Malaria parasite is subject to multiple selective pressures within-host and on population level. Within-host parasite dynamics is primarily driven by its intrinsic traits (invasion of erythrocytes and merozoite replication rates), as well as their interactions with host immunity. On population level, host demographics, behavior and environments (mosquito abundance, biting rate/patterns) play a significant role. Selective pressures can drive parasite evolution, and determine such traits, such as virulence, transmissibility, drug resistance.
Most conventional approaches to parasite fitness and selection employ populations based models which allow only limited account of parasite diversity (e.g. 1, 2). Here we develop an agent based approach to within-host malaria, that accommodates many salient features – RBC depletion, immune stimulation and clearing, antigenic variation. The latter is controlled by a family of variable surface antigens (e.g. PfEMP1), which allow immune evasion by parasite via variant switching (3, 4).
In out setup (see e.g. 5), each parasite strain has a specific genetic makeup (collection of “variants”), drawn from large genetic pool (4). Multiple strains (quasi-species) compete within-host through cross-reactive immunity. Furthermore, mixed stains can recombine in “mosquito agent” and produce new parasite types injected into other randomly drawn hosts.
The resulting agent-based community (ABM) is used to study evolution of virulence, transmissibility, persistence (V-T-P) in long term community histories. We explore quantitative relationship between environmental inputs (mosquito EIR), host intrinsic traits (immune competence), and their evolutionary outcomes. We also testes the hypothesis on “evolution of virulence through imperfect vaccination” for our ABM, and studied the effect of EIR on multiplicity of infection (c.f. 6).