This thesis experimentally tests the within-host competitive interactions between malaria strains of <i>Plasmodium chabaudi</i> in laboratory mice, a system widely used as a model for human malaria. A real-time quantitative PCR assay was developed to track different parasite clones in mixed-clone infections over time. Several experiments were then carried out using this molecular tool. In all these experiments, it was shown that intense competition occurs between <i>Plasmodium</i> clones occupying the same host: this competition as most likely the result of a limited amount of resources, such as red blood cells, and cross-reactive immune responses. There was a direct relationship between virulence and in-host competitiveness, thus supporting a fundamental theoretical assumption. Host genotype also was an important determinant: competition was shown to be more intense in a resistant than a susceptible mouse strain. Timing of infection was very important too: the later a parasite clone arrived after another had established, the more it suffered from competition. How in-host competitiveness related to between-host transmission, was assessed by feeding infected mice to <i>Anopheles stephensi</i> mosquitoes. This showed a straight relationship between in-host competitiveness and mosquito transmission, thus suggesting that competitive suppression in the mouse host translated into reduced transmission in the mosquito vector. Finally, it was shown that drug treatment could disrupt competitive interactions between drug-resistant and –sensitive clones: the result could be competitive release of drug resistant strains followed by an enhanced spread of drug resistance. The results from this thesis confirm many assumptions underlying models on the evolution of virulence and drug resistance. They thereby suggest that reducing the number of mixed malaria infections could have beneficial effects by reducing the evolutionary selection for increased virulence.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:649254 |
| Date | January 2004 |
| Creators | De Roode, Jacobus Cornelis |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/13602 |
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