ArticleAntimicrobial agents and chemotherapy2015
Limited Ability of Posaconazole To Cure both Acute and Chronic Trypanosoma cruzi Infections Revealed by Highly Sensitive In Vivo Imaging.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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84 citing papers in PubMed, 143 citations in OpenAlex.
- IID432, a parasite-selective topoisomerase II inhibitor, achieves rapid single-dose parasite clearance in a murine chronic Chagas model.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 2: from molecule to confirmed hit.The Journal of antimicrobial chemotherapy · 2026Review
- Discovery of IID432 for Chagas Disease: A Cyanotriazole Inhibitor ofJournal of medicinal chemistry · 2026Article
- Advances and challenges in the search for new treatments for Chagas disease.Memorias do Instituto Oswaldo Cruz · 2026Review
- Induced pluripotent stem cell-derived human macrophages as an infection model for Trypanosoma cruzi.PLoS neglected tropical diseases · 2025Article
- Antitrypanosomal quinazolines targeting lysyl-tRNA synthetase show partial efficacy in a mouse model of acute Chagas disease.Science translational medicine · 2025Article
- Intermittent suppressive posaconazole therapy is ineffective at mitigating cardiac and digestive tract pathologies in an experimental model of chronic Chagas disease.Antimicrobial agents and chemotherapy · 2025Article
- Drug repurposing reveals posaconazole as a CYP11A1 inhibitor enhancing anti-tumor immunity.iScience · 2025Article
- Pharmacokinetic-pharmacodynamic modeling of benznidazole and its antitrypanosomal activity in a murine model of chronic Chagas disease.PLoS neglected tropical diseases · 2025Article
- System-based insights into parasitological and clinical treatment failure in Chagas disease.mSystems · 2025Review
- Reporter genes and transgenicFrontiers in medicine · 2025Review
- Animal models for exploring Chagas disease pathogenesis and supporting drug discovery.Clinical microbiology reviews · 2024Review
- Enteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy.Nature communications · 2024Article
- A panel of phenotypically and genotypically diverse bioluminescent:fluorescent Trypanosoma cruzi strains as a resource for Chagas disease research.PLoS neglected tropical diseases · 2024Article
- Small molecule mediators of host-T. cruzi-environment interactions in Chagas disease.PLoS pathogens · 2024Review
- Fifteen Years after the Definition ofLife (Basel, Switzerland) · 2023Review
- Short-course combination treatment for experimental chronic Chagas disease.Science translational medicine · 2023Article
- Anti-Trypanosoma cruzi activity of Coptis rhizome extract and its constituents.Tropical medicine and health · 2023Article
- Impact of Laboratory-Adapted IntracellularMicroorganisms · 2023Article
- State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation.Research and reports in tropical medicine · 2023Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The antifungal drug posaconazole has shown significant activity against Trypanosoma cruzi in vitro and in experimental murine models. Despite this, in a recent clinical trial it displayed limited curative potential. Drug testing is problematic in experimental Chagas disease because of difficulties in demonstrating sterile cure, particularly during the chronic stage of infection when parasite burden is extremely low and tissue distribution is ill defined. To better assess posaconazole efficacy against acute and chronic Chagas disease, we have exploited a highly sensitive bioluminescence imaging system which generates data with greater accuracy than other methods, including PCR-based approaches. Mice inoculated with bioluminescent T. cruzi were assessed by in vivo and ex vivo imaging, with cyclophosphamide-induced immunosuppression used to enhance the detection of relapse. Posaconazole was found to be significantly inferior to benznidazole as a treatment for both acute and chronic T. cruzi infections. Whereas 20 days treatment with benznidazole was 100% successful in achieving sterile cure, posaconazole failed in almost all cases. Treatment of chronic infections with posaconazole did however significantly reduce infection-induced splenomegaly, even in the absence of parasitological cure. The imaging-based screening system also revealed that adipose tissue is a major site of recrudescence in mice treated with posaconazole in the acute, but not the chronic stage of infection. This in vivo screening model for Chagas disease is predictive, reproducible and adaptable to diverse treatment schedules. It should provide greater assurance that drugs are not advanced prematurely into clinical trial.
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