33 results on '"Morillo, Carlos A."'
Search Results
2. COVID-19: Implications for People with Chagas Disease.
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Zaidel EJ, Forsyth CJ, Novick G, Marcus R, Ribeiro ALP, Pinazo MJ, Morillo CA, Echeverría LE, Shikanai-Yasuda MA, Buekens P, Perel P, Meymandi SK, Ralston K, Pinto F, and Sosa-Estani S
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- COVID-19 therapy, Chagas Cardiomyopathy diagnosis, Chagas Cardiomyopathy epidemiology, Chagas Disease therapy, Comorbidity, Cross-Sectional Studies, Follow-Up Studies, Forecasting, Health Services Accessibility trends, Health Services Needs and Demand trends, Humans, Risk Factors, COVID-19 diagnosis, COVID-19 epidemiology, Chagas Disease diagnosis, Chagas Disease epidemiology, Neglected Diseases
- Abstract
As the global COVID-19 pandemic advances, it increasingly impacts those vulnerable populations who already bear a heavy burden of neglected tropical disease. Chagas disease (CD), a neglected parasitic infection, is of particular concern because of its potential to cause cardiac, gastrointestinal, and other complications which could increase susceptibility to COVID-19. The over one million people worldwide with chronic Chagas cardiomyopathy require special consideration because of COVID-19's potential impact on the heart, yet the pandemic also affects treatment provision to people with acute or chronic indeterminate CD. In this document, a follow-up to the WHF-IASC Roadmap on CD, we assess the implications of coinfection with SARS-CoV-2 and Trypanosoma cruzi , the etiological agent of CD. Based on the limited evidence available, we provide preliminary guidance for testing, treatment, and management of patients affected by both diseases, while highlighting emerging healthcare access challenges and future research needs., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)
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- 2020
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3. Myocardial Involvement in Chagas Disease and Insulin Resistance: A Non-Metabolic Model of Cardiomyopathy.
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Echeverría LE, Rojas LZ, López LA, Rueda-Ochoa OL, Gómez-Ochoa SA, and Morillo CA
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- Chagas Cardiomyopathy diagnosis, Chagas Cardiomyopathy etiology, Chagas Cardiomyopathy metabolism, Chagas Disease diagnosis, Colombia epidemiology, Cross-Sectional Studies, Female, Humans, Incidence, Male, Middle Aged, Myocardium metabolism, Retrospective Studies, Risk Factors, Blood Glucose metabolism, Chagas Disease complications, Insulin Resistance, Myocardium pathology
- Abstract
Background: Heart failure (HF) and type 2 Diabetes Mellitus (T2DM) represent two chronic interrelated conditions accounting for significant morbidity and mortality worldwide. Insulin resistance (IR) has been identified as a risk factor for HF; however, the risk of IR that HF confers has not been well elucidated. The present study aims to analyze the association between myocardial involvement in Chronic Chagas Cardiomyopathy (CCM) and IR, taking advantage of this non-metabolic model of the disease., Methods: Cross-sectional study performed during the period 2015-2016. Adults with a serological diagnosis of Chagas disease were included, being divided into two groups: CCM and non-CCM. IR was determined by HOMA-IR index. Bivariate analysis and multivariate logistic regression were performed to determine the association between IR as an outcome and CCM as primary exposure., Results: 200 patients were included in the study, with a mean age of 54.7 years and a female predominance (53.5%). Seventy-four (37.0%) patients were found to have IR, with a median HOMA-IR index of 3.9 (Q1 = 3.1; Q3 = 5.1). Multiple metabolic variables were significantly associated with IR. In a model analyzing only individuals with an altered HWI, an evident association between CCM and IR was observed (OR 4.08; 95% CI 1.55-10.73, p = 0.004)., Conclusion: CCM was significantly associated with IR in patients with an altered HWI. The presence of this association in a non-metabolic model of HF (in which the myocardial involvement is expected to be mediated mostly by the parasitic infection) may support the evidence of a direct unidirectional correlation between this last and IR., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)
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- 2020
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4. Chagas heart disease: A contemporary review.
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Velasco A and Morillo CA
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- 3-Iodobenzylguanidine, Animals, Arrhythmias, Cardiac complications, Chagas Cardiomyopathy complications, Chagas Disease complications, Electrocardiography, Heart physiopathology, Heart Diseases complications, Humans, Insect Vectors, Insecta, Prognosis, Radionuclide Imaging, Risk, Treatment Outcome, Trypanosoma cruzi, Arrhythmias, Cardiac diagnostic imaging, Chagas Cardiomyopathy diagnostic imaging, Chagas Disease diagnostic imaging
- Abstract
Chagas disease is caused by a parasite infection endemic of the Americas. Traditionally observed in rural areas of Latin America, current migration trends have turned Chagas disease into a global epidemic. Acute infection is rarely severe and once it resolves, some patients can develop cardiomyopathy as part of the chronic form many years later. Multiple factors related with both the host and the parasite determine the susceptibility and progression to cardiomyopathy. Current imaging techniques are able to identify cardiac autonomic denervation, perfusion abnormalities, and myocardial fibrosis at an early of stage before the development of symptoms. The prognosis of patients with Chagasic cardiomyopathy remains poor and life-threatening ventricular arrhythmias can occur at an early stage. Treatment of chronic Chagas cardiomyopathy is challenging with a great need for more studies in the field.
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- 2020
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5. WHF IASC Roadmap on Chagas Disease.
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Echeverría LE, Marcus R, Novick G, Sosa-Estani S, Ralston K, Zaidel EJ, Forsyth C, RIbeiro ALP, Mendoza I, Falconi ML, Mitelman J, Morillo CA, Pereiro AC, Pinazo MJ, Salvatella R, Martinez F, Perel P, Liprandi ÁS, Piñeiro DJ, and Molina GR
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- Chagas Disease epidemiology, Global Health, Humans, Morbidity trends, World Health Organization, Chagas Disease prevention & control, Practice Guidelines as Topic
- Abstract
Background: Chagas Disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi , with some of the most serious manifestations affecting the cardiovascular system. It is a chronic, stigmatizing condition, closely associated with poverty and affecting close to 6 million people globally. Although historically the disease was limited to endemic areas of Latin America recent years have seen an increasing global spread. In addition to the morbidity and mortality associated with the disease, the social and economic burdens on individuals and society are substantial. Often called the 'silent killer', Chagas disease is characterized by a long, asymptomatic phase in affected individuals. Approximately 30% then go on develop chronic Chagas cardiomyopathy and other serious cardiac complications such as stroke, rhythm disturbances and severe heart failure., Methods: In a collaboration of the World Hearth Federation (WHF) and the Inter-American Society of Cardiology (IASC) a writing group consisting of 20 diverse experts on Chagas disease (CD) was convened. The group provided up to date expert knowledge based on their area of expertise. An extensive review of the literature describing obstacles to diagnosis and treatment of CD along with proposed solutions was conducted. A survey was sent to all WHF Members and, using snowball sampling to widen the consultation, to a variety of health care professionals working in the CD global health community. The results were analyzed, open comments were reviewed and consolidated, and the findings were incorporated into this document, thus ensuring a consensus representation., Results: The WHF IASC Roadmap on Chagas Disease offers a comprehensive summary of current knowledge on prevention, diagnosis and management of the disease. In providing an analysis of 'roadblocks' in access to comprehensive care for Chagas disease patients, the document serves as a framework from which strategies for implementation such as national plans can be formulated. Several dimensions are considered in the analysis: healthcare system capabilities, governance, financing, community awareness and advocacy., Conclusion: The WHF IASC Roadmap proposes strategies and evidence-based solutions for healthcare professionals, health authorities and governments to help overcome the barriers to comprehensive care for Chagas disease patients. This roadmap describes an ideal patient care pathway, and explores the roadblocks along the way, offering potential solutions based on available research and examples in practice. It represents a call to action to decision-makers and health care professionals to step up efforts to eradicate Chagas disease., Competing Interests: MLF has received financial support for inscription to an international meeting from Philips/Agimed Argentina. RM previously worked in a consultancy role for Exeltis and Bayer. GM has received grants for global health research and projects from Novartis. LEE has received a research grant for work on Chagas cardiomyopathy from Roche. He is also a member of the steering committee of the PARACHUTE-HF trial., (Copyright: © 2020 The Author(s).)
