SC or IM 35days
Hepatic abscess, ameboma and other detraintestinal disease Same as mild to moderate infection Dehydroemetine or emetine, 1mg/kg SC or IM 810days followed by (in abscess only) chloroquine, 500mg bid 2days then 500mg qd 21days Luminal agent
Diloxanide furoate not available in U.S. Diloxanide furoate not available in U.S. Diloxanide furoate not available in U.S.
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Treatment for asymptomatic patient

• Luminal agents alone should be used (not
  absorbed)
• Iodoquinol 650 mg tid x 20 days
• Paromomycin 25-35 mg/kg/d in 3 divided doses x 7
  days

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Metronidazole (nitroimidazole)

• DOC for treatment of extraluminal amoebiasis
• Kills trophozoites but has no effect on the cysts
• Most effective drug available for invasive
  amoebiasis involving the intestine or the liver,
  but less against in the lumen of the gut
• MOA damage to the DNA of the trophozoite by
  toxic oxygen products generated from the drug
• Pharmacokinetics
• Given orally
• Rapidly and completely absorbed.
• Peak conc 13 hours
• T1/2 7 hours
• Excreted in urine
• Also used in Giardiasis (DOC), Trichomoniasis
  (DOC)

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Metronidazole (nitroimidazole)

• S/E
• Frequent GI intolerance, metallic taste,
  headache, dark urine (harmless)
• Occasional peripheral neuropathy (with prolonged
  use, usually reversible), phlebitis at injection
  sites, disulfiram-like reaction with alcohol,
  insomnia, stomatitis.
• Drug interaction
• Disulfiram and ethanol avoid co-administration
• Barbiturates may decrease metronidazole levels

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Iodoquinol

• Lumninal agent
• 90 not absorbed
• Unknown mechanism
• Effective for trophozoite in lumen but not in
  bowel wall or tissue
• S/E
• GIT
• Increase protein bound iodine
• Dermatitis, urticaria
• Neurotoxin
• Nephrotoxin

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Diloxanide furoate

• Luminal agent
• Inactive against tissue trophozoite
• Unknown mechanism
• Direct amoebicidal action, affecting the amoebae
  before encystment
• DOC for asymptomatic infection
• No serious side effects
• Contraindicated in pregnancy
• S/E
• Itchy rash (urticaria)
• Itching (pruritus)
• Excess gas in the stomach and intestines
  (flatulence)
• Vomiting

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Paromomycin sulfate

• An aminoglycoside
• Luminal only
• S/E
• GIT
• Renal toxicity
• Caution with GIT ulceration since drug can be
  absorbed with more toxicity

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Emetine Dehydroemetine

• For tissue trophozoite
• Oral unreliable
• IM or SC is preferred never IV toxic
• Only for 35 days not more than 10days
• Dehydroemetine is preferred (less tosic)
• For severe amoebiasis where metronidazole cannot
  be used
• Combine with luminal agent
• S/E
• Pain at injection site sterile abscess
• Arrythmia, CHF, hypotension
• Contraindication
• Cardiac disease
• Renal disease ( cannot be excreted may
  accumulated )
• Young children pregnancy

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Thank you!