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      Enfermedad de chagas: realidad de una patología frecuente en Santander, Colombia Translated title: Chagas disease: reality of a frequent pathology in Santander, Colombia

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          Abstract

          Introducción: la tripanosomiasis americana o enfermedad de Chagas es una de las parasitosis transmitidas por insectos hematófagos de mayor importancia epidemiológica en América Latina y es producida por el protozoo Trypanosoma cruzi, se presentan dos fases clínicas importantes: aguda y crónica. Objetivo: presentar una actualización de la enfermedad de Chagas de forma integral, especificando contenidos claves como su definición, etiología, ciclo de vida, epidemiología, diagnóstico, manifestaciones clínicas y tratamiento. Metodología de búsqueda: se llevó a cabo una revisión bibliográfica en bases de datos y bibliotecas virtuales como OvidSP, Medline, EBSCO host, Pubmed, Uptodate, New England Journal of Medicine, Cochrane y SciELO, usando palabras clave como cardiomiopatía chagásica, enfermedad de Chagas, Trypanosoma cruzi e insectos. Resultados: el tipo de lesión cardíaca más frecuente en la enfermedad de Chagas crónica es la cardiomiopatía, cuyo diagnóstico y pronóstico clínico está ligado a una continua monitorización del electrocardiograma y la ecocardiografía. Para una detección por laboratorio es necesario identificar clínicamente la fase de la enfermedad para escoger la prueba diagnóstica que tenga mayor sensibilidad. Desde el punto de vista terapéutico se tienen pocas alternativas farmacológicas para la erradicación del parásito, por lo cual se requieren modelos de prevención y promoción acordes a la población colombiana en general. Conclusión: la compresión de la enfermedad en todos sus aspectos es una herramienta fundamental en la creación de nuevas alternativas preventivas y de tratamiento, para controlar este tipo infección que en la actualidad agobia a la población de zonas urbanas y rurales principalmente de América Latina, mejorando de esta manera la calidad de vida de los pacientes. MÉD.UIS. 2015;28(1):81-90

          Translated abstract

          Introduction: the American Trypanosomiasis or Chagas disease is one of the parasitic diseases that has most epidemiological importance in Latin America and is transmitted by blood-sucking insects and it is caused by the protozoan Trypanosoma cruzi. This disease presents itself in two important clinical phases: acute and chronic. Objective: submit an update on the Chagas disease, specifying key information like its definition, etiology, life cycle, epidemiology, diagnosis, clinical manifestations and treatment. Methodology: we reviewed a great amount of literature found in databases and virtual libraries such as: OvidSP, Medline, EBSCO host, Pubmed, Uptodate, New England Journal of Medicine, Cochrane and SciELO, using words like Chagas cardiomyopathy, Chagas disease, Trypanosoma cruzi, Insects. Discussion: the most common type of cardiac damage in chronic Chagas is the cardiomyopathy, whose clinical diagnosis and prognosis is linked to a continuous variety of monitoring methods such as echocardiography and electrocardiograms, for laboratory detection clinically necessary to identify the phase of the disease to select the diagnostic test be more sensitive. Now from a therapeutic point of view, there is a low amount of pharmacological alternatives for the eradication of the parasite, reason for which it is important to have prevention models for the Colombian population in general. Conclusion: understanding and knowing the disease in all its aspects is a fundamental tool in the creation of new prevention options and treatments to control this type of disease, which currently affects a big amount of the population found in urban areas all over the world but most importantly in Latin America, and this way helping improve the quality of life of each patient. MÉD.UIS. 2015;28(1):81-90

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          Most cited references86

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          Randomized trial of posaconazole and benznidazole for chronic Chagas' disease.

