c49f23e96a658b80d82038a32b9b2247 pmc_34207764.pdf 3cb98182a9b03a11077a9f18adcc8390af20f9b2 pmc_34207764.pdf 82909866dd8ded2c97a220e15303474301740966ed851737fc13e7a32bd8bf7a pmc_34207764.pdf Title: Benznidazole Treatment: Time- and Dose-Dependence Varies with the Trypanosoma cruzi Strain Subject: As the development of new drugs for Chagas disease is not a priority due to its neglected disease status, an option for increasing treatment adherence is to explore alternative treatment regimens, which may decrease the incidence of side effects. Therefore, we evaluated the efficacy of different therapeutic schemes with benznidazole (BNZ) on the acute and chronic phases of the disease, using mice infected with strains that have different BNZ susceptibilities. Our results show that the groups of animals infected by VL-10 strain, when treated in the chronic phase with a lower dose of BNZ for a longer period of time (40 mg/kg/day for 40 days) presented better treatment efficacy than with the standard protocol (100 mg/kg/day for 20 days) although the best result in the treatment of the animals infected by the VL-10 strain was with100 mg/kg/day for 40 days. In the acute infection by the Y and VL-10 strains of T. cruzi, the treatment with a standard dose, but with a longer time of treatment (100 mg/kg/day for 40 days) presented the best results. Given these data, our results indicate that for BNZ, the theory of dose and time proportionality does not apply to the phases of infection. Keywords: chagas disease; Trypanosoma cruzi; benznidazole; therapeutic strategies; mice Author: Kátia da Silva Fonseca, Luísa Perin, Nívia Carolina Nogueira de Paiva, Beatriz Cristiane da Silva, Thays Helena Chaves Duarte, Flávia de Souza Marques, Guilherme de Paula Costa, Israel Molina, Rodrigo Correa-Oliveira, Paula Melo de Abreu Vieira and Cláudia Martins Carneiro Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jun 9 13:27:57 2021 CEST ModDate: Wed Jun 9 13:33:20 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1351211 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MWRLBT+VnURWPalladioL Type 1 Custom yes yes no 10 0 ZVVWEW+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 RCRHQD+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 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Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 577 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Animals and Ethics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Therapeutic Schemes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Cure Criteria Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: Survival Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Parasitemia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Immunosuppression and Fresh Blood Examination Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Real-Time Polymerase Chain Reaction (qPCR) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Info: Title: Benznidazole Treatment: Time- and Dose-Dependence Varies with the Trypanosoma cruzi Strain Author: Kátia da Silva Fonseca, Luísa Perin, Nívia Carolina Nogueira de Paiva, Beatriz Cristiane da Silva, Thays Helena Chaves Duarte, Flávia de Souza Marques, Guilherme de Paula Costa, Israel Molina, Rodrigo Correa-Oliveira, Paula Melo de Abreu Vieira and Cláudia Martins Carneiro Subject: As the development of new drugs for Chagas disease is not a priority due to its neglected disease status, an option for increasing treatment adherence is to explore alternative treatment regimens, which may decrease the incidence of side effects. Therefore, we evaluated the efficacy of different therapeutic schemes with benznidazole (BNZ) on the acute and chronic phases of the disease, using mice infected with strains that have different BNZ susceptibilities. Our results show that the groups of animals infected by VL-10 strain, when treated in the chronic phase with a lower dose of BNZ for a longer period of time (40 mg/kg/day for 40 days) presented better treatment efficacy than with the standard protocol (100 mg/kg/day for 20 days) although the best result in the treatment of the animals infected by the VL-10 strain was with100 mg/kg/day for 40 days. In the acute infection by the Y and VL-10 strains of T. cruzi, the treatment with a standard dose, but with a longer time of treatment (100 mg/kg/day for 40 days) presented the best results. Given these data, our results indicate that for BNZ, the theory of dose and time proportionality does not apply to the phases of infection. 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