Saturday, May 18, 2024
5/18/2024
DESCRIPTION (provided by applicant): This application is to develop a standardized and FDA cleared rapid serodiagnostic and confirmatory test for detection of Trypanosoma cruzi (T. cruzi) infections. T. cruzi is transmitted via blood transfusions, is prevalent in Latin America, and is the causative agent for fatal chagas disease. Positive blood donors have been identified, and transmission via the insect vector has been reported in the USA. Current methods to detect infection involve serological screening using whole parasites, or crude lysates and confirmation tests in the USA use a complex radioimmunoprecipitation assay (RIPA). In this application, we have described a number of multi-antigenic fusion recombinant proteins including proprietary ITC6 and ITC8.2. The ITC8.2 has been used extensively in rapid assay formats (Trypanosoma DetectTM). This recombinant contains TcF (currently used in Abbott assay and contains four different repeating epitopes) fused with five additional peptide epitopes and has been employed as the central diagnostic target antigen. All the ITC fusion recombinants were developed during the Phase II tenure of this project and found to be far superior serological marker to the TcF alone. A number of investigations and numerous publications published or in press, confirmed the utility of ITC recombinants as dependable diagnostic targets for T. cruzi infection. In this application we are proposing to continue to develop the ITC based diagnostic assays for chagas disease by manufacturing transfer of assay from R&D to ensure compliance with cGMP and documentation requirements per FDA regulations. Initial discussion with FDA led to development of current protocol for expanded field studies using archived samples in a number of South American countries and Mexico. The data from the field studies will be used for FDA submission and FDA Premarket notification 510(k) clearance. For this purpose we have assembled several sites to perform evaluations. Finally we have developed an alternate to conventional Immunoblot confirmatory assay which is called "Rapid Multi-antigenic Assay (RMA)". The RMA is lateral flow based, uses multiple recombinants and peptides, and does not require extensive washes and accessories. The RMA will be cost effective and therefore will likely to be used by more diagnostic centers and clinics in Latin American countries where Chagas disease is prevalent. In the USA, Trypanosoma Detect will have utility in diagnosis of T. cruzi infections in prospective USA cardiac surgery patients with high risk factors for Chagas' diseases and a confirmatory RMA for use in the USA blood banks. PUBLIC HEALTH RELEVANCE: Thirteen million people are chronically infected with T. cruzi and one-third of those infected will develop debilitating heart and gastrointestinal disease. 200,000 additional infections occur annually. There are a number new treatments are becoming available. Therefore there is a need for sensitive and specific diagnostic test for diagnosis of Chagas disease. In addition, number of cases of Chagas disease incidence in the USA is increasing mainly through blood transfusion from donors of Central America and Mexico origins where Chagas disease is highly endemic. In conclusion rapid diagnostic and confirmatory tests will be highly valuable in Latin America countries and in the USA in a point-of-care situation as well as in blood banks. Public Health Relevance: Thirteen million people are chronically infected with T. cruzi and one-third of those infected will develop debilitating heart and gastrointestinal disease. 200,000 additional infections occur annually. There are a number new treatments are becoming available. Therefore there is a need for sensitive and specific diagnostic test for diagnosis of Chagas disease. In addition, number of cases of Chagas disease incidence in the USA is increasing mainly through blood transfusion from donors of Central America and Mexico origins where Chagas disease is highly endemic. In conclusion rapid diagnostic and confirmatory tests will be highly valuable in Latin America countries and in the USA in a point-of-care situation as well as in blood banks.
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