1. Benznidazole Treatment: Time- and Dose-Dependence Varies with the Trypanosoma cruzi Strain
- Author
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Beatriz Cristiane da Silva, Thays Helena Chaves Duarte, Nívia Carolina Nogueira de Paiva, Kátia da Silva Fonseca, Israel Molina, Paula Melo de Abreu Vieira, Guilherme de Paula Costa, Flávia de Souza Marques, Luísa Perin, Cláudia Martins Carneiro, Rodrigo Correa-Oliveira, Institut Català de la Salut, [Fonseca KDS, Perin L, de Paiva NCN, da Silva BC] Laboratory of Immunopathology, Nucleus of Biological Sciences Research, Federal University of Ouro Preto, Ouro Preto, Brazil. [Duarte THC, Marques FS] Laboratory of Morphopathology, Department of Biological Sciences, Nucleus of Biological Sciences Research, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Brazil. [Molina I] Laboratory of Immunopathology, Nucleus of Biological Sciences Research, Federal University of Ouro Preto, Ouro Preto, Brazil. Unitat de Medicina Tropical i Salut Internacional, Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. PROSICS Barcelona, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Microbiology (medical) ,Chagas disease ,mice ,Medicaments antiinfecciosos - Ús terapèutic ,Trypanosoma cruzi ,Dose dependence ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Pharmacology ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Article ,enfermedades parasitarias::infecciones por protozoos::infecciones por Euglenozoa::tripanosomiasis::enfermedad de Chagas [ENFERMEDADES] ,Mice ,Immunology and Allergy ,Medicine ,Ratolins ,Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice [ORGANISMS] ,therapeutic strategies ,Molecular Biology ,chagas disease ,benznidazole ,General Immunology and Microbiology ,biology ,Strain (chemistry) ,business.industry ,Incidence (epidemiology) ,biology.organism_classification ,medicine.disease ,Treatment efficacy ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiparasitic Agents [CHEMICALS AND DRUGS] ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antiparasitarios [COMPUESTOS QUÍMICOS Y DROGAS] ,Infectious Diseases ,Benznidazole ,Therapeutic strategies ,Treatment time ,business ,Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones [ORGANISMOS] ,Chagas, Malaltia de - Tractament ,Parasitic Diseases::Protozoan Infections::Euglenozoa Infections::Trypanosomiasis::Chagas Disease [DISEASES] ,medicine.drug - Abstract
Trypanosoma cruzi; Benznidazol; Estratègies terapèutiques Trypanosoma cruzi; Benznidazol; Estrategias terapéuticas Trypanosoma cruzi; Benznidazole; Therapeutic strategies 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. Funding was provided by the Universidade Federal de Ouro Preto (UFOP), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), research fellowships from CNPq (Carneiro CM, Correa-Oliveira R), CAPES—Science Without Borders and Senior Research Visitor (Molina I, Correa-Oliveira R), and BERENICE (Collaborative Project supported by the European Commission under the Health Innovation Work Programme of the 7th Framework Programme). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Published
- 2021