Department of Medicine, Imperial College London, London, UK; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Nuffield Department of Clinical Medicine, Centre for Tropical Medicine, Oxford, UK.
Lancet. 2015 Feb 26;385 Suppl 1:S102. doi: 10.1016/S0140-6736(15)60417-2.
Dengue infection can result in a wide spectrum of disease. The defining feature of severe disease is increased capillary permeability, which can lead to hypovolaemic shock. Microvascular and endothelial dysfunction might underlie hypovolaemic shock, but they have not been assessed clinically. We aimed to investigate the use of microvascular assessment as a prognostic method in dengue.
This is an ongoing prospective observational study that aims to recruit 300 participants: children over the age of 3 years and adults presenting to two outpatient departments in Vietnam with fever of less than 72 h duration and suspected dengue, and patients admitted to hospital with warning signs or severe disease. Participants are being clinically assessed daily for 6 days, and 2 weeks later. Microvascular imaging using sublingual sidestream darkfield imaging (SDF) and endothelial function testing using peripheral artery tonometry are being performed at enrolment, defervescence, and follow-up
To date, 167 patients have been recruited (92 outpatient arm, 75 inpatient arm, median age 27 years [IQR 21-33], 78 male [47%]). Dengue has been confirmed in 67 individuals in the outpatient arm, of whom 29 (43%) developed warning signs, three (4%) developed severe disease, and 35 had uncomplicated dengue; the other 25 outpatients (27%) were diagnosed as other febrile illness. At enrolment, the reactive hyperaemic index, a marker of endothelial function, was lowest in the patients who went on to develop severe dengue (median 1·54, IQR 1·36-1·77) followed by those who developed warning signs (1·78, 1·43-2·36) and then uncomplicated dengue (2·18, 1·65-2·24). Initial SDF results showed a lower proportion of perfused vessels and mean flow index during the febrile phase of dengue compared with follow-up, and were worst in the severe group at defervescence.
This study of vascular function at serial timepoints in dengue is, to our knowledge, the first and most comprehensive. Our preliminary results suggest that microvascular and endothelial dysfunction are associated with severity of dengue, and occur before the appearance of severe clinical manifestations. These techniques might be useful in risk prediction in dengue. A limitation is that a formal sample size could not be calculated because no previous microvascular data in dengue exist.
Wellcome Trust.
登革热感染可导致广泛的疾病谱。重症的特征是毛细血管通透性增加，可导致低血容量性休克。微血管和内皮功能障碍可能是低血容量性休克的基础，但尚未在临床上进行评估。我们旨在研究微血管评估作为登革热的预后方法。
这是一项正在进行的前瞻性观察性研究，旨在招募 300 名参与者：年龄在 3 岁以上的儿童和在越南的两个门诊部门就诊的发热时间少于 72 小时且疑似登革热的成年人，以及有预警信号或重症的住院患者。参与者每天进行临床评估 6 天，然后在 2 周后进行评估。在登记、退热和随访时使用舌下侧流暗场成像（SDF）进行微血管成像，使用外周动脉张力测定进行内皮功能测试。
迄今为止，已经招募了 167 名患者（92 名门诊组，75 名住院组，中位年龄 27 岁[IQR 21-33]，78 名男性[47%]）。门诊组中已经确诊 67 人患有登革热，其中 29 人（43%）出现预警信号，3 人（4%）出现重症，35 人患有单纯性登革热；另外 25 名门诊患者（27%）被诊断为其他发热性疾病。在登记时，内皮功能的反应性充血指数最低的是发展为重症登革热的患者（中位数 1.54，IQR 1.36-1.77），其次是出现预警信号的患者（1.78，1.43-2.36），然后是单纯性登革热患者（2.18，1.65-2.24）。在登革热发热期，与随访相比，初始 SDF 结果显示灌注血管和平均血流指数的比例较低，在退热时重症组最差。
我们的研究是首次也是最全面的，对登革热的血管功能进行了一系列时间点的研究。我们的初步结果表明，微血管和内皮功能障碍与登革热的严重程度相关，并且在出现严重临床症状之前就已经发生。这些技术可能有助于登革热的风险预测。一个限制是，由于以前没有登革热的微血管数据，因此无法计算正式的样本量。
惠康信托基金会。
