Department of Medicine, Imperial College, Hammersmith Campus, London, UK.
Curr Opin Infect Dis. 2013 Jun;26(3):284-9. doi: 10.1097/QCO.0b013e32835fb938.
Dengue is one of the most rapidly spreading vector-borne diseases in the world, with the incidence increasing 30-fold in the past 50 years. There are currently no licensed treatments or vaccines for dengue. This review covers the recent advances in our understanding of dengue pathogenesis, including host and viral determinants.
The pathogenesis of severe dengue is thought to be immune-mediated due to the timing of the clinical manifestations and higher incidence in secondary infections with a heterologous serotype. Recent evidence has provided further information of neutralizing versus enhancing monoclonal antibodies and their target epitopes on the dengue virion, which has major implications for vaccine design. The role of T-cell immunopathology has also been advanced with recent evidence of cross-reactive high pro-inflammatory cytokine producing T cells predominating in severe dengue. Recent large genome-wide association studies have identified specific susceptibility loci associated with severe disease. Epidemiological studies have served to define certain at-risk groups and specific viral virulence factors have recently been described.
The pathogenesis of dengue is likely to be a complex interplay of host immunity and genetic predisposition combined with certain viral virulence factors. Better understanding of the underlying mechanisms leading to severe dengue is crucial if we are to develop prognostic markers, novel diagnostics and therapeutics and ultimately a balanced and safe vaccine.
登革热是世界上传播速度最快的虫媒传染病之一，在过去 50 年中，发病率增加了 30 倍。目前尚无针对登革热的许可治疗方法或疫苗。本文综述了登革热发病机制的最新研究进展，包括宿主和病毒决定因素。
严重登革热的发病机制被认为是免疫介导的，因为临床表现的时间和异型血清型二次感染的发生率更高。最近的证据提供了更多关于中和与增强单克隆抗体及其在登革热病毒粒子上的靶表位的信息，这对疫苗设计具有重要意义。T 细胞免疫病理学的作用也得到了进一步发展，最近的证据表明，严重登革热中主要存在交叉反应性高促炎细胞因子产生 T 细胞。最近的全基因组关联研究确定了与严重疾病相关的特定易感基因座。流行病学研究有助于确定某些高危人群，最近还描述了特定的病毒毒力因子。
登革热的发病机制可能是宿主免疫和遗传易感性与某些病毒毒力因素的复杂相互作用。如果我们要开发预后标志物、新型诊断和治疗方法，并最终开发出平衡和安全的疫苗，那么更好地了解导致严重登革热的潜在机制至关重要。
