Within-host infection dynamics

Modeling the interactions between parasites and hosts is a big focus of research in disease ecology and evolution. Yet, a quantitative understanding of what controls infection dynamics within host remains far from reach, even for highly controlled laboratory disease systems. This lack of quantitative models is partially due to a failure to take advantage of opportunities for reciprocal feedback between data and theory. Using a combination of theoretical and experimental approaches, we have revealed processes that underlie within-host dynamics of experimental rodent malaria infections, and how differences in these processes give rise to the variation observed in patterns of disease across parasite genotypes.

For instance, we have demonstrated parasite genetic variation in traits directly involved in host exploitation. But we have also shown that these traits depend on the host environment in which parasites find themselves, i.e., genetically-identical parasites demonstrate true plasticity across infections. Given that the within-host environment varies over the course of a single infection, parasites would seem to have the capacity to respond to these changes. While within-host models often allow for variation across parasite genotypes, and even include complex and variable host responses within infections, the parasites themselves are usually treated as static creatures whose traits do not vary. This view, while mathematically convenient, is biologically naïve.

We are developing models that include parasite plasticity to determine whether this really does play an important role in driving observed patterns of infection dynamics.

One benefit of having a good model of disease dynamics is that it can be used predictively. We have used our model of the rodent malaria system to predict how different drug treatment regimes could affect the risk of spreading resistant parasites. A massive amount of experimental work later, and it appears that the model did a pretty good job.

Relevant papers:

Metcalf, C.J.E., Long, G.H., Mideo N., Forester J.S., Bjørnstad O.N., Graham A.L. (2012) Revealing mechanisms underlying variation in malaria virulence: effective propagation and host control of uninfected red blood cell supply. Journal of the Royal Society Interface, 9: 2804-2813.PDF

Mideo N., Savill N.J., Chadwick W., Schneider P., Read A.F., Day T., & Reece S.E. (2011) Causes of variation in malaria infection dynamics: insights from theory and data. American Naturalist, 178: 174-188. PDFAPPENDICES

Mideo N., Read A.F., & Day T. (2008) Modelling malaria pathogenesis. Cellular Microbiology 10: 1947-1955.PDF

Mideo N., Barclay V.C., Chan B.H.K., Savill N.J., Read A.F., & Day T. (2008) Understanding and predicting strain-specific patterns of pathogenesis in the rodent malaria, Plasmodium chabaudi. American Naturalist 172: E214-238.PDF