Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal d...

Autores
Muñoz Calderon, Arturo Alejandro; Díaz Bello, Zoraida; Alarcón de Noya, Belkisyolé; Schijman, Alejandro Gabriel
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Oral transmission of Chagas disease (OChD) is an increasingly important aspect in the epidemiology. Venezuela has reported the two largest outbreaks described so far, affecting a total of 192 people mostly children. The long-term impact after treatment on the dynamics of infection in natural populations of T. cruzi is still unclear. In this sense, we proposed a genetic characterization of T. cruzi populations present in peripheral blood in order to differentiate responder or non-responder patients and predict the response to treatment (Tmt). We performed quantification of the parasitic load by qPCR, genetic typing of T. cruzi populations by multiplex qPCR of nuclear genome markers and RFLP-PCR for the hypervariable region of T. cruzi kDNA to demonstrate changes in Minicircle signatures (Ms) of the parasite populations present in 41 clinical samples from 15 patients. To reflect the genetic diversity found, Jaccard distances (Jd) values were compared. This clinical monitoring confirmed the presence of T. cruzi DNA in 26 post-treatment samples up to 9 years after Tmt. These results reveal 100 % therapeutic failure for both outbreaks of OChD, classifying these patients as non-responders to Tmt. All samples showed homogeneity at the DTU level, being typified as TcI. The Ms showed a high degree of polymorphism, with 73 % of total post-Tmt samples with Jd values close to 1. Analyzing the dynamics of each patient`s population separately, in all post-Tmt samples the change in Ms variability respect to pre-Tmt sample was not statistically significant. This variability does not reflect a natural or induced clonal selection process driven by the etiological Tmt; on the contrary, it could be associated with the clonal histotropism process evidenced in natural T. cruzi infections. In conclusion, these strategies of molecular characterization of parasite DNA were useful to detect Tmt failure and find out the lack of parasite population selection with Tmt in these OChD settings.
Fil: Muñoz Calderon, Arturo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Díaz Bello, Zoraida. Instituto de Medicina Tropical "Dr. Felix Pifano"; Venezuela
Fil: Alarcón de Noya, Belkisyolé. Instituto de Medicina Tropical "Dr. Felix Pifano"; Venezuela
Fil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimenta
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Materia
Trypanosoma cruzi
Oral Chagas disease
Treatment
Follow up
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/202025
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/202025
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugsMuñoz Calderon, Arturo AlejandroDíaz Bello, ZoraidaAlarcón de Noya, BelkisyoléSchijman, Alejandro GabrielTrypanosoma cruziOral Chagas diseaseTreatmentFollow uphttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Oral transmission of Chagas disease (OChD) is an increasingly important aspect in the epidemiology. Venezuela has reported the two largest outbreaks described so far, affecting a total of 192 people mostly children. The long-term impact after treatment on the dynamics of infection in natural populations of T. cruzi is still unclear. In this sense, we proposed a genetic characterization of T. cruzi populations present in peripheral blood in order to differentiate responder or non-responder patients and predict the response to treatment (Tmt). We performed quantification of the parasitic load by qPCR, genetic typing of T. cruzi populations by multiplex qPCR of nuclear genome markers and RFLP-PCR for the hypervariable region of T. cruzi kDNA to demonstrate changes in Minicircle signatures (Ms) of the parasite populations present in 41 clinical samples from 15 patients. To reflect the genetic diversity found, Jaccard distances (Jd) values were compared. This clinical monitoring confirmed the presence of T. cruzi DNA in 26 post-treatment samples up to 9 years after Tmt. These results reveal 100 % therapeutic failure for both outbreaks of OChD, classifying these patients as non-responders to Tmt. All samples showed homogeneity at the DTU level, being typified as TcI. The Ms showed a high degree of polymorphism, with 73 % of total post-Tmt samples with Jd values close to 1. Analyzing the dynamics of each patient`s population separately, in all post-Tmt samples the change in Ms variability respect to pre-Tmt sample was not statistically significant. This variability does not reflect a natural or induced clonal selection process driven by the etiological Tmt; on the contrary, it could be associated with the clonal histotropism process evidenced in natural T. cruzi infections. In conclusion, these strategies of molecular characterization of parasite DNA were useful to detect Tmt failure and find out the lack of parasite population selection with Tmt in these OChD settings.Fil: Muñoz Calderon, Arturo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Díaz Bello, Zoraida. Instituto de Medicina Tropical "Dr. Felix Pifano"; VenezuelaFil: Alarcón de Noya, Belkisyolé. Instituto de Medicina Tropical "Dr. Felix Pifano"; VenezuelaFil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentaSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/202025Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugs; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 123-1230025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:36Zoai:ri.conicet.gov.ar:11336/202025instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:33:36.659CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugs
title Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugs
spellingShingle Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugs
Muñoz Calderon, Arturo Alejandro
Trypanosoma cruzi
Oral Chagas disease
Treatment
Follow up
title_short Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugs
title_full Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugs
title_fullStr Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugs
title_full_unstemmed Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugs
title_sort Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugs
dc.creator.none.fl_str_mv Muñoz Calderon, Arturo Alejandro
Díaz Bello, Zoraida
Alarcón de Noya, Belkisyolé
Schijman, Alejandro Gabriel
author Muñoz Calderon, Arturo Alejandro
author_facet Muñoz Calderon, Arturo Alejandro
Díaz Bello, Zoraida
Alarcón de Noya, Belkisyolé
Schijman, Alejandro Gabriel
author_role author
author2 Díaz Bello, Zoraida
Alarcón de Noya, Belkisyolé
Schijman, Alejandro Gabriel
author2_role author
author
author
dc.subject.none.fl_str_mv Trypanosoma cruzi
Oral Chagas disease
Treatment
Follow up
topic Trypanosoma cruzi
Oral Chagas disease
Treatment
Follow up
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Oral transmission of Chagas disease (OChD) is an increasingly important aspect in the epidemiology. Venezuela has reported the two largest outbreaks described so far, affecting a total of 192 people mostly children. The long-term impact after treatment on the dynamics of infection in natural populations of T. cruzi is still unclear. In this sense, we proposed a genetic characterization of T. cruzi populations present in peripheral blood in order to differentiate responder or non-responder patients and predict the response to treatment (Tmt). We performed quantification of the parasitic load by qPCR, genetic typing of T. cruzi populations by multiplex qPCR of nuclear genome markers and RFLP-PCR for the hypervariable region of T. cruzi kDNA to demonstrate changes in Minicircle signatures (Ms) of the parasite populations present in 41 clinical samples from 15 patients. To reflect the genetic diversity found, Jaccard distances (Jd) values were compared. This clinical monitoring confirmed the presence of T. cruzi DNA in 26 post-treatment samples up to 9 years after Tmt. These results reveal 100 % therapeutic failure for both outbreaks of OChD, classifying these patients as non-responders to Tmt. All samples showed homogeneity at the DTU level, being typified as TcI. The Ms showed a high degree of polymorphism, with 73 % of total post-Tmt samples with Jd values close to 1. Analyzing the dynamics of each patient`s population separately, in all post-Tmt samples the change in Ms variability respect to pre-Tmt sample was not statistically significant. This variability does not reflect a natural or induced clonal selection process driven by the etiological Tmt; on the contrary, it could be associated with the clonal histotropism process evidenced in natural T. cruzi infections. In conclusion, these strategies of molecular characterization of parasite DNA were useful to detect Tmt failure and find out the lack of parasite population selection with Tmt in these OChD settings.
Fil: Muñoz Calderon, Arturo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Díaz Bello, Zoraida. Instituto de Medicina Tropical "Dr. Felix Pifano"; Venezuela
Fil: Alarcón de Noya, Belkisyolé. Instituto de Medicina Tropical "Dr. Felix Pifano"; Venezuela
Fil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimenta
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
description Oral transmission of Chagas disease (OChD) is an increasingly important aspect in the epidemiology. Venezuela has reported the two largest outbreaks described so far, affecting a total of 192 people mostly children. The long-term impact after treatment on the dynamics of infection in natural populations of T. cruzi is still unclear. In this sense, we proposed a genetic characterization of T. cruzi populations present in peripheral blood in order to differentiate responder or non-responder patients and predict the response to treatment (Tmt). We performed quantification of the parasitic load by qPCR, genetic typing of T. cruzi populations by multiplex qPCR of nuclear genome markers and RFLP-PCR for the hypervariable region of T. cruzi kDNA to demonstrate changes in Minicircle signatures (Ms) of the parasite populations present in 41 clinical samples from 15 patients. To reflect the genetic diversity found, Jaccard distances (Jd) values were compared. This clinical monitoring confirmed the presence of T. cruzi DNA in 26 post-treatment samples up to 9 years after Tmt. These results reveal 100 % therapeutic failure for both outbreaks of OChD, classifying these patients as non-responders to Tmt. All samples showed homogeneity at the DTU level, being typified as TcI. The Ms showed a high degree of polymorphism, with 73 % of total post-Tmt samples with Jd values close to 1. Analyzing the dynamics of each patient`s population separately, in all post-Tmt samples the change in Ms variability respect to pre-Tmt sample was not statistically significant. This variability does not reflect a natural or induced clonal selection process driven by the etiological Tmt; on the contrary, it could be associated with the clonal histotropism process evidenced in natural T. cruzi infections. In conclusion, these strategies of molecular characterization of parasite DNA were useful to detect Tmt failure and find out the lack of parasite population selection with Tmt in these OChD settings.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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Journal
http://purl.org/coar/resource_type/c_5794
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status_str publishedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/202025
Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugs; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 123-123
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/202025
identifier_str_mv Genetic diversity of natural populations of Trypanosoma cruzi in clinical samples from patients with oral Chagas disease in Venezuela: Follow-up after treatment with trypanocidal drugs; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 123-123
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdf
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dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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