Student Theses and Dissertations

Date of Award

1981

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Cohn Laboratory

Abstract

The study of the parasitic protozoa presents a multifaceted opportunity for biological research. These organisms are eucaryotic cells with many of the biological systems described in higher eucaryotic cells. However, they are adapted to highly specialized environments, invoking sometimes subtle and often unique variations of these biological systems. More important, an understanding of the biology of the parasite and the differences between the parasite and mammalian cells can be invaluable in the development of pharmacological and immunological methods of control of the parasite. The subject of this thesis, the parasitic amoeba Entamoeba hystolytica, is an ideal subject for such research. While the pathogenic form may be grown in vitro, it is in nature an obligate parasite. It has specifically adapted to growth in the human intestine and has retained or evolved several unique biochemical pathways. Furthermore, E. histolytica displays several interesting phenomena, including immune avoidance and contact dependent cytotoxicity, which have yet to be explained. Finally, amoebic dysentery, the disease caused by infection with E.histolytica, remains a problem both in the tropics and across the globe. Though sometimes labeled a "tropical disease," amoebic dysentery is more properly a disease of poor sanitation and hygiene. While the highest rates of infection are often associated with the tropics, as high as 50 to 83% in parts of Egypt and Mexico (1), it ranges as far north as man is found. Significant endemic rates are found among the indigenous peoples of Canada and Alaska, and surveys of persons passing cysts in Leningrad range from 14 to 25% (2). Estimates for the United States range from 1.5 to 33% (2), depending upon regions and populations surveyed. It should be noted that the true infection rate is probably higher than these estimates as a single stool examination can miss as many as two-thirds of E. histolytica infections (1). Treatment of the disease is readily accomplished, with metronidazole as the preferred drug. Reinfection is, however, common in areas of high endemic infections. Left untreated, the disease can result in severe wasting, metastatic infections, and death. The known life cycle of E. histolytica is deceptively simple. It consists of only two main stages, trophozoite and cyst, and transition forms (fig 1) (3). The amoeboid trophozoite is the form of the parasite responsible for the pathogenesis of the disease. It is an anaerobic organism, capable of survival only within the host. It is readily destroyed by heat and osmotic shock. It is also destroyed by gastric juices and is thus not infective by oral route. The infective stage of the parasite is a dormant cyst formed by the encystation of a single trophozoite. The mature cyst contains four nuclei, the result of two consecutive mitotic divisions, and is surrounded by a polysaccharide wall. It can survive in moist environments for a month or more. It is sensitive to heat but is not killed by most chlorine based water treatment systems (4). Upon ingestion, the cyst passes through the stomach into the intestine where the combination of digestive enzymes and anaerobic conditions cause excystation. Each cyst produces four trophozoites which can then proceed to populate the large intestine of the new host.

Comments

A thesis submitted to the Faculty of the Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy

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