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bioRxiv · 10.1101/2022.07.25.501361

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

Bustamante, J.·Padilla, A.·White, B.·Auckland, L.·Busselman, R.·Collins, S.·Malcolm, E.·Wilson, B.·Saunders, A.·Hamer, S.·Tarleton, R. L.
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Abstract

Trypanosoma cruzi naturally infects a wide variety of wild and domesticated mammals, in addition to humans. Depending on the infection dose and other factors, the acute infection can be life-threatening, and in all cases, the risk of chagasic heart disease is high in persistently infected hosts. Domestic, working, and semi-feral dogs in the Americas are at significant risk of T. cruzi and in certain settings in the southern United States, the risk of new infections can exceed 30% per year, even with the use of vector control protocols. In this study, we explored whether intermittent low-dose treatment with the trypanocidal compound benznidazole (BNZ) during the transmission season, could alter the number of new infections in dogs in an area of known, intense transmission pressure. Preliminary studies in mice suggested that twice-weekly administration of BNZ could prevent or truncate infections when parasites were delivered at the mid-point between BNZ doses. Pre-transmission season screening of 126 dogs identified 53 dogs (42.1%) as T. cruzi infection positive, based upon blood PCR and Luminex-based serology. Serial monitoring of the 67 uninfected dogs during the high transmission season (May to October) revealed 15 (22.4%) new infections, 6 in the untreated control group and 9 in the group receiving BNZ prophylaxis, indicating no impact of this prophylaxis regimen on the incidence of new infections. Although these studies suggest that rigorously timed and more potent dosing regimen may be needed to achieve an immediate benefit of prophylaxis, additional studies would be needed to determine if drug prophylaxis reduced disease severity despite this failure to prevent new infections. Author SummaryTrypanosoma cruzi, the parasite that causes Chagas disease, circulates extensively in the southern U.S. and working dog populations in south-central Texas are at very high risk of infection, and morbidity and early mortality due to this infection. In this study, we used low level administration of an FDA-approved drug during the transmission season to attempt to prevent new infections in these dogs. Although that effort failed, the study revealed new information about the transmission dynamics and generation of antibody responses and immune control of infection in this high-transmission setting.

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Bustamante, J., Padilla, A., White, B., Auckland, L., Busselman, R., Collins, S., Malcolm, E., Wilson, B., Saunders, A., Hamer, S., Tarleton, R. L.. 2022-07-25. Prophylactic low-dose, bi-weekly benznidazole treatment fails to prevent Trypanosoma cruzi infection in dogs under intense transmission pressure. https://doi.org/10.1101/2022.07.25.501361

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