Reproducibility matters: intra- and inter-sample variation of the point-of-care circulating cathodic antigen test in two Schistosoma mansoni endemic areas in Uganda
Reproducibility matters: intra- and inter-sample variation of the point-of-care circulating cathodic antigen test in two Schistosoma mansoni endemic areas in Uganda
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DOI：
10.1098/rstb.2022.0275
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发表时间：
2023-10-09
影响因子：
6.3
通讯作者：
Lamberton，Poppy H. L.
中科院分区：
文献类型：
--
作者：
Kabbas-Pinango，Elias;Arinaitwe，Moses;Lamberton，Poppy H. L.
超过2.4亿人感染血吸虫病。使用Kato-Katz厚涂片（Kato-Katz）检测粪便中的曼氏血吸虫卵具有高度特异性，但缺乏敏感性。基于尿液的床旁循环阴极抗原检测（POC-CCA）具有较高的灵敏度，但问题包括特异性，批次之间的差异和痕量结果的解释。一个半定量的G分数和潜在的类分析没有假设的痕迹读数有助于解决这些问题。然而，POC-CCA的样本内和样本间变异仍然未知。我们收集了3天的粪便和尿液从349和621名参与者，分别从高和中度流行地区。我们对每个样品进行了一式两份Kato-Katz和一次POC-CCA。在高流行社区，我们还对每位参与者的一份尿样进行了三次POC-CCA技术重复。进行潜在类别分析以估计样本内（测试技术重现性）和样本间（每日）变异对灵敏度和特异性的相对贡献。Kato-Katzs的样本内变异高于样本间变异，而POC-CCA的样本内变异则相反。POC-CCA G3阈值最准确地评估个体感染。然而，为了达到世卫组织对流行率、监测和评估所要求的95%特异性的目标产品概况，需要G4的阈值，但这是以降低灵敏度为代价的。这篇文章是主题"与被忽视的热带病作斗争的挑战和机遇：从伦敦NTDs宣言开始的十年“的一部分。
Over 240 million people are infected with schistosomiasis. DetectingSchistosoma mansonieggs in stool using Kato–Katz thick smears (Kato-Katzs) is highly specific but lacks sensitivity. The urine-based point-of-care circulating cathodic antigen test (POC-CCA) has higher sensitivity, but issues include specificity, discrepancy between batches and interpretation of trace results. A semi-quantitative G-score and latent class analyses making no assumptions about trace readings have helped address some of these issues. However, intra-sample and inter-sample variation remains unknown for POC-CCAs. We collected 3 days of stool and urine from 349 and 621 participants, from high- and moderate-endemicity areas, respectively. We performed duplicate Kato-Katzs and one POC-CCA per sample. In the high-endemicity community, we also performed three POC-CCA technical replicates on one urine sample per participant. Latent class analysis was performed to estimate the relative contribution of intra- (test technical reproducibility) and inter-sample (day-to-day) variation on sensitivity and specificity. Within-sample variation for Kato-Katzs was higher than between-sample, with the opposite true for POC-CCAs. A POC-CCA G3 threshold most accurately assesses individual infections. However, to reach the WHO target product profile of the required 95% specificity for prevalence and monitoring and evaluation, a threshold of G4 is needed, but at the cost of reducing sensitivity.This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.