scholarly journals Serological Diagnosis of Chronic Chagas Disease: Is It Time for a Change?

2016 ◽  
Vol 54 (6) ◽  
pp. 1566-1572 ◽  
Author(s):  
Alba Abras ◽  
Montserrat Gállego ◽  
Teresa Llovet ◽  
Silvia Tebar ◽  
Mercedes Herrero ◽  
...  
Keyword(s):  
Chagas Disease ◽  
False Positive ◽  
Disease Diagnosis ◽  
Cross Reactivity ◽  
Human Migration ◽  
Serological Diagnosis ◽  
Content Type ◽  
New Generation ◽  
Single Technique ◽  
Chronic Chagas Disease

Chagas disease has spread to areas that are nonendemic for the disease with human migration. Since no single reference standard test is available, serological diagnosis of chronic Chagas disease requires at least two tests. New-generation techniques have significantly improved the accuracy of Chagas disease diagnosis by the use of a large mixture of recombinant antigens with different detection systems, such as chemiluminescence. The aim of the present study was to assess the overall accuracy of a new-generation kit, the Architect Chagas (cutoff, ≥1 sample relative light units/cutoff value [S/CO]), as a single technique for the diagnosis of chronic Chagas disease. The Architect Chagas showed a sensitivity of 100% (95% confidence interval [CI], 99.5 to 100%) and a specificity of 97.6% (95% CI, 95.2 to 99.9%). Five out of six false-positive serum samples were a consequence of cross-reactivity withLeishmaniaspp., and all of them achieved results of <5 S/CO. We propose the Architect Chagas as a single technique for screening in blood banks and for routine diagnosis in clinical laboratories. Only gray-zone and positive sera with a result of ≤6 S/CO would need to be confirmed by a second serological assay, thus avoiding false-positive sera and the problem of cross-reactivity withLeishmaniaspecies. The application of this proposal would result in important savings in the cost of Chagas disease diagnosis and therefore in the management and control of the disease.

scholarly journals Cross-Reactivity Using Chimeric Trypanosoma cruzi Antigens: Diagnostic Performance in Settings Where Chagas Disease and American Cutaneous or Visceral Leishmaniasis Are Coendemic

2019 ◽  
Vol 57 (8) ◽  
Author(s):  
Ramona Tavares Daltro ◽  
Leonardo Maia Leony ◽  
Natália Erdens Maron Freitas ◽  
Ângelo Antônio Oliveira Silva ◽  
Emily Ferreira Santos ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Chagas Disease ◽  
Diagnostic Performance ◽  
Latent Class ◽  
Cross Reactivity ◽  
Chimeric Proteins ◽  
Serum Samples ◽  
Perfect Agreement ◽  
Content Type ◽  
Chronic Chagas Disease

ABSTRACT Chimeric T. cruzi antigens have been proposed as a diagnostic tool for chronic Chagas disease (CD) in both settings where Chagas disease is endemic and those where it is not endemic. Antibody response varies in accordance to each T. cruzi strain, presenting challenges to the use of antigens lacking demonstrated cross-reactivity with Leishmania spp. Our group expressed four chimeric proteins (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) and previously assessed their diagnostic performance to determine cross-reactivity with Leishmania spp. Here, we validated our findings using serum samples from different Brazilian geographic areas reporting endemic Chagas disease, endemic visceral or American cutaneous leishmaniasis (ACL), or both. Overall, 829 serum samples were evaluated using commercial and IBMP enzyme-linked immunosorbent assays. Due to the absence of a reference assay to diagnosis CD, latent class analysis (LCA) was performed through the use of a statistical model. The incidence of cross-reactivity for ACL-positive samples varied from 0.35% (IBMP-8.3) to 0.70% (IBMP-8.1 and IBMP-8.2). Regarding visceral leishmaniasis (VL)-positive samples, the IBMP-8.2 and IBMP-8.3 antigens cross-reacted with six (3.49%) and with only one sample (0.58%), respectively. No cross-reactivity with either ACL or VL was observed for the IBMP-8.4 antigen. Similarly, no cross-reactions were found when VL-positive samples were assayed with IBMP-8.1. The agreement among the results obtained using IBMP antigens ranged from 97.3% for IBMP-8.2 and 99% for IBMP-8.1 and IBMP-8.3 to 100% for IBMP-8.4, demonstrating almost perfect agreement with LCA. Accordingly, in light of the negligible cross-reactivity with both ACL and VL, we suggest the use of IBMP antigens in regions where T. cruzi and Leishmania spp. are coendemic.

scholarly journals Characterization of an Immunodominant Antigenic Epitope from Trypanosoma cruzi as a Biomarker of Chronic Chagas' Disease Pathology

2011 ◽  
Vol 19 (2) ◽  
pp. 167-173 ◽  
Author(s):  
M. Carmen Thomas ◽  
Ana Fernández-Villegas ◽  
Bartolomé Carrilero ◽  
Concepción Marañón ◽  
Daniel Saura ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Chronic Phase ◽  
Diagnostic Technique ◽  
High Sensitivity ◽  
Disease Diagnosis ◽  
Antigenic Epitope ◽  
Serum Samples ◽  
Content Type ◽  
Chronic Chagas Disease

ABSTRACTNowadays, the techniques available for chronic Chagas' disease diagnosis are very sensitive; however, they do not allow discrimination of the patient's clinical stages of the disease. The present paper describes that three out of the five different repeats contained in theTrypanosoma cruziTcCA-2 membrane protein (3972-FGQAAAGDKPPP, 6303-FGQAAAGDKPAP, and 3973-FGQAAAGDKPSL) are recognized with high sensitivity (>90%) by sera from chronic Chagas' disease patients and that they are not recognized by sera from patients in the acute phase of the disease. A total of 133 serum samples from chagasic patients and 50 serum samples from healthy donors were tested. In addition, sera from 15 patients with different autoimmune diseases, 43 serum samples from patients suffering an infectious disease other than Chagas' disease, and 38 serum samples from patients with nonchagasic cardiac disorders were also included in this study. The residue 3973 peptide shows a specificity of >98%, as it is not recognized by individuals with autoimmune and inflammatory processes or by patients with a nonchagasic cardiomyopathy. Remarkably, the levels of antibody against the 3973 epitope detected by the sera from Chagas' disease patients in the symptomatic chronic phase, involving cardiac or digestive alterations, are higher than those detected by the sera from Chagas' disease patients in the indeterminate phase of the disease. It is suggested that the diagnostic technique described could also be used to indicate the degree of pathology. The amino acids F, Q, and DKP located in the peptide at positions 1, 3, and 8 to 10, respectively, are essential to conform to the immunodominant antigenic epitope.

scholarly journals In-house ELISA method to analyze anti-Trypanosoma cruzi IgG reactivity for differential diagnosis and evaluation of Chagas disease morbidity

2012 ◽  
Vol 45 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Lilian da Silva Santos ◽  
Rosália Morais Torres ◽  
Girley Francisco Machado-de-Assis ◽  
Maria Terezinha Bahia ◽  
Helen Rodrigues Martins ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Chagas Disease ◽  
Clinical Status ◽  
High Specificity ◽  
Disease Diagnosis ◽  
Cross Reactivity ◽  
Serological Method ◽  
Serum Dilution ◽  
Specificity And Sensitivity ◽  
American Tegumentary Leishmaniasis

INTRODUCTION: The goal was to develop an in-house serological method with high specificity and sensitivity for diagnosis and monitoring of Chagas disease morbidity. METHODS: With this purpose, the reactivities of anti-T. cruzi IgG and subclasses were tested in successive serum dilutions of patients from Berilo municipality, Jequitinhonha Valley, Minas Gerais, Brazil. The performance of the in-house ELISA was also evaluated in samples from other relevant infectious diseases, including HIV, hepatitis C (HCV), syphilis (SYP), visceral leishmaniasis (VL), and American tegumentary leishmaniasis (ATL), and noninfected controls (NI). Further analysis was performed to evaluate the applicability of this in-house methodology for monitoring Chagas disease morbidity into three groups of patients: indeterminate (IND), cardiac (CARD), and digestive/mixed (DIG/Mix), based on their clinical status. RESULTS: The analysis of total IgG reactivity at serum dilution 1:40 was an excellent approach to Chagas disease diagnosis (100% sensitivity and specificity). The analysis of IgG subclasses showed cross-reactivity, mainly with NI, VL, and ATL, at all selected serum dilutions. Based on the data analysis, the IND group displayed higher IgG3 levels and the DIG/Mix group presented higher levels of total IgG as compared with the IND and CARD groups. CONCLUSIONS: These findings demonstrated that methodology presents promising applicability in the analysis of anti-T. cruzi IgG reactivity for the differential diagnosis and evaluation of Chagas disease morbidity.

scholarly journals Benznidazole-Related Adverse Drug Reactions and Their Relationship to Serum Drug Concentrations in Patients with Chronic Chagas Disease

2012 ◽  
Vol 57 (1) ◽  
pp. 390-395 ◽  
Author(s):  
María-Jesús Pinazo ◽  
Laura Guerrero ◽  
Elizabeth Posada ◽  
Elena Rodríguez ◽  
Dolors Soy ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Serum Concentrations ◽  
Duration Of Treatment ◽  
Content Type ◽  
Drug Concentrations ◽  
Trough Serum ◽  
The Mean ◽  
Chronic Chagas Disease ◽  
Optimal Regimen

ABSTRACTFor treating Chagas disease (CD), a current worldwide health problem, only benznidazole and nifurtimox have been approved to be used. In both cases, unwanted drug-related adverse events (ADRs) are frequent when these drugs are used in adults in the chronic stage. The main objective of this study was to establish benznidazole ADRs and their relationship to serum concentrations in patients with chronicTrypanosoma cruziinfection in order to perform more accurate dosages to minimize ADRs. A total of 54 patients were recruited over 12 months. Of these 54 patients, 53 (98%) experienced at least one ADR during follow-up, and the overall average ADR incidence was 2.4 episodes/patient/month. Benznidazole treatment was discontinued in 11 patients, 7 among them due to severe adverse effects. The mean duration of treatment before withdrawal was 11 days. Benznidazole serum concentrations were recorded on days 15, 30, 45, and 60 of follow-up and evaluated according to clinical and epidemiological variables and ADR severity. No relationship was found between the benznidazole serum concentration and the ADRs. The mean (standard deviation) trough serum benznidazole concentrations (all below 20 mcg/ml) on days 15, 30, 45, and 60 were 6.4 (1.9), 6.1 (1.8), 6.2 (2.2), and 5.7 (1.7) μg/ml, respectively. Benznidazole serum concentrations do not appear to be related to the appearance of serious ADRs. Further, well-controlled studies are necessary to establish the optimal regimen for benznidazole in adults with chronic CD.

scholarly journals Autoimmunity in Chagas' heart disease

1995 ◽  
Vol 113 (2) ◽  
pp. 757-766 ◽  
Author(s):  
Edécio Cunha-Neto ◽  
Jorge Kalil
Keyword(s):  
Chagas Disease ◽  
Heart Tissue ◽  
Cross Reactivity ◽  
Autoimmune Response ◽  
Mammalian Host ◽  
Inflammatory Cell Infiltrate ◽  
Cell Infiltrate ◽  
Published Evidence ◽  
Definition Of ◽  
Chronic Chagas Disease

The time scale dissociation between high parasitemia and tissue pathology, allied to the absence of parasites in the heart lesions of chronic Chagas' disease cardiopathy, casted doubt on the direct participation of Trypanosoma cruzi in tissue lesions. Moreover, the heart tissue lesions in chronic Chagas' disease cardiopathy are associated to an inflammatory mononuclear cell infiltrate, presumably the ultimate effectors of tissue damage. It has been hypothesized that the inflammatory cell infiltrate could mediate a delayed hypersensitivity process directed to the heart tissue components, an autoimmune response triggered by immunological cross-reactivity in the course of a protective immune response against some T.cruzi antigen homologous to heart proteins. However, little is known about the efector role of the T cells in the infiltrate, or about the nature of the antigen that lead to their accumulation in tissue. In this paper, we will review the published evidence on autoimmunity and immunological cross-reactivity between T. cruzi and the mammalian host, along with data generated in our laboratory. The definition of the precise role played by autoimmunity in the pathogenesis of Chagas' disease cardiopathy may have important consequences both for immunoprophylaxis and for the therapeutic approach of chronic Chagas' disease.

scholarly journals Towards a Paradigm Shift in the Treatment of Chronic Chagas Disease

2013 ◽  
Vol 58 (2) ◽  
pp. 635-639 ◽  
Author(s):  
R. Viotti ◽  
B. Alarcón de Noya ◽  
T. Araujo-Jorge ◽  
M. J. Grijalva ◽  
F. Guhl ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Paradigm Shift ◽  
Chronic Phase ◽  
World Health ◽  
Chronic Patients ◽  
Content Type ◽  
Current Medical Practice ◽  
Health Organization ◽  
Criteria For Evaluation ◽  
Chronic Chagas Disease

ABSTRACTTreatment for Chagas disease with currently available medications is recommended universally only for acute cases (all ages) and for children up to 14 years old. The World Health Organization, however, also recommends specific antiparasite treatment for all chronic-phaseTrypanosoma cruzi-infected individuals, even though in current medical practice this remains controversial, and most physicians only prescribe palliative treatment for adult Chagas patients with dilated cardiomyopathy. The present opinion, prepared by members of the NHEPACHA network (Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas/New Tools for the Diagnosis and Evaluation of Chagas Disease Patients), reviews the paradigm shift based on clinical and immunological evidence and argues in favor of antiparasitic treatment for all chronic patients. We review the tools needed to monitor therapeutic efficacy and the potential criteria for evaluation of treatment efficacy beyond parasitological cure. Etiological treatment should now be mandatory for all adult chronic Chagas disease patients.

scholarly journals Accuracy of chimeric proteins in the serological diagnosis of chronic chagas disease – a Phase II study

2017 ◽  
Vol 11 (3) ◽  
pp. e0005433 ◽  
Author(s):  
Fred Luciano Neves Santos ◽  
Paola Alejandra Fiorani Celedon ◽  
Nilson Ivo Tonin Zanchin ◽  
Wayner Vieira de Souza ◽  
Edimilson Domingos da Silva ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Serological Diagnosis ◽  
Chimeric Proteins ◽  
Chronic Chagas Disease

scholarly journals Evaluation of the Elecsys Chagas Assay for Detection ofTrypanosoma cruzi-Specific Antibodies in a Multicenter Study in Europe and Latin America

2018 ◽  
Vol 56 (5) ◽  
Author(s):  
Maria Delmans Flores-Chavez ◽  
Vittorio Sambri ◽  
Volkmar Schottstedt ◽  
Fernando Aparicio Higuera-Escalante ◽  
Dieter Roessler ◽  
...  
Keyword(s):  
Latin America ◽  
Pregnant Women ◽  
Chagas Disease ◽  
Blood Donors ◽  
Relative Sensitivity ◽  
Disease Diagnosis ◽  
Hospitalized Patients ◽  
World Health ◽  
Content Type ◽  
Health Organization

ABSTRACTSerology is the preferred method to confirm a Chagas disease diagnosis and to screen blood donors. A battery of assays is often required due to the limited accuracy of single assays. The Elecsys Chagas assay is a newly developed, double-antigen sandwich assay for use on the Elecsys and cobas e immunoassay analyzers, intended to identify individuals infected withTrypanosoma cruzi, for diagnosis and screening. The performance of the Elecsys Chagas assay was evaluated in comparison with those of other widely usedT. cruziantibody assays, at multiple sites (Europe/Latin America). Relative sensitivity and specificity were assessed by using samples from blood donors, pregnant women, and hospitalized patients from regions where Chagas disease is endemic and from regions of nonendemicity. The Elecsys Chagas assay had an overall relative sensitivity of 100% (n= 674). Overall relative specificities were 99.90% (n= 14,681), 100% (n= 313), and 100% (n= 517) for samples from blood donors, pregnant women, and hospitalized patients, respectively. The analytical specificity was 99.83% (n= 594). The Elecsys Chagas assay detectedT. cruziantibodies in two World Health Organization (WHO) standardT. cruzireference panels (panels 09/188 and 09/186) at a 1:512 dilution, corresponding to a cutoff sensitivity of approximately 1 mIU/ml. The Elecsys Chagas assay demonstrated robust performance under routine conditions at multiple sites in Europe and Latin America. In contrast to other available Chagas assays, the Elecsys assay uses a reduced number of recombinantT. cruziantigens, resulting in a significantly smaller number of cross-reactions and improved analytical specificity while being highly sensitive.

scholarly journals Evaluation of Nifurtimox Treatment of Chronic Chagas Disease by Means of Several Parasitological Methods

2013 ◽  
Vol 57 (9) ◽  
pp. 4518-4523 ◽  
Author(s):  
Catalina Muñoz ◽  
Inés Zulantay ◽  
Werner Apt ◽  
Sylvia Ortiz ◽  
Alejandro G. Schijman ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Drug Efficacy ◽  
Triatoma Infestans ◽  
Kinetoplast Dna ◽  
Content Type ◽  
Negative Results ◽  
Pcr Targeting ◽  
Dna Pcr ◽  
Chronic Chagas Disease

ABSTRACTCurrently, evaluation of drug efficacy for Chagas disease remains a controversial issue with no consensus. In this work, we evaluated the parasitological efficacy of Nifurtimox treatment in 21 women with chronic Chagas disease from an area of endemicity in Chile who were treated according to current protocols. Under pre- and posttherapy conditions, blood (B) samples and xenodiagnosis (XD) samples from these patients were subjected to analysis by real-time PCR targeting the nuclear satellite DNA ofTrypanosoma cruzi(Sat DNA PCR-B, Sat DNA PCR-XD) and by PCR targeting the minicircle of kinetoplast DNA ofT. cruzi(kDNA PCR-B, kDNA PCR-XD) and byT. cruzigenotyping using hybridization minicircle tests in blood and fecal samples ofTriatoma infestansfeed by XD. In pretherapy, kDNA PCR-B and kDNA PCR-XD detectedT. cruziin 12 (57%) and 18 (86%) cases, respectively, whereas Sat DNA quantitative PCR-B (qPCR-B) and Sat DNA qPCR-XD were positive in 18 cases (86%) each. RegardingT. cruzigenotype analysis, it was possible to observe in pretherapy the combination of TcI, TcII, and TcV lineages, including mixtures ofT. cruzistrains in most of the cases. At 13 months posttherapy,T. cruziDNA was detectable in 6 cases (29.6%) and 4 cases (19.1%) by means of Sat DNA PCR-XD and kDNA PCR-XD, respectively, indicating treatment failure with recovery of live parasites refractory to chemotherapy. In 3 cases, it was possible to identify persistence of the baseline genotypes. The remaining 15 baseline PCR-positive cases gave negative results by all molecular and parasitological methods at 13 months posttreatment, suggesting parasite response. Within this follow-up period, kDNA PCR-XD and Sat DNA qPCR-XD proved to be more sensitive tools for the parasitological evaluation of the efficacy of Nifurtimox treatment than the corresponding PCR methods performed directly from blood samples.

scholarly journals Chronic Chagas Disease Diagnosis: A Comparative Performance of Commercial Enzyme Immunoassay Tests

2016 ◽  
Vol 94 (5) ◽  
pp. 1034-1039 ◽  
Author(s):  
Fred Luciano Neves Santos ◽  
Wayner Vieira de Souza ◽  
Michelle da Silva Barros ◽  
Mineo Nakazawa ◽  
Marco Aurélio Krieger ◽  
...  
Keyword(s):  
Enzyme Immunoassay ◽  
Chagas Disease ◽  
Disease Diagnosis ◽  
Comparative Performance ◽  
Commercial Enzyme ◽  
Commercial Enzyme Immunoassay ◽  
Chronic Chagas Disease
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