As vector control succeeds in preventing newT. cruzi infections, endemic countries will be left with urgent questions about how best to prevent vertical transmission and the severe complications of chronic infection, and how to monitor cure in infected individuals being treated. Efficient screening of target populations, accurate diagnosis of T. cruzi-infected individuals, and identification of persons at risk for developing cardiac and gastrointestinal disease are essential to successful application of drug therapy, while reliable assessment of treatment efficacy in different patient groups is indispensible to establish rational policy. The overall aim of Research Project 2 is to address the central diagnostic challenges of Chagas disease -- efficient population screening, timely identification of antitrypanosomal treatment failures, and early detection of persons most likely to progress to severe disease - through optimal application of existing assaysand development of novel diagnostic tools using genomic and proteomic approaches. Specimens for these evaluations will come from 4 major sources, pregnant mothers and their infants enrolled in a study of congenital Chagas disease at the Hospital Japones in Santa Cruz, Bolivia that we expect to start in late 2006 with R21 funding;a nested cohort of seronegative and seropositive residents of the 6 Arequipa study communities described in Research Project 1;a specimen bank amassed by Dr. Carlos, LaFuente, our Santa Cruz collaborator that includes specimens from well-characterized patients with chagasic cardiopathy and gastrointestinal disease, and from patients with other potentially cross-reacting diseases;and specimens from our group's unrelated studies in Lima that will be used as non-endemic controls. We will use these specimens to achieve our 3 specific aims: (1) to develop sensitive, practical, inexpensive tools for Chagas disease screening of children, pregnant women and other population groups by adapting existing TESA-blot and Falcon assay screening test-enzyme-linked immunosorbent assay (FAST-ELISA) techniques to a rapid point-of- care format;(2) to develop and evaluate hovel assaysto monitor response to antitrypanosomal treatment using conventional and Real Time (RT)-PCR techniques, proteomic identification of biomarkers, and adaptation of the TESA-blot for use in cases of congenital Chagas disease;and (3) to identify parasite and host markers associated with specific cardiac and gastrointestinal sequelae of T.cruzi infection through proteomics techniques based on the Surface Enhanced Laser Desorption lonisation Time of Flight Mass Spectrometry (SELDI-ToF MS). These techniques will provide immediately applicable tools for Chagas disease controls programs to use in the screening and treatment management of T.cruzi infected patients, as well as proteomic biomarkers that may provide insight into treatment responses and prognosis, and ultimately be able to be adapted for novel diagnostic tools.
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