Dynamic interactions in malaria: host heterogeneity meets parasite polymorphism.

The spectrum of disease severity in Plasmodium falciparum malaria can be attributed to heterogeneity in parasite virulence or to heterogeneity in host factors. However, the two are not necessarily separate explanations for the same phenomena: they may actually complement each other. The conjoint effects of host and parasite heterogeneity can serve to explain certain intriguing epidemiological observations, such as, why there is a reduction in incidence of severe malaria in certain host genotypes without a concomitant reduction in mild disease. By assuming that severe disease is caused by a rare independently transmitted parasite strain, and that the probability of disease is nonlinearly related to the number of effective infections by a certain strain, the disproportionate reduction in the rate of the rarer disease within resistant host genotypes may be explained. Conversely, heterogeneity in host resistance may, under certain circumstances, facilitate the maintenance of diversity in parasite virulence. In this paper we discuss the coevolutionary consequences of heterogeneity in host resistance and diversity in parasite virulence by using a simple mathematical model that attempts to integrate the population genetics of the system with its ecological dynamics. This allows a unified perspective on malaria transmission that synthesises current evidence regarding the effects of host and parasite heterogeneities on malarial disease.