Dengue virus (DENV) is a major public health problem of growing global importance with ~2.5 billion people at risk of infection, 50-100 million cases reported annually and associated costs of $2.1 billion per year in the Western Hemisphere [1,2]. DENV is a mosquito-borne virus and the causative agent of dengue fever, dengue hemorrhagic fever and dengue shock syndrome and is often misdiagnosed due to the non-specific clinical manifestations of this febrile illness [3]. With more than 17 million Americans traveling to endemic areas, dengue infections are now more common in travelers returning to the U.S. than malaria [16]. There is an urgent need for rapid, sensitive and specific point-of-care-compatible DENV diagnostic tools for improved patient care and public health surveillance. In this application, we will explore the discovery that a novel capture technology, CAP-TECH, designed for the specific capture of DENV (ViCAP-DENV) constructed on point-of-care-compatible solid-phase paramagnetic microparticles and their use in a fluorescent immunoassay (FIA) enabled the rapid detection of DENV in minutes. Further, in a comparative study, the sensitivity of fluorescent signal observed by the ViCAP-DENV FIA prototype was comparable to the signal observed by qRT-PCR, but in a fraction of the time and cost. Our overriding hypothesis is that the use of a diagnostic tool, such as ViCAP-DENV FIA, will enable the rapid and sensitive detection of Dengue virus in blood samples, the eventual use of which could improve patient outcomes. Further optimization of ViCAP-DENV and the FIA (Aim 1) and an initial clinical evaluation of ViCAP- DENV FIA performance in a side-by-side comparison study against FDA-approved DENV test methods using de-identified serum samples collected by the Sustainable Sciences Institute and the Nicaraguan Ministry of Health (Aim 2), will provide the foundational work for future product development and field-testing evaluations in Phase II. The success of this application will provide a novel and cost-effective point-of-care-compatible test design for the rapid diagnosis of viral infection from samples within minutes.
Public Health Relevance Statement: Public Health Relevance: In this application, we will explore the discovery that a novel capture technology, CAP-TECH, designed for the specific capture of Dengue Virus (DENV) signatures, constructed on point-of-care-compatible paramagnetic microparticles and their use in a fluorescent immunoassay enabled the rapid detection of DENV in minutes, the results of which were comparable to qRT-PCR. The success of this application will provide a novel and cost- effective point-of-care-compatible test design for the rapid diagnosis of viral infection fro samples within minutes.
NIH Spending Category: Biodefense; Bioengineering; Biotechnology; Clinical Research; Emerging Infectious Diseases; Infectious Diseases; Prevention; Rare Diseases; Vector-Borne Diseases
Project Terms: Acute; Address; American; Area; base; Binding (Molecular Function); Blood specimen; Case Study; Centers for Disease Control and Prevention (U.S.); Clinical; comparative; Comparative Study; cost; cost effective; cross reactivity; Culicidae; Data; Dengue; Dengue Hemorrhagic Fever; Dengue Shock Syndrome; Dengue Virus; design; Detection; Development; Diagnostic; Early Diagnosis; Effectiveness; Enzyme-Linked Immunosorbent Assay; evaluation/testing; FDA approved; Feasibility Studies; Fever; Fluorescence; Future; Goals; Health; Hemorrhagic Shock; Immunoassay; improved; Infection; Infection Control; Institutes; Kinetics; Lead; Malaria; Methods; Microspheres; Nicaraguan; Noise; novel; Outcome; Patient Care; Patients; Performance; Phase; phase 1 study; Pilot Projects; Plasma; point of care; Population Surveillance; product development; prototype; PTPN11 gene; public health medicine (field); Publishing; rapid detection; rapid diagnosis; reagent testing; Reporter; Reproducibility; research clinical testing; Reverse Transcriptase Polymerase Chain Reaction; Risk; Sampling; Science; Sensitivity and Specificity; Series; Serotyping; Serum; Side; Signal Transduction; Solid; Specificity; Staging; success; Syndrome; Technology; Test Result; Testing; Time; tool; Travel; Viral; viral detection; Viral Hemorrhagic Fevers; Virus; Virus Diseases; Work