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- 2020
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6. Efficacy of the Benznidazole+Posaconazole combination therapy in parasitemia reduction: An experimental murine model of acute Chagas.
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Echeverría LE, González CI, Hernandez JCM, Díaz ML, Eduardo Nieto J, López-Romero LA, Rivera JD, Suárez EU, Ochoa SAG, Rojas LZ, and Morillo CA
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- Acute Disease, Animals, DNA, Protozoan, Disease Models, Animal, Disease Progression, Drug Therapy, Combination, Parasite Load, Rats, Rats, Wistar, Chagas Disease drug therapy, Nitroimidazoles administration & dosage, Parasitemia drug therapy, Triazoles administration & dosage, Trypanocidal Agents administration & dosage
- Abstract
Introduction: Benznidazole (BZL) and Nifurtimox (NFX) are the pharmacological treatment for acute phase Chagas Disease (CD); however, therapy resistance and residual mortality development remain important unresolved issues. Posaconazole (POS) has shown a trypanocidal effect in vivo and in vitro. Thus, this study aimed at comparing the T. Cruzi parasitic load-reducing effect of the combination of BZL+POS against that of monotherapy with either, during acute phase CD, in an experimental murine model., Methods: Nineteen Wistar rats were randomly allocated to four groups and inoculated with the trypomastigotes of T. cruzi strain´s JChVcl1. The rats were administered anti-parasites from day 20-29 post-infection. The Pizzi and Brener method was used for parasitemia measurement. Longitudinal data analysis for the continuous outcome of repeated measures was performed using parasitemia as the outcome measured at days 20, 22, 24, 27, and 29 post-infection., Results: All four groups had similar parasitic loads (p=0.143) prior to therapy initiation. Among the three treatment groups, the BZL+POS (n=5) group showed the highest mean parasitic load reduction (p=0.000) compared with the control group. Likewise, the BZL+POS group rats showed an earlier therapeutic effect and were the only ones without parasites in their myocardial samples., Conclusions: Treatment of acute phase CD with BZL+POS was more efficacious at parasitemia and myocardial injury reduction, compared with monotherapy with either.
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- 2020
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7. American Trypanosomiasis (Chagas Disease).
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Echeverria LE and Morillo CA
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- Animals, Clinical Trials as Topic, Disease Progression, Disease Vectors, Humans, Nitroimidazoles therapeutic use, Triatominae parasitology, Trypanocidal Agents therapeutic use, Trypanosoma cruzi isolation & purification, Chagas Cardiomyopathy drug therapy, Chagas Cardiomyopathy mortality, Chagas Disease complications, Chagas Disease drug therapy
- Abstract
American trypanosomiasis is caused by a parasite endemic of the Americas. Current migration has globalized Chagas disease. Acute infection usually resolves spontaneously. Nonetheless, 20% to 40% develop cardiomyopathy 20 to 30 years later. Progression to cardiomyopathy is devastatingly rapid, manifesting with heart failure and sudden death. Etiologic treatment is highly effective and recommended in those with acute infections, congenital infections, and parasite reactivation, and women of childbearing age, but in asymptomatic Trypanosoma cruzi carriers and patients with early cardiomyopathy remains controversial and under investigation. Progression of heart failure is rapid and accounts for most of the morbidity and related mortality., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2019
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8. Recommendations for Multimodality Cardiac Imaging in Patients with Chagas Disease: A Report from the American Society of Echocardiography in Collaboration With the InterAmerican Association of Echocardiography (ECOSIAC) and the Cardiovascular Imaging Department of the Brazilian Society of Cardiology (DIC-SBC).
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Acquatella H, Asch FM, Barbosa MM, Barros M, Bern C, Cavalcante JL, Echeverria Correa LE, Lima J, Marcus R, Marin-Neto JA, Migliore R, Milei J, Morillo CA, Nunes MCP, Campos Vieira ML, and Viotti R
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- Brazil, Humans, International Cooperation, United States, Cardiology, Chagas Disease diagnosis, Echocardiography standards, Multimodal Imaging standards, Practice Guidelines as Topic, Societies, Medical
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- 2018
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9. Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial.
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Morillo CA, Waskin H, Sosa-Estani S, Del Carmen Bangher M, Cuneo C, Milesi R, Mallagray M, Apt W, Beloscar J, Gascon J, Molina I, Echeverria LE, Colombo H, Perez-Molina JA, Wyss F, Meeks B, Bonilla LR, Gao P, Wei B, McCarthy M, and Yusuf S
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- Administration, Oral, Adult, Chronic Disease, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Prospective Studies, Single-Blind Method, Chagas Disease drug therapy, Nitroimidazoles therapeutic use, Triazoles therapeutic use, Trypanocidal Agents therapeutic use, Trypanosoma cruzi
- Abstract
Background: Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers., Objectives: The purpose of this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers., Methods: A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days., Results: Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p < 0.0001 vs. posaconazole/placebo). Posaconazole monotherapy or posaconazole combined with benznidazole achieved high RT-PCR conversion rates during treatment (30 days; 93.3% and 88.9% and 60 days; 90%, and 92.3%) that were similar to benznidazole (89.7% and 89.3%); all were superior to placebo or posaconazole (10% and 16.7%, p < 0.0001). This was not observed at 360 days; benznidazole + posaconazole and benznidazole monotherapy (both 96%) versus placebo (17%) and posaconazole (16%, p < 0.0001). Serious adverse events were rare (6 patients) and were observed in the benznidazole-treated patients. Permanent discontinuation was reported in 19 patients (31.7%) receiving either benznidazole monotherapy or combined with posaconazole., Conclusions: Posaconazole demonstrated trypanostatic activity during treatment, but it is ineffective long-term in asymptomatic T. cruzi carriers. Benznidazole monotherapy is superior to posaconazole, with high RT-PCR conversion rates sustained at 1 year. Side effects lead to therapy discontinuation in 32%. No advantages were observed with combined therapy versus benznidazole monotherapy. (A Study of the Use of Oral Posaconazole [POS] in the Treatment of Asymptomatic Chronic Chagas Disease [P05267] [STOP CHAGAS]: NCT01377480)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2017
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10. Reply: a vision of future treatment in chagas heart disease.
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Nunes MC, Dones W, Morillo CA, Encina JJ, and Ribeiro AL
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- Humans, Chagas Disease epidemiology
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- 2014
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11. Reply: catheter ablation to treat sustained ventricular tachycardia in patients with chagas cardiomyopathy and implantable cardioverter-defibrillator.
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Nunes MC, Carmo AA, Dones W, Morillo CA, Encina JJ, and Ribeiro AL
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- Humans, Chagas Disease epidemiology
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- 2014
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12. Cytokine profiling in Chagas disease: towards understanding the association with infecting Trypanosoma cruzi discrete typing units (a BENEFIT TRIAL sub-study).
