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Title: Toward Chagas Disease Eradication: Benznidazole Resistance in Trypanosoma Cruzi, Clinical Awareness in the United States, and the Rights of Migrants
Authors: Gilsilvetti, Mateo
Advisors: Dobson, Andrew
Department: Ecology and Evolutionary Biology
Certificate Program: Global Health and Health Policy Program
Class Year: 2019
Abstract: Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi that impacts over 10 million people throughout the world and disproportionately impacts individuals of low socioeconomic status. The large influx of migrants from endemic areas to North America, Europe, and the Pacific indicates that Chagas disease is becoming a serious public health concern in non-endemic areas. The disease, if left untreated, causes the development of Chagas induced heart disease and severe gastrointestinal complications that prove to be fatal. Because this disease affects vulnerable migrant populations, we discuss understanding Chagas disease as part of health as a human right. Understanding health, with relation to Chagas disease as a human right, creates legal obligations to ensure timely, affordable, and quality care. The realization of the right to health in the context of Chagas also involves the active participation of all levels of care. To test the quality of care of Chagas disease in the United States, with the help of the Latin American Society of Chagas, we developed a survey distributed to medical professionals to test Chagas disease competency and awareness in the United States. The survey found concerning levels of awareness in cardiologists, gastroenterologists, obstetrics and gynecologists, and substantial levels of awareness in primary care and infectious disease specialists. The mechanisms of action of the main drug used to treat the condition, benznidazole, and the resistance to these drugs in T. cruzi is poorly understood. We performed some functional genomics experiments on T. cruzi (Gal61S-C11) strain with the aim of testing the role of 8 genes found differentially expressed in transcriptome and proteome analyses of resistant parasites on the resistance pathways of benznidazole. For this, we ovexpressed target genes in sensitive T. cruzi parasites and evaluated the resistance in parasite growth to benznidazole. Because benznidazole is known to cause the creation of reactive oxygen species (ROS), which leads to parasite mortality, we also evaluated the susceptibility of the parasites to oxidative stress using mitochondrial membrane potential analysis. We found that T. cruzi parasites transfected with gene (TCSYLVIO.3602) exhibited high alteration in mitochondrial membrane potential and mitigate the effect of benznidazole on growth curvatures, suggesting that gene (TCSYLVIO.3602) contributes to benznidazole resistance in T. cruzi.
Type of Material: Princeton University Senior Theses
Language: en
Appears in Collections:Global Health and Health Policy Program, 2017-2022
Ecology and Evolutionary Biology, 1992-2022

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