Table_1_Diagnostic performance of a urine-based ELISA assay for the screening of human schistosomiasis japonica: A comparative study.XLSX

The current study developed and evaluated the performance of a urine-based enzyme-linked immunosorbent assay (ELISA) for the screening of Schistosoma japonicum infection in a human cohort (n = 412) recruited from endemic areas, Northern Samar, the Philippines. The diagnostic performance of the urine ELISA assay was further compared with the Kato-Katz (KK) technique, serum-based ELISA assays, point-of-care circulating cathodic antigen (POC-CCA) urine cassette test, and droplet digital (dd)PCR assays performed on feces, serum, urine, and saliva samples, which were designated as F_ddPCR, SR_ddPCR, U_ddPCR, and SL_ddPCR, respectively. When urine samples concentrated 16× were assessed, the SjSAP4 + Sj23-LHD-ELISA (U) showed sensitivity/specificity values of 47.2/93.8% for the detection of S. japonicum infection in KK-positive individuals (n = 108). The prevalence of S. japonicum infection in the total cohort determined by the urine ELISA assay was 48.8%, which was lower than that obtained with the F_ddPCR (74.5%, p < 0.001), SR_ddPCR (67.2%, p < 0.001), and SjSAP4 + Sj23-LHD-ELISA (S) (66.0%, p < 0.001), but higher than that determined by the Sj23-LHD-ELISA (S) (24.5%, p < 0.001), POC-CCA assay (12.4%, p < 0.001), and SL_ddPCR (25.5%, p < 0.001). Using the other diagnostic tests as a reference, the urine ELISA assay showed a sensitivity between 47.2 and 56.9%, a specificity between 50.7 and 55.2%, and an accuracy between 49.3 and 53.4%. The concentrated urine SjSAP4 + Sj23-LHD-ELISA developed in the current study was more sensitive than both the KK test and POC-CCA assay, and showed a comparable level of diagnostic accuracy to that of the U_ddPCR. However, its diagnostic performance was less robust than that of the F_ddPCR, SR_ddPCR, and SjSAP4 + Sj23-LHD-ELISA (S) assays. Although they are convenient and involve a highly acceptable non-invasive procedure for clinical sample collection, the insufficient sensitivity of the three urine-based assays (the urine ELISA assay, the U_ddPCR test, and the POC-CCA assay) will limit their value for the routine screening of schistosomiasis japonica in the post mass drug administration (MDA) era, where low-intensity infections are predominant in many endemic areas.

本研究开发并评估了一种基于尿液的酶联免疫吸附试验（ELISA）的性能，用于筛查菲律宾北萨马省流行区招募的人类队列（n=412）中的日本血吸虫（Schistosoma japonicum）感染。本研究进一步将该尿液ELISA检测法的诊断性能，与加藤-Katz（KK）检测技术、血清型ELISA检测法、即时检测循环阴极抗原（POC-CCA）尿液试条检测法，以及分别针对粪便、血清、尿液和唾液样本的液滴数字聚合酶链式反应（ddPCR）检测法进行对比，上述ddPCR检测法分别命名为粪便ddPCR（F_ddPCR）、血清ddPCR（SR_ddPCR）、尿液ddPCR（U_ddPCR）和唾液ddPCR（SL_ddPCR）。当对16倍浓缩的尿液样本进行检测时，SjSAP4+Sj23-LHD-ELISA（U）针对加藤-Katz检测阳性个体（n=108）的检测灵敏度和特异度分别为47.2%和93.8%。本研究通过尿液ELISA检测确定的全队列日本血吸虫感染率为48.8%，该感染率低于粪便ddPCR（74.5%，p<0.001）、血清ddPCR（67.2%，p<0.001）以及SjSAP4+Sj23-LHD-ELISA（血清组，S）（66.0%，p<0.001），但高于Sj23-LHD-ELISA（血清组，S）（24.5%，p<0.001）、POC-CCA检测法（12.4%，p<0.001）以及唾液ddPCR（25.5%，p<0.001）。以其余诊断检测方法为参照标准，尿液ELISA检测法的灵敏度介于47.2%至56.9%之间，特异度介于50.7%至55.2%之间，准确率介于49.3%至53.4%之间。本研究开发的16倍浓缩尿液版SjSAP4+Sj23-LHD-ELISA，其灵敏度优于加藤-Katz检测法与POC-CCA检测法，诊断准确率与尿液ddPCR（U_ddPCR）相当。不过其诊断性能仍不及粪便ddPCR、血清ddPCR以及SjSAP4+Sj23-LHD-ELISA（血清组）检测法。尽管此类尿液检测方法操作便捷，且临床样本采集为无创操作，受试者接受度极高，但三种尿液检测方法（尿液ELISA检测法、尿液ddPCR检测法以及POC-CCA检测法）的灵敏度不足，这将限制其在群体性药物治疗（MDA）后时代的日本血吸虫病常规筛查中的应用价值——此时许多流行区以低强度感染为主。