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Poveda C, Fresno M, Gironès N, Martins-Filho OA, Ramírez JD, Santi-Rocca J, Marin-Neto JA, Morillo CA, Rosas F, and Guhl F
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- Adult, Chagas Cardiomyopathy immunology, Chronic Disease, Discriminant Analysis, Humans, Middle Aged, Principal Component Analysis, Chagas Disease immunology, Chagas Disease parasitology, Cytokines metabolism, Trypanosoma cruzi physiology
- Abstract
Background: Chagas disease caused by the protozoan Trypanosoma cruzi is an important public health problem in Latin America. The immunological mechanisms involved in Chagas disease pathogenesis remain incompletely elucidated. The aim of this study was to explore cytokine profiles and their possible association to the infecting DTU and the pathogenesis of Chagas disease., Methods: 109 sero-positive T. cruzi patients and 21 negative controls from Bolivia and Colombia, were included. Flow cytometry assays for 13 cytokines were conducted on human sera. Patients were divided into two groups: in one we compared the quantification of cytokines between patients with and without chronic cardiomyopathy; in second group we compared the levels of cytokines and the genetic variability of T. cruzi., Results: Significant difference in anti-inflammatory and pro-inflammatory cytokines profiles was observed between the two groups cardiac and non-cardiac. Moreover, serum levels of IFN-γ, IL-12, IL-22 and IL-10 presented an association with the genetic variability of T.cruzi, with significant differences in TcI and mixed infections TcI/TcII., Conclusion: Expression of anti-inflammatory and pro-inflammatory cytokines may play a relevant role in determining the clinical presentation of chronic patients with Chagas disease and suggests the occurrence of specific immune responses, probably associated to different T. cruzi DTUs.
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- 2014
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13. Chagas disease: an overview of clinical and epidemiological aspects.
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Nunes MC, Dones W, Morillo CA, Encina JJ, and Ribeiro AL
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- Chagas Disease physiopathology, Chagas Disease therapy, Death, Sudden, Cardiac prevention & control, Humans, Prognosis, Chagas Disease epidemiology
- Abstract
Chagas disease, caused by the parasite Trypanosoma cruzi, is a serious health problem in Latin America and is an emerging disease in non-endemic countries. In recent decades, the epidemiological profile of the disease has changed due to new patterns of immigration and successful control in its transmission, leading to the urbanization and globalization of the disease. Dilated cardiomyopathy is the most important and severe manifestation of human chronic Chagas disease and is characterized by heart failure, ventricular arrhythmias, heart blocks, thromboembolic phenomena, and sudden death. This article will present an overview of the clinical and epidemiological aspects of Chagas disease. It will focus on several clinical aspects of the disease, such as chronic Chagas disease without detectable cardiac pathology, as well as dysautonomia, some specific features, and the principles of treatment of chronic cardiomyopathy., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2013
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14. Chagas disease: 101 years of solitude! Time for action.
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Armaganijan L and Morillo CA
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- Atrial Fibrillation complications, Chagas Cardiomyopathy complications, Chagas Disease complications, Humans, Incidence, Latin America epidemiology, Natriuretic Peptide, Brain blood, Stroke epidemiology, Stroke mortality, Survival Rate, Trypanosoma cruzi, Biomedical Research trends, Chagas Disease epidemiology, Chagas Disease prevention & control
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- 2010
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15. Role of the IFNG +874T/A polymorphism in Chagas disease in a Colombian population.
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Torres OA, Calzada JE, Beraún Y, Morillo CA, González A, González CI, and Martín J
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- Adult, Animals, Chagas Cardiomyopathy genetics, Chagas Cardiomyopathy immunology, Chagas Disease parasitology, Chagas Disease physiopathology, Colombia, Disease Progression, Genotype, Humans, Middle Aged, Trypanosoma cruzi, Chagas Disease genetics, Chagas Disease immunology, Genetic Predisposition to Disease, Interferon-gamma genetics, Polymorphism, Single Nucleotide
- Abstract
Genetic susceptibility to Trypanosoma cruzi infection and the development of cardiomyopathy is complex, heterogeneous, and likely involves several genes. Previous studies have implicated cytokine and chemokine genes in susceptibility to Chagas disease. Here we investigated the association between the interferon-gamma gene (IFNG) +874T/A polymorphism and Chagas disease, focusing on susceptibility and severity. This study included 236 chagasic patients (asymptomatic, n=116; cardiomyopathic, n=120) and 282 healthy controls from a Colombian population where T. cruzi is highly endemic. Individuals were genotyped for functional single nucleotide polymorphism (SNP; rs2430561; A/T) of the IFNG gene by amplification refractory mutational system PCR (ARMS-PCR). Moreover, clinical manifestations of Chagas in patients were analyzed. We found a significant difference in the distribution of the IFNG +874 "A" allele between patients and healthy controls (P=0.003; OR=1.46, 95% CI, 1.13-1.89). The frequency of the IFNG +874 genotype A/A, which is associated with reduced production of interferon-gamma, was increased in the patients relative to controls (38.1% vs. 26.6%). We compared the frequencies of IFNG alleles and genotypes between asymptomatic patients and those with chagasic cardiomyopathy and found no significant difference. Our data suggest that the IFNG +874T/A genetic polymorphism may be involved in susceptibility but not in the progression of Chagas disease in this Colombian population., (Copyright 2010 Elsevier B.V. All rights reserved.)
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- 2010
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16. Association of the macrophage migration inhibitory factor -173G/C polymorphism with Chagas disease.
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Torres OA, Calzada JE, Beraún Y, Morillo CA, González CI, González A, and Martín J
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- Adolescent, Adult, Aged, Alleles, Colombia, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Meta-Analysis as Topic, Middle Aged, Odds Ratio, Peru, Polymerase Chain Reaction, Young Adult, Chagas Disease genetics, Macrophage Migration-Inhibitory Factors genetics, Polymorphism, Single Nucleotide
- Abstract
Our aim was to evaluate the association of functional polymorphism of macrophage migration inhibitory factor (MIF) gene with Chagas disease. Our study includes two independent cohorts: 240 chagasic patients and 199 controls from Colombia; and 74 chagasic patients and 85 controls from Peru. The single nucleotide polymorphism (SNP) -173 G/C of MIF gene was determined using a polymerase chain reaction (PCR) system with pre-developed TaqMan assay. We observed a statistically significant difference in the distribution of -173*C allele of MIF gene between patients and controls in the Colombian cohort (OR = 1.6, 95% CI = 1.12-2.18, p = 0.006). Similar association was found in the Peruvian cohort (OR = 2.4, 95% CI = 1.31-4.38, p = 0.003). A meta-analysis of the Colombian and Peruvian cohorts demonstrated that the -173 C allele confers a risk effect in chagasic patients (pooled OR = 1.75, 95% CI = 1.30-2.33, p = 0.0002). In addition, a gene dose of the MIF -173 C allele was observed (pooled OR = 4.01, 95% CI = 1.25-12.85, p = 0.004). Our results suggest that the MIF -173G/C polymorphism confers susceptibility to Chagas disease in the populations under study.
