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基于连续酶联免疫吸附测定(ELISA)反应的牛副结核病群体内流行率估计的贝叶斯混合模型

Bayesian mixture models for within-herd prevalence estimates of bovine paratuberculosis based on a continuous ELISA response.

作者信息

Nielsen S S, Toft N, Jørgensen E, Bibby B M

机构信息

Department of Large Animal Sciences, Faculty of Life Sciences, University of Copenhagen, Grønnegårdsvej 8, DK-1870 Frederiksberg C, Denmark.

出版信息

Prev Vet Med. 2007 Oct 16;81(4):290-305. doi: 10.1016/j.prevetmed.2007.05.014. Epub 2007 Jun 18.

Abstract

Diagnostic inference by use of assays such as ELISA is usually done by dichotomizing the optical density (OD)-values based on a predetermined cut-off. For paratuberculosis, a slowly developing infection in cattle and other ruminants, it is known that laboratory factors as well as animal specific covariates influence the OD-value, but while laboratory factors are adjusted for, the animal specific covariates are seldom utilized when establishing cut-offs. Furthermore, when dichotomizing an OD-value, information is lost. Considering the poor diagnostic performance of ELISAs for diagnosis of paratuberculosis, a framework for utilizing the continuous OD-values as well as known coavariates could be useful in addition to the traditional approaches, e.g. for estimating within-herd prevalences. The objective of this study was to develop a Bayesian mixture model with two components describing the continuous OD response of infected and non-infected cows, while adjusting for known covariates. Based on this model, four different within-herd prevalence indicators were considered: the mean prevalence in the herd; the age adjusted prevalence of the herd for better between-herd comparisons; the rank of the age adjusted prevalence to better compare across time; and a threshold-based prevalence to describe differences between herds. For comparison, the within-herd prevalence and associated rank using a traditional dichotomization approach based on a single cut-off for an OD corrected for laboratory variation was estimated in a Bayesian model with priors for sensitivity and specificity. The models were applied to the OD-values of a milk ELISA using samples from all lactating cows in 100 Danish dairy herds in three sampling rounds 13 months apart. The results of the comparison showed that including covariates in the mixture model reduced the uncertainty of the prevalence estimates compared to the cut-off based estimates. This allowed a more informative ranking of the herds where low ranking and high ranking herds were easier to identify.

摘要

通过使用酶联免疫吸附测定(ELISA)等检测方法进行诊断推断时,通常是根据预先设定的临界值将光密度(OD)值进行二分。对于副结核病,这是一种在牛和其他反刍动物中缓慢发展的感染,已知实验室因素以及动物特异性协变量会影响OD值,但在确定临界值时,虽然对实验室因素进行了调整,但很少利用动物特异性协变量。此外,在对OD值进行二分时,信息会丢失。考虑到ELISA在诊断副结核病方面的诊断性能较差,除了传统方法外,利用连续OD值以及已知协变量的框架可能会很有用,例如用于估计牛群内的患病率。本研究的目的是开发一种贝叶斯混合模型,该模型有两个成分来描述感染和未感染奶牛的连续OD反应,同时对已知协变量进行调整。基于该模型,考虑了四种不同的牛群内患病率指标:牛群中的平均患病率;为了更好地进行牛群间比较而进行年龄调整后的牛群患病率;为了更好地进行跨时间比较而进行年龄调整后的患病率排名;以及基于阈值的患病率来描述牛群之间的差异。为了进行比较,在一个具有灵敏度和特异性先验的贝叶斯模型中,估计了使用基于单一临界值对实验室变异进行校正后的OD值的传统二分法的牛群内患病率及相关排名。这些模型应用于一种牛奶ELISA的OD值,该ELISA使用了来自100个丹麦奶牛场所有泌乳奶牛的样本,分三轮采样,间隔13个月。比较结果表明,与基于临界值的估计相比,在混合模型中纳入协变量降低了患病率估计的不确定性。这使得对牛群的排名更具信息性,低排名和高排名的牛群更容易识别。

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