International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients

BACKGROUND: A century after its discovery, Chagas disease still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The purpose of this study was to evaluate the performan...

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Autores: Schijman, Alejandro G, Bisio, Margarita, Orellana, Liliana, Sued, Mariela, Duffy, Tomás, Mejia Jaramillo, Ana M, Cura, Carolina, Auter, Frederic, Veron, Vincent, Qvarnstrom, Yvonne, Deborggraeve, Stijn, Hijar, Gisely, Zulantay, Inés, Lucero, Raúl Horacio, Velazquez, Elsa, Tellez, Tatiana, Sanchez Leon, Zunilda, Galvão, Lucia, Nolder, Debbie, Monje Rumi, María, Levi, José E, Ramirez, Juan D, Zorrilla, Pilar, Flores-Chavez, Maria, Jercic, Maria I, Crisante, Gladys, Añez, Néstor, De Castro, Ana M, Gonzalez, Clara I, Acosta Viana, Karla, Yachelini, Pedro, Torrico, Faustino, Robello, Carlos, Diosque, Patricio, Triana Chavez, Omar, Aznar, Christine, Russomando, Graciela, Büscher, Philippe, Assal, Azzedine, Guhl, Felipe, Sosa Estani, Sergio, DaSilva, Alexandre, Britto, Constança, Luquetti, Alejandro, Ladzins, Janis
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6943
Acceso en línea:http://hdl.handle.net/20.500.12105/6943
Access Level:acceso abierto
Palabra clave:Chagas Disease
DNA, Protozoan
Humans
International Cooperation
Parasitology
Polymerase Chain Reaction
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/6943
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients
title International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients
spellingShingle International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients
Schijman, Alejandro G
Chagas Disease
DNA, Protozoan
Humans
International Cooperation
Parasitology
Polymerase Chain Reaction
title_short International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients
title_full International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients
title_fullStr International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients
title_full_unstemmed International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients
title_sort International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients
dc.creator.none.fl_str_mv Schijman, Alejandro G
Bisio, Margarita
Orellana, Liliana
Sued, Mariela
Duffy, Tomás
Mejia Jaramillo, Ana M
Cura, Carolina
Auter, Frederic
Veron, Vincent
Qvarnstrom, Yvonne
Deborggraeve, Stijn
Hijar, Gisely
Zulantay, Inés
Lucero, Raúl Horacio
Velazquez, Elsa
Tellez, Tatiana
Sanchez Leon, Zunilda
Galvão, Lucia
Nolder, Debbie
Monje Rumi, María
Levi, José E
Ramirez, Juan D
Zorrilla, Pilar
Flores-Chavez, Maria
Jercic, Maria I
Crisante, Gladys
Añez, Néstor
De Castro, Ana M
Gonzalez, Clara I
Acosta Viana, Karla
Yachelini, Pedro
Torrico, Faustino
Robello, Carlos
Diosque, Patricio
Triana Chavez, Omar
Aznar, Christine
Russomando, Graciela
Büscher, Philippe
Assal, Azzedine
Guhl, Felipe
Sosa Estani, Sergio
DaSilva, Alexandre
Britto, Constança
Luquetti, Alejandro
Ladzins, Janis
author Schijman, Alejandro G
author_facet Schijman, Alejandro G
Bisio, Margarita
Orellana, Liliana
Sued, Mariela
Duffy, Tomás
Mejia Jaramillo, Ana M
Cura, Carolina
Auter, Frederic
Veron, Vincent
Qvarnstrom, Yvonne
Deborggraeve, Stijn
Hijar, Gisely
Zulantay, Inés
Lucero, Raúl Horacio
Velazquez, Elsa
Tellez, Tatiana
Sanchez Leon, Zunilda
Galvão, Lucia
Nolder, Debbie
Monje Rumi, María
Levi, José E
Ramirez, Juan D
Zorrilla, Pilar
Flores-Chavez, Maria
Jercic, Maria I
Crisante, Gladys
Añez, Néstor
De Castro, Ana M
Gonzalez, Clara I
Acosta Viana, Karla
Yachelini, Pedro
Torrico, Faustino
Robello, Carlos
Diosque, Patricio
Triana Chavez, Omar
Aznar, Christine
Russomando, Graciela
Büscher, Philippe
Assal, Azzedine
Guhl, Felipe
Sosa Estani, Sergio
DaSilva, Alexandre
Britto, Constança
Luquetti, Alejandro
Ladzins, Janis
author_role author
author2 Bisio, Margarita
Orellana, Liliana
Sued, Mariela
Duffy, Tomás
Mejia Jaramillo, Ana M
Cura, Carolina
Auter, Frederic
Veron, Vincent
Qvarnstrom, Yvonne
Deborggraeve, Stijn
Hijar, Gisely
Zulantay, Inés
Lucero, Raúl Horacio
Velazquez, Elsa
