Point-of-care diagnostic test for T. cruzi (Chagas) infection

Project Summary Chagas disease, caused by infection with the parasite Trypanosoma cruzi, is the most prevalent parasitic disease in the western hemisphere, infecting 8-11 million individuals and with over 70 million at risk. The infection is transmitted by an insect vector that is native to Latin America, but can also be acquired through blood transfusion, organ transplant, or congenitally. Following a brief acute phase, the parasite persists for years in infected carriers, often asymptomatically, but can cause cardiomyopathy and other pathological conditions leading to severe morbidity and mortality. In the U.S., T. cruzi is prevalent in Latin American immigrant populations, where it poses an underrecognized health risk. The gradual encroachment of the insect vector into the southernmost regions of the U.S. has also raised the threat of autochthonous transmission. Chagas disease is challenging to diagnose due to the combination of genotypic and hence antigenic variation across its geographical range, complex immunological interactions with the human host, and cross-reactivities with other parasites. Serology has become the mainstay for diagnosis, especially for chronic infection, but the above challenges have hampered the accuracy of serologic tests such that multiple assays are commonly used in a triangulation algorithm to establish final results. The majority of those at risk for T. cruzi infection live in low-resource, underdeveloped areas where contact with the vector insects is hard to avoid, but medical care is relatively primitive and laboratory infrastructure is absent. For these reasons, rapid, point-of-care tests have become increasingly desirable as tools for diagnosis and epidemiological surveillance of Chagas disease. However, the current generation of Chagas rapid tests is limited by suboptimal performance, both in sensitivity and specificity, largely due to the reliance on recombinant antigens which are specific to certain T. cruzi lineages and often fail to detect Mexican and Central American Chagas cases. To date, only one Chagas rapid test has been cleared by FDA. We propose to complete development of a rapid test for Chagas disease, based on a native protein antigen from cultured T. cruzi termed TESA (Trypanosomal Excreted/Secreted Antigens). We have developed procedures to produce with high yield, enrich and concentrate the antigenic component of TESA, making it suitable for use in a lateral flow assay. In Phase I studies, the prototype TESA rapid test has shown clinical sensitivity and specificity approaching 100% across a range of samples from diverse regions spanning the endemic geography of Latin America, including Mexico and Central America. In Phase II, we will complete development of the TESA lateral flow rapid test in a cost-effective format suitable for point-of-care use in low-resource settings. The clinical and analytical performance of the test will be evaluated in a clinical study involving over 1,000 Chagas patients and controls to be carried out at sites in the U.S. and in an endemic region in Latin America. The clinical study results will support a 510(k) submission to FDA for clearance of the TESA lateral flow rapid test for in vitro diagnosis of Chagas disease.