ArticlePLoS neglected tropical diseases2013
In vivo imaging of trypanosome-brain interactions and development of a rapid screening test for drugs against CNS stage trypanosomiasis.
Article in PLoS neglected tropical diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 68 citations in OpenAlex.
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- Neuropathogenesis caused byMicrobial cell (Graz, Austria) · 2021Article
- Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice.Nature communications · 2021Article
- In Vitro and in Vivo Activity of mTOR Kinase and PI3K Inhibitors AgainstMolecules (Basel, Switzerland) · 2020Article
- Anti-Trypanosomal Proteasome Inhibitors Cure Hemolymphatic and Meningoencephalic Murine Infection Models of African Trypanosomiasis.Tropical medicine and infectious disease · 2020Article
- The Drugs of Sleeping Sickness: Their Mechanisms of Action and Resistance, and a Brief History.Tropical medicine and infectious disease · 2020Review
- In Vivo Bioluminescence Imaging to Assess Compound Efficacy Against Trypanosoma brucei.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Update on human African trypanosomiasis (sleeping sickness).Journal of neurology · 2019Review
- Using detergent-enhanced LAMP for African trypanosome detection in human cerebrospinal fluid and implications for disease staging.PLoS neglected tropical diseases · 2019Article
- Characterization of Evolutionarily ConservedJournal of parasitology research · 2019Article
- Development of NanoLuc-PEST expressing Leishmania mexicana as a new drug discovery tool for axenic- and intramacrophage-based assays.PLoS neglected tropical diseases · 2018Article
- In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging.Virulence · 2018Review
- Metabolic Profiling of Central Nervous System Disease in Trypanosoma brucei rhodesiense Infection.The Journal of infectious diseases · 2017Article
- The mouse cortical meninges are the site of immune responses to many different pathogens, and are accessible to intravital imaging.Methods (San Diego, Calif.) · 2017Review
- Kynurenine Pathway Activation in Human African Trypanosomiasis.The Journal of infectious diseases · 2017Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
HUMAN AFRICAN TRYPANOSOMIASIS (HAT) MANIFESTS IN TWO STAGES OF DISEASE: firstly, haemolymphatic, and secondly, an encephalitic phase involving the central nervous system (CNS). New drugs to treat the second-stage disease are urgently needed, yet testing of novel drug candidates is a slow process because the established animal model relies on detecting parasitemia in the blood as late as 180 days after treatment. To expedite compound screening, we have modified the GVR35 strain of Trypanosoma brucei brucei to express luciferase, and have monitored parasite distribution in infected mice following treatment with trypanocidal compounds using serial, non-invasive, bioluminescence imaging. Parasites were detected in the brains of infected mice following treatment with diminazene, a drug which cures stage 1 but not stage 2 disease. Intravital multi-photon microscopy revealed that trypanosomes enter the brain meninges as early as day 5 post-infection but can be killed by diminazene, whereas those that cross the blood-brain barrier and enter the parenchyma by day 21 survived treatment and later caused bloodstream recrudescence. In contrast, all bioluminescent parasites were permanently eliminated by treatment with melarsoprol and DB829, compounds known to cure stage 2 disease. We show that this use of imaging reduces by two thirds the time taken to assess drug efficacy and provides a dual-modal imaging platform for monitoring trypanosome infection in different areas of the brain.
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