Investigative Workshop: Modeling Toxoplasma gondii
Topic: Mathematical modeling of life cycle, stage conversion, and clonal expansion of Toxoplasma gondii
Meeting dates: May 13-15, 2010
Organizers:
Xiaopeng Zhao (Biomedical Engineering Dept., University of Tennessee, Knoxville)
Chunlei Su (Department of Microbiology, University of Tennessee, Knoxville)
Jitender P. Dubey (Laboratory of Parasitic Diseases, United States Department of Agriculture)
Michel Langlais (Institut Mathematiques de Bordeaux, Universite Victor Segalen Bordeaux)
Suzanne Lenhart (NIMBioS Associate Director for Education and Outreach; Department of Mathematics, University of Tennessee, Knoxville)
Jaewook Joo (Department of Physics and Astronomy, University of Tennessee, Knoxville)
Objectives: Toxoplasma gondii (T. gondii) is considered as one of the most successful parasites for its unusual ability to infect a wide range of intermediate hosts, including all mammals and birds. Up to 11% of the human population in the US and 20% in the world are chronically infected. Toxoplasmosis can cause life-threatening encephalitis in immunocompromised persons such as AIDS patients and recipients of organ transplants and cancer chemotherapy. Infection acquired during pregnancy may spread and cause severe problems to the fetus such as damages to the baby's eyes, nervous system, skin, and ears. Toxoplasmosis also has significant effects on human and animal behavior and may lead to neuropsychiatric disorders, e.g. schizophrenia.
T. gondii has a complex life cycle that involves multiple hosts and includes sexual and asexual replications. After ingestion by the hosts, sporozoites rapidly differentiate into tachyzoites, fast-replicating parasites which disseminate within the host and lead to the acute phase of infection. Most of tachyzoites are eliminated by the innate and adaptive cell-mediated immune responses of immunocompetent hosts, but some differentiate into the dormant bradyzoites. The differentiation of tachyzoites into the bradyzoite stage plays indispensible roles in the development of tissue cysts and, thus, in the life-long persistence of parasites in the host. T. gondii has high genetic diversity, with hundreds of genotypes existing globally. However, only one lineage (type II) is widespread and predominates in the global populations, a phenomenon known as clonal expansion.
This workshop aims to explore mathematical tools and problems in describing the life cycle, stage conversion, and clonal expansion of T. gondii by bringing together expertise in parasitic diseases, epidemiology, population genetics, disease modeling, network dynamics, evolutionary dynamics, and nonlinear analysis. We will also explore various modeling and analysis methods for their potential applications in public health strategies and in diagnosis, suppression, and prevention of Toxoplasmosis.
Participants:
Folashade Agusto (NIMBioS); Gustavo Arrizabalaga (Univ. Idaho); Jheelam Banerjee (Vanderbilt Univ. Medical Center); John Baroch (USDA); Sharon Bewick (NIMBioS); Hema Casala (Texas Tech); Jitender P. Dubey ( USDA); Zhilan Feng (Purdue Univ.); Vitaly Ganusov (Univ. Tennessee); Solange Gennari (Univ. de São Paulo, Brazil); Emmanuelle Gilot-Fromont (Ecole Nationale Veterinaire de Lyon); Michael Gilchrist (Univ. Tennessee); Sandra Halonen (Montana State Univ.); Will Harris (Georgetown College); James Haven (Hunter College, City Univ. New York); Jaewook Joo (Univ. Tennessee); Asis Khan ( Washington Univ. - St. Louis); Michel Langlais (Université de Bordeaux II, France); Suzanne Lenhart (Univ. Tennessee); Diego Fernando Aranda Lozano (District Health Secretariat, Bogota D.C. – Colombia); Debashree Majumdar (Univ. Tennessee); Aurelien Mazurie (Montana State Univ.); Natalie Miller (UPenn); Dana Mordue (New York Med. Coll.); Lina Marcela Ocampo (Qundío University); Agricola Odoi (Univ. Tennessee); Jay Radke (Montana State Univ.); Benjamin Rosenthal (USDA); Elliot Shwab (Univ. Tennessee); Chunlei Su (Univ. Tennessee); Adam Sullivan (Univ. Tennessee); Yasuhiro Suzuki (Univ. Kentucky); Paul Tian (William & Mary); Elizabeth VanWormer (Univ. California, Davis); Jorge X. Velasco-Hernandez (UAM-Iztapalapa, Mexico); Isabelle Villena (Univ. Reims); Yiding Yang (Purdue Univ.); Xiaopeng Zhao (Univ. Tennessee)
Participant Podcasts
Here's what participants said about their experience at the NIMBioS Investigative Workshop on Modeling Toxoplasma gondii.
Yasuhiro Suzuki, Dept. of Microbiology, Immunology and Molecular Genetics,Univ. of Kentucky
Chunlei Su, Dept. of Microbiology, Univ. of Tennessee, Knoxville
Jorge X. Velasco-Hernandez, Dept. of Mathematics, UAM-Iztapalapa, Mexico
Summary Report on the NIMBioS Investigative Workshop: Mathematical modeling of life cycle, stage conversion, and clonal expansion of Toxoplasma gondii, May 13-15, 2010
The workshop included 45 participants, including seven international scholars from four countries (France, Mexico, Brazil, and Columbia) and 38 domestic researchers and students from all over the United States. Participants were from diverse areas in biology, animal management, mathematics, physics, and engineering. The workshop consisted of presentations, breakout group discussions, and plenary discussions. Based on the discussions at the workshop, we identified the following issues and recommendations:
- T. gondii has a complex life cycle that involves all warm blooded animals as intermediate hosts and felines as definitive hosts. The complex epidemic network makes T. gondii a very successful parasite with robust transmission mechanisms. One interesting question is why the life cycles of different parasite species utilize different configurations and topologies of host network. Even closely related species may have verydifferent life cycle topologies, e.g. Toxoplasma, Hammondia, Neospora, Sarcocystis, and Eimeria in the phylum Apicomplexa. Simple mathematical models can be built to explore the stabilities and epidemic characteristics of different life cycles, which may yield insights on evolutionary advantages of complex life cycles versus simple life cycles.
- Mathematical models can also be developed to investigate host-pathogen interactions of T. gondii infection in vitro and in vivo, taking in to consideration differences among different strain types of the parasite and the cell or host parasitized. Particularly, models may help to understand the delicate balance between T. gondii invasion dynamics and host immune response. Both differential equation based models and individual based models will be useful.
- Within-host dynamics and between-host dynamics are typically investigated by separate groups of researchers. It is thus a great challenge to understand how properties at the individual level will influence the transmission of the disease at the population level. Models and analyses that integrate within-host dynamics with transmission dynamics can provide insights on such questions.
Future plans: We plan to propose a working group on dynamic modeling of toxoplasmosis. The group will develop mathematical models to understand the mechanisms of host-pathogen interactions for T. gondii infection, particularly on the interplay between stage conversion of the parasite and immune response of the host. To understand the competition between different strains of the parasites, the group will also investigate the coupling between within-host and between-host dynamics to explore the implications for evolutionary strategies of the parasites.
NIMBioS Investigative Workshops involve 30-40 participants, focus on a broad topic or a set of related topics, attempt to summarize/synthesize the state of the art and identify future directions, and have potential for leading to one or more future
