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Characterization and Follow-Up of Trypanosoma cruzi Natural Populations Refractory to Etiological Chemotherapy in Oral Chagas Disease Patients

We aimed to characterize the genetic constitution of natural T. cruzi populations involved in an Oral Chagas Disease (OCD) outbreak at a rural school of the community of Chichiriviche de la Costa, Venezuela, which affected patients did not respond to the etiological treatment. Peripheral blood sampl...

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Autores principales: Muñoz-Calderón, Arturo, Díaz-Bello, Zoraida, Alarcón de Noya, Belkisyolé, Noya-González, Oscar O., Schijman, Alejandro G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121101/
https://www.ncbi.nlm.nih.gov/pubmed/33996636
http://dx.doi.org/10.3389/fcimb.2021.665063
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author Muñoz-Calderón, Arturo
Díaz-Bello, Zoraida
Alarcón de Noya, Belkisyolé
Noya-González, Oscar O.
Schijman, Alejandro G.
author_facet Muñoz-Calderón, Arturo
Díaz-Bello, Zoraida
Alarcón de Noya, Belkisyolé
Noya-González, Oscar O.
Schijman, Alejandro G.
author_sort Muñoz-Calderón, Arturo
collection PubMed
description We aimed to characterize the genetic constitution of natural T. cruzi populations involved in an Oral Chagas Disease (OCD) outbreak at a rural school of the community of Chichiriviche de la Costa, Venezuela, which affected patients did not respond to the etiological treatment. Peripheral blood samples and/or hemocultures were obtained from twenty-nine OCD patients at time of diagnosis or along nine years of Post-treatment (Tx) follow-up. The IgG serology, T. cruzi discrete typing units (DTU), satellite DNA-qPCR parasitic loads, and minicircle signatures were determined at Pre-Tx and after Tx. The serological titles and parasitic loads changed after treatment, with a significant decrease of IgG titers (Spearman’s r value= -0.961) and median parasite loads from 2.869 [IQR = 2.113 to 3.720] to 0.105 [IQR = -1.147 to 1.761] log10 par eq. /mL at Pre-Tx and Post-Tx, respectively, suggesting infection evolution from acute to chronic phase, without seroconversion or parasitological eradication, which was indicative of treatment failure. All patients were infected with T. cruzi DTU I populations. At Pre-Tx their median Jaccard genetic distances were 0.775 [IQR = 0.708 to 0.882], decreasing in genetic variability towards the end of follow-up (Mann-Whitney U test p= 0.0031). Interestingly, no Post-Tx minicircle signature was identical to its Pre-Tx counterpart population in a same patient, revealing selection of parasite subpopulations between the primary infection and Post-Tx. The parasitic populations isolated from hemocultures showed a lower number of bands in the minicircle signatures with respect to the signatures obtained directly from the patients’ blood samples, demonstrating a process of parasitic selection and reduction of the population variability that initially infected the patients. Decrease of parasitic loads after treatment as well as Pre- and Post-Tx intra-TcI diversity might be a consequence of both, natural evolution of the acute infection to the chronic phase and persistence of refractory populations due to Tx selection.
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spelling pubmed-81211012021-05-15 Characterization and Follow-Up of Trypanosoma cruzi Natural Populations Refractory to Etiological Chemotherapy in Oral Chagas Disease Patients Muñoz-Calderón, Arturo Díaz-Bello, Zoraida Alarcón de Noya, Belkisyolé Noya-González, Oscar O. Schijman, Alejandro G. Front Cell Infect Microbiol Cellular and Infection Microbiology We aimed to characterize the genetic constitution of natural T. cruzi populations involved in an Oral Chagas Disease (OCD) outbreak at a rural school of the community of Chichiriviche de la Costa, Venezuela, which affected patients did not respond to the etiological treatment. Peripheral blood samples and/or hemocultures were obtained from twenty-nine OCD patients at time of diagnosis or along nine years of Post-treatment (Tx) follow-up. The IgG serology, T. cruzi discrete typing units (DTU), satellite DNA-qPCR parasitic loads, and minicircle signatures were determined at Pre-Tx and after Tx. The serological titles and parasitic loads changed after treatment, with a significant decrease of IgG titers (Spearman’s r value= -0.961) and median parasite loads from 2.869 [IQR = 2.113 to 3.720] to 0.105 [IQR = -1.147 to 1.761] log10 par eq. /mL at Pre-Tx and Post-Tx, respectively, suggesting infection evolution from acute to chronic phase, without seroconversion or parasitological eradication, which was indicative of treatment failure. All patients were infected with T. cruzi DTU I populations. At Pre-Tx their median Jaccard genetic distances were 0.775 [IQR = 0.708 to 0.882], decreasing in genetic variability towards the end of follow-up (Mann-Whitney U test p= 0.0031). Interestingly, no Post-Tx minicircle signature was identical to its Pre-Tx counterpart population in a same patient, revealing selection of parasite subpopulations between the primary infection and Post-Tx. The parasitic populations isolated from hemocultures showed a lower number of bands in the minicircle signatures with respect to the signatures obtained directly from the patients’ blood samples, demonstrating a process of parasitic selection and reduction of the population variability that initially infected the patients. Decrease of parasitic loads after treatment as well as Pre- and Post-Tx intra-TcI diversity might be a consequence of both, natural evolution of the acute infection to the chronic phase and persistence of refractory populations due to Tx selection. Frontiers Media S.A. 2021-04-28 /pmc/articles/PMC8121101/ /pubmed/33996636 http://dx.doi.org/10.3389/fcimb.2021.665063 Text en Copyright © 2021 Muñoz-Calderón, Díaz-Bello, Alarcón de Noya, Noya-González and Schijman https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Muñoz-Calderón, Arturo
Díaz-Bello, Zoraida
Alarcón de Noya, Belkisyolé
Noya-González, Oscar O.
Schijman, Alejandro G.
Characterization and Follow-Up of Trypanosoma cruzi Natural Populations Refractory to Etiological Chemotherapy in Oral Chagas Disease Patients
title Characterization and Follow-Up of Trypanosoma cruzi Natural Populations Refractory to Etiological Chemotherapy in Oral Chagas Disease Patients
title_full Characterization and Follow-Up of Trypanosoma cruzi Natural Populations Refractory to Etiological Chemotherapy in Oral Chagas Disease Patients
title_fullStr Characterization and Follow-Up of Trypanosoma cruzi Natural Populations Refractory to Etiological Chemotherapy in Oral Chagas Disease Patients
title_full_unstemmed Characterization and Follow-Up of Trypanosoma cruzi Natural Populations Refractory to Etiological Chemotherapy in Oral Chagas Disease Patients
title_short Characterization and Follow-Up of Trypanosoma cruzi Natural Populations Refractory to Etiological Chemotherapy in Oral Chagas Disease Patients
title_sort characterization and follow-up of trypanosoma cruzi natural populations refractory to etiological chemotherapy in oral chagas disease patients
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121101/
https://www.ncbi.nlm.nih.gov/pubmed/33996636
http://dx.doi.org/10.3389/fcimb.2021.665063
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