Development of a novel test for the early detection of Dengue Virus infection

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DESCRIPTION (provided by applicant): 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.