Tellez, Tatiana
Sanchez Leon, Zunilda
Galvão, Lucia
Nolder, Debbie
Monje Rumi, María
Levi, José E
Ramirez, Juan D
Zorrilla, Pilar
Flores-Chavez, Maria
Jercic, Maria I
Crisante, Gladys
Añez, Néstor
De Castro, Ana M
Gonzalez, Clara I
Acosta Viana, Karla
Yachelini, Pedro
Torrico, Faustino
Robello, Carlos
Diosque, Patricio
Triana Chavez, Omar
Aznar, Christine
Russomando, Graciela
Büscher, Philippe
Assal, Azzedine
Guhl, Felipe
Sosa Estani, Sergio
DaSilva, Alexandre
Britto, Constança
Luquetti, Alejandro
Ladzins, Janis
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
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author
author
author
author
author
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author
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author
dc.contributor.none.fl_str_mv Organización Panamericana de la Salud
United Nations University
Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina)
World Health Organization (WHO/OMS)

dc.subject.none.fl_str_mv Chagas Disease
DNA, Protozoan
Humans
International Cooperation
Parasitology
Polymerase Chain Reaction
topic Chagas Disease
DNA, Protozoan
Humans
International Cooperation
Parasitology
Polymerase Chain Reaction
description BACKGROUND: A century after its discovery, Chagas disease still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The purpose of this study was to evaluate the performance of PCR methods in detection of Trypanosoma cruzi DNA by an external quality evaluation. METHODOLOGY/FINDINGS: An international collaborative study was launched by expert PCR laboratories from 16 countries. Currently used strategies were challenged against serial dilutions of purified DNA from stocks representing T. cruzi discrete typing units (DTU) I, IV and VI (set A), human blood spiked with parasite cells (set B) and Guanidine Hidrochloride-EDTA blood samples from 32 seropositive and 10 seronegative patients from Southern Cone countries (set C). Forty eight PCR tests were reported for set A and 44 for sets B and C; 28 targeted minicircle DNA (kDNA), 13 satellite DNA (Sat-DNA) and the remainder low copy number sequences. In set A, commercial master mixes and Sat-DNA Real Time PCR showed better specificity, but kDNA-PCR was more sensitive to detect DTU I DNA. In set B, commercial DNA extraction kits presented better specificity than solvent extraction protocols. Sat-DNA PCR tests had higher specificity, with sensitivities of 0.05-0.5 parasites/mL whereas specific kDNA tests detected 5.10(-3) par/mL. Sixteen specific and coherent methods had a Good Performance in both sets A and B (10 fg/µl of DNA from all stocks, 5 par/mL spiked blood). The median values of sensitivities, specificities and accuracies obtained in testing the Set C samples with the 16 tests determined to be good performing by analyzing Sets A and B samples varied considerably. Out of them, four methods depicted the best performing parameters in all three sets of samples, detecting at least 10 fg/µl for each DNA stock, 0.5 par/mL and a sensitivity between 83.3-94.4%, specificity of 85-95%, accuracy of 86.8-89.5% and kappa index of 0.7-0.8 compared to consensus PCR reports of the 16 good performing tests and 63-69%, 100%, 71.4-76.2% and 0.4-0.5, respectively compared to serodiagnosis. Method LbD2 used solvent extraction followed by Sybr-Green based Real time PCR targeted to Sat-DNA; method LbD3 used solvent DNA extraction followed by conventional PCR targeted to Sat-DNA. The third method (LbF1) used glass fiber column based DNA extraction followed by TaqMan Real Time PCR targeted to Sat-DNA (cruzi 1/cruzi 2 and cruzi 3 TaqMan probe) and the fourth method (LbQ) used solvent DNA extraction followed by conventional hot-start PCR targeted to kDNA (primer pairs 121/122). These four methods were further evaluated at the coordinating laboratory in a subset of human blood samples, confirming the performance obtained by the participating laboratories. CONCLUSION/SIGNIFICANCE: This study represents a first crucial step towards international validation of PCR procedures for detection of T. cruzi in human blood samples.
