Skip to main content
What can we help you find?

Frequency Variation… 2023 Antimicrobial Agents and Chemotherapy article

Title: Frequency Variation and Dose Modification of Benznidazole Administration for the Treatment of Trypanosoma cruzi Infection in Mice, Dogs, and Nonhuman Primates

Authors: Juan M. Bustamante, Brooke E. White, Gregory K. Wilkerson, Carolyn L. Hodo, Lisa D. Auckland, Wei Wang, Stephanie McCain, Sarah A. Hamer, Ashley B. Saunders, and Rick L. Tarleton

Journal/Date of Publication: Antimicrobial Agents and Chemotherapy, 2023

DOI: 10.1128/aac.00132-23

Objective: Treatment of chronic Trypanosoma cruzi (Chagas disease) infections in animals, with a focus on the effectiveness of higher dose, intermittent benznidazole treatment protocols.

Type of Study: Prospective

Conclusions:

  1. Twice-weekly high-dose benznidazole treatment over several months led to parasitological cures in some animals (mice, dogs, and macaques), though results varied.
  2. Shorter or less frequent treatment regimens were less effective.
  3. Parasites did not develop resistance to benznidazole even after failed treatment regimens, and re-treatment was still effective.
  4. The protocol has potential applications for high-risk animals (example: working dogs, zoo animals), but its utility in humans remains uncertain due to the risk of adverse effects.

Clinical application:

  1. Higher benznidazole doses, administered intermittently, can cure T. cruzi in mice, dogs, and macaques.
  2. The twice-weekly regimen is promising for chronically infected dogs and non-human primates, providing an alternative to daily dosing protocols.
  3. Retreatment is viable if initial protocols fail, as parasites did not exhibit resistance.
  4. Dogs showed declining antibody levels, suggesting effective parasite clearance.
  5. The protocol could be especially beneficial for high-value animals in endemic regions.
  6. Long-term, high-dose benznidazole treatment shows limited toxicity in dogs and non-human primates, making it a potential option in veterinary settings.
  7. The absence of uniform outcomes suggests treatment duration may need to be tailored to individual cases.
Schematic representation of the study in chronically infected macaques treated weekly and biweekly with BNZ as described in caption
Figure 3. (A) Schematic representation of the study in chronically infected macaques treated weekly and biweekly with BNZ. A total of 10 macaques chronically infected with T. cruzi were used in this study; eight were treated with BNZ weekly at a concentration of 37.5 mg/kg (2.5 times the standard daily dose) over 28 weeks, follow by a cessation of the treatment between week 28 and 38 due to COVID-19 research restrictions. Two animals were kept as untreated controls. At week 38, five macaques (four treated and one untreated) were necropsied to collect the tissues for assessment of parasites persistence by qPCR. With the remaining five macaques, one of them was continued untreated and the other four were treated with a second round of BNZ delivered biweekly at the same concentration as before, over a 15-week period (from week 43 to 58). At the 62-week time point, this second set of macaques (four treated and one untreated) were necropsied to collect the tissues for assessment of parasites persistence by qPCR. (B) Macaque identification, pretreatment, and end of treatment course 1 (28 weeks) blood qPCR status, and tissue PCR results at necropsy are shown. Totals for tissue PCR indicate the number of T. cruzi DNA-positive PCRs per total number of tissue specimens tested singly or in pools of five from the indicated tissues.

Print