InterJournal Complex Systems, 1853
Status: Accepted
Manuscript Number: [1853]
Submission Date: 2006
An agent-based model for Leishmania infection
Author(s): Garrett Dancik ,Karin Dorman ,Doug Jones

Subject(s): CX.3

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Abstract:

An agent-based model for Leishmania major infection Leishmania are protozoan parasites, endemic in 88 countries, that are transmitted through the bites of infected sandflies. Over twenty species of Leishmania cause disease, which can be either cutaneous, where skin ulcers and permanent scarring occur on exposed surfaces of the body; or visceral, with a mortality rate of almost 100% if left untreated. C3HeB/FeJ mice are resistant to L. major infection, but develop chronic cutaneous lesions when infected with L. amazonensis. The mechanism of resistance in these mice is well understood: secretion of IL-12 by dendritic cells promotes a Th1 response, CD4+ Th1 cells activate macrophages through IFN-gamma; production, and activated macropohages clear the parasite. The in vivo factors that are necessary for host susceptibility to L. amazonensis, however, remain ambiguous. Although susceptibility is traditionally attributed to a weakened Th1 response, it is possible that other factors significantly contribute to disease. Through computer simulation, biologists can gain insight into the factors that favor parasite survival. Here we describe an agent-based model for L. major infection in C3HeB/FeJ mice. This model consists of macrophages, CD4+ Th1 cells, the Leishmania parasite, and chemokine, which influences the movement of cells. A replicated Latin hypercube sampling method was used to assess the sensitivity of various model output measures to the values of model parameters. These results indicate that the strength of the Th1 response, resting macrophage speed, and the transfer threshold of infected macrophages (which determines when infected macrophages transfer parasite to additional cells) have a large impact on the time it takes for the infection to be resolved. Parasite load at the peak of infection depends primarily on the timing of the Th1 response and on the transfer threshold of infected macrophages. These results reveal that the exploration of other factors, such as the transfer threshold of infected macrophages, in addition to the strength of the Th1 response, will be important for understanding L. amazonensis disease.

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