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- 2009
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17. Longitudinal strain by speckle tracking and echocardiographic parameters as predictors of adverse cardiovascular outcomes in chronic Chagas cardiomyopathy
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Echeverría, Luis Eduardo, Rojas, Lyda Z., Rueda-Ochoa, Oscar L., Gómez-Ochoa, Sergio Alejandro, Mayer, Miguel A., Becerra-Motta, Lisbeth Paola, Luengas, Carlos, Chaves, Angel M., Rodríguez, Jaime A., and Morillo, Carlos A.
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- 2022
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18. Direct evidence gap on fixed versus adjusted‐dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: Systematic review and individual patient data meta‐analysis.
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Ciapponi, Agustín, Barreira, Fabiana, Perelli, Lucas, Bardach, Ariel, Gascón, Joaquim, Molina, Israel, Morillo, Carlos, Prado, Nilda, Riarte, Adelina, Torrico, Faustino, Villar, Juan Carlos, Reidel, Sara, Gibbons, Luz, and Sosa‐Estani, Sergio
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CHAGAS' disease ,CHRONIC diseases ,CARDIOMYOPATHIES ,RANDOMIZED controlled trials ,ADULTS - Abstract
Objectives: To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted‐dose for Trypanosoma cruzi‐seropositive adults without cardiomyopathy. Methods: We conducted a systematic review and individual participant data (IPD) meta‐analysis following Cochrane methods, and the PRISMA‐IPD statement for reporting. Randomised controlled trials (RCTs) allocating participants to fixed or adjusted doses of BZN for T. cruzi‐seropositive adults without cardiomyopathy were included. We searched (December 2021) Cochrane, MEDLINE, EMBASE, LILACS and trial registries and contacted Chagas experts. Selection, data extraction, risk of bias assessment using the Cochrane tool, and a GRADE summary of finding tables were performed independently by pairs of reviewers. We conducted a random‐effects IPD meta‐analysis using the one‐stage strategy, or, if that was impossible, the two‐stage strategy. Results: Five RCTs (1198 patients) were included, none directly comparing fixed with adjusted doses of BZN. Compared to placebo, BZN therapy was strongly associated with negative qPCR and sustainable parasitological clearance regardless of the type of dose and subgroup analysed. For negative qPCR, the fixed/adjusted rate of odds ratios (RORF/A) was 8.83 (95% CI 1.02–76.48); for sustained parasitological clearance, it was 4.60 (95% CI 0.40–52.51), probably indicating at least non‐inferior effect of fixed doses, with no statistically significant interactions by scheme for global and most subgroup estimations. The RORF/A for treatment interruption due to adverse events was 0.44 (95% CI 0.14–1.38), probably indicating no worse tolerance of fixed doses. Conclusions: We found no direct comparison between fixed and adjusted doses of BZN. However, fixed doses versus placebo are probably not inferior to weight‐adjusted doses of BZN versus placebo in terms of parasitological efficacy and safety. Network IPD meta‐analysis, through indirect comparisons, may well provide the best possible answers in the near future. Registration: The study protocol was registered in PROSPERO (CRD42019120905). [ABSTRACT FROM AUTHOR]
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- 2023
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19. COVID-19: Implications for People with Chagas Disease
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Zaidel, Ezequiel José, Forsyth, Colin J., Novick, Gabriel, Marcus, Rachel, Ribeiro, Antonio Luiz P., Pinazo, Maria-Jesus, Morillo, Carlos A., Echeverría, Luis Eduardo, Shikanai-Yasuda, Maria Aparecida, Buekens, Pierre, Perel, Pablo, Meymandi, Sheba K., Ralston, Kate, Pinto, Fausto, Sosa-Estani, Sergio, and Repositório da Universidade de Lisboa
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Chagas Cardiomyopathy ,Chagas disease ,lcsh:Diseases of the circulatory (Cardiovascular) system ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Epidemiology ,Neglected tropical disease ,Review ,Comorbidity ,030204 cardiovascular system & hematology ,Health Services Accessibility ,03 medical and health sciences ,0302 clinical medicine ,COVID-19 ,Chagas Disease ,Neglected Tropical Disease ,Risk Factors ,Tropical Medicine , Cardiology ,Pandemic ,Health care ,medicine ,Humans ,030212 general & internal medicine ,Intensive care medicine ,Community and Home Care ,Health Services Needs and Demand ,business.industry ,lcsh:Public aspects of medicine ,Neglected Diseases ,Tropical disease ,lcsh:RA1-1270 ,medicine.disease ,Cross-Sectional Studies ,lcsh:RC666-701 ,Etiology ,Coinfection ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies ,Forecasting - Abstract
© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/, As the global COVID-19 pandemic advances, it increasingly impacts those vulnerable populations who already bear a heavy burden of neglected tropical disease. Chagas disease (CD), a neglected parasitic infection, is of particular concern because of its potential to cause cardiac, gastrointestinal, and other complications which could increase susceptibility to COVID-19. The over one million people worldwide with chronic Chagas cardiomyopathy require special consideration because of COVID-19's potential impact on the heart, yet the pandemic also affects treatment provision to people with acute or chronic indeterminate CD. In this document, a follow-up to the WHF-IASC Roadmap on CD, we assess the implications of coinfection with SARS-CoV-2 and Trypanosoma cruzi, the etiological agent of CD. Based on the limited evidence available, we provide preliminary guidance for testing, treatment, and management of patients affected by both diseases, while highlighting emerging healthcare access challenges and future research needs., The authors would like to thank Marina Certo, DNDi Platforms Coordination Officer, for invaluable support of the writing group. DNDi is grateful to its donors, public and private, who have provided funding to DNDi since its inception in 2003. A full list of DNDi donors can be found at http://www.dndi.org/donors/donors. MASY is grateful for financial support from FAPESP 2012/50273-0. ALPR is grateful for support from CNPq (310679/2016-8 and 465518/2014-1) and FAPEMIG (PPM-00428-17).
