The diagnostic value of two antigenic domains derived from the Trypanosoma cruzi Tc323 protein in chronic Chagas disease: a study in Brazil

The diagnosis of chronic infection with the parasite Trypanosoma cruzi relies on detecting specific IgG antibodies using two or three (in the case of discordance) serological assays based on different principles. This diagnostic algorithm poses challenges in identifying patients with chronic Chagas...

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Main Authors: Micaela S. Ossowski, Ângelo Antônio Oliveira Silva, Emily Ferreira Santos, Leonardo Maia Leony, Fred Luciano Neves Santos, Karina A. Gómez
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1605755/full
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author Micaela S. Ossowski
Ângelo Antônio Oliveira Silva
Ângelo Antônio Oliveira Silva
Emily Ferreira Santos
Emily Ferreira Santos
Leonardo Maia Leony
Leonardo Maia Leony
Fred Luciano Neves Santos
Fred Luciano Neves Santos
Fred Luciano Neves Santos
Karina A. Gómez
author_facet Micaela S. Ossowski
Ângelo Antônio Oliveira Silva
Ângelo Antônio Oliveira Silva
Emily Ferreira Santos
Emily Ferreira Santos
Leonardo Maia Leony
Leonardo Maia Leony
Fred Luciano Neves Santos
Fred Luciano Neves Santos
Fred Luciano Neves Santos
Karina A. Gómez
author_sort Micaela S. Ossowski
collection DOAJ
description The diagnosis of chronic infection with the parasite Trypanosoma cruzi relies on detecting specific IgG antibodies using two or three (in the case of discordance) serological assays based on different principles. This diagnostic algorithm poses challenges in identifying patients with chronic Chagas disease (CCD), particularly in endemic areas where financial and human resources are scarce. The discovery of new antigens capable of achieving 100% sensitivity and specificity is a priority in this field. Previously, we introduced two recombinant domains, designated as rTcD3 and rTcD6 derived from a hypothetical protein from T. cruzi, as potential candidates for the diagnosis of CCD. In the current study, we extended our results by assessing the diagnostic accuracy of rTcD3 and rTcD6 in a large cohort of infected and non-infected individuals from various regions of Brazil. Both antigens showed a specificity of 97.9%, while sensitivity was 79.5% for rTcD3 and 81.5% for rTcD6. In addition, cross-reactivity analysis on 764 samples from individuals with other parasitic, bacterial and viral infections was estimated to be less than 0.9%. Specifically, one (for rTcD3) and two (for rTcD6) samples positive for leptospirosis reacted with both antigens, while 2 out of 764 samples from individuals infected with Leishmania spp., resulted in a false positive for rTcD3, while four samples behaved similarly for rTcD6. Furthermore, a false-positive reaction was also observed in one HIV-positive sample rTcD6. In conclusion, this study provides further evidence supporting the diagnostic potential of a specific and sensitive IgG-ELISA based on rTcD3 and rTcD6 for detecting chronic T. cruzi infection across various regions of the Americas, with minimal cross-reactivity with other pathogens.
