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检测和分析丝氨酸蛋白酶抑制剂(Serpin)和RP26特异性抗体以监测埃及血吸虫传播

Detection and analysis of Serpin and RP26 specific antibodies for monitoring Schistosoma haematobium transmission.

作者信息

Kokubo-Tanaka Mio, Kildemoes Anna Overgaard, Chadeka Evans Asena, Cheruiyot Benard Ngetich, Moriyasu Taeko, Sassa Miho, Nakamura Risa, Kikuchi Mihoko, Fujii Yoshito, de Dood Claudia J, Corstjens Paul L A M, Kaneko Satoshi, Maruyama Haruhiko, Njenga Sammy M, de Vrueh Remco, Hokke Cornelis Hendrik, Hamano Shinjiro

机构信息

Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.

Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

出版信息

PLoS Negl Trop Dis. 2025 Jan 24;19(1):e0012813. doi: 10.1371/journal.pntd.0012813. eCollection 2025 Jan.

Abstract

BACKGROUND

Schistosoma haematobium is the causative pathogen for urogenital schistosomiasis. To achieve progress towards schistosomiasis elimination, there is a critical need for developing highly sensitive and specific tools to monitor transmission in near-elimination settings. Although antibody detection is a promising approach, it is usually unable to discriminate active infections from past ones. Moreover, crude antigens such as soluble egg antigen (SEA) show cross-reactivity with other parasitic infections, and it is difficult to formulate the standard preparations. To resolve these issues, the performances of recombinant antigens have been evaluated. The antibody responses against recombinant S. haematobium serine-protease inhibitor (ShSerpin) and RP26 were previously shown to reflect active schistosome infection in humans. Furthermore, antibody detection using multiple recombinant antigens has been reported to improve the accuracy of antibody-based assays compared to single-target assays. Therefore, we examined the performances of ShSerpin, RP26 and the mixture of these antigens for detecting S. haematobium low-intensity infection and assessed the potential for transmission monitoring.

METHODOLOGY/PRINCIPAL FINDINGS: We collected urine and plasma samples from school-aged children in Kwale, Kenya and evaluated S. haematobium prevalence by number of eggs in urine and worm-derived circulating anodic antigen (CAA) in plasma. Among 269 pupils, 50.2% were CAA-positive by the lateral flow test utilizing up-converting phosphor particles (UCP-LF CAA), while only 14.1% were egg-positive. IgG levels to S. haematobium SEA (ShSEA), ShSerpin, RP26, and the mixture of ShSerpin and RP26 were measured by ELISA. The mixture of ShSerpin and RP26 showed the highest sensitivity, 88.7%(125/141)among the four antigens in considering indecisive UCP-LF CAA results as negative.

CONCLUSION/SIGNIFICANCE: IgG detection against the ShSerpin-RP26 mixture demonstrated better sensitivity for detection of active S. haematobium infection. This recombinant antigen mixture is simpler to produce with higher reproducibility and can potentially replace ShSEA in monitoring transmission under near-elimination settings.

摘要

背景

埃及血吸虫是泌尿生殖系统血吸虫病的病原体。为在消除血吸虫病方面取得进展,迫切需要开发高度敏感和特异的工具,以监测接近消除状态下的传播情况。虽然抗体检测是一种有前景的方法,但它通常无法区分现症感染和既往感染。此外,粗抗原如可溶性虫卵抗原(SEA)与其他寄生虫感染存在交叉反应,且难以制备标准制剂。为解决这些问题,已对重组抗原的性能进行了评估。先前已表明,针对重组埃及血吸虫丝氨酸蛋白酶抑制剂(ShSerpin)和RP26的抗体反应可反映人类现症血吸虫感染。此外,与单靶点检测相比,使用多种重组抗原进行抗体检测已被报道可提高基于抗体检测的准确性。因此,我们检测了ShSerpin、RP26以及这些抗原混合物在检测埃及血吸虫低强度感染方面的性能,并评估了其用于传播监测的潜力。

方法/主要发现:我们从肯尼亚夸莱的学龄儿童中收集尿液和血浆样本,并通过尿液中的虫卵数量和血浆中虫源性循环阳极抗原(CAA)评估埃及血吸虫的流行情况。在269名学生中,利用上转换磷光颗粒的侧向流动试验(UCP-LF CAA)检测到50.2%的学生CAA呈阳性,而只有14.1%的学生虫卵呈阳性。通过ELISA检测针对埃及血吸虫SEA(ShSEA)、ShSerpin、RP26以及ShSerpin和RP26混合物的IgG水平。在将不确定的UCP-LF CAA结果视为阴性的情况下,ShSerpin和RP26的混合物在四种抗原中显示出最高的敏感性,为88.7%(125/141)。

结论/意义:针对ShSerpin-RP26混合物的IgG检测在检测现症埃及血吸虫感染方面显示出更好的敏感性。这种重组抗原混合物生产更简单,具有更高的可重复性,并且在接近消除状态下的传播监测中有可能取代ShSEA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f1c/11759395/85ad6f48f920/pntd.0012813.g001.jpg

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