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Updated: May 8, 2026
Quantitative 3D Imaging of Trypanosoma cruzi-Infected Cells, Dormant Amastigotes, and T Cells in Intact Clarified Organs
Published on: June 23, 2022
New, combined, and reduced dosing treatment protocols cure Trypanosoma cruzi infection in mice
Juan M Bustamante1, Julie M Craft, Byron D Crowe
1Center for Tropical and Emerging Global Diseases.
Abstract:
The development of treatment protocols with reduced toxicity and equivalent or improved efficacy for Trypanosoma cruzi infection is a priority. We tested the effectiveness of benznidazole (BZ), nifurtimox (NFX), other prospective drugs in intermittent and combined treatment protocols to cure T. cruzi infection initiated with susceptible and drug-resistant parasite strains. A 40-day course of BZ, NFX, or the oxaborale AN4169 cured 100% of mice, whereas posaconazole (POS), and NTLA-1 (a nitro-triazole) cured approximately 90% and 20% of mice, respectively. Reducing the overall dosage of BZ or NFX by using an intermittent (once every 5 days) schedule or combining 5 daily doses of POS with 7 intermittent doses of BZ also provided approximately 100% cure. T. cruzi strains resistant to BZ were also found to be resistant to other drugs (POS), and extending the time of treatment or combining drugs did not increase cure rates with these isolates. Thus, dosing schedules for anti-T. cruzi compounds should be determined empirically, and compounds targeting different pathways may be combined to yield effective therapies with reduced toxicity. This work also suggests that standard treatment protocols using BZ and NFX may be significantly overdosing patients, perhaps contributing to the adverse events.
Insights
New treatment strategies for Trypanosoma cruzi infection show promise. Intermittent dosing and drug combinations of benznidazole (BZ) and nifurtimox (NFX) achieved high cure rates in mice, suggesting current protocols may over-dose patients.
Area of Science:
- Parasitology
- Infectious Diseases
- Drug Development
Background:
- Trypanosoma cruzi infection requires treatment protocols with reduced toxicity and improved efficacy.
- Standard treatments like benznidazole (BZ) and nifurtimox (NFX) can have significant adverse events.
- Investigating alternative dosing and drug combinations is crucial for better patient outcomes.
Purpose of the Study:
- To evaluate intermittent and combined treatment protocols for Trypanosoma cruzi infection.
- To assess the efficacy of benznidazole (BZ), nifurtimox (NFX), and other drugs against susceptible and resistant strains.
- To identify optimal dosing strategies that minimize toxicity and maximize cure rates.
Main Methods:
- Testing of benznidazole (BZ), nifurtimox (NFX), oxaborale AN4169, posaconazole (POS), and NTLA-1 in mice.
- Evaluation of continuous 40-day courses, intermittent dosing (every 5 days), and drug combinations.
- Assessment of treatment efficacy against both drug-susceptible and drug-resistant Trypanosoma cruzi strains.
Main Results:
- BZ, NFX, and AN4169 achieved 100% cure rates in mice over 40 days.
- Intermittent BZ or NFX, and a combination of POS with intermittent BZ, also yielded approximately 100% cure.
- Drug-resistant T. cruzi strains showed cross-resistance to POS; extended treatment or combinations did not improve cure rates.
Conclusions:
- Empirical determination of dosing schedules is essential for anti-T. cruzi compounds.
- Combining drugs targeting different pathways may offer effective therapies with reduced toxicity.
- Current BZ and NFX protocols might significantly over-dose patients, potentially causing adverse events.
