ArticlePLoS neglected tropical diseases2013
Benznidazole and posaconazole in experimental Chagas disease: positive interaction in concomitant and sequential treatments.
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 45 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 121 citations in OpenAlex.
- Monotherapy and combination chemotherapy for Chagas disease treatment: a systematic review of clinical efficacy and safety based on randomized controlled trials.Parasitology · 2022Pooled it
- Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity.Memorias do Instituto Oswaldo Cruz · 2014Guideline
- Population pharmacokinetic-pharmacodynamic analysis of benznidazole monotherapy and combination therapy with fosravuconazole in chronic Chagas disease (BENDITA).PLoS neglected tropical diseases · 2025Trial
- Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial.The Lancet. Infectious diseases · 2018Trial
- Development of a community-based intervention for the control of Chagas disease based on peridomestic animal management: an eco-bio-social perspective.Transactions of the Royal Society of Tropical Medicine and Hygiene · 2015Trial
- Design, Synthesis, and Trypanosomicidal Evaluation of Eugenol-Based Azole Hybrids: Discovery of anACS omega · 2025Article
- Progress and Prospects of Triazoles in Advanced Therapies for Parasitic Diseases.Tropical medicine and infectious disease · 2025Review
- Fifteen Years after the Definition ofLife (Basel, Switzerland) · 2023Review
- Short-course combination treatment for experimental chronic Chagas disease.Science translational medicine · 2023Article
- Preclinical Studies and Drug Combination of Low-Cost Molecules for Chagas Disease.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Vaccine-linked chemotherapy with a low dose of benznidazole plus a bivalent recombinant protein vaccine prevents the development of cardiac fibrosis caused by Trypanosoma cruzi in chronically-infected BALB/c mice.PLoS neglected tropical diseases · 2022Article
- Potential of Triterpenic Natural Compound Betulinic Acid for Neglected Tropical Diseases New Treatments.Biomedicines · 2022Review
- Combination therapy using nitro compounds improves the efficacy of experimental Chagas disease treatment.Parasitology · 2021Article
- Benznidazole Treatment: Time- and Dose-Dependence Varies with thePathogens (Basel, Switzerland) · 2021Article
- Combination With Tomatidine Improves the Potency of Posaconazole AgainstFrontiers in cellular and infection microbiology · 2021Article
- Review on Experimental Treatment Strategies AgainstJournal of experimental pharmacology · 2021Review
- Synergistic effect and ultrastructural changes in Trypanosoma cruzi caused by isoobtusilactone A in short exposure of time.PloS one · 2021Article
- In vitro susceptibility to benznidazole, nifurtimox and posaconazole of Trypanosoma cruzi isolates from ParaguayBiomedica : revista del Instituto Nacional de Salud · 2020Article
- Combination Therapy Using Benznidazole and Aspirin during the Acute Phase of Experimental Chagas Disease Prevents Cardiovascular Dysfunction and Decreases Typical Cardiac Lesions in the Chronic Phase.Antimicrobial agents and chemotherapy · 2020Article
- Current trends in the pharmacological management of Chagas disease.International journal for parasitology. Drugs and drug resistance · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrent chemotherapy for Chagas disease is unsatisfactory due to its limited efficacy, particularly in the chronic phase, with frequent side effects that can lead to treatment discontinuation. Combined therapy is envisioned as an ideal approach since it may improve treatment efficacy whilst decreasing toxicity and the likelihood of resistance development. We evaluated the efficacy of posaconazole in combination with benznidazole on Trypanosoma cruzi infection in vivo. METHODS AND
findingsBenznidazole and posaconazole were administered individually or in combination in an experimental acute murine infection model. Using a rapid treatment protocol for 7 days, the combined treatments were more efficacious in reducing parasitemia levels than the drugs given alone, with the effects most evident in combinations of sub-optimal doses of the drugs. Subsequently, the curative action of these drug combinations was investigated, using the same infection model and 25, 50, 75 or 100 mg/kg/day (mpk) of benznidazole in combination with 5, 10 or 20 mpk of posaconazole, given alone or concomitantly for 20 days. The effects of the combination treatments on parasitological cures were higher than the sum of such effects when the drugs were administered separately at the same doses, indicating synergistic activity. Finally, sequential therapy experiments were carried out with benznidazole or posaconazole over a short interval (10 days), followed by the second drug administered for the same period of time. It was found that the sequence of benznidazole (100 mpk) followed by posaconazole (20 mpk) provided cure rates comparable to those obtained with the full (20 days) treatments with either drug alone, and no cure was observed for the short treatments with drugs given alone.
conclusionsOur data demonstrate the importance of investigating the potential beneficial effects of combination treatments with marketed compounds, and showed that combinations of benznidazole with posaconazole have a positive interaction in murine models of Chagas disease.
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Registered trials
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