PDF(Pubmed)
Abstract：
UNASSIGNED: Viremia is a critical factor in understanding the pathogenesis of dengue infection, but limited data exist on viremia kinetics. This study aimed to investigate the kinetics of viremia and its effects on subsequent platelet count, severe dengue, and plasma leakage.
UNASSIGNED: We pooled data from three studies conducted in Vietnam between 2000 and 2016, involving 2340 dengue patients with daily viremia measurements and platelet counts after symptom onset. Viremia kinetics were assessed using a random effects model that accounted for left-censored data. The effects of viremia on subsequent platelet count and clinical outcomes were examined using a landmark approach with a random effects model and logistic regression model with generalized estimating equations, respectively. The rate of viremia decline was derived from the model of viremia kinetics. Its effect on the clinical outcomes was assessed by logistic regression models.
UNASSIGNED: Viremia levels rapidly decreased following symptom onset, with variations observed depending on the infecting serotype. DENV-1 exhibited the highest mean viremia levels during the first 5-6 days, while DENV-4 demonstrated the shortest clearance time. Higher viremia levels were associated with decreased subsequent platelet counts from day 6 onwards. Elevated viremia levels on each illness day increased the risk of developing severe dengue and plasma leakage. However, the effect size decreased with later illness days. A more rapid decline in viremia is associated with a reduced risk of the clinical outcomes.
UNASSIGNED: This study provides comprehensive insights into viremia kinetics and its effect on subsequent platelet count and clinical outcomes in dengue patients. Our findings underscore the importance of measuring viremia levels during the early febrile phase for dengue studies and support the use of viremia kinetics as outcome for phase-2 dengue therapeutic trials.
UNASSIGNED: Wellcome Trust and European Union Seventh Framework Programme.
UNASSIGNED: We pooled data from three studies conducted in Vietnam between 2000 and 2016, involving 2340 dengue patients with daily viremia measurements and platelet counts after symptom onset. Viremia kinetics were assessed using a random effects model that accounted for left-censored data. The effects of viremia on subsequent platelet count and clinical outcomes were examined using a landmark approach with a random effects model and logistic regression model with generalized estimating equations, respectively. The rate of viremia decline was derived from the model of viremia kinetics. Its effect on the clinical outcomes was assessed by logistic regression models.
UNASSIGNED: Viremia levels rapidly decreased following symptom onset, with variations observed depending on the infecting serotype. DENV-1 exhibited the highest mean viremia levels during the first 5-6 days, while DENV-4 demonstrated the shortest clearance time. Higher viremia levels were associated with decreased subsequent platelet counts from day 6 onwards. Elevated viremia levels on each illness day increased the risk of developing severe dengue and plasma leakage. However, the effect size decreased with later illness days. A more rapid decline in viremia is associated with a reduced risk of the clinical outcomes.
UNASSIGNED: This study provides comprehensive insights into viremia kinetics and its effect on subsequent platelet count and clinical outcomes in dengue patients. Our findings underscore the importance of measuring viremia levels during the early febrile phase for dengue studies and support the use of viremia kinetics as outcome for phase-2 dengue therapeutic trials.
UNASSIGNED: Wellcome Trust and European Union Seventh Framework Programme.
摘要：
■病毒血症是了解登革热感染发病机制的关键因素，但是关于病毒血症动力学的数据有限。本研究旨在探讨病毒血症的动力学及其对随后血小板计数的影响。严重的登革热,和等离子体泄漏。
■我们汇集了2000年至2016年在越南进行的三项研究的数据，涉及2340例登革热患者，症状发作后每天进行病毒血症测量和血小板计数。使用考虑左删失数据的随机效应模型评估病毒血症动力学。病毒血症对随后的血小板计数和临床结果的影响，使用具有随机效应模型的里程碑方法和具有广义估计方程的逻辑回归模型进行检查。分别。病毒血症下降的速率来自病毒血症动力学模型。通过逻辑回归模型评估其对临床结果的影响。
■病毒血症在症状发作后迅速下降，根据感染血清型观察到的变化。DENV-1在前5-6天表现出最高的平均病毒血症水平，而DENV-4显示了最短的清除时间。从第6天开始，较高的病毒血症水平与随后的血小板计数降低有关。每个疾病日的病毒血症水平升高会增加发生严重登革热和血浆渗漏的风险。然而,随着患病天数的延长，效应大小逐渐减少。病毒血症的更快下降与临床结果的风险降低相关。
■本研究提供了对登革热患者的病毒血症动力学及其对随后的血小板计数和临床结果的影响的全面见解。我们的发现强调了在登革热研究中测量早期高热期病毒血症水平的重要性，并支持将病毒血症动力学用作2期登革热治疗试验的结果。
■惠康信托基金和欧盟第七框架计划。
■我们汇集了2000年至2016年在越南进行的三项研究的数据，涉及2340例登革热患者，症状发作后每天进行病毒血症测量和血小板计数。使用考虑左删失数据的随机效应模型评估病毒血症动力学。病毒血症对随后的血小板计数和临床结果的影响，使用具有随机效应模型的里程碑方法和具有广义估计方程的逻辑回归模型进行检查。分别。病毒血症下降的速率来自病毒血症动力学模型。通过逻辑回归模型评估其对临床结果的影响。
■病毒血症在症状发作后迅速下降，根据感染血清型观察到的变化。DENV-1在前5-6天表现出最高的平均病毒血症水平，而DENV-4显示了最短的清除时间。从第6天开始，较高的病毒血症水平与随后的血小板计数降低有关。每个疾病日的病毒血症水平升高会增加发生严重登革热和血浆渗漏的风险。然而,随着患病天数的延长，效应大小逐渐减少。病毒血症的更快下降与临床结果的风险降低相关。
■本研究提供了对登革热患者的病毒血症动力学及其对随后的血小板计数和临床结果的影响的全面见解。我们的发现强调了在登革热研究中测量早期高热期病毒血症水平的重要性，并支持将病毒血症动力学用作2期登革热治疗试验的结果。
■惠康信托基金和欧盟第七框架计划。
