title: An integrated model of Plasmodium falciparum dynamics.
abstract: The within-host and between-host dynamics of malaria are linked in myriad ways, but most obviously by gametocytes, the parasite blood forms transmissible from human to mosquito. Gametocyte dynamics depend on those of non-transmissible blood forms, which stimulate immune responses, impeding transmission as well as within-host parasite densities. These dynamics can, in turn, influence antigenic diversity and recombination between genetically distinct parasites. Here, we embed a differential-equation model of parasite-immune system interactions within each of the individual humans represented in a discrete-event model of Plasmodium falciparum transmission, and examine the effects of human population turnover, parasite antigenic diversity, recombination, and gametocyte production on the dynamics of malaria. Our results indicate that the local persistence of P. falciparum increases with turnover in the human population and antigenic diversity in the parasite, particularly in combination, and that antigenic diversity arising from meiotic recombination in the parasite has complex differential effects on the persistence of founder and progeny genotypes. We also find that reductions in the duration of individual human infectivity to mosquitoes, even if universal, produce population-level effects only if near-absolute, and that, in competition, the persistence and prevalence of parasite genotypes with gametocyte production concordant with data exceed those of genotypes with higher gametocyte production. This new, integrated approach provides a framework for investigating relationships between pathogen dynamics within an individual host and pathogen dynamics within interacting host and vector populations.
authors.affiliation: Department of Organismic and Evolutionary Biology, Division of Engineering and Applied Sciences, Harvard University, 33 Oxford Street, Cambridge, MA 02138, USA. mckenzel@mail.nih.gov
authors.forename: F Ellis
authors.initials: FE
authors.lastname: McKenzie
authors.forename: William H
authors.initials: WH
authors.lastname: Bossert
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000276:immunology; D005838:Genotype; D006790:Host-Parasite Interactions; D006801:Humans; D007303:Insect Vectors / Q000469:parasitology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000635:transmission; D018448:Models, Immunological; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan