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, S. L. and Ward, T. H. (2015) A sensitive and reproducible in vivo imaging mouse model for evaluation of drugs against late-stage human African trypanosomiasis. Journal of Antimicrobial Chemotherapy, 70(2), pp. 510-517. (doi:10.1093/jac/dku393) (PMID:25298516)

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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.<p></p> 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).<p></p> 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.<p></p> 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.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bradley, Mrs Barbara and Rodgers, Dr Jean
Authors: Burrell-Saward, H., Rodgers, J., Bradley, B., Croft, S. L., and Ward, T. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Journal of Antimicrobial Chemotherapy
Publisher:Oxford University Press
ISSN:0305-7453
ISSN (Online):1460-2091

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
522031In vivo imaging models of African trypanosomiasis to support drug discovery programmes.Michael BarrettGates Foundation (GATES)OPPGH5337III - PARASITOLOGY
656351In vivo imaging models of African trypanosomiasis to support drug discovery programmesMichael BarrettGates Foundation (GATES)OPPGH5337III - PARASITOLOGY