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dc.contributor.author
Ramirez Gomez, Juan Carlos
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Acevedo, Gonzalo Raúl
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Torres, Carolina
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Parrado, Rudy
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De La Barra, Anabelle
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Villarroel, Sandro
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García, Lineth
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Gascon, Joaquim
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Ortiz, Lourdes
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Torrico, Faustino
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Ribeiro, Isabela
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Schijman, Alejandro Gabriel
dc.date.available
2022-05-13T20:35:13Z
dc.date.issued
2022-03
dc.identifier.citation
Ramirez Gomez, Juan Carlos; Acevedo, Gonzalo Raúl; Torres, Carolina; Parrado, Rudy; De La Barra, Anabelle; et al.; Genetic polymorphism of Trypanosoma cruzi bloodstream populations in adult chronic indeterminate Chagas disease patients from the E1224 clinical trial; Oxford University Press; Journal of Antimicrobial Chemotherapy; 77; 3; 3-2022; 578-584
dc.identifier.issn
0305-7453
dc.identifier.uri
http://hdl.handle.net/11336/157526
dc.description.abstract
Background: The role that the genetic diversity of natural Trypanosoma cruzi populations plays in response to trypanocidal treatment of chronic Chagas disease (CD) patients remains to be understood. We analysed the genetic polymorphisms of parasite bloodstream populations infecting chronic CD patients enrolled in the E1224 clinical trial. Methods: A total of 506 baseline and post-treatment follow-up samples from 188 patients were analysed. T. cruzi satellite DNA (satDNA) was amplified and sequenced using cruzi1/cruzi2 primers, and samples with TcI/ III, TcII, TcIV or hybrid satDNA sequences were identified. Minicircle signatures were obtained after kinetoplast DNA amplification using 121/122 primers and restriction enzyme digestion. Genetic distances between baseline and post-treatment minicircle signatures were estimated using the Jaccard coefficient. Results: At baseline, 74.3% TcII, 17.9% hybrid and 7.8% TcI/III satDNA sequences were found, whereas at the end of follow-up the distribution was 55.2% TcII, 35.2% hybrid and 9.5% TcI/III. The placebo arm was the treatment group with the highest variation of satDNA sequences between baseline and post-treatment follow-up. Genetic distances between baseline and post-treatment minicircle signatures were similar among all treatment arms. No association between minicircle signature variability and satDNA type distribution was found. Conclusions: Genetic variability of T. cruzi bloodstream populations during post-treatment follow-up did not differ from that observed during chronic infection in the absence of treatment, suggesting that there were no selection events of E1224-resistant parasite populations. This is the first report documenting the genetic polymorphism of natural T. cruzi populations in chronic patients in the context of clinical trials with trypanocidal drugs.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford University Press
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
TRYPANOSOMA CRUZI
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GENETIC POLYMORPHISM
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CHAGAS DISEASE
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CLINICAL TRIAL
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TRYPANOCIDAL TREATMENT
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Enfermedades Infecciosas
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Genetic polymorphism of Trypanosoma cruzi bloodstream populations in adult chronic indeterminate Chagas disease patients from the E1224 clinical trial
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-05-12T06:30:02Z
dc.identifier.eissn
1460-2091
dc.journal.volume
77
dc.journal.number
3
dc.journal.pagination
578-584
dc.journal.pais
Reino Unido
dc.journal.ciudad
Oxford
dc.description.fil
Fil: Ramirez Gomez, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
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Fil: Acevedo, Gonzalo Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Torres, Carolina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones en Bacteriología y Virología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
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Fil: Parrado, Rudy. Universidad Mayor de San Simón; Bolivia
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Fil: De La Barra, Anabelle. Universidad Mayor de San Simón; Bolivia
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Fil: Villarroel, Sandro. Universidad Mayor de San Simón; Bolivia
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Fil: García, Lineth. Universidad Mayor de San Simón; Bolivia
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Fil: Gascon, Joaquim. Universidad de Barcelona; España
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Fil: Ortiz, Lourdes. Universidad Autónoma Juan Misael Saracho; Bolivia
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Fil: Torrico, Faustino. Colectivo de Estudios Aplicados y Desarrollo Social; Bolivia
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Fil: Ribeiro, Isabela. Drugs for Neglected Diseases Initiative; Suiza
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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
dc.journal.title
Journal of Antimicrobial Chemotherapy
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkab446/6448275
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1093/jac/dkab446
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