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协调不同研究设计得出的异质性登革病毒感染风险估计值。

Reconciling heterogeneous dengue virus infection risk estimates from different study designs.

作者信息

Huang Angkana T, Buddhari Darunee, Kaewhiran Surachai, Iamsirithaworn Sopon, Khampaen Direk, Farmer Aaron, Fernandez Stefan, Thomas Stephen J, Barraquer Isabel Rodriguez, Hunsawong Taweewun, Srikiatkhachorn Anon, Dos Santos Gabriel Ribeiro, O'Driscoll Megan, Hamins-Puertolas Marco, Endy Timothy, Rothman Alan L, Cummings Derek A T, Anderson Kathryn, Salje Henrik

机构信息

University of Cambridge, Cambridge, UK.

Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

出版信息

medRxiv. 2024 Sep 10:2024.09.09.24313375. doi: 10.1101/2024.09.09.24313375.

Abstract

Uncovering rates at which susceptible individuals become infected with a pathogen, i.e. the force of infection (FOI), is essential for assessing transmission risk and reconstructing distribution of immunity in a population. For dengue, reconstructing exposure and susceptibility statuses from the measured FOI is of particular significance as prior exposure is a strong risk factor for severe disease. FOI can be measured via many study designs. Longitudinal serology are considered gold standard measurements, as they directly track the transition of seronegative individuals to seropositive due to incident infections (seroincidence). Cross-sectional serology can provide estimates of FOI by contrasting seroprevalence across ages. Age of reported cases can also be used to infer FOI. Agreement of these measurements, however, have not been assessed. Using 26 years of data from cohort studies and hospital-attended cases from Kamphaeng Phet province, Thailand, we found FOI estimates from the three sources to be highly inconsistent. Annual FOI estimates from seroincidence was 2.46 to 4.33-times higher than case-derived FOI. Correlation between seroprevalence-derived and case-derived FOI was moderate (correlation coefficient=0.46) and no systematic bias. Through extensive simulations and theoretical analysis, we show that incongruences between methods can result from failing to account for dengue antibody kinetics, assay noise, and heterogeneity in FOI across ages. Extending standard inference models to include these processes reconciled the FOI and susceptibility estimates. Our results highlight the importance of comparing inferences across multiple data types to uncover additional insights not attainable through a single data type/analysis.

摘要

揭示易感个体感染病原体的速率,即感染力(FOI),对于评估传播风险和重建人群中的免疫分布至关重要。对于登革热而言,根据测量的FOI重建暴露和易感性状态具有特别重要的意义,因为既往暴露是重症疾病的一个重要危险因素。FOI可以通过多种研究设计来测量。纵向血清学被认为是金标准测量方法,因为它们直接追踪血清阴性个体因新发感染(血清发病率)转变为血清阳性的过程。横断面血清学可以通过对比不同年龄组的血清阳性率来提供FOI的估计值。报告病例的年龄也可用于推断FOI。然而,尚未评估这些测量方法之间的一致性。利用泰国彭世洛府队列研究和医院就诊病例的26年数据,我们发现来自这三种来源的FOI估计值高度不一致。血清发病率得出的年度FOI估计值比病例来源的FOI高2.46至4.33倍。血清阳性率来源的FOI与病例来源的FOI之间的相关性中等(相关系数 = 0.46)且无系统偏差。通过广泛的模拟和理论分析,我们表明方法之间的不一致可能是由于未考虑登革热抗体动力学、检测噪声以及不同年龄组FOI的异质性。扩展标准推断模型以纳入这些过程可使FOI和易感性估计值趋于一致。我们的结果强调了比较多种数据类型推断结果以揭示单一数据类型/分析无法获得的更多见解的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/502f/11419196/67d511f12966/nihpp-2024.09.09.24313375v1-f0001.jpg

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