publishDate 2011
dc.date.none.fl_str_mv 2011
2011-01-11
2011
2011-01-11
2018
2018-12-26
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/6943
url http://hdl.handle.net/20.500.12105/6943
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLOS)
publisher.none.fl_str_mv Public Library of Science (PLOS)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patientsSchijman, Alejandro GBisio, MargaritaOrellana, LilianaSued, MarielaDuffy, TomásMejia Jaramillo, Ana MCura, CarolinaAuter, FredericVeron, VincentQvarnstrom, YvonneDeborggraeve, StijnHijar, GiselyZulantay, InésLucero, Raúl HoracioVelazquez, ElsaTellez, TatianaSanchez Leon, ZunildaGalvão, LuciaNolder, DebbieMonje Rumi, MaríaLevi, José ERamirez, Juan DZorrilla, PilarFlores-Chavez, MariaJercic, Maria ICrisante, GladysAñez, NéstorDe Castro, Ana MGonzalez, Clara IAcosta Viana, KarlaYachelini, PedroTorrico, FaustinoRobello, CarlosDiosque, PatricioTriana Chavez, OmarAznar, ChristineRussomando, GracielaBüscher, PhilippeAssal, AzzedineGuhl, FelipeSosa Estani, SergioDaSilva, AlexandreBritto, ConstançaLuquetti, AlejandroLadzins, JanisChagas DiseaseDNA, ProtozoanHumansInternational CooperationParasitologyPolymerase Chain ReactionBACKGROUND: A century after its discovery, Chagas disease still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The purpose of this study was to evaluate the performance of PCR methods in detection of Trypanosoma cruzi DNA by an external quality evaluation. METHODOLOGY/FINDINGS: An international collaborative study was launched by expert PCR laboratories from 16 countries. Currently used strategies were challenged against serial dilutions of purified DNA from stocks representing T. cruzi discrete typing units (DTU) I, IV and VI (set A), human blood spiked with parasite cells (set B) and Guanidine Hidrochloride-EDTA blood samples from 32 seropositive and 10 seronegative patients from Southern Cone countries (set C). Forty eight PCR tests were reported for set A and 44 for sets B and C; 28 targeted minicircle DNA (kDNA), 13 satellite DNA (Sat-DNA) and the remainder low copy number sequences. In set A, commercial master mixes and Sat-DNA Real Time PCR showed better specificity, but kDNA-PCR was more sensitive to detect DTU I DNA. In set B, commercial DNA extraction kits presented better specificity than solvent extraction protocols. Sat-DNA PCR tests had higher specificity, with sensitivities of 0.05-0.5 parasites/mL whereas specific kDNA tests detected 5.10(-3) par/mL. Sixteen specific and coherent methods had a Good Performance in both sets A and B (10 fg/µl of DNA from all stocks, 5 par/mL spiked blood). The median values of sensitivities, specificities and accuracies obtained in testing the Set C samples with the 16 tests determined to be good performing by analyzing Sets A and B samples varied considerably. Out of them, four methods depicted the best performing parameters in all three sets of samples, detecting at least 10 fg/µl for each DNA stock, 0.5 par/mL and a sensitivity between 83.3-94.4%, specificity of 85-95%, accuracy of 86.8-89.5% and kappa index of 0.7-0.8 compared to consensus PCR reports of the 16 good performing tests and 63-69%, 100%, 71.4-76.2% and 0.4-0.5, respectively compared to serodiagnosis. Method LbD2 used solvent extraction followed by Sybr-Green based Real time PCR targeted to Sat-DNA; method LbD3 used solvent DNA extraction followed by conventional PCR targeted to Sat-DNA. The third method (LbF1) used glass fiber column based DNA extraction followed by TaqMan Real Time PCR targeted to Sat-DNA (cruzi 1/cruzi 2 and cruzi 3 TaqMan probe) and the fourth method (LbQ) used solvent DNA extraction followed by conventional hot-start PCR targeted to kDNA (primer pairs 121/122). These four methods were further evaluated at the coordinating laboratory in a subset of human blood samples, confirming the performance obtained by the participating laboratories. CONCLUSION/SIGNIFICANCE: This study represents a first crucial step towards international validation of PCR procedures for detection of T. cruzi in human blood samples.Public Library of Science (PLOS)Organización Panamericana de la SaludUnited Nations UniversityConsejo Nacional de Investigaciones Científicas y Técnicas (Argentina)World Health Organization (WHO/OMS)20182018-12-2620112011-01-1120112011-01-11research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/6943reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/69432026-06-12T12:43:37Z
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