title: A new experimental model for assessing drug efficacy against Trypanosoma cruzi infection based on highly sensitive in vivo imaging.
abstract: The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, one of the world's major neglected infections. Although development of improved antiparasitic drugs is considered a priority, there have been no significant treatment advances in the past 40 years. Factors that have limited progress include an incomplete understanding of pathogenesis, tissue tropism, and disease progression. In addition, in vivo models, which allow parasite burdens to be tracked throughout the chronic stage of infection, have been lacking. To address these issues, we have developed a highly sensitive in vivo imaging system based on bioluminescent T. cruzi, which express a red-shifted luciferase that emits light in the tissue-penetrating orange-red region of the spectrum. The exquisite sensitivity of this noninvasive murine model has been exploited to monitor parasite burden in real time throughout the chronic stage, has allowed the identification of the gastrointestinal tract as the major niche of long-term infection, and has demonstrated that chagasic heart disease can develop in the absence of locally persistent parasites. Here, we review the parameters of the imaging system and describe how this experimental model can be incorporated into drug development programs as a valuable tool for assessing efficacy against both acute and chronic T. cruzi infections.
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lewis
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Amanda Fortes
authors.initials: AF
authors.lastname: Francisco
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Taylor
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK john.kelly@lshtm.ac.uk.
authors.forename: John M
authors.initials: JM
authors.lastname: Kelly
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000175:diagnosis* / Q000188:drug therapy* / Q000469:parasitology; D003952:Diagnostic Imaging / Q000379:methods / Q000592:standards; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D016896:Treatment Outcome; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D014344:Trypanocidal Agents
keywords: Chagas disease; drugs; imaging; trypanosomes