Population Modeling of Influenza A/H1N1 Virus Kinetics and Symptom Dynamics
Population Modeling of Influenza A/H1N1 Virus Kinetics and Symptom Dynamics
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DOI：
10.1128/jvi.01318-10
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发表时间：
2011-03-01
影响因子：
5.4
通讯作者：
Carrat, Fabrice
中科院分区：
文献类型：
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作者：
Canini, Laetitia;Carrat, Fabrice
流感病毒动力学（VK）被用作传染性的替代物，而流感的自然史由症状动力学（SD）描述。我们使用了一个原始的病毒动力学/症状动力学（VKSD）模型来表征人类流感病毒感染和疾病，基于人口的方法。我们结合结构方程和统计模型来描述个体内和个体间的变异性。结构方程描述了基于靶上皮细胞、病毒、先天宿主反应和全身症状的流感。该模型拟合的个人VK和SD数据从44名志愿者实验挑战与流感病毒A/H1N1。根据最佳拟合模型估计值计算感染和疾病参数。我们预测细胞因子水平和NK细胞活性将分别在接种后2.2天和4.2天达到峰值。病毒滴度阈值以上的VK曲线下面积，持续7.0至1.3天，无全身症状的参与者比有全身症状的参与者低15倍（P < 0.001）。潜伏期（定义为接种和感染之间的时间）为0.7至1.9天。潜伏期定义为从接种到首次出现症状的时间，从1.0天到2.4天不等。我们的方法扩展了以前的工作，包括先天反应，并提供现实的估计感染和疾病参数，考虑到强个体间的变异性。这种方法可以帮助优化流感VK和SD的研究，并预测抗病毒药物对感染性和症状的影响。
Influenza virus kinetics (VK) is used as a surrogate of infectiousness, while the natural history of influenza is described by symptom dynamics (SD). We used an original virus kinetics/symptom dynamics (VKSD) model to characterize human influenza virus infection and illness, based on a population approach. We combined structural equations and a statistical model to describe intra- and interindividual variability. The structural equations described influenza based on the target epithelial cells, the virus, the innate host response, and systemic symptoms. The model was fitted to individual VK and SD data obtained from 44 volunteers experimentally challenged with influenza A/H1N1 virus. Infection and illness parameters were calculated from best-fitted model estimates. We predicted that the cytokine level and NK cell activity would peak at days 2.2 and 4.2 after inoculation, respectively. Infectiousness, measured as the area under the VK curve above a viral titer threshold, lasted between 7.0 and 1.3 days and was 15 times lower in participants without systemic symptoms than in those with systemic symptoms (P < 0.001). The latent period, defined as the time between inoculation and infectiousness, varied from 0.7 to 1.9 days. The incubation period, defined as the time from inoculation to first symptoms, varied from 1.0 to 2.4 days. Our approach extends previous work by including the innate response and providing realistic estimates of infection and illness parameters, taking into account the strong interindividual variability. This approach could help to optimize studies of influenza VK and SD and to predict the effect of antivirals on infectiousness and symptoms.