Virulence evolution of pathogens

Over the last 10 years, in collaboration with Prof. Andrew Read and colleagues (www.thereadgroup.net),  a comprehensive body of empirical and theoretical data has been built up to show that human disease interventions such as vaccines can cause pathogens to evolve higher virulence. Using malaria as an example disease, and a combination of both empirical and theoretical studies, constructed this edifice by (1) performing extensive experimental testing of the key assumptions of virulence evolution theory in a rodent malaria laboratory model, namely that more virulent parasites have higher transmission (fitness) than less virulent parasites in the absence of host death, but pay a high fitness cost if they do kill their host, (2) analysing human malaria data from the field for evidence in support of these assumptions, (3) demonstrating that these assumptions hold when hosts are vaccinated or made more resistant by other means, (4) building theoretical evolutionary-epidemiological models to predict that imperfect vaccines may lead to the evolution of more virulent parasites and higher levels of disease in the general population, (5) testing (partially!) this prediction using experimental evolution in laboratory mice, and (6) dissecting out some of the virulence mechanisms and selective forces involved in this experimental evolution.

The research group is now translating this work to human malaria. If the hypothesis is correct that immunity promotes virulence evolution, and that death acts as a brake on virulence, then this should be observable in natural populations that differ in levels of immunity. Thus we are studying natural parasite populations from high, medium and low transmission areas around east Africa using whole genome microarrays to study gene expression levels all the parasite's genes at once. This is being done in collaboration with Dr. Zbynek Bozdech in Singapore. We have sorted out the technical hurdles involved in applying field parasites to microarrays, and are about to carry out the field experiments with a Project Grant funded by the Wellcome Trust.

Collaborators: Prof. A. Read, Dr. S. Gandon, Dr. S. Nee, Dr. H. Ferguson, Dr. A. Rowe, Dr. Z. Bozdech, Prof. K. Marsh.