Schistosomiasis Control Initiative (SCI), Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
Parasit Vectors. 2018 Feb 23;11(1):111. doi: 10.1186/s13071-018-2700-4.
Kato-Katz examination of stool smears is the field-standard method for detecting Schistosoma mansoni infection. However, Kato-Katz misses many active infections, especially of light intensity. Point-of-care circulating cathodic antigen (CCA) is an alternative field diagnostic that is more sensitive than Kato-Katz when intensity is low, but interpretation of CCA-trace results is unclear. To evaluate trace results, we tested urine and stool specimens from 398 pupils from eight schools in Burundi using four approaches: two in Burundi and two in a laboratory in Leiden, the Netherlands. In Burundi, we used Kato-Katz and point-of-care CCA (CCAB). In Leiden, we repeated the CCA (CCAL) and also used Up-Converting Phosphor Circulating Anodic Antigen (CAA).
We applied Bayesian latent class analyses (LCA), first considering CCA traces as negative and then as positive. We used the LCA output to estimate validity of the prevalence estimates of each test in comparison to the population-level infection prevalence and estimated the proportion of trace results that were likely true positives.
Kato-Katz yielded the lowest prevalence (6.8%), and CCAB with trace considered positive yielded the highest (53.5%). There were many more trace results recorded by CCA in Burundi (32.4%) than in Leiden (2.3%). Estimated prevalence with CAA was 46.5%. LCA indicated that Kato-Katz had the lowest sensitivity: 15.9% [Bayesian Credible Interval (BCI): 9.2-23.5%] with CCA-trace considered negative and 15.0% with trace as positive (BCI: 9.6-21.4%), implying that Kato-Katz missed approximately 85% of infections. CCAB underestimated disease prevalence when trace was considered negative and overestimated disease prevalence when trace was considered positive, by approximately 12 percentage points each way, and CAA overestimated prevalence in both models. Our results suggest that approximately 52.2% (BCI: 37.8-5.8%) of the CCAB trace readings were true infections.
Whether measured in the laboratory or the field, CCA outperformed Kato-Katz at the low infection intensities in Burundi. CCA with trace as negative likely missed many infections, whereas CCA with trace as positive overestimated prevalence. In the absence of a field-friendly gold standard diagnostic, the use of a variety of diagnostics with differing properties will become increasingly important as programs move towards elimination of schistosomiasis. It is clear that CCA is a valuable tool for the detection and mapping of S. mansoni infection in the field and CAA may be a valuable field tool in the future.
加藤厚涂片检查是检测曼氏血吸虫感染的现场标准方法。然而，加藤厚涂片检查会漏掉许多活动性感染，尤其是感染强度较低的情况。即时检测循环阴极抗原（CCA）是一种替代现场诊断方法，在感染强度较低时比加藤厚涂片检查更敏感，但 CCA 痕迹结果的解释尚不清楚。为了评估痕迹结果，我们使用四种方法检测了来自布隆迪 8 所学校的 398 名学生的尿液和粪便标本：两种在布隆迪，两种在荷兰莱顿的实验室。在布隆迪，我们使用了加藤厚涂片检查和即时检测 CCA（CCA-B）。在莱顿，我们重复了 CCA（CCA-L），并使用上转换磷循环阳极抗原（CAA）。
我们应用了贝叶斯潜在类别分析（LCA），首先将 CCA 痕迹视为阴性，然后视为阳性。我们使用 LCA 输出来估计每种测试的患病率估计值与人群感染率的比较，并估计了可能为真正阳性的痕迹结果的比例。
加藤厚涂片检查的患病率最低（6.8%），而将 CCA-B 痕迹视为阳性的患病率最高（53.5%）。在布隆迪，CCA 记录的痕迹结果比在莱顿多得多（32.4%）。用 CAA 估计的患病率为 46.5%。LCA 表明加藤厚涂片检查的敏感性最低：将 CCA 痕迹视为阴性时为 15.9%（贝叶斯可信区间[BCI]：9.2-23.5%），将痕迹视为阳性时为 15.0%（BCI：9.6-21.4%），这意味着加藤厚涂片检查漏诊了大约 85%的感染。当 CCA-B 痕迹被视为阴性时，CCAB 低估了疾病的患病率，而当 CCA-B 痕迹被视为阳性时，CCAB 高估了疾病的患病率，两种情况都相差约 12 个百分点，而 CAA 在两种模型中都高估了患病率。我们的结果表明，大约 52.2%（BCI：37.8-5.8%）的 CCA-B 痕迹读数是真正的感染。
无论在实验室还是现场测量，CCA 在布隆迪的低感染强度下均优于加藤厚涂片检查。CCA 痕迹视为阴性可能会漏诊许多感染，而 CCA 痕迹视为阳性则会高估患病率。在没有现场友好型金标准诊断的情况下，使用具有不同特性的各种诊断方法将变得越来越重要，因为这些方法将逐渐被用于消除血吸虫病。显然，CCA 是现场检测和绘制曼氏血吸虫感染图的一种有价值的工具，而 CAA 可能是未来一种有价值的现场工具。
