Mathematical Modeling of Malaria Infection with Innate and Adaptive Immunity in Individuals and Agent-Based Communities

Department of Mathematics, Case Western Reserve University, Cleveland, Ohio, United States of America.
PLoS ONE (Impact Factor: 3.23). 03/2012; 7(3):e34040. DOI: 10.1371/journal.pone.0034040
Source: PubMed


Agent-based modeling of Plasmodium falciparum infection offers an attractive alternative to the conventional Ross-Macdonald methodology, as it allows simulation of heterogeneous communities subjected to realistic transmission (inoculation patterns).
We developed a new, agent based model that accounts for the essential in-host processes: parasite replication and its regulation by innate and adaptive immunity. The model also incorporates a simplified version of antigenic variation by Plasmodium falciparum. We calibrated the model using data from malaria-therapy (MT) studies, and developed a novel calibration procedure that accounts for a deterministic and a pseudo-random component in the observed parasite density patterns. Using the parasite density patterns of 122 MT patients, we generated a large number of calibrated parameters. The resulting data set served as a basis for constructing and simulating heterogeneous agent-based (AB) communities of MT-like hosts. We conducted several numerical experiments subjecting AB communities to realistic inoculation patterns reported from previous field studies, and compared the model output to the observed malaria prevalence in the field. There was overall consistency, supporting the potential of this agent-based methodology to represent transmission in realistic communities.
Our approach represents a novel, convenient and versatile method to model Plasmodium falciparum infection.

Download full-text


Available from: Charles H King
  • Source
    • "Stochasticity is incorporated ad hoc into the models by the emergence of new variants (which are not recognized by immune system) at random times, usually driven by a Poisson process (see Nowak and May, 2000 and references therein). Very recently Gurarie et al. (2012) implemented a discrete time computer model for the case of malaria. This modeling approach, termed agent-based, consists of a set of coupled difference equations that describe the transition between successive iterations of the parasite population (i.e. "

    Full-text · Dataset · Nov 2015
  • Source
    • "Very recently Gurarie et al. (see ref. [18]) implemented a discrete time computer model for the case of malaria. This modeling approach, termed agent-based, consists in a set of coupled difference equations that describe the transition between successive iterations of the parasite population (i.e. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We present a novel model that describes the within-host evolutionary dynamics of parasites undergoing antigenic variation. The approach uses a multi-type branching process with two types of entities defined according to their relationship with the immune system: clans of resistant parasitic cells (i.e. groups of cells sharing the same antigen not yet recognized by the immune system) that may become sensitive, and individual sensitive cells that can acquire a new resistance thus giving rise to the emergence of a new clan. The simplicity of the model allows analytical treatment to determine the subcritical and supercritical regimes in the space of parameters. By incorporating a density-dependent mechanism the model is able to capture additional relevant features observed in experimental data, such as the characteristic parasitemia waves. In summary our approach provides a new general framework to address the dynamics of antigenic variation which can be easily adapted to cope with broader and more complex situations. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Sep 2015 · Journal of Theoretical Biology
  • Source
    • "In very low transmission settings such as Cambodia, asymptomatic infections remain the major reservoir of malaria parasites contributing to maintain disease transmission [9-11]. As a consequence, the detection and treatment of the asymptomatic carriers is a crucial step in progress towards malaria elimination [12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To achieve the goal of malaria elimination in low transmission areas such as in Cambodia, new, inexpensive, high-throughput diagnostic tools for identifying very low parasite densities in asymptomatic carriers are required. This will enable a switch from passive to active malaria case detection in the field. DNA extraction and real-time PCR assays were implemented in an "in-house" designed mobile laboratory allowing implementation of a robust, sensitive and rapid malaria diagnostic strategy in the field. This tool was employed in a survey organized in the context of the MalaResT project (NCT01663831). The real-time PCR screening and species identification assays were performed in the mobile laboratory between October and November 2012, in Rattanakiri Province, to screen approximately 5,000 individuals in less than four weeks and treat parasite carriers within 24--48 hours after sample collection. An average of 240 clinical samples (and 40 quality control samples) was tested every day, six/seven days per week. Some 97.7% of the results were available <24 hours after the collection. A total of 4.9% were positive for malaria. Plasmodium vivax was present in 61.1% of the positive samples, Plasmodium falciparum in 45.9%, Plasmodium malariae in 7.0% and Plasmodium ovale in 2.0%. The operational success of this diagnostic set-up proved that molecular testing and subsequent treatment is logistically achievable in field settings. This will allow the detection of clusters of asymptomatic carriers and to provide useful epidemiological information. Fast results will be of great help for staff in the field to track and treat asymptomatic parasitaemic cases. The concept of the mobile laboratory could be extended to other countries for the molecular detection of malaria or other pathogens, or to culture vivax parasites, which does not support long-time delay between sample collection and culture.
    Full-text · Article · Nov 2013 · Malaria Journal
Show more