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Micro Chapter 53 Entamoeba histolytica Causes amebiasis; may cause destruction of host tissue, especially in colon o Lesions start as small ulcerations of intestinal epithelium; amebas in lesions spread laterally as they encounter deeper layers of colon (flask-shaped ulcers) o May spread through portal circulation to produce abscesses in liver (less commonly lung or brain) Often cause few or no symptoms Morphologically indistinguishable from Entamoeba histolytica (avirulent strain); identified only by biochemical or nucleic acid-based techniques Transmitted through fecal-oral route 2 forms: actively growing vegetative trophozoite and dormant highly resistant cyst Patients w/diarrhea pose minor threat of transmission because they excrete actively growing yet labile trophozoites easily destroyed by drying in environment or acid in stomach if ingested o Asymptomatic patients excrete cyst form of parasite o Doesn’t require period of maturation in environment, so transmission not restricted to warm climate Can be anal-oral or oral-genital transmission (sexual transmission) Amebae adhere to colon via surface lectin on receptors on host cells containing digalactose residues o Attachment to cells inhibited by adding galactose, intestinal mucus Damage to host cell: receptor-mediated attachment to target cell via Gal-galNAc binding lectin, contactdependent killing (insertion of pore-forming proteins (ameba-pores) into host PM), ingestion of killed host cell by ameba o Pathogenic strains of amebas kill neutrophils and non-activated macrophages o Certain activated macrophages can kill amebas (host immunity) o Giving steroids (suppress cell-mediated immunity) causes disseminated infection despite high titers of antibodies o Amebae produce cysteine proteinase that digests IgA, IgG, and other proteins involved in humoral immune response Diagnosed by microscopic identification of trophozoites in freshly passed dysenteric stool or scrapings from colonic ulcers obtained through sigmoidoscope o Stool immunoassay for E. histolytica antigen may be more sensitive than microscopic exam and in some formats capable of distinguishing between E. histolytica and E. dispar o Isoenzyme analysis of cultured organisms or PCR required to make definitive diagnosis o Antiameba antibodies persist for years after infection, so serology can’t distinguish past from present Drug of choice for active amebic infection is metronidazole; penetrates well into most tissues, including brain o Amebas carry out anaerobic metabolism and convert metronidazole to active form o Less efficient at killing amebas in intestinal lumen, so diloxanide, paromomycin, or diiodohydroxyquin used for that w/metronidazole Giardia lamblia Patients w/diarrhea pose minor threat of transmission because they excrete actively growing yet labile trophozoites easily destroyed by drying in environment or acid in stomach if ingested Causes giardiasis; zoonosis that may be acquired by ingestion of water contaminated by feces from animal or human carriers; cysts resistant to chlorine, so outbreaks in municipal water systems happen o Can spread fecal-oral Acquired by ingestion of cyst form; highly resistant to environment; can be found in “pure” mountain streams o Stomach acid stimulates cysts to transform into vegetative trophozoite form in duodenum o Trophozoites attach to epithelium of duodenum and jejunum using ventral sucking disc o Vegetative forms have characteristic face w/mustache flagella Signs of malnutrition resulting from malabsorption may occur as result of extensive, prolonged infection Not invasive and doesn’t produce bloody diarrhea or metastatic infection o o Host responds w/submucosal infiltrate of lymphocytes and effacement of intestinal villi Malabsorption of fats can lead to greasy, foul-smelling stools; diarrhea associated w/unabsorbed fatty acids in lumen; deficiencies of fat-soluble vitamins; and weight loss Diagnosed by identification of parasites in stool or duodenal aspirates (cysts) o Cysts small, ovoid, non-motile bodies w/4 nuclei o Antigen detection assay for giardiasis available; more sensitive than single microscopic stool exam Treated w/metronidazole, but relapses can occur Tinidazole and nitazoxanide can be used to treat Can be prevented by boiling or filtering drinking water or treating it w/adequate amounts of iodine or chlorine Cryptosporidium Causes zoonosis obtained from cattle; can spread from person to person in close quarters (i.e., day care) Particularly troublesome in patients w/advanced AIDS who lack immune mechanisms necessary to resolve Oocysts found in most surface waters in country, are highly resistant to chlorine, and infectious particles expelled in huge numbers in watery stool Infectious oocysts forms produced in intestine and spread to other animals; don’t invade past intestinal mucosa or disseminate to produce systemic infection o Carry out entire life cycle among microvilli of small intestine, where they multiply at apical end of epithelial cells and are released back to luminal surface o In immunocompetent individuals, life cycle takes place once or twice, resulting in single episode of diarrhea that lasts 2 weeks or less o In immunocompromised patients, life cycle of organism repeated many times and associated w/persistent and intractable watery diarrhea Diagnosis made by identifying acid-fast cysts in stool; can use stool antigen detection assay Nitazoxanide has activity against cryptosporidia in immunocompetent hosts, but doesn’t help compromised o Supportive therapy w/rehydration and antimotility agents is mainstay of immunocompromised; successful treatment w/antiretroviral therapy and restoration of cell-mediated immunity can improve Cyclospora cayetanensis Protozoal parasite that produces acid-fast cysts in stools; larger than cryptosporidia Outbreaks have been linked to ingestion of raspberries imported from Central America Oocysts not infectious when excreted in human feces; parasite becomes infectious (sporulate) only after days to weeks of incubation in environmental sites w/warm temps and high humidity, so most infections acquired by ingestion of contaminated food or water Intracellular infection of apical intestinal epithelial cells; don’t invade beyond intestinal mucosa Infection causes watery diarrhea associated w/loss of appetite, bloating, cramps, nausea, vomiting, fatigue, muscle aches, and low-grade fever Relapses common Diagnosis depends on identification of large acid-fast oocysts in stool Treatment w/trimethoprim/sulfamethoxazole relieves symptoms and shortens course of infection Other Intestinal Parasites Isospora belli – protozoan that causes transient watery diarrhea in healthy individuals; occurs more frequently in tropical areas; in U.S., occurs mostly in AIDS patients (get persistent watery diarrhea) o Diagnosis made by examination of stool for characteristic oocysts o Trimethoprim/sulfamethoxazole effective in controlling infection in immunocompromised patients Microsporidia – obligate intracellular parasites very small, lack mitochondria, and possess small rRNA (prokaryotic origin) o Various species associated w/infections of GI tract, respiratory tract, urinary tract, liver, brain, & eye o Symptomatic intestinal infection associated w/Enterocytozoon bieneusi Causes transient diarrhea in healthy hosts but protracted watery diarrhea in AIDS patients Organism infects mucosal epithelial cells; can disseminate to distant sites in AIDS patients (biliary tree and cause cholangitis) Diagnosis made by microscopic examination of stool or intestinal biopsy material (stained) Common antibacterial and antiprotozoal drugs not very effective Albendazole (antihelminthic drug) isolated from fungus Aspergillus fumigatus (fumagillin) used with some success Trichomonas vaginalis Common inhabitant of vagina in 15% or more of women that occasionally causes vaginitis Trichomonas hominis less commonly found in GI tract; T. tenax found in mouth Infection transmitted by sexual intercourse Vaginitis associated w/frothy creamy discharge; most male partners of symptomatic women become infected but majority of infections in men asymptomatic o Male symptoms can include mild urethritis, epididymitis, or prostatitis Flagellates found in wet preps of vaginal secretions from infected women; infection of male partners safely assumed; single dose metronidazole or tinidazole treatment recommended In pregnant women, trichomoniasis associated w/adverse pregnancy outcomes; single-dose metronidazole safe and effective