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BACKGROUND. Disease due to dengue viruses is a growing global health threat, causing 100-400 million cases annually. An ideal dengue vaccine should demonstrate durable protection against all 4 serotypes in phase III efficacy trials, however the lack of circulating serotypes may lead to incomplete efficacy data. Controlled human infection models help downselect vaccine candidates and supply critical data to supplement efficacy trials. We evaluated the efficacy of a leading live-attenuated tetravalent dengue vaccine candidate, TV005, against infection with a newly established dengue serotype 3 or an established serotype 2 challenge virus. METHODS. Two randomized, controlled clinical trials were performed. In study 1, a total of 42 participants received TV005 or placebo (n = 21 each), and 6 months later, all were challenged with dengue 2 virus (rDEN2[DELTA]30) at a dose of 103 PFU. In study 2, a total of 23 participants received TV005 and 20 received placebo, and 6 months later, all were challenged with 104 PFU dengue 3 virus (rDEN3[DELTA]30). The study participants were closely monitored for safety, viremia, and immunologic responses. Infection, measured by post-challenge viremia, and the occurrence of rash and neutropenia were the primary endpoints. Secondary endpoints included safety, immunologic, and virologic profiles following vaccination with TV005 and subsequent challenge with the rDEN2[DELTA]30 or rDEN3[DELTA]30 strain. RESULTS. TV005 was well tolerated and protected all vaccinated volunteers from viremia with DENV2 or DENV3 (none infected in either group). Placebo recipients had post-challenge viremia (100% in study 1, 85% in study 2), and all experienced rash following challenge with either serotype. CONCLUSIONS. TV005 is a leading tetravalent dengue vaccine candidate that fully protected against infection with DENV2 and DENV3 in an established controlled human infection model. TRIAL REGISTRATION. ClinicalTrials.gov NCT02317900 and NCT02873260. FUNDING. Intramural Research Program, NIH (contract HHSN272200900010C)., Introduction Dengue viruses are estimated to cause 100-400 million symptomatic illnesses each year, with a significant and expanding burden of severe disease and mortality in both endemic populations and travelers [...]

Arthropod-borne viruses represent a crucial public health threat. Current arboviral serology assays are either labor intensive or incapable of distinguishing closely related viruses, and many zoonotic arboviruses that may transition to humans lack any serologic assays. In this study, we present a programmable phage display platform, ArboScan, that evaluates antibody binding to overlapping peptides that represent the proteomes of 691 human and zoonotic arboviruses. We confirm that ArboScan provides detailed antibody binding information from animal sera, human sera, and an arthropod blood meal. ArboScan identifies distinguishing features of antibody responses based on exposure history in a Colombian cohort of Zika patients. Finally, ArboScan details epitope level information that rapidly identifies candidate epitopes with potential protective significance. ArboScan thus represents a resource for characterizing human and animal arbovirus antibody responses at cohort scale. Arboviruses are transmitted by arthropods and include a number of critical human and zoonotic pathogens. Here the authors report a phage display library, ArboScan, for evaluating antibody binding to the peptidome of 691 human and zoonotic arthropod borne viruses, and use it to profile anti-arbovirus antibodies from diverse samples. [ABSTRACT FROM AUTHOR]

Beyond the challenges of diagnosis, complexity measurement in clients with mental illness is an important but under-recognized area. Accurate and appropriate psychiatric diagnoses are essential, and further complexity measurements could contribute to improving patient understanding, referral, and service matching and coordination, outcome evaluation, and system-level care planning. Myriad conceptualizations, frameworks, and definitions of patient complexity exist, which are operationalized by a variety of complexity measuring tools. A limited number of these tools are developed for people with mental illness, and they differ in the extent to which they capture clinical, psychosocial, economic, and environmental domains. Guided by the PRISMA Extension for Scoping Reviews, this review evaluates the tools best suited for different mental health settings. The search found 5345 articles published until November 2023 and screened 14 qualified papers and corresponding tools. For each of these, detailed data on their use of psychiatric diagnostic categories, definition of complexity, primary aim and purpose, context of use and settings for their validation, best target populations, historical references, extent of biopsychosocial information inclusion, database and input technology required, and performance assessments were extracted, analyzed, and presented for comparisons. Two tools—the INTERMED, a clinician-scored and multiple healthcare data-sourced tool, and the VCAT, a computer-based instrument that utilizes healthcare databases to generate a comprehensive picture of complexity—are exemplary among the tools reviewed. Information on these limited but suitable tools related to their unique characteristics and utilities, and specialized recommendations for their use in mental health settings could contribute to improved patient care. [ABSTRACT FROM AUTHOR]