I investigated RBC selectivity as a potential virulence factor further in a rodent malaria model using <i>Plasmodium chabaudi</i>. The experimental design allowed me to look at the selectivity index in congenic lines, which significantly differed in their virulence to the host. Supporting my <i>P. falciparum</i> data, no association between the selectivity index and virulence was seen. This is the first description of the selectivity index in <i>P. chabaudi</i> and RBC invasion was found to be very unselective as expected for a malaria parasite which does not exhibit a reticulocytes preference. The Kenyan field isolates were also typed for their RBC invasion pathway profile by measuring their invasion into enzyme-treated RBC. Although invasion profiles of field isolates have been reported previously, as far as I am aware, this is the first report looking at invasion profiles of field isolates in relation to disease severity. In line with previous results, field isolates invade RBC by multiple invasion pathways. No difference between the invasion profiles of isolates from uncomplicated or severe malaria patients was seen. Overall my thesis presents a detailed study of potential <i>P. falciparum</i> virulence factors related to invasion, working both with clinical isolates and laboratory strains. Severe malaria in Africa was not found to be associated with parasite multiplication rates, RBC selectivity or specific invasion pathways. Other virulence factors such as resetting and platelet-mediated clumping may be of major importance in this region. This work suggests the possibility of differences in malaria virulence factors between sub-Saharan Africa and Asia, which may need to be taken into consideration for drug and vaccine design.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:649451 |
| Date | January 2005 |
| Creators | Deans, Anne-Marie |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/14761 |
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