London School of Hygiene & Tropical Medicine, London, UK; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, Germany.
Duke-National University of Singapore Medical School, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
Lancet. 2019 Jan 26;393(10169):350-363. doi: 10.1016/S0140-6736(18)32560-1.
Mortality from severe dengue is low, but the economic and resource burden on health services remains substantial in endemic settings. Unfortunately, progress towards development of effective therapeutics has been slow, despite notable advances in the understanding of disease pathogenesis and considerable investment in antiviral drug discovery. For decades antibody-dependent enhancement has been the prevalent model to explain dengue pathogenesis, but it was only recently demonstrated in vivo and in clinical studies. At present, the current mainstay of management for most symptomatic dengue patients remains careful observation and prompt but judicious use of intravenous hydration therapy for those with substantial vascular leakage. Various new promising technologies for diagnosis of dengue are currently in the pipeline. New sample-in, answer-out nucleic acid amplification technologies for point-of-care use are being developed to improve performance over current technologies, with the potential to test for multiple pathogens using a single specimen. The search for biomarkers that reliably predict development of severe dengue among symptomatic individuals is also a major focus of current research efforts. The first dengue vaccine was licensed in 2015 but its performance depends on serostatus. There is an urgent need to identify correlates of both vaccine protection and disease enhancement. A crucial assessment of vector control tools should guide a research agenda for determining the most effective interventions, and how to best combine state-of-the-art vector control with vaccination.
重症登革热的死亡率较低，但在流行地区，卫生服务机构仍面临巨大的经济和资源负担。不幸的是，尽管在疾病发病机制的理解方面取得了显著进展，并且在抗病毒药物发现方面投入了大量资金，但在开发有效治疗方法方面进展缓慢。几十年来，抗体依赖性增强一直是解释登革热发病机制的主要模型，但直到最近才在体内和临床研究中得到证实。目前，对于大多数有症状的登革热患者，管理的主要方法仍然是仔细观察，并在有大量血管渗漏的患者中及时但明智地使用静脉补液治疗。目前有许多新的有前途的登革热诊断技术正在研发中。目前正在开发用于即时护理的新型样本输入、答案输出核酸扩增技术，以提高现有技术的性能，有可能使用单个标本测试多种病原体。寻找可靠预测有症状个体发生重症登革热的生物标志物也是当前研究工作的主要重点。第一种登革热疫苗于 2015 年获得许可，但它的性能取决于血清状态。迫切需要确定疫苗保护和疾病增强的相关因素。对媒介控制工具的关键评估应指导研究议程，以确定最有效的干预措施，以及如何将最先进的媒介控制与疫苗接种最佳结合。
