LAboratory of Mathematical Parallel Systems

Modelling the population dynamics of Plasmodium falciparum gametocytes in humans during malaria infection

    Dr. James McCaw
    University of Melbourne
    Thursday, December 12, 2019 - 11:00am to 12:00pm
    N638 Ross

    Gametocytes differentiated from asexual blood-stage malaria parasites are transmissible from humans to mosquitoes. The concentration of mature gametocytes in blood is a key determinant of transmissibility. While mathematical models of blood-stage asexual parasitemia are well established and have proven invaluable in deepening our understanding of the biology of malaria infection there is a distinct lack of model-based analyses of gametocyte population dynamics. This limits our ability to gain insight into the quantitative relationship between asexual parasitemia, gametocytemia and transmissibility.
    Here we introduce a modelling framework for the population dynamics of Plasmodium falciparum gametocytes in the human host which incorporates improved measurements of parasitemia in humans, a novel mathematical model of gametocyte population dynamics, and model validation using a Bayesian hierarchical inference method. Our work is based on recent advances in experimental medicine using human volunteer infection studies (VIS) and our existing expertise in within-host models of malaria infection.
    Our novel mathematical model for blood-stage malaria infection provides an excellent fit to the available clinical data from 17 human volunteers infected with P. falciparum, and reliably predicts observed gametocyte levels. We estimated P. falciparum’s sexual commitment rate and gametocyte sequestration time in humans to be 0.54% (95% credible interval: 0.30–1.00) per asexual replication cycle and 8.39 (6.54–10.59) days respectively for the 3D7 parasite strain. Furthermore, we used the data-calibrated model to predict the effects of those gametocyte population dynamics parameters on human-to-mosquito transmissibility, providing a method to link within-human host kinetics of malaria infection to epidemiological-scale infection and transmission patterns. Work with: P. Cao, K.A. Collins, S.G. Zaloumis, T. Wattanakul, J. Tarning, J.A. Simpson, J.S. McCarthy