Understanding dynamics of Plasmodium falciparum gametocytes production: Insights from an age-structured model
Résumé
Many models of within-host malaria infection dynamics have been formulated since the pioneering work of Anderson et al. in 1989. Biologically, the goal of these models is to understand what governs the severity of infections, the patterns of infectiousness, and the variation thereof across individual hosts. Mathematically, these models are based on dynamical systems, with standard approaches ranging from Kcompartments ordinary differential equations (ODEs) to delay differential equations (DDEs), in order to capture the relatively constant duration of replication and bursting once a parasite infects a host red blood cell. Using malariatherapy data, which offers fine-scale resolution on the dynamics of infection across a number of individual hosts, we compare the fit of one of these standard approaches (K-compartments ODEs) with a partial differential equations (PDEs) model, which explicitly tracks the "age" of an infected cell. We find that the PDE model outperforms the Kcompartments ODEs, particularly early on in infections, where ODEs wildly overestimate parasite densities. Further, the PDE model highlights a strong qualitative connection between the density of transmissible parasite stages (i.e., gametocytes) and the density of host-damaging (and asexually-replicating) parasite stages, which is difficult to capture by the K-compartments ODEs model. This finding provides a simple tool for predicting which hosts are most infectious to mosquitoes-vectors of Plasmodium parasites-which is a crucial component of global efforts to control and eliminate malaria.
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