The proposed project aims to build a diagnostic test for chronic T. cruzi infection and Chagas disease that not only improves testing performance but that can be readily integrated with similarly developed tests for most clinically important parasitoses. Current assays for Chagas disease, and other parasitic infections, lack desired levels of specificity, and require multiple independent assays and testing formats. Consequently, testing a single specimen for several different clinically important parasitic diseases becomes cost prohibitive and time consuming, delaying disease detection and treatment. We propose to address this problem by creating a single, all-in-one diagnostic test able to detect ten or more different clinically important parasitic diseases. Importantly, the proposed strategy could be expanded to a nearly arbitrary number of infectious diseases without resultant increases in final test cost. Towards a multiplexed parasitic disease test, we will first create an improved test for Chagas disease, that impacts about 350,000 individuals in the US, and 8 million in the Americas. To accomplish this, we will apply bacterial display peptide libraries, next-generation sequencing, and computational bioinformatics to identify a set of motifs and consensus peptides corresponding to antigenic peptide epitopes that when combined yield optimal sensitivity and specificity values in the discovery set. The motif and peptide panels will be validated using an independent specimen set. Assay reproducibility and stability will be measured. This project may thus lead to clinically useful tests to improve the rates of detection parasitic diseases their resultant complications.
Public Health Relevance Statement: A majority of individuals with chronic parasitic infections are undiagnosed. In particular, an estimated 350,000 individuals in the US are chronically infected with T. cruzi, the causative agent of Chagas disease. Although molecular diagnostics are available to detect Chagas and other parasitoses, they lack the ability to be parallelized into a single testing assay that could be deployed broadly to screen at risk populations for these clinically important diseases. The proposed project aims to develop the capability to detect tens of different potential parasitic infectious using a single blood test, and could be expanded to many other infectious diseases.
Project Terms: Acanthamoeba; Acute Disease; Address; Americas; Angiostrongylus cantonensis; Antibodies; Antibody Repertoire; Antibody Specificity; Antigen Targeting; Antigens; Archives; Autoimmune Diseases; Balamuthia mandrillaris; Bar Codes; Binding; Bioinformatics; Biological Assay; biomarker discovery; Blinded; Blood Cells; Blood Tests; Cardiac; Celiac Disease; Centers for Disease Control and Prevention (U.S.); Chagas Disease; Chronic; Chronic Disease; Clinical; Collection; Communicable Diseases; Computer software; Consensus; cost; Custom; Data; Data Set; Databases; Detection; Diagnostic; diagnostic accuracy; diagnostic panel; Diagnostic Sensitivity; Diagnostic Specificity; Diagnostic tests; digital; Disease; Echinococcus granulosus; Entamoeba histolytica; Enzyme-Linked Immunosorbent Assay; Epitopes; exhibitions; Exhibits; Family; gastrointestinal; Gold; Heart Diseases; Human; Immunoassay; improved; Individual; Infection; Knowledge; Laboratories; Lead; Leishmania; Measures; Methodology; Methods; Microscopic; molecular diagnostics; Naegleria fowleri; neglect; next generation sequencing; novel; Outcome; parallelization; Parasites; Parasitic Diseases; Parasitic infection; pathogen; Peptide Library; Peptides; performance tests; Phase; Populations at Risk; Preparation; prevent; Process; Randomized; Reproducibility; Sampling; Sensitivity and Specificity; Serodiagnoses; Serologic tests; Serological; specific biomarkers; Specificity; Specimen; Taenia solium; Technology; Test Result; Testing; Time; Toxocara; Toxoplasma gondii; Trypanosoma cruzi; United States; Validation
