登革热,自1950年代以来,热带和亚热带的主要疾病和死亡原因,在西半球迅速蔓延.世界上超过30%的人口面临传播四种相关登革热病毒(DENV)中任何一种的蚊子的风险。感染诱导对特定血清型的终生保护,但是连续暴露于不同的DENV会增加严重形式的登革热(DF)的可能性,登革热出血热(DHF),或登革热休克综合征(DSS)。及时的支持性治疗降低了发展登革热相关病理生理学严重谱的风险。没有疫苗,最有效的保护措施是防止蚊虫叮咬。这里,我们讨论了登革热共病性质的某些方面,包括其中枢神经系统(CNS)病理的潜力。我们研究了细胞介导和体液免疫对病毒感染的基本机制,以及这些过程在DENV感染的调节控制中的具体含义,包括DENV逃避免疫监视。根据医疗保健中转化科学的新兴模式,它整合了翻译研究(即,从患者到长凳再回到患者)和翻译有效性(即,在临床环境中整合和利用最好的可用证据),我们研究了对临床实践指南的新颖和及时的循证修订,这些修订对于优化DENV感染和登革热病理的管理至关重要.我们研究了远程医疗和利益相关者参与在以患者为中心的当代模式中的作用,以有效性为中心和以证据为基础的医疗保健。
背景:血脑屏障,中枢神经系统,DAMP-与损伤相关的分子模式,DENV-登革热病毒,DF-登革热,DHF-登革热出血热,DSS-登革热休克综合征,DALYs-稳定性调整寿命年,IFN-g-干扰素-γ,ILX-interleukinX,JAK/STAT-Janus激酶(JAK)/信号转导和转录激活因子(STAT),LT-大肠杆菌热不稳定肠毒素制剂通过突变缺乏GM1结合(LT[G33D]),MCP-1-单核细胞趋化蛋白1,M-CSF-巨噬细胞集落刺激事实,MHC-主要组织相容性复合体,MIF-巨噬细胞移动抑制因子,[MIP-1]-α/-β-巨噬细胞炎性蛋白-1α和β,单克隆抗体,单克隆抗体,NS1-登革病毒的非结构蛋白1,NK-自然杀伤细胞,PAMP-病原体相关分子模式,PBMC-外周血单核细胞,TBF-b-转化生长因子-β,TNF-α-肿瘤坏死-α,VHFs-病毒性出血热,世界卫生组织-世界卫生组织。
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.