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

Project Summary Chagas diseasecaused by infection with the parasite Trypanosoma cruziis the most prevalent parasitic disease in the western hemisphereinfectingmillion individuals and with overmillion at riskThe infection is transmitted by an insect vectorbut can also be acquired through blood transfusionorgan transplantor congenitallyFollowing a brief acute phasethe parasite persists for years in infected carriersoften asymptomaticallybut can cause cardiomyopathy and other pathological conditions leading to severe morbidity and mortalityIn the U Sthe prevalence of Tcruzi infection measured in immigrant populations has led to the implementation of blood screening assays to prevent transfusion transmissionThe gradual encroachment of the insect vector into the southernmost regions of the U Shas also raised the threat of autochthonous transmissionChagas disease is challenging to diagnose due to the combination of genotypic and hence antigenic variation across its geographical rangecomplex immunological interactions with the human hostand cross reactivities with other parasitesSerology has become the mainstay for diagnosisespecially for chronic infectionbut the above challenges have hampered the accuracy of serologic tests such that multiple assays are commonly used in a triangulation algorithm to establish final resultsThe majority of those at risk for Tcruzi infection live in low resourceunderdeveloped areas where contact with the vector insects is hard to avoidbut medical care is relatively primitive and laboratory infrastructure is absentFor these reasonsrapidpoint of care tests have become increasingly desirable as tools for diagnosis and epidemiological surveillance of Chagas diseaseThe current generation of Chagas rapid tests is limited by suboptimal performanceboth with respect to sensitivity and specificityhoweverlargely due to the reliance on recombinant antigens which are specific to certain Tcruzi strains or lineages or stages of infectionTo dateonly one Chagas rapid test has been cleared by FDAIn this projectwe propose to develop a rapid test for Chagas diseasebased on a semi purified native protein preparation from cultured Tcruzi termed TESATrypanosomal Excreted Secreted AntigensIn preliminary studies by applicants and othersTESA immunoblots have shown clinical sensitivity and specificity approachingacross a range of genotypes and lineagesWe have developed a purification procedure to enrich and concentrate the antigenic component of TESAmaking it suitable for use in a lateral flow assay formatWe have used this antigen in a prototype simplified lateral flow assaywhich exhibited greater analytical sensitivity than the FDA cleared rapid test and broad detection of Tcruzi infections across Latin AmericaIn Phase Iwe will develop a completeTESAbased lateral flow rapid test suitable for point of care use in low resource settingsTESA lateral flow test results will be read using a field friendlyultraportablelow cost reader that will provide objective interpretation and enable wireless upload of data to local devices or remote serversPhase II will support complete development to commercial stageclinical evaluation and FDA submission of the TESA lateral flow test for in vitro diagnosis of Chagas disease Project Narrative This project addresses the critical need for an accurate rapidpoint of care test for Chagas diseaseThis parasitic infection has emerged as a threat to public health and the blood supply both within the U Sand internationallyyet only one FDA clearedcommercial rapid test for Chagas disease is currently availableIn Phase Iwe propose to develop a Chagas disease lateral flow rapid test based on native antigens of the parasiteIn Phase II we will refine this assay into a manufactured productcarry out a clinical study to support aksubmission to FDAand achieve clearance of the Chagas point of care test for in vitro diagnosis of infected individuals