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从基于虫卵到基于抗原的消除指标转换:一项贝叶斯潜在类别分析研究

Translating From Egg- to Antigen-Based Indicators for Elimination Targets: A Bayesian Latent Class Analysis Study.

作者信息

Clark Jessica, Moses Arinaitwe, Nankasi Andrina, Faust Christina L, Adriko Moses, Ajambo Diana, Besigye Fred, Atuhaire Arron, Wamboko Aidah, Rowel Candia, Carruthers Lauren V, Francoeur Rachel, Tukahebwa Edridah M, Lamberton Poppy H L, Prada Joaquin M

机构信息

Wellcome Centre for Integrative Parasitology, Institute of Biodiversity, Animal Health & Comparative Medicine, University of Glasgow, Glasgow, United Kingdom.

Vector Control Division, Ministry of Health, Kampala, Uganda.

出版信息

Front Trop Dis. 2022 Feb 18;3:825721. doi: 10.3389/fitd.2022.825721.

Abstract

Schistosomiasis is a parasitic disease affecting over 240-million people. World Health Organization (WHO) targets for Schistosoma mansoni elimination are based on Kato-Katz egg counts, without translation to the widely used, urine-based, point-of-care circulating cathodic antigen diagnostic (POC-CCA). We aimed to standardize POC-CCA score interpretation and translate them to Kato-Katz-based standards, broadening diagnostic utility in progress towards elimination. A Bayesian latent-class model was fit to data from 210 school-aged-children over four timepoints pre- to six-months-post-treatment. We used 1) Kato-Katz and established POC-CCA scoring (Negative, Trace, +, ++ and +++), and 2) Kato-Katz and G-Scores (a new, alternative POC-CCA scoring (G1 to G10)). We established the functional relationship between Kato-Katz counts and POC-CCA scores, and the score-associated probability of true infection. This was combined with measures of sensitivity, specificity, and the area under the curve to determine the optimal POC-CCA scoring system and positivity threshold. A simulation parametrized with model estimates established antigen-based elimination targets. True infection was associated with POC-CCA scores of ≥ + or ≥G3. POC-CCA scores cannot predict Kato-Katz counts because low infection intensities saturate the POC-CCA cassettes. Post-treatment POC-CCA sensitivity/specificity fluctuations indicate a changing relationship between egg excretion and antigen levels (living worms). Elimination targets can be identified by the POC-CCA score distribution in a population. A population with ≤2% ++/+++, or ≤0.5% G7 and above, indicates achieving current WHO Kato-Katz-based elimination targets. Population-level POC-CCA scores can be used to access WHO elimination targets prior to treatment. Caution should be exercised on an individual level and following treatment, as POC-CCAs lack resolution to discern between WHO Kato-Katz-based moderate- and high-intensity-infection categories, with limited use in certain settings and evaluations.

摘要

血吸虫病是一种影响超过2.4亿人的寄生虫病。世界卫生组织(WHO)针对曼氏血吸虫消除的目标是基于加藤厚涂片法虫卵计数,而未转化为广泛使用的基于尿液的即时循环阴极抗原诊断法(POC-CCA)。我们旨在规范POC-CCA评分的解读,并将其转化为基于加藤厚涂片法的标准,以扩大在消除进程中的诊断效用。将一个贝叶斯潜在类别模型拟合至210名学龄儿童在治疗前至治疗后六个月的四个时间点的数据。我们使用了1)加藤厚涂片法和既定的POC-CCA评分(阴性、微量、+、++和+++),以及2)加藤厚涂片法和G评分(一种新的替代性POC-CCA评分(G1至G10))。我们确定了加藤厚涂片法虫卵计数与POC-CCA评分之间的函数关系,以及与评分相关的真实感染概率。这与敏感性、特异性和曲线下面积的测量值相结合,以确定最佳的POC-CCA评分系统和阳性阈值。用模型估计值进行参数化的模拟确定了基于抗原的消除目标。真实感染与POC-CCA评分≥+或≥G3相关。POC-CCA评分无法预测加藤厚涂片法虫卵计数,因为低感染强度会使POC-CCA检测盒饱和。治疗后POC-CCA敏感性/特异性的波动表明虫卵排泄与抗原水平(活虫)之间的关系在变化。消除目标可通过人群中的POC-CCA评分分布来确定。一个人群中≤2%为++/+++,或≤0.5%为G7及以上,表明实现了当前WHO基于加藤厚涂片法的消除目标。人群水平的POC-CCA评分可用于在治疗前评估WHO的消除目标。在个体层面和治疗后应谨慎使用,因为POC-CCA缺乏分辨WHO基于加藤厚涂片法的中度和高强度感染类别的分辨率,在某些环境和评估中的用途有限。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/799d/7612949/3acf7e42d1d6/EMS146323-f001.jpg

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