Circulating antigen tests and urine reagent strips for diagnosis of active schistosomiasis in endemic areas.
Circulating antigen tests and urine reagent strips for diagnosis of active schistosomiasis in endemic areas.
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DOI：
10.1002/14651858.cd009579.pub2
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发表时间：
2015-03-11
影响因子：
8.4
通讯作者：
Leeflang, Mariska M. G.
中科院分区：
文献类型：
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作者：
Ochodo, Eleanor A.;Gopalakrishna, Gowri;Spek, Bea;Reitsma, Johannes B.;van Lieshout, Lisette;Polman, Katja;Lamberton, Poppy;Bossuyt, Patrick M. M.;Leeflang, Mariska M. G.
用于诊断血吸虫病的医疗点（POC）检测包括基于循环抗原检测和尿试剂试纸的检测。如果他们有足够的诊断准确性，他们可以取代传统的显微镜，因为他们提供了一个更快的答案，更容易使用。总结尿试剂试纸检测活动性血血吸虫感染的诊断准确性，以镜检为参比标准；b)以显微镜为参考标准，在曼氏血吸虫或血血吸虫或两者同时流行的地理区域进行循环抗原检测，以检测活动性血吸虫感染。截至2014年6月30日，我们在没有语言限制的情况下检索了MEDLINE、EMBASE、BIOSIS、MEDION和Health Technology Assessment （HTA）电子数据库。我们纳入了以显微镜作为参考标准的研究：对于血链球菌，用过滤、离心或沉淀法制备的尿液显微镜；对于mansoni链球菌，采用Kato - Katz厚涂片粪便显微镜。我们只纳入了居住在流行地区的参与者的研究。两位综述作者独立提取数据，使用QUADAS‐2评估数据质量，并在适当时进行meta分析。利用测试阈值的可变性，我们对所有符合条件的测试（除了曼氏链球菌的循环阴极抗原（CCA） POC，其中双变量随机效应模型更合适）使用了分层总结接收者操作特征（HSROC）模型。我们调查了异质性，并在数据充足的情况下进行了间接比较。敏感性和特异性的结果以95%置信区间（CI）的百分比表示。我们纳入了90项研究；88人来自非洲实地。血红梭菌感染率中位数为41%(1%至89%)，曼氏梭菌感染率中位数为36%（8%至95%）。根据现行标准，研究设计和行为报告不足。与显微镜检查相比，在试纸上检测微量血尿具有最高的灵敏度和特异性（灵敏度75%，95%置信区间71%至79%；特异性87%，95%置信区间84%至90%；74项研究，102,447名受试者）。对于蛋白尿，敏感性为61%，特异性为82%（82,113名参与者）；对于白细胞增多症，敏感性为58%，特异性为61%（1532名参与者）。然而，当我们比较单独的人群（P = 0.25）或在同一个体中进行直接比较（配对研究，P = 0.21）时，发现微量血尿和蛋白尿的尿液试剂条之间的总体测试准确性差异没有差异。当测试以更高质量的参考标准进行评估时（当分析多个样本时），微血尿（71%对75%）和蛋白尿（49%对61%）的敏感性略低。这些试验的特异性具有可比性。抗原测定与显微镜相比，CCA试验显示出相当大的异质性；meta分析敏感性估计为39%，95% CI为6%至73%；特异性78%，95% CI 55% ~ 100%（4项研究，901名受试者）。与显微镜检测相比，CCA检测在单一阈值检测微量阳性曼索尼梭菌的meta分析估计为：灵敏度89% (95% CI 86%至92%)；与更高质量的参考标准相比，敏感性结果具有可比性（89%对88%），但特异性更高（66%对55%）。对于CAA测试，敏感性从47%到94%，特异性从8%到100%（4项研究，1583名参与者）。在评估的血链球菌感染检测中，微血尿正确检测出镜检中感染和非感染的比例最大。mansoni的CCA POC检测检测到镜检发现的很大一部分感染，但在感染流行率中等至高的流行地区，它将很大一部分镜检阴性误诊为阳性，可能是因为该检测可能比镜检更敏感。其他有明确结论的可靠证据。最后一次检索（2014年6月30日）中发现的所有符合条件的已发表研究均被纳入。在生活在流行地区的人群中，护理点检测检测血吸虫感染的效果如何？血吸虫病，又称血吸虫病，是一种常见于热带和亚热带地区的寄生虫病。点护理测试和尿试剂条测试比显微镜更快，更容易使用。我们估计与显微镜相比，这些护理点检测检测血吸虫病感染的能力有多好。我们检索了截至2014年6月30日以任何语言发表的研究，并考虑了该研究提供偏倚结果的风险。结果如何？我们纳入了涉及近20万人的90项研究，其中88项研究在非洲的实地环境中进行。研究设计和行为的报道与目前的预期不符。根据我们的统计模型，我们发现：•尿血吸虫病尿试纸中，血试纸优于蛋白试纸和白细胞试纸（血试纸的敏感性和特异性分别为75%和87%，蛋白试纸的敏感性和特异性分别为61%和82%，白细胞试纸的敏感性和特异性分别为58%和61%）。
•对于尿路血吸虫病，寄生虫抗原检测的灵敏度为39%，特异性为78%，低于尿试纸检测。
•对于肠道血吸虫病，寄生虫抗原尿检检测出许多通过显微镜鉴定的感染，但错误地将许多未感染者标记为患病（敏感性89%，特异性55%）。使用这些测试的后果是什么？如果取1000人，其中镜检尿血吸虫病410人，用试纸检尿血会将77名未感染者误分类为感染者，从而可能受到不必要的治疗；而且它会错误地将102名感染者归类为未感染者，从而可能无法接受治疗。如果我们取1000人，其中360人在显微镜检查中有肠道血吸虫病，那么抗原测试将288名未感染者错误地分类为感染者。这些人可能会得到不必要的治疗。该测试还会错误地将40名感染者归类为未感染者，从而可能无法接受治疗。尿路血吸虫病，尿试血检漏检和非感染者检出，但优于蛋白或白细胞检查。寄生虫抗原检测不准确。对于肠血吸虫病，寄生虫抗原尿检将许多显微镜检查阴性的人归类为感染者。这一发现可以用显微镜的低灵敏度来解释。
