Research
Study Systems
Current
Malaria
We work on malaria both because it is a hugely important disease of humans, and because malaria parasites are perhaps the group of eukaryotic microparasites about which are most known. Most importantly, cryopreserved isolates are available, and a large number of molecular genetic and immunological typing methods (and reagents) are available which we can use to in our experiments.
We are interested in the ecology and
evolution of virulence, transmission and in-host dynamics. Experimental analysis of these phenotypes requires an in
vivo system. For the most part, we work with the rodent malaria Plasmodium chabaudi, which is an ideal experimental
virulence model for any microparasite whose biology accords with classic models of virulence evolution (pathogen-encoded
virulence determinants, virulence-transmission trade-offs).
P. chabaudi is certainly the best of the malaria models for investigating the questions we are interested in. It shares a number of relevant features with the most virulent human malaria, Plasmodium falciparum: (i) Blood forms of P. chabaudi do not have a marked preference for different cell types. (ii) Schizogony is highly synchronous. (iii) Sequestration of mature trophozoites/schizonts occurs. (iv) There is antigenic variation, and blood infections persist for several weeks. (v) Gametocyte production occurs mainly after the peak parasitaemia. (vi) In mosquitoes, low oocyst numbers are produced, but sporozoites have good infectivity to mice. Finally, and perhaps most importantly, recent analyses of malaria therapy data in humans have shown that, like P. chabaudi, a major determinant of severe disease and death is the inability to control the consequences of first peak of asexual parasites.
Thicket rats are the natural hosts of P. chabaudi, but as with Drosophila in jars, selection on life
history traits can fruitfully be examined in a novel environment. It is difficult to assess the extent to which the non-natural
host might limit the ability to extrapolate the results to other malaria. However, one advantage is that there is probably
more genetic variation revealed by novel environments, and so it may be possible to study virulence phenotypes that selection
would have otherwise removed.
For the most part, we use Anopheles stephensi because it is a conveniently maintained malaria vector. P. chabaudi does not require a secure insectary.