- Published
- 2020
20. Fixed vs adjusted-dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: A systematic review and meta-analysis
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Ciapponi, Agustín, Barreira, Fabiana, Perelli, Lucas, Bardach, Ariel, Gascon, Joaquim, Molina Romero, Israel, Morillo, Carlos, Prado, Nilda, Riarte, Adelina, Torrico, Faustino, Ribeiro, Isabela, Villar, Juan Carlos, Sosa-Estani, Sergio, and Universitat Autònoma de Barcelona
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0301 basic medicine ,Databases, Factual ,Epidemiology ,RC955-962 ,Cardiovascular Medicine ,Pathology and Laboratory Medicine ,law.invention ,Medical Conditions ,Mathematical and Statistical Techniques ,0302 clinical medicine ,Randomized controlled trial ,systematic review ,law ,Arctic medicine. Tropical medicine ,Medicine and Health Sciences ,Randomized Controlled Trials as Topic ,Protozoans ,benznidazole ,Statistics ,Eukaryota ,chagas ,Metaanalysis ,Research Assessment ,Serology ,Treatment Outcome ,Infectious Diseases ,Systematic review ,Cardiovascular Diseases ,Nitroimidazoles ,Benznidazole ,Meta-analysis ,Physical Sciences ,purl.org/becyt/ford/3 [https] ,Patient Safety ,Public aspects of medicine ,RA1-1270 ,Cardiomyopathies ,Research Article ,Neglected Tropical Diseases ,medicine.drug ,Adult ,Trypanosoma ,medicine.medical_specialty ,Drug Research and Development ,Systematic Reviews ,Trypanosoma cruzi ,030231 tropical medicine ,Cardiology ,MEDLINE ,Research and Analysis Methods ,Placebo ,03 medical and health sciences ,purl.org/becyt/ford/3.3 [https] ,Internal medicine ,Parasitic Diseases ,medicine ,Humans ,Chagas Disease ,Clinical Trials ,Statistical Methods ,Adverse effect ,Pharmacology ,Protozoan Infections ,business.industry ,Organisms ,Public Health, Environmental and Occupational Health ,Biology and Life Sciences ,Triazoles ,Tropical Diseases ,Parasitic Protozoans ,Randomized Controlled Trials ,Clinical trial ,030104 developmental biology ,Medical Risk Factors ,Nifurtimox ,Clinical Medicine ,business ,Mathematics - Abstract
Chagas disease is a neglected disease that remains a public health threat, particularly in Latin America. The most important treatment options are nitroimidazole derivatives, such as nifurtimox and benznidazole (BZN). Some studies suggest that for adults seropositive to T. cruzi but without clinically evident chronic Chagas cardiomyopathy (CCC), a simple fixed-dose scheme of BZN could be equivalent to a weight-adjusted dose. We compared the efficacy and safety of a fixed dose of BZN with an adjusted dose for T. cruzi seropositive adults without CCC. We used the Cochrane methods, and reported according to the PRISMA statement. We included randomized controlled trials (RCTs) allocating participants to fixed and/or adjusted doses of BZN for T. cruzi seropositive adults without CCC. We searched (December 2019) Cochrane, MEDLINE, EMBASE, LILACS, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP), and contacted Chagas experts. Selection, data extraction, and risk of bias assessment, using the Cochrane tool, were performed independently by pairs of reviewers. Discrepancies were solved by consensus within the team. Primary outcomes were parasite‐related outcomes and efficacy or patient‐related safety outcomes. We conducted a meta-analysis using RevMan 5.3 software and used GRADE summary of finding tables to present the certainty of evidence by outcome. We identified 655 records through our search strategy and 10 studies (four of them ongoing) met our inclusion criteria. We did not find any study directly comparing fixed vs adjusted doses of BZN, however, some outcomes allowed subgroup comparisons between fixed and adjusted doses of BZN against placebo. Moderate-certainty evidence suggests no important subgroup differences for positive PCR at one year and for three safety outcomes (drug discontinuation, peripheral neuropathy, and mild rash). The same effect was observed for any serious adverse events (low-certainty evidence). All subgroups showed similar effects (I2 0% for all these subgroup comparisons but 32% for peripheral neuropathy), supporting the equivalence of BZN schemes. We conclude that there is no direct evidence comparing fixed and adjusted doses of BZN. Based on low to very low certainty of evidence for critical clinical outcomes and moderate certainty of evidence for important outcomes, fixed and adjusted doses may be equivalent in terms of safety and efficacy. An individual patient data network meta-analysis could better address this issue., Author summary Chagas disease is a major public health problem that requires, among other control interventions, an optimal trypanocidal therapy that achieves the best possible compliance to cure active infection, mainly in children and young populations, women before they become pregnant to prevent congenital transmission, and chronic populations who are currently not being treated and with a risk of progression to cardiomyopathy. Some studies suggest that a simple fixed-dose scheme of benznidazole could be equivalent to the dose adjusted by weight for the treatment of adults seropositive to T. cruzi without clinically evident chronic Chagas cardiomyopathy. To confirm or reject this potential equivalence of schemes, we conducted a rigorous systematic review and meta-analysis of randomized controlled trials by reviewing and analyzing the totality of available literature on the subject. Although we did not find direct evidence addressing this question, it appears that an adjusted dose is probably equivalent in terms of important safety and efficacy outcomes, while the effect on critical outcomes is uncertain. Since we did not find any ongoing study comparing fixed versus adjusted doses of benznidazole, we are conducting an individual patient data network meta-analysis to address this question.
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- 2020
21. Survival after heart transplantation for Chagas cardiomyopathy using a conventional protocol: A 10‐year experience in a single center.
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Echeverría, Luis E., Figueredo, Antonio, Rodriguez, María J., Salazar, Leonardo, Pizarro, Camilo, Morillo, Carlos A., Rojas, Lyda Z., Gómez‐Ochoa, Sergio A., and Castillo, Victor R.
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HEART transplantation ,LIFESAVING ,CAUSES of death ,CARDIOMYOPATHIES ,HEART failure patients ,PROGNOSIS - Abstract
Background: Heart transplant (HT) remains the most frequently indicated therapy for patients with end‐stage heart failure that improves prognosis in Chagas cardiomyopathy (CCM). However, the lack of benznidazole therapy and availability of RT‐PCR follow‐up in many centers is a major limitation to perform this life‐saving intervention, as there are concerns related with the risk of reactivation. We aimed to describe the outcomes of a cohort of patients with CCM who underwent HT using a conventional protocol with mycophenolate mofetil, without benznidazole prophylaxis or RT‐PCR follow‐up. Methods: Retrospective cohort study. Between 2008 and 2018, 43 patients with CCM underwent HT. A descriptive analysis to characterize outcomes as rejection, infectious and neoplastic complications and a survival analysis was carried out. Results: Median of follow‐up was 4.3 (IR 4.28) years. Survival at 1 month, 1 year, and 5 years was 95%, 85%, and 75%, respectively, infections being the main cause of death (60%). Reactivations occurred in only three patients (7.34%) and were not related to mortality. Conclusion: This cohort showed a favorable survival and a low reactivation rate without an impact on mortality. Our results suggest that performing HT in patients with CCM following conventional guidelines and recommendations for other etiologies is a safe approach. [ABSTRACT FROM AUTHOR]
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- 2021
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22. Circulating Trypanosoma cruzi load and major cardiovascular outcomes in patients with chronic Chagas cardiomyopathy: a prospective cohort study.
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Echeverría, Luis E., Rojas, Lyda Z., Rueda‐Ochoa, Oscar L., Gómez‐Ochoa, Sergio Alejandro, González Rugeles, Clara Isabel, Díaz, Martha Lucía, Marcus, Rachel, and Morillo, Carlos A.
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TRYPANOSOMA cruzi ,LONGITUDINAL method ,COHORT analysis ,CARDIOMYOPATHIES ,POLYMERASE chain reaction - Abstract
Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2020
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23. COVID-19: Implications for People with Chagas Disease.
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José Zaidel, Ezequiel, Forsyth, Colin J., Novick, Gabriel, Marcus, Rachel, Ribeiro, Antonio Luiz P., Pinazo, María-Jesus, Morillo, Carlos A., Eduardo Echeverría, Luis, Shikanai-Yasuda, Maria Aparecida, Buekens, Pierre, Perel, Pablo, Meymandi, Sheba K., Ralston, Kate, Pinto, Fausto, and Sosa-Estani, Sergio
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As the global COVID-19 pandemic advances, it increasingly impacts those vulnerable populations who already bear a heavy burden of neglected tropical disease. Chagas disease (CD), a neglected parasitic infection, is of particular concern because of its potential to cause cardiac, gastrointestinal, and other complications which could increase susceptibility to COVID-19. The over one million people worldwide with chronic Chagas cardiomyopathy require special consideration because of COVID-19's potential impact on the heart, yet the pandemic also affects treatment provision to people with acute or chronic indeterminate CD. In this document, a follow-up to the WHF-IASC Roadmap on CD, we assess the implications of coinfection with SARS-CoV-2 and Trypanosoma cruzi, the etiological agent of CD. Based on the limited evidence available, we provide preliminary guidance for testing, treatment, and management of patients affected by both diseases, while highlighting emerging healthcare access challenges and future research needs. [ABSTRACT FROM AUTHOR]
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- 2020
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24. WHF IASC Roadmap on Chagas Disease.
