Inference on disease dynamics is typically performed using case reporting time series of symptomatic disease. The inferred dynamics will vary depending on the reporting patterns and surveillance system for the disease in question, and the inference will miss mild or underreported epidemics. To eliminate the variation introduced by differing reporting patterns and to capture asymptomatic or subclinical infection, inferential methods can be applied to serological data sets instead of case reporting data. To reconstruct complete disease dynamics, one would need to collect a serological time series. In the statistical analysis presented here, we consider a particular kind of serological time series with repeated, periodic collections of population-representative serum. We refer to this study design as a serial seroepidemiology (SSE) design, and we base the analysis on our epidemiological knowledge of influenza. We consider a study duration of three to four years, during which a single antigenic type of influenza would be circulating, and we evaluate our ability to reconstruct disease dynamics based on serological data alone. We show that the processes of reinfection, antibody generation, and antibody waning confound each other and are not always statistically identifiable, especially when dynamics resemble a non-oscillating endemic equilibrium behavior. We introduce some constraints to partially resolve this confounding, and we show that transmission rates and basic reproduction numbers can be accurately estimated in SSE study designs. Seasonal forcing is more difficult to identify as serology-based studies only detect oscillations in antibody titers of recovered individuals, and these oscillations are typically weaker than those observed for infected individuals. To accurately estimate the magnitude and timing of seasonal forcing, serum samples should be collected every two months and 200 or more samples should be included in each collection; this sample size estimate is sensitive to the antibody waning rate and the assumed level of seasonal forcing.

译文

:通常使用病例报告的症状性疾病时间序列来进行疾病动态的推断。推断的动态将取决于所讨论疾病的报告模式和监视系统而有所不同,并且推断将错过轻度或报告不足的流行病。为了消除由不同报告模式引起的差异并捕获无症状或亚临床感染,可以将推论方法应用于血清学数据集,而不是病例报告数据。要重建完整的疾病动态,就需要收集血清学时间序列。在这里介绍的统计分析中,我们考虑了一种具有重复性,周期性收集人群代表性血清的血清学时间序列。我们将此研究设计称为串行血清流行病学(SSE)设计,并基于我们对流感的流行病学知识进行分析。我们认为研究周期为三到四年,在此期间将传播一种抗原类型的流感,并且我们仅根据血清学数据评估我们重建疾病动态的能力。我们表明,再感染,抗体生成和抗体减弱的过程相互混淆,并不总是统计上可识别的,尤其是当动态类似于非振荡的地方性平衡行为时。我们介绍了一些约束条件以部分解决这种混淆,并且我们表明可以在SSE研究设计中准确估算传输速率和基本繁殖数。季节性强迫更难确定,因为基于血清学的研究仅能检测出恢复个体的抗体滴度中的振荡,并且这些振荡通常比对感染个体观察到的振荡弱。为了准确估计季节性强迫的强度和时间,应每两个月收集一次血清样本,每次收集应包括200个或更多样本;该样本量估计值对抗体的减弱速率和假定的季节性强迫水平敏感。

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