Authors: Pimenta Del Rei, Rodrigo; Leony, Leonardo Maia; Fiorani Celedon, Paola Alejandra; Zanchin, Nilson Ivo Tonin; Galvão dos Reis, Mitermayer; de Miranda Gomes, Yara; Schijman, Alejandro Gabriel; Longhi, Silvia Andrea; Neves Santos, Fred Luciano
Publication Date: 2019.
Background Laboratory diagnosis of chronic Chagas disease is a troubling factor due to lack of reference tests. The WHO suggests the use of two distinct commercial serological tests in parallel. The performance of commercial immunoassays might fluctuate depending on the antigenic matrices and the local strains of T. cruzi in different geographical settings. The use of antigenic matrices based on chimeric proteins can solve these limitations. Here, we evaluated the diagnostic performance of two chimeric T. cruzi antigens (IBMP-8.1 and -8.4) to diagnose chronic Chagas disease in individuals from endemic South American countries. Methodology/Principal findings IBMP-8.1 and IBMP-8.4 chimeric antigens were expressed as soluble proteins in E. coli and purified using chromatography methods. Reactivity of IBMP-8.1 and IBMP-8.4 was assessed using an in-house ELISA with sera from 122 non-infected and 215 T. cruzi-infected individuals from Argentina, Bolivia, and Paraguay. Cut-off values were based on ROC curves and performance parameters were determined using a dichotomous approach. Area under the curve values were > 99.7% for both IBMP-8.1 and IBMP-8.4 antigens. IgG levels in T. cruzi-positive and negative samples were higher for IBMP-8.4 than IBMP-8.1. Both IBMP-8.1 and -8.4 were 100% specific, while IBMP-8.4 were 100% sensitive compared to IBMP-8.1 (95.3%). Admitting RI values of 1.0 ± 0.10 as the inconclusive interval, 6.2% of the samples tested using IBMP-8.1 and 2.1% using IBMP-8.4 fell inside the grey zone. Based on accuracy and diagnostic odds ratio values, IBMP-8.4 presented the best performance. Differences in sensitivity and IgG levels among the samples from Argentina, Bolivia, and Paraguay were not significant. Conclusions/Significance Our findings showed a notable performance of IBMP-8.1 and -8.4 chimeric antigens in diagnosing chronic Chagas disease in individuals from endemic South American countries, confirming our hypothesis that these antigens could be used in geographical areas where distinct T. cruzi DTUs occur.
Author affiliation: Pimenta Del Rei, Rodrigo. Faculty of Technology and Sciences of Bahia; Brasil
Author affiliation: Leony, Leonardo Maia. Fundación Oswaldo Cruz; Brasil
Author affiliation: Fiorani Celedon, Paola Alejandra. Molecular Biology Institute of Parana; Brasil
Author affiliation: Zanchin, Nilson Ivo Tonin. Fundación Oswaldo Cruz; Brasil
Author affiliation: Galvão dos Reis, Mitermayer. Fundación Oswaldo Cruz; Brasil. Federal University of Bahia; Brasil. University of Yale; Estados Unidos
Author affiliation: de Miranda Gomes, Yara. Fundación Oswaldo Cruz; Brasil
Author affiliation: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Author affiliation: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Author affiliation: Neves Santos, Fred Luciano. Fundación Oswaldo Cruz; Brasil
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas