Amebiasis is infection with the parasitic intestinal protozoan Entamoeba histolytica (the “tissue-lysing ameba”). Most infections are probably asymptomatic, but E. histolytica can cause disease ranging from dysentery to extraintestinal infections, including liver abscesses.
Life Cycle and Transmission
E. histolytica exists in two stages: a hardy multinucleate cyst form (Fig. 209-1) and the motile trophozoite stage (Fig. 209-2). Infection (of which humans are the natural hosts) is acquired by ingestion of cysts contained in fecally contaminated food or water or, more rarely, through oral-anal sexual contact. Cysts survive stomach acidity and excyst within the small intestine to form the 20- to 50-μm trophozoite stage. Trophozoites can live within the large-bowel lumen without causing disease or can invade the intestinal mucosa, causing amebic colitis. In some cases, E. histolytica trophozoites invade through the mucosa and into the bloodstream, traveling through the portal circulation to reach the liver and causing amebic liver abscesses. Motile trophozoites may be excreted into the stool—a diagnostically important event—but are rapidly killed upon exposure to air or stomach acid and therefore are not infectious. Trophozoite cysts within the large bowel are excreted in the stool, continuing the life cycle.
Entamoeba cyst. Three of the four nuclei are clearly visible. (Courtesy of Dr. George Healy, Centers for Disease Control and Prevention.)
E. histolytica trophozoite with ingested red blood cells. Note the single nucleus with central nucleolus. (Courtesy of the Centers for Disease Control and Prevention.)
Molecular diagnostics continue to clarify what was once a confusing picture of the true incidence and prevalence of E. histolytica infection and disease. It was a staple of most textbooks that 10% of the world's population was infected with E. histolytica. We now know that most asymptomatic individuals harboring amebic trophozoites or cysts in their stools are infected with a noninvasive species: Entamoeba dispar or Entamoeba moshkovskii. E. dispar appears not to cause disease, even in the most profoundly immunosuppressed individuals; furthermore, at this time, there is little evidence to suggest that E. moshkovskii causes disease, although epidemiologic studies of this species are in their infancy. In contrast, E. histolytica infection can cause disease, although not all patients develop symptoms. It remains unclear how frequently people infected with E. histolytica do develop symptoms; in one study in a highly endemic area, only 10% of infected patients developed symptoms over a 1-year observation period. A remarkable feature of amebiasis is its more common occurrence in men than in women, although the prevalence of infection with E. histolytica does not appear to differ between the sexes. This pattern is particularly pronounced for amebic liver abscess, whose prevalence is ∼7 times higher among men than among women. The explanation for this difference remains unknown, but less efficient complement-mediated killing of amebic trophozoites by serum from men than by serum from women has been reported.
E. histolytica infections are most common in areas of the world where poor sanitation and crowding compromise the barriers to contamination of food and drinking water with human feces. Endemic areas include parts of Mexico, India, and nations in the tropical regions of Africa, South and Central America, and Asia. E. histolytica was present in ∼2.1% of individuals presenting with diarrhea in a large series from Bangladesh and in 1.4% of the asymptomatic control group. In 2007, amebiasis was listed as the sixth most common cause of disease in Mexico, with an incidence of ∼544 cases per 100,000 population. In the United States and other developed countries, disease is unusual and is found almost exclusively in travelers or immigrants from endemic areas. Rarely, outbreaks take place in institutionalized populations, and infections have been documented with increased frequency among men who have sex with men; however, most of the latter cases have been asymptomatic and probably represent E. dispar infections.
Pathogenesis and Pathology
E. histolytica trophozoites possess a potent repertoire of adhesins, proteinases, pore-forming proteins, and other effector molecules that enable them to lyse cells and tissue, induce both cellular necrosis and apoptosis, and resist both innate and adaptive immune defenses. Disease begins when E. histolytica trophozoites adhere to colonic mucosal epithelial cells. Disruption of the colonic mucin barrier is seen in pathologic sections from the diseased colon, but it is not clear whether this disruption is caused by the parasite, facilitating its adherence to mucosal cells, or occurs as a consequence of the adhesion event, with subsequent mucosal damage. Adherence is mediated primarily by a family of surface lectin molecules capable of binding to galactose and N-acetylgalactosamine residues. E. histolytica can lyse host cells upon contact through a family of amphipathic peptides called amoebapores that form barrel-stave pores in target cell membranes. Both cellular necrosis and apoptosis can occur after E. histolytica comes into contact with host cells, and which outcome predominates may relate to inherent characteristics of the target cell or the tissue environment. One consistent and unequivocal finding is the important role played by amebic cysteine proteinases in the disease process. E. histolytica possesses a large family of cysteine proteinases that are capable of lysing the extracellular matrix between host cells (thus detaching cells and facilitating invasion) and cleaving host defense molecules (including complement components and antibodies). Studies in animal models, including chimeric mice with human intestinal xenografts, have shown that inhibition of E. histolytica cysteine proteinase activity, via either direct gene targeting or chemical inhibitors, significantly reduces disease. The ultimate effect of all these amebic virulence factors on the human colon is the production of small ulcers that have heaped borders and contain focal areas of epithelial cell loss, a modest inflammatory response, and mucosal hemorrhage. ...