USMLE – Amebiasis
The protozoan Entamoeba histolytica infects approximately 500 million persons in developing countries, such as India, Mexico, and Colombia, resulting in approximately 40 million cases of dysentery and liver abscess. E. histolytica cysts, which have a chitin wall and four nuclei, are the infectious form because they are resistant to gastric acid. In the colonic lumen, cysts release trophozoites, the ameboid form, that reproduce under anaerobic conditions without harming the host. Because the parasites lack mitochondria or Krebs cycle enzymes, amebae are obligate fermenters of glucose to ethanol. Metronidazole, the best drug to treat invasive infections with entamoebae (as well as other parasites such as Giardia and trichomonads), targets ferredoxin-dependent pyruvate oxidoreductase, an enzyme critical in such fermentation that is present in these organisms but is absent in humans. Remarkably, the genes encoding the fermentation enzymes of amebae appear to derive from an anaerobic bacterial en dosymbiont, which is different from the bacterium from which mammalian mitochondria derive.
Amebae cause dysentery – bloody diarrhea, intestinal pain, fever-when they attach to the colonic epithelium, lyse colonic epithelial cells, and invade the bowel wall. Ameba proteins that may be involved in tissue invasion include (1) cysteine proteinases, which are able to break down proteins of the extracellular matrix; (2) a lectin on the parasite surface that binds to carbohydrates on the surface of colonic epithelial cells and red blood cells; and (3) a channel-forming protein called the amebapore, which makes holes in the plasma membrane of host cells and lyses them. The amebapore is a small peptide that has the same structure as the NK-lysin of killer lymphocytes.
A major unresolved question in the pathogenesis of amebiasis is why only 10% of persons infected develop dysentery. One explanation is the existence of two genetically distinct forms of amebae: E. histolytica that causes disease and Entamoeba dispar that does not. The cysts of virulent and nonvirulent amebae have a similar structure in stool, but the presence of trophozoites containing ingested red blood cells is indicative of tissue invasion by virulent E. histolytica parasites.
Amebiasis most frequently involves the cecum and ascending colon, followed in order by the sigmoid, rectum, and appendix. In severe full-blown cases, however, the entire colon is involved. Amebae can mimic the appearance of macrophages because of their comparable size and large number of vacuoles; the parasites, however, have a smaller nucleus, which contains a large karyosome. Amebae invade the crypts of the colonic glands, burrow through the tunica propria, and are halted by the muscularis mucosae. There the amebae fan out laterally to create a flask-shaped ulcer with a narrow neck and broad base. As the lesion progresses, the overlying surface mucosa is deprived of its blood supply and sloughs. The earliest amebic lesions show neutrophilic infiltrates in the mucosa, which later develop into ulcers that contain few host inflammatory cells and areas of extensive liquefactive necrosis. The mucosa between ulcers is often normal or mildly inflamed. An uncommon lesion is the ameboma, a napkin-like constrictive lesion, which represents a focus of profuse granulation tissue response to the parasites and is sometimes mistaken for a colonic tumor.
In about 40% of patients with amebic dysentery, parasites penetrate portal vessels and embolize to the liver to produce solitary, or less often multiple, discrete abscesses, some exceeding 10 cm in diameter. Amebic liver abscesses have a scant inflammatory reaction at their margins and a shaggy fibrin lining, Because of hemorrhage into the cavities, the abscesses are sometimes filled with a chocolate-colored, odorless, pasty material likened to anchovy paste. Secondary bacterial infection may make these abscesses purulent. As the amebic abscesses enlarge, they produce pain by pressing on the liver capsule and can be visualized with ultrasound examination. Amebic liver abscesses are treated with drainage and drugs or with drugs alone. Rarely, amebic abscesses reach the lung and the heart by direct extension or spread through the blood into the kidneys and brain.