Abstract
Malaria Plasmodium falciparum (Pf) species contains multiple parasite strains with different immunogenic profiles and expressed phenotypes. These strains interact (compete, cooperate) within host and in transmission (mosquito) environment, so host immunity and environment play important part in evolution and selection of parasite quasi-species. Conventional population-based models (e.g. Ross-MacDonald) have limited capacity to accommodate parasite diversity. An alternative Individual-based approach (IBM) offers greater flexibility.
Here we develop an IBM for multi-strain Pf malaria with genetically structured parasite and immune regulation. Parasite diversity is not constrained (could increase through recombination), yet the model allows efficient simulations of individual histories, as well as large communities and host ensembles over extended time period with multiple transmission cycles.
We employ our model to study competition and selection of mixed malaria strains in individual hosts and in host populations. The model offers different ways of quantifying parasite fitness, and selecting most viable types, under selective pressures. We explore the relationship between selected clones, in terms of their genetic makeup and associated fitness traits.
The model analysis revealed peculiar features of multi-strain malaria: winners of mixed competition in single-infection histories (individual hosts), may not succeed in host communities over multiple transmission cycles. So short-term competitive fitness does not guarantee strain survival. The latter in fact, was strongly associated with cooperative behavior, i.e. strain potential to co-exist and persist in different mixed combinations within-host. We examined network structure of such surviving cooperative cliques. These networks are found to have a few persistent core nodes, each one carrying a subordinate (transient) cluster. Our results shed new light on relative importance of competitive vs. cooperative behavior. Other potential applications of our model (future development) include spatially distributed host-mosquito systems, and putative vaccine that target dominant var-genes and persistent clusters.
Footnotes
(dxg5{at}case.edu)