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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/270673
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-22T11:58:56Zoai: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:34982025-10-22 11:58:56.558CONICET 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
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv 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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