Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate mon...
- Autores
- White, Brooke E.; Hodo, Carolyn L; Hamer, Sarah; Saunders, Ashley B; Laucella, Susana Adriana; Hall, Daniel B; Tarleton, Rick L.
- Año de publicación
- 2025
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Infection with the protozoan parasite Trypanosoma cruzi is generally well-controlledby host immune responses, but appears to be rarely eliminated. The resulting persistent, low-levelinfection results in cumulative tissue damage with the greatest impact generally in the heart in theform of chagasic cardiomyopathy. The relative success in immune control of T. cruzi infection usually averts acute phase death but has the negative consequence that the low-levelpresence of T. cruzi in hosts is challenging to detect unequivocally. Thus, it is difficult to identify those who are infected and, as well, problematic to gauge the impact of treatment, particularly in the evaluation of the relative efficacy of new drugs. In this study, we employ DNA fragmentation and high numbers of replicate PCR reaction (‘deep-sampling’) and to extend the quantitative range of detecting T. cruzi in blood by at least three orders of magnitude relative to current protocols. When combined with sampling blood at multiple time points, deep sampling of fragmented DNA allowed for detection of T. cruzi in all infected hosts in multiple host species, including humans, macaques, and dogs. In addition, we provide evidence for a number of characteristics not previously rigorously quantified in the population of hosts with naturally acquired T. cruzi infection, including, a >6 log variation between chronically infected individuals in the stable parasite levels, a continuing decline in parasite load during the second and third years of infection in some hosts, and the potential for parasite load to change dramatically when health conditions change. Although requiring strict adherence to contamination– prevention protocols and significant resources, deep-samplingPCR provides an important new tool for assessing therapies and for addressing long-standingquestions in T. cruzi infection and Chagas disease.
Fil: White, Brooke E.. Center For Tropical And Emerging Global Diseases; Estados Unidos
Fil: Hodo, Carolyn L. University Of Texas Health Science Center At Houston.; Estados Unidos
Fil: Hamer, Sarah. Texas A&M University; Estados Unidos
Fil: Saunders, Ashley B. Texas A&M University; Estados Unidos
Fil: Laucella, Susana Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Hall, Daniel B. University of Georgia; Estados Unidos
Fil: Tarleton, Rick L.. University of Georgia; Estados Unidos - Materia
-
Chagas
Trypanosoma cruzi
PCR
parasite load - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/270673
Ver los metadatos del registro completo
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CONICET Digital (CONICET) |
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Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatmentWhite, Brooke E.Hodo, Carolyn LHamer, SarahSaunders, Ashley BLaucella, Susana AdrianaHall, Daniel BTarleton, Rick L.ChagasTrypanosoma cruziPCRparasite loadhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Infection with the protozoan parasite Trypanosoma cruzi is generally well-controlledby host immune responses, but appears to be rarely eliminated. The resulting persistent, low-levelinfection results in cumulative tissue damage with the greatest impact generally in the heart in theform of chagasic cardiomyopathy. The relative success in immune control of T. cruzi infection usually averts acute phase death but has the negative consequence that the low-levelpresence of T. cruzi in hosts is challenging to detect unequivocally. Thus, it is difficult to identify those who are infected and, as well, problematic to gauge the impact of treatment, particularly in the evaluation of the relative efficacy of new drugs. In this study, we employ DNA fragmentation and high numbers of replicate PCR reaction (‘deep-sampling’) and to extend the quantitative range of detecting T. cruzi in blood by at least three orders of magnitude relative to current protocols. When combined with sampling blood at multiple time points, deep sampling of fragmented DNA allowed for detection of T. cruzi in all infected hosts in multiple host species, including humans, macaques, and dogs. In addition, we provide evidence for a number of characteristics not previously rigorously quantified in the population of hosts with naturally acquired T. cruzi infection, including, a >6 log variation between chronically infected individuals in the stable parasite levels, a continuing decline in parasite load during the second and third years of infection in some hosts, and the potential for parasite load to change dramatically when health conditions change. Although requiring strict adherence to contamination– prevention protocols and significant resources, deep-samplingPCR provides an important new tool for assessing therapies and for addressing long-standingquestions in T. cruzi infection and Chagas disease.Fil: White, Brooke E.. Center For Tropical And Emerging Global Diseases; Estados UnidosFil: Hodo, Carolyn L. University Of Texas Health Science Center At Houston.; Estados UnidosFil: Hamer, Sarah. Texas A&M University; Estados UnidosFil: Saunders, Ashley B. Texas A&M University; Estados UnidosFil: Laucella, Susana Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hall, Daniel B. University of Georgia; Estados UnidosFil: Tarleton, Rick L.. University of Georgia; Estados UnidoseLife Sciences Publications2025-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/270673White, Brooke E.; Hodo, Carolyn L; Hamer, Sarah; Saunders, Ashley B; Laucella, Susana Adriana; et al.; Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment; eLife Sciences Publications; eLife; 14; 4-2025; 1-192050-084XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/104547info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.104547info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:26:15Zoai:ri.conicet.gov.ar:11336/270673instacron: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 10:26:15.774CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment |
title |
Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment |
spellingShingle |
Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment White, Brooke E. Chagas Trypanosoma cruzi PCR parasite load |
title_short |
Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment |
title_full |
Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment |
title_fullStr |
Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment |
title_full_unstemmed |
Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment |
title_sort |
Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment |
dc.creator.none.fl_str_mv |
White, Brooke E. Hodo, Carolyn L Hamer, Sarah Saunders, Ashley B Laucella, Susana Adriana Hall, Daniel B Tarleton, Rick L. |
author |
White, Brooke E. |
author_facet |
White, Brooke E. Hodo, Carolyn L Hamer, Sarah Saunders, Ashley B Laucella, Susana Adriana Hall, Daniel B Tarleton, Rick L. |
author_role |
author |
author2 |
Hodo, Carolyn L Hamer, Sarah Saunders, Ashley B Laucella, Susana Adriana Hall, Daniel B Tarleton, Rick L. |
author2_role |
author author author author author author |
dc.subject.none.fl_str_mv |
Chagas Trypanosoma cruzi PCR parasite load |
topic |
Chagas Trypanosoma cruzi PCR parasite load |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Infection with the protozoan parasite Trypanosoma cruzi is generally well-controlledby host immune responses, but appears to be rarely eliminated. The resulting persistent, low-levelinfection results in cumulative tissue damage with the greatest impact generally in the heart in theform of chagasic cardiomyopathy. The relative success in immune control of T. cruzi infection usually averts acute phase death but has the negative consequence that the low-levelpresence of T. cruzi in hosts is challenging to detect unequivocally. Thus, it is difficult to identify those who are infected and, as well, problematic to gauge the impact of treatment, particularly in the evaluation of the relative efficacy of new drugs. In this study, we employ DNA fragmentation and high numbers of replicate PCR reaction (‘deep-sampling’) and to extend the quantitative range of detecting T. cruzi in blood by at least three orders of magnitude relative to current protocols. When combined with sampling blood at multiple time points, deep sampling of fragmented DNA allowed for detection of T. cruzi in all infected hosts in multiple host species, including humans, macaques, and dogs. In addition, we provide evidence for a number of characteristics not previously rigorously quantified in the population of hosts with naturally acquired T. cruzi infection, including, a >6 log variation between chronically infected individuals in the stable parasite levels, a continuing decline in parasite load during the second and third years of infection in some hosts, and the potential for parasite load to change dramatically when health conditions change. Although requiring strict adherence to contamination– prevention protocols and significant resources, deep-samplingPCR provides an important new tool for assessing therapies and for addressing long-standingquestions in T. cruzi infection and Chagas disease. Fil: White, Brooke E.. Center For Tropical And Emerging Global Diseases; Estados Unidos Fil: Hodo, Carolyn L. University Of Texas Health Science Center At Houston.; Estados Unidos Fil: Hamer, Sarah. Texas A&M University; Estados Unidos Fil: Saunders, Ashley B. Texas A&M University; Estados Unidos Fil: Laucella, Susana Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Hall, Daniel B. University of Georgia; Estados Unidos Fil: Tarleton, Rick L.. University of Georgia; Estados Unidos |
description |
Infection with the protozoan parasite Trypanosoma cruzi is generally well-controlledby host immune responses, but appears to be rarely eliminated. The resulting persistent, low-levelinfection results in cumulative tissue damage with the greatest impact generally in the heart in theform of chagasic cardiomyopathy. The relative success in immune control of T. cruzi infection usually averts acute phase death but has the negative consequence that the low-levelpresence of T. cruzi in hosts is challenging to detect unequivocally. Thus, it is difficult to identify those who are infected and, as well, problematic to gauge the impact of treatment, particularly in the evaluation of the relative efficacy of new drugs. In this study, we employ DNA fragmentation and high numbers of replicate PCR reaction (‘deep-sampling’) and to extend the quantitative range of detecting T. cruzi in blood by at least three orders of magnitude relative to current protocols. When combined with sampling blood at multiple time points, deep sampling of fragmented DNA allowed for detection of T. cruzi in all infected hosts in multiple host species, including humans, macaques, and dogs. In addition, we provide evidence for a number of characteristics not previously rigorously quantified in the population of hosts with naturally acquired T. cruzi infection, including, a >6 log variation between chronically infected individuals in the stable parasite levels, a continuing decline in parasite load during the second and third years of infection in some hosts, and the potential for parasite load to change dramatically when health conditions change. Although requiring strict adherence to contamination– prevention protocols and significant resources, deep-samplingPCR provides an important new tool for assessing therapies and for addressing long-standingquestions in T. cruzi infection and Chagas disease. |
publishDate |
2025 |
dc.date.none.fl_str_mv |
2025-04 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/270673 White, Brooke E.; Hodo, Carolyn L; Hamer, Sarah; Saunders, Ashley B; Laucella, Susana Adriana; et al.; Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment; eLife Sciences Publications; eLife; 14; 4-2025; 1-19 2050-084X CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/270673 |
identifier_str_mv |
White, Brooke E.; Hodo, Carolyn L; Hamer, Sarah; Saunders, Ashley B; Laucella, Susana Adriana; et al.; Serial ‘deep-sampling’ PCR of fragmented DNA reveals the wide range of Trypanosoma cruzi burden among chronically infected human, macaque, and canine hosts, and allows accurate monitoring of parasite load following treatment; eLife Sciences Publications; eLife; 14; 4-2025; 1-19 2050-084X 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://elifesciences.org/articles/104547 info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.104547 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
eLife Sciences Publications |
publisher.none.fl_str_mv |
eLife Sciences Publications |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |