Mu Yi, Weerakoon Kosala G, Olveda Remigio M, Ross Allen G, McManus Donald P, Cai Pengfei
Molecular Parasitology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Department of Health, Research Institute for Tropical Medicine, Manila, Philippines.
Front Microbiol. 2022 Nov 14;13:1051575. doi: 10.3389/fmicb.2022.1051575. eCollection 2022.
The current study developed and evaluated the performance of a urine-based enzyme-linked immunosorbent assay (ELISA) for the screening of infection in a human cohort ( = 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 infection in KK-positive individuals (n = 108). The prevalence of 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%, < 0.001), SR_ddPCR (67.2%, < 0.001), and SjSAP4 + Sj23-LHD-ELISA (S) (66.0%, < 0.001), but higher than that determined by the Sj23-LHD-ELISA (S) (24.5%, < 0.001), POC-CCA assay (12.4%, < 0.001), and SL_ddPCR (25.5%, < 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测定（ELISA），用于对从菲律宾北萨马省流行地区招募的412名人类队列中的感染进行筛查。将尿液ELISA检测的诊断性能与加藤-厚涂片法（KK）、基于血清的ELISA检测、即时检测循环阴极抗原（POC-CCA）尿液检测盒以及分别对粪便、血清、尿液和唾液样本进行的液滴数字（dd）PCR检测进行了进一步比较，这些检测分别被指定为F_ddPCR、SR_ddPCR、U_ddPCR和SL_ddPCR。当评估浓缩16倍的尿液样本时，SjSAP4 + Sj23-LHD-ELISA（U）在检测KK阳性个体（n = 108）中的感染时，敏感性/特异性值为47.2/93.8%。通过尿液ELISA检测确定的整个队列中的感染率为48.8%，低于F_ddPCR（74.5%，P < 0.001）、SR_ddPCR（67.2%，P < 0.001）和SjSAP4 + Sj23-LHD-ELISA（S）（66.0%，P < 0.001），但高于Sj23-LHD-ELISA（S）（24.5%，P < 0.001）、POC-CCA检测（12.4%，P < 0.001）和SL_ddPCR（25.5%，P < 0.001）。以其他诊断测试为参考，尿液ELISA检测的敏感性在47.2%至56.9%之间，特异性在50.7%至55.2%之间，准确性在49.3%至53.4%之间。本研究中开发的浓缩尿液SjSAP4 + Sj23-LHD-ELISA比KK检测和POC-CCA检测更敏感，并且与U_ddPCR的诊断准确性相当。然而，其诊断性能不如F_ddPCR、SR_ddPCR和SjSAP4 + Sj23-LHD-ELISA（S）检测。尽管这三种基于尿液的检测（尿液ELISA检测、U_ddPCR检测和POC-CCA检测）方便且涉及临床样本采集的高度可接受的非侵入性程序，但在许多流行地区低强度感染占主导的大规模药物管理（MDA）后时代，这三种检测的敏感性不足将限制它们在日本血吸虫病常规筛查中的价值。