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Eduardo Echeverría, Luis, Marcus, Rachel, Novick, Gabriel, Sosa-Estani, Sergio, Ralston, Kate, Jose Zaidel, Ezequiel, Forsyth, Colin, Ribeiro, Antonio Luiz P., Mendoza, Iván, Luis Falconi, Mariano, Mitelman, Jorge, Morillo, Carlos A., Cristina Pereiro, Ana, Pinazo, María Jesús, Salvatella, Roberto, Martinez, Felipe, Perel, Pablo, Sosa Liprandi, Álvaro, José, Daniel, and Piñeiro
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Background: Chagas Disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi, with some of the most serious manifestations affecting the cardiovascular system. It is a chronic, stigmatizing condition, closely associated with poverty and affecting close to 6 million people globally. Although historically the disease was limited to endemic areas of Latin America recent years have seen an increasing global spread. In addition to the morbidity and mortality associated with the disease, the social and economic burdens on individuals and society are substantial. Often called the 'silent killer', Chagas disease is characterized by a long, asymptomatic phase in affected individuals. Approximately 30% then go on develop chronic Chagas cardiomyopathy and other serious cardiac complications such as stroke, rhythm disturbances and severe heart failure. Methods: In a collaboration of the World Hearth Federation (WHF) and the Inter-American Society of Cardiology (IASC) a writing group consisting of 20 diverse experts on Chagas disease (CD) was convened. The group provided up to date expert knowledge based on their area of expertise. An extensive review of the literature describing obstacles to diagnosis and treatment of CD along with proposed solutions was conducted. A survey was sent to all WHF Members and, using snowball sampling to widen the consultation, to a variety of health care professionals working in the CD global health community. The results were analyzed, open comments were reviewed and consolidated, and the findings were incorporated into this document, thus ensuring a consensus representation. Results: The WHF IASC Roadmap on Chagas Disease offers a comprehensive summary of current knowledge on prevention, diagnosis and management of the disease. In providing an analysis of 'roadblocks' in access to comprehensive care for Chagas disease patients, the document serves as a framework from which strategies for implementation such as national plans can be formulated. Several dimensions are considered in the analysis: healthcare system capabilities, governance, financing, community awareness and advocacy. Conclusion: The WHF IASC Roadmap proposes strategies and evidence-based solutions for healthcare professionals, health authorities and governments to help overcome the barriers to comprehensive care for Chagas disease patients. This roadmap describes an ideal patient care pathway, and explores the roadblocks along the way, offering potential solutions based on available research and examples in practice. It represents a call to action to decision-makers and health care professionals to step up efforts to eradicate Chagas disease. [ABSTRACT FROM AUTHOR]
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- 2020
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25. Perfiles de citocinas en la enfermedad de Chagas: hacia la comprensión de la asociación con unidades de tipificación discretas de Trypanosoma cruzi infecciosas (un subestudio de ensayo de beneficios)
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Poveda, Cristina, Fresno, Manuel, Gironès, Núria, Martins-Filho, Olindo A., Ramírez, Juan David, Santi-Rocca, Julien, Marin-Neto, José A., Morillo, Carlos A., Rosas, Fernando, and Guhl, Felipe
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Chagas disease ,Genetic polymorphism ,Protozoan infections ,Trypanosoma cruzi ,parasitic diseases ,Cytokines ,Immune response ,Cardiomyopathies ,Parasitic diseases - Abstract
Background Chagas disease caused by the protozoan Trypanosoma cruzi is an important public health problem in Latin America. The immunological mechanisms involved in Chagas disease pathogenesis remain incompletely elucidated. The aim of this study was to explore cytokine profiles and their possible association to the infecting DTU and the pathogenesis of Chagas disease. Methods 109 sero-positive T. cruzi patients and 21 negative controls from Bolivia and Colombia, were included. Flow cytometry assays for 13 cytokines were conducted on human sera. Patients were divided into two groups: in one we compared the quantification of cytokines between patients with and without chronic cardiomyopathy; in second group we compared the levels of cytokines and the genetic variability of T. cruzi. Results Significant difference in anti-inflammatory and pro-inflammatory cytokines profiles was observed between the two groups cardiac and non-cardiac. Moreover, serum levels of IFN-?, IL-12, IL-22 and IL-10 presented an association with the genetic variability of T.cruzi, with significant differences in TcI and mixed infections TcI/TcII. Conclusion Expression of anti-inflammatory and pro-inflammatory cytokines may play a relevant role in determining the clinical presentation of chronic patients with Chagas disease and suggests the occurrence of specific immune responses, probably associated to different T. cruzi DTUs.
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- 2014
26. Electrophysiological characteristics of Chagas disease
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Cedraz, Swellen Schuenemann, da Silva, Paulo Christo Coutinho, Minowa, Ricardo Katsumi Yendo, de Aragão, Juliano Furtado, Silva, Danilo Victor, Morillo, Carlos, Moreira, Dalmo Antonio Ribeiro, Habib, Ricardo Garbe, Valdigem, Bruno Pereira, and Armaganijan, Luciana Vidal
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Chagas disease ,Arrhythmias, cardiac ,cardiac ,Cardiac electrophysiology ,Eletrocardiografia ,Arrhythmias ,Volume sistólico ,Doença de Chagas ,Arritmias cardíacas ,Electrocardiography ,Eletrofisiologia cardíaca ,Stroke volume ,cardiovascular system ,Original Article ,cardiovascular diseases - Abstract
OBJETIVO: A doença de Chagas constitui importante problema de saúde pública global devido às mudanças nos padrões migratórios. O estudo eletrofisiológico é usualmente indicado na avaliação da função do nó sinusal, condução pelo nó atrioventricular e sistema His-Purkinje e mecanismos das arritmias. O objetivo deste estudo foi descrever as características do estudo eletrofisiológico em pacientes com doença de Chagas. MÉTODOS: Estudo retrospectivo e descritivo de 115 pacientes consecutivos com doença de Chagas submetidos ao estudo eletrofisiológico nos últimos 3 anos em centro terciário no Brasil. Características basais, eletrocardiográficas, ecocardiográficas e de Holter de 24 horas foram avaliadas e correlacionadas aos achados do estudo eletrofisiológico. RESULTADOS: Os tempos corrigidos de recuperação do nó sinusal e condução sinoatrial foram anormais em 6,9% e 26,1% dos pacientes, respectivamente. Apresentaram condução atrioventricular anormal 37 (32,2%) pacientes. A condução intraventricular mostrou-se alterada em 39 (33,9%) pacientes. Em aproximadamente 48%, houve indução de arritmias ventriculares sustentadas, sendo a maioria monomórfica (83,6%). A morfologia de bloqueio de ramo direito foi a mais comumente observada (52,7%). Dentre as arritmias, 51% associaram-se a sintomas/instabilidade hemodinâmica, 60% necessitaram de cardioversão elétrica e 27,3% de estimulação rápida. O sítio de origem mais comum foi a parede inferosseptal do ventrículo esquerdo (18,2%), seguido pela parede posterobasal (11%). Pacientes com fração de ejeção60% (OR: 1,94; IC95%: 1,12-3,38; p=0,01). A presença de arritmias ventriculares complexas no Holter não foi preditiva de indução de arritmias ventriculares. CONCLUSÕES: Chagásicos com fração de ejeção baixa apresentam maior risco de arritmias ventriculares induzidas. Disfunção do nó sinusal e anormalidades da condução atrioventricular e do sistema His-Purkinje ocorrem em aproximadamente um terço dos pacientes. Arritmias ventriculares complexas no Holter não foram preditoras de indução de arritmias ventriculares nessa amostra populacional. OBJECTIVE: Chagas disease has become a global problem due to changing migration patterns. An electrophysiological study is generally indicated for assessing sinus node function, conduction through the atrioventricular node and His-Purkinje system, in addition to evaluating the mechanisms of arrhythmia. The aim of this study was to describe the characteristics of electrophysiological study findings in patients with Chagas disease. METHODS: A retrospective descriptive study of 115 consecutive patients with Chagas disease undergoing an electrophysiological study over the last three years in a tertiary hospital in Brazil. Baseline characteristics, electrocardiogram, echocardiogram, and 24-hour Holter monitoring findings were recorded and correlated with the electrophysiological study findings. RESULTS: The corrected sinus node recovery time and sinoatrial conduction time were abnormal in 6.9% and 26.1% of patients, respectively. Thirty-seven (32.2%) had abnormal atrioventricular conduction. Intraventricular conduction was abnormal in 39 (33.9%). Approximately 48% had induced sustained ventricular arrhythmias, most of which were monomorphic (83.6%). Right bundle branch block was the most common morphology (52.7%). Fifty-one percent were associated with symptoms/hemodynamic instability, 60% required electrical cardioversion, and 27.3% needed overdrive suppression. The most common site of origin was the left ventricular inferoseptal wall (18.2%), followed by the left ventricular posterobasal wall (11%). Patients with an ejection fraction60% (OR: 1.94; 95%CI: 1.12-3.38; p=0.01). The presence of complex ventricular arrhythmias on Holter did not predict inducible ventricular arrhythmias. CONCLUSIONS: Chagas patients with a low ejection fraction have an increased risk of inducible ventricular arrhythmias. Sinus node dysfunction, and atrioventricular node and His-Purkinje conduction abnormalities occur in about one-third of patients. Complex ventricular arrhythmias on Holter were not associated with an increased risk of inducible ventricular arrhythmias.
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- 2013
27. Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis.
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Rojas, Lyda Z., Glisic, Marija, Pletsch-Borba, Laura, Echeverría, Luis E., Bramer, Wichor M., Bano, Arjola, Stringa, Najada, Zaciragic, Asija, Kraja, Bledar, Asllanaj, Eralda, Chowdhury, Rajiv, Morillo, Carlos A., Rueda-Ochoa, Oscar L., Franco, Oscar H., and Muka, Taulant
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CHAGAS' disease ,ELECTROCARDIOGRAPHY ,META-analysis ,TRYPANOSOMIASIS ,PSYCHOMETRICS - Abstract
Background: Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population. Methods: Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model. Results: Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants. Conclusions: This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease. [ABSTRACT FROM AUTHOR]
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- 2018
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28. Cytokine Profiling in Chagas Disease: Towards Understanding the Association with Infecting Trypanosoma cruzi Discrete Typing Units (A BENEFIT TRIAL Sub-Study).
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Poveda, Cristina, Fresno, Manuel, Gironès, Núria, Martins-Filho, Olindo A., Ramírez, Juan David, Santi-Rocca, Julien, Marin-Neto, José A., Morillo, Carlos A., Rosas, Fernando, and Guhl, Felipe
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CHAGAS' disease ,CYTOKINES ,TRYPANOSOMA cruzi ,PUBLIC health ,BIOLOGICAL assay ,HUMAN genetic variation ,PATIENTS - Abstract
Background: Chagas disease caused by the protozoan Trypanosoma cruzi is an important public health problem in Latin America. The immunological mechanisms involved in Chagas disease pathogenesis remain incompletely elucidated. The aim of this study was to explore cytokine profiles and their possible association to the infecting DTU and the pathogenesis of Chagas disease. Methods: 109 sero-positive T. cruzi patients and 21 negative controls from Bolivia and Colombia, were included. Flow cytometry assays for 13 cytokines were conducted on human sera. Patients were divided into two groups: in one we compared the quantification of cytokines between patients with and without chronic cardiomyopathy; in second group we compared the levels of cytokines and the genetic variability of T. cruzi. Results: Significant difference in anti-inflammatory and pro-inflammatory cytokines profiles was observed between the two groups cardiac and non-cardiac. Moreover, serum levels of IFN-γ, IL-12, IL-22 and IL-10 presented an association with the genetic variability of T.cruzi, with significant differences in TcI and mixed infections TcI/TcII. Conclusion: Expression of anti-inflammatory and pro-inflammatory cytokines may play a relevant role in determining the clinical presentation of chronic patients with Chagas disease and suggests the occurrence of specific immune responses, probably associated to different T. cruzi DTUs. [ABSTRACT FROM AUTHOR]
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- 2014
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29. Infection With Trypanosoma cruzi and Progression to Cardiomyopathy What is the Evidence and Is the Tide Finally Turning?
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Morillo, Carlos A.
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TRYPANOSOMA cruzi , *BACTERIAL diseases , *CARDIOMYOPATHIES , *MORTALITY , *PARASITES , *IMMUNITY - Abstract
The author reflects on the evidences of the existence of Trypanosoma cruzi in the American continent. The author states that one of the challenges brought by T cruzi is the difficulty in verifying the exact effect of the disease. He mentions that the T cruzi has evolved for almost 10 centuries and was responsible for 12,500 deaths in 2006. He adds that one third of T cruzi infected patients develop cardiomyopathy due to parasite persistence and the immunity response of human host to infection.
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- 2013
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30. Interleukin-1 Gene Cluster Polymorphism in Chagas Disease in a Colombian Case-Control Study
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Flórez, Oscar, Zafra, German, Morillo, Carlos, Martín, Javier, and González, Clara Isabel
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GENETIC polymorphisms , *CHAGAS' disease , *TRYPANOSOMA , *DNA polymerases - Abstract
Abstract: The aim of this study was to assess the possible association between the IL1A, IL1B and IL1RN gene polymorphisms and Chagas disease. Our study population consisted of 130 serologically positive cardiomyopathic patients and 130 seropositive and asymptomatic individuals from a Colombian population where Trypanosoma cruzi infection is endemic. Genotyping of the IL1A (−889C/T, +4845G/T), IL1B (−511C/T, −31T/C, +3954T/C, +5810G/A) and IL1RN (+8006T/C, +8061C/T, +11100T/C) polymorphisms was performed by polymerase chain reaction–restriction fragment length polymorphism and polymerase chain reaction sequence-specific primer methods. Statistically significant differences in the distribution of the IL1B +5810 genotypes were observed comparing cardiomyopathic patients and asymptomatic individuals (p = 0.036). Frequency of the GG genotype was higher in the cardiomyopathic patient group than in the asymptomatic group (13% versus 5%, p = 0.03, odds ratio [OR] = 2.64, 95% confidence interval [CI] = 0.99–7.33). Differences in the distribution of the allele frequencies were also observed, being the +5810G allele overrepresented in patients with cardiomyopathy (37% versus 27%, p = 0.014, OR = 1.59, 95% CI = 1.08–2.36). Examination of markers in the IL1A (−889 and +4845), IL1B (−511, −31, and +3954) and IL1RN (+11100) genes revealed that the overall distribution of alleles and genotypes in patients with chagasic cardiomyopathy and asymptomatic were not significantly different. Our results show that in Colombian population the IL1B+5810G allele was associated with an increased risk chagasic cardiomyopathy. In addition, we demonstrated that homozygosity for the IL1B +5810G risk allele increased significantly the susceptibility to cardiomyopathy. This implies that the effect of IL1B gene on chagasic cardiomyopathy predisposition is dose dependent. We found that the haplotype CT of IL1B −31 and +3954 polymorphisms showed higher association with risk to chagasic cardiomyopathy (pc = 0.008, OR = 12.53) and the extended haplotype (CCTCATT) was significantly more frequent in asymptomatic than in cardiomyopathic patients (p = 0.0014, pc = 0.011, OR = 0.17). Therefore this study suggests that IL1 gene cluster polymorphisms may play a relevant role in the susceptibility to development of chagasic chronic cardiomyopathy. [Copyright &y& Elsevier]
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- 2006
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31. Profiles of cardiovascular biomarkers according to severity stages of Chagas cardiomyopathy.
