This thesis focuses on the determinants of virulence in single and mixed-clone malaria infections, and the consequent impact of these infections for host- and parasite-fitness. Controlled experiments were conducted using a rodent model of malarial disease, <i>Plasmodium chabaudi. </i>Mice were infected with precise numbers of virulent and avirulent parasites. In the mixtures, known ratios of two clones that differed in virulence were used. Virulence was quantified in terms of host morbidity and mortality. Experiments investigating how virulence is determined in mixtures revealed that both the proportion of virulent clone in the innocula, and the genetic diversity of the infection determine virulence. Replacing virulent parasites with avirulent ones in a mixture was shown to confer protection for the host. These results challenge the various assumptions made in the models of the evolution of virulence about how virulence is determined in mixtures. They also suggest that selection against virulence can be reduced if virulent clones coinfect with avirulent ones, because host mortality is reduced in mixtures when the avirulent clone dominates. In single infections, the inoculating dose of virulent and avirulent parasites affected the virulence of the infection. Larger doses caused greater anaemia. They also caused additional weight loss, and death, but only for the virulent clone. Clone differences in virulence were maintained over the range of doses. Dose effects were manifested through the timing and/or magnitude of peak parasite densities, broadly supporting the idea that disease severity is due to the time the host has to control parasite densities and ameliorate the effects of parasites. To investigate the correlates of mortality, multivariate analyses were conducted. These generally showed that both the initial weight and red blood cell density of mice, and the rate at which they lost red blood cells and weight affected their probability of survival.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:662960 |
| Date | January 2001 |
| Creators | Timms, Rebecca |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/13132 |
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