Prospective evaluation of a rapid diagnostic test for Trypanosoma brucei gambiense infection developed using recombinant antigens

BackgroundDiagnosis and treatment are central elements of strategies to control Trypanosoma brucei gambiense human African trypanosomiasis (HAT). Serological screening is a key entry point in diagnostic algorithms. The Card Agglutination Test for Trypanosomiasis (CATT) has been the most widely used screening test for decades, despite a number of practical limitations that were partially addressed by the introduction of rapid diagnostic tests (RDTs). However, current RDTs are manufactured using native antigens, which are challenging to produce.Methodology/Principal findingsThe objective of this study was to evaluate the accuracy of a new RDT developed using recombinant antigens (SD BIOLINE HAT 2.0), in comparison with an RDT produced using native antigens (SD BIOLINE HAT) and CATT. A total of 57,632 individuals were screened in the Democratic Republic of the Congo, either passively at 10 health centres, or actively by 5 mobile teams, and 260 HAT cases were confirmed by parasitology. The highest sensitivity was achieved with the SD BIOLINE HAT 2.0 (71.2%), followed by CATT (62.5%) and the SD BIOLINE HAT (59.0%). The most specific test was CATT (99.2%), while the specificity of the SD BIOLINE HAT and SD BIOLINE HAT 2.0 were 98.9% and 98.1%, respectively. Sensitivity of the tests was lower than previously reported, as they identified cases from partially overlapping sub-populations. All three tests were significantly more sensitive in passive than in active screening. Combining two or three tests resulted in a markedly increased sensitivity: When the SD BIOLINE HAT was combined with the SD BIOLINE HAT 2.0, sensitivity reached 98.4% in passive and 83.0% in active screening.Conclusions/SignificanceThe recombinant antigen-based RDT was more sensitive than, and as specific as, the SD BIOLINE HAT. It was as sensitive as, but slightly less specific than CATT. While the practicality and cost-effectiveness of algorithms including several screening tests would need to be investigated, using two or more tests appears to enhance sensitivity of diagnostic algorithms, although some decrease in specificity is observed as well.背景 诊断与治疗是控制布氏冈比亚锥虫（Trypanosoma brucei gambiense）所致人类非洲锥虫病（Human African trypanosomiasis, HAT）的核心策略要素。血清学筛查是诊断流程的关键切入点。数十年来，锥虫病卡片凝集试验（Card Agglutination Test for Trypanosomiasis, CATT）一直是应用最为广泛的筛查手段，尽管其存在诸多实际局限性，而快速诊断检测（rapid diagnostic tests, RDTs）的问世则部分弥补了这些不足。然而，当前的RDTs均采用天然抗原制备，其生产难度较大。 研究方法与主要结果 本研究旨在评估一种采用重组抗原开发的新型RDT（SD BIOLINE HAT 2.0）的检测准确性，并与采用天然抗原制备的RDT（SD BIOLINE HAT）及CATT进行对比。研究共在刚果民主共和国筛查了57632名个体，其中10个卫生中心开展被动筛查，5支流动医疗队开展主动筛查，最终经寄生虫学检查确诊的HAT病例共计260例。SD BIOLINE HAT 2.0的灵敏度最高，达71.2%，其次为CATT（62.5%）与SD BIOLINE HAT（59.0%）。特异性最高的检测手段为CATT（99.2%），SD BIOLINE HAT与SD BIOLINE HAT 2.0的特异性分别为98.9%与98.1%。本次研究中三种检测手段的灵敏度均低于既往报道，这是因为本次筛查覆盖的亚群与既往研究存在部分重叠。三种检测手段在被动筛查中的灵敏度均显著高于主动筛查。联合两项或三项检测可显著提升灵敏度：当SD BIOLINE HAT与SD BIOLINE HAT 2.0联用时，被动筛查的灵敏度可达98.4%，主动筛查则可达83.0%。 结论与意义 基于重组抗原的RDT灵敏度优于SD BIOLINE HAT，且特异性与其相当；其灵敏度与CATT相当，但特异性略低于CATT。尽管包含多种筛查手段的检测流程的实用性与成本效益尚待进一步研究，但联合两项或多项检测似乎可提升诊断流程的灵敏度，不过同时也会伴随特异性的一定程度下降。