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      WHF IASC Roadmap on Chagas Disease

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          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.

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          Most cited references124

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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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            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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              Chagas Cardiomyopathy: An Update of Current Clinical Knowledge and Management: A Scientific Statement From the American Heart Association

              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.
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                Author and article information

                Contributors
                Role: Post Graduate
                Journal
                Glob Heart
                Glob Heart
                2211-8179
                Global Heart
                Ubiquity Press
                2211-8160
                2211-8179
                30 March 2020
                2020
                : 15
                : 1
                : 26
                Affiliations
                [1 ]Department of Cardiology, Cardiovascular Foundation of Colombia, Floridablanca, CO
                [2 ]LASOCHA, Washington DC, US
                [3 ]Medstar Union Memorial Hospital, Baltimore, MD, US
                [4 ]Swiss Medical Group, Buenos Aires, AR
                [5 ]Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, US
                [6 ]Drugs for Neglected Diseases initiative-Latin America, Rio de Janeiro, BR
                [7 ]World Heart Federation, Geneva, CH
                [8 ]Sanatorio Güemes, Buenos Aires, AR
                [9 ]Pharmacology Department, School of Medicine, University of Buenos Aires, Buenos Aires, AR
                [10 ]Internal Medicine Department, School of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, BR
                [11 ]Hospital das Clínicas, UFMG, Belo Horizonte, BR
                [12 ]Central University of Venezuela, Caracas, VE
                [13 ]Cardiology Division, Italian Hospital of Buenos Aires, Buenos Aires, AR
                [14 ]University Institute of the Italian Hospital of Buenos Aires, Buenos Aires, AR
                [15 ]Faculty of Medicine, University of Buenos Aires, Buenos Aires, AR
                [16 ]School of Medicine, Barcélo University, Buenos Aires, AR
                [17 ]Department of Cardiac Sciences, Cumming School of Medicine Division of Cardiology, Libin Cardiovascular Institute, University of Calgary, Calgary, CA
                [18 ]Southeastern Alberta Region, Alberta Health Services, Foothills Medical Centre, CA
                [19 ]Mundo Sano Foundation, Buenos Aires, AR
                [20 ]ISGlobal, Hospital Clínic, University of Barcelona, Barcelona, ES
                [21 ]PAHO/WHO, Montevideo, UY
                [22 ]National University of Cordoba, Cordoba, AR
                [23 ]DAMIC Institute/Rusculleda Foundation, Cordoba, AR
                [24 ]Centre for Global Chronic Conditions, London School of Hygiene and Tropical Medicine, London, GB
                [25 ]Medical School of Cardiology, University of Buenos Aires, Buenos Aires, AR
                [26 ]Faculty of Medicine, University of Buenos Aires, Buenos Aires, AR
                [27 ]School of Medicine, CES University, Medellín, CO
                Author notes
                Corresponding author: Luis Eduardo Echeverría ( luisedo10@ 123456gmail.com )
                Article
                10.5334/gh.484
                7218776
                32489799
                85aee420-932f-4bca-8979-8b9c444bd135
                Copyright: © 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/.

                History
                : 27 December 2019
                : 17 January 2020
                Funding
                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.
                Categories
                Original Research

                chagas disease,cardiomyopathy,neglected tropical disease,heart failure

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