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spelling doaj-art-ce49ffe3abc24be4a751df7b0990067c2025-08-20T03:44:58ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-06-011610.3389/fmicb.2025.16057551605755The diagnostic value of two antigenic domains derived from the Trypanosoma cruzi Tc323 protein in chronic Chagas disease: a study in BrazilMicaela S. Ossowski0Ângelo Antônio Oliveira Silva1Ângelo Antônio Oliveira Silva2Emily Ferreira Santos3Emily Ferreira Santos4Leonardo Maia Leony5Leonardo Maia Leony6Fred Luciano Neves Santos7Fred Luciano Neves Santos8Fred Luciano Neves Santos9Karina A. Gómez10Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Buenos Aires, ArgentinaAdvanced Health Public Laboratory, Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ-BA), Salvador, BrazilInterdisciplinary Research Group in Biotechnology and Epidemiology of Infectious Diseases (GRUPIBE), Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ-BA), Salvador, BrazilAdvanced Health Public Laboratory, Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ-BA), Salvador, BrazilInterdisciplinary Research Group in Biotechnology and Epidemiology of Infectious Diseases (GRUPIBE), Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ-BA), Salvador, BrazilAdvanced Health Public Laboratory, Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ-BA), Salvador, BrazilInterdisciplinary Research Group in Biotechnology and Epidemiology of Infectious Diseases (GRUPIBE), Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ-BA), Salvador, BrazilAdvanced Health Public Laboratory, Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ-BA), Salvador, BrazilInterdisciplinary Research Group in Biotechnology and Epidemiology of Infectious Diseases (GRUPIBE), Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ-BA), Salvador, BrazilIntegrated Translational Program in Chagas Disease from Fiocruz (Fio-Chagas), Rio de Janeiro, BrazilInstituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Buenos Aires, ArgentinaThe diagnosis of chronic infection with the parasite Trypanosoma cruzi relies on detecting specific IgG antibodies using two or three (in the case of discordance) serological assays based on different principles. This diagnostic algorithm poses challenges in identifying patients with chronic Chagas disease (CCD), particularly in endemic areas where financial and human resources are scarce. The discovery of new antigens capable of achieving 100% sensitivity and specificity is a priority in this field. Previously, we introduced two recombinant domains, designated as rTcD3 and rTcD6 derived from a hypothetical protein from T. cruzi, as potential candidates for the diagnosis of CCD. In the current study, we extended our results by assessing the diagnostic accuracy of rTcD3 and rTcD6 in a large cohort of infected and non-infected individuals from various regions of Brazil. Both antigens showed a specificity of 97.9%, while sensitivity was 79.5% for rTcD3 and 81.5% for rTcD6. In addition, cross-reactivity analysis on 764 samples from individuals with other parasitic, bacterial and viral infections was estimated to be less than 0.9%. Specifically, one (for rTcD3) and two (for rTcD6) samples positive for leptospirosis reacted with both antigens, while 2 out of 764 samples from individuals infected with Leishmania spp., resulted in a false positive for rTcD3, while four samples behaved similarly for rTcD6. Furthermore, a false-positive reaction was also observed in one HIV-positive sample rTcD6. In conclusion, this study provides further evidence supporting the diagnostic potential of a specific and sensitive IgG-ELISA based on rTcD3 and rTcD6 for detecting chronic T. cruzi infection across various regions of the Americas, with minimal cross-reactivity with other pathogens.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1605755/fullTrypanosoma cruzichronic Chagas diseaseTc323diagnosisELISA
spellingShingle Micaela S. Ossowski
Ângelo Antônio Oliveira Silva
Ângelo Antônio Oliveira Silva
Emily Ferreira Santos
Emily Ferreira Santos
Leonardo Maia Leony
Leonardo Maia Leony
Fred Luciano Neves Santos
Fred Luciano Neves Santos
Fred Luciano Neves Santos
Karina A. Gómez
The diagnostic value of two antigenic domains derived from the Trypanosoma cruzi Tc323 protein in chronic Chagas disease: a study in Brazil
Frontiers in Microbiology
Trypanosoma cruzi
chronic Chagas disease
Tc323
diagnosis
ELISA
title The diagnostic value of two antigenic domains derived from the Trypanosoma cruzi Tc323 protein in chronic Chagas disease: a study in Brazil
title_full The diagnostic value of two antigenic domains derived from the Trypanosoma cruzi Tc323 protein in chronic Chagas disease: a study in Brazil
title_fullStr The diagnostic value of two antigenic domains derived from the Trypanosoma cruzi Tc323 protein in chronic Chagas disease: a study in Brazil
title_full_unstemmed The diagnostic value of two antigenic domains derived from the Trypanosoma cruzi Tc323 protein in chronic Chagas disease: a study in Brazil
title_short The diagnostic value of two antigenic domains derived from the Trypanosoma cruzi Tc323 protein in chronic Chagas disease: a study in Brazil
title_sort diagnostic value of two antigenic domains derived from the trypanosoma cruzi tc323 protein in chronic chagas disease a study in brazil
topic Trypanosoma cruzi
chronic Chagas disease
Tc323
diagnosis
ELISA
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1605755/full
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