MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom.
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
PLoS Comput Biol. 2020 May 4;16(5):e1007840. doi: 10.1371/journal.pcbi.1007840. eCollection 2020 May.
We present a flexible, open source R package designed to obtain biological and epidemiological insights from serological datasets. Characterising past exposures for multi-strain pathogens poses a specific statistical challenge: observed antibody responses measured in serological assays depend on multiple unobserved prior infections that produce cross-reactive antibody responses. We provide a general modelling framework to jointly infer infection histories and describe immune responses generated by these infections using antibody titres against current and historical strains. We do this by linking latent infection dynamics with a mechanistic model of antibody kinetics that generates expected antibody titres over time. Our aim is to provide a flexible package to identify infection histories that can be applied to a range of pathogens. We present two case studies to illustrate how our model can infer key immunological parameters, such as antibody titre boosting, waning and cross-reaction, as well as latent epidemiological processes such as attack rates and age-stratified infection risk.
我们提出了一个灵活的、开源的 R 包,旨在从血清数据集获得生物学和流行病学的见解。描述多菌株病原体的过去暴露情况带来了一个特殊的统计挑战:在血清学检测中观察到的抗体反应取决于多个未观察到的先前感染,这些感染会产生交叉反应的抗体反应。我们提供了一个通用的建模框架,用于联合推断感染史,并使用针对当前和历史菌株的抗体滴度来描述这些感染产生的免疫反应。我们通过将潜在的感染动力学与抗体动力学的机制模型联系起来来实现这一点,该模型会生成随时间变化的预期抗体滴度。我们的目标是提供一个灵活的包来识别可以应用于多种病原体的感染史。我们提出了两个案例研究来说明我们的模型如何推断关键的免疫学参数,例如抗体滴度增强、衰减和交叉反应,以及潜伏的流行病学过程,例如发病率和年龄分层的感染风险。