title: Viral immune evasion in dengue: toward evidence-based revisions of clinical practice guidelines.
abstract: Dengue, a leading cause of illness and death in the tropics and subtropics since the 1950׳s, is fast spreading in the Western hemisphere. Over 30% of the world׳s population is at risk for the mosquitoes that transmit any one of four related Dengue viruses (DENV). Infection induces lifetime protection to a particular serotype, but successive exposure to a different DENV increases the likelihood of severe form of dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Prompt supportive treatment lowers the risk of developing the severe spectrum of Dengue-associated physiopathology. Vaccines are not available, and the most effective protective measure is to prevent mosquito bites. Here, we discuss selected aspects of the syndemic nature of Dengue, including its potential for pathologies of the central nervous system (CNS). We examine the fundamental mechanisms of cell-mediated and humoral immunity to viral infection in general, and the specific implications of these processes in the regulatory control of DENV infection, including DENV evasion from immune surveillance. In line with the emerging model of translational science in health care, which integrates translational research (viz., going from the patient to the bench and back to the patient) and translational effectiveness (viz., integrating and utilizing the best available evidence in clinical settings), we examine novel and timely evidence-based revisions of clinical practice guidelines critical in optimizing the management of DENV infection and Dengue pathologies. We examine the role of tele-medicine and stakeholder engagement in the contemporary model of patient centered, effectiveness-focused and evidence-based health care.
  
  
  BACKGROUND
  BBB - blood-brain barrier, CNS - central nervous system, DAMP - damage-associated molecular patterns, DENV - dengue virus, DF - dengue fever, DHF - dengue hemorrhagic fever, DSS - dengue shock syndrome, DALYs - isability adjusted life years, IFN-g - interferon-gamma, ILX - interleukinX, JAK/STAT - janus kinase (JAK) / Signal transducer and activator of transcription (STAT), LT - Escherichia coli heat-labile enterotoxin formulations deficient in GM1 binding by mutation (LT[G33D]), MCP-1 - monocyte chemotactic protein 1, M-CSF - macrophage colony-stimulating fact, MHC - major histocompatibility complex, MIF - macrophage migration inhibitory factor, [MIP-1]-α / -β - macrophage inflammatory protein-1 alpha and beta, mAb - monoclonal antibody, NS1 - non-structural protein 1 of dengue virus, NK - natural killer cells, PAMP - pathogen-associated molecular patterns, PBMC - peripheral blood mononuclear cells, TBF-b - transforming growth factor-beta, TNF-α - tumor necrosis-alpha, VHFs - virus hemorrhagic fevers, WHO - World Health Organization.
authors: UCLA Center for the Health Sciences 63-090, 10833 Le Conte Avenue, Los Angeles, CA 90095-16682 ; Evidence-Based Decision Practice-Based Research Network.
authors: Francesco
authors: F
authors: Chiappelli
authors: Evidence-Based Decision Practice-Based Research Network ; Faculdade de Medicina. Universidade Federal de Minas Gerais.
authors: Silvana Maria Eloi
authors: SM
authors: Santos
authors: Evidence-Based Decision Practice-Based Research Network.
authors: Xenia Maria
authors: XM
authors: Caldeira Brant
authors: UCLA Center for the Health Sciences 63-090, 10833 Le Conte Avenue, Los Angeles, CA 90095-16682 ; Evidence-Based Decision Practice-Based Research Network.
authors: Andre
authors: A
authors: Bakhordarian
authors: UCLA David Geffen School of Medicine (Psychiatry).
authors: April D
authors: AD
authors: Thames
authors: UCLA Center for the Health Sciences 63-090, 10833 Le Conte Avenue, Los Angeles, CA 90095-16682 ; UCLA School of Dentistry (Public Health Dentistry), UCLA Institute of the Environment and Sustainability, UCLA Center for Tropical Research.
authors: Carl A
authors: CA
authors: Maida
authors: UCLA Center for the Health Sciences 63-090, 10833 Le Conte Avenue, Los Angeles, CA 90095-16682.
authors: Angela M
authors: AM
authors: Du
authors: UCLA Center for the Health Sciences 63-090, 10833 Le Conte Avenue, Los Angeles, CA 90095-16682.
authors: Allison L
authors: AL
authors: Jan
authors: UCLA Center for the Health Sciences 63-090, 10833 Le Conte Avenue, Los Angeles, CA 90095-16682.
authors: Melissa
authors: M
authors: Nahcivan
authors: UCLA Center for the Health Sciences 63-090, 10833 Le Conte Avenue, Los Angeles, CA 90095-16682.
authors: Mia T
authors: MT
authors: Nguyen
authors: UCLA Center for the Health Sciences 63-090, 10833 Le Conte Avenue, Los Angeles, CA 90095-16682.
authors: Nateli
authors: N
authors: Sama
keywords: Dengue fever; Dengue shock syndrome; Dengue virus; M1 & M2 macrophages; TH17; Tregs; comparative effectiveness analysis; disability adjusted life years; immune evasion; patient-centered evaluation; patient-centered research; stakeholders engagement; syndemics; tele-medicine; translational science