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Differential tissue distribution of discrete typing units after drug combination therapy in experimental Trypanosoma cruzi mixed infection

Published online by Cambridge University Press:  21 July 2021

Mariana Strauss ,
M. Silvina Lo Presti Open the ORCID record for M. Silvina Lo Presti [Opens in a new window] ,
Juan C. Ramírez ,
P. Carolina Bazán ,
Daniela A. Velázquez López ,
Alejandra L. Báez ,
Patricia A. Paglini ,
Alejandro G. Schijman  and
Héctor W. Rivarola
Mariana Strauss*
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
M. Silvina Lo Presti*
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
Juan C. Ramírez
Affiliation:
Laboratorio de Biología Molecular de la Enfermedad de Chagas (LaBMECh), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina
P. Carolina Bazán
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
Daniela A. Velázquez López
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
Alejandra L. Báez
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
Patricia A. Paglini
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
Alejandro G. Schijman
Affiliation:
Laboratorio de Biología Molecular de la Enfermedad de Chagas (LaBMECh), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina
Héctor W. Rivarola
Affiliation:
Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU-Córdoba, Argentina
*
Author for correspondence: Mariana Strauss, E-mail: marianastr86@gmail.com, M. Silvina Lo Presti, E-mail: silvinalopresti@unc.edu.ar
Author for correspondence: Mariana Strauss, E-mail: marianastr86@gmail.com, M. Silvina Lo Presti, E-mail: silvinalopresti@unc.edu.ar
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Abstract

The aim of the present work was to evaluate the distribution of the different clones of the parasite prevailing after treatment with benznidazole (BZ) and clomipramine (CLO), in mice infected with Trypanosoma cruzi, Casibla isolate which consists of a mixture of two discrete typing units (DTUs). Albino Swiss mice were infected and treated with high and low concentrations of BZ (100 or 6.25 mg/kg), CLO (5 or 1.25 mg/kg), or the combination of both low doses (BZ6.25 + CLO1.25), during the acute phase of experimental infection. Treatment efficacy was evaluated by comparing parasitaemia, survival and tissular parasite presence. For DTUs genotyping, blood, skeletal and cardiac muscle samples were analysed by multiplex quantitative polymerase chain reaction. The combined treatment had similar outcomes to BZ6.25; BZ100 was the most effective treatment, but it failed to reach parasite clearance and produced greater histological alterations. Non-treated mice and the ones treated with monotherapies showed both DTUs while BZ6.25 + CLO1.25 treated mice showed only TcVI parasites in all the tissues studied. These findings suggest that the treatment may modify the distribution of infecting DTUs in host tissues. Coinfection with T. cruzi clones belonging to different DTUs reveals a complex scenario for the treatment of Chagas disease and search for new therapies.

Keywords

Benznidazoleclomipramineclonal histotropismdiscrete typing unitsexperimental infection modelTrypanosoma cruzi
Type
Research Article
Information
Parasitology , Volume 148 , Issue 13 , November 2021 , pp. 1595 - 1601
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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