          Current therapeutic options for Chagas' disease are limited to benznidazole and nifurtimox, which have been associated with low cure rates in the chronic stage of the disease and which have considerable toxicity. Posaconazole has shown trypanocidal activity in murine models. We performed a prospective, randomized clinical trial to assess the efficacy and safety of posaconazole as compared with the efficacy and safety of benznidazole in adults with chronic Trypanosoma cruzi infection. We randomly assigned patients to receive posaconazole at a dose of 400 mg twice daily (high-dose posaconazole), posaconazole at a dose of 100 mg twice daily (low-dose posaconazole), or benznidazole at a dose of 150 mg twice daily; all the study drugs were administered for 60 days. We assessed antiparasitic activity by testing for the presence of T. cruzi DNA, using real-time polymerase-chain-reaction (rt-PCR) assays, during the treatment period and 10 months after the end of treatment. Posaconazole absorption was assessed on day 14. The intention-to-treat population included 78 patients. During the treatment period, all the patients tested negative for T. cruzi DNA on rt-PCR assay beyond day 14, except for 2 patients in the low-dose posaconazole group who tested positive on day 60. During the follow-up period, in the intention-to-treat analysis, 92% of the patients receiving low-dose posaconazole and 81% receiving high-dose posaconazole, as compared with 38% receiving benznidazole, tested positive for T. cruzi DNA on rt-PCR assay (P<0.01 for the comparison of the benznidazole group with either posaconazole group); in the per-protocol analysis, 90% of the patients receiving low-dose posaconazole and 80% of those receiving high-dose posaconazole, as compared with 6% receiving benznidazole, tested positive on rt-PCR assay (P<0.001 for the comparison of the benznidazole group with either posaconazole group). In the benznidazole group, treatment was discontinued in 5 patients because of severe cutaneous reactions; in the posaconazole groups, 4 patients had aminotransferase levels that were more than 3 times the upper limit of the normal range, but there were no discontinuations of treatment. Posaconazole showed antitrypanosomal activity in patients with chronic Chagas' disease. However, significantly more patients in the posaconazole groups than in the benznidazole group had treatment failure during follow-up. (Funded by the Ministry of Health, Spain; CHAGASAZOL ClinicalTrials.gov number, NCT01162967.).
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            Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches.

            A critical review of the development of specific chemotherapeutic approaches for the management of American Trypanosomiasis or Chagas disease is presented, including controversies on the pathogenesis of the disease, the initial efforts that led to the development of currently available drugs (nifurtimox and benznidazole), limitations of these therapies and novel approaches for the development of anti-Trypanosoma cruzi drugs, based on our growing understanding of the biology of this parasite. Among the later, the most promising approaches are ergosterol biosynthesis inhibitors such as posaconazole and ravuconazole, poised to enter clinical trials for chronic Chagas disease in the short term; inhibitors of cruzipain, the main cysteine protease of T. cruzi, essential for its survival and proliferation in vitro and in vivo; bisphosphonates, metabolic stable pyrophosphate analogs that have trypanocidal activity through the inhibition of the parasite's farnesyl-pyrophosphate synthase or hexokinase; inhibitors of trypanothione synthesis and redox metabolism and inhibitors of hypoxanthine-guanine phosphoribosyl-transferase, an essential enzyme for purine salvage in T. cruzi and related organisms. Finally, the economic and political challenges faced by development of drugs for the treatment of neglected tropical diseases, which afflict almost exclusively poor populations in developing countries, are analyzed and recent potential solutions for this conundrum are discussed. 2009 Elsevier B.V. All rights reserved.
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              Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease.

              Chagas disease caused by Trypanosoma cruzi remains an important neglected tropical disease and a cause of significant morbidity and mortality. No longer confined to endemic areas of Latin America, it is now found in non-endemic areas due to immigration. The parasite may persist in any tissue, but in recent years, there has been increased recognition of adipose tissue both as an early target of infection and a reservoir of chronic infection. The major complications of this disease are cardiomyopathy and megasyndromes involving the gastrointestinal tract. The pathogenesis of Chagas disease is complex and multifactorial involving many interactive pathways. The significance of innate immunity, including the contributions of cytokines, chemokines, reactive oxygen species, and oxidative stress, has been emphasized. The role of the components of the eicosanoid pathway such as thromboxane A(2) and the lipoxins has been demonstrated to have profound effects as both pro- and anti-inflammatory factors. Additionally, we discuss the vasoconstrictive actions of thromboxane A(2) and endothelin-1 in Chagas disease. Human immunity to T. cruzi infection and its role in pathogen control and disease progression have not been fully investigated. However, recently, it was demonstrated that a reduction in the anti-inflammatory cytokine IL-10 was associated with clinically significant chronic chagasic cardiomyopathy.

                Author and article information

                Journal
                muis
                Medicas UIS
                Medicas UIS
                Universidad Industrial de Santander (Bucaramanga, Santander, Colombia )
                0121-0319
                1794-5240
                April 2015
                : 28
                : 1
                : 81-90
                Affiliations
                [02] Bucaramanga Santander orgnameUniversidad de Santander UDES orgdiv1Facultad de Salud orgdiv2Escuela de Medicina Colombia
                [03] Bucaramanga Santander orgnameHospital Universitario de Santander Colombia
                [01] Bucaramanga Santander orgnameUniversidad Industrial de Santander Colombia
                Article
                S0121-03192015000100008 S0121-0319(15)02800108
                64f82d6c-e00b-4b52-9fae-79c29f19b8f4

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 10 September 2014
                : 21 December 2014
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 50, Pages: 10
                Product

                SciELO Colombia

                Categories
                Revisión de tema

                Insects,Trypanosoma cruzi,Chagas Disease,Chagas Cardiomyopathy,Insectos,Enfermedad de Chagas,Cardiomiopatía Chagásica

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