Amebiasis Paul R. Earl Facultad de Ciencias Biológicas Universidad Autónoma de Nuevo León San Nicolas, NL, Mexico pearl

1. AmebiasisPaul R. EarlFacultad de Ciencias BiológicasUniversidad Autónoma de Nuevo LeónSan Nicolas, NL, Mexico pearl@dsi.uanl.mx

2. Amebiasis or amebic dysentary is caused by the protozoan Entamoeba histolytica. Improved sanitation and clean water supply decrease the incidence of amebiasis. The amount of chlorine normally used to control pathogens is inadequate in killing the cysts. Drinking water can be rendered safe by boiling or iodination with tetraglycine hydroperiodide. Nevertheless, drinking water is usually not much of the problem.

3. Generalities. Amebiasis is an intestinal infection in which cysts are passed in the feces. Symptoms can include fever, chills and diarrhea, sometimes bloody or with mucus and often with cramps. Some people may have only mild abdominal discomfort or no symptoms at all. Symptoms can start 2 or more weeks after infection. Rarely, trophozoites (the mobile amebas) may invade the liver, lung or brain, or perforate the colon causing septicemia.

4. E. dispar is a nonpathogenic protozoon morphologically identical to E histolytica. Previously reported asymptomatic infections due to the so-called nonpathogenic strains of E histolytica now are recognized to be due to E. dispar. These 2 species of Entameba can be distinguished by monoclonal antibodies. Other morphologically distinct organisms, such as Entamoeba coli ( E. coli ! ! ) and Entamoeba hartmanni are also nonpathogenic.

5. Amebiasis is the third leading parasitic cause of death worldwide, surpassed only by malaria and schistosomiasis. On a global basis, amebiasis affects approximately 50 million persons each year, resulting in nearly 100,000 deaths.

6. Laboratory diagnosis. An iodine-stained cyst of the pathogen Entamoeba hystolytica with 4 nuclei is illustrated. The harmless commensal Entamoeba coli has larger cyts with 8 nuclei. Furthermore, recall that E. histolytica has a lookalike E. dispars that is harmless.

9. The cyst of E histolytica averages 12 m, ranging from 5-20 m. It has 1-4 nuclei that are morphologically similar to the nuclei of the trophozoite. The cyst may have iodine-stainable glycogen clumps and chromatoid bodies with smooth rounded edges. The ending –oid means LIKE so chromatoid bodies are like chromatin in that they stain with hematoxylin.

10. TrophozoitesEntamoeba coli Entamoeba histolytica15 mm - 40 mm in size 10 mm - 35 mm sizeNondirectional motility Unidirectional motilityMultiple pseudopodia Single pseudopodiaNo ingested erythrocytes Ingested erythrocytesCytoplasm rough looking Finely granular cytoplasmLarge, eccentric karyosome Small, central karyosomeClumped nuclear chromatin Finely beaded chromatin

11. CystsEntamoeba coli Entamoeba histolytica10 mm - 35 mm in size 10 mm - 20 mm in sizeMay have 8 nuclei Never more than 4 nucleiKaryosomes eccentric Karyosomes small, centralNuclear chromatin clumped Chromatin finely beadedSplintered chromatoidal bars Rounded chromatoidal bars

12. Leukocytosis and mild anemia can occur. Erythrocyte sedimentation rate generally is elevated. Liver function tests reveal elevated alkaline phosphatase in 80% of patients, elevated transaminases and reduced albumin. Urinalysis may reveal proteinuria.Rectosigmoidoscopy and colonoscopy may show small mucosal ulcers covered with yellowish exudates. The intervening mucosa appears normal. Biopsy results and scrapings of ulcer edge may locate trophozoites.

13. Symptoms and pathology. Primary intestinal flask-shaped (button hole) necrotic ulcers occur in the submucosa of the large intestine, most commonly the cecal and sigmoidorectal regions.Ulcers contain necrotic debris, actively feeding trophozoites with ingested erythrocytes, cytolyzed cells and mucous; polymorphonuclear leukocytes and round inflammatory cells.

14. Extraintestinal features. Hematogenous spread may result in abscesses of the liver, spleen, lung or brain. Hepatic amebiasis (abscess, hepatitis) is the most common and grave complication: Enlarged, tender liver and upper abdominal pain that may radiate to the right shoulder. Mild jaundice may be evident, transaminases and alkaline phosphatase elevations may be seen.

15. Drugs for treatment. Five pharmaceuticals are briefly noted. Asymptomatic intestinal infection may be treated with iodoquinol, paromomycin or diloxanide furoate. Recommended drugs for treatment of symptomatic intestinal disease and for hepatic abscess are metronidazole and tinidazole. Since these drugs may not eliminate the cysts of the intestine, immediately follow metronidazole and tinidazole with iodoquinol, paromomycin or diloxanide furoate.

16. 1/ Metronidazole (Flagyl, Protostat). Kills trophozoites of E. histolytica in intestine and tissue. Does not eradicate cysts from intestines. Adult oral dose: 500-750 mg 3 times per day for 10 day. Elimination is accelerated by simultaneous use of phenytoin and phenobarbital; clearance is decreased by cimetidine.

17. 2/Tinidazole (Fasigyn). 5-nitroimidazole derivative with selective antimicrobial activity against anaerobic bacteria and protozoa. Not available in United States. Adult oral dose: 600 mg bid or 800 mg 2 times a day for 5 days. Pediatric dose 50-60 mg/kg for 5 days, not to exceed 2 g/day.

18. 3/Paromomycin (Humatin). Amebicidal aminoglycoside antibiotic that is poorly absorbed. Active only against intestinal form of amebiasis. Used to eradicate cysts of E. histolytica following treatment with metronidazole or tinidazole for an invasive disease. Adult oral dose: 25-35 mg/kg/day divided 3 times for 7 days. Pediatric dose: Administer as in adults.

19. 4/Diloxanide furoate (Furamid, Entamizole, Furamide). Luminal amebicide; acts primarily in bowel lumen since it is poorly absorbed. Used to eradicate cysts of E. histolytica after treatment of invasive disease. Available through US CDC Drug Service (404-639-3670). Adult oral dose 500 mg 2 times a day for 10 days. Pediatric dose 20 mg/kg/ divided twice a day for 10 days, not to exceed 1500 mg/day.

20. 5/Iodoquinol (Yodoxin). Halogenated hydroxyquinoline. Luminal amebicide; acts primarily in bowel lumen since it is poorly absorbed. Best tolerated when given with meals. Since active only against intraluminal form of amebiasis, used to eradicate cysts of E. histolytica after treatment of invasive disease. Adult oral dose 650 mg 2 times a day for 20 days. Pediatric dose: 30-40 mg/kg/day divided 2 times for 20 days; not to exceed 2 g/day.

21. The control of infection. The epidemiology of amebiasis is folkloric, beginning with infected foodhandlers. While elements of truth are scattered through this neglected syndrome, much more can be done. Frankly, the ecology is unknown. Are there reservoir animals?

22. What civic water treatments kill and which ones tolerate E. histolytica? What part does chronic malnutrition play in susceptibility to infection? What part does exposure then the rise of natural antibodies play in defense? What are the water-borne pathogens intimately associated with E. histolytica? Has radioactivity been used to trace ecological dispersion of an element like phosphorus in a parasite? If ever, how is E. histolytica considered in civic water management?

23. The main point of this lecture is to sketch E. histolytica as a distinct pathogen differing from E. coli and E. dispar. More, decades pass without fruitful reseach results. Perhaps you find this a challenge.