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Title: Pathogenic mechanisms in amoebiasis
Author: Knight, R.
Awarding Body: London School of Hygiene & Tropical Medicine
Current Institution: London School of Hygiene and Tropical Medicine (University of London)
Date of Award: 1977
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The delicate balance between host and parasite in the pathogenesis of amebobiasis has been studied in vitro and in vivo. The cytopathic effect of Entamoeba Histolytica upon a tissue cell monolayer is described using light and electron microscopy, and the system has been quantitated by labelling the monolayer with 51Chromium. The findings emphasize the importance of contact between amoeba and cell, and suggest mechanisms by which damage may occur. The quantitative model allows the dynamics of the interaction to be studied in detail. The method has been applied to several of the physiological variables that affect an amoebic inoculum, and also to the comparison of amoebic strains. The general uniformity of a series of personally isolated strains is shown by antigenic analysis and sensitivity to drugs and low temperature. Two new methods of measuring the median lethal dose of amoebicidal drugs have been devised. Some of the possible roles of cell mediated immunity in amoebiasis have been investigated using mouse spleen cell cultures. A synergistic relationship was found between E. Histolytica in mice and concurrent infection with Schistosoma mansoni or Trichuris muris. The relevance of local tissue damage and immunosupression is discussed. The importance of dietary factors has been studied in rats; protein deficiency increases susceptibility but carbohydrate supplementation appears to have a protective effect. Two methods were used to produce anoxic liver damage in the hamster; [...] A study of strain competition in vitro led to the development of a mathematical model of amoebic infection, which allows valuable interpretations to be made from epidemiological data. Many of the problems of amoebic pathogenesis in man can only be studied in this way. It is concluded that while amoebic strains do show some intrinsic differences, the outcome of infection in man is determined mainly by host factors.
Supervisor: Woodruff, A. W. Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral