scholarly journals Indeterminate form of Chagas disease: historical, conceptual, clinical, and prognostic aspects

2021 ◽  
Vol 54 ◽  
Author(s):  
Alejandro Marcel Hasslocher-Moreno ◽  
Sergio Salles Xavier ◽  
Roberto Magalhães Saraiva ◽  
Andréa Silvestre de Sousa
Keyword(s):  
Chagas Disease ◽  
Indeterminate Form

scholarly journals Circulating miRNAs as Potential Biomarkers Associated with Cardiac Remodeling and Fibrosis in Chagas Disease Cardiomyopathy

2019 ◽  
Vol 20 (16) ◽  
pp. 4064 ◽  
Author(s):  
Carolina Kymie Vasques Nonaka ◽  
Carolina Thé Macêdo ◽  
Bruno Raphael Ribeiro Cavalcante ◽  
Adriano Costa de Alcântara ◽  
Daniela Nascimento Silva ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Cardiac Fibrosis ◽  
Left Ventricular ◽  
Pharmacological Therapy ◽  
Functional Class ◽  
Diagnostic Methods ◽  
Individual Risk ◽  
Indeterminate Form ◽  
Potential Biomarkers

Chagas disease (CD) affects approximately 6–7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (n = 28), CD indeterminate form (n = 10) and healthy controls (n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.

scholarly journals Echocardiographic Study of the Coronary Sinus in the Indeterminate Form of Chagas Disease

2018 ◽  
Vol 51 (6) ◽  
pp. 827-830
Author(s):  
Glauco Andre Machado ◽  
Dalton Alexandre dos Anjos ◽  
Flávia de Freitas Rodrigues ◽  
Renata Fockink dos Anjos ◽  
Marcelo Barbosa Melo Luckemeyer ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Coronary Sinus ◽  
Echocardiographic Study ◽  
Indeterminate Form

scholarly journals T-Cell Immunophenotyping and Cytokine Production Analysis in Patients with Chagas Disease 4 Years after Benznidazole Treatment

2019 ◽  
Vol 87 (8) ◽  
Author(s):  
Mauricio Llaguno ◽  
Marcos Vinicius da Silva ◽  
Lara Rocha Batista ◽  
Djalma Alexandre Alves da Silva ◽  
Rodrigo Cunha de Sousa ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Chronic Phase ◽  
Interleukin 10 ◽  
T Helper ◽  
T Helper 1 ◽  
Cardiac Damage ◽  
Disease Treatment ◽  
Indeterminate Form ◽  
Ifn Γ

ABSTRACT The major problem with Chagas disease is evolution of the chronic indeterminate form to a progressive cardiac disease. Treatment diminishes parasitemia but not clinical progression, and the immunological features involved are unclear. Here, we studied the clinical course and the immune response in patients with chronic-phase Chagas disease at 48 months after benznidazole treatment. Progression to the cardiac form of Chagas disease or its aggravation was associated with higher in vitro antigen-specific production of interferon gamma (IFN-γ) in patients with cardiac Chagas disease than in patients with the indeterminate form. Predominance of IFN-γ production over interleukin-10 (IL-10) production in antigen-specific cultures was associated with cardiac involvement. Significantly higher numbers of antigen-specific T helper 1 cells (T-Bet+ IFN-γ+) and a significantly higher IFN-γ+/IL-10+ ratio were observed in patients with cardiac Chagas disease than in patients with the indeterminate form. Cardiac damage was associated with higher numbers of T helper cells than cytotoxic T lymphocytes producing IFN-γ. Patients with cardiac Chagas disease had predominant CD25− and CD25low T regulatory (Treg) subpopulations, whereas patients with the indeterminate form manifested a higher relative mean percentage of CD25high Treg subpopulations. These findings suggest that at 48 months after benznidazole treatment, the disease can worsen or progress to the cardiac form. The progression may be related to increased IFN-γ production (mostly from CD4+ T cells) relative to IL-10 production and increased Treg percentages. Patients with the indeterminate form of Chagas disease show a more balanced ratio of proinflammatory and anti-inflammatory cytokines.

scholarly journals The indeterminate form of human chronic Chagas' disease: a clinical epidemological review

1989 ◽  
Vol 22 (3) ◽  
pp. 147-156 ◽  
Author(s):  
João Carlos Pinto Dias
Keyword(s):  
Natural History ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Clinical Findings ◽  
X Rays ◽  
Classical Concept ◽  
Positive Serology ◽  
Indeterminate Form ◽  
History Of ◽  
Chronic Chagas Disease

Data on the epidemiology and the natural history of the indeterminate form of human chronic Chagas' disease (IFCCD) are discussed, revealing its great importance in endemic areas of Brazil. The work shows that IFCCD presents a gradual and very slow course, causing a benign picture in the studied patients. Evolution patterns, prognostic and anatomopathological features are also discussed. For practical purposes, the classical concept of IFCCD proved to be simple, operational and consistent, It is defined by the absence of symptoms and clinical findings in chronic infected patients with positive serology and/or parasitological examinations for Trypanosoma cruzi coupled with normal electrocardiographic and radiological exams (heart, oesophagus and colon X-Rays). If a patient is submitted to more rigorous and sophisticated tests, these can reveal some alterations, generally small ones and unable to interfere with the prognosis of the infection. It is suggested that research lines specially related to the evolution ary factors and immunological involvement during this phase be adopted.

scholarly journals Early impairment of myocardial deformation assessed by regional speckle-tracking echocardiography in the indeterminate form of Chagas disease without fibrosis detected by cardiac magnetic resonance

2020 ◽  
Vol 14 (11) ◽  
pp. e0008795
Author(s):  
Minna Moreira Dias Romano ◽  
Henrique Turin Moreira ◽  
José Antônio Marin-Neto ◽  
Priscila Elias Baccelli ◽  
Fawaz Alenezi ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Myocardial Fibrosis ◽  
Chagas Disease ◽  
Speckle Tracking ◽  
Longitudinal Strain ◽  
Speckle Tracking Echocardiography ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Indeterminate Form

Chagas disease (CD) will account for 200,000 cardiovascular deaths worldwide over the next 5 years. Early detection of chronic Chagas cardiomyopathy (CCC) is a challenge. We aimed to test if speckle-tracking echocardiography (STE) can detect incipient myocardial damage in CD. METHODS: Among 325 individuals with positive serological tests, 25 (age 55±12yrs) were selected to compose the group with indeterminate form of Chagas disease (IFCD), based on stringent criteria of being asymptomatic and with normal EKG/X-ray studies. This group was compared with a group of 20 patients with CCC (55±11yrs) and a group of 20 non-infected matched control (NC) subjects (48±10yrs). CD patients and NC were submitted to STE and CD patients were submitted to cardiac magnetic resonance (CMR) with late gadolinium administration to detect cardiac fibrosis by the late enhancement technique. Global longitudinal strain (GLS), circumferential (GCS) and radial strain (GRS) were defined as the average of segments measured from three apical view (GLS) and short axis views (GRS and GCS). Regional left ventricular (LV) longitudinal strain (Reg LS) was measured from each of the 17 segments. Twist was measured as systolic peak difference between basal and apical rotation and indexed to LV length to express torsion. RESULTS: STE global indices (GLS, GCS, twist and torsion) were reduced in CCC vs NC (GLS: -14±6.3% vs -19.3±1.6%, p = 0.001; GCS: -13.6±5.2% vs -17.3 ±2.8%; p = 0.008; twist: 8±7° vs 14±7°, p = 0.01 and torsion: 0.96±1°/cm vs 1.9±1°/cm, p = 0.005), but showed no differences in IFCD vs NC. RegLS was reduced in IFCD vs NC in four LV segments: basal-inferior (-16.3±3.3% vs -18.6±2.2%, p = 0.013), basal inferoseptal (-13.1±3.4 vs -15.2±2.7, p = 0.019), mid-inferoseptal (-17.7±3.2 vs -19.4±2, p = 0.032) and mid-inferolateral (-15.2±3.5 vs -17.8±2.8, p = 0.014). These abnormalities in RegLS occurred in the absence of myocardial fibrosis detectable with CMR in nearly 92% of subjects with IFCD, while myocardial fibrosis was present in 65% with CCC. CONCLUSION: RegLS detects early regional impairment of myocardial strain that is independent from fibrosis in IFCD subjects.

scholarly journals Progression Rate from the Indeterminate Form to the Cardiac Form in Patients with Chronic Chagas Disease: Twenty-Two-Year Follow-Up in a Brazilian Urban Cohort

2020 ◽  
Vol 5 (2) ◽  
pp. 76 ◽  
Author(s):  
Alejandro Marcel Hasslocher-Moreno ◽  
Sergio Salles Xavier ◽  
Roberto Magalhães Saraiva ◽  
Luiz Henrique Conde Sangenis ◽  
Marcelo Teixeira de Holanda ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Proportional Hazards ◽  
Heart Diseases ◽  
Cox Proportional Hazards ◽  
Progression Rate ◽  
Proportional Hazards Regression ◽  
Indeterminate Form ◽  
Electrocardiographic Changes ◽  
Chronic Chagas Disease

Most patients with chronic Chagas disease (CD) present the indeterminate form and are at risk to develop the cardiac form. However, the actual rate of progression to the cardiac form is still unknown. Methods: In total, 550 patients with the indeterminate CD form were followed by means of annual electrocardiogram at our outpatient clinic. The studied endpoint was progression to cardiac form defined by the appearance of electrocardiographic changes typical of CD. The progression rate was calculated as the cumulative progression rate and the incidence progression rate per 100 patient years. Results: Thirty-seven patients progressed to the CD cardiac form within a mean of 73 ± 48 months of follow-up, which resulted in a 6.9% cumulative progression rate and incidence rate of 1.48 cases/100 patient years. Patients who progressed were older (mean age 47.8 ± 12.2 years), had a higher prevalence of associated heart diseases (p < 0.0001), positive xenodiagnosis (p = 0.007), and were born in the most endemic Brazilian states (p = 0.018). Previous co-morbidities remained the only variable associated with CD progression after multivariate Cox proportional hazards regression analysis (p = 0.002). Conclusion: The progression rate to chronic CD cardiac form is low and inferior to rates previously reported in other studies.

scholarly journals Trypanosoma cruzi Infection Induces Differential Modulation of Costimulatory Molecules and Cytokines by Monocytes and T Cells from Patients with Indeterminate and Cardiac Chagas' Disease

2007 ◽  
Vol 75 (4) ◽  
pp. 1886-1894 ◽  
Author(s):  
Paulo E. A. Souza ◽  
Manoel O. C. Rocha ◽  
Cristiane A. S. Menezes ◽  
Janete S. Coelho ◽  
Andréa C. L. Chaves ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Molecular Mechanisms ◽  
Costimulatory Molecule ◽  
Costimulatory Molecules ◽  
Necrosis Factor Alpha ◽  
Pathogenic Potential ◽  
Indeterminate Form

ABSTRACT Interactions between macrophages and lymphocytes through costimulatory molecules and cytokines are essential for mounting an efficient immune response and controlling its pathogenic potential. Here we demonstrate the immunomodulatory capacity of Trypanosoma cruzi, the causative agent of Chagas' disease, through its ability to induce differential expression of costimulatory molecules and cytokines by monocytes and T cells. Costimulatory molecule and cytokine modulation was evaluated using cells from noninfected individuals and from patients with the asymptomatic indeterminate form and those with the severe cardiac clinical form of Chagas' disease. Our results show that while exposure of monocytes to live T. cruzi leads to an increase in the frequency of CD80+ monocytes in all groups, it decreases both the frequency and intensity of CD86 expression by monocytes from patients with the cardiac form but not from those with the indeterminate form. Conversely, exposure of lymphocytes to monocytes infected with T. cruzi increased the surface expression of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) by T cells from indeterminate but not from cardiac patients, compared to that from control patients. These data suggest that T. cruzi induces a potentially down-regulatory environment in indeterminate subjects, which is associated with higher CD80 and CTLA-4 expression. To test the functional importance of this modulation, we evaluated the expression of cytokines after in vitro infection. Although exposure of lymphocytes to parasite-infected monocytes induced high expression of inflammatory and anti-inflammatory cytokines by T cells in all groups, indeterminate patients displayed a higher ratio of monocytes expressing interleukin 10 than tumor necrosis factor alpha following infection than did controls. These data show the ability of T. cruzi to actively change the expression of costimulatory molecules and cytokines, suggesting molecular mechanisms for the differential clinical evolution of human Chagas' disease.

Long-term follow-up of patients with Chagas' disease: Emphasis on the indeterminate form

1999 ◽  
Vol 5 (3) ◽  
pp. 70
Author(s):  
Barbara M. Ianni ◽  
Edmundo Arteaga ◽  
Antonio Carlos Pereira-Barretto ◽  
Charles Mady
Keyword(s):  
Chagas Disease ◽  
Long Term Follow Up ◽  
Indeterminate Form
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