Amoebiasis - Causes and Pathogenesis

Causes of amebiasis

The causes of amebiasis are Entamoeba histolytica, which belongs to the kingdom Protozoa, subtype Sarcodina, class Rhizopoda, order Amoebia, family Entamoebidae.

The life cycle of E. histolytica includes two stages - vegetative (trophozoite) and resting stage (cyst). The small vegetative form (luminal form, or forma minuta) has dimensions from 7 to 25 μm. The division of the cytoplasm into ecto- and endoplasm is poorly expressed. This non-pathogenic, commensal form lives in the lumen of the human colon, feeds on bacteria by endocytosis, is mobile, and reproduces vegetatively. The tissue form (20-25 μm) is found in the affected tissues and organs of the host. It has an oval nucleus, well-defined glassy ectoplasm and granular endoplasm, is very mobile, and forms wide blunt pseudopodia. The large vegetative form (forma magna) is formed from the tissue form. The body is grey, round, large (up to 60 µm or more when moving), the ectoplasm is light, the endoplasm is granular, cloudy and dark; the digestive vacuoles contain phagocytized erythrocytes. This is why it is also called "erythrophage". As they move through the large intestine, the amoebas transform into pre-cystic stages, and then into cysts. The cysts are round or oval (10-15 µm) with a smooth double-contour membrane. Immature cysts contain one or two nuclei, mature cysts contain four nuclei with karyosomes.

Cysts are resistant to environmental factors: at a temperature of 20 °C they remain viable in the soil for several days, in winter conditions (-20 °C) - up to 3 months. Due to resistance to disinfectants (chlorine, ozone) in concentrations used in water treatment plants, viable cysts can end up in drinking water. High temperatures are fatal for them; when dried and heated, cysts quickly die. Vegetative forms are unstable in the external environment and have no epidemiological significance.

When a person is infected, amoeba cysts enter the mouth with water or food products, and then the intestine. In the distal parts of the small intestine, the cyst membrane dissolves under the action of intestinal enzymes. Four metacystic mononuclear amoebas emerge from the mature cyst, which, in turn, divide in two every 2 hours. As a result of subsequent divisions, they turn into vegetative luminal stages (see above). It is known that there are two types of amoebas in the population: potentially pathogenic strains of E. histolytica and non-pathogenic for humans E. dispar, which are morphologically identical and can only be distinguished by DNA analysis.

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Pathogenesis of amoebiasis

The reason why E. histolytica switches from the luminal state to tissue parasitism is not fully understood. It is believed that the main virulence factor in E. histolytica is cysteine proteinases, which are absent in E. dispar. The following factors are important in the development of invasive forms of amoebiasis: invasion intensity, changes in the physicochemical environment of the intestinal contents, immunodeficiency, starvation, stress, etc. Relatively frequent development of invasive forms is noted in women during pregnancy and lactation, and in HIV-infected individuals. Probably, amoebas switch to tissue parasitism with the acquisition of properties characteristic of other pathogenic microorganisms, such as adhesiveness, invasiveness, the ability to affect the host's defense mechanisms, etc. It has been established that trophozoites attach to epithelial cells due to a specific lectin - galactose-N-acetylgalactosamine.

E. histolytica has been found to contain hemolysins, proteases, and in some strains, hyaluronidase, which can play a significant role in the destruction of the epithelial barrier by amoebae. The parasite's trophozoites are capable of causing contact lysis of neutrophilic leukocytes with the release of monooxidants that enhance the process of tissue melting. Amoebae have an inhibitory effect on monocytes and macrophages, which promotes their survival. They are capable of specifically blocking the production of IL (IL-1beta, IL-8) by intestinal cells, breaking down complement (C3 ₎, IgA, IgG, thus influencing the inflammatory processes at the site of parasite penetration. Under the influence of cytolysins and proteolytic enzymes of amoebae, the mucous membrane and adjacent layers of the intestinal wall are damaged. The primary manifestation of amebiasis is the formation of small areas of necrosis in the mucous membrane of the colon, which progress to ulceration. Synchronicity in the development of ulcers is not observed. Ulcers increase not only along the periphery (due to the submucosal layer), but also in depth, reaching the muscular and even serous membrane lining the walls of the colon. A deep necrotic process leads to the occurrence of adhesions of the peritoneum and can cause perforated peritonitis. Amebic ulcers are most often localized in the area of the cecum. Next in order of decreasing frequency of damage are the rectum and sigmoid colon, appendix and terminal ileum. In general, due to the fact that the intestinal lesion is segmental and usually spreads slowly, the intoxication syndrome is weakly expressed. Typical amebic ulcers are sharply demarcated from the surrounding tissues and have uneven edges. At the bottom of the ulcer there are necrotic masses consisting of fibrin and containing trophozoites of amoebas. The inflammatory reaction is weakly expressed. The necrotic process in the center, undermined and raised edges of the ulcer, reactive hyperemia and hemorrhagic changes around it are the most typical features of ulcerations in intestinal amebiasis. Due to the regenerative process leading to the restoration of the defect by proliferation of fibrous tissue, strictures and stenosis of the intestine may occur. In chronic amebiasis, an ameboma is sometimes formed in the intestinal wall - a tumor-like growth located mainly in the ascending, blind or rectum. An ameboma consists of fibroblasts, collagen and cellular elements and contains a relatively small number of amoebas.

As a result of penetration of amoebas into the blood vessels of the intestinal wall, they are carried by the bloodstream to other organs, where lesions in the form of abscesses occur. Most often, abscesses form in the liver, less often in the lungs, brain, kidneys, and pancreas. Their contents are gelatinous, yellowish in color; in large abscesses, the pus is red-brown. Single abscesses are often located in the right lobe of the liver, closer to the diaphragm or the lower surface of the organ. In large abscesses, the outer zone consists of relatively healthy tissue containing amoeba trophozoites and fibrin. In chronic abscesses, there is usually a thick capsule, the contents are yellowish in color, with a putrid odor. As a result of a liver abscess breaking through under the diaphragm after its melting, purulent pleurisy develops. In the lungs, abscesses are in most cases localized in the lower or middle lobe of the right lung.