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Echeverría, Luis E., Rojas, Lyda Z., Calvo, Lauren S., Roa, Zayne M., Rueda-Ochoa, Oscar L., Morillo, Carlos A., Muka, Taulant, and Franco, Oscar H.
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BIOMARKERS , *CHAGAS' disease , *CARDIOMYOPATHIES , *ELECTROCARDIOGRAPHY , *TROPONIN , *DIAGNOSIS - Abstract
Background/objectives Up 30 to 40% of Chagas patients exhibit cardiomyopathy with different degrees of cardiac involvement. Biomarkers may help in differentiation of the severity of Chagas cardiomyopathy (CCM). This study sought to examine the diagnostic value of a panel of biomarkers to distinguish the severity of (CCM). Methods 100 patients with CCM were included in this cross-sectional study. Based on electrocardiogram and echocardiogram, CCM patients were classified in three stages according to disease's severity. Levels of high-sensitivity cardiac troponin T (Hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), soluble ST2 (sST2) and cystatin-c (Cys-c) were measured. Logistic regression models were used to assess the association between levels of natural log-transformed values of biomarkers and stages C/D versus B. We also calculated the area under curve (AUC) for each of the models. Results In models adjusted for age, sex, body mass index, kidney function and medication use, increased levels of NT-proBNP (per 1 unit natural log-transformed values, odds ratio (OR) = 5.55; 95CI%:1.65–18.72) and Hs-cTnT (per 1 unit natural log-transformed values, OR = 7.11; 95CI%:1.41–35.90) showed significant association with the severity of CCM per 1 unit increase of biomarkers. The accuracy of NT-proBNP and Hs-cTnT for diagnosis of the severity of CCM was high: AUC of 0.968 and 0.956 respectively. No significant difference was found in the AUC between NT-proBNP and Hs-cTnT. No association was found between Gal-3, NGAL, sST2 and Cys-C and severity of CCM. Conclusions NT-proBNP and Hs-cTnT have both same diagnostic value in distinguishing severity of CCM. [ABSTRACT FROM AUTHOR]
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- 2017
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32. Electrophysiological characteristics of Chagas disease.
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Schuenemann Cedraz, Swellen, Coutinho da Silva, Paulo Christo, Yendo Minowa, Ricardo Katsumi, Furtado de Aragão, Juliano, Silva, Danilo Victor, Morillo, Carlos, Ribeiro Moreira, Dalmo Antonio, Garbe Habib, Ricardo, Pereira Valdigem, Bruno, and Vidal Armaganijan, Luciana
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CHAGAS' disease , *SINOATRIAL node , *PURKINJE fibers , *ARRHYTHMIA , *AMBULATORY electrocardiography - Abstract
Objective: Chagas disease has become a global problem due to changing migration patterns. An electrophysiological study is generally indicated for assessing sinus node function, conduction through the atrioventricular node and His-Purkinje system, in addition to evaluating the mechanisms of arrhythmia. The aim of this study was to describe the characteristics of electrophysiological study findings in patients with Chagas disease. Methods: A retrospective descriptive study of 115 consecutive patients with Chagas disease undergoing an electrophysiological study over the last three years in a tertiary hospital in Brazil. Baseline characteristics, electrocardiogram, echocardiogram, and 24-hour Holter monitoring findings were recorded and correlated with the electrophysiological study findings. Results: The corrected sinus node recovery time and sinoatrial conduction time were abnormal in 6.9% and 26.1% of patients, respectively. Thirty-seven (32.2%) had abnormal atrioventricular conduction. Intraventricular conduction was abnormal in 39 (33.9%). Approximately 48% had induced sustained ventricular arrhythmias, most of which were monomorphic (83.6%). Right bundle branch block was the most common morphology (52.7%). Fifty-one percent were associated with symptoms/hemodynamic instability, 60% required electrical cardioversion, and 27.3% needed overdrive suppression. The most common site of origin was the left ventricular inferoseptal wall (18.2%), followed by the left ventricular posterobasal wall (11%). Patients with an ejection fraction<40% had a 1.94-fold increased risk of ventricular arrhythmias compared to those with an ejection fraction>60% (OR: 1.94; 95%CI: 1.12-3.38; p=0.01). The presence of complex ventricular arrhythmias on Holter did not predict inducible ventricular arrhythmias. Conclusions: Chagas patients with a low ejection fraction have an increased risk of inducible ventricular arrhythmias. Sinus node dysfunction, and atrioventricular node and His-Purkinje conduction abnormalities occur in about one-third of patients. Complex ventricular arrhythmias on Holter were not associated with an increased risk of inducible ventricular arrhythmias. [ABSTRACT FROM AUTHOR]
- Published
- 2013
33. Chagas Cardiomyopathy: An Update of Current Clinical Knowledge and Management: A Scientific Statement From the American Heart Association.
- Author
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Nunes, Maria Carmo Pereira, Beaton, Andrea, Acquatella, Harry, Bern, Caryn, Bolger, Ann F., Echeverría, Luis E., Dutra, Walderez O., Gascon, Joaquim, Morillo, Carlos A., Oliveira-Filho, Jamary, Ribeiro, Antonio Luiz Pinho, Marin-Neto, Jose Antonio, Echeverría, Luis E, and American Heart Association Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Stroke Council
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CHAGAS' disease , *CARDIOMYOPATHIES , *TRYPANOSOMA cruzi , *CHAGAS' disease prevention , *HEART failure , *ARRHYTHMIA , *INFECTIOUS disease transmission - Abstract
Background: Chagas disease, resulting from the protozoan Trypanosoma cruzi, is an important cause of heart failure, stroke, arrhythmia, and sudden death. Traditionally regarded as a tropical disease found only in Central America and South America, Chagas disease now affects at least 300 000 residents of the United States and is growing in prevalence in other traditionally nonendemic areas. Healthcare providers and health systems outside of Latin America need to be equipped to recognize, diagnose, and treat Chagas disease and to prevent further disease transmission.Methods and Results: The American Heart Association and the Inter-American Society of Cardiology commissioned this statement to increase global awareness among providers who may encounter patients with Chagas disease outside of traditionally endemic environments. In this document, we summarize the most updated information on diagnosis, screening, and treatment of T cruzi infection, focusing primarily on its cardiovascular aspects. This document also provides quick reference tables, highlighting salient considerations for a patient with suspected or confirmed Chagas disease.Conclusions: This statement provides a broad summary of current knowledge and practice in the diagnosis and management of Chagas cardiomyopathy. It is our intent that this document will serve to increase the recognition of Chagas cardiomyopathy in low-prevalence areas and to improve care for patients with Chagas heart disease around the world. [ABSTRACT FROM AUTHOR]- Published
- 2018
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