Background

Seroepidemiological surveillance data has been demonstrated to be useful for estimating the cumulative incidence of influenza, and measures the difference between pre- and post-epidemic seropositive fractions. Despite this, such studies relied on a chosen cut-off value for seropositivity. The aim of the present study is to develop a method to analyze distributions of serial cross-sectional seroepidemiological surveillance datasets using an epidemiological model so that the transmission potential can be estimated without imposing a cut-off value.

Methods

A mathematical model of influenza transmission with a discrete antibody titer level was constructed. The final size equation for pre- and post-epidemic titer levels was derived. Subsequently, using the estimated distribution of the dilution increase caused by infection and the measurement error distribution, the model parameters were optimized using the maximum likelihood method. A bootstrap-based confidence interval calculation and sensitivity analysis were also performed.

Results

Without imposing a cut-off value, the cumulative incidence was quantified, thereby yielding an estimate of the basic reproduction number. For the purpose of exposition, the proposed method was applied to influenza A/Victoria/3/75(H3N2) data, and serological data between 1975 and 1976 were compared. The estimated reproduction number was greater than that using the cut-off value of the hemagglutination inhibition level with titer level 20 (dilution 1:20) or above to define positives.

Conclusion

The proposed method without a cut-off value offers an unbiased approach to estimating the cumulative incidence along with the reproduction number. If a cut-off value is required, the results imply that titer level 20 or above may better represent a reasonable cut-off value for calculating the incidence, but it could underestimate the basic reproduction number.

中文翻译：

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一种使用系列横断面血清流行病学数据估算流感传播性的方法

背景

血清流行病学监测数据已被证明可用于估计流感的累积发病率，并可测量流行前和流行后血清阳性率之间的差异。尽管如此，此类研究仍依赖于选择的血清阳性阈值。本研究的目的是开发一种使用流行病学模型分析连续横断面血清流行病学监测数据集分布的方法，以便可以在不施加临界值的情况下估算传播潜力。

方法

构建了具有离散抗体效价水平的流感传播数学模型。得出了流行前和流行后滴度水平的最终尺寸方程。随后，使用由感染引起的稀释增加的估计分布和测量误差分布，使用最大似然法对模型参数进行优化。还进行了基于引导的置信区间计算和敏感性分析。

结果

在不施加临界值的情况下，对累积发生率进行了量化，从而得出了基本再现次数的估计值。为了说明的目的，将所提出的方法应用于A / Victoria / 3/75（H3N2）流感数据，并比较了1975年至1976年之间的血清学数据。估计的繁殖数量大于使用血凝抑制水平的临界值（效价为20（稀释度1:20）或更高）定义阳性的数量。

结论

所提出的没有截断值的方法提供了一种无偏方法来估计累积发生率以及复制次数。如果需要一个临界值，则结果表明效价水平20或更高可能更好地代表了一个合理的临界值来计算发病率，但它可能低估了基本繁殖数量。