Browsing by Author "Clark, Eva H."
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Item Biomarkers in Trypanosomacruzi -Infected and Uninfected Individuals with Varying Severity of Cardiomyopathy in Santa Cruz, Bolivia(PLOS Neglected Tropical Diseases, 2014) Okamoto, Emi E.; Sherbuk, Jacqueline E.; Clark, Eva H.; Marks, Morgan A.; Gandarilla, Omar; Galdos-Cardenas, Gerson; Vasquez-Villar, Angel; Choi, JeongBackground: Twenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc2) individuals. Methods: Participants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc2 groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve.0.60, logistic regression was performed. Results: Analyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities. Conclusions: BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes.Item Hyperendemic Chagas Disease and the Unmet Need for Pacemakers in the Bolivian Chaco(Alain Debrabant, US Food and Drug Administration, United States of America, 2014-06-05) Clark, Eva H.; Sherbuk, Jackie; Okamoto, Emi; Jois, Malasa; Galdos-Cardenas, Gerson; Vela-Guerra, Julio; Menacho-Mendez, Gilberto SilvioMorbidity and mortality from Chagas cardiomyopathy have declined over the last three decades because of disruption of domestic vector-borne transmission, improved Trypanosoma cruzi infection treatment programs, and increasing availability of advanced cardiac care. However, the Gran Chaco, an ecological zone that includes parts of Argentina, Bolivia, and Paraguay, continues to struggle with extremely high rates of vector infestation and T. cruzi infection. In addition, this region is one of the poorest in the world, with most individuals living on less than US$2 per day. We estimate that thousands of patients are in need of pacemakers secondary to advanced Chagas cardiomyopathy. However, the vast majority of these individuals lack the resources to obtain these life-saving devices. A collaborative effort must be made by pacemaker donation programs, local implantation hospitals, and the governments of countries affected by Chagas disease to address this unmet need. With the necessary cooperation and infrastructure, pacemaker reuse programs have the potential to offer thousands of low-cost devices to impoverished patients with advancing Chagas cardiomyopathy.