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Prophylactic low-dose… 2022 PLoS Neglected Tropical Diseases article

Title: Prophylactic low-dose, bi-weekly benznidazole treatment fails to prevent Trypanosoma cruzi infection in dogs under intense transmission pressure

Authors: Juan M. Bustamante, Angel M. Padilla, Brooke White, Lisa D. Auckland, Rachel E. Busselman, Stephanie Collins, Elizabeth L. Malcolm, Briana F. Wilson, Ashley B. Saunders, Sarah A. Hamer, and Rick L. Tarleton

Journal/Date of Publication: PLoS Neglected Tropical Diseases, 2022

DOI: 10.1371/journal.pntd.0010688

Objective: The focus of the study is the prevention of Trypanosoma cruzi infection (Chagas disease) in dogs, especially in environments with high transmission pressure, such as large dog kennels in southern Texas.

Type of study: Prospective

Conclusions: 

  1. Low-dose, bi-weekly benznidazole treatment did not prevent new T. cruzi infections in dogs under intense transmission pressure.
  2. 22.4% of dogs developed new infections, with no significant difference between the treated and control groups.
  3. More potent or frequent dosing may be necessary, and while this regimen did not prevent infections, the impact on clinical disease severity was not assessed in this study.

Clinical application:

  1. Current low-dose benznidazole regimen is ineffective in preventing T. cruzi infections in dogs in high transmission areas.
  2. More aggressive or frequent prophylactic treatment might be necessary.
  3. Prophylactic treatment did not show immediate benefits but its impact on disease severity or progression requires further study.
  4. The study highlights the risk of Chagas disease in working dogs, even under vector control measures.
  5. Regular PCR and serological monitoring can help in early detection of T. cruzi infection.
  6. Seasonal variation in transmission risk may suggest the need for earlier prophylaxis initiation.
  7. Prophylactic failure underscores the need for alternative approaches, including vaccine development or enhanced vector control.
  8. Further studies in dogs are key as they can serve as sentinels for human health because they have a similar disease progression, share the same environment, and exposure risks as humans.
multi-panel figure depicting results of serology of T. cruzi negative dogs in study as described in caption
Figure 2. Initial screening results with multiplex serology and PCR to identify T. cruzi-negative dogs to enroll in the prophylaxis study.(A) Schematic representation of dog screening and prophylaxis trial. Heatmaps of antibody levels (mean fluorescence intensity; MFI) and qPCR measurement of T. cruzi DNA in blood were used to classify dogs as uninfected (B), T. cruzi-infected (C), or seronegative but with a blood PCR result that did not reach the cut-off for being considered positive (D). Recombinant T. cruzi proteins are defined in the Materials and Methods; lysate = a sonicate of T. cruzi trypomastigotes and amastigotes; GFP = recombinant green fluorescent protein (negative antigen control); Parvo = Parvovirus vaccine antigen (positive serological control).

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