A sensitive and reproducible in vivo imaging mouse model for evaluation of drugs against late-stage human African trypanosomiasis.


Burrell-Saward, H; Rodgers, J; Bradley, B; Croft, SL; Ward, TH; (2014) A sensitive and reproducible in vivo imaging mouse model for evaluation of drugs against late-stage human African trypanosomiasis. The Journal of antimicrobial chemotherapy, 70 (2). pp. 510-7. ISSN 0305-7453 DOI: 10.1093/jac/dku393

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Abstract

OBJECTIVES: To optimize the Trypanosoma brucei brucei GVR35 VSL-2 bioluminescent strain as an innovative drug evaluation model for late-stage human African trypanosomiasis.<br/> 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).<br/> 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.<br/> 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.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Antimicrobial Resistance Centre (AMR)
Neglected Tropical Diseases Network
PubMed ID: 25298516
Web of Science ID: 350211600022
URI: http://researchonline.lshtm.ac.uk/id/eprint/2006385

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