title: A sensitive and reproducible in vivo imaging mouse model for evaluation of drugs against late-stage human African trypanosomiasis.
abstract: OBJECTIVE
  To optimize the Trypanosoma brucei brucei GVR35 VSL-2 bioluminescent strain as an innovative drug evaluation model for late-stage human African trypanosomiasis.
  
  
  METHODS
  An IVIS® Lumina II imaging system was used to detect bioluminescent T. b. brucei GVR35 parasites in mice to evaluate parasite localization and disease progression. Drug treatment was assessed using qualitative bioluminescence imaging and real-time quantitative PCR (qPCR).
  
  
  RESULTS
  We have shown that drug dose-response can be evaluated using bioluminescence imaging and confirmed quantification of tissue parasite load using qPCR. The model was also able to detect drug relapse earlier than the traditional blood film detection and even in the absence of any detectable peripheral parasites.
  
  
  CONCLUSIONS
  We have developed and optimized a new, efficient method to evaluate novel anti-trypanosomal drugs in vivo and reduce the current 180 day drug relapse experiment to a 90 day model. The non-invasive in vivo imaging model reduces the time required to assess preclinical efficacy of new anti-trypanosomal drugs.
authors.affiliation: Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Hollie
authors.initials: H
authors.lastname: Burrell-Saward
authors.affiliation: Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Rodgers
authors.affiliation: Institute of Infection and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bradley
authors.affiliation: Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Simon L
authors.initials: SL
authors.lastname: Croft
authors.affiliation: Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK theresa.ward@lshtm.ac.uk.
authors.forename: Theresa H
authors.initials: TH
authors.lastname: Ward
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods; D008549:Melarsoprol / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D059208:Parasite Load; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000175:diagnosis* / Q000469:parasitology*
chemical_list: D014344:Trypanocidal Agents; D008549:Melarsoprol
keywords: Trypanosoma brucei brucei; bioluminescence imaging; luciferase