ArticleScientific reports2016
Nitroheterocyclic drugs cure experimental Trypanosoma cruzi infections more effectively in the chronic stage than in the acute stage.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 100 citations in OpenAlex.
- Human Histatin 5 Exerts Anti-Trypanosomal Activity AgainstInternational journal of molecular sciences · 2026Article
- Overcoming Trypanosoma cruzi persistence with a mechanistically distinct drug combination.npj antimicrobials and resistance · 2026Article
- Influence of Chagas Disease on the Pharmacokinetics of Benznidazole in the Dog Model.ACS pharmacology & translational science · 2026Article
- The patent landscape of Chagas disease vaccines indicates major underinvestment in an emerging global health threat.Nature biotechnology · 2025Article
- Antitrypanosomal quinazolines targeting lysyl-tRNA synthetase show partial efficacy in a mouse model of acute Chagas disease.Science translational medicine · 2025Article
- Statins do not reduce the parasite burden during experimentalAntimicrobial agents and chemotherapy · 2025Article
- Pharmacokinetic-pharmacodynamic modeling of benznidazole and its antitrypanosomal activity in a murine model of chronic Chagas disease.PLoS neglected tropical diseases · 2025Article
- Discovery and Early Optimization of 1Journal of medicinal chemistry · 2025Article
- Animal models for exploring Chagas disease pathogenesis and supporting drug discovery.Clinical microbiology reviews · 2024Review
- Review
- Short-course combination treatment for experimental chronic Chagas disease.Science translational medicine · 2023Article
- Persistent Biofluid Small-Molecule Alterations Induced byACS infectious diseases · 2023Article
- Benznidazole treatment leads to DNA damage in Trypanosoma cruzi and the persistence of rare widely dispersed non-replicative amastigotes in mice.PLoS pathogens · 2023Article
- Persistent biofluid small molecule alterations induced bybioRxiv : the preprint server for biology · 2023Article
- Further Investigations of Nitroheterocyclic Compounds as Potential Antikinetoplastid Drug Candidates.Biomolecules · 2023Review
- Anti-Trypanosoma cruzi activity of Coptis rhizome extract and its constituents.Tropical medicine and health · 2023Article
- Identification of Aryl Polyamines Derivatives as Anti-Pharmaceutics · 2022Article
- Fexinidazole interferes with the growth and structural organization of Trypanosoma cruzi.Scientific reports · 2022Article
- Comparing in vivo bioluminescence imaging and the Multi-Cruzi immunoassay platform to develop improved Chagas disease diagnostic procedures and biomarkers for monitoring parasitological cure.PLoS neglected tropical diseases · 2022Article
- The translational challenge in Chagas disease drug development.Memorias do Instituto Oswaldo Cruz · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
The insect-transmitted protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, and infects 5-8 million people in Latin America. Chagas disease is characterised by an acute phase, which is partially resolved by the immune system, but then develops as a chronic life-long infection. There is a consensus that the front-line drugs benznidazole and nifurtimox are more effective against the acute stage in both clinical and experimental settings. However, confirmative studies have been restricted by difficulties in demonstrating sterile parasitological cure. Here, we describe a systematic study of nitroheterocyclic drug efficacy using highly sensitive bioluminescence imaging of murine infections. Unexpectedly, we find both drugs are more effective at curing chronic infections, judged by treatment duration and therapeutic dose. This was not associated with factors that differentially influence plasma drug concentrations in the two disease stages. We also observed that fexinidazole and fexinidazole sulfone are more effective than benznidazole and nifurtimox as curative treatments, particularly for acute stage infections, most likely as a result of the higher and more prolonged exposure of the sulfone derivative. If these findings are translatable to human patients, they will have important implications for treatment strategies.
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