Point‐of‐care (POC) tests for diagnosing schistosomiasis include tests based on circulating antigen detection and urine reagent strip tests. If they had sufficient diagnostic accuracy they could replace conventional microscopy as they provide a quicker answer and are easier to use. To summarise the diagnostic accuracy of: a) urine reagent strip tests in detecting active Schistosoma haematobium infection, with microscopy as the reference standard; and b) circulating antigen tests for detecting active Schistosoma infection in geographical regions endemic for Schistosoma mansoni or S. haematobium or both, with microscopy as the reference standard. We searched the electronic databases MEDLINE, EMBASE, BIOSIS, MEDION, and Health Technology Assessment (HTA) without language restriction up to 30 June 2014. We included studies that used microscopy as the reference standard: for S. haematobium, microscopy of urine prepared by filtration, centrifugation, or sedimentation methods; and for S. mansoni, microscopy of stool by Kato‐Katz thick smear. We included studies on participants residing in endemic areas only. Two review authors independently extracted data, assessed quality of the data using QUADAS‐2, and performed meta‐analysis where appropriate. Using the variability of test thresholds, we used the hierarchical summary receiver operating characteristic (HSROC) model for all eligible tests (except the circulating cathodic antigen (CCA) POC for S. mansoni, where the bivariate random‐effects model was more appropriate). We investigated heterogeneity, and carried out indirect comparisons where data were sufficient. Results for sensitivity and specificity are presented as percentages with 95% confidence intervals (CI). We included 90 studies; 88 from field settings in Africa. The median S. haematobium infection prevalence was 41% (range 1% to 89%) and 36% for S. mansoni (range 8% to 95%). Study design and conduct were poorly reported against current standards. Tests for S. haematobium Urine reagent test strips versus microscopy Compared to microscopy, the detection of microhaematuria on test strips had the highest sensitivity and specificity (sensitivity 75%, 95% CI 71% to 79%; specificity 87%, 95% CI 84% to 90%; 74 studies, 102,447 participants). For proteinuria, sensitivity was 61% and specificity was 82% (82,113 participants); and for leukocyturia, sensitivity was 58% and specificity 61% (1532 participants). However, the difference in overall test accuracy between the urine reagent strips for microhaematuria and proteinuria was not found to be different when we compared separate populations (P = 0.25), or when direct comparisons within the same individuals were performed (paired studies; P = 0.21). When tests were evaluated against the higher quality reference standard (when multiple samples were analysed), sensitivity was marginally lower for microhaematuria (71% vs 75%) and for proteinuria (49% vs 61%). The specificity of these tests was comparable. Antigen assay Compared to microscopy, the CCA test showed considerable heterogeneity; meta‐analytic sensitivity estimate was 39%, 95% CI 6% to 73%; specificity 78%, 95% CI 55% to 100% (four studies, 901 participants). Tests for S. mansoni Compared to microscopy, the CCA test meta‐analytic estimates for detecting S. mansoni at a single threshold of trace positive were: sensitivity 89% (95% CI 86% to 92%); and specificity 55% (95% CI 46% to 65%; 15 studies, 6091 participants) Against a higher quality reference standard, the sensitivity results were comparable (89% vs 88%) but specificity was higher (66% vs 55%). For the CAA test, sensitivity ranged from 47% to 94%, and specificity from 8% to 100% (four studies, 1583 participants). Among the evaluated tests for S. haematobium infection, microhaematuria correctly detected the largest proportions of infections and non‐infections identified by microscopy. The CCA POC test for S. mansoni detects a very large proportion of infections identified by microscopy, but it misclassifies a large proportion of microscopy negatives as positives in endemic areas with a moderate to high prevalence of infection, possibly because the test is potentially more sensitive than microscopy. 23 April 2019 No update planned Other Reliable evidence with clear conclusions. All eligible published studies found in the last search (30 Jun, 2014) were included. How well do point‐of‐care tests detect Schistosoma infections in people living inendemic areas? Schistosomiasis, also known as bilharzia, is a parasitic disease common in the tropical and subtropics. Point‐of‐care tests and urine reagent strip tests are quicker and easier to use than microscopy. We estimate how well these point‐of‐care tests are able to detect schistosomiasis infections compared with microscopy. We searched for studies published in any language up to 30 June 2014, and we considered the study’s risk of providing biased results. What do the results say? We included 90 studies involving almost 200,000 people, with 88 of these studies carried out in Africa in field settings. Study design and conduct were poorly reported against current expectations. Based on our statistical model, we found: • Among the urine strips for detecting urinary schistosomiasis, the strips for detecting blood were better than those detecting protein or white cells (sensitivity and specificity for blood 75% and 87%; for protein 61% and 82%; and for white cells 58% and 61%, respectively).
• For urinary schistosomiasis, the parasite antigen test performance was worse (sensitivity, 39% and specificity, 78%) than urine strips for detecting blood.
• For intestinal schistosomiasis, the parasite antigen urine test, detected many infections identified by microscopy but wrongly labelled many uninfected people as sick (sensitivity, 89% and specificity, 55%). What are the consequences of using these tests? If we take 1000 people, of which 410 have urinary schistosomiasis on microscopy testing, then using the strip detecting blood in the urine would misclassify 77 uninfected people as infected, and thus may receive unnecessary treatment; and it would wrongly classify 102 infected people as uninfected, who thus may not receive treatment. If we take 1000 people, of which 360 have intestinal schistosomiasis on microscopy testing, then the antigen test would misclassify 288 uninfected people as infected. These people may be given unnecessary treatment. This test also would wrongly classify 40 infected people as uninfected who thus may not receive treatment. Conclusion of review For urinary schistosomiasis, the urine strip for detecting blood leads to some infected people being missed and some non‐infected people being diagnosed with the condition, but is better than the protein or white cell tests. The parasite antigen test is not accurate. For intestinal schistosomiasis, the parasite antigen urine test classifies many microscopy negative people as being infected. This finding may be explained by the low sensitivity of microscopy.