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      Chagas Cardiomyopathy: From Romaña Sign to Heart Failure and Sudden Cardiac Death

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          Abstract

          Despite nearly a century of research and accounting for the highest disease burden of any parasitic disease in the Western Hemisphere, Chagas disease (CD) is still a challenging diagnosis, primarily due to its poor recognition outside of Latin America. Although initially considered endemic to Central and South America, globalization, urbanization, and increased migration have spread the disease worldwide in the last few years, making it a significant public health threat. The international medical community’s apparent lack of interest in this disease that was previously thought to be geographically restricted has delayed research on the complex host–parasite relationship that determines myocardial involvement and its differential behavior from other forms of cardiomyopathy, particularly regarding treatment strategies. Multiple cellular and molecular mechanisms that contribute to degenerative, inflammatory, and fibrotic myocardial responses have been identified and warrant further research to expand the therapeutic arsenal and impact the high burden attributed to CD. Altogether, cardiac dysautonomia, microvascular disturbances, parasite-mediated myocardial damage, and chronic immune-mediated injury are responsible for the disease’s clinical manifestations, ranging from asymptomatic disease to severe cardiac and gastrointestinal involvement. It is crucial for healthcare workers to better understand CD transmission and disease dynamics, including its behavior on both its acute and chronic phases, to make adequate and evidence-based decisions regarding the disease. This review aims to summarize the most recent information on the epidemiology, pathogenesis, clinical presentation, diagnosis, screening, and treatment of CD, emphasizing on Chagasic cardiomyopathy’s (Ch-CMP) clinical presentation and pathobiological mechanisms leading to sudden cardiac death.

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          The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications.

          The protozoan Trypanosoma cruzi, its mammalian reservoirs, and vectors have existed in nature for millions of years. The human infection, named Chagas disease, is a major public health problem for Latin America. T. cruzi is genetically highly diverse and the understanding of the population structure of this parasite is critical because of the links to transmission cycles and disease. At present, T. cruzi is partitioned into six discrete typing units (DTUs), TcI-TcVI. Here we focus on the current status of taxonomy-related areas such as population structure, phylogeographical and eco-epidemiological features, and the correlation of DTU with natural and experimental infection. We also summarize methods for DTU genotyping, available for widespread use in endemic areas. For the immediate future multilocus sequence typing is likely to be the gold standard for population studies. We conclude that greater advances in our knowledge on pathogenic and epidemiological features of these parasites are expected in the coming decade through the comparative analysis of the genomes from isolates of various DTUs. Copyright © 2012 Elsevier B.V. All rights reserved.
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            Clinical and epidemiological aspects of Chagas disease.

            A. Prata (2001)
            Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. During the past decades, after urban migrations, Chagas disease became frequent in cities and a health problem in non-endemic countries, where it can be transmitted vertically and by blood transfusion or organ transplantation. Microepidemics of acute Chagas disease have been reported, probably due to oral transmission. Heart involvement is the major feature of the disease because of its characteristics, frequency, and consequences, and is also the source of most controversies. The indeterminate clinical form, despite its good prognosis on at least a medium-term basis (5-10 years), has acquired increasing importance due to the controversial meaning of the abnormality of some tests and the myocardial focal lesions found in many patients. Simultaneous evaluation of the parasympathetic and of the sympathetic system in the heart has been done by spectral analysis of heart rate. The physiopathological and clinical significance of denervation in Chagas disease is still incompletely understood. There are major divergences of opinion on specific treatment during the chronic phase because of the doubts about cure rates. Changes of Chagas disease prevalence in many countries have been certified by the Pan American Health Organization, and are ascribed to large-scale vector-control programmes with modern pyrethroid insecticides and to improvement in lifestyle.
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              Pathogenesis of chronic Chagas heart disease.

              Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damage. The pathogenesis of chronic Chagas heart disease is dependent on a low-grade but incessant systemic infection with documented immune-adverse reaction. Parasite persistence and immunological mechanisms are inextricably related in the myocardial aggression in the chronic phase of Chagas heart disease. Most clinical studies have been performed in very small number of patients. Future research should explore the clinical potential implications and therapeutic opportunities of these 2 fundamental underlying pathogenetic mechanisms.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                22 April 2021
                May 2021
                : 10
                : 5
                : 505
                Affiliations
                [1 ]School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 110131, Colombia; germanj.medina@ 123456urosario.edu.co (G.J.M.-R.); juans.bernal@ 123456urosario.edu.co (S.G.-B.); mjrodriguez@ 123456cardioinfantil.org (M.J.R.); jforero@ 123456cardioinfantil.org (J.F.F.); hmedina@ 123456cardioinfantil.org (H.M.M.)
                [2 ]Division of Cardiology, Fundación Cardio-Infantil-Instituto de Cardiología, Bogotá 110131, Colombia; rimedina@ 123456cardioinfantil.org (R.M.-M.); fmanrique@ 123456cardioinfantil.org (F.T.M.)
                [3 ]Internal Medicine Residency Program, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; duranca@ 123456ccf.org
                [4 ]Department of Infectious Diseases, Fundación Cardio-Infantil-Instituto de Cardiología, Bogotá 110131, Colombia; aarangod@ 123456cardioinfantil.org
                [5 ]Division of Radiology, Fundación Cardio-Infantil-Instituto de Cardiología, Bogotá 110131, Colombia
                Author notes
                [* ]Correspondence: antonia.pino@ 123456urosario.edu.co ; Tel.: +57-(1)-667-2727
                Author information
                https://orcid.org/0000-0002-6065-0078
                https://orcid.org/0000-0003-2874-3669
                https://orcid.org/0000-0001-8442-529X
                https://orcid.org/0000-0001-5070-838X
                https://orcid.org/0000-0003-0393-8742
                Article
                pathogens-10-00505
                10.3390/pathogens10050505
                8145478
                33922366
                9a90aba9-cd6b-478a-ba64-0b9f7130cbef
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 19 March 2021
                : 13 April 2021
                Categories
                Review

                ch-cmp/chagas cardiomyopathy,chagas disease,trypanosoma,heart failure,sudden cardiac death

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