A. Organism

1. Entameba histolytica
2. "Tissue-lysing" ameba, single celled protozoan
3. Casues amebic colitis and amebic liver abscess [2,3]
   1. Diarrhea, often bloody, in colon
   2. May penetrate colonic mucosa and invade liver via portal system
   3. Untreated amebic liver abscess can be fatal
4. Ameba is highly active, phagocytic, proteolytic, cytolytic
5. Exists as either infectious cyst or ameboid trophozoite stage
   1. Cysts are 10-15µm diameter, surrounded by refractile wall which may contain chitin
   2. Trophozoites highly motile, peomorphic shape, 10-50µM variable diameter
6. Humans (possibly other primates) are only natural host
7. Second leading cause of death from parasitic disease worldwide
   1. About 500 million infected person worldwide
   2. Many of these may be infected with Entameba dispar, a nonpathogenic ameba
   3. About 75,000 people die annually of amebic infection

B. Pathophysiology

1. Infection usually begins with ingestion of cysts from contaminated food or water
   1. Many exposed persons will develop no symptoms
   2. ~4-10% initially asymptomatic, infected individuals develop symptoms over 1 year
2. ingested ameba travel to colon
3. Stimulate Intense Colitis
   1. Secretes proteinases that dissolve host tissues
   2. Stimulates host cell IL-1ß production after cell damage
   3. IL-1ß stimulates NF-kB mediated cytokine and chemokine production from local cells
   4. Cytokines stimulate neutrophil and macrophage influx and activation
   5. Macrophages release TNFa, neutrophils release proteinases
   6. Overall result is mucosal ulceration
4. Liver Abcess
   1. Ameba can break intestinal mucosal barrier and enter portal system
   2. Create unique abscesses - well demarcated wall with liquified central hepatocytes
   3. Rim of connective tissue with fue inflammatory cells surrounds abscess
   4. Presentation with liver abscess usually months to years after exposure
   5. Diagnosis only by serological testing (stool cultures negative)
   6. Aspiration of liver abscess is dangerous and usually only shows neutrophils
   7. Stool ova and parasites are typically negative with amebic abscess

C. Clinical Course

1. Careful medical history critical to determining exposure
2. Elevated risk of severe or fatal disease in high risk populations:
   1. Pregnant women
   2. Immunocompromise
   3. Glucocorticoid therapy
3. Colitis
   1. Bloody diarrhea, abdominal pain and tenderness
   2. Fever <40% of cases
   3. Fecal leukocytes may be present
   4. Fulminant amebic colitis can occur infrequently
   5. Toxic megacolon ~0.5%
4. Fulminant Colitis
   1. Fever, marked leukocytosis
   2. Severe abdominal pain with peritoneal signs
   3. Parlytic ileus and colonic mucosal sloughing
   4. Intestinal perforation in ~75% with fulminant colitis
   5. Mortality as high as 40%
5. Liver Abscess [2]
   1. Usually acute symptoms
   2. Fever, right upper quadrant pain, substantial hepatic tenderness
   3. Leukocytosis without eosinophilia, mild anemia, elevated alkaline phosphatase
   4. Jaundice unusual
   5. Pelural effusion, rales in right lung base may occur
6. Uncommon Complications
   1. Pleuropulmonary amebiasis - cough, pleuritic chest pain, respiratory distress, empyema
   2. Amebic brain abscess - <1/1000 liver abscess cases
   3. Urinary tract problems

D. Diagnosis

1. Standard: demonstration of E. histolytica in stool or colonic mucosa
2. Alternative: ELISA assays that identify E. histolytica antigens in stool
3. Stool polymerase chain reactions (PCR) are beling developed
4. Sigmoidoscopy or occasionally colonoscopy may be used if highly suspicious
5. Serological testing is very useful for diagnosing liver abscess due to ameba

E. Treatment

1. Colitis or Uncomplicated Liver Abscess, Normal Host [4]
   1. Metronidazole (Flagyl®): 750mg po (or IV) tid x 5-10 days
   2. Tinidazole (Tindamax®) also effective and may be better tolerated: 2gm po qd x 3 days [5]
   3. Generally combine with iodoquinol 650mg tid x 20 days OR paromomycin 500mg tid x 7 days
   4. Severe or extraintestinal disease should be treated with 7-10 days metronidazole or 5 days tinidazole [5]
2. Liver Abscess
   1. Metronidazole effective, often after first dose (750mg po tid)
   2. Reduction in symptoms usually within 72-96 hours
   3. Surgical drainage is not required
3. Paromomycin
   1. Luminal aminoglycoside, nonabsorbed
   2. Dose 10mg/kg po tid (up to 500mg dose) for 5-10 days
   3. For treatment of luminal E. histolytica, given after metronidazole
4. Aspiration or surgical drainage only when diagnosis is in question

References

1. Stanley SL Jr. 2003. Lancet. 361(9362):1025
2. Haque R, Huston CD, Hughes M, et al. 2003. NEJM. 348(16):1565
3. Indik JH and Masters L. 1998. Arch Intern Med. 158(12):1374 (Case Report)
4. Thielman NM and Guerrant RL. 2004. NEJM. 350(1):38
5. Tinidazole. 2004. Med Let. 46(1190):70