An agent-based model for Leishmania major infection

Leishmania are protozoan parasites transmitted by bites of infected sandflies. Over 20 species of Leishmania, endemic in 88 countries, are capable of causing human disease. Disease is either cutaneous, where skin ulcers occur on exposed surfaces of the body, or visceral, with near certain mortality if left untreated. C3HeB/FeJ mice are resistant to L. major, but develop chronic cutaneous lesions when infected with another species L. amazonensis. The well-characterized mechanism of resistance to L. major depends on a Th1 immune response, macrophage activation, and elimination of the parasite [Sacks 2002]. The factors that account for host susceptibility to L. amazonensis, however, are not completely understood, despite being generally attributed to a weakened Th1 response [Vanloubbeck 2004]. Computer simulation can provide insight into the differences between these species. Toward this goal, we describe an agent-based model for L. major infection and explore the sensitivity of predictions to model parameters. Results indicate that the strength of the Th1 response, resting macrophage speed, and parasite transfer threshold of infected macrophages (which determines when infected macrophages transfer parasite to additional cells) influence time to heal infection, while the timing of the adaptive immune response, macrophage speed, and transfer threshold impact parasite